Comparative study of quantal and semiclassical treatments of charge transfer between O+ and He

NASA Astrophysics Data System (ADS)

Zhao, L. B.; Joseph, D. C.; Saha, B. C.; Liebermann, H. P.; Funke, P.; Buenker, R. J.

2009-03-01

A comparative study for the electron capture process O+(S40,D20,P20)+He→O(P3)+He+ is reported. The cross sections are calculated using fully quantal and semiclassical molecular-orbital close-coupling (MOCC) approaches in the adiabatic representation. Detailed comparison of transition probabilities and cross sections is made from both MOCC approaches and displays close agreement above ˜125eV/u . The remarkable discrepancies between the earlier semiclassical and quantal MOCC approaches may be attributed to the insufficient step-size resolution in their semiclassical calculation [M. Kimura , Phys. Rev. A 50, 4854 (1994)]. Our results have also been compared with experiment and found to be in good agreement.

The quantal release at a neuro-neuronal synapse is regulated by the content of acetylcholine in the presynaptic cell.

PubMed

Poulain, B; Baux, G; Tauc, L

1986-01-01

Transmitter release was studied with respect to the presynaptic acetylcholine (ACh) content at a central identified inhibitory synapse (Cl- conductance) of Aplysia californica. Statistical analysis of the synaptic noise evoked by sustained depolarization of the presynaptic neuron allowed us to calculate the quantal parameters of the postsynaptic responses. Loading of the presynaptic neurone with injected ACh led to an increase in the postsynaptic responses whereas the calculated miniature postsynaptic current (MPSC) was unmodified. Destruction of choline by choline oxidase either applied extracellularly and coupled to intense stimulations of the presynaptic cell or injected into the presynaptic neuron induced a depression of the postsynaptic response although the amplitude of the calculated MPSC remained constant. As the size of the MPSC, i.e. the size of the quantum, did not change in these experiments, it was concluded that the presynaptic ACh content controls the number of quanta released by a given presynaptic depolarization. As additional evidence, effects of abrupt increase in tonicity of the external medium were studied. The observed transient enhancement of the quantal content of the postsynaptic response could be attributed to an increase in the presynaptic concentration of ACh, resulting from the reduction in cellular volume.

Two neuropeptides colocalized in a command-like neuron use distinct mechanisms to enhance its fast synaptic connection.

PubMed

Koh, H Y; Vilim, F S; Jing, J; Weiss, K R

2003-09-01

In many neurons more than one peptide is colocalized with a classical neurotransmitter. The functional consequence of such an arrangement has been rarely investigated. Here, within the feeding circuit of Aplysia, we investigate at a single synapse the actions of two modulatory neuropeptides that are present in a cholinergic interneuron. In combination with previous work, our study shows that the command-like neuron for feeding, CBI-2, contains two neuropeptides, feeding circuit activating peptide (FCAP) and cerebral peptide 2 (CP2). Previous studies showed that high-frequency prestimulation or repeated stimulation of CBI-2 increases the size of CBI-2 to B61/62 excitatory postsynaptic potentials (EPSPs) and shortens the latency of firing of neuron B61/62 in response to CBI-2 stimulation. We find that both FCAP and CP2 mimic these two effects. The variance method of quantal analysis indicates that FCAP increases the calculated quantal size (q) and CP2 increases the calculated quantal content (m) of EPSPs. Since the PSP amplitude represents the product of q and m, the joint action of the two peptides is expected to be cooperative. This observation suggests a possible functional implication for multiple neuropeptides colocalized with a classical neurotransmitter in one neuron.

A new potential energy surface for vibration-vibration coupling in HF-HF collisions. Formulation and quantal scattering calculations

NASA Astrophysics Data System (ADS)

Schwenke, David W.; Truhlar, Donald G.

1988-04-01

We present new ab initio calculations of the HF-HF interaction potential for the case where both molecules are simultaneously displaced from their equilibrium internuclear distance. These and previous ab initio calculations are then fit to a new analytic representation which is designed to be efficient to evaluate and to provide an especially faithful account of the forces along the vibrational coordinates. We use the new potential for two sets of quantal scattering calculations for collisions in three dimensions with total angular momentum zero. First we test that the angular harmonic representation of the anisotropy is adequate by comparing quantal rigid rotator calculations to those carried out for potentials involving higher angular harmonics and for which the expansion in angular harmonics is systematically increased to convergence. Then we carry out large-scale quantal calculations of vibration-vibration energy transfer including the coupling of both sets of vibrational and rotational coordinates. These calculations indicate that significant rotational energy transfer accompanies the vibration-to-vibration energy transfer process.

Magnetron sputtered diamond-like carbon microelectrodes for on-chip measurement of quantal catecholamine release from cells

PubMed Central

Gao, Yuanfang; Chen, Xiaohui; Gupta, Sanju; Gillis, Kevin D.; Gangopadhyay, Shubhra

2008-01-01

Carbon electrodes are widely used in electrochemistry due to their low cost, wide potential window, and low and stable background noise. Carbon-fiber electrodes (CFE) are commonly used to electrochemically measure “quantal” catecholamine release via exocytosis from individual cells, but it is difficult to integrate CFEs into lab-on-a-chip devices. Here we report the development of nitrogen doped diamond-like carbon (DLC:N) microelectrodes on a chip to monitor quantal release of catecholamines from cells. Advantages of DLC:N microelectrodes are that they are batch producible at low cost, and are harder and more durable than graphite films. The DLC:N microelectrodes were prepared by a magnetron sputtering process with nitrogen doping. The 30 μm by 40 μm DLC:N microelectrodes were patterned onto microscope glass slides by photolithography and lift-off technology. The properties of the DLC:N microelectrodes were characterized by AFM, Raman spectroscopy and cyclic voltammetry. Quantal catecholamine release was recorded amperometrically from bovine adrenal chromaffin cells on the DLC:N microelectrodes. Amperometric spikes due to quantal release of catecholamines were similar in amplitude and area as those recorded using CFEs and the background current and noise levels of microchip DLC:N electrodes were also comparable to CFEs. Therefore, DLC:N microelectrodes are suitable for microchip-based high-throughput measurement of quantal exocytosis with applications in basic research, drug discovery and cell-based biosensors. PMID:18493856

POLO2: a user's guide to multiple Probit Or LOgit analysis

Treesearch

Robert M. Russell; N. E. Savin; Jacqueline L. Robertson

1981-01-01

This guide provides instructions for the use of POLO2, a computer program for multivariate probit or logic analysis of quantal response data. As many as 3000 test subjects may be included in a single analysis. Including the constant term, up to nine explanatory variables may be used. Examples illustrating input, output, and uses of the program's special features...

Electroporation followed by electrochemical measurement of quantal transmitter release from single cells using a patterned microelectrode.

PubMed

Ghosh, Jaya; Liu, Xin; Gillis, Kevin D

2013-06-07

An electrochemical microelectrode located immediately adjacent to a single neuroendocrine cell can record spikes of amperometric current that result from exocytosis of oxidizable transmitter from individual vesicles, i.e., quantal exocytosis. Here, we report the development of an efficient method where the same electrochemical microelectrode is used to electropermeabilize an adjacent chromaffin cell and then measure the consequent quantal catecholamine release using amperometry. Trains of voltage pulses, 5-7 V in amplitude and 0.1-0.2 ms in duration, were used to reliably trigger release from cells using gold electrodes. Amperometric spikes induced by electropermeabilization had similar areas, peak heights and durations as amperometric spikes elicited by depolarizing high K(+) solutions, therefore release occurs from individual secretory granules. Uptake of trypan blue stain into cells demonstrated that the plasma membrane is permeabilized by the voltage stimulus. Voltage pulses did not degrade the electrochemical sensitivity of the electrodes assayed using a test analyte. Surprisingly, robust quantal release was elicited upon electroporation in the absence of Ca(2+) in the bath solution (0 Ca(2+)/5 mM EGTA). In contrast, electropermeabilization-induced transmitter release required Cl(-) in the bath solution in that bracketed experiments demonstrated a steep dependence of the rate of electropermeabilization-induced transmitter release on [Cl(-)] between 2 and 32 mM. Using the same electrochemical electrode to electroporate and record quantal release of catecholamines from an individual chromaffin cell allows precise timing of the stimulus, stimulation of a single cell at a time, and can be used to load membrane-impermeant substances into a cell.

Desensitization shortens the high-quantal-content endplate current time course in frog muscle with intact cholinesterase.

PubMed

Giniatullin, R A; Talantova, M; Vyskocil, F

1997-08-01

1. The desensitization induced by bath-applied carbachol or acetylcholine (ACh) and potentiated by proadifen (SKF 525A) was studied in the frog sartorius with intact synaptic acetylcholinesterase (AChE). 2. The reduction in the density and number of postsynaptic receptors produced by desensitization lowered the amplitude of the endplate currents (EPCs) and shortened the EPC decay when the quantal content (m) of the EPC was about 170 and when multiple release of quanta at single active zones was highly probably. The shortening of high-quantal-content EPCs persisted for at least 15 min after the wash-out of agonists, at a time when the amplitude had recovered fully. 3. The decay times of the low-quantal-content EPCs recorded from preparations pretreated with 5 mM Mg2+ (m approximately 70) and single-quantum miniature endplate currents (MEPCs) were not affected by carbachol, ACh or proadifen. 4. The desensitization of ACh receptors potentiated by proadifen, prevented completely the 6- to 8-fold prolongation of EPC which was induced by neostigmine inhibition of synaptic AChE. 5. It is assumed that high-quantal-content EPCs increase the incidence of multiple quanta release at single active zones and the probability of repetitive binding of ACh molecules which leads to EPC prolongation. The shortening which persists after complete recovery of the amplitude during wash-out of the exogenous agonist is probably due to 'trapping' of ACh molecules onto rapidly desensitized receptors and the reduced density of functional AChRs during the quantum action.

Time-Dependent Thomas-Fermi Approach for Electron Dynamics in Metal Clusters

NASA Astrophysics Data System (ADS)

Domps, A.; Reinhard, P.-G.; Suraud, E.

1998-06-01

We propose a time-dependent Thomas-Fermi approach to the (nonlinear) dynamics of many-fermion systems. The approach relies on a hydrodynamical picture describing the system in terms of collective flow. We investigate in particular an application to electron dynamics in metal clusters. We make extensive comparisons with fully fledged quantal dynamical calculations and find overall good agreement. The approach thus provides a reliable and inexpensive scheme to study the electronic response of large metal clusters.

Charge Exchange in Slow Collisions of O+ with He

NASA Astrophysics Data System (ADS)

Zhao, L. B.; Joseph, D. C.; Saha, B. C.; Lebermann, H. P.; Funke, P.; Buenker, R. J.

2009-03-01

A comparative study is reported for the charge transfer in collisions of O^+ with He using the fully quantal and semiclassical molecular-orbital close-coupling (MOCC) approaches in the adiabatic representation. The electron capture processes O^+(^4S^o, ^2D^o, ^2P^o) + He -> O(^3P) + He^+ are recalculated. The semiclassical MOCC approach was examined by a detailed comparision of cross sections and transition probabilities from both the fully quantal and semiclassical MOCC approaches. The discrepancies reported previously between the semiclassical and the quantal MOCC cross sections may be attributed due to the insufficient step-size resolution of the semiclassical calculations. Our results are also compared with the experimental cross sections and found good agreements. This work is supported by NSF, CREST program (Grant#0630370).

Quantal diffusion description of multinucleon transfers in heavy-ion collisions

NASA Astrophysics Data System (ADS)

Ayik, S.; Yilmaz, B.; Yilmaz, O.; Umar, A. S.

2018-05-01

Employing the stochastic mean-field (SMF) approach, we develop a quantal diffusion description of the multi-nucleon transfer in heavy-ion collisions at finite impact parameters. The quantal transport coefficients are determined by the occupied single-particle wave functions of the time-dependent Hartree-Fock equations. As a result, the primary fragment mass and charge distribution functions are determined entirely in terms of the mean-field properties. This powerful description does not involve any adjustable parameter, includes the effects of shell structure, and is consistent with the fluctuation-dissipation theorem of the nonequilibrium statistical mechanics. As a first application of the approach, we analyze the fragment mass distribution in 48Ca+ 238U collisions at the center-of-mass energy Ec.m.=193 MeV and compare the calculations with the experimental data.

Cholinergic regulation of the evoked quantal release at frog neuromuscular junction

PubMed Central

Nikolsky, Eugeny E; Vyskočil, František; Bukharaeva, Ella A; Samigullin, Dmitry; Magazanik, Lev G

2004-01-01

The effects of cholinergic drugs on the quantal contents of the nerve-evoked endplate currents (EPCs) and the parameters of the time course of quantal release (minimal synaptic latency, main modal value of latency histogram and variability of synaptic latencies) were studied at proximal, central and distal regions of the frog neuromuscular synapse. Acetylcholine (ACh, 5 × 10−4 m), carbachol (CCh, 1 × 10−5 m) or nicotine (5 × 10−6 m) increased the numbers of EPCs with long release latencies mainly in the distal region of the endplate (90–120 μm from the last node of Ranvier), where the synchronization of transmitter release was the most pronounced. The parameters of focally recorded motor nerve action potentials were not changed by either ACh or CCh. The effects of CCh and nicotine on quantal dispersion were reduced substantially by 5 × 10−7 m (+)tubocurarine (TC). The muscarinic agonists, oxotremorine and the propargyl ester of arecaidine, as well as antagonists such as pirenzepine, AF-DX 116 and methoctramine, alone or in combination, did not affect the dispersion of the release. Muscarinic antagonists did not block the dispersion action of CCh. Cholinergic drugs either decreased the quantal content mo (muscarinic agonist, oxotremorine M, and nicotinic antagonist, TC), or decreased mo and dispersed the release (ACh, CCh and nicotine). The effects on mo were not related either to the endplate region or to the initial level of release dispersion. It follows that the mechanisms regulating the amount and the time course of transmitter release are different and that, among other factors, they are altered by presynaptic nicotinic receptors. PMID:15254150

Efficiency of synaptic transmission of single-photon events from rod photoreceptor to rod bipolar dendrite.

PubMed

Schein, Stan; Ahmad, Kareem M

2006-11-01

A rod transmits absorption of a single photon by what appears to be a small reduction in the small number of quanta of neurotransmitter (Q(count)) that it releases within the integration period ( approximately 0.1 s) of a rod bipolar dendrite. Due to the quantal and stochastic nature of release, discrete distributions of Q(count) for darkness versus one isomerization of rhodopsin (R*) overlap. We suggested that release must be regular to narrow these distributions, reduce overlap, reduce the rate of false positives, and increase transmission efficiency (the fraction of R* events that are identified as light). Unsurprisingly, higher quantal release rates (Q(rates)) yield higher efficiencies. Focusing here on the effect of small changes in Q(rate), we find that a slightly higher Q(rate) yields greatly reduced efficiency, due to a necessarily fixed quantal-count threshold. To stabilize efficiency in the face of drift in Q(rate), the dendrite needs to regulate the biochemical realization of its quantal-count threshold with respect to its Q(count). These considerations reveal the mathematical role of calcium-based negative feedback and suggest a helpful role for spontaneous R*. In addition, to stabilize efficiency in the face of drift in degree of regularity, efficiency should be approximately 50%, similar to measurements.

A health risk benchmark for the neurologic effects of styrene: comparison with NOAEL/LOAEL approach.

PubMed

Rabovsky, J; Fowles, J; Hill, M D; Lewis, D C

2001-02-01

Benchmark dose (BMD) analysis was used to estimate an inhalation benchmark concentration for styrene neurotoxicity. Quantal data on neuropsychologic test results from styrene-exposed workers [Mutti et al. (1984). American Journal of Industrial Medicine, 5, 275-286] were used to quantify neurotoxicity, defined as the percent of tested workers who responded abnormally to > or = 1, > or = 2, or > or = 3 out of a battery of eight tests. Exposure was based on previously published results on mean urinary mandelic- and phenylglyoxylic acid levels in the workers, converted to air styrene levels (15, 44, 74, or 115 ppm). Nonstyrene-exposed workers from the same region served as a control group. Maximum-likelihood estimates (MLEs) and BMDs at 5 and 10% response levels of the exposed population were obtained from log-normal analysis of the quantal data. The highest MLE was 9 ppm (BMD = 4 ppm) styrene and represents abnormal responses to > or = 3 tests by 10% of the exposed population. The most health-protective MLE was 2 ppm styrene (BMD = 0.3 ppm) and represents abnormal responses to > or = 1 test by 5% of the exposed population. A no observed adverse effect level/lowest observed adverse effect level (NOAEL/LOAEL) analysis of the same quantal data showed workers in all styrene exposure groups responded abnormally to > or = 1, > or = 2, or > or = 3 tests, compared to controls, and the LOAEL was 15 ppm. A comparison of the BMD and NOAEL/LOAEL analyses suggests that at air styrene levels below the LOAEL, a segment of the worker population may be adversely affected. The benchmark approach will be useful for styrene noncancer risk assessment purposes by providing a more accurate estimate of potential risk that should, in turn, help to reduce the uncertainty that is a common problem in setting exposure levels.

From rationality to cooperativeness: The totally mixed Nash equilibrium in Markov strategies in the iterated Prisoner's Dilemma.

PubMed

Menshikov, Ivan S; Shklover, Alexsandr V; Babkina, Tatiana S; Myagkov, Mikhail G

2017-01-01

In this research, the social behavior of the participants in a Prisoner's Dilemma laboratory game is explained on the basis of the quantal response equilibrium concept and the representation of the game in Markov strategies. In previous research, we demonstrated that social interaction during the experiment has a positive influence on cooperation, trust, and gratefulness. This research shows that the quantal response equilibrium concept agrees only with the results of experiments on cooperation in Prisoner's Dilemma prior to social interaction. However, quantal response equilibrium does not explain of participants' behavior after social interaction. As an alternative theoretical approach, an examination was conducted of iterated Prisoner's Dilemma game in Markov strategies. We built a totally mixed Nash equilibrium in this game; the equilibrium agrees with the results of the experiments both before and after social interaction.

From rationality to cooperativeness: The totally mixed Nash equilibrium in Markov strategies in the iterated Prisoner’s Dilemma

PubMed Central

Myagkov, Mikhail G.

2017-01-01

In this research, the social behavior of the participants in a Prisoner's Dilemma laboratory game is explained on the basis of the quantal response equilibrium concept and the representation of the game in Markov strategies. In previous research, we demonstrated that social interaction during the experiment has a positive influence on cooperation, trust, and gratefulness. This research shows that the quantal response equilibrium concept agrees only with the results of experiments on cooperation in Prisoner’s Dilemma prior to social interaction. However, quantal response equilibrium does not explain of participants’ behavior after social interaction. As an alternative theoretical approach, an examination was conducted of iterated Prisoner's Dilemma game in Markov strategies. We built a totally mixed Nash equilibrium in this game; the equilibrium agrees with the results of the experiments both before and after social interaction. PMID:29190280

Stability of Mixed-Strategy-Based Iterative Logit Quantal Response Dynamics in Game Theory

PubMed Central

Zhuang, Qian; Di, Zengru; Wu, Jinshan

2014-01-01

Using the Logit quantal response form as the response function in each step, the original definition of static quantal response equilibrium (QRE) is extended into an iterative evolution process. QREs remain as the fixed points of the dynamic process. However, depending on whether such fixed points are the long-term solutions of the dynamic process, they can be classified into stable (SQREs) and unstable (USQREs) equilibriums. This extension resembles the extension from static Nash equilibriums (NEs) to evolutionary stable solutions in the framework of evolutionary game theory. The relation between SQREs and other solution concepts of games, including NEs and QREs, is discussed. Using experimental data from other published papers, we perform a preliminary comparison between SQREs, NEs, QREs and the observed behavioral outcomes of those experiments. For certain games, we determine that SQREs have better predictive power than QREs and NEs. PMID:25157502

An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size.

PubMed

Wojcik, S M; Rhee, J S; Herzog, E; Sigler, A; Jahn, R; Takamori, S; Brose, N; Rosenmund, C

2004-05-04

Quantal neurotransmitter release at excitatory synapses depends on glutamate import into synaptic vesicles by vesicular glutamate transporters (VGLUTs). Of the three known transporters, VGLUT1 and VGLUT2 are expressed prominently in the adult brain, but during the first two weeks of postnatal development, VGLUT2 expression predominates. Targeted deletion of VGLUT1 in mice causes lethality in the third postnatal week. Glutamatergic neurotransmission is drastically reduced in neurons from VGLUT1-deficient mice, with a specific reduction in quantal size. The remaining activity correlates with the expression of VGLUT2. This reduction in glutamatergic neurotransmission can be rescued and enhanced with overexpression of VGLUT1. These results show that the expression level of VGLUTs determines the amount of glutamate that is loaded into vesicles and released and thereby regulates the efficacy of neurotransmission.

Estimating synaptic parameters from mean, variance, and covariance in trains of synaptic responses.

PubMed

Scheuss, V; Neher, E

2001-10-01

Fluctuation analysis of synaptic transmission using the variance-mean approach has been restricted in the past to steady-state responses. Here we extend this method to short repetitive trains of synaptic responses, during which the response amplitudes are not stationary. We consider intervals between trains, long enough so that the system is in the same average state at the beginning of each train. This allows analysis of ensemble means and variances for each response in a train separately. Thus, modifications in synaptic efficacy during short-term plasticity can be attributed to changes in synaptic parameters. In addition, we provide practical guidelines for the analysis of the covariance between successive responses in trains. Explicit algorithms to estimate synaptic parameters are derived and tested by Monte Carlo simulations on the basis of a binomial model of synaptic transmission, allowing for quantal variability, heterogeneity in the release probability, and postsynaptic receptor saturation and desensitization. We find that the combined analysis of variance and covariance is advantageous in yielding an estimate for the number of release sites, which is independent of heterogeneity in the release probability under certain conditions. Furthermore, it allows one to calculate the apparent quantal size for each response in a sequence of stimuli.

Multinucleon transfer in central collisions of 238U+238U

NASA Astrophysics Data System (ADS)

Ayik, S.; Yilmaz, B.; Yilmaz, O.; Umar, A. S.; Turan, G.

2017-08-01

Quantal diffusion mechanism of nucleon exchange is studied in the central collisions of 238U+238U in the framework of the stochastic mean-field (SMF) approach. For bombarding energies considered in this work, the dinuclear structure is maintained during the collision. Hence, it is possible to describe nucleon exchange as a diffusion process for mass and charge asymmetry. Quantal neutron and proton diffusion coefficients, including memory effects, are extracted from the SMF approach and the primary fragment distributions are calculated.

Multifactorial analysis of human blood cell responses to clinical total body irradiation

NASA Technical Reports Server (NTRS)

Yuhas, J. M.; Stokes, T. R.; Lushbaugh, C. C.

1972-01-01

Multiple regression analysis techniques are used to study the effects of therapeutic radiation exposure, number of fractions, and time on such quantal responses as tumor control and skin injury. The potential of these methods for the analysis of human blood cell responses is demonstrated and estimates are given of the effects of total amount of exposure and time of protraction in determining the minimum white blood cell concentration observed after exposure of patients from four disease groups.

The Quantal Larynx: The Stable Regions of Laryngeal Biomechanics and Implications for Speech Production.

PubMed

Moisik, Scott Reid; Gick, Bryan

2017-03-01

Recent proposals suggest that (a) the high dimensionality of speech motor control may be reduced via modular neuromuscular organization that takes advantage of intrinsic biomechanical regions of stability and (b) computational modeling provides a means to study whether and how such modularization works. In this study, the focus is on the larynx, a structure that is fundamental to speech production because of its role in phonation and numerous articulatory functions. A 3-dimensional model of the larynx was created using the ArtiSynth platform (http://www.artisynth.org). This model was used to simulate laryngeal articulatory states, including inspiration, glottal fricative, modal prephonation, plain glottal stop, vocal-ventricular stop, and aryepiglotto-epiglottal stop and fricative. Speech-relevant laryngeal biomechanics is rich with "quantal" or highly stable regions within muscle activation space. Quantal laryngeal biomechanics complement a modular view of speech control and have implications for the articulatory-biomechanical grounding of numerous phonetic and phonological phenomena.

The probability of quantal secretion near a single calcium channel of an active zone.

PubMed Central

Bennett, M R; Farnell, L; Gibson, W G

2000-01-01

A Monte Carlo analysis has been made of calcium dynamics and quantal secretion at microdomains in which the calcium reaches very high concentrations over distances of <50 nm from a channel and for which calcium dynamics are dominated by diffusion. The kinetics of calcium ions in microdomains due to either the spontaneous or evoked opening of a calcium channel, both of which are stochastic events, are described in the presence of endogenous fixed and mobile buffers. Fluctuations in the number of calcium ions within 50 nm of a channel are considerable, with the standard deviation about half the mean. Within 10 nm of a channel these numbers of ions can give rise to calcium concentrations of the order of 100 microM. The temporal changes in free calcium and calcium bound to different affinity indicators in the volume of an entire varicosity or bouton following the opening of a single channel are also determined. A Monte Carlo analysis is also presented of how the dynamics of calcium ions at active zones, after the arrival of an action potential and the stochastic opening of a calcium channel, determine the probability of exocytosis from docked vesicles near the channel. The synaptic vesicles in active zones are found docked in a complex with their calcium-sensor associated proteins and a voltage-sensitive calcium channel, forming a secretory unit. The probability of quantal secretion from an isolated secretory unit has been determined for different distances of an open calcium channel from the calcium sensor within an individual unit: a threefold decrease in the probability of secretion of a quantum occurs with a doubling of the distance from 25 to 50 nm. The Monte Carlo analysis also shows that the probability of secretion of a quantum is most sensitive to the size of the single-channel current compared with its sensitivity to either the binding rates of the sites on the calcium-sensor protein or to the number of these sites that must bind a calcium ion to trigger exocytosis of a vesicle. PMID:10777721

Essays on inference in economics, competition, and the rate of profit

NASA Astrophysics Data System (ADS)

Scharfenaker, Ellis S.

This dissertation is comprised of three papers that demonstrate the role of Bayesian methods of inference and Shannon's information theory in classical political economy. The first chapter explores the empirical distribution of profit rate data from North American firms from 1962-2012. This chapter address the fact that existing methods for sample selection from noisy profit rate data in the industrial organization field of economics tends to be conditional on a covariate's value that risks discarding information. Conditioning sample selection instead on the profit rate data's structure by means of a two component (signal and noise) Bayesian mixture model we find the the profit rate sample to be time stationary Laplace distributed, corroborating earlier estimates of cross section distributions. The second chapter compares alternative probabilistic approaches to discrete (quantal) choice analysis and examines the various ways in which they overlap. In particular, the work on individual choice behavior by Duncan Luce and the extension of this work to quantal response problems by game theoreticians is shown to be related both to the rational inattention work of Christopher Sims through Shannon's information theory as well as to the maximum entropy principle of inference proposed physicist Edwin T. Jaynes. In the third chapter I propose a model of ``classically" competitive firms facing informational entropy constraints in their decisions to potentially enter or exit markets based on profit rate differentials. The result is a three parameter logit quantal response distribution for firm entry and exit decisions. Bayesian methods are used for inference into the the distribution of entry and exit decisions conditional on profit rate deviations and firm level data from Compustat is used to test these predictions.

The quantal nature of Ca2+ sparks and in situ operation of the ryanodine receptor array in cardiac cells.

PubMed

Wang, Shi Qiang; Stern, Michael D; Ríos, Eduardo; Cheng, Heping

2004-03-16

Intracellular Ca(2+) release in many types of cells is mediated by ryanodine receptor Ca(2+) release channels (RyRCs) that are assembled into two-dimensional paracrystalline arrays in the endoplasmic/sarcoplasmic reticulum. However, the in situ operating mechanism of the RyRC array is unknown. Here, we found that the elementary Ca(2+) release events, Ca(2+) sparks from individual RyRC arrays in rat ventricular myocytes, exhibit quantized Ca(2+) release flux. Analysis of the quantal property of Ca(2+) sparks provided a view of unitary Ca(2+) current and gating kinetics of the RyRC in intact cells and revealed that spark activation involves dynamic recruitment of small, variable cohorts of RyRCs. Intriguingly, interplay of RyRCs in multichannel sparks renders an unusual, thermodynamically irreversible mode of channel gating that is unshared by an RyRC acting solo, nor by RyRCs in vitro. Furthermore, an array-based inhibitory feedback, overriding the regenerative Ca(2+)-induced Ca(2+) release of RyRCs, provides a supramolecular mechanism for the microscopic stability of intracellular Ca(2+) signaling.

Quantum aspects of brain activity and the role of consciousness.

PubMed Central

Beck, F; Eccles, J C

1992-01-01

The relationship of brain activity to conscious intentions is considered on the basis of the functional microstructure of the cerebral cortex. Each incoming nerve impulse causes the emission of transmitter molecules by the process of exocytosis. Since exocytosis is a quantal phenomenon of the presynaptic vesicular grid with a probability much less than 1, we present a quantum mechanical model for it based on a tunneling process of the trigger mechanism. Consciousness manifests itself in mental intentions. The consequent voluntary actions become effective by momentary increases of the probability of vesicular emission in the thousands of synapses on each pyramidal cell by quantal selection. PMID:1333607

A Monte Carlo model reveals independent signaling at central glutamatergic synapses.

PubMed Central

Franks, Kevin M; Bartol, Thomas M; Sejnowski, Terrence J

2002-01-01

We have developed a biophysically realistic model of receptor activation at an idealized central glutamatergic synapse that uses Monte Carlo techniques to simulate the stochastic nature of transmission following release of a single synaptic vesicle. For the a synapse with 80 AMPA and 20 NMDA receptors, a single quantum, with 3000 glutamate molecules, opened approximately 3 NMDARs and 20 AMPARs. The number of open receptors varied directly with the total number of receptors, and the fraction of open receptors did not depend on the ratio of co-localized AMPARs and NMDARs. Variability decreased with increases in either total receptor number or quantal size, and differences between the variability of AMPAR and NMDAR responses were due solely to unequal numbers of receptors at the synapse. Despite NMDARs having a much higher affinity for glutamate than AMPARs, quantal release resulted in similar occupancy levels in both receptor types. Receptor activation increased with number of transmitter molecules released or total receptor number, whereas occupancy levels were only dependent on quantal size. Tortuous diffusion spaces reduced the extent of spillover and the activation of extrasynaptic receptors. These results support the conclusion that signaling is spatially independent within and between central glutamatergic synapses. PMID:12414671

Errors in the estimation of the variance: implications for multiple-probability fluctuation analysis.

PubMed

Saviane, Chiara; Silver, R Angus

2006-06-15

Synapses play a crucial role in information processing in the brain. Amplitude fluctuations of synaptic responses can be used to extract information about the mechanisms underlying synaptic transmission and its modulation. In particular, multiple-probability fluctuation analysis can be used to estimate the number of functional release sites, the mean probability of release and the amplitude of the mean quantal response from fits of the relationship between the variance and mean amplitude of postsynaptic responses, recorded at different probabilities. To determine these quantal parameters, calculate their uncertainties and the goodness-of-fit of the model, it is important to weight the contribution of each data point in the fitting procedure. We therefore investigated the errors associated with measuring the variance by determining the best estimators of the variance of the variance and have used simulations of synaptic transmission to test their accuracy and reliability under different experimental conditions. For central synapses, which generally have a low number of release sites, the amplitude distribution of synaptic responses is not normal, thus the use of a theoretical variance of the variance based on the normal assumption is not a good approximation. However, appropriate estimators can be derived for the population and for limited sample sizes using a more general expression that involves higher moments and introducing unbiased estimators based on the h-statistics. Our results are likely to be relevant for various applications of fluctuation analysis when few channels or release sites are present.

The 'sniffer-patch' technique for detection of neurotransmitter release.

PubMed

Allen, T G

1997-05-01

A wide variety of techniques have been employed for the detection and measurement of neurotransmitter release from biological preparations. Whilst many of these methods offer impressive levels of sensitivity, few are able to combine sensitivity with the necessary temporal and spatial resolution required to study quantal release from single cells. One detection method that is seeing a revival of interest and has the potential to fill this niche is the so-called 'sniffer-patch' technique. In this article, specific examples of the practical aspects of using this technique are discussed along with the procedures involved in calibrating these biosensors to extend their applications to provide quantitative, in addition to simple qualitative, measurements of quantal transmitter release.

Time-dependent variational approach in terms of squeezed coherent states: Implication to semi-classical approximation

NASA Technical Reports Server (NTRS)

Tsue, Yasuhiko

1994-01-01

A general framework for time-dependent variational approach in terms of squeezed coherent states is constructed with the aim of describing quantal systems by means of classical mechanics including higher order quantal effects with the aid of canonicity conditions developed in the time-dependent Hartree-Fock theory. The Maslov phase occurring in a semi-classical quantization rule is investigated in this framework. In the limit of a semi-classical approximation in this approach, it is definitely shown that the Maslov phase has a geometric nature analogous to the Berry phase. It is also indicated that this squeezed coherent state approach is a possible way to go beyond the usual WKB approximation.

The quantal nature of calcium release to caffeine in single smooth muscle cells results from activation of the sarcoplasmic reticulum Ca(2+)-ATPase.

PubMed

Steenbergen, J M; Fay, F S

1996-01-26

Calcium release from intracellular stores occurs in a graded manner in response to increasing concentrations of either inositol 1,4,5-trisphosphate or caffeine. To investigate the mechanism responsible for this quantal release phenomenon, [Ca2+] changes inside intracellular stores in isolated single smooth muscle cells were monitored with mag-fura 2. Following permeabilization with saponin or alpha-toxin the dye, loaded via its acetoxymethyl ester, was predominantly trapped in the sarcoplasmic reticulum (SR). Low caffeine concentrations in the absence of ATP induced only partial Ca2+ release; however, after inhibiting the calcium pump with thapsigargin the same stimulus released twice as much Ca2+. When the SR Ca(2+)-ATPase was rendered non-functional by depleting its "ATP pool," submaximal caffeine doses almost fully emptied the stores of Ca2+. We conclude that quantal release of Ca2+ in response to caffeine in these smooth muscle cells is largely due to the activity of the SR Ca(2+)-ATPase, which appears to return a portion of the released Ca2+ back to the SR, even in the absence of ATP. Apparently the SR Ca(2+)-ATPase is fueled by ATP, which is either compartmentalized or bound to the SR.

Increased expression of the Drosophila vesicular glutamate transporter leads to excess glutamate release and a compensatory decrease in quantal content.

PubMed

Daniels, Richard W; Collins, Catherine A; Gelfand, Maria V; Dant, Jaime; Brooks, Elizabeth S; Krantz, David E; DiAntonio, Aaron

2004-11-17

Quantal size is a fundamental parameter controlling the strength of synaptic transmission. The transmitter content of synaptic vesicles is one mechanism that can affect the physiological response to the release of a single vesicle. At glutamatergic synapses, vesicular glutamate transporters (VGLUTs) are responsible for filling synaptic vesicles with glutamate. To investigate how VGLUT expression can regulate synaptic strength in vivo, we have identified the Drosophila vesicular glutamate transporter, which we name DVGLUT. DVGLUT mRNA is expressed in glutamatergic motoneurons and a large number of interneurons in the Drosophila CNS. DVGLUT protein resides on synaptic vesicles and localizes to the presynaptic terminals of all known glutamatergic neuromuscular junctions as well as to synapses throughout the CNS neuropil. Increasing the expression of DVGLUT in motoneurons leads to an increase in quantal size that is accompanied by an increase in synaptic vesicle volume. At synapses confronted with increased glutamate release from each vesicle, there is a compensatory decrease in the number of synaptic vesicles released that maintains normal levels of synaptic excitation. These results demonstrate that (1) expression of DVGLUT determines the size and glutamate content of synaptic vesicles and (2) homeostatic mechanisms exist to attenuate the excitatory effects of excess glutamate release.

The ALS gene FUS regulates synaptic transmission at the Drosophila neuromuscular junction

PubMed Central

Machamer, James B.; Collins, Sarah E.; Lloyd, Thomas E.

2014-01-01

Mutations in the RNA binding protein Fused in sarcoma (FUS) are estimated to account for 5–10% of all inherited cases of amyotrophic lateral sclerosis (ALS), but the function of FUS in motor neurons is poorly understood. Here, we investigate the early functional consequences of overexpressing wild-type or ALS-associated mutant FUS proteins in Drosophila motor neurons, and compare them to phenotypes arising from loss of the Drosophila homolog of FUS, Cabeza (Caz). We find that lethality and locomotor phenotypes correlate with levels of FUS transgene expression, indicating that toxicity in developing motor neurons is largely independent of ALS-linked mutations. At the neuromuscular junction (NMJ), overexpression of either wild-type or mutant FUS results in decreased number of presynaptic active zones and altered postsynaptic glutamate receptor subunit composition, coinciding with a reduction in synaptic transmission as a result of both reduced quantal size and quantal content. Interestingly, expression of human FUS downregulates endogenous Caz levels, demonstrating that FUS autoregulation occurs in motor neurons in vivo. However, loss of Caz from motor neurons increases synaptic transmission as a result of increased quantal size, suggesting that the loss of Caz in animals expressing FUS does not contribute to motor deficits. These data demonstrate that FUS/Caz regulates NMJ development and plays an evolutionarily conserved role in modulating the strength of synaptic transmission in motor neurons. PMID:24569165

Electron capture in collisions of ? with H and ? with C

NASA Astrophysics Data System (ADS)

Stancil, P. C.; Gu, J.-P.; Havener, C. C.; Krstic, P. S.; Schultz, D. R.; Kimura, M.; Zygelman, B.; Hirsch, G.; Buenker, R. J.; Bannister, M. E.

1998-08-01

A comprehensive theoretical and experimental study of electron capture in collisions of 0953-4075/31/16/017/img15 with H and 0953-4075/31/16/017/img16 with C extending over the energy range 0953-4075/31/16/017/img17 to 0953-4075/31/16/017/img18 is presented. A variety of theoretical approaches were used including those based on quantal molecular-orbital close-coupling (MOCC), multielectron hidden crossings (MEHC), quantal decay and classical trajectory Monte Carlo techniques. Radiative charge transfer cross sections were computed using the optical potential/distorted wave (OPDW) and fully quantal (FQ) approaches. The MOCC, OPDW and FQ calculations incorporated ab initio potentials, nonadiabatic coupling matrix elements and transition moments computed at the configuration-interaction level. Ab initio potential surfaces in the plane of complex internuclear distance were obtained for the MEHC calculations. Merged-beam measurements were performed between 0953-4075/31/16/017/img19 and 0953-4075/31/16/017/img20 for the 0953-4075/31/16/017/img21 collision system. Diagnostics of the 0953-4075/31/16/017/img15 beam with a crossed electron beam could find no presence of a 0953-4075/31/16/017/img15 metastable component. The current results, in conjunction with previous measurements, are used to deduce a set of recommended cross sections.

Application of Dirac's Generalized Hamiltonian Dynamics to Atomic and Molecular Systems

NASA Astrophysics Data System (ADS)

Uzer, Turgay

2002-10-01

Incorporating electronic degrees of freedom into classical treatments of atoms and molecules is a challenging problem from both the practical and fundamental points of view. Because it goes to the heart of classical-quantal correspondence, there are now a number of prescriptions which differ by the extent of quantal information that they include. We reach back to Dirac for inspiration, who, half a century ago, designed a so-called Generalized Hamiltonian Dynamics (GHD) with applications to field theory in mind. Physically, the GHD is a purely classical formalism for systems with constraints; it incorporates the constraints into the Hamiltonian. We apply the GHD to atomic and molecular physics by choosing integrals of motion as the constraints. We show that this purely classical formalism allows the derivation of energies of non-radiating states.

The Study of Dynamical Potentials of Highly Excited Vibrational States of HOBr

PubMed Central

Wang, Aixing; Sun, Lifeng; Fang, Chao; Liu, Yibao

2013-01-01

The vibrational nonlinear dynamics of HOBr in the bending and O–Br stretching coordinates with anharmonicity and Fermi 2:1 coupling are studied with dynamical potentials in this article. The result shows that the H–O stretching vibration mode has significantly different effects on the coupling between the O–Br stretching mode and the H–O–Br bending mode under different Polyad numbers. The dynamical potentials and the corresponding phase space trajectories are obtained when the Polyad number is 27, for instance, and the fixed points in the dynamical potentials of HOBr are shown to govern the various quantal environments in which the vibrational states lie. Furthermore, it is also found that the quantal environments could be identified by the numerical values of action integrals, which is consistent with former research. PMID:23462512

G protein betagamma-subunits activated by serotonin mediate presynaptic inhibition by regulating vesicle fusion properties.

PubMed

Photowala, Huzefa; Blackmer, Trillium; Schwartz, Eric; Hamm, Heidi E; Alford, Simon

2006-03-14

Neurotransmitters are thought to be released as quanta, where synaptic vesicles deliver packets of neurotransmitter to the synaptic cleft by fusion with the plasma membrane. However, synaptic vesicles may undergo incomplete fusion. We provide evidence that G protein-coupled receptors inhibit release by causing such incomplete fusion. 5-hydroxytryptamine (5-HT) receptor signaling potently inhibits excitatory postsynaptic currents (EPSCs) between lamprey reticulospinal axons and their postsynaptic targets by a direct action on the vesicle fusion machinery. We show that 5-HT receptor-mediated presynaptic inhibition, at this synapse, involves a reduction in EPSC quantal size. Quantal size was measured directly by comparing unitary quantal amplitudes of paired EPSCs before and during 5-HT application and indirectly by determining the effect of 5-HT on the relationship between mean-evoked EPSC amplitude and variance. Results from FM dye-labeling experiments indicate that 5-HT prevents full fusion of vesicles. 5-HT reduces FM1-43 staining of vesicles with a similar efficacy to its effect on the EPSC. However, destaining of FM1-43-labeled vesicles is abolished by lower concentrations of 5-HT that leave a substantial EPSC. The use of a water-soluble membrane impermeant quenching agent in the extracellular space reduced FM1-43 fluorescence during stimulation in 5-HT. Thus vesicles contact the extracellular space during inhibition of synaptic transmission by 5-HT. We conclude that 5-HT, via free Gbetagamma, prevents the collapse of synaptic vesicles into the presynaptic membrane.

Metabotropic and ionotropic glutamate receptors mediate the modulation of acetylcholine release at the frog neuromuscular junction.

PubMed

Tsentsevitsky, Andrei; Nurullin, Leniz; Nikolsky, Evgeny; Malomouzh, Artem

2017-07-01

There is some evidence that glutamate (Glu) acts as a signaling molecule at vertebrate neuromuscular junctions where acetylcholine (ACh) serves as a neurotransmitter. In this study, performed on the cutaneous pectoris muscle of the frog Rana ridibunda, Glu receptor mechanisms that modulate ACh release processes were analyzed. Electrophysiological experiments showed that Glu reduces both spontaneous and evoked quantal secretion of ACh and synchronizes its release in response to electrical stimulation. Quisqualate, an agonist of ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptors and metabotropic Group I mGlu receptors, also exerted Glu-like inhibitory effects on the secretion of ACh but had no effect on the kinetics of quantal release. Quisqualate's inhibitory effect did not occur when a blocker of Group I mGlu receptors (LY 367385) or an inhibitor of phospholipase C (U73122) was present. An increase in the degree of synchrony of ACh quantal release, such as that produced by Glu, was obtained after application of N-methyl-D-aspartic acid (NMDA). The presence of Group I mGlu and NMDA receptors in the neuromuscular synapse was confirmed by immunocytochemistry. Thus, the data suggest that both metabotropic Group I mGlu receptors and ionotropic NMDA receptors are present at the neuromuscular synapse of amphibians, and that the activation of these receptors initiates different mechanisms for the regulation of ACh release from motor nerve terminals. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Quantal and Nonquantal Transmission in Calyx-Bearing Fibers of the Turtle Posterior Crista

PubMed Central

Holt, Joseph C.; Chatlani, Shilpa; Lysakowski, Anna; Goldberg, Jay M.

2010-01-01

Intracellular recordings were made from nerve fibers in the posterior ampullary nerve near the neuroepithelium. Calyx-bearing afferents were identified by their distinctive efferent-mediated responses. Such fibers receive inputs from both type I and type II hair cells. Type II inputs are made by synapses on the outer face of the calyx ending and on the boutons of dimorphic fibers. Quantal activity, consisting of brief mEPSPs, is reduced by lowering the external concentration of Ca2+ and blocked by the AMPA-receptor antagonist CNQX. Poisson statistics govern the timing of mEPSPs, which occur at high rates (250–2,500/s) in the absence of mechanical stimulation. Excitation produced by canal-duct indentation can increase mEPSP rates to nearly 5,000/s. As the rate increases, mEPSPs can change from a monophasic depolarization to a biphasic depolarizing– hyperpolarizing sequence, both of whose components are blocked by CNQX. Blockers of voltage-gated currents affect mEPSP size, which is decreased by TTX and is increased by linopirdine. mEPSP size decreases several fold after impalement. The size decrease, although it may be triggered by the depolarization occurring during impalement, persists even at hyperpolarized membrane potentials. Nonquantal transmission is indicated by shot-noise calculations and by the presence of voltage modulations after quantal activity is abolished pharmacologically. An ultrastructural study shows that inner-face inputs from type I hair cells outnumber outer-face inputs from type II hair cells by an almost 6:1 ratio. PMID:17596419

Vesicular glutamate transporter VGLUT2 expression levels control quantal size and neuropathic pain.

PubMed

Moechars, Diederik; Weston, Matthew C; Leo, Sandra; Callaerts-Vegh, Zsuzsanna; Goris, Ilse; Daneels, Guy; Buist, A; Cik, M; van der Spek, P; Kass, Stefan; Meert, Theo; D'Hooge, Rudi; Rosenmund, Christian; Hampson, R Mark

2006-11-15

Uptake of L-glutamate into synaptic vesicles is mediated by vesicular glutamate transporters (VGLUTs). Three transporters (VGLUT1-VGLUT3) are expressed in the mammalian CNS, with partial overlapping expression patterns, and VGLUT2 is the most abundantly expressed paralog in the thalamus, midbrain, and brainstem. Previous studies have shown that VGLUT1 is necessary for glutamatergic transmission in the hippocampus, but the role of VGLUT2 in excitatory transmission is unexplored in glutamatergic neurons and in vivo. We examined the electrophysiological and behavioral consequences of loss of either one or both alleles of VGLUT2. We show that targeted deletion of VGLUT2 in mice causes perinatal lethality and a 95% reduction in evoked glutamatergic responses in thalamic neurons, although hippocampal synapses function normally. Behavioral analysis of heterozygous VGLUT2 mice showed unchanged motor function, learning and memory, acute nociception, and inflammatory pain, but acquisition of neuropathic pain, maintenance of conditioned taste aversion, and defensive marble burying were all impaired. Reduction or loss of VGLUT2 in heterozygous and homozygous VGLUT2 knock-outs led to a graded reduction in the amplitude of the postsynaptic response to single-vesicle fusion in thalamic neurons, indicating that the vesicular VGLUT content is critically important for quantal size and demonstrating that VGLUT2-mediated reduction of excitatory drive affects specific forms of sensory processing.

Electron capture cross sections by O+ from atomic He

NASA Astrophysics Data System (ADS)

Joseph, Dwayne C.; Saha, Bidhan C.

2009-11-01

The adiabatic representation is used in both the quantal and semi classical molecular orbital close coupling methods (MOCC) to evaluate charge exchange cross sections. Our results show good agreement with experimental cross sections

Benchmark Dose for Urinary Cadmium based on a Marker of Renal Dysfunction: A Meta-Analysis

PubMed Central

Woo, Hae Dong; Chiu, Weihsueh A.; Jo, Seongil; Kim, Jeongseon

2015-01-01

Background Low doses of cadmium can cause adverse health effects. Benchmark dose (BMD) and the one-sided 95% lower confidence limit of BMD (BMDL) to derive points of departure for urinary cadmium exposure have been estimated in several previous studies, but the methods to derive BMD and the estimated BMDs differ. Objectives We aimed to find the associated factors that affect BMD calculation in the general population, and to estimate the summary BMD for urinary cadmium using reported BMDs. Methods A meta-regression was performed and the pooled BMD/BMDL was estimated using studies reporting a BMD and BMDL, weighted by sample size, that were calculated from individual data based on markers of renal dysfunction. Results BMDs were highly heterogeneous across studies. Meta-regression analysis showed that a significant predictor of BMD was the cut-off point which denotes an abnormal level. Using the 95th percentile as a cut off, BMD5/BMDL5 estimates for 5% benchmark responses (BMR) of β2-microglobulinuria (β2-MG) estimated was 6.18/4.88 μg/g creatinine in conventional quantal analysis and 3.56/3.13 μg/g creatinine in the hybrid approach, and BMD5/BMDL5 estimates for 5% BMR of N-acetyl-β-d-glucosaminidase (NAG) was 10.31/7.61 μg/g creatinine in quantal analysis and 3.21/2.24 g/g creatinine in the hybrid approach. However, the meta-regression showed that BMD and BMDL were significantly associated with the cut-off point, but BMD calculation method did not significantly affect the results. The urinary cadmium BMDL5 of β2-MG was 1.9 μg/g creatinine in the lowest cut-off point group. Conclusion The BMD was significantly associated with the cut-off point defining the abnormal level of renal dysfunction markers. PMID:25970611

Controlled On-chip Stimulation of Quantal Catecholamine Release from Chromaffin Cells Using Photolysis of Caged Ca2+ on Transparent Indium-Tin-Oxide Microchip Electrodes

PubMed Central

Chen, Xiaohui; Gao, Yuanfang; Hossain, Maruf; Gangopadhyay, Shubhra; Gillis, Kevin D.

2008-01-01

Photorelease of caged Ca2+ is a uniquely powerful tool to study the dynamics of Ca2+-triggered exocytosis from individual cells. Using photolithography and other microfabrication techniques, we have developed transparent microchip devices to enable photorelease of caged Ca2+ together with electrochemical detection of quantal catecholamine secretion from individual cells or cell arrays as a step towards developing high-throughput experimental devices. A 100 nm - thick transparent Indium-Tin-Oxide (ITO) film was sputter-deposited onto glass coverslips, which were then patterned into 24 cell-sized working electrodes (∼20 μm by 20 μm). We loaded bovine chromaffin cells with acetoxymethyl (AM) ester derivatives of the Ca2+ cage NP-EGTA and Ca2+ indicator dye Fura-4F, then transferred these cells onto the working ITO electrodes for amperometric recordings. Upon flash photorelease of caged Ca2+, a uniform rise of [Ca2+]i within the target cell leads to quantal release of oxidizable catecholamines measured amperometrically by the underlying ITO electrode. We observed a burst of amperometric spikes upon rapid elevation of [Ca2+]i and a “priming” effect of sub-stimulatory [Ca2+]i on the response of cells to subsequent [Ca2+]i elevation, similar to previous reports using different techniques. We conclude that UV photolysis of caged Ca2+ is a suitable stimulation technique for higher-throughput studies of Ca2+-dependent exocytosis on transparent electrochemical microelectrode arrays. PMID:18094774

Exploring the importance of quantum effects in nucleation: The archetypical Nen case

NASA Astrophysics Data System (ADS)

Unn-Toc, Wesley; Halberstadt, Nadine; Meier, Christoph; Mella, Massimo

2012-07-01

The effect of quantum mechanics (QM) on the details of the nucleation process is explored employing Ne clusters as test cases due to their semi-quantal nature. In particular, we investigate the impact of quantum mechanics on both condensation and dissociation rates in the framework of the microcanonical ensemble. Using both classical trajectories and two semi-quantal approaches (zero point averaged dynamics, ZPAD, and Gaussian-based time dependent Hartree, G-TDH) to model cluster and collision dynamics, we simulate the dissociation and monomer capture for Ne8 as a function of the cluster internal energy, impact parameter and collision speed. The results for the capture probability Ps(b) as a function of the impact parameter suggest that classical trajectories always underestimate capture probabilities with respect to ZPAD, albeit at most by 15%-20% in the cases we studied. They also do so in some important situations when using G-TDH. More interestingly, dissociation rates kdiss are grossly overestimated by classical mechanics, at least by one order of magnitude. We interpret both behaviours as mainly due to the reduced amount of kinetic energy available to a quantum cluster for a chosen total internal energy. We also find that the decrease in monomer dissociation energy due to zero point energy effects plays a key role in defining dissociation rates. In fact, semi-quantal and classical results for kdiss seem to follow a common "corresponding states" behaviour when the proper definition of internal and dissociation energies are used in a transition state model estimation of the evaporation rate constants.

The Model Averaging for Dichotomous Response Benchmark Dose (MADr-BMD) Tool

EPA Pesticide Factsheets

Providing quantal response models, which are also used in the U.S. EPA benchmark dose software suite, and generates a model-averaged dose response model to generate benchmark dose and benchmark dose lower bound estimates.

The mechanism of action of aniracetam at synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors: indirect and direct effects on desensitization.

PubMed

Lawrence, J Josh; Brenowitz, Stephan; Trussell, Laurence O

2003-08-01

The mechanism of action of aniracetam on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors was examined in outside-out patches and at glutamatergic synapses in neurons of the chick cochlear nucleus. A combination of rapid-flow analysis, using glutamate as an agonist, and kinetic modeling indicated that aniracetam slows both the rate of channel closing, and the microscopic rates of desensitization, even for partially liganded receptors. Little effect was observed on the rate of recovery from desensitization or on the response to the weakly desensitizing agonist kainate. Aniracetam's effects on receptor deactivation saturated at lower concentrations than its effects on desensitization, suggesting that cooperativity between homologous binding sites was required to regulate desensitization. Analysis of responses to paired pulses of agonist also indicated that AMPA receptors must desensitize partially even after agonist exposures too brief to permit rebinding. In the presence of aniracetam, evoked excitatory synaptic currents (EPSCs) and miniature EPSCs in low quantal-content conditions had decay times similar to the time course of receptor deactivation. Under these conditions, the time course of both transmitter release and clearance must be <1 to 2 ms. However, in high quantal-content conditions, the evoked EPSC in aniracetam decayed with a time course intermediate between deactivation and desensitization, suggesting that the time course of transmitter clearance is prolonged because of pooling of transmitter in the synaptic cleft. Moreover, by comparing the amounts of paired-pulse synaptic depression and patch desensitization prevented by aniracetam, we conclude that significant desensitization occurs in response to rebinding of transmitter to the AMPA receptors.

Presynaptic NCAM Is Required for Motor Neurons to Functionally Expand Their Peripheral Field of Innervation in Partially Denervated Muscles

PubMed Central

Chipman, Peter H.; Schachner, Melitta

2014-01-01

The function of neural cell adhesion molecule (NCAM) expression in motor neurons during axonal sprouting and compensatory reinnervation was explored by partially denervating soleus muscles in mice lacking presynaptic NCAM (Hb9creNCAMflx). In agreement with previous studies, the contractile force of muscles in wild-type (NCAM+/+) mice recovered completely 2 weeks after 75% of the motor innervation was removed because motor unit size increased by 2.5 times. In contrast, similarly denervated muscles in Hb9creNCAMflx mice failed to recover the force lost due to the partial denervation because motor unit size did not change. Anatomical analysis indicated that 50% of soleus end plates were completely denervated 1–4 weeks post-partial denervation in Hb9creNCAMflx mice, while another 25% were partially reinnervated. Synaptic vesicles (SVs) remained at extrasynaptic regions in Hb9creNCAMflx mice rather than being distributed, as occurs normally, to newly reinnervated neuromuscular junctions (NMJs). Electrophysiological analysis revealed two populations of NMJs in partially denervated Hb9creNCAMflx soleus muscles, one with high (mature) quantal content, and another with low (immature) quantal content. Extrasynaptic SVs in Hb9creNCAMflx sprouts were associated with L-type voltage-dependent calcium channel (L-VDCC) immunoreactivity and maintained an immature, L-VDCC-dependent recycling phenotype. Moreover, acute nifedipine treatment potentiated neurotransmission at newly sprouted NMJs, while chronic intraperitoneal treatment with nifedipine during a period of synaptic consolidation enhanced functional motor unit expansion in the absence of presynaptic NCAM. We propose that presynaptic NCAM bridges a critical link between the SV cycle and the functional expansion of synaptic territory through the regulation of L-VDCCs. PMID:25100585

The anatomy of choice: dopamine and decision-making

PubMed Central

Friston, Karl; Schwartenbeck, Philipp; FitzGerald, Thomas; Moutoussis, Michael; Behrens, Timothy; Dolan, Raymond J.

2014-01-01

This paper considers goal-directed decision-making in terms of embodied or active inference. We associate bounded rationality with approximate Bayesian inference that optimizes a free energy bound on model evidence. Several constructs such as expected utility, exploration or novelty bonuses, softmax choice rules and optimism bias emerge as natural consequences of free energy minimization. Previous accounts of active inference have focused on predictive coding. In this paper, we consider variational Bayes as a scheme that the brain might use for approximate Bayesian inference. This scheme provides formal constraints on the computational anatomy of inference and action, which appear to be remarkably consistent with neuroanatomy. Active inference contextualizes optimal decision theory within embodied inference, where goals become prior beliefs. For example, expected utility theory emerges as a special case of free energy minimization, where the sensitivity or inverse temperature (associated with softmax functions and quantal response equilibria) has a unique and Bayes-optimal solution. Crucially, this sensitivity corresponds to the precision of beliefs about behaviour. The changes in precision during variational updates are remarkably reminiscent of empirical dopaminergic responses—and they may provide a new perspective on the role of dopamine in assimilating reward prediction errors to optimize decision-making. PMID:25267823

The anatomy of choice: dopamine and decision-making.

PubMed

Friston, Karl; Schwartenbeck, Philipp; FitzGerald, Thomas; Moutoussis, Michael; Behrens, Timothy; Dolan, Raymond J

2014-11-05

This paper considers goal-directed decision-making in terms of embodied or active inference. We associate bounded rationality with approximate Bayesian inference that optimizes a free energy bound on model evidence. Several constructs such as expected utility, exploration or novelty bonuses, softmax choice rules and optimism bias emerge as natural consequences of free energy minimization. Previous accounts of active inference have focused on predictive coding. In this paper, we consider variational Bayes as a scheme that the brain might use for approximate Bayesian inference. This scheme provides formal constraints on the computational anatomy of inference and action, which appear to be remarkably consistent with neuroanatomy. Active inference contextualizes optimal decision theory within embodied inference, where goals become prior beliefs. For example, expected utility theory emerges as a special case of free energy minimization, where the sensitivity or inverse temperature (associated with softmax functions and quantal response equilibria) has a unique and Bayes-optimal solution. Crucially, this sensitivity corresponds to the precision of beliefs about behaviour. The changes in precision during variational updates are remarkably reminiscent of empirical dopaminergic responses-and they may provide a new perspective on the role of dopamine in assimilating reward prediction errors to optimize decision-making.

The current state of knowledge on the use of the benchmark dose concept in risk assessment.

PubMed

Sand, Salomon; Victorin, Katarina; Filipsson, Agneta Falk

2008-05-01

This review deals with the current state of knowledge on the use of the benchmark dose (BMD) concept in health risk assessment of chemicals. The BMD method is an alternative to the traditional no-observed-adverse-effect level (NOAEL) and has been presented as a methodological improvement in the field of risk assessment. The BMD method has mostly been employed in the USA but is presently given higher attention also in Europe. The review presents a number of arguments in favor of the BMD, relative to the NOAEL. In addition, it gives a detailed overview of the several procedures that have been suggested and applied for BMD analysis, for quantal as well as continuous data. For quantal data the BMD is generally defined as corresponding to an additional or extra risk of 5% or 10%. For continuous endpoints it is suggested that the BMD is defined as corresponding to a percentage change in response relative to background or relative to the dynamic range of response. Under such definitions, a 5% or 10% change can be considered as default. Besides how to define the BMD and its lower bound, the BMDL, the question of how to select the dose-response model to be used in the BMD and BMDL determination is highlighted. Issues of study design and comparison of dose-response curves and BMDs are also covered. Copyright (c) 2007 John Wiley & Sons, Ltd.

APPLICATION OF BENCHMARK DOSE METHODOLOGY TO DATA FROM PRENATAL DEVELOPMENTAL TOXICITY STUDIES

EPA Science Inventory

The benchmark dose (BMD) concept was applied to 246 conventional developmental toxicity datasets from government, industry and commercial laboratories. Five modeling approaches were used, two generic and three specific to developmental toxicity (DT models). BMDs for both quantal ...

PACAP/PAC1R signaling modulates acetylcholine release at neuronal nicotinic synapses

PubMed Central

Pugh, Phyllis C.; Jayakar, Selwyn S.; Margiotta, Joseph F.

2009-01-01

Neuropeptides collaborate with conventional neurotransmitters to regulate synaptic output. Pituitary adenylate cyclase-activating polypeptide (PACAP) co-localizes with acetylcholine in presynaptic nerve terminals, is released by stimulation, and enhances nicotinic acetylcholine receptor- (nAChR-) mediated responses. Such findings implicate PACAP in modulating nicotinic neurotransmission, but relevant synaptic mechanisms have not been explored. We show here that PACAP acts via selective high-affinity G-protein coupled receptors (PAC1Rs) to enhance transmission at nicotinic synapses on parasympathetic ciliary ganglion (CG) neurons by rapidly and persistently increasing the frequency and amplitude of spontaneous, impulse-dependent nicotinic excitatory postsynaptic currents (sEPSCs). Of the canonical adenylate cyclase (AC) and phospholipase-C (PLC) transduction cascades stimulated by PACAP/PAC1R signaling, only AC-generated signals are critical for synaptic modulation since the increases in sEPSC frequency and amplitude were mimicked by 8-Bromo-cAMP, blocked by inhibiting AC or cAMP-dependent protein kinase (PKA), and unaffected by inhibiting PLC. Despite its ability to increase agonist-induced nAChR currents, PACAP failed to influence nAChR-mediated impulse-independent miniature EPSC amplitudes (quantal size). Instead, evoked transmission assays reveal that PACAP/PAC1R signaling increased quantal content, indicating it modulates synaptic function by increasing vesicular ACh release from presynaptic terminals. Lastly, signals generated by the retrograde messenger, nitric oxide- (NO-) are critical for the synaptic modulation since the PACAP-induced increases in spontaneous EPSC frequency, amplitude and quantal content were mimicked by NO donor and absent after inhibiting NO synthase (NOS). These results indicate that PACAP/PAC1R activation recruits AC-dependent signaling that stimulates NOS to increase NO production and control presynaptic transmitter output at neuronal nicotinic synapses. PMID:19958833

Presynaptic and postsynaptic effects of the venom of the Australian tiger snake at the neuromuscular junction

PubMed Central

Datyner, M. E.; Gage, P. W.

1973-01-01

1. Crude venom (TSV) from the Australian tiger snake (Notechis scutatus scutatus) has both presynaptic and postsynaptic effects at the neuromuscular junctions of toads. 2. TSV (50 μg/ml) rapidly blocked indirectly elicited muscle twitches without affecting the compound action potential in the sciatic nerve or twitches elicited by direct stimulation. 3. Low concentrations of the venom (1-10 μg/ml) reduced the amplitude of miniature endplate potentials (m.e.p.ps) and inhibited the depolarization of muscle fibres normally caused by carbachol. It was concluded that a fraction of the venom binds to acetylcholine receptors. 4. The frequency of m.e.p.ps was at first increased by TSV at a concentration of 1 μg/ml. Occasional, high frequency `bursts' of m.e.p.ps were recorded in some preparations. The mean frequency of m.e.p.ps appeared to fall after several hours in the venom. 5. The quantal content of endplate potentials (e.p.ps) was reduced by the venom. With low concentrations (1 μg/ml), an initial increase in quantal content was often seen. When the quantal content was markedly depressed there was no parallel reduction in the amplitude of nerve terminal spikes recorded extracellularly, though a later fall in size and slowing of time course was often seen. 6. There was evidence that TSV eventually changed the normal Poisson characteristics of the spontaneous release of quanta and this may be correlated with electronmicroscopic changes in nerve terminals. 7. Tiger snake antivenene counteracted the postsynaptic, but not the presynaptic effects of TSV when they had developed. PMID:4367126

State-selective charge exchange in slow collisions of Si3+ ions with H atoms: A molecular state close coupling treatment*)

NASA Astrophysics Data System (ADS)

Joseph, Dwayne C.; Saha, Bidhan C.

2012-11-01

Charge transfer cross sections are calculated by employing both the quantal and semiclassical ɛ(R) molecular orbital close coupling (MOCC) approximations in the adiabatic representation and compared with other theoretical and experimental results

Physiological pharmacokinetic modeling

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

Menzel, D.B.

1987-10-01

Risk assessment often defines the approach and the degree of regulation, decisions in risk assessment often have major regulatory impacts. Chemicals that have economic value or that were byproducts of the chemical industry are common subjects of such decisions. Regrettably, decisions related to risk assessment, science, or regulatory matters will frequently be made with incomplete information and on the basis of intuitive reasoning. Statistical fits to experimental data have been used to estimate risks in humans from experimental data in animals. These treatments have not taken into account the obvious differences in physiology, biochemistry, and size between aniamals and humans.more » In this article the use of mathematical models based on continuous relationships, rather than quantal events, are discussed. The mathematical models can be used to adjust the dose in the quantal response model, but the emphasis will be on how these mathematical models are conceived and what implications their use holds for risk assessment. Experiments with humans that produce toxic effects cannot be done. Data for human toxicity will always be lacking.« less

An intangible energy in the functioning biosystem. I: A search for its fate and a proposed method of delivery.

PubMed

Reid, B L

1995-06-01

This paper treats evidence for an increasing recognition of a force with intangible properties in biosystems with special reference to its ability to transport electrons at near 0 degree Kelvin. It is implied that such force, whose demonstration at these temperatures is an experimental contrivance to emphasise its strictly quantal status, can be operative at room temperature. A discussion is entered as to a mode for delivery of intangible energy from demonstrable non-local origins, locally to the cell to provide for structure and function. Extensive use is made of theory of the structure of the photon from de Broglie and others to accommodate a co-existence of real (electromagnetic) and quantal (intangible) fields within the photon and to discuss how such co-existence may have been copied or otherwise made manifest in a macroscopic structure such as the cell. Cell function is then viewed as concurrent real and intangible effects following stimuli derived from perturbation of the real or electromagnetic component.

An improved filter elution and cell culture assay procedure for evaluating public groundwater systems for culturable enteroviruses.

PubMed

Dahling, Daniel R

2002-01-01

Large-scale virus studies of groundwater systems require practical and sensitive procedures for both sample processing and viral assay. Filter adsorption-elution procedures have traditionally been used to process large-volume water samples for viruses. In this study, five filter elution procedures using cartridge filters were evaluated for their effectiveness in processing samples. Of the five procedures tested, the third method, which incorporated two separate beef extract elutions (one being an overnight filter immersion in beef extract), recovered 95% of seeded poliovirus compared with recoveries of 36 to 70% for the other methods. For viral enumeration, an expanded roller bottle quantal assay was evaluated using seeded poliovirus. This cytopathic-based method was considerably more sensitive than the standard plaque assay method. The roller bottle system was more economical than the plaque assay for the evaluation of comparable samples. Using roller bottles required less time and manipulation than the plaque procedure and greatly facilitated the examination of large numbers of samples. The combination of the improved filter elution procedure and the roller bottle assay for viral analysis makes large-scale virus studies of groundwater systems practical. This procedure was subsequently field tested during a groundwater study in which large-volume samples (exceeding 800 L) were processed through the filters.

Uniform semiclassical sudden approximation for rotationally inelastic scattering

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

Korsch, H.J.; Schinke, R.

1980-08-01

The infinite-order-sudden (IOS) approximation is investigated in the semiclassical limit. A simplified IOS formula for rotationally inelastic differential cross sections is derived involving a uniform stationary phase approximation for two-dimensional oscillatory integrals with two stationary points. The semiclassical analysis provides a quantitative description of the rotational rainbow structure in the differential cross section. The numerical calculation of semiclassical IOS cross sections is extremely fast compared to numerically exact IOS methods, especially if high ..delta..j transitions are involved. Rigid rotor results for He--Na/sub 2/ collisions with ..delta..j< or approx. =26 and for K--CO collisions with ..delta..j< or approx. =70 show satisfactorymore » agreement with quantal IOS calculations.« less

Non-stochastic sampling error in quantal analyses for Campylobacter species on poultry products

USDA-ARS?s Scientific Manuscript database

Using primers and fluorescent probes specific for the most common foodborne Campylobacter species (C. jejuni = Cj and C. coli = Cc), we developed a multiplex, most probable number (MPN) assay using quantitative PCR (qPCR) as the determinant for binomial detection: number of p positives out of n = 6 ...

Quantum Optical Aspects of Topological Phases, Such as Berry’s Phase

DTIC Science & Technology

1993-11-10

by Franson, and by Home, Shimosy and Zeilinger , in two recent Physical Review Leuers (62, 2205 and 2209 (1989)), in order to observe a purely quantal...interferometer. We also set up a two-photon interferometer, similar to the ones suggested by Franson, and by Home, Shimony and Zeilinger , in two

Quantal Study of the Exchange Reaction for N + N2 using an ab initio Potential Energy Surface

NASA Technical Reports Server (NTRS)

Wang, Dunyou; Stallcop, James R.; Huo, Winifred M.; Dateo, Christopher E.; Schwenke, David W.; Partridge, Harry; Kwak, Dochan (Technical Monitor)

2002-01-01

The N + N2 exchange rate is calculated using a time-dependent quantum dynamics method on a newly determined ab initio potential energy surface (PES) for the ground A" state. This ab initio PES shows a double barrier feature in the interaction region with the barrier height at 47.2 kcal/mol, and a shallow well between these two barriers, with the minimum at 43.7 kcal/mol. A quantum dynamics wave packet calculation has been carried out using the fitted PES to compute the cumulative reaction probability for the exchange reaction of N + N2(J=O). The J - K shift method is then employed to obtain the rate constant for this reaction. The calculated rate constant is compared with experimental data and a recent quasi-classical calculation using a LEPS PES. Significant differences are found between the present and quasiclassical results. The present rate calculation is the first accurate 3D quantal dynamics study for N + N2 reaction system and the ab initio PES reported here is the first such surface for N3.

Fabrication of two-layer poly(dimethyl siloxane) devices for hydrodynamic cell trapping and exocytosis measurement with integrated indium tin oxide microelectrodes arrays

PubMed Central

Gao, Changlu; Sun, Xiuhua; Gillis, Kevin D.

2016-01-01

The design, fabrication and test of a microfluidic cell trapping device to measure single cell exocytosis were reported. Research on the patterning of double layer template based on repetitive standard photolithography of AZ photoresist was investigated. The replicated poly(dimethyl siloxane) devices with 2.5 μm deep channels were proved to be efficient for stopping cells. Quantal exocytosis measurement can be achieved by targeting single or small clumps of chromaffin cells on top of the 10 μm ×10 μm indium tin oxide microelectrodes arrays with the developed microdevice. And about 72% of the trapping sites can be occupied by cells with hydrodynamic trapping method and the recorded amperometric signals are comparable to the results with traditional carbon fiber microelectrodes. The method of manufacturing the microdevices is simple, low-cost and easy to perform. The manufactured device offers a platform for the high throughput detection of quantal catecholamine exocytosis from chromaffin cells with sufficient sensitivity and broad application. PMID:23329291

Single-Pixel Optical Fluctuation Analysis of Calcium Channel Function in Active Zones of Motor Nerve Terminals

PubMed Central

Luo, Fujun; Dittrich, Markus; Stiles, Joel R.; Meriney, Stephen D.

2011-01-01

We used high-resolution fluorescence imaging and single-pixel optical fluctuation analysis to estimate the opening probability of individual voltage-gated calcium (Ca2+) channels during an action potential and the number of such Ca2+ channels within active zones of frog neuromuscular junctions. Analysis revealed ~36 Ca2+ channels within each active zone, similar to the number of docked synaptic vesicles but far less than the total number of transmembrane particles reported based on freeze-fracture analysis (~200–250). The probability that each channel opened during an action potential was only ~0.2. These results suggest why each active zone averages only one quantal release event during every other action potential, despite a substantial number of docked vesicles. With sparse Ca2+ channels and low opening probability, triggering of fusion for each vesicle is primarily controlled by Ca2+ influx through individual Ca2+ channels. In contrast, the entire synapse is highly reliable because it contains hundreds of active zones. PMID:21813687

BMDS 2.0 BETA WITH NEW QUANTAL MODEL DEVELOPMENT EXTERNAL REVIEW REPORTS AND SUPPORTING DOCUMENTS

EPA Science Inventory

With the availability of BMDS 2.0 on the BMDS web site, EPA is providing (a) results of the external review (charge to reviewers and reviewer comments), (b) EPA responses to the review comments, and (c) a report describing development and testing of the models in BMDS 2.0 with ne...

The Quantal Larynx: The Stable Regions of Laryngeal Biomechanics and Implications for Speech Production

ERIC Educational Resources Information Center

Moisik, Scott Reid; Gick, Bryan

2017-01-01

Purpose: Recent proposals suggest that (a) the high dimensionality of speech motor control may be reduced via modular neuromuscular organization that takes advantage of intrinsic biomechanical regions of stability and (b) computational modeling provides a means to study whether and how such modularization works. In this study, the focus is on the…

Benchmark dose analysis via nonparametric regression modeling

PubMed Central

Piegorsch, Walter W.; Xiong, Hui; Bhattacharya, Rabi N.; Lin, Lizhen

2013-01-01

Estimation of benchmark doses (BMDs) in quantitative risk assessment traditionally is based upon parametric dose-response modeling. It is a well-known concern, however, that if the chosen parametric model is uncertain and/or misspecified, inaccurate and possibly unsafe low-dose inferences can result. We describe a nonparametric approach for estimating BMDs with quantal-response data based on an isotonic regression method, and also study use of corresponding, nonparametric, bootstrap-based confidence limits for the BMD. We explore the confidence limits’ small-sample properties via a simulation study, and illustrate the calculations with an example from cancer risk assessment. It is seen that this nonparametric approach can provide a useful alternative for BMD estimation when faced with the problem of parametric model uncertainty. PMID:23683057

The Recurrent Case for the Renshaw Cell

PubMed Central

Bhumbra, Gardave S.; Bannatyne, B. Anne; Watanabe, Masahiko; Todd, Andrew J.

2014-01-01

Although Renshaw cells (RCs) were discovered over half a century ago, their precise role in recurrent inhibition and ability to modulate motoneuron excitability have yet to be established. Indirect measurements of recurrent inhibition have suggested only a weak modulatory effect but are limited by the lack of observed motoneuron responses to inputs from single RCs. Here we present dual recordings between connected RC–motoneuron pairs, performed on mouse spinal cord. Motoneuron responses demonstrated that Renshaw synapses elicit large inhibitory conductances and show short-term potentiation. Anatomical reconstruction, combined with a novel method of quantal analysis, showed that the strong inhibitory input from RCs results from the large number of synaptic contacts that they make onto individual motoneurons. We used the NEURON simulation environment to construct realistic electrotonic models, which showed that inhibitory conductances from Renshaw inputs exert considerable shunting effects in motoneurons and reduce the frequency of spikes generated by excitatory inputs. This was confirmed experimentally by showing that excitation of a single RC or selective activation of the recurrent inhibitory pathway to generate equivalent inhibitory conductances both suppress motoneuron firing. We conclude that recurrent inhibition is remarkably effective, in that a single action potential from one RC is sufficient to silence a motoneuron. Although our results may differ from previous indirect observations, they underline a need for a reevaluation of the role that RCs perform in one of the first neuronal circuits to be discovered. PMID:25232126

Social Learning in the Ultimatum Game

PubMed Central

Zhang, Boyu

2013-01-01

In the ultimatum game, two players divide a sum of money. The proposer suggests how to split and the responder can accept or reject. If the suggestion is rejected, both players get nothing. The rational solution is that the responder accepts even the smallest offer but humans prefer fair share. In this paper, we study the ultimatum game by a learning-mutation process based on quantal response equilibrium, where players are assumed boundedly rational and make mistakes when estimating the payoffs of strategies. Social learning is never stabilized at the fair outcome or the rational outcome, but leads to oscillations from offering 40 percent to 50 percent. To be precise, there is a clear tendency to increase the mean offer if it is lower than 40 percent, but will decrease when it reaches the fair offer. If mutations occur rarely, fair behavior is favored in the limit of local mutation. If mutation rate is sufficiently high, fairness can evolve for both local mutation and global mutation. PMID:24023950

Detection of endogenous lithium in neuropsychiatric disorders--a model for biological transmutation.

PubMed

Kurup, Ravi Kumar; Kurup, Parameswara Achutha

2002-01-01

The human hypothalamus produces an endogenous membrane Na(+)-K(+) ATPase inhibitor, digoxin. A digoxin induced model of cellular/neuronal quantal state and perception has been described by the authors. Biological transmutation has been described in microbial systems in the quantal state. The study focuses on the plasma levels of digoxin, RBC membrane Na(+)-K(+) ATPase activity, plasma levels of magnesium and lithium in neuropsychiatric and systemic disorders. Inhibition of RBC membrane Na(+)-K(+) ATPase activity was observed in most cases along with an increase in the levels of serum digoxin and lithium and a decrease in the level of serum Mg(++). The generation of endogenous lithium would obviously occur due to biological transmutation from magnesium. Digoxin and lithium together can produce added membrane Na(+)-K(+) ATPase inhibition. The role of membrane Na(+)-K(+) ATPase inhibition in the pathogenesis of neuropsychiatric and systemic disorders is discussed. The inhibition of membrane Na(+)-K(+) ATPase can contribute to an increase in intracellular calcium and a decrease in magnesium, which can result in a defective neurotransmitter transport mechanism, mitochondrial dysfunction and apoptosis, defective golgi body function and protein processing dysfunction, immune dysfunction and oncogenesis. Copyright 2002 John Wiley & Sons, Ltd.

Receptor-mediated presynaptic facilitation of quantal release of acetylcholine induced by pralidoxime in Aplysia.

PubMed

Fossier, P; Baux, G; Poulain, B; Tauc, L

1990-09-01

1. Possible interactions of contrathion (pralidoxime sulfomethylate), a reactivator of phosphorylated acetylcholinesterase (AChE), with the regulation of cholinergic transmission were investigated on an identified synapse in the buccal ganglion of Aplysia californica. 2. Transmitter release was evoked either by a presynaptic action potential or, under voltage clamp, by a long depolarization of the presynaptic cell. At concentrations higher than 10(-5) M, bath-applied contrathion decreased the amplitude of miniature postsynaptic currents and increased their decay time. At the same time, the quantal release of ACh was transiently facilitated. The facilitatory effect of contrathion was prevented by tubocurarine but not by atropine. Because in this preparation, these drugs block, respectively, the presynaptic nicotinic-like and muscarinic-like receptors involved in positive and negative feedback of ACh release, we proposed that contrathion activates presynaptic nicotinic-like receptors. 3. Differential desensitization of the presynaptic receptors is proposed to explain the transience of the facilitatory action of contrathion on ACh release. 4. The complexity of the synaptic action of contrathion raises the possibility that its therapeutic effects in AChE poisonings are not limited to AChE reactivation.

The Unitality of Quantum B-algebras

NASA Astrophysics Data System (ADS)

Han, Shengwei; Xu, Xiaoting; Qin, Feng

2018-02-01

Quantum B-algebras as a generalization of quantales were introduced by Rump and Yang, which cover the majority of implicational algebras and provide a unified semantic for a wide class of substructural logics. Unital quantum B-algebras play an important role in the classification of implicational algebras. The main purpose of this paper is to construct unital quantum B-algebras from non-unital quantum B-algebras.

The effects of two phospholipase A2 inhibitors on the neuromuscular blocking activities of homologous phospholipases A2 from the venom of Pseudechis australis, the Australian king brown snake.

PubMed

Fatehi, M; Rowan, E G; Harvey, A L

1995-12-01

Previous studies have shown that homologous phospholipases A2 (PLA2) (Pa-3, Pa-9C, Pa-10F and Pa-11) from the venom of the Australian king brown snake, Pseudechis australis, significantly reduce the resting membrane potentials and quantal contents of endplate potentials recorded from endplate regions of mouse triangularis sterni nerve-muscle preparations. It is not clear whether PLA2 activity is essential for their neuromuscular activities. Therefore, pharmacological studies were carried out to determine whether neuromuscular activity of the toxins changed after treatment with the phospholipase A2 inhibitors 7,7-dimethyl-eicosadienoic acid (DEDA) and manoalide. After incubation of the toxins with manoalide (120 nM), or DEDA (50 microM), no PLA2 activity against 1-stearoyl 2-[3H]arachidonoylglycerophosphocholine was detected. After incubation with manoalide and/or DEDA, the toxins did not depolarize muscle fibre membranes up to 60 min after administration. However, manoalide and DEDA had different influences on the inhibitory effect of these toxic enzymes on acetylcholine release from nerve terminals. Manoalide abolished the inhibitory effect of the toxins on evoked release of acetylcholine. In contrast, DEDA was not able to prevent the reduction of quantal content of endplate potentials induced by the toxins. This study provides evidence that the depolarizing action and the inhibitory effect on release of acetylcholine exerted by these toxic PLA2 from king brown snake are independent phenomena. The evidence for this conclusion was that inhibition of enzymatic activity with an arachidonic acid analogue (DEDA) abolished the depolarizing effect of the toxins but not the effects on the quantal release of acetylcholine from mouse motor nerve terminals. The data suggest that the depolarizing effect of these toxins is probably due to the enzymatic activity. Since manoalide interacts with lysine residues of PLA2 polypeptides, and, as shown here, manoalide prevented inhibition of neurotransmitter release, lysine residues may play an important role in the inhibitory activity of these toxins.

Interaction of aberrations, diffraction, and quantal fluctuations determine the impact of pupil size on visual quality.

PubMed

Xu, Renfeng; Wang, Huachun; Thibos, Larry N; Bradley, Arthur

2017-04-01

Our purpose is to develop a computational approach that jointly assesses the impact of stimulus luminance and pupil size on visual quality. We compared traditional optical measures of image quality and those that incorporate the impact of retinal illuminance dependent neural contrast sensitivity. Visually weighted image quality was calculated for a presbyopic model eye with representative levels of chromatic and monochromatic aberrations as pupil diameter was varied from 7 to 1 mm, stimulus luminance varied from 2000 to 0.1  cd/m², and defocus varied from 0 to -2 diopters. The model included the effects of quantal fluctuations on neural contrast sensitivity. We tested the model's predictions for five cycles per degree gratings by measuring contrast sensitivity at 5  cyc/deg. Unlike the traditional Strehl ratio and the visually weighted area under the modulation transfer function, the visual Strehl ratio derived from the optical transfer function was able to capture the combined impact of optics and quantal noise on visual quality. In a well-focused eye, provided retinal illuminance is held constant as pupil size varies, visual image quality scales approximately as the square root of illuminance because of quantum fluctuations, but optimum pupil size is essentially independent of retinal illuminance and quantum fluctuations. Conversely, when stimulus luminance is held constant (and therefore illuminance varies with pupil size), optimum pupil size increases as luminance decreases, thereby compensating partially for increased quantum fluctuations. However, in the presence of -1 and -2 diopters of defocus and at high photopic levels where Weber's law operates, optical aberrations and diffraction dominate image quality and pupil optimization. Similar behavior was observed in human observers viewing sinusoidal gratings. Optimum pupil size increases as stimulus luminance drops for the well-focused eye, and the benefits of small pupils for improving defocused image quality remain throughout the photopic and mesopic ranges. However, restricting pupils to <2  mm will cause significant reductions in the best focus vision at low photopic and mesopic luminances.

Emergence of scale-free characteristics in socio-ecological systems with bounded rationality

PubMed Central

Kasthurirathna, Dharshana; Piraveenan, Mahendra

2015-01-01

Socio–ecological systems are increasingly modelled by games played on complex networks. While the concept of Nash equilibrium assumes perfect rationality, in reality players display heterogeneous bounded rationality. Here we present a topological model of bounded rationality in socio-ecological systems, using the rationality parameter of the Quantal Response Equilibrium. We argue that system rationality could be measured by the average Kullback–-Leibler divergence between Nash and Quantal Response Equilibria, and that the convergence towards Nash equilibria on average corresponds to increased system rationality. Using this model, we show that when a randomly connected socio-ecological system is topologically optimised to converge towards Nash equilibria, scale-free and small world features emerge. Therefore, optimising system rationality is an evolutionary reason for the emergence of scale-free and small-world features in socio-ecological systems. Further, we show that in games where multiple equilibria are possible, the correlation between the scale-freeness of the system and the fraction of links with multiple equilibria goes through a rapid transition when the average system rationality increases. Our results explain the influence of the topological structure of socio–ecological systems in shaping their collective cognitive behaviour, and provide an explanation for the prevalence of scale-free and small-world characteristics in such systems. PMID:26065713

The Effect of Neural Noise on Spike Time Precision in a Detailed CA3 Neuron Model

PubMed Central

Kuriscak, Eduard; Marsalek, Petr; Stroffek, Julius; Wünsch, Zdenek

2012-01-01

Experimental and computational studies emphasize the role of the millisecond precision of neuronal spike times as an important coding mechanism for transmitting and representing information in the central nervous system. We investigate the spike time precision of a multicompartmental pyramidal neuron model of the CA3 region of the hippocampus under the influence of various sources of neuronal noise. We describe differences in the contribution to noise originating from voltage-gated ion channels, synaptic vesicle release, and vesicle quantal size. We analyze the effect of interspike intervals and the voltage course preceding the firing of spikes on the spike-timing jitter. The main finding of this study is the ranking of different noise sources according to their contribution to spike time precision. The most influential is synaptic vesicle release noise, causing the spike jitter to vary from 1 ms to 7 ms of a mean value 2.5 ms. Of second importance was the noise incurred by vesicle quantal size variation causing the spike time jitter to vary from 0.03 ms to 0.6 ms. Least influential was the voltage-gated channel noise generating spike jitter from 0.02 ms to 0.15 ms. PMID:22778784

Emergence of scale-free characteristics in socio-ecological systems with bounded rationality.

PubMed

Kasthurirathna, Dharshana; Piraveenan, Mahendra

2015-06-11

Socio-ecological systems are increasingly modelled by games played on complex networks. While the concept of Nash equilibrium assumes perfect rationality, in reality players display heterogeneous bounded rationality. Here we present a topological model of bounded rationality in socio-ecological systems, using the rationality parameter of the Quantal Response Equilibrium. We argue that system rationality could be measured by the average Kullback--Leibler divergence between Nash and Quantal Response Equilibria, and that the convergence towards Nash equilibria on average corresponds to increased system rationality. Using this model, we show that when a randomly connected socio-ecological system is topologically optimised to converge towards Nash equilibria, scale-free and small world features emerge. Therefore, optimising system rationality is an evolutionary reason for the emergence of scale-free and small-world features in socio-ecological systems. Further, we show that in games where multiple equilibria are possible, the correlation between the scale-freeness of the system and the fraction of links with multiple equilibria goes through a rapid transition when the average system rationality increases. Our results explain the influence of the topological structure of socio-ecological systems in shaping their collective cognitive behaviour, and provide an explanation for the prevalence of scale-free and small-world characteristics in such systems.

The Role of Neurotrophins in Neurotransmitter Release

PubMed Central

Tyler, William J.; Perrett, Stephen P.; Pozzo-Miller, Lucas D.

2009-01-01

The neurotrophins (NTs) have recently been shown to elicit pronounced effects on quantal neurotransmitter release at both central and peripheral nervous system synapses. Due to their activity-dependent release, as well as the subcellular localization of both protein and receptor, NTs are ideally suited to modify the strength of neuronal connections by “fine-tuning” synaptic activity through direct actions at presynaptic terminals. Here, using BDNF as a prototypical example, the authors provide an update of recent evidence demonstrating that NTs enhance quantal neurotransmitter release at synapses through presynaptic mechanisms. The authors further propose that a potential target for NT actions at presynaptic terminals is the mechanism by which terminals retrieve synaptic vesicles after exocytosis. Depending on the temporal demands placed on synapses during high-frequency synaptic transmission, synapses may use two alternative modes of synaptic vesicle retrieval, the conventional slow endosomal recycling or a faster rapid retrieval at the active zone, referred to as “kiss-and-run.” By modulating Ca2+ microdomains associated with voltage-gated Ca2+ channels at active zones, NTs may elicit a switch from the slow to the fast mode of endocytosis of vesicles at presynaptic terminals during high-frequency synaptic transmission, allowing more reliable information transfer and neuronal signaling in the central nervous system. PMID:12467374

The role of neurotrophins in neurotransmitter release.

PubMed

Tyler, William J; Perrett, Stephen P; Pozzo-Miller, Lucas D

2002-12-01

The neurotrophins (NTs) have recently been shown to elicit pronounced effects on quantal neurotransmitter release at both central and peripheral nervous system synapses. Due to their activity-dependent release, as well as the subcellular localization of both protein and receptor, NTs are ideally suited to modify the strength of neuronal connections by "fine-tuning" synaptic activity through direct actions at presynaptic terminals. Here, using BDNF as a prototypical example, the authors provide an update of recent evidence demonstrating that NTs enhance quantal neurotransmitter release at synapses through presynaptic mechanisms. The authors further propose that a potential target for NT actions at presynaptic terminals is the mechanism by which terminals retrieve synaptic vesicles after exocytosis. Depending on the temporal demands placed on synapses during high-frequency synaptic transmission, synapses may use two alternative modes of synaptic vesicle retrieval, the conventional slow endosomal recycling or a faster rapid retrieval at the active zone, referred to as "kiss-and-run." By modulating Ca2+ microdomains associated with voltage-gated Ca2+ channels at active zones, NTs may elicit a switch from the slow to the fast mode of endocytosis of vesicles at presynaptic terminals during high-frequency synaptic transmission, allowing more reliable information transfer and neuronal signaling in the central nervous system.

An intangible energy in the functioning biosystem. II: Useful parallels with circuit theory and with non-linear optics.

PubMed

Reid, B L

1995-06-01

The argument is developed that a structure and function already exists in selected inanimate systems for an intangible energy dissipating these systems and that, in so doing, this energy exhibits certain properties, readily recognised in the functioning biosystem. The central thesis is that, during dissipation, the structure of the biosystem affords opportunity for an enhanced display of these properties, so that this structure can be rationally recognised as obligatory in the transition, inanimate to animate matter. The systems chosen are those of reactance in linear circuit theory of electronics, and some recent developments in non-linear optics, both of which rely on imaginary or quantal force to display observable effects. Discussion occurs on the fashion which the development of a statistical formalism as a basis for the study of squeezed states of light in these non-linear systems, has, at the same time, overcome a long standing veto on the practical use of quantal energy associated with the Uncertainty Principle of Heisenberg. These ideas are used to vindicate the suggestion that a theoretical basis is presently available for an engineering type approach, toward an intangible force as it exists in the biosystem. The origins and properties of such a force continue to be considered by many as immersed in mysticism.

Nonparametric estimation of benchmark doses in environmental risk assessment

PubMed Central

Piegorsch, Walter W.; Xiong, Hui; Bhattacharya, Rabi N.; Lin, Lizhen

2013-01-01

Summary An important statistical objective in environmental risk analysis is estimation of minimum exposure levels, called benchmark doses (BMDs), that induce a pre-specified benchmark response in a dose-response experiment. In such settings, representations of the risk are traditionally based on a parametric dose-response model. It is a well-known concern, however, that if the chosen parametric form is misspecified, inaccurate and possibly unsafe low-dose inferences can result. We apply a nonparametric approach for calculating benchmark doses, based on an isotonic regression method for dose-response estimation with quantal-response data (Bhattacharya and Kong, 2007). We determine the large-sample properties of the estimator, develop bootstrap-based confidence limits on the BMDs, and explore the confidence limits’ small-sample properties via a short simulation study. An example from cancer risk assessment illustrates the calculations. PMID:23914133

Noise deconvolution based on the L1-metric and decomposition of discrete distributions of postsynaptic responses.

PubMed

Astrelin, A V; Sokolov, M V; Behnisch, T; Reymann, K G; Voronin, L L

1997-04-25

A statistical approach to analysis of amplitude fluctuations of postsynaptic responses is described. This includes (1) using a L1-metric in the space of distribution functions for minimisation with application of linear programming methods to decompose amplitude distributions into a convolution of Gaussian and discrete distributions; (2) deconvolution of the resulting discrete distribution with determination of the release probabilities and the quantal amplitude for cases with a small number (< 5) of discrete components. The methods were tested against simulated data over a range of sample sizes and signal-to-noise ratios which mimicked those observed in physiological experiments. In computer simulation experiments, comparisons were made with other methods of 'unconstrained' (generalized) and constrained reconstruction of discrete components from convolutions. The simulation results provided additional criteria for improving the solutions to overcome 'over-fitting phenomena' and to constrain the number of components with small probabilities. Application of the programme to recordings from hippocampal neurones demonstrated its usefulness for the analysis of amplitude distributions of postsynaptic responses.

Topology-dependent rationality and quantal response equilibria in structured populations

NASA Astrophysics Data System (ADS)

Roman, Sabin; Brede, Markus

2017-05-01

Given that the assumption of perfect rationality is rarely met in the real world, we explore a graded notion of rationality in socioecological systems of networked actors. We parametrize an actors' rationality via their place in a social network and quantify system rationality via the average Jensen-Shannon divergence between the games Nash and logit quantal response equilibria. Previous work has argued that scale-free topologies maximize a system's overall rationality in this setup. Here we show that while, for certain games, it is true that increasing degree heterogeneity of complex networks enhances rationality, rationality-optimal configurations are not scale-free. For the Prisoner's Dilemma and Stag Hunt games, we provide analytic arguments complemented by numerical optimization experiments to demonstrate that core-periphery networks composed of a few dominant hub nodes surrounded by a periphery of very low degree nodes give strikingly smaller overall deviations from rationality than scale-free networks. Similarly, for the Battle of the Sexes and the Matching Pennies games, we find that the optimal network structure is also a core-periphery graph but with a smaller difference in the average degrees of the core and the periphery. These results provide insight on the interplay between the topological structure of socioecological systems and their collective cognitive behavior, with potential applications to understanding wealth inequality and the structural features of the network of global corporate control.

Surface-modified CMOS IC electrochemical sensor array targeting single chromaffin cells for highly parallel amperometry measurements.

PubMed

Huang, Meng; Delacruz, Joannalyn B; Ruelas, John C; Rathore, Shailendra S; Lindau, Manfred

2018-01-01

Amperometry is a powerful method to record quantal release events from chromaffin cells and is widely used to assess how specific drugs modify quantal size, kinetics of release, and early fusion pore properties. Surface-modified CMOS-based electrochemical sensor arrays allow simultaneous recordings from multiple cells. A reliable, low-cost technique is presented here for efficient targeting of single cells specifically to the electrode sites. An SU-8 microwell structure is patterned on the chip surface to provide insulation for the circuitry as well as cell trapping at the electrode sites. A shifted electrode design is also incorporated to increase the flexibility of the dimension and shape of the microwells. The sensitivity of the electrodes is validated by a dopamine injection experiment. Microwells with dimensions slightly larger than the cells to be trapped ensure excellent single-cell targeting efficiency, increasing the reliability and efficiency for on-chip single-cell amperometry measurements. The surface-modified device was validated with parallel recordings of live chromaffin cells trapped in the microwells. Rapid amperometric spikes with no diffusional broadening were observed, indicating that the trapped and recorded cells were in very close contact with the electrodes. The live cell recording confirms in a single experiment that spike parameters vary significantly from cell to cell but the large number of cells recorded simultaneously provides the statistical significance.

Topology-dependent rationality and quantal response equilibria in structured populations.

PubMed

Roman, Sabin; Brede, Markus

2017-05-01

Given that the assumption of perfect rationality is rarely met in the real world, we explore a graded notion of rationality in socioecological systems of networked actors. We parametrize an actors' rationality via their place in a social network and quantify system rationality via the average Jensen-Shannon divergence between the games Nash and logit quantal response equilibria. Previous work has argued that scale-free topologies maximize a system's overall rationality in this setup. Here we show that while, for certain games, it is true that increasing degree heterogeneity of complex networks enhances rationality, rationality-optimal configurations are not scale-free. For the Prisoner's Dilemma and Stag Hunt games, we provide analytic arguments complemented by numerical optimization experiments to demonstrate that core-periphery networks composed of a few dominant hub nodes surrounded by a periphery of very low degree nodes give strikingly smaller overall deviations from rationality than scale-free networks. Similarly, for the Battle of the Sexes and the Matching Pennies games, we find that the optimal network structure is also a core-periphery graph but with a smaller difference in the average degrees of the core and the periphery. These results provide insight on the interplay between the topological structure of socioecological systems and their collective cognitive behavior, with potential applications to understanding wealth inequality and the structural features of the network of global corporate control.

Synaptic and vesicular co-localization of the glutamate transporters VGLUT1 and VGLUT2 in the mouse hippocampus.

PubMed

Herzog, Etienne; Takamori, Shigeo; Jahn, Reinhard; Brose, Nils; Wojcik, Sonja M

2006-11-01

Vesicular glutamate transporters (VGLUTs) are essential to glutamatergic synapses and determine the glutamatergic phenotype of neurones. The three known VGLUT isoforms display nearly identical uptake characteristics, but the associated expression domains in the adult rodent brain are largely segregated. Indeed, indirect evidence obtained in young VGLUT1-deficient mice indicated that in cells that co-express VGLUT1 and VGLUT2, the transporters may be targeted to different synaptic vesicles, which may populate different types of synapses formed by the same neurone. Direct evidence for a systematic segregation of VGLUT1 and VGLUT2 to distinct synapses and vesicles is lacking, and the mechanisms that may convey this segregation are not known. We show here that VGLUT1 and VGLUT2 are co-localized in many layers of the young hippocampus. Strikingly, VGLUT2 co-localizes with VGLUT1 in the mossy fibers at early stages. Furthermore, we show that a fraction of VGLUT1 and VGLUT2 is carried by the same vesicles at these stages. Hence, hippocampal neurones co-expressing VGLUT1 and VGLUT2 do not appear to sort them to separate vesicle pools. As the number of transporter molecules per vesicle affects quantal size, the developmental window where VGLUT1 and VGLUT2 are co-expressed may allow for greater plasticity in the control of quantal release.

Fully quantal calculation of H{sub 2} translation-rotation states in the (p-H{sub 2}){sub 2}@5{sup 12}6{sup 4} clathrate hydrate inclusion compound

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

Felker, Peter M., E-mail: felker@chem.ucla.edu

2014-11-14

The quantal translation-rotation (TR) states of the (p-H{sub 2}){sub 2}@5{sup 12}6{sup 4} clathrate hydrate inclusion compound have been computed. The ten-dimensional problem (in the rigid-cage and rigid-H{sub 2} approximation) is solved by first approximating the H{sub 2} moieties as spherically symmetric and solving for their 6D translational eigenstates. These are then combined with H{sub 2} free rotational states in a product basis that is used to diagonalize the full TR hamiltonian. The computed low-energy eigenstates have translational components that are essentially identical to the 6D translational eigenstates and rotational components that are 99.9% composed of rotationally unexcited H{sub 2} moieties.more » In other words, TR coupling is minimal for the low-energy states of the species. The low-energy level structure is found to be substantially more congested than that of the more tightly packed (p-H{sub 2}){sub 4}@5{sup 12}6{sup 4} clathrate species. The level structure is also shown to be understandable in terms of a model of (H{sub 2}){sub 2} as a semirigid diatomic species consisting of two spherically symmetric H{sub 2} pseudo-atoms.« less

Comparison of the Dichotomous and Polychotomous Quantal Response Models.

DTIC Science & Technology

1983-12-01

containers are submitted to a drop height test, the response is "broken" or "not broken" . In drug testing, if the houseflies are exposed to a...particular insecticide, the number of houseflies that are either dead or alive can be observed. Usually, the tolerance distribution assumes the form of a...01,02,...,0s. In the housefly example, for a - 3. 01 = dead, 02 = moribund, 03 - alive. For s > 3, the 0 i’s represent decreasing degrees of

The boundary is mixed

NASA Astrophysics Data System (ADS)

Bianchi, Eugenio; Haggard, Hal M.; Rovelli, Carlo

2017-08-01

We show that in Oeckl's boundary formalism the boundary vectors that do not have a tensor form represent, in a precise sense, statistical states. Therefore the formalism incorporates quantum statistical mechanics naturally. We formulate general-covariant quantum statistical mechanics in this language. We illustrate the formalism by showing how it accounts for the Unruh effect. We observe that the distinction between pure and mixed states weakens in the general covariant context, suggesting that local gravitational processes are naturally statistical without a sharp quantal versus probabilistic distinction.

An Extension of the Krieger-Li-Iafrate Approximation to the Optimized-Effective-Potential Method

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

Wilson, B.G.

1999-11-11

The Krieger-Li-Iafrate approximation can be expressed as the zeroth order result of an unstable iterative method for solving the integral equation form of the optimized-effective-potential method. By pre-conditioning the iterate a first order correction can be obtained which recovers the bulk of quantal oscillations missing in the zeroth order approximation. A comparison of calculated total energies are given with Krieger-Li-Iafrate, Local Density Functional, and Hyper-Hartree-Fock results for non-relativistic atoms and ions.

Quantal Response: Nonparametric Modeling

DTIC Science & Technology

2017-01-01

DATES COVERED (From ‐ To) 4. TITLE AND SUBTITLE    5a. CONTRACT NUMBER  5b. GRANT NUMBER  5c. PROGRAM  ELEMENT  NUMBER 6. AUTHOR(S)    5d...creasing function as P(x) = G ( f (x) ) , where G is a monotone function such as the standard logistic, normal, or Cauchy CDF. Finite -dimensional...examples with dimension k = 5 where various colors distinguish the basis elements . Figure 3 shows logistic response estimates for these 3 basis sets

Relativistic extended Thomas-Fermi calculations with exchange term contributions

NASA Astrophysics Data System (ADS)

Haddad, S.; Weigel, M. K.

1994-10-01

In this investigation we present self-consistent relativistic extended Thomas-Fermi (ETF) and extended Thomas-Fermi-Fock (ETFF) approaches, derived from the semiclassical treatment of the relativistic nuclear Hartree-Fock problem. The approximations are used to describe the ground-state properties of finite nuclei. The resulting equations are solved numerically for several one-boson-exchange (OBE) lagrangians. The results are discussed and compared with the outcome of full quantal Hartree and Hartree-Fock calculations, other semiclassical treatments and experimental data.

Quantal Response: Estimation and Inference

DTIC Science & Technology

2014-09-01

considered. The CI-based test is just another way of looking at the Wald test. A small-sample simulation illustrates aberrant behavior of the Wald/CI...asymptotic power computation (Eq. 36) exhibits this behavior but not to such an extent as the simulated small-sample power. Sample size is n = 11 and...as |m1−m0| increases, but the power of the Wald test actually decreases for large |m1−m0| and eventually π → α . This type of behavior was reported as

Considerations in the statistical analysis of clinical trials in periodontitis.

PubMed

Imrey, P B

1986-05-01

Adult periodontitis has been described as a chronic infectious process exhibiting sporadic, acute exacerbations which cause quantal, localized losses of dental attachment. Many analytic problems of periodontal trials are similar to those of other chronic diseases. However, the episodic, localized, infrequent, and relatively unpredictable behavior of exacerbations, coupled with measurement error difficulties, cause some specific problems. Considerable controversy exists as to the proper selection and treatment of multiple site data from the same patient for group comparisons for epidemiologic or therapeutic evaluative purposes. This paper comments, with varying degrees of emphasis, on several issues pertinent to the analysis of periodontal trials. Considerable attention is given to the ways in which measurement variability may distort analytic results. Statistical treatments of multiple site data for descriptive summaries are distinguished from treatments for formal statistical inference to validate therapeutic effects. Evidence suggesting that sites behave independently is contested. For inferential analyses directed at therapeutic or preventive effects, analytic models based on site independence are deemed unsatisfactory. Methods of summarization that may yield more powerful analyses than all-site mean scores, while retaining appropriate treatment of inter-site associations, are suggested. Brief comments and opinions on an assortment of other issues in clinical trial analysis are preferred.

Muscle paralyzing effect of the juice from the trunk of the banana tree.

PubMed

Singh, Y N; Dryden, W F

1985-01-01

The effect of an extract from the trunk of the banana tree (Musa sapientum) was investigated in isolated skeletal muscle preparations from the chick, mouse and frog using twitch tension and intracellular recording techniques. The extract produced, in the same concentration range and after an initial period of twitch augmentation, paralysis of skeletal muscle in both directly and indirectly stimulated preparations. It also had a dose-dependent stimulant effect on the muscle causing a contracture. The neuromuscular blockade was reversed by calcium, but only when added before complete paralysis of the muscle. On the other hand, neostigmine usually hastened the blockade and aggravated the contracture. The frequency of the miniature endplate potential in the mouse phrenic nerve-diaphragm preparation greatly increased initially, declining to an elevated plateau. Effects on quantal content of endplate potentials (e.p.p.s) were studied in the transected mouse phrenic nerve-hemidiaphragm using trains of e.p.p.s. In the presence of the extract, only a few e.p.p. trains could normally be evoked, probably due to nerve terminal block. When quantal content could be measured at low concentrations of the extract, an increase was usually obtained. Muscle action potentials in the frog sartorius muscle were decreased in amplitude until no further potentials could be generated. The results suggest that the nature of the block produced by the extract resembles that of a potent local anaesthetic with an initial atypical labilizing effect on cell calcium rather than a conventional curariform block.

Quantal basis of vesicle growth and information content, a unified approach.

PubMed

Nitzany, Eyal; Hammel, Ilan; Meilijson, Isaac

2010-09-07

Secretory vesicles express a periodic multimodal size distribution. The successive modes are integral multiples of the smallest mode (G(1)). The vesicle content ranges from macromolecules (proteins, mucopolysaccharides and hormones) to low molecular weight molecules (neurotransmitters). A steady-state model has been developed to emulate a mechanism for the introduction of vesicles of monomer size, which grow by a unit addition mechanism, G(1)+G(n)-->G(n+1) which, at a later stage are eliminated from the system. We describe a model of growth and elimination transition rates which adequately illustrates the distributions of vesicle population size at steady-state and upon elimination. Consequently, prediction of normal behavior and pathological perturbations is feasible. Careful analysis of spontaneous secretion, as compared to short burst-induced secretion, suggests that the basic character-code for reliable communication should be within a range of only 8-10 vesicles' burst which may serve as a yes/no message. Copyright 2010 Elsevier Ltd. All rights reserved.

Real-Time Imaging Reveals Properties of Glutamate-Induced Arc/Arg 3.1 Translation in Neuronal Dendrites.

PubMed

Na, Youn; Park, Sungjin; Lee, Changhee; Kim, Dong-Kyu; Park, Joo Min; Sockanathan, Shanthini; Huganir, Richard L; Worley, Paul F

2016-08-03

The immediate early gene Arc (also Arg3.1) produces rapid changes in synaptic properties that are linked to de novo translation. Here we develop a novel translation reporter that exploits the rapid maturation and "flash" kinetics of Gaussia luciferase (Gluc) to visualize Arc translation. Following glutamate stimulation, discrete Arc-Gluc bioluminescent flashes representing sites of de novo translation are detected within 15 s at distributed sites in dendrites, but not spines. Flashes are episodic, lasting ∼20 s, and may be unitary or repeated at ∼minute intervals at the same sites. Analysis of flash amplitudes suggests they represent the quantal product of one or more polyribosomes, while inter-flash intervals appear random, suggesting they arise from a stochastic process. Surprisingly, glutamate-induced translation is dependent on Arc open reading frame. Combined observations support a model in which stalled ribosomes are reactivated to rapidly generate Arc protein. Copyright © 2016 Elsevier Inc. All rights reserved.

Time dependent three-dimensional body frame quantal wave packet treatment of the H + H2 exchange reaction on the Liu-Siegbahn-Truhlar-Horowitz (LSTH) surface

NASA Technical Reports Server (NTRS)

Neuhauser, Daniel; Baer, Michael; Judson, Richard S.; Kouri, Donald J.

1989-01-01

The first successful application of the three-dimensional quantum body frame wave packet approach to reactive scattering is reported for the H + H2 exchange reaction on the LSTH potential surface. The method used is based on a procedure for calculating total reaction probabilities from wave packets. It is found that converged, vibrationally resolved reactive probabilities can be calculated with a grid that is not much larger than required for the pure inelastic calculation. Tabular results are presented for several energies.

Electron Capture in Proton Collisions with CO.

NASA Astrophysics Data System (ADS)

Stancil, P. C.; Schultz, D. R.; Kimura, M.; Gu, J.-P.; Hirsch, G.; Buenker, R. J.; Li, Y.

1999-10-01

Electron capture by protons following collisions with carbon monoxide is studied with a variety of theoretical approaches including quantal and semiclassical molecular-orbital close-coupling (MOCC) and classical trajectory Monte Carlo (CTMC) techniques. The MOCC treatments utilize potential surfaces and couplings computed for a range of H^+-CO orientation angles and C-O separations. Results including integral, differential, electronic state-selective, and vibrational state-selective cross sections will be presented for low- to intermediate-energies. Comparison with experiment will be made where possible and the relevance of the reaction in astrophysics and atmospheric physics will be discussed.

The Maintenance of Synaptic Homeostasis at the Drosophila Neuromuscular Junction Is Reversible and Sensitive to High Temperature.

PubMed

Yeates, Catherine J; Zwiefelhofer, Danielle J; Frank, C Andrew

2017-01-01

Homeostasis is a vital mode of biological self-regulation. The hallmarks of homeostasis for any biological system are a baseline set point of physiological activity, detection of unacceptable deviations from the set point, and effective corrective measures to counteract deviations. Homeostatic synaptic plasticity (HSP) is a form of neuroplasticity in which neurons and circuits resist environmental perturbations and stabilize levels of activity. One assumption is that if a perturbation triggers homeostatic corrective changes in neuronal properties, those corrective measures should be reversed upon removal of the perturbation. We test the reversibility and limits of HSP at the well-studied Drosophila melanogaster neuromuscular junction (NMJ). At the Drosophila NMJ, impairment of glutamate receptors causes a decrease in quantal size, which is offset by a corrective, homeostatic increase in the number of vesicles released per evoked presynaptic stimulus, or quantal content. This process has been termed presynaptic homeostatic potentiation (PHP). Taking advantage of the GAL4/GAL80 TS /UAS expression system, we triggered PHP by expressing a dominant-negative glutamate receptor subunit at the NMJ. We then reversed PHP by halting expression of the dominant-negative receptor. Our data show that PHP is fully reversible over a time course of 48-72 h after the dominant-negative glutamate receptor stops being genetically expressed. As an extension of these experiments, we find that when glutamate receptors are impaired, neither PHP nor NMJ growth is reliably sustained at high culturing temperatures (30-32°C). These data suggest that a limitation of homeostatic signaling at high temperatures could stem from the synapse facing a combination of challenges simultaneously.

Wave vector modification of the infinite order sudden approximation

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

Sachs, J.G.; Bowman, J.M.

1980-10-15

A simple method is proposed to modify the infinite order sudden approximation (IOS) in order to extend its region of quantitative validity. The method involves modifying the phase of the IOS scattering matrix to include a part calculated at the outgoing relative kinetic energy as well as a part calculated at the incoming kinetic energy. An immediate advantage of this modification is that the resulting S matrix is symmetric. We also present a closely related method in which the relative kinetic energies used in the calculation of the phase are determined from quasiclassical trajectory calculations. A set of trajectories ismore » run with the initial state being the incoming state, and another set is run with the initial state being the outgoing state, and the average final relative kinetic energy of each set is obtained. One part of the S-operator phase is then calculated at each of these kinetic energies. We apply these methods to vibrationally inelastic collinear collisions of an atom and a harmonic oscillator, and calculate transition probabilities P/sub n/1..-->..nf for three model systems. For systems which are sudden, or nearly so, the agreement with exact quantum close-coupling calculations is substantially improved over standard IOS ones when ..delta..n=such thatub f/-n/sub i/ is large, and the corresponding transition probability is small, i.e., less than 0.1. However, the modifications we propose will not improve the accuracy of the IOS transition probabilities for any collisional system unless the standard form of IOS already gives at least qualitative agreement with exact quantal calculations. We also suggest comparisons between some classical quantities and sudden predictions which should help in determining the validity of the sudden approximation. This is useful when exact quantal data is not available for comparison.« less

Rainbows in rotationally inelastic scattering: a comparative study of different model potential surfaces and dynamical approximations

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

Schinke, R.; Korsch, H.J.; Poppe, D.

1982-12-15

Rainbow structures in rotationally elastic and inelastic differential cross sections in atom--diatom collisions are investigated by comparison of three model potential energy surfaces labeled I, II, and III which are represented by V(R,..gamma..) = V/sub 0/(R)+V/sub 2/(R)P/sub 2/(cos ..gamma..). The cross sections are calculated within the quantal infinite-order-sudden (IOS) approximation. The anisotropic part V/sub 2/ is the same for all potentials and purely repulsive. The isotropic part V/sub 0/ for potential I is also repulsive and the differential cross sections show the well-studied rotational rainbow structures. Structural changes occur for collisions in potential II and III which have V/sub 0/more » terms being attractive at intermediate and large atom--molecule separations and having well depths of 10% and 25% of the collision energy, respectively. For example, the elastic cross section has no classical rainbow in the case of potential I but three in the case of potential III. The rainbow structures are analyzed within the classical and semiclassical versions of the IOS approximation and interpreted in terms of catastrophe theory. The quantitative comparison of the classical with the quantal IOS cross sections manifests possible quantum effects, i.e., tunneling into nonclassical regions and interference effects due to the superposition of several contributions (up to six in the present study). They can be very prominent and thus we conclude that much caution is needed if experimental data are compared with classical calculations. The accuracy of the IOS approximation is tested by comparison of classical IOS cross sections with cross sections obtained from exact classical trajectory calculations. The agreement is generally good with the exemption of the rainbow region and small angle, rotationally elastic scattering.« less

Heterogeneous distribution of exocytotic microdomains in adrenal chromaffin cells resolved by high-density diamond ultra-microelectrode arrays.

PubMed

Gosso, Sara; Turturici, Marco; Franchino, Claudio; Colombo, Elisabetta; Pasquarelli, Alberto; Carbone, Emilio; Carabelli, Valentina

2014-08-01

Here we describe the ability of a high-density diamond microelectrode array targeted to resolve multi-site detection of fast exocytotic events from single cells. The array consists of nine boron-doped nanocrystalline diamond ultra-microelectrodes (9-Ch NCD-UMEA) radially distributed within a circular area of the dimensions of a single cell. The device can be operated in voltammetric or chronoamperometric configuration. Sensitivity to catecholamines, tested by dose-response calibrations, set the lowest detectable concentration of adrenaline to ∼5 μm. Catecholamine release from bovine or mouse chromaffin cells could be triggered by electrical stimulation or external KCl-enriched solutions. Spikes detected from the cell apex using carbon fibre microelectrodes showed an excellent correspondence with events measured at the bottom of the cell by the 9-Ch NCD-UMEA, confirming the ability of the array to resolve single quantal secretory events. Subcellular localization of exocytosis was provided by assigning each quantal event to one of the nine channels based on its location. The resulting mapping highlights the heterogeneous distribution of secretory activity in cell microdomains of 12-27 μm2. In bovine chromaffin cells, secretion was highly heterogeneous with zones of high and medium activity in 54% of the cell surface and zones of low or no activity in the remainder. The 'non-active' ('silent') zones covered 24% of the total and persisted for 6-8 min, indicating stable location. The 9-Ch NCD-UMEA therefore appears suitable for investigating the microdomain organization of neurosecretion with high spatial resolution. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Maintained cocaine self-administration is determined by quantal responses: implications for the measurement of antagonist potency.

PubMed

Norman, Andrew B; Tabet, Michael R; Norman, Mantana K; Tsibulsky, Vladimir L

2014-02-01

The change in frequency of cocaine self-administration as a function of the unit dose is widely assumed to represent a graded pharmacodynamic response. Alternatively, a pharmacological theory states that during maintained self-administration, a quantal response occurs at a minimum maintained cocaine concentration (satiety threshold). Rats self-administered cocaine at unit doses spanning an 8-fold range from 0.75 to 6 µmol/kg. Despite an approximately 7-fold difference in the interinjection intervals, there were no differences in the plasma cocaine concentration at the time of lever press across this range of unit doses, consistent with the satiety threshold representing an equiactive cocaine concentration. Because self-administration always occurs when cocaine concentrations decline back to the satiety threshold, this behavior represents a process of automatic back titration of equiactive agonist concentrations. Therefore, the lower frequency of self-administration at higher unit doses is caused by an increase in the duration of the cocaine-induced satiety response, and the graded dose-frequency relationship is due to cocaine pharmacokinetics. After the interinjection intervals at a particular unit dose were stable, rats were injected with the competitive D₁-like dopamine receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH23390; 15 nmol/kg intravenously) and the session continued. At all cocaine unit doses, SCH23390 accelerated self-administration with a concomitant increase in the calculated satiety threshold, and these equiactive cocaine concentration ratios were independent of the cocaine unit dose. Therefore, the measurement of antagonist potency requires only a single unit dose of cocaine, selected on the basis of convenience, and using multiple cocaine unit doses is redundant.

The Maintenance of Synaptic Homeostasis at the Drosophila Neuromuscular Junction Is Reversible and Sensitive to High Temperature

PubMed Central

Zwiefelhofer, Danielle J.

2017-01-01

Abstract Homeostasis is a vital mode of biological self-regulation. The hallmarks of homeostasis for any biological system are a baseline set point of physiological activity, detection of unacceptable deviations from the set point, and effective corrective measures to counteract deviations. Homeostatic synaptic plasticity (HSP) is a form of neuroplasticity in which neurons and circuits resist environmental perturbations and stabilize levels of activity. One assumption is that if a perturbation triggers homeostatic corrective changes in neuronal properties, those corrective measures should be reversed upon removal of the perturbation. We test the reversibility and limits of HSP at the well-studied Drosophila melanogaster neuromuscular junction (NMJ). At the Drosophila NMJ, impairment of glutamate receptors causes a decrease in quantal size, which is offset by a corrective, homeostatic increase in the number of vesicles released per evoked presynaptic stimulus, or quantal content. This process has been termed presynaptic homeostatic potentiation (PHP). Taking advantage of the GAL4/GAL80TS/UAS expression system, we triggered PHP by expressing a dominant-negative glutamate receptor subunit at the NMJ. We then reversed PHP by halting expression of the dominant-negative receptor. Our data show that PHP is fully reversible over a time course of 48–72 h after the dominant-negative glutamate receptor stops being genetically expressed. As an extension of these experiments, we find that when glutamate receptors are impaired, neither PHP nor NMJ growth is reliably sustained at high culturing temperatures (30–32°C). These data suggest that a limitation of homeostatic signaling at high temperatures could stem from the synapse facing a combination of challenges simultaneously. PMID:29255795

Presynaptic membrane receptors in acetylcholine release modulation in the neuromuscular synapse.

PubMed

Tomàs, Josep; Santafé, Manel M; Garcia, Neus; Lanuza, Maria A; Tomàs, Marta; Besalduch, Núria; Obis, Teresa; Priego, Mercedes; Hurtado, Erica

2014-05-01

Over the past few years, we have studied, in the mammalian neuromuscular junction (NMJ), the local involvement in transmitter release of the presynaptic muscarinic ACh autoreceptors (mAChRs), purinergic adenosine autoreceptors (P1Rs), and trophic factor receptors (TFRs; for neurotrophins and trophic cytokines) during development and in the adult. At any given moment, the way in which a synapse works is largely the logical outcome of the confluence of these (and other) metabotropic signalling pathways on intracellular kinases, which phosphorylate protein targets and materialize adaptive changes. We propose an integrated interpretation of the complementary function of these receptors in the adult NMJ. The activity of a given receptor group can modulate a given combination of spontaneous, evoked, and activity-dependent release characteristics. For instance, P1Rs can conserve resources by limiting spontaneous quantal leak of ACh (an A1 R action) and protect synapse function, because stimulation with adenosine reduces the magnitude of depression during repetitive activity. The overall outcome of the mAChRs seems to contribute to upkeep of spontaneous quantal output of ACh, save synapse function by decreasing the extent of evoked release (mainly an M2 action), and reduce depression. We have also identified several links among P1Rs, mAChRs, and TFRs. We found a close dependence between mAChR and some TFRs and observed that the muscarinic group has to operate correctly if the tropomyosin-related kinase B receptor (trkB) is also to operate correctly, and vice versa. Likewise, the functional integrity of mAChRs depends on P1Rs operating normally. Copyright © 2014 Wiley Periodicals, Inc.

Discharge regularity in the turtle posterior crista: comparisons between experiment and theory.

PubMed

Goldberg, Jay M; Holt, Joseph C

2013-12-01

Intra-axonal recordings were made from bouton fibers near their termination in the turtle posterior crista. Spike discharge, miniature excitatory postsynaptic potentials (mEPSPs), and afterhyperpolarizations (AHPs) were monitored during resting activity in both regularly and irregularly discharging units. Quantal size (qsize) and quantal rate (qrate) were estimated by shot-noise theory. Theoretically, the ratio, σV/(dμV/dt), between synaptic noise (σV) and the slope of the mean voltage trajectory (dμV/dt) near threshold crossing should determine discharge regularity. AHPs are deeper and more prolonged in regular units; as a result, dμV/dt is larger, the more regular the discharge. The qsize is larger and qrate smaller in irregular units; these oppositely directed trends lead to little variation in σV with discharge regularity. Of the two variables, dμV/dt is much more influential than the nearly constant σV in determining regularity. Sinusoidal canal-duct indentations at 0.3 Hz led to modulations in spike discharge and synaptic voltage. Gain, the ratio between the amplitudes of the two modulations, and phase leads re indentation of both modulations are larger in irregular units. Gain variations parallel the sensitivity of the postsynaptic spike encoder, the set of conductances that converts synaptic input into spike discharge. Phase variations reflect both synaptic inputs to the encoder and postsynaptic processes. Experimental data were interpreted using a stochastic integrate-and-fire model. Advantages of an irregular discharge include an enhanced encoder gain and the prevention of nonlinear phase locking. Regular and irregular units are more efficient, respectively, in the encoding of low- and high-frequency head rotations, respectively.

Discharge regularity in the turtle posterior crista: comparisons between experiment and theory

PubMed Central

Holt, Joseph C.

2013-01-01

Intra-axonal recordings were made from bouton fibers near their termination in the turtle posterior crista. Spike discharge, miniature excitatory postsynaptic potentials (mEPSPs), and afterhyperpolarizations (AHPs) were monitored during resting activity in both regularly and irregularly discharging units. Quantal size (qsize) and quantal rate (qrate) were estimated by shot-noise theory. Theoretically, the ratio, σV/(dμV/dt), between synaptic noise (σV) and the slope of the mean voltage trajectory (dμV/dt) near threshold crossing should determine discharge regularity. AHPs are deeper and more prolonged in regular units; as a result, dμV/dt is larger, the more regular the discharge. The qsize is larger and qrate smaller in irregular units; these oppositely directed trends lead to little variation in σV with discharge regularity. Of the two variables, dμV/dt is much more influential than the nearly constant σV in determining regularity. Sinusoidal canal-duct indentations at 0.3 Hz led to modulations in spike discharge and synaptic voltage. Gain, the ratio between the amplitudes of the two modulations, and phase leads re indentation of both modulations are larger in irregular units. Gain variations parallel the sensitivity of the postsynaptic spike encoder, the set of conductances that converts synaptic input into spike discharge. Phase variations reflect both synaptic inputs to the encoder and postsynaptic processes. Experimental data were interpreted using a stochastic integrate-and-fire model. Advantages of an irregular discharge include an enhanced encoder gain and the prevention of nonlinear phase locking. Regular and irregular units are more efficient, respectively, in the encoding of low- and high-frequency head rotations, respectively. PMID:24004525

Wave vector modification of the infinite order sudden approximation

NASA Astrophysics Data System (ADS)

Sachs, Judith Grobe; Bowman, Joel M.

1980-10-01

A simple method is proposed to modify the infinite order sudden approximation (IOS) in order to extend its region of quantitative validity. The method involves modifying the phase of the IOS scattering matrix to include a part calculated at the outgoing relative kinetic energy as well as a part calculated at the incoming kinetic energy. An immediate advantage of this modification is that the resulting S matrix is symmetric. We also present a closely related method in which the relative kinetic energies used in the calculation of the phase are determined from quasiclassical trajectory calculations. A set of trajectories is run with the initial state being the incoming state, and another set is run with the initial state being the outgoing state, and the average final relative kinetic energy of each set is obtained. One part of the S-operator phase is then calculated at each of these kinetic energies. We apply these methods to vibrationally inelastic collinear collisions of an atom and a harmonic oscillator, and calculate transition probabilities Pn1→nf for three model systems. For systems which are sudden, or nearly so, the agreement with exact quantum close-coupling calculations is substantially improved over standard IOS ones when Δn=‖nf-ni‖ is large, and the corresponding transition probability is small, i.e., less than 0.1. However, the modifications we propose will not improve the accuracy of the IOS transition probabilities for any collisional system unless the standard form of IOS already gives at least qualitative agreement with exact quantal calculations. We also suggest comparisons between some classical quantities and sudden predictions which should help in determining the validity of the sudden approximation. This is useful when exact quantal data is not available for comparison.

Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles

PubMed Central

Leitz, Jeremy; Kavalali, Ege T

2014-01-01

Presynaptic terminals release neurotransmitters spontaneously in a manner that can be regulated by Ca2+. However, the mechanisms underlying this regulation are poorly understood because the inherent stochasticity and low probability of spontaneous fusion events has curtailed their visualization at individual release sites. Here, using pH-sensitive optical probes targeted to synaptic vesicles, we visualized single spontaneous fusion events and found that they are retrieved extremely rapidly with faster re-acidification kinetics than their action potential-evoked counterparts. These fusion events were coupled to postsynaptic NMDA receptor-driven Ca2+ signals, and at elevated Ca2+ concentrations there was an increase in the number of vesicles that would undergo fusion. Furthermore, spontaneous vesicle fusion propensity in a synapse was Ca2+-dependent but regulated autonomously: independent of evoked fusion probability at the same synapse. Taken together, these results expand classical quantal analysis to incorporate endocytic and exocytic phases of single fusion events and uncover autonomous regulation of spontaneous fusion. DOI: http://dx.doi.org/10.7554/eLife.03658.001 PMID:25415052

Emotion modelling towards affective pathogenesis.

PubMed

Bas, James Le

2009-12-01

Objective: There is a need in psychiatry for models that integrate pathological states with normal systems. The interaction of arousal and emotion is the focus of an exploration of affective pathogenesis. Method: Given that the explicit causes of affective disorder remain nascent, methods of linking emotion and disorder are evaluated. Results: A network model of emotional families is presented, in which emotions exist as quantal gradients. Morbid emotional states are seen as the activation of distal emotion sites. The phenomenology of affective disorders is described with reference to this model. Recourse is made to non-linear dynamic theory. Conclusions: Metaphoric emotion models have face validity and may prove a useful heuristic.

Susceptibility of Skeletal Muscle to Coxsackie A2 Virus Infection: Effects of Botulinum Toxin and Denervation

NASA Astrophysics Data System (ADS)

Andrew, Clifford G.; Drachman, Daniel B.; Pestronk, Alan; Narayan, Opendra

1984-02-01

Coxsackie A viruses can infect denervated but not innervated mature skeletal muscles. The role of synaptic transmission in preventing susceptibility to Coxsackievirus infection was studied by surgically denervating leg muscles of mice or injecting the muscles with botulinum toxin to block quantal release of acetylcholine. Control muscles were injected with heat-inactivated toxin. Subsequent injection of Coxsackie A2 virus resulted in extensive virus replication and tissue destruction in the denervated and botulinum toxin-treated muscles, while the control muscles showed only minimal changes. This suggests that the susceptibility of skeletal muscle to Coxsackievirus infection is regulated by synaptic transmission.

Observing shape resonances in ultraslow H^++H elastic scattering

NASA Astrophysics Data System (ADS)

Macek, J. H.; Schultz, D. R.; Ovchinnikov, S. Yu.; Krstic, P. S.

2004-05-01

We have calculated highly accurate elastic and charge transfer cross sections for proton-hydrogen scattering at energies 0.0001-10 eV, using fully quantal approach (P.S. Krstic and D.R. Schultz, J. Phys. B 32, 3485 (1999)). A number of resonances are observed. We calculate the positions and widths of the shape resonances in the effective potentials for various orbital angular momenta (J. H. Macek and S. Yu. Ovchinnikov, Phys. Rev. A 50, 468 (1994)). These correlate well with the observed resonances. We acknowledge support from the US DOE through ORNL, managed by UT-Battelle, LLC under contract DE-AC05-00OR22725.

Effect of oxotremorine on resting membrane potential and cell volume in skeletal muscle fibers in rats after in vivo blockade of NO-synthase.

PubMed

Khairova, R A; Malomuzh, A I; Naumenko, N V; Urazaev, A Kh

2003-02-01

Denervation of rat phrenic muscle or block of NO-synthase in vivo increased the cross-section area of muscle fibers and decreased membrane resting potential. Oxotremorine prevented the development of denervation-induced or denervation-like (i.e. induced by NO-synthase blockade) membrane depolarization and increase of the cross-sectional area of muscle fibers. Pirenzepine abolished the effects of oxotremorine. It was concluded that non-quantal acetylcholine can be involved in the regulation of skeletal muscle fiber volume via activation of M1 muscarinic receptors followed by NO synthesis.

Regulation of Oligomeric Organization of the Serotonin 5-Hydroxytryptamine 2C (5-HT2C) Receptor Observed by Spatial Intensity Distribution Analysis*

PubMed Central

Ward, Richard J.; Pediani, John D.; Godin, Antoine G.; Milligan, Graeme

2015-01-01

The questions of whether G protein-coupled receptors exist as monomers, dimers, and/or oligomers and if these species interconvert in a ligand-dependent manner are among the most contentious current issues in biology. When employing spatial intensity distribution analysis to laser scanning confocal microscope images of cells stably expressing either a plasma membrane-associated form of monomeric enhanced green fluorescent protein (eGFP) or a tandem version of this fluorophore, the eGFP tandem was identified as a dimer. Similar studies on cells stably expressing an eGFP-tagged form of the epidermal growth factor receptor demonstrated that, although largely a monomer in the basal state, this receptor rapidly became predominantly dimeric upon the addition of its ligand epidermal growth factor. In cells induced to express an eGFP-tagged form of the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor, global analysis of construct quantal brightness was consistent with the predominant form of the receptor being dimeric. However, detailed spatial intensity distribution analysis demonstrated the presence of multiple forms ranging from monomers to higher-order oligomers. Furthermore, treatment with chemically distinct 5-HT2C receptor antagonists resulted in a time-dependent change in the quaternary organization to one in which there was a preponderance of receptor monomers. This antagonist-mediated effect was reversible, because washout of the ligand resulted in the regeneration of many of the oligomeric forms of the receptor. PMID:25825490

Inorganic and organic mercury chloride toxicity to Coturnix: Sensitivity related to age and quantal assessment of physiologic responses

USGS Publications Warehouse

Hill, E.F.

1982-01-01

The toxicities of mercuric chloride (HgCl(,2)) and methylmercuric chloride (CH(,3)HgCl) were compared for coturnix (Coturnix coturnix japonica) from hatching to adulthood. Comparisons were based on: (1) Median lethal dosages (LD50) derived by administering single peroral and single intramuscular dosages of mercury, (2) median lethal concentrations (LC50) derived by feeding mercury for 5 days, (3) median toxic concentrations (TC50) derived by feeding mercury 9 weeks and measuring plasma enzyme activity, plasma electrolytes, and other blood constituents, and (4) transient changes of various blood chemistries following a single peroral dose of mercury. Acute peroral and intramuscular LD50s for HgCl(,2) and CH(,3)HgCl increased by two- to threefold for coturnix chicks from hatching to 4 weeks of age. Concomitantly, the LC50s also increased, but the important difference between test procedures was that with both single dose routes of exposure the toxicity ratios, i.e., HgCl(,2)/CH(,3)HgCl, at each age were about 2 to 2.5 compared to about 100 for the LC50s. For example, at 2 weeks of age the peroral LD50s for HgCl(,2) and CH(,3)HgCl were 42 and 18 mg/kg; the dietary LC50s were 5086 and 47 ppm for HgCl(,2) and CH(,3)HgCl. The 9 week feeding trial was not associated with gross effects from either HgCl(,2) at 0.5 to 32 ppm or CH(,3)HgCl at 0.125 to 8 ppm. However, subtle responses were detected for the plasma enzymes aspartate aminotransferase, lactate dehydrogenase, and ornithine carbamoyl transferase and could be quantified by probit analysis. This quantal procedure was based on establishment of a normal value for each enzyme and classing outliers as respondents. A 'hazard index' based on the TC50 for an enzyme divided by the LD50 or LC50 was introduced. The single oral dosages of HgCl(,2) and CH(,3)HgCl showed that ratios of alanine aminotransferase, lactate dehydrogenase, and orinthine carbamoyl transferase for the liver and kidneys of adult coturnix were opposite from that accepted for mammals. It was concluded that a chronic study of sublethal responses of young birds should be required in addition to the current toxicity screens used for regulatory purposes.

Inorganic and organic mercury chloride toxicity to Coturnix: sensitivity related to age and quantal assessment of physiologic responses

USGS Publications Warehouse

Hill, E.F.

1981-01-01

The toxicities of mercuric chloride (HgCl(,2)) and methylmercuric chloride (CH(,3)HgCl) were compared for coturnix (Coturnix coturnix japonica) from hatching to adulthood. Comparisons were based on: (1) Median lethal dosages (LD50) derived by administering single peroral and single intramuscular dosages of mercury, (2) median lethal concentrations (LC50) derived by feeding mercury for 5 days, (3) median toxic concentrations (TC50) derived by feeding mercury 9 weeks and measuring plasma enzyme activity, plasma electrolytes, and other blood constituents, and (4) transient changes of various blood chemistries following a single peroral dose of mercury. Acute peroral and intramuscular LD50s for HgCl(,2) and CH(,3)HgCl increased by two- to threefold for coturnix chicks from hatching to 4 weeks of age. Concomitantly, the LC50s also increased, but the important difference between test procedures was that with both single dose routes of exposure the toxicity ratios, i.e., HgCl(,2)/CH(,3)HgCl, at each age were about 2 to 2.5 compared to about 100 for the LC50s. For example, at 2 weeks of age the peroral LD50s for HgCl(,2) and CH(,3)HgCl were 42 and 18 mg/kg; the dietary LC50s were 5086 and 47 ppm for HgCl(,2) and CH(,3)HgCl. The 9 week feeding trial was not associated with gross effects from either HgCl(,2) at 0.5 to 32 ppm or CH(,3)HgCl at 0.125 to 8 ppm. However, subtle responses were detected for the plasma enzymes aspartate aminotransferase, lactate dehydrogenase, and ornithine carbamoyl transferase and could be quantified by probit analysis. This quantal procedure was based on establishment of a normal value for each enzyme and classing outliers as respondents. A 'hazard index' based on the TC50 for an enzyme divided by the LD50 or LC50 was introduced. The single oral dosages of HgCl(,2) and CH(,3)HgCl showed that ratios of alanine aminotransferase, lactate dehydrogenase, and orinthine carbamoyl transferase for the liver and kidneys of adult coturnix were opposite from that accepted for mammals. It was concluded that a chronic study of sublethal responses of young birds should be required in addition to the current toxicity screens used for regulatory purposes.

Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release.

PubMed Central

Debanne, D; Guérineau, N C; Gähwiler, B H; Thompson, S M

1996-01-01

1. Excitatory synaptic transmission between pairs of monosynaptically coupled pyramidal cells was examined in rat hippocampal slice cultures. Action potentials were elicited in single CA3 pyramidal cells impaled with microelectrodes and unitary excitatory postsynaptic currents (EPSCs) were recorded in whole-cell voltage-clamped CA1 or CA3 cells. 2. The amplitude of successive unitary EPSCs in response to single action potentials varied. The amplitude of EPSCs was altered by adenosine or changes in the [Mg2+]/[CA2+] ratio. We conclude that single action potentials triggered the release of multiple quanta of glutamate. 3. When two action potentials were elicited in the presynaptic cell, the amplitude of the second EPSC was inversely related to the amplitude of the first. Paired-pulse facilitation (PPF) was observed when the first EPSC was small, i.e. the second EPSC was larger than the first, whereas paired-pulse depression (PPD) was observed when the first EPSC was large. 4. The number of trials displaying PPD was greater when release probability was increased, and smaller when release probability was decreased. 5. PPD was not postsynaptically mediated because it was unaffected by decreasing ionic flux with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or receptor desensitization with aniracetam. 6. PPF was maximal at an interstimulus interval of 70 ms and recovered within 500 ms. Recovery from PPD occurred within 5 s. 7. We propose that multiple release sites are formed by the axon of a CA3 pyramidal cell and a single postsynaptic CA1 or CA3 cell. PPF is observed if the first action potential fails to release transmitter at most release sites. PPD is observed if the first action potential successfully triggers release at most release sites. 8. Our observations of PPF are consistent with the residual calcium hypothesis. We conclude that PPD results from a decrease in quantal content, perhaps due to short-term depletion of readily releasable vesicles. PMID:9011608

α‐Conotoxin M1 (CTx) blocks αδ binding sites of adult nicotinic receptors while ACh binding at αε sites elicits only small and short quantal synaptic currents

PubMed Central

Dudel, Josef

2014-01-01

Abstract In ‘embryonic’ nicotinic receptors, low CTx concentrations are known to block only the αδ binding site, whereas binding of ACh at the αγ‐site elicits short single channel openings and short bursts. In adult muscles the αγ‐ is replaced by the αε‐site. Quantal EPSCs (qEPSCs) were elicited in adult muscles by depolarization pulses and recorded through a perfused macropatch electrode. One to 200 nmol L−1 CTx reduced amplitudes and decay time constants of qEPSCs, but increased their rise times. CTx block at the αδ binding sites was incomplete: The qEPSCs still contained long bursts from not yet blocked receptors, whereas their average decay time constants were reduced by a short burst component generated by ACh binding to the αε‐site. Two nanomolar CTx applied for 3 h reduced the amplitudes of qEPSCs to less than half with a constant slope. The equilibrium concentration of the block is below 1 nmol L−1 and lower than that of embryonic receptors. CTx‐block increased in proportion to CTx concentrations (average rate 2 × 104 s−1·mol−1 L). Thus, the reactions of ‘embryonic’ and of adult nicotinic receptors to block by CTx are qualitatively the same. – The study of the effects of higher CTx concentrations or of longer periods of application of CTx was limited by presynaptic effects of CTx. Even low CTx concentrations severely reduced the release of quanta by activating presynaptic M2 receptors at a maximal rate of 6 × 105 s−1·mol−1 L. When this dominant inhibition was prevented by blocking the M2 receptors with methoctramine, activation of M1 receptors was unmasked and facilitated release. PMID:25501436

Dynamics of platelet glycoprotein IIb-IIIa receptor expression and fibrinogen binding. I. Quantal activation of platelet subpopulations varies with adenosine diphosphate concentration.

PubMed Central

Frojmovic, M. M.; Mooney, R. F.; Wong, T.

1994-01-01

We have previously reported that maximal platelet activation with adenosine diphosphate (100 microM ADP) causes rapid expression of all GPIIb-IIIa receptors for fibrinogen (FgR) (< 1-3 s), measured with FITC-labeled PAC1 by flow cytometry. We have extended these studies to examine the effects of ADP concentration on the graded expression and Fg occupancy of GPIIb-IIIa receptors. Human citrated platelet-rich plasma, diluted 10-fold with Walsh-albumin-Mg+2 (2 mM), was treated with ADP (0.1-100 microM). The rates of GPIIb-IIIa receptor expression or Fg binding were measured in unstirred samples by flow cytometry, using FITC-labeled monoclonal antibodies (mAb) PAC1 and 9F9, respectively, from on-rates, using increasing times between mAb and ADP additions. Fibrinogen receptors were all expressed rapidly at low (1 microM) or high (100 microM) ADP (few seconds), whereas Fg occupancy was 50% of maximal by about 2 min. The maximal extent of GPIIb-IIIa receptor expression and Fg occupancy was determined from maximal binding (Flmax) at 30 min incubation with PAC1 or 9F9. On-rates and maximal extents of binding for either PAC1 or 9F9 probes showed identical [ADP]-response profiles ("KD" approximately 1.4 +/- 0.1 microM). However, Flmax studies showed bimodal histograms consisting of "resting" (Po) and maximally "activated" (P*) platelets for both PAC1 and 9F9 binding, with the fraction of "activated" platelets increasing with ADP concentration. The data best fit a model where platelet subpopulations are "quantally" transformed from Po to P*, expressing all GPIIb-IIIa receptors, rapidly filled by Fg, but "triggered" at critical ADP concentrations. Larger, but not the largest, platelets appear to be the most sensitive subpopulation. The implications for clinical studies are discussed, and the relationship to dynamics of aggregation are described in a companion paper. PMID:7858143

Genetic variance of tolerance and the toxicant threshold model.

PubMed

Tanaka, Yoshinari; Mano, Hiroyuki; Tatsuta, Haruki

2012-04-01

A statistical genetics method is presented for estimating the genetic variance (heritability) of tolerance to pollutants on the basis of a standard acute toxicity test conducted on several isofemale lines of cladoceran species. To analyze the genetic variance of tolerance in the case when the response is measured as a few discrete states (quantal endpoints), the authors attempted to apply the threshold character model in quantitative genetics to the threshold model separately developed in ecotoxicology. The integrated threshold model (toxicant threshold model) assumes that the response of a particular individual occurs at a threshold toxicant concentration and that the individual tolerance characterized by the individual's threshold value is determined by genetic and environmental factors. As a case study, the heritability of tolerance to p-nonylphenol in the cladoceran species Daphnia galeata was estimated by using the maximum likelihood method and nested analysis of variance (ANOVA). Broad-sense heritability was estimated to be 0.199 ± 0.112 by the maximum likelihood method and 0.184 ± 0.089 by ANOVA; both results implied that the species examined had the potential to acquire tolerance to this substance by evolutionary change. Copyright © 2012 SETAC.

Activity-dependent regulation of release probability at excitatory hippocampal synapses: a crucial role of FMRP in neurotransmission

PubMed Central

Wang, Xiao-Sheng; Peng, Chun-Zi; Cai, Wei-Jun; Xia, Jian; Jin, Daozhong; Dai, Yuqiao; Luo, Xue-Gang; Klyachko, Vitaly A.; Deng, Pan-Yue

2014-01-01

Transcriptional silencing of the Fmr1 gene encoding fragile X mental retardation protein (FMRP) causes Fragile X Syndrome (FXS), the most common form of inherited intellectual disability and the leading genetic cause of autism. FMRP has been suggested to play important roles in regulating neurotransmission and short-term synaptic plasticity at excitatory hippocampal and cortical synapses. However, the origins and the mechanisms of these FMRP actions remain incompletely understood, and the role of FMRP in regulating synaptic release probability and presynaptic function remains debated. Here we used variance-mean analysis and peak scaled nonstationary variance analysis to examine changes in both pre- and postsynaptic parameters during repetitive activity at excitatory CA3-CA1 hippocampal synapses in a mouse model of FXS. Our analyses revealed that loss of FMRP did not affect the basal release probability or basal synaptic transmission, but caused an abnormally elevated release probability specifically during repetitive activity. These abnormalities were not accompanied by changes in EPSC kinetics, quantal size or postsynaptic AMPA receptor conductance. Our results thus indicate that FMRP regulates neurotransmission at excitatory hippocampal synapses specifically during repetitive activity via modulation of release probability in a presynaptic manner. Our study suggests that FMRP function in regulating neurotransmitter release is an activity-dependent phenomenon that may contribute to the pathophysiology of FXS. PMID:24646437

Factors Underlying Bursting Behavior in a Network of Cultured Hippocampal Neurons Exposed to Zero Magnesium

PubMed Central

Mangan, Patrick S.; Kapur, Jaideep

2010-01-01

Factors contributing to reduced magnesium-induced neuronal action potential bursting were investigated in primary hippocampal cell culture at high and low culture density. In nominally zero external magnesium medium, pyramidal neurons from high-density cultures produced recurrent spontaneous action potential bursts superimposed on prolonged depolarizations. These bursts were partially attenuated by the NMDA receptor antagonist D-APV. Pharmacological analysis of miniature excitatory postsynaptic currents (EPSCs) revealed 2 components: one sensitive to D-APV and another to the AMPA receptor antagonist DNQX. The components were kinetically distinct. Participation of NMDA receptors in reduced magnesium-induced synaptic events was supported by the localization of the NR1 subunit of the NMDA receptor with the presynaptic vesicular protein synaptophysin. Presynaptically, zero magnesium induced a significant increase in EPSC frequency likely attributable to increased neuronal hyperexcitability induced by reduced membrane surface charge screening. Mean quantal content was significantly increased in zero magnesium. Cells from low-density cultures did not exhibit action potential bursting in zero magnesium but did show increased EPSC frequency. Low-density neurons had less synaptophysin immunofluorescence and fewer active synapses as determined by FM1-43 analysis. These results demonstrate that multiple factors are involved in network bursting. Increased probability of transmitter release presynaptically, enhanced NMDA receptor-mediated excitability postsynaptically, and extent of neuronal interconnectivity contribute to initiation and maintenance of elevated network excitability. PMID:14534286

PREFACE: Quantum information processing

NASA Astrophysics Data System (ADS)

Briggs, Andrew; Ferry, David; Stoneham, Marshall

2006-05-01

Microelectronics and the classical information technologies transformed the physics of semiconductors. Photonics has given optical materials a new direction. Quantum information technologies, we believe, will have immense impact on condensed matter physics. The novel systems of quantum information processing need to be designed and made. Their behaviours must be manipulated in ways that are intrinsically quantal and generally nanoscale. Both in this special issue and in previous issues (see e.g., Spiller T P and Munro W J 2006 J. Phys.: Condens. Matter 18 V1-10) we see the emergence of new ideas that link the fundamentals of science to the pragmatism of market-led industry. We hope these papers will be followed by many others on quantum information processing in the Journal of Physics: Condensed Matter.

Graphical method for comparative statistical study of vaccine potency tests.

PubMed

Pay, T W; Hingley, P J

1984-03-01

Producers and consumers are interested in some of the intrinsic characteristics of vaccine potency assays for the comparative evaluation of suitable experimental design. A graphical method is developed which represents the precision of test results, the sensitivity of such results to changes in dosage, and the relevance of the results in the way they reflect the protection afforded in the host species. The graphs can be constructed from Producer's scores and Consumer's scores on each of the scales of test score, antigen dose and probability of protection against disease. A method for calculating these scores is suggested and illustrated for single and multiple component vaccines, for tests which do or do not employ a standard reference preparation, and for tests which employ quantitative or quantal systems of scoring.

Metabolic Control of Vesicular Glutamate Transport and Release

PubMed Central

Juge, Narinobu; Gray, John A.; Omote, Hiroshi; Miyaji, Takaaki; Inoue, Tsuyoshi; Hara, Chiaki; Uneyama, Hisayuki; Edwards, Robert H.; Nicoll, Roger A.; Moriyama, Yoshinori

2010-01-01

Fasting has been used to control epilepsy since antiquity, but the mechanism of coupling between metabolic state and excitatory neurotransmission remains unknown. Previous work has shown that the vesicular glutamate transporters (VGLUTs) required for exocytotic release of glutamate undergo an unusual form of regulation by Cl−. Using functional reconstitution of the purified VGLUTs into proteoliposomes, we now show that Cl− acts as an allosteric activator, and the ketone bodies that increase with fasting inhibit glutamate release by competing with Cl− at the site of allosteric regulation. Consistent with these observations, acetoacetate reduced quantal size at hippocampal synapses, and suppresses glutamate release and seizures evoked with 4-aminopyridine in the brain. The results indicate an unsuspected link between metabolic state and excitatory neurotransmission through anion-dependent regulation of VGLUT activity. PMID:20920794

Thermospheric production of O(1S) by dissociative recombination of vibrationally excited O2(+)

NASA Technical Reports Server (NTRS)

Yee, Jeng-Hwa; Killeen, T. L.

1986-01-01

High spectral resolution line profiles at 5577 A of the nighttime, F-region O(1S) emission measured by the Fabry-Perot interferometer on board the Dynamics Explorer satellite are analyzed using a continuous O(1S) relaxation model. The model is an improvement over the previous model of Killeen and Hays (1981) in that energy loss via elastic collision is considered in addition to the single collision, excitation exchange thermalization process. The results show that the active channel for O(1S) production is capture into the 1Sigma(+)u repulsive state of O2 and that the main contributor to its production is the dissociative recombination of O2(+) ions in vibrational levels v = 1 and 2 in agreement with the quantal calculations of Guberman (1983).

Optogenetic Acidification of Synaptic Vesicles and Lysosomes

PubMed Central

Grauel, M. Katharina; Wozny, Christian; Bentz, Claudia; Blessing, Anja; Rosenmund, Tanja; Jentsch, Thomas J.; Schmitz, Dietmar; Hegemann, Peter; Rosenmund, Christian

2016-01-01

Acidification is required for the function of many intracellular organelles, but methods to acutely manipulate their intraluminal pH have not been available. Here we present a targeting strategy to selectively express the light-driven proton pump Arch3 on synaptic vesicles. Our new tool, pHoenix, can functionally replace endogenous proton pumps, enabling optogenetic control of vesicular acidification and neurotransmitter accumulation. Under physiological conditions, glutamatergic vesicles are nearly full, as additional vesicle acidification with pHoenix only slightly increased the quantal size. By contrast, we found that incompletely filled vesicles exhibited a lower release probability than full vesicles, suggesting preferential exocytosis of vesicles with high transmitter content. Our subcellular targeting approach can be transferred to other organelles, as demonstrated for a pHoenix variant that allows light-activated acidification of lysosomes. PMID:26551543

Optogenetic acidification of synaptic vesicles and lysosomes.

PubMed

Rost, Benjamin R; Schneider, Franziska; Grauel, M Katharina; Wozny, Christian; Bentz, Claudia; Blessing, Anja; Rosenmund, Tanja; Jentsch, Thomas J; Schmitz, Dietmar; Hegemann, Peter; Rosenmund, Christian

2015-12-01

Acidification is required for the function of many intracellular organelles, but methods to acutely manipulate their intraluminal pH have not been available. Here we present a targeting strategy to selectively express the light-driven proton pump Arch3 on synaptic vesicles. Our new tool, pHoenix, can functionally replace endogenous proton pumps, enabling optogenetic control of vesicular acidification and neurotransmitter accumulation. Under physiological conditions, glutamatergic vesicles are nearly full, as additional vesicle acidification with pHoenix only slightly increased the quantal size. By contrast, we found that incompletely filled vesicles exhibited a lower release probability than full vesicles, suggesting preferential exocytosis of vesicles with high transmitter content. Our subcellular targeting approach can be transferred to other organelles, as demonstrated for a pHoenix variant that allows light-activated acidification of lysosomes.

A Static and Dynamic Investigation of Quantum Nonlinear Transport in Highly Dense and Mobile 2D Electron Systems

NASA Astrophysics Data System (ADS)

Dietrich, Scott

Heterostructures made of semiconductor materials may be one of most versatile environments for the study of the physics of electron transport in two dimensions. These systems are highly customizable and demonstrate a wide range of interesting physical phenomena. In response to both microwave radiation and DC excitations, strongly nonlinear transport that gives rise to non-equilibrium electron states has been reported and investigated. We have studied GaAs quantum wells with a high density of high mobility two-dimensional electrons placed in a quantizing magnetic field. This study presents the observation of several nonlinear transport mechanisms produced by the quantum nature of these materials. The quantum scattering rate, 1tau/q, is an important parameter in these systems, defining the width of the quantized energy levels. Traditional methods of extracting 1tau/q involve studying the amplitude of Shubnikov-de Haas oscillations. We analyze the quantum positive magnetoresistance due to the cyclotron motion of electrons in a magnetic field. This method gives 1tau/q and has the additional benefit of providing access to the strength of electron-electron interactions, which is not possible by conventional techniques. The temperature dependence of the quantum scattering rate is found to be proportional to the square of the temperature and is in very good agreement with theory that considers electron-electron interactions in 2D systems. In quantum wells with a small scattering rate - which corresponds to well-defined Landau levels - quantum oscillations of nonlinear resistance that are independent of magnetic field strength have been observed. These oscillations are periodic in applied bias current and are connected to quantum oscillations of resistance at zero bias: either Shubnikov-de Haas oscillations for single subband systems or magnetointersubband oscillations for two subband systems. The bias-induced oscillations can be explained by a spatial variation of electron density across the sample. The theoretical model predicts the period of these oscillations to depend on the total electron density, which has been confirmed by controlling the density through a voltage top-gate on the sample. The peculiar nonlinear mechanism of quantal heating has garned much attention recently. This bulk phenomenon is a quantum manifestation of Joule heating where an applied bias current causes selective flattening in the electron distribution function but conserves overall broadening. This produces a highly non-equilibrium distribution of electrons that drastically effects the transport properties of the system. Recent studies have proposed contributions from edge states and/or skipping orbitals. We have shown that these contributions are minimal by studying the transition to the zero differential conductance state and comparing results between Hall and Corbino geometries. This demonstrated quantal heating as the dominant nonlinear mechanism in these systems. To study the dynamics of quantal heating, we applied microwave radiation simultaneously from two sources at frequencies ƒ1 and ƒ2 and measured the response of the system at the difference frequency, ƒ=|ƒ 1-ƒ2|. This provides direct access to the rate of inelastic scattering processes, 1tau/in, that tend to bring the electron distribution back to thermal equilibrium. While conventional measurements of the temperature dependence indicate that 1tau/in is proportional to temperature, recent DC investigations and our new dynamic measurements show either T2 or T3 dependence in different magnetic fields. Our microwave experiment is the first direct access to the inelastic relaxation rate and confirms the non-linear temperature dependence.

Bayesian analysis of the kinetics of quantal transmitter secretion at the neuromuscular junction.

PubMed

Saveliev, Anatoly; Khuzakhmetova, Venera; Samigullin, Dmitry; Skorinkin, Andrey; Kovyazina, Irina; Nikolsky, Eugeny; Bukharaeva, Ellya

2015-10-01

The timing of transmitter release from nerve endings is considered nowadays as one of the factors determining the plasticity and efficacy of synaptic transmission. In the neuromuscular junction, the moments of release of individual acetylcholine quanta are related to the synaptic delays of uniquantal endplate currents recorded under conditions of lowered extracellular calcium. Using Bayesian modelling, we performed a statistical analysis of synaptic delays in mouse neuromuscular junction with different patterns of rhythmic nerve stimulation and when the entry of calcium ions into the nerve terminal was modified. We have obtained a statistical model of the release timing which is represented as the summation of two independent statistical distributions. The first of these is the exponentially modified Gaussian distribution. The mixture of normal and exponential components in this distribution can be interpreted as a two-stage mechanism of early and late periods of phasic synchronous secretion. The parameters of this distribution depend on both the stimulation frequency of the motor nerve and the calcium ions' entry conditions. The second distribution was modelled as quasi-uniform, with parameters independent of nerve stimulation frequency and calcium entry. Two different probability density functions for the distribution of synaptic delays suggest at least two independent processes controlling the time course of secretion, one of them potentially involving two stages. The relative contribution of these processes to the total number of mediator quanta released depends differently on the motor nerve stimulation pattern and on calcium ion entry into nerve endings.

Understanding the fusion cross section among light nuclei around the Coulomb barrier

NASA Astrophysics Data System (ADS)

Del Zoppo, Antonio; La Cognata, Marco

2017-11-01

In this work we investigate fusion induced by a radioactive 8Li projectile on a 4He gas target, at center-of-mass energies between 0.6 and 5 MeV. The main result is the tendency of the dimensionless fusion cross section to form well visible plateaus alternated to steep rises. This is likely to be the most genuine consequence of the discrete nature of the intervening angular momenta observed so far in fusion reactions right above the Coulomb barrier. A partial-wave analysis, exclusively based on a pure quantal penetration fusion model, identifies a remarkably low-height barrier. Indeed, these plateaus allow enhanced experimental sensitivity to the fusion barrier given that the most barrier-sensitive lowest partial waves are well separated. We expect that the present results for 8Li+4He will promote further investigations of the fusion reaction mechanism between very light ions at energies much below the interaction barrier. For the moment, we believe that understanding the plateau origin in the cross section above the barrier will almost certainly be useful to corroborate the extrapolation to the important astrophysical region below the Coulomb barrier, not only in the case of the 8Li+4He fusion but also for other systems, such as the 12C+12C.

Comparative study of the requantization of the time-dependent mean field for the dynamics of nuclear pairing

NASA Astrophysics Data System (ADS)

Ni, Fang; Nakatsukasa, Takashi

2018-04-01

To describe quantal collective phenomena, it is useful to requantize the time-dependent mean-field dynamics. We study the time-dependent Hartree-Fock-Bogoliubov (TDHFB) theory for the two-level pairing Hamiltonian, and compare results of different quantization methods. The one constructing microscopic wave functions, using the TDHFB trajectories fulfilling the Einstein-Brillouin-Keller quantization condition, turns out to be the most accurate. The method is based on the stationary-phase approximation to the path integral. We also examine the performance of the collective model which assumes that the pairing gap parameter is the collective coordinate. The applicability of the collective model is limited for the nuclear pairing with a small number of single-particle levels, because the pairing gap parameter represents only a half of the pairing collective space.

The ambiguity of simplicity in quantum and classical simulation

NASA Astrophysics Data System (ADS)

Aghamohammadi, Cina; Mahoney, John R.; Crutchfield, James P.

2017-04-01

A system's perceived simplicity depends on whether it is represented classically or quantally. This is not so surprising, as classical and quantum physics are descriptive frameworks built on different assumptions that capture, emphasize, and express different properties and mechanisms. What is surprising is that, as we demonstrate, simplicity is ambiguous: the relative simplicity between two systems can change sign when moving between classical and quantum descriptions. Here, we associate simplicity with small model-memory. We see that the notions of absolute physical simplicity at best form a partial, not a total, order. This suggests that appeals to principles of physical simplicity, via Ockham's Razor or to the ;elegance; of competing theories, may be fundamentally subjective. Recent rapid progress in quantum computation and quantum simulation suggest that the ambiguity of simplicity will strongly impact statistical inference and, in particular, model selection.

Charge Transfer Between Ground-State Si(3+) and He at Electron-Volt Energies

NASA Technical Reports Server (NTRS)

Fang, Z.; Kwong, Victor H. S.

1997-01-01

The charge-transfer rate coefficient for the reaction Si(3+)(3s(sup 2)S) + He yields products is measured by means of a combined technique of laser ablation and ion storage. A cylindrical radio-frequency ion trap was used to store Si(3+) ions produced by laser ablation of solid silicon targets. The rate coefficient of the reaction was derived from the decay rate of the ion signal. The measured rate coefficient is 6.27(exp +0.68)(sub -0.52) x 10(exp -10)cu cm/s at T(sub equiv) = 3.9 x 10(exp 3)K. This value is about 30% higher than the Landau-Zener calculation of Butler and Dalgarno and is larger by about a factor of 3 than the recent full quantal calculation of Honvault et al.

Dose-response relationships in a microneutralization test for foot-and-mouth disease viruses.

PubMed Central

Booth, J. C.; Rweyemamu, M. M.; Pay, T. W.

1978-01-01

Two-dimensional quantal microneutralization tests on foot-and-mouth disease viruses, in which neutralizing antibody activity was titrated against a serial range of virus doses, demonstrated a variety of dose-response curves some of which were rectilinear, others clearly curvilinear. Moreover, in the case of the non-linear responses obtained with some antisera, the shape of the curve was such that antibody titres recorded with doses of virus ranging from 10(3)-10(5) TCD50 were closely similar. Studies were carried out on the effect of varying the conditions of the test on the shape of the dose-response curve: significant differences were obtained after treatment of the antiserum-virus mixtures with anti-species globulin, and when the test was assayed in cells of differing susceptibility to infection. PMID:202650

Metabolic control of vesicular glutamate transport and release.

PubMed

Juge, Narinobu; Gray, John A; Omote, Hiroshi; Miyaji, Takaaki; Inoue, Tsuyoshi; Hara, Chiaki; Uneyama, Hisayuki; Edwards, Robert H; Nicoll, Roger A; Moriyama, Yoshinori

2010-10-06

Fasting has been used to control epilepsy since antiquity, but the mechanism of coupling between metabolic state and excitatory neurotransmission remains unknown. Previous work has shown that the vesicular glutamate transporters (VGLUTs) required for exocytotic release of glutamate undergo an unusual form of regulation by Cl(-). Using functional reconstitution of the purified VGLUTs into proteoliposomes, we now show that Cl(-) acts as an allosteric activator, and the ketone bodies that increase with fasting inhibit glutamate release by competing with Cl(-) at the site of allosteric regulation. Consistent with these observations, acetoacetate reduced quantal size at hippocampal synapses and suppresses glutamate release and seizures evoked with 4-aminopyridine in the brain. The results indicate an unsuspected link between metabolic state and excitatory neurotransmission through anion-dependent regulation of VGLUT activity. Copyright © 2010 Elsevier Inc. All rights reserved.

Potential uncertainty reduction in model-averaged benchmark dose estimates informed by an additional dose study.

PubMed

Shao, Kan; Small, Mitchell J

2011-10-01

A methodology is presented for assessing the information value of an additional dosage experiment in existing bioassay studies. The analysis demonstrates the potential reduction in the uncertainty of toxicity metrics derived from expanded studies, providing insights for future studies. Bayesian methods are used to fit alternative dose-response models using Markov chain Monte Carlo (MCMC) simulation for parameter estimation and Bayesian model averaging (BMA) is used to compare and combine the alternative models. BMA predictions for benchmark dose (BMD) are developed, with uncertainty in these predictions used to derive the lower bound BMDL. The MCMC and BMA results provide a basis for a subsequent Monte Carlo analysis that backcasts the dosage where an additional test group would have been most beneficial in reducing the uncertainty in the BMD prediction, along with the magnitude of the expected uncertainty reduction. Uncertainty reductions are measured in terms of reduced interval widths of predicted BMD values and increases in BMDL values that occur as a result of this reduced uncertainty. The methodology is illustrated using two existing data sets for TCDD carcinogenicity, fitted with two alternative dose-response models (logistic and quantal-linear). The example shows that an additional dose at a relatively high value would have been most effective for reducing the uncertainty in BMA BMD estimates, with predicted reductions in the widths of uncertainty intervals of approximately 30%, and expected increases in BMDL values of 5-10%. The results demonstrate that dose selection for studies that subsequently inform dose-response models can benefit from consideration of how these models will be fit, combined, and interpreted. © 2011 Society for Risk Analysis.

Statistical analysis of nonmonotonic dose-response relationships: research design and analysis of nasal cell proliferation in rats exposed to formaldehyde.

PubMed

Gaylor, David W; Lutz, Werner K; Conolly, Rory B

2004-01-01

Statistical analyses of nonmonotonic dose-response curves are proposed, experimental designs to detect low-dose effects of J-shaped curves are suggested, and sample sizes are provided. For quantal data such as cancer incidence rates, much larger numbers of animals are required than for continuous data such as biomarker measurements. For example, 155 animals per dose group are required to have at least an 80% chance of detecting a decrease from a 20% incidence in controls to an incidence of 10% at a low dose. For a continuous measurement, only 14 animals per group are required to have at least an 80% chance of detecting a change of the mean by one standard deviation of the control group. Experimental designs based on three dose groups plus controls are discussed to detect nonmonotonicity or to estimate the zero equivalent dose (ZED), i.e., the dose that produces a response equal to the average response in the controls. Cell proliferation data in the nasal respiratory epithelium of rats exposed to formaldehyde by inhalation are used to illustrate the statistical procedures. Statistically significant departures from a monotonic dose response were obtained for time-weighted average labeling indices with an estimated ZED at a formaldehyde dose of 5.4 ppm, with a lower 95% confidence limit of 2.7 ppm. It is concluded that demonstration of a statistically significant bi-phasic dose-response curve, together with estimation of the resulting ZED, could serve as a point-of departure in establishing a reference dose for low-dose risk assessment.

Perspective: Quantum mechanical methods in biochemistry and biophysics.

PubMed

Cui, Qiang

2016-10-14

In this perspective article, I discuss several research topics relevant to quantum mechanical (QM) methods in biophysical and biochemical applications. Due to the immense complexity of biological problems, the key is to develop methods that are able to strike the proper balance of computational efficiency and accuracy for the problem of interest. Therefore, in addition to the development of novel ab initio and density functional theory based QM methods for the study of reactive events that involve complex motifs such as transition metal clusters in metalloenzymes, it is equally important to develop inexpensive QM methods and advanced classical or quantal force fields to describe different physicochemical properties of biomolecules and their behaviors in complex environments. Maintaining a solid connection of these more approximate methods with rigorous QM methods is essential to their transferability and robustness. Comparison to diverse experimental observables helps validate computational models and mechanistic hypotheses as well as driving further development of computational methodologies.

Cluster of wound botulism in California: clinical, electrophysiologic, and pathologic study.

PubMed

Maselli, R A; Ellis, W; Mandler, R N; Sheikh, F; Senton, G; Knox, S; Salari-Namin, H; Agius, M; Wollmann, R L; Richman, D P

1997-10-01

Over a period of 15 months we have seen 6 patients with long-standing history of subcutaneous heroin injections who experienced acute blurred vision, dysphagia, dysarthria, and generalized weakness. Decreased or absent deep tendon reflexes, pupillary abnormalities, incremental responses to fast repetitive nerve stimulation, and positive serology for Clostridia botulinum toxin A were found, but not in all cases. Muscle biopsies showed variable signs of neurogenic atrophy. In vitro electrophysiology studies revealed decreased end-plate potentials quantal content, confirming the presynaptic nature of the disorder. Mechanical ventilation was required in 5 patients. Half of the patients were treated with polyvalent antitoxiin. Prognosis was favorable, though recovery was slow. In conclusion, acute bulbar weakness with visual symptoms in patients with subcutaneous heroin abuse strongly suggets the possibility of wound botulism. High diagnostic suspicion combined with histology and in vitro electrophysiology confirmation of presynaptic failure, especially in seronegative cases, may significantly improve morbidity.

Protein kinase C involvement in the acetylcholine release reduction induced by amyloid-beta(25-35) aggregates on neuromuscular synapses.

PubMed

Tomàs, Marta; Garcia, Neus; Santafé, Manuel M; Lanuza, Maria; Tomàs, Josep

2009-01-01

Using intracellular recording of the diaphragm muscle of adult rats, we have investigated the short-term functional effects of amyloid-beta (Abeta(25-35) peptide aggregates on the modulation of acetylcholine (ACh) release and the involvement of protein kinase C (PKC). The non-aggregated form of this peptide does not change the evoked and spontaneous transmitter release parameters on the neuromuscular synapse. However, the aggregated form of Abeta(25-35) acutely interferes with evoked quantal ACh release (approximately 40% reduction) when synaptic activity in the ex vivo neuromuscular preparation is maintained by low frequency (1 Hz) electrical stimulation. This effect is partially dependent on the activity of PKC that may have a permissive action. The end result of Abeta(25-35) is in opposition to the PKC-dependent maintenance effect on ACh release manifested in active synapses.

Striatal dopamine neurotransmission: regulation of release and uptake

PubMed Central

Sulzer, David; Cragg, Stephanie J.; Rice, Margaret E.

2016-01-01

Dopamine (DA) transmission is governed by processes that regulate release from axonal boutons in the forebrain and the somatodendritic compartment in midbrain, and by clearance by the DA transporter, diffusion, and extracellular metabolism. We review how axonal DA release is regulated by neuronal activity and by autoreceptors and heteroreceptors, and address how quantal release events are regulated in size and frequency. In brain regions densely innervated by DA axons, DA clearance is due predominantly to uptake by the DA transporter, whereas in cortex, midbrain, and other regions with relatively sparse DA inputs, the norepinephrine transporter and diffusion are involved. We discuss the role of DA uptake in restricting the sphere of influence of DA and in temporal accumulation of extracellular DA levels upon successive action potentials. The tonic discharge activity of DA neurons may be translated into a tonic extracellular DA level, whereas their bursting activity can generate discrete extracellular DA transients. PMID:27141430

Evidence that protons act as neurotransmitters at vestibular hair cell-calyx afferent synapses.

PubMed

Highstein, Stephen M; Holstein, Gay R; Mann, Mary Anne; Rabbitt, Richard D

2014-04-08

Present data support the conclusion that protons serve as an important neurotransmitter to convey excitatory stimuli from inner ear type I vestibular hair cells to postsynaptic calyx nerve terminals. Time-resolved pH imaging revealed stimulus-evoked extrusion of protons from hair cells and a subsequent buildup of [H(+)] within the confined chalice-shaped synaptic cleft (ΔpH ∼ -0.2). Whole-cell voltage-clamp recordings revealed a concomitant nonquantal excitatory postsynaptic current in the calyx terminal that was causally modulated by cleft acidification. The time course of [H(+)] buildup limits the speed of this intercellular signaling mechanism, but for tonic signals such as gravity, protonergic transmission offers a significant metabolic advantage over quantal excitatory postsynaptic currents--an advantage that may have driven the proliferation of postsynaptic calyx terminals in the inner ear vestibular organs of contemporary amniotes.

Protons Regulate Vesicular Glutamate Transporters through an Allosteric Mechanism.

PubMed

Eriksen, Jacob; Chang, Roger; McGregor, Matt; Silm, Katlin; Suzuki, Toshiharu; Edwards, Robert H

2016-05-18

The quantal nature of synaptic transmission requires a mechanism to transport neurotransmitter into synaptic vesicles without promoting non-vesicular efflux across the plasma membrane. Indeed, the vesicular transport of most classical transmitters involves a mechanism of H(+) exchange, which restricts flux to acidic membranes such as synaptic vesicles. However, vesicular transport of the principal excitatory transmitter glutamate depends primarily on membrane potential, which would drive non-vesicular efflux, and the role of protons is unclear. Adapting electrophysiology to record currents associated with the vesicular glutamate transporters (VGLUTs), we characterize a chloride conductance that is gated by lumenal protons and chloride and supports glutamate uptake. Rather than coupling stoichiometrically to glutamate flux, lumenal protons and chloride allosterically activate vesicular glutamate transport. Gating by protons serves to inhibit what would otherwise be substantial non-vesicular glutamate efflux at the plasma membrane, thereby restricting VGLUT activity to synaptic vesicles. Copyright © 2016 Elsevier Inc. All rights reserved.

Readily releasable pool of synaptic vesicles measured at single synaptic contacts.

PubMed

Trigo, Federico F; Sakaba, Takeshi; Ogden, David; Marty, Alain

2012-10-30

To distinguish between different models of vesicular release in brain synapses, it is necessary to know the number of vesicles of transmitter that can be released immediately at individual synapses by a high-calcium stimulus, the readily releasable pool (RRP). We used direct stimulation by calcium uncaging at identified, single-site inhibitory synapses to investigate the statistics of vesicular release and the size of the RRP. Vesicular release, detected as quantal responses in the postsynaptic neuron, showed an unexpected stochastic variation in the number of quanta from stimulus to stimulus at high intracellular calcium, with a mean of 1.9 per stimulus and a maximum of three or four. The results provide direct measurement of the RRP at single synaptic sites. They are consistent with models in which release proceeds from a small number of vesicle docking sites with an average occupancy around 0.7.

A Unified Probabilistic Framework for Dose-Response Assessment of Human Health Effects.

PubMed

Chiu, Weihsueh A; Slob, Wout

2015-12-01

When chemical health hazards have been identified, probabilistic dose-response assessment ("hazard characterization") quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. We developed a unified framework for probabilistic dose-response assessment. We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose-response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, "effect metrics" can be specified to define "toxicologically equivalent" sizes for this underlying individual response; and d) dose-response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose-response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Probabilistically derived exposure limits are based on estimating a "target human dose" (HDMI), which requires risk management-informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%-10% effect sizes. Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk management decisions.

Spatial intensity distribution analysis quantifies the extent and regulation of homodimerization of the secretin receptor

PubMed Central

Ward, Richard J.; Pediani, John D.; Harikumar, Kaleeckal G.; Miller, Laurence J.

2017-01-01

Previous studies have indicated that the G-protein-coupled secretin receptor is present as a homodimer, organized through symmetrical contacts in transmembrane domain IV, and that receptor dimerization is critical for high-potency signalling by secretin. However, whether all of the receptor exists in the dimeric form or if this is regulated is unclear. We used measures of quantal brightness of the secretin receptor tagged with monomeric enhanced green fluorescent protein (mEGFP) and spatial intensity distribution analysis to assess this. Calibration using cells expressing plasma membrane-anchored forms of mEGFP initially allowed us to demonstrate that the epidermal growth factor receptor is predominantly monomeric in the absence of ligand and while wild-type receptor was rapidly converted into a dimeric form by ligand, a mutated form of this receptor remained monomeric. Equivalent studies showed that, at moderate expression levels, the secretin receptor exists as a mixture of monomeric and dimeric forms, with little evidence of higher-order complexity. However, sodium butyrate-induced up-regulation of the receptor resulted in a shift from monomeric towards oligomeric organization. In contrast, a form of the secretin receptor containing a pair of mutations on the lipid-facing side of transmembrane domain IV was almost entirely monomeric. Down-regulation of the secretin receptor-interacting G-protein Gαs did not alter receptor organization, indicating that dimerization is defined specifically by direct protein–protein interactions between copies of the receptor polypeptide, while short-term treatment with secretin had no effect on organization of the wild-type receptor but increased the dimeric proportion of the mutated receptor variant. PMID:28424368

Effect of Rhodopsin Phosphorylation on Dark Adaptation in Mouse Rods

PubMed Central

Berry, Justin; Frederiksen, Rikard; Yao, Yun; Nymark, Soile

2016-01-01

Rhodopsin is a prototypical G-protein-coupled receptor (GPCR) that is activated when its 11-cis-retinal moiety is photoisomerized to all-trans retinal. This step initiates a cascade of reactions by which rods signal changes in light intensity. Like other GPCRs, rhodopsin is deactivated through receptor phosphorylation and arrestin binding. Full recovery of receptor sensitivity is then achieved when rhodopsin is regenerated through a series of steps that return the receptor to its ground state. Here, we show that dephosphorylation of the opsin moiety of rhodopsin is an extremely slow but requisite step in the restoration of the visual pigment to its ground state. We make use of a novel observation: isolated mouse retinae kept in standard media for routine physiologic recordings display blunted dephosphorylation of rhodopsin. Isoelectric focusing followed by Western blot analysis of bleached isolated retinae showed little dephosphorylation of rhodopsin for up to 4 h in darkness, even under conditions when rhodopsin was completely regenerated. Microspectrophotometeric determinations of rhodopsin spectra show that regenerated phospho-rhodopsin has the same molecular photosensitivity as unphosphorylated rhodopsin and that flash responses measured by trans-retinal electroretinogram or single-cell suction electrode recording displayed dark-adapted kinetics. Single quantal responses displayed normal dark-adapted kinetics, but rods were only half as sensitive as those containing exclusively unphosphorylated rhodopsin. We propose a model in which light-exposed retinae contain a mixed population of phosphorylated and unphosphorylated rhodopsin. Moreover, complete dark adaptation can only occur when all rhodopsin has been dephosphorylated, a process that requires >3 h in complete darkness. SIGNIFICANCE STATEMENT G-protein-coupled receptors (GPCRs) constitute the largest superfamily of proteins that compose ∼4% of the mammalian genome whose members share a common membrane topology. Signaling by GPCRs regulate a wide variety of physiological processes, including taste, smell, hearing, vision, and cardiovascular, endocrine, and reproductive homeostasis. An important feature of GPCR signaling is its timely termination. This normally occurs when, after their activation, GPCRs are rapidly phosphorylated by specific receptor kinases and subsequently bound by cognate arrestins. Recovery of receptor sensitivity to the ground state then requires dephosphorylation of the receptor and unbinding of arrestin, processes that are poorly understood. Here we investigate in mouse rod photoreceptors the relationship between rhodopsin dephosphorylation and recovery of visual sensitivity. PMID:27358455

A computational study of astrocytic glutamate influence on post-synaptic neuronal excitability.

PubMed

Flanagan, Bronac; McDaid, Liam; Wade, John; Wong-Lin, KongFatt; Harkin, Jim

2018-04-01

The ability of astrocytes to rapidly clear synaptic glutamate and purposefully release the excitatory transmitter is critical in the functioning of synapses and neuronal circuits. Dysfunctions of these homeostatic functions have been implicated in the pathology of brain disorders such as mesial temporal lobe epilepsy. However, the reasons for these dysfunctions are not clear from experimental data and computational models have been developed to provide further understanding of the implications of glutamate clearance from the extracellular space, as a result of EAAT2 downregulation: although they only partially account for the glutamate clearance process. In this work, we develop an explicit model of the astrocytic glutamate transporters, providing a more complete description of the glutamate chemical potential across the astrocytic membrane and its contribution to glutamate transporter driving force based on thermodynamic principles and experimental data. Analysis of our model demonstrates that increased astrocytic glutamate content due to glutamine synthetase downregulation also results in increased postsynaptic quantal size due to gliotransmission. Moreover, the proposed model demonstrates that increased astrocytic glutamate could prolong the time course of glutamate in the synaptic cleft and enhances astrocyte-induced slow inward currents, causing a disruption to the clarity of synaptic signalling and the occurrence of intervals of higher frequency postsynaptic firing. Overall, our work distilled the necessity of a low astrocytic glutamate concentration for reliable synaptic transmission of information and the possible implications of enhanced glutamate levels as in epilepsy.

Metamaterial bricks and quantization of meta-surfaces

PubMed Central

Memoli, Gianluca; Caleap, Mihai; Asakawa, Michihiro; Sahoo, Deepak R.; Drinkwater, Bruce W.; Subramanian, Sriram

2017-01-01

Controlling acoustic fields is crucial in diverse applications such as loudspeaker design, ultrasound imaging and therapy or acoustic particle manipulation. The current approaches use fixed lenses or expensive phased arrays. Here, using a process of analogue-to-digital conversion and wavelet decomposition, we develop the notion of quantal meta-surfaces. The quanta here are small, pre-manufactured three-dimensional units—which we call metamaterial bricks—each encoding a specific phase delay. These bricks can be assembled into meta-surfaces to generate any diffraction-limited acoustic field. We apply this methodology to show experimental examples of acoustic focusing, steering and, after stacking single meta-surfaces into layers, the more complex field of an acoustic tractor beam. We demonstrate experimentally single-sided air-borne acoustic levitation using meta-layers at various bit-rates: from a 4-bit uniform to 3-bit non-uniform quantization in phase. This powerful methodology dramatically simplifies the design of acoustic devices and provides a key-step towards realizing spatial sound modulators. PMID:28240283

ESTIMATION OF THE NUMBER OF INFECTIOUS BACTERIAL OR VIRAL PARTICLES BY THE DILUTION METHOD

PubMed Central

Seligman, Stephen J.; Mickey, M. Ray

1964-01-01

Seligman, Stephen J. (University of California, Los Angeles), and M. Ray Mickey. Estimation of the number of infectious bacterial or viral particles by the dilution method. J. Bacteriol. 88:31–36. 1964.—For viral or bacterial systems in which discrete foci of infection are not obtainable, it is possible to obtain an estimate of the number of infectious particles by use of the quantal response if the assay system is such that one infectious particle can elicit the response. Unfortunately, the maximum likelihood estimate is difficult to calculate, but, by the use of a modification of Haldane's approximation, it is possible to construct a table which facilitates calculation of both the average number of infectious particles and its relative error. Additional advantages of the method are that the number of test units per dilution can be varied, the dilutions need not bear any fixed relation to each other, and the one-particle hypothesis can be readily tested. PMID:14197902

Distance-dependent gradient in NMDAR-driven spine calcium signals along tapering dendrites

PubMed Central

Walker, Alison S.; Grillo, Federico; Jackson, Rachel E.; Rigby, Mark; Lowe, Andrew S.; Vizcay-Barrena, Gema; Fleck, Roland A.; Burrone, Juan

2017-01-01

Neurons receive a multitude of synaptic inputs along their dendritic arbor, but how this highly heterogeneous population of synaptic compartments is spatially organized remains unclear. By measuring N-methyl-d-aspartic acid receptor (NMDAR)-driven calcium responses in single spines, we provide a spatial map of synaptic calcium signals along dendritic arbors of hippocampal neurons and relate this to measures of synapse structure. We find that quantal NMDAR calcium signals increase in amplitude as they approach a thinning dendritic tip end. Based on a compartmental model of spine calcium dynamics, we propose that this biased distribution in calcium signals is governed by a gradual, distance-dependent decline in spine size, which we visualized using serial block-face scanning electron microscopy. Our data describe a cell-autonomous feature of principal neurons, where tapering dendrites show an inverse distribution of spine size and NMDAR-driven calcium signals along dendritic trees, with important implications for synaptic plasticity rules and spine function. PMID:28209776

Vesicular secretion of auxin

PubMed Central

Schlicht, Markus; Volkmann, Dieter; Mancuso, Stefano

2008-01-01

The plant hormone auxin is secreted in root apices via phospholipase Dζ2 (PLDζ2) activity which produces specific population of phosphatidic acid that stimulates secretion of vesicles enriched with auxin. These vesicles were reported to be localized at plant synapses which are active in auxin secretion, especially at the transition zone of the root apex. There are several implications of this vesicular secretion of auxin. In root apices, auxin emerges as plant neurotransmitter-like signal molecule which coordinates activities of adjacent cells via electric and chemical signaling. Putative quantal release of auxin after electrical stimulation, if confirmed, would be part of neuronal communication between plant cells. As auxin transport across plant synapses is tightly linked with integrated sensory perception of environment, especially of omnipresent gravity and light, this process is proposed to mediate the plant perception of environment. These neuronal features allow sessile plants to integrate multitude of sensory signals into the adaptive behavior of whole plants and the animal-like exploratory behavior of growing roots. PMID:19704646

Metamaterial bricks and quantization of meta-surfaces

NASA Astrophysics Data System (ADS)

Memoli, Gianluca; Caleap, Mihai; Asakawa, Michihiro; Sahoo, Deepak R.; Drinkwater, Bruce W.; Subramanian, Sriram

2017-02-01

Controlling acoustic fields is crucial in diverse applications such as loudspeaker design, ultrasound imaging and therapy or acoustic particle manipulation. The current approaches use fixed lenses or expensive phased arrays. Here, using a process of analogue-to-digital conversion and wavelet decomposition, we develop the notion of quantal meta-surfaces. The quanta here are small, pre-manufactured three-dimensional units--which we call metamaterial bricks--each encoding a specific phase delay. These bricks can be assembled into meta-surfaces to generate any diffraction-limited acoustic field. We apply this methodology to show experimental examples of acoustic focusing, steering and, after stacking single meta-surfaces into layers, the more complex field of an acoustic tractor beam. We demonstrate experimentally single-sided air-borne acoustic levitation using meta-layers at various bit-rates: from a 4-bit uniform to 3-bit non-uniform quantization in phase. This powerful methodology dramatically simplifies the design of acoustic devices and provides a key-step towards realizing spatial sound modulators.

Low-energy electron scattering from water molecules: A study of angular distributions

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

Gianturco, F.A.; Scialla, S.

1987-12-01

We report quantal calculations of elastic differential and momentum transfercross sections for the scattering of electrons by H/sub 2/O at low and intermediatecollision energies, i.e., from 2 to 20 eV. The fixed-nuclei approximation (FNA) was employed and a single-center expanded (SCE) wave function was used to represent the molecular target. The well-known divergence in the forward direction was corrected via Born closure formulas (see the text) and a parameter-free model, previously tested for methane targets, was used to describe exchange and polarization effects. The present results can be used to adequately describe angular distributions even at very small angles andmore » can be extended beyond the largest angles that have been experimentally measured. The behavior of momentum-transfer cross sections as a function of energy, and the comparison of our results with other static-exchange (SE) calculations, which use an entirely different approach, are presented and discussed.« less

An essential role of acetylcholine-glutamate synergy at habenular synapses in nicotine dependence

PubMed Central

Frahm, Silke; Antolin-Fontes, Beatriz; Görlich, Andreas; Zander, Johannes-Friedrich; Ahnert-Hilger, Gudrun; Ibañez-Tallon, Ines

2015-01-01

A great deal of interest has been focused recently on the habenula and its critical role in aversion, negative-reward and drug dependence. Using a conditional mouse model of the ACh-synthesizing enzyme choline acetyltransferase (Chat), we report that local elimination of acetylcholine (ACh) in medial habenula (MHb) neurons alters glutamate corelease and presynaptic facilitation. Electron microscopy and immuno-isolation analyses revealed colocalization of ACh and glutamate vesicular transporters in synaptic vesicles (SVs) in the central IPN. Glutamate reuptake in SVs prepared from the IPN was increased by ACh, indicating vesicular synergy. Mice lacking CHAT in habenular neurons were insensitive to nicotine-conditioned reward and withdrawal. These data demonstrate that ACh controls the quantal size and release frequency of glutamate at habenular synapses, and suggest that the synergistic functions of ACh and glutamate may be generally important for modulation of cholinergic circuit function and behavior. DOI: http://dx.doi.org/10.7554/eLife.11396.001 PMID:26623516

Highly sensitive detection of quantal dopamine secretion from pheochromocytoma cells using neural microelectrode array electrodeposited with polypyrrole graphene.

PubMed

Wang, Li; Xu, Huiren; Song, Yilin; Luo, Jinping; Wei, Wenjing; Xu, Shengwei; Cai, Xinxia

2015-04-15

For the measurement of events of dopamine (DA) release as well as the coordinating neurotransmission in the nerve system, a neural microelectrode array (nMEA) electrodeposited directionally with polypyrrole graphene (PG) nanocomposites was fabricated. The deposited graphene significantly increased the surface area of working electrode, which led to the nMEA (with diameter of 20 μm) with excellent selectivity and sensitivity to DA. Furthermore, PG film modification exhibited low detection limit (4 nM, S/N = 3.21), high sensitivity, and good linearity in the presence of ascorbic acid (e.g., 13933.12 μA mM(-1) cm(-2) in the range of 0.8-10 μM). In particular, the nMEA combined with the patch-clamp system was used to detect quantized DA release from pheochromocytoma cells under 100 mM K(+) stimulation. The nMEA that integrates 60 microelectrodes is novel for detecting a large number of samples simultaneously, which has potential for neural communication research.

Mimicking Neurotransmitter Release in Chemical Synapses via Hysteresis Engineering in MoS2 Transistors.

PubMed

Arnold, Andrew J; Razavieh, Ali; Nasr, Joseph R; Schulman, Daniel S; Eichfeld, Chad M; Das, Saptarshi

2017-03-28

Neurotransmitter release in chemical synapses is fundamental to diverse brain functions such as motor action, learning, cognition, emotion, perception, and consciousness. Moreover, improper functioning or abnormal release of neurotransmitter is associated with numerous neurological disorders such as epilepsy, sclerosis, schizophrenia, Alzheimer's disease, and Parkinson's disease. We have utilized hysteresis engineering in a back-gated MoS 2 field effect transistor (FET) in order to mimic such neurotransmitter release dynamics in chemical synapses. All three essential features, i.e., quantal, stochastic, and excitatory or inhibitory nature of neurotransmitter release, were accurately captured in our experimental demonstration. We also mimicked an important phenomenon called long-term potentiation (LTP), which forms the basis of human memory. Finally, we demonstrated how to engineer the LTP time by operating the MoS 2 FET in different regimes. Our findings could provide a critical component toward the design of next-generation smart and intelligent human-like machines and human-machine interfaces.

Metamaterial bricks and quantization of meta-surfaces.

PubMed

Memoli, Gianluca; Caleap, Mihai; Asakawa, Michihiro; Sahoo, Deepak R; Drinkwater, Bruce W; Subramanian, Sriram

2017-02-27

Controlling acoustic fields is crucial in diverse applications such as loudspeaker design, ultrasound imaging and therapy or acoustic particle manipulation. The current approaches use fixed lenses or expensive phased arrays. Here, using a process of analogue-to-digital conversion and wavelet decomposition, we develop the notion of quantal meta-surfaces. The quanta here are small, pre-manufactured three-dimensional units-which we call metamaterial bricks-each encoding a specific phase delay. These bricks can be assembled into meta-surfaces to generate any diffraction-limited acoustic field. We apply this methodology to show experimental examples of acoustic focusing, steering and, after stacking single meta-surfaces into layers, the more complex field of an acoustic tractor beam. We demonstrate experimentally single-sided air-borne acoustic levitation using meta-layers at various bit-rates: from a 4-bit uniform to 3-bit non-uniform quantization in phase. This powerful methodology dramatically simplifies the design of acoustic devices and provides a key-step towards realizing spatial sound modulators.

Neuromuscular transmission and muscle fatigue changes by nanostructured oxygen.

PubMed

Ivannikov, Maxim V; Sugimori, Mutsuyuki; Llinás, Rodolfo R

2017-04-01

Oxygen (O 2 ) nanobubbles offer a new method for tissue oxygenation. The effects of O 2 nanobubbles on transmission at neuromuscular junctions (NMJs) and muscle function were explored in murine diaphragm. Electrophysiological parameters, NMJ ultrastructure, muscle force, and muscle fatigue were studied during superfusion with solutions with different oxygen levels or oxygen nanobubbles. High frequency nerve stimulation of muscles superfused with O 2 nanobubble solution slowed neurotransmission decline over those with either control or hyperoxic solution. O 2 nanobubble solution increased the amplitude of evoked end plate potentials and quantal content but did not affect spontaneous activity. Electron microscopy of stimulated O 2 nanobubble treated NMJs showed accumulation of large synaptic vesicles and endosome-like structures. O 2 nanobubble solution had no effects on isometric muscle force, but it significantly decreased fatigability and maximum force recovery time in nerve stimulated muscles. O 2 nanobubbles increase neurotransmission and reduce the probability of neurotransmission failure in muscle fatigue. Muscle Nerve 55: 555-563, 2017. © 2016 Wiley Periodicals, Inc.

On use of the multistage dose-response model for assessing laboratory animal carcinogenicity

PubMed Central

Nitcheva, Daniella; Piegorsch, Walter W.; West, R. Webster

2007-01-01

We explore how well a statistical multistage model describes dose-response patterns in laboratory animal carcinogenicity experiments from a large database of quantal response data. The data are collected from the U.S. EPA’s publicly available IRIS data warehouse and examined statistically to determine how often higher-order values in the multistage predictor yield significant improvements in explanatory power over lower-order values. Our results suggest that the addition of a second-order parameter to the model only improves the fit about 20% of the time, while adding even higher-order terms apparently does not contribute to the fit at all, at least with the study designs we captured in the IRIS database. Also included is an examination of statistical tests for assessing significance of higher-order terms in a multistage dose-response model. It is noted that bootstrap testing methodology appears to offer greater stability for performing the hypothesis tests than a more-common, but possibly unstable, “Wald” test. PMID:17490794

The homeobox gene Msx in development and transdifferentiation of jellyfish striated muscle.

PubMed

Galle, Sabina; Yanze, Nathalie; Seipel, Katja

2005-01-01

Bilaterian Msx homeobox genes are generally expressed in areas of cell proliferation and in association with multipotent progenitor cells. Likewise, jellyfish Msx is expressed in progenitor cells of the developing entocodon, a cell layer giving rise to the striated and smooth muscles of the medusa. However, in contrast to the bilaterian homologs, Msx gene expression is maintained at high levels in the differentiated striated muscle of the medusa in vivo and in vitro. This tissue exhibits reprogramming competence. Upon induction, the Msx gene is immediately switched off in the isolated striated muscle undergoing transdifferentiation, to be upregulated again in the emerging smooth muscle cells which, in a stem cell like manner, undergo quantal cell divisions producing two cell types, a proliferating smooth muscle cell and a differentiating nerve cell. This study indicates that the Msx protein may be a key component of the reprogramming machinery responsible for the extraordinary transdifferentation and regeneration potential of striated muscle in the hydrozoan jellyfish.

F-actin-based Ca signaling-a critical comparison with the current concept of Ca signaling.

PubMed

Lange, Klaus; Gartzke, Joachim

2006-11-01

A short comparative survey on the current idea of Ca signaling and the alternative concept of F-actin-based Ca signaling is given. The two hypotheses differ in one central aspect, the mechanism of Ca storage. The current theory rests on the assumption of Ca-accumulating endoplasmic/sarcoplasmic reticulum-derived vesicles equipped with an ATP-dependent Ca pump and IP3- or ryanodine-sensitive channel-receptors for Ca-release. The alternative hypothesis proceeds from the idea of Ca storage at the high-affinity binding sites of actin filaments. Cellular sites of F-actin-based Ca storage are microvilli and the submembrane cytoskeleton. Several specific features of Ca signaling such as store-channel coupling, quantal Ca release, spiking and oscillations, biphasic and "phasic" uptake kinetics, and Ca-induced Ca release (CICR), which are not adequately described by the current concept, are inherent properties of the F-actin system and its dynamic state of treadmilling. Copyright 2006 Wiley-Liss, Inc.

Quantum mechanical treatment of the F+H2 --> HF+H reaction

NASA Astrophysics Data System (ADS)

Baer, Michael; Jellinek, Julius; Kouri, D. J.

1983-03-01

In this paper is presented a quantum dynamical study of the F+H2 reaction within the infinite order sudden approximation for the energy range Etot=0.28-0.50 eV. Results at various stages of the calculation are given ranging from the most detailed phases and S matrices to the total integral cross sections. The accuracy of the IOS is assessed by comparisons of the average l-labeled quantal IOS results with exact classical, initial-l labeled classical IOS, and l-initial labeled quantum IOS results. Comparison with experiment indicates that the qualitative state-to-state angular distributions are reproduced within this method. On the other hand, vibrational branching ratios for the product HF molecule are only partially reproduced. The main part of the discussion in the paper is devoted to the recent hypothesis concerning the existence of a superposition of resonances which strongly influence the angular distributions as a function of final vibrational state of the HF product.

Selective accumulation of biotin in arterial chemoreceptors: requirement for carotid body exocytotic dopamine secretion

PubMed Central

Ortega‐Sáenz, Patricia; Macías, David; Levitsky, Konstantin L.; Rodríguez‐Gómez, José A.; González‐Rodríguez, Patricia; Bonilla‐Henao, Victoria; Arias‐Mayenco, Ignacio

2016-01-01

Key points Biotin, a vitamin whose main role is as a coenzyme for carboxylases, accumulates at unusually large amounts within cells of the carotid body (CB).In biotin‐deficient rats biotin rapidly disappears from the blood; however, it remains at relatively high levels in CB glomus cells. The CB contains high levels of mRNA for SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin.Animals with biotin deficiency exhibit pronounced metabolic lactic acidosis. Remarkably, glomus cells from these animals have normal electrical and neurochemical properties. However, they show a marked decrease in the size of quantal dopaminergic secretory events.Inhibitors of the vesicular monoamine transporter 2 (VMAT2) mimic the effect of biotin deficiency. In biotin‐deficient animals, VMAT2 protein expression decreases in parallel with biotin depletion in CB cells.These data suggest that dopamine transport and/or storage in small secretory granules in glomus cells depend on biotin. Abstract Biotin is a water‐soluble vitamin required for the function of carboxylases as well as for the regulation of gene expression. Here, we report that biotin accumulates in unusually large amounts in cells of arterial chemoreceptors, carotid body (CB) and adrenal medulla (AM). We show in a biotin‐deficient rat model that the vitamin rapidly disappears from the blood and other tissues (including the AM), while remaining at relatively high levels in the CB. We have also observed that, in comparison with other peripheral neural tissues, CB cells contain high levels of SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin. Biotin‐deficient rats show a syndrome characterized by marked weight loss, metabolic lactic acidosis, aciduria and accelerated breathing with normal responsiveness to hypoxia. Remarkably, CB cells from biotin‐deficient animals have normal electrophysiological and neurochemical (ATP levels and catecholamine synthesis) properties; however, they exhibit a marked decrease in the size of quantal catecholaminergic secretory events, which is not seen in AM cells. A similar differential secretory dysfunction is observed in CB cells treated with tetrabenazine, a selective inhibitor of the vesicular monoamine transporter 2 (VMAT2). VMAT2 is highly expressed in glomus cells (in comparison with VMAT1), and in biotin‐deficient animals VMAT2 protein expression decreases in parallel with the decrease of biotin accumulated in CB cells. These data suggest that biotin has an essential role in the homeostasis of dopaminergic transmission modulating the transport and/or storage of transmitters within small secretory granules in glomus cells. PMID:27570189

Distribution of acetylcholine receptors at frog neuromuscular junctions with a discussion of some physiological implications.

PubMed Central

Matthews-Bellinger, J; Salpeter, M M

1978-01-01

1. The distribution of acetylcholine receptors (AChR) at frog cutaneous pectoris neuromuscular junctions was studied quantitatively using [1125]alpha-bungarotoxin (alpha-BTX) labelling and EM autoradiography. 2. We found that, as in mouse end-plates, the AChR is localized uniformly along the thickened post-junctional membrane. In the frog muscle this specialized membrane constitutes approximately the top 50% of the junctional folds. 3. The receptor site density is approximately 26,000 +/- 6000 sites/micrometer2 on the thickened post-junctional membrane and falls sharply to approximately 50 sites/micrometer2 within 15 micrometer from the axon terminal. 4. alpha-BTX site density on the presynaptic axonal membrane was directly determined to be at most 5% of the value on the thickened post-junctional membrane. 5. The high post junctional AChR site density leads us to conclude that: (a) each quantum of ACh needs to spread only over a very small post-junctional area (to be called the 'critical area') before it encounters as many AChR (plus AchE) sites as there are ACh molecules in the quantum (for a packet of 10(4) ACh molecules this critical area is approximately 0.3 micrometer2), (b) the average concentration of ACh prevailing in the cleft over this critical area during a quantal response will be approximately 10(-3)M (independent of the size of the quantal packet), and (c) since 10(-3)M-ACh is large compared to any estimates of the dissociation constant Kd for ACh binding to the AChR, the ACh will essentially saturate the AChR within the critical area (provided the ACh binding rate is sufficiently faster than the ACh spreading rate). 6. The total receptive surface for a frog end-plate is calculated to be approximately 1500 micrometer2, and therefore an end-plate potential resulting from 300 quanta will be due to the activation of less than 10% of the total receptive area. 7. Free diffusion would allow each small post-junctional critical area to be reached in less than 15 musec. Therefore, either the recorded rise time of the miniature end-plate is not predominantly a function of ACh diffusion time, or, as suggested by Gage & McBurney (1975), the net rate of movement of ACh in the cleft is much slower than indicated by the free diffusion constant. Images Fig. 1a and b Fig. 2 Figs. 3, 5 Fig. 4 PMID:307600

A Unified Probabilistic Framework for Dose–Response Assessment of Human Health Effects

PubMed Central

Slob, Wout

2015-01-01

Background When chemical health hazards have been identified, probabilistic dose–response assessment (“hazard characterization”) quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. Objectives We developed a unified framework for probabilistic dose–response assessment. Methods We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose–response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, “effect metrics” can be specified to define “toxicologically equivalent” sizes for this underlying individual response; and d) dose–response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose–response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Results Probabilistically derived exposure limits are based on estimating a “target human dose” (HDMI), which requires risk management–informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%–10% effect sizes. Conclusions Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk management decisions. Citation Chiu WA, Slob W. 2015. A unified probabilistic framework for dose–response assessment of human health effects. Environ Health Perspect 123:1241–1254; http://dx.doi.org/10.1289/ehp.1409385 PMID:26006063

Subchronic mercury exposure in coturnix and a method of hazard evaluation

USGS Publications Warehouse

Hill, E.F.; Soares, J.H.

1984-01-01

The sublethal toxicity of inorganic (HgCI 2) and organic (CH3HgCI) mercury chloride was studied in coturnix (Corurnix japonica) by feeding them mercuric compounds (CH3HgCI at concentrations of 0.125,0.5,2 and 8 ppm; HgCI2 at 0.5, 2, 8 and 32 ppm) in ad libitum diets from hatching to adulthood. Differences of response to the mercurials were compared on the basis of selected indicator enzymes and plasma chemistries. Comparisons of response to equivalent concentrations of the two mercurials and dose-response relationships were made at 1,3,5,7 and 9 weeks. Changes of activity were detected for brain acetylcholinesterase (AChE) and the plasma enzymes aspartate aminotransferase (ASA T), butyrylcholinesterase (BChE), lactate dehydrogenase (LDH) and ornithine carbamoyl transferase (OCT). Changes of ASA T, LDH and OCT were then quantified by probit analysis and the mercurials were compared through their median effective concentrations (EC50). This quantal procedure was based on the establishment of normal control values for each enzyme and then classifying mercury-treated outliers (more than + 2 SD) as respondents. The EC50 values at 9 weeks for ASA T, LDH and OCT, respectively, were 9, 3 and 63 ppm for HgCl 2, and 5, 1 and 4 ppm for CH3HgCI. These results provided the basis for two hazard indices that were calculated by dividing the EC50 into the oral LD50 and the 5-d dietary LC50. Mercury also had contradictory effects on gonadal maturation in both sexes.

The minimal local-asperity hypothesis of early retinal lateral inhibition.

PubMed

Balboa, R M; Grzywacz, N M

2000-07-01

Recently we found that the theories related to information theory existent in the literature cannot explain the behavior of the extent of the lateral inhibition mediated by retinal horizontal cells as a function of background light intensity. These theories can explain the fall of the extent from intermediate to high intensities, but not its rise from dim to intermediate intensities. We propose an alternate hypothesis that accounts for the extent's bell-shape behavior. This hypothesis proposes that the lateral-inhibition adaptation in the early retina is part of a system to extract several image attributes, such as occlusion borders and contrast. To do so, this system would use prior probabilistic knowledge about the biological processing and relevant statistics in natural images. A key novel statistic used here is the probability of the presence of an occlusion border as a function of local contrast. Using this probabilistic knowledge, the retina would optimize the spatial profile of lateral inhibition to minimize attribute-extraction error. The two significant errors that this minimization process must reduce are due to the quantal noise in photoreceptors and the straddling of occlusion borders by lateral inhibition.

Mitochondrial Superoxide Production Negatively Regulates Neural Progenitor Proliferation and Cerebral Cortical Development

PubMed Central

Hou, Yan; Ouyang, Xin; Wan, Ruiqian; Cheng, Heping; Mattson, Mark P.; Cheng, Aiwu

2012-01-01

Although high amounts of reactive oxygen species (ROS) can damage cells, ROS can also play roles as second messengers, regulating diverse cellular processes. Here we report that embryonic mouse cerebral cortical neural progenitor cells (NPCs) exhibit intermittent spontaneous bursts of mitochondrial superoxide (SO) generation (mitochondrial SO flashes) that require transient opening of membrane permeability transition pores (mPTP). This quantal SO production negatively regulates NPC self-renewal. Mitochondrial SO scavengers and mPTP inhibitors reduce SO flash frequency and enhance NPC proliferation, whereas prolonged mPTP opening and SO generation increase SO flash incidence and decrease NPC proliferation. The inhibition of NPC proliferation by mitochondrial SO involves suppression of extracellular signal-regulated kinases. Moreover, mice lacking SOD2 (SOD2−/− mice) exhibit significantly fewer proliferative NPCs and differentiated neurons in the embryonic cerebral cortex at mid-gestation compared with wild type littermates. Cultured SOD2−/− NPCs exhibit a significant increase in SO flash frequency and reduced NPC proliferation. Taken together, our findings suggest that mitochondrial SO flashes negatively regulate NPC self-renewal in the developing cerebral cortex. PMID:22949407

Dopamine Induces Oscillatory Activities in Human Midbrain Neurons with Parkin Mutations.

PubMed

Zhong, Ping; Hu, Zhixing; Jiang, Houbo; Yan, Zhen; Feng, Jian

2017-05-02

Locomotor symptoms in Parkinson's disease (PD) are accompanied by widespread oscillatory neuronal activities in basal ganglia. Here, we show that activation of dopamine D1-class receptors elicits a large rhythmic bursting of spontaneous excitatory postsynaptic currents (sEPSCs) in midbrain neurons differentiated from induced pluripotent stem cells (iPSCs) of PD patients with parkin mutations, but not normal subjects. Overexpression of wild-type parkin, but not its PD-causing mutant, abolishes the oscillatory activities in patient neurons. Dopamine induces a delayed enhancement in the amplitude of spontaneous, but not miniature, EPSCs, thus increasing quantal content. The results suggest that presynaptic regulation of glutamatergic transmission by dopamine D1-class receptors is significantly potentiated by parkin mutations. The aberrant dopaminergic regulation of presynaptic glutamatergic transmission in patient-specific iPSC-derived midbrain neurons provides a mechanistic clue to PD pathophysiology, and it demonstrates the usefulness of this model system in understanding how mutations of parkin cause movement symptoms in Parkinson's disease. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Use of the mouse jumping test for estimating antagonistic potencies of morphine antagonists.

PubMed

Cowan, A

1976-03-01

The potencies of 19 reference morphine antagonists have been compared in a modified version of the mouse jumping test. Mice were each implanted subcutaneously with one 75 mg pellet of morphine. Antagonist challenge took place 72 h later and the incidence of repetitive vertical-jumping was monitored over 1 h. A high Pearson correlation coefficient (r = 0.997) was found between quantitative assays based on the total number of jumps per mouse and quantal assays based on mice jumping at least 6 times. A comparison of relative potencies obtained with the mouse test and with non-withdrawn morphine-dependent monkeys gave a Spearman rank order coefficient of 0.91 while a similar comparison with values obtained with the guinea-pig isolated ileum preparation also gave a high correlation coefficient (r= 0.92). Whereas it is difficult to assess the antagonistic component of buprenorphine and cyclorphan with the ileum preparation, both compounds can be satisfactorily assayed in the mouse jumping test. The reported antagonistic properties of ketocyclazocine and profadol could not be confirmed in the mouse model.

Bassoon-disruption slows vesicle replenishment and induces homeostatic plasticity at a CNS synapse

PubMed Central

Mendoza Schulz, Alejandro; Jing, Zhizi; María Sánchez Caro, Juan; Wetzel, Friederike; Dresbach, Thomas; Strenzke, Nicola; Wichmann, Carolin; Moser, Tobias

2014-01-01

Endbulb of Held terminals of auditory nerve fibers (ANF) transmit auditory information at hundreds per second to bushy cells (BCs) in the anteroventral cochlear nucleus (AVCN). Here, we studied the structure and function of endbulb synapses in mice that lack the presynaptic scaffold bassoon and exhibit reduced ANF input into the AVCN. Endbulb terminals and active zones were normal in number and vesicle complement. Postsynaptic densities, quantal size and vesicular release probability were increased while vesicle replenishment and the standing pool of readily releasable vesicles were reduced. These opposing effects canceled each other out for the first evoked EPSC, which showed unaltered amplitude. We propose that ANF activity deprivation drives homeostatic plasticity in the AVCN involving synaptic upscaling and increased intrinsic BC excitability. In vivo recordings from individual mutant BCs demonstrated a slightly improved response at sound onset compared to ANF, likely reflecting the combined effects of ANF convergence and homeostatic plasticity. Further, we conclude that bassoon promotes vesicular replenishment and, consequently, a large standing pool of readily releasable synaptic vesicles at the endbulb synapse. PMID:24442636

Dysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes.

PubMed

Chao, Hsiao-Tuan; Chen, Hongmei; Samaco, Rodney C; Xue, Mingshan; Chahrour, Maria; Yoo, Jong; Neul, Jeffrey L; Gong, Shiaoching; Lu, Hui-Chen; Heintz, Nathaniel; Ekker, Marc; Rubenstein, John L R; Noebels, Jeffrey L; Rosenmund, Christian; Zoghbi, Huda Y

2010-11-11

Mutations in the X-linked MECP2 gene, which encodes the transcriptional regulator methyl-CpG-binding protein 2 (MeCP2), cause Rett syndrome and several neurodevelopmental disorders including cognitive disorders, autism, juvenile-onset schizophrenia and encephalopathy with early lethality. Rett syndrome is characterized by apparently normal early development followed by regression, motor abnormalities, seizures and features of autism, especially stereotyped behaviours. The mechanisms mediating these features are poorly understood. Here we show that mice lacking Mecp2 from GABA (γ-aminobutyric acid)-releasing neurons recapitulate numerous Rett syndrome and autistic features, including repetitive behaviours. Loss of MeCP2 from a subset of forebrain GABAergic neurons also recapitulates many features of Rett syndrome. MeCP2-deficient GABAergic neurons show reduced inhibitory quantal size, consistent with a presynaptic reduction in glutamic acid decarboxylase 1 (Gad1) and glutamic acid decarboxylase 2 (Gad2) levels, and GABA immunoreactivity. These data demonstrate that MeCP2 is critical for normal function of GABA-releasing neurons and that subtle dysfunction of GABAergic neurons contributes to numerous neuropsychiatric phenotypes.

Two synaptobrevin molecules are sufficient for vesicle fusion in central nervous system synapses

PubMed Central

Sinha, Raunak; Ahmed, Saheeb; Jahn, Reinhard; Klingauf, Jurgen

2011-01-01

Exocytosis of synaptic vesicles (SVs) during fast synaptic transmission is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly formed by the coil-coiling of three members of this protein family: vesicle SNARE protein, synaptobrevin 2 (syb2), and the presynaptic membrane SNAREs syntaxin-1A and SNAP-25. However, it is controversially debated how many SNARE complexes are minimally needed for SV priming and fusion. To quantify this effective number, we measured the fluorescence responses from single fusing vesicles expressing pHluorin (pHl), a pH-sensitive variant of GFP, fused to the luminal domain of the vesicular SNARE syb2 (spH) in cultured hippocampal neurons lacking endogenous syb2. Fluorescence responses were quantal, with the unitary signals precisely corresponding to single pHluorin molecules. Using this approach we found that two copies of spH per SV fully rescued evoked fusion whereas SVs expressing only one spH were unable to rapidly fuse upon stimulation. Thus, two syb2 molecules and likely two SNARE complexes are necessary and sufficient for SV fusion during fast synaptic transmission. PMID:21844343

Selective accumulation of biotin in arterial chemoreceptors: requirement for carotid body exocytotic dopamine secretion.

PubMed

Ortega-Sáenz, Patricia; Macías, David; Levitsky, Konstantin L; Rodríguez-Gómez, José A; González-Rodríguez, Patricia; Bonilla-Henao, Victoria; Arias-Mayenco, Ignacio; López-Barneo, José

2016-12-15

Biotin, a vitamin whose main role is as a coenzyme for carboxylases, accumulates at unusually large amounts within cells of the carotid body (CB). In biotin-deficient rats biotin rapidly disappears from the blood; however, it remains at relatively high levels in CB glomus cells. The CB contains high levels of mRNA for SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin. Animals with biotin deficiency exhibit pronounced metabolic lactic acidosis. Remarkably, glomus cells from these animals have normal electrical and neurochemical properties. However, they show a marked decrease in the size of quantal dopaminergic secretory events. Inhibitors of the vesicular monoamine transporter 2 (VMAT2) mimic the effect of biotin deficiency. In biotin-deficient animals, VMAT2 protein expression decreases in parallel with biotin depletion in CB cells. These data suggest that dopamine transport and/or storage in small secretory granules in glomus cells depend on biotin. Biotin is a water-soluble vitamin required for the function of carboxylases as well as for the regulation of gene expression. Here, we report that biotin accumulates in unusually large amounts in cells of arterial chemoreceptors, carotid body (CB) and adrenal medulla (AM). We show in a biotin-deficient rat model that the vitamin rapidly disappears from the blood and other tissues (including the AM), while remaining at relatively high levels in the CB. We have also observed that, in comparison with other peripheral neural tissues, CB cells contain high levels of SLC5a6, a biotin transporter, and SLC19a3, a thiamine transporter regulated by biotin. Biotin-deficient rats show a syndrome characterized by marked weight loss, metabolic lactic acidosis, aciduria and accelerated breathing with normal responsiveness to hypoxia. Remarkably, CB cells from biotin-deficient animals have normal electrophysiological and neurochemical (ATP levels and catecholamine synthesis) properties; however, they exhibit a marked decrease in the size of quantal catecholaminergic secretory events, which is not seen in AM cells. A similar differential secretory dysfunction is observed in CB cells treated with tetrabenazine, a selective inhibitor of the vesicular monoamine transporter 2 (VMAT2). VMAT2 is highly expressed in glomus cells (in comparison with VMAT1), and in biotin-deficient animals VMAT2 protein expression decreases in parallel with the decrease of biotin accumulated in CB cells. These data suggest that biotin has an essential role in the homeostasis of dopaminergic transmission modulating the transport and/or storage of transmitters within small secretory granules in glomus cells. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Testing the hypothesis of neurodegeneracy in respiratory network function with a priori transected arterially perfused brain stem preparation of rat

PubMed Central

Jones, Sarah E.

2016-01-01

Degeneracy of respiratory network function would imply that anatomically discrete aspects of the brain stem are capable of producing respiratory rhythm. To test this theory we a priori transected brain stem preparations before reperfusion and reoxygenation at 4 rostrocaudal levels: 1.5 mm caudal to obex (n = 5), at obex (n = 5), and 1.5 (n = 7) and 3 mm (n = 6) rostral to obex. The respiratory activity of these preparations was assessed via recordings of phrenic and vagal nerves and lumbar spinal expiratory motor output. Preparations with a priori transection at level of the caudal brain stem did not produce stable rhythmic respiratory bursting, even when the arterial chemoreceptors were stimulated with sodium cyanide (NaCN). Reperfusion of brain stems that preserved the pre-Bötzinger complex (pre-BötC) showed spontaneous and sustained rhythmic respiratory bursting at low phrenic nerve activity (PNA) amplitude that occurred simultaneously in all respiratory motor outputs. We refer to this rhythm as the pre-BötC burstlet-type rhythm. Conserving circuitry up to the pontomedullary junction consistently produced robust high-amplitude PNA at lower burst rates, whereas sequential motor patterning across the respiratory motor outputs remained absent. Some of the rostrally transected preparations expressed both burstlet-type and regular PNA amplitude rhythms. Further analysis showed that the burstlet-type rhythm and high-amplitude PNA had 1:2 quantal relation, with burstlets appearing to trigger high-amplitude bursts. We conclude that no degenerate rhythmogenic circuits are located in the caudal medulla oblongata and confirm the pre-BötC as the primary rhythmogenic kernel. The absence of sequential motor patterning in a priori transected preparations suggests that pontine circuits govern respiratory pattern formation. PMID:26888109

Testing the hypothesis of neurodegeneracy in respiratory network function with a priori transected arterially perfused brain stem preparation of rat.

PubMed

Jones, Sarah E; Dutschmann, Mathias

2016-05-01

Degeneracy of respiratory network function would imply that anatomically discrete aspects of the brain stem are capable of producing respiratory rhythm. To test this theory we a priori transected brain stem preparations before reperfusion and reoxygenation at 4 rostrocaudal levels: 1.5 mm caudal to obex (n = 5), at obex (n = 5), and 1.5 (n = 7) and 3 mm (n = 6) rostral to obex. The respiratory activity of these preparations was assessed via recordings of phrenic and vagal nerves and lumbar spinal expiratory motor output. Preparations with a priori transection at level of the caudal brain stem did not produce stable rhythmic respiratory bursting, even when the arterial chemoreceptors were stimulated with sodium cyanide (NaCN). Reperfusion of brain stems that preserved the pre-Bötzinger complex (pre-BötC) showed spontaneous and sustained rhythmic respiratory bursting at low phrenic nerve activity (PNA) amplitude that occurred simultaneously in all respiratory motor outputs. We refer to this rhythm as the pre-BötC burstlet-type rhythm. Conserving circuitry up to the pontomedullary junction consistently produced robust high-amplitude PNA at lower burst rates, whereas sequential motor patterning across the respiratory motor outputs remained absent. Some of the rostrally transected preparations expressed both burstlet-type and regular PNA amplitude rhythms. Further analysis showed that the burstlet-type rhythm and high-amplitude PNA had 1:2 quantal relation, with burstlets appearing to trigger high-amplitude bursts. We conclude that no degenerate rhythmogenic circuits are located in the caudal medulla oblongata and confirm the pre-BötC as the primary rhythmogenic kernel. The absence of sequential motor patterning in a priori transected preparations suggests that pontine circuits govern respiratory pattern formation. Copyright © 2016 the American Physiological Society.

σ2-Adaptin Facilitates Basal Synaptic Transmission and Is Required for Regenerating Endo-Exo Cycling Pool Under High-Frequency Nerve Stimulation in Drosophila.

PubMed

Choudhury, Saumitra Dey; Mushtaq, Zeeshan; Reddy-Alla, Suneel; Balakrishnan, Sruthi S; Thakur, Rajan S; Krishnan, Kozhalmannom S; Raghu, Padinjat; Ramaswami, Mani; Kumar, Vimlesh

2016-05-01

The functional requirement of adapter protein 2 (AP2) complex in synaptic membrane retrieval by clathrin-mediated endocytosis is not fully understood. Here we isolated and functionally characterized a mutation that dramatically altered synaptic development. Based on the aberrant neuromuscular junction (NMJ) synapse, we named this mutation angur (a Hindi word meaning "grapes"). Loss-of-function alleles of angur show more than twofold overgrowth in bouton numbers and a dramatic decrease in bouton size. We mapped the angur mutation to σ2-adaptin, the smallest subunit of the AP2 complex. Reducing the neuronal level of any of the subunits of the AP2 complex or disrupting AP2 complex assembly in neurons phenocopied the σ2-adaptin mutation. Genetic perturbation of σ2-adaptin in neurons leads to a reversible temperature-sensitive paralysis at 38°. Electrophysiological analysis of the mutants revealed reduced evoked junction potentials and quantal content. Interestingly, high-frequency nerve stimulation caused prolonged synaptic fatigue at the NMJs. The synaptic levels of subunits of the AP2 complex and clathrin, but not other endocytic proteins, were reduced in the mutants. Moreover, bone morphogenetic protein (BMP)/transforming growth factor β (TGFβ) signaling was altered in these mutants and was restored by normalizing σ2-adaptin in neurons. Thus, our data suggest that (1) while σ2-adaptin facilitates synaptic vesicle (SV) recycling for basal synaptic transmission, its activity is also required for regenerating SVs during high-frequency nerve stimulation, and (2) σ2-adaptin regulates NMJ morphology by attenuating TGFβ signaling. Copyright © 2016 by the Genetics Society of America.

Deficits in morphofunctional maturation of hippocampal mossy fiber synapses in a mouse model of intellectual disability.

PubMed

Lanore, Frederic; Labrousse, Virginie F; Szabo, Zsolt; Normand, Elisabeth; Blanchet, Christophe; Mulle, Christophe

2012-12-05

The grik2 gene, coding for the kainate receptor subunit GluK2 (formerly GluR6), is associated with autism spectrum disorders and intellectual disability. Here, we tested the hypothesis that GluK2 could play a role in the appropriate maturation of synaptic circuits involved in learning and memory. We show that both the functional and morphological maturation of hippocampal mossy fiber to CA3 pyramidal cell (mf-CA3) synapses is delayed in mice deficient for the GluK2 subunit (GluK2⁻/⁻). In GluK2⁻/⁻ mice this deficit is manifested by a transient reduction in the amplitude of AMPA-EPSCs at a critical time point of postnatal development, whereas the NMDA component is spared. By combining multiple probability peak fluctuation analysis and immunohistochemistry, we have provided evidence that the decreased amplitude reflects a decrease in the quantal size per mf-CA3 synapse and in the number of active synaptic sites. Furthermore, we analyzed the time course of structural maturation of CA3 synapses by confocal imaging of YFP-expressing cells followed by tridimensional (3D) anatomical reconstruction of thorny excrescences and presynaptic boutons. We show that major changes in synaptic structures occur subsequently to the sharp increase in synaptic transmission, and more importantly that the course of structural maturation of synaptic elements is impaired in GluK2⁻/⁻ mice. This study highlights how a mutation in a gene linked to intellectual disability in the human may lead to a transient reduction of synaptic strength during postnatal development, impacting on the proper formation of neural circuits linked to memory.

Expression of VGLUTs contributes to degeneration and acquisition of learning and memory.

PubMed

Cheng, Xiao-Rui; Yang, Yong; Zhou, Wen-Xia; Zhang, Yong-Xiang

2011-03-01

Vesicular glutamate transporters (VGLUTs), which include VGLUT1, VGLUT2 and VGLUT3, are responsible for the uploading of L-glutamate into synaptic vesicles. The expression pattern of VGLUTs determines the level of synaptic vesicle filling (i.e., glutamate quantal size) and directly influences glutamate receptors and glutamatergic synaptic transmission; thus, VGLUTs may play a key role in learning and memory in the central nervous system. To determine whether VGLUTs contribute to the degeneration or acquisition of learning and memory, we used an animal model for the age-related impairment of learning and memory, senescence-accelerated mouse/prone 8 (SAMP8). KM mice were divided into groups based on their learning and memory performance in a shuttle-box test. The expression of VGLUTs and synaptophysin (Syp) mRNA and protein in the cerebral cortex and hippocampus were investigated with real-time fluorescence quantitative PCR and western blot, respectively. Our results demonstrate that, in the cerebral cortex, protein expression of VGLUT1, VGLUT2, VGLUT3 and Syp was decreased in SAMP8 with age and increased in KM mice, which displayed an enhanced capacity for learning and memory. The protein expression of VGLUT2 and Syp was decreased in the hippocampus of SAMP8 with aging. The expression level of VGLUT1 and VGLUT2 proteins were highest in KM mouse group with a 76-100% avoidance score in the shuttle-box test. These data demonstrate that protein expression of VGLUT1, VGLUT2 and Syp decreases age-dependently in SAMP8 and increases in a learning- and memory-dependent manner in KM mice. Correlation analysis indicated the protein expression of VGLUT1, VGLUT2 and Syp has a positive correlation with the capacity of learning and memory. Copyright © 2011 Elsevier Inc. All rights reserved.

Acoustic landmarks contain more information about the phone string than other frames for automatic speech recognition with deep neural network acoustic model

NASA Astrophysics Data System (ADS)

He, Di; Lim, Boon Pang; Yang, Xuesong; Hasegawa-Johnson, Mark; Chen, Deming

2018-06-01

Most mainstream Automatic Speech Recognition (ASR) systems consider all feature frames equally important. However, acoustic landmark theory is based on a contradictory idea, that some frames are more important than others. Acoustic landmark theory exploits quantal non-linearities in the articulatory-acoustic and acoustic-perceptual relations to define landmark times at which the speech spectrum abruptly changes or reaches an extremum; frames overlapping landmarks have been demonstrated to be sufficient for speech perception. In this work, we conduct experiments on the TIMIT corpus, with both GMM and DNN based ASR systems and find that frames containing landmarks are more informative for ASR than others. We find that altering the level of emphasis on landmarks by re-weighting acoustic likelihood tends to reduce the phone error rate (PER). Furthermore, by leveraging the landmark as a heuristic, one of our hybrid DNN frame dropping strategies maintained a PER within 0.44% of optimal when scoring less than half (45.8% to be precise) of the frames. This hybrid strategy out-performs other non-heuristic-based methods and demonstrate the potential of landmarks for reducing computation.

Is Hidden Crossings Theory a New MOCC Method?

NASA Astrophysics Data System (ADS)

Krstić, Predrag; Schultz, David

1998-05-01

We find un unitary transformation of the scaled adiabatic Hamiltonian of a two-center, one-electron collision system which yields a new representation for the matrix elements of nonadiabatic radial coupling, valid for low-to-intermediate collision velocities. These are given in analytic form once the topology of the branch points of the adiabatic Hamiltonian in the plane of complex internuclear distance R is known. The matrix elements do not depend on origin of electronic coordinates and properly vanish at large internuclear distances. The role of the rotational couplings in the new representation is also discussed. The aproach is appropriately extended and compared with the PSS treatment in the fully quantal description of the collision. We apply new radial and rotational matrix elements in the standard Molecular Orbital Close Coupling (MOCC) approach to describe excitation and ionization in collisions of antiprotons with He^+ and of alpha-particles with hydrogen(P.S. Krstić et al, J. Phys. B. 31, in press (1998).). The results are compared with those obtained from the standard MOCC method and from the direct solutions of the Schrödinger equation on lattice (LTDSE)(D.R. Schultz et al, Phys. Rev. A 56, 3710 (1997)).

Charge Transfer Processes in Collisions of Si4+ Ions with He Atoms at Intermediate Energies

NASA Astrophysics Data System (ADS)

Suzuki, R.; Watanabe, A.; Sato, H.; Gu, J. P.; Hirsch, G.; Buenker, R. J.; Kimura, M.; Stancil, P. C.

Charge transfer in collisions of Si4+ ions with He atoms below 100 keV/u is studied by using a molecular orbital representation within both the semiclassical and quantal representations. Single transfer reaction Si4++He →Si3++He+ has been studied by a number of theoretical investigations. In addition to the reaction (1), the first semiclassical MOCC calculations are performed for the double transfer channel Si4++HE→Si2++He2+ Nine molecular states that connect both with single and double electron transfer processes are considered in the present model. Electronic states and corresponding couplings are determined by the multireference single- and double- excitation configuration interaction method. The present cross sections tie well with the earlier calculations of Stancil et al., Phys. Rev. A 55, 1064 (1997) at lower energies, but show a rather different magnitude from those of Bacchus-Montabonel and Ceyzeriat, Phys. Rev. A 58, 1162 (1998). The present rate constant is found to be significantly different from the experimental finding of Fang and Kwong, Phys. Rev. A 59, 342 (1996) at 4,600 K, and hence does not support the experiment.

Partial dehydration and cryopreservation of Citrus seeds.

PubMed

Graiver, Natalia; Califano, Alicia; Zaritzky, Noemí

2011-11-01

Three categories of seed storage behavior are generally recognized among plant species: orthodox, intermediate and recalcitrant. Intermediate seeds cannot be stored in liquid nitrogen (LN) without a previous partial dehydration process. The water content (WC) of the seeds at the moment of immersion in LN must be regarded as the most critical factor in cryopreservation. The purpose of this study was to investigate the basis of the optimal hydration status for cryopreservation of Citrus seeds: C. sinensis (sweet orange), C. paradisi (grapefruit), C. reticulata (mandarin) in LN. To study the tolerance to dehydration and LN exposure, seeds were desiccated by equilibration at relative humidities between 11 and 95%. Sorption isotherms were determined and modeled; lipid content of the seeds was measured. Seed desiccation sensitivity was quantified by the quantal response model. Differential scanning calorimetry (DSC) thermograms were determined on cotyledon tissue at different moisture contents to measure ice melting enthalpies and unfrozen WC. Samples of total seed lipid extract were also analyzed by DSC to identify lipid transitions in the thermograms. The limit of hydration for LN Citrus seeds treatment corresponded to the unfrozen WC in the tissue, confirming that seed survival strictly depended on avoidance of intracellular ice formation. Copyright © 2011 Society of Chemical Industry.

Multilevel eEmpirical Bayes modeling for improved estimation of toxicant formulations tosuppress parasitic sea lamprey in the Upper Great Lakes

USGS Publications Warehouse

Hatfield, Laura A.; Gutreuter, Steve; Boogaard, Michael A.; Carlin, Bradley P.

2011-01-01

Estimation of extreme quantal-response statistics, such as the concentration required to kill 99.9% of test subjects (LC99.9), remains a challenge in the presence of multiple covariates and complex study designs. Accurate and precise estimates of the LC99.9 for mixtures of toxicants are critical to ongoing control of a parasitic invasive species, the sea lamprey, in the Laurentian Great Lakes of North America. The toxicity of those chemicals is affected by local and temporal variations in water chemistry, which must be incorporated into the modeling. We develop multilevel empirical Bayes models for data from multiple laboratory studies. Our approach yields more accurate and precise estimation of the LC99.9 compared to alternative models considered. This study demonstrates that properly incorporating hierarchical structure in laboratory data yields better estimates of LC99.9 stream treatment values that are critical to larvae control in the field. In addition, out-of-sample prediction of the results of in situ tests reveals the presence of a latent seasonal effect not manifest in the laboratory studies, suggesting avenues for future study and illustrating the importance of dual consideration of both experimental and observational data.

Exocytosis and Endocytosis: Modes, Functions, and Coupling Mechanisms*

PubMed Central

Wu, Ling-Gang; Hamid, Edaeni; Shin, Wonchul; Chiang, Hsueh-Cheng

2016-01-01

Vesicle exocytosis releases content to mediate many biological events, including synaptic transmission essential for brain functions. Following exocytosis, endocytosis is initiated to retrieve exocytosed vesicles within seconds to minutes. Decades of studies in secretory cells reveal three exocytosis modes coupled to three endocytosis modes: (a) full-collapse fusion, in which vesicles collapse into the plasma membrane, followed by classical endocytosis involving membrane invagination and vesicle reformation; (b) kiss-and-run, in which the fusion pore opens and closes; and (c) compound exocytosis, which involves exocytosis of giant vesicles formed via vesicle-vesicle fusion, followed by bulk endocytosis that retrieves giant vesicles. Here we review these exo- and endocytosis modes and their roles in regulating quantal size and synaptic strength, generating synaptic plasticity, maintaining exocytosis, and clearing release sites for vesicle replenishment. Furthermore, we highlight recent progress in understanding how vesicle endocytosis is initiated and is thus coupled to exocytosis. The emerging model is that calcium influx via voltage-dependent calcium channels at the calcium microdomain triggers endocytosis and controls endocytosis rate; calmodulin and synaptotagmin are the calcium sensors; and the exocytosis machinery, including SNARE proteins (synaptobrevin, SNAP25, and syntaxin), is needed to coinitiate endocytosis, likely to control the amount of endocytosis. PMID:24274740

On the Natural and Unnatural History of the Voltage-Gated Na(+) Channel.

PubMed

Moczydlowski, E G

2016-01-01

This review glances at the voltage-gated sodium (Na(+)) channel (NaV) from the skewed perspective of natural history and the history of ideas. Beginning with the earliest natural philosophers, the objective of biological science and physiology was to understand the basis of life and discover its intimate secrets. The idea that the living state of matter differs from inanimate matter by an incorporeal spirit or mystical force was central to vitalism, a doctrine based on ancient beliefs that persisted until the last century. Experimental electrophysiology played a major role in the abandonment of vitalism by elucidating physiochemical mechanisms that explained the electrical excitability of muscle and nerve. Indeed, as a principal biomolecule underlying membrane excitability, the NaV channel may be considered as the physical analog or surrogate for the vital spirit once presumed to animate higher forms of life. NaV also epitomizes the "other secret of life" and functions as a quantal transistor element of biological intelligence. Subplots of this incredible but true story run the gamut from electric fish to electromagnetism, invention of the battery, venomous animals, neurotoxins, channelopathies, arrhythmia, anesthesia, astrobiology, etc. Copyright © 2016 Elsevier Inc. All rights reserved.

Exogenous ciliary neurotrophic factor (CNTF) reduces synaptic depression during repetitive stimulation.

PubMed

Garcia, Neus; Santafé, Manel M; Tomàs, Marta; Priego, Mercedes; Obis, Teresa; Lanuza, Maria A; Besalduch, Nuria; Tomàs, Josep

2012-09-01

It has been shown that ciliary neurotrophic factor (CNTF) has trophic and maintenance effects on several types of peripheral and central neurons, glia, and cells outside the nervous system. Both CNTF and its receptor, CNTF-Rα, are expressed in the muscle. We use confocal immunocytochemistry to show that the trophic cytokine and its receptor are present in the pre- and post-synaptic sites of the neuromuscular junctions (NMJs). Applied CNTF (7.5-200 ng/ml, 60 min-3 h) does not acutely affect spontaneous potentials (size or frequency) or quantal content of the evoked acetylcholine release from post-natal (in weak or strong axonal inputs on dually innervated end plates or in the most mature singly innervated synapses at P6) or adult (P30) NMJ of Levator auris longus muscle of the mice. However, CNTF reduces roughly 50% the depression produced by repetitive stimulation (40 Hz, 2 min) on the adult NMJs. Our findings indicate that, unlike neurotrophins, exogenous CNTF does not acutely modulate transmitter release locally at the mammalian neuromuscular synapse but can protect mature end plates from activity-induced synaptic depression. © 2012 Peripheral Nerve Society.

Role of voltage-sensitive receptors in nicotinic transmission.

PubMed Central

Lester, H A; Koblin, D D; Sheridan, R E

1978-01-01

This paper compares the conductance induced by bath-applied acetyl-choline (ACh) and by the same transmitter released from nerve terminals at Electrophorus electroplaques. For the former case, dose-response relations are characterized by the maximal agonist-induced conductance, rgamma (130 mmho/cm2), and by the concentration which induces half this conductance; this concentration is termed Kapp and equals 50 micron at -85 mV. For the latter case, neurally evoked postsynaptic currents (PSCs) are characterized by the peak conductance during strongly facilitated release, gPSC, and by the rate constant for decay, alpha. Since gPSC roughly equals rgamma, it is concluded that the PSC activates nearly all available receptor channels. These and other data agree with recent estimates that during the growth phase of the quantal response, (a) the ACh concentration is at least several hundred micromolar; and (b) most nearby channels are activated. However both alpha and Kapp increase during depolarization, at a rate of about e-fold per 86 mV. These observations on voltage sensitivity suggest that a suprathreshold synaptic event is rapidly terminated because the action potential abruptly releases ACh molecules from receptors. PMID:630039

A highly Ca2+-sensitive pool of granules is regulated by glucose and protein kinases in insulin-secreting INS-1 cells.

PubMed

Yang, Yan; Gillis, Kevin D

2004-12-01

We have used membrane capacitance measurements and carbon-fiber amperometry to assay exocytosis triggered by photorelease of caged Ca(2+) to directly measure the Ca(2+) sensitivity of exocytosis from the INS-1 insulin-secreting cell line. We find heterogeneity of the Ca(2+) sensitivity of release in that a small proportion of granules makes up a highly Ca(2+)-sensitive pool (HCSP), whereas the bulk of granules have a lower sensitivity to Ca(2+). A substantial HCSP remains after brief membrane depolarization, suggesting that the majority of granules with high sensitivity to Ca(2+) are not located close to Ca(2+) channels. The HCSP is enhanced in size by glucose, cAMP, and a phorbol ester, whereas the Ca(2+)-sensitive rate constant of exocytosis from the HCSP is unaffected by cAMP and phorbol ester. The effects of cAMP and phorbol ester on the HCSP are mediated by PKA and PKC, respectively, because they can be blocked with specific protein kinase inhibitors. The size of the HCSP can be enhanced by glucose even in the presence of high concentrations of phorbol ester or cAMP, suggesting that glucose can increase granule pool sizes independently of activation of PKA or PKC. The effects of PKA and PKC on the size of the HCSP are not additive, suggesting they converge on a common mechanism. Carbon-fiber amperometry was used to assay quantal exocytosis of serotonin (5-HT) from insulin-containing granules following preincubation of INS-1 cells with 5-HT and a precursor. The amount or kinetics of release of 5-HT from each granule is not significantly different between granules with higher or lower sensitivity to Ca(2+), suggesting that granules in these two pools do not differ in morphology or fusion kinetics. We conclude that glucose and second messengers can modulate insulin release triggered by a high-affinity Ca(2+) sensor that is poised to respond to modest, global elevations of [Ca(2+)](i).

Generalised Spin Dynamics and Induced Bounds of Automorphic [A]nX, [AX]n NMR Systems via Dual Tensorial Sets: An Invariant Cardinality Role for CFP

NASA Astrophysics Data System (ADS)

Temme, Francis P.

For uniform spins and their indistinguishable point sets of tensorial bases defining automorphic group-based Liouvillian NMR spin dynamics, the role of recursively-derived coefficients of fractional parentage (CFP) bijections and Schur duality-defined CFP(0)(n) ≡ ¦GI¦(n) group invariant cardinality is central both to understanding the impact of time-reversal invariance(TRI) spin physics, and to analysis as density-matrix formalisms over democratic recoupled (DR) dual tensorial sets, {T{ṽ}k(11.1)(SU2 × ln)}. Over abstract spin space, these tensorial sets are (ṽ) invariant-theoretic forms which lie beyond the Liouvillian graph recoupling and Racah-forms envisaged by Sanctuary [1]. This is a direct consequence of the dominance of the ln group. It leads to new views on the value of projective group actions as mappings over specialised Liouvillian carrier spaces, and on the need for the replacement of Racah-Wigner (R-W) orthogonality for distinct point sets, by criteria based on explicit properties of invariants [J. Phys.: Math. & Theor. A 41, 015210 (2008)] for multiple invariant systems. Ũ × P group actions over disjoint (L) carrier subspaces, leading to exclusively combinatorial views of the nature of quantal completeness for indistinguishable point-based tensorial sets. Such generalised invariant-theoretic approaches lie beyond the range of Lévi-Civitá generator views, or of Lévy-Leblond and Lévy-Nahas [9] with its additional cyclic-commutators defining mono-invariant DR forms. Comparison of the latter with generalised multiple-invariant techniques provides an answer to the question of precisely why [A]n≥4(X) and [AX]n≥4 NMR system spin dynamics are not ameniable to conventional R-W analysis of recoupled discrete-point tensorial systems. Our work augments earlier Hilbert space views, both of Louck and Biedenharn [21] on boson pattern projective mapping, and of Corio [19]. The roles of recent ln group action and (λ ⊢ n)-Schur combinatorial concepts, as well as of polyhedral-combinatorial modelling over invariance algebras, contribute significantly to our understanding of invariant-based techniques of Liouville dual tensorial sets for automorphic NMR spin physics.1

Depopulation of metastable helium by radiative association with hydrogen and lithium ions

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

Augustovičová, L.; Soldán, P.; Kraemer, W. P., E-mail: pavel.soldan@mff.cuni.cz

2014-02-10

Depopulation of metastable He(2{sup 3}S) by radiative association with hydrogen and lithium ions is investigated using a fully quantal approach. Rate coefficients for spontaneous and stimulated radiative association of the HeH{sup +}, HeD{sup +}, and LiHe{sup +} molecular ions on the spin-triplet manifold are presented as functions of temperature considering the association to rotational-vibrational states of the lowest triplet electronic states a {sup 3}Σ{sup +} and b {sup 3}Σ{sup +} from the continuum states of the b {sup 3}Σ{sup +} electronic state. Evaluation of the rate coefficients is based on highly accurate quantum calculations, taking into account all possible state-to-statemore » transitions at thermal energies (for spontaneous association) or at higher background energies (stimulated association). As expected, calculations show that the rate coefficients for radiative association to the a state are several orders of magnitude larger than the one for the b state formation. A noticeable effect by blackbody background radiation on the radiative association is only obtained for the b → b process. Aspects of the formation and abundance of the metastable HeH{sup +}(a {sup 3}Σ{sup +}) in astrophysical environments are briefly discussed.« less

In-vivo imaging of photoreceptor structure and laser injury pathophysiology in the snake eye

NASA Astrophysics Data System (ADS)

Zwick, Harry; Elliot, Rowe; Li, Guo; Akers, Andre; Edsall, Peter R.; Stuck, Bruce E.

1999-06-01

Confocal scanning laser ophthalmoscopy (CSLO) combined with the high numerical aperture of the snake eye was used to evaluate laser injury at the photoreceptor and vascular retinal layers. An Argon laser source focused within a 35 micron retinal spot was used to produce a range of exposures from 152 to 1000 μjoules in the retinas of the Checkered Garter and Great Plains Rat snake. Anesthesia was induced with ketamine and xylazine. In vivo exposure sites measured post exposure showed unique photoreceptor damage characterized by surviving photoreceptors that were highly reflective and saturated, swollen and revealed more complex mode structure than normal photoreceptors when imaged under higher magnification. Evidence of oxidative stress was observed in photoreceptor cells peripheral to the lesion site as a late developing fluorescence (1-2 hour post exposure) following injection of Dichlorodihydrofluorescein diacetate, a marker of oxidative stress. At the anterior retina, acute exposure produced `sticky' blood cells, identified as leukocytes with Acridine orange. These findings indicate that laser retinal injury in large eyes, such as the human eye may involve pathophysiological cellular dynamics in both posterior and anterior retina and in normal retina adjacent to lesion sites. Photoreceptor movement outside the lesion site may relate to alterations in photoreceptor orientation and the efficiency of the photoreceptors quantal catch.

Hypertonic enhancement of transmitter release from frog motor nerve terminals: Ca2+ independence and role of integrins

NASA Technical Reports Server (NTRS)

Kashani, A. H.; Chen, B. M.; Grinnell, A. D.

2001-01-01

Hyperosmotic solutions cause markedly enhanced spontaneous quantal release of neurotransmitter from many nerve terminals. The mechanism of this enhancement is unknown. We have investigated this phenomenon at the frog neuromuscular junction with the aim of determining the degree to which it resembles the modulation of release by stretch, which has been shown to be mediated by mechanical tension on integrins.The hypertonicity enhancement, like the stretch effect, does not require Ca2+ influx or release from internal stores, although internal release may contribute to the effect. The hypertonicity effect is sharply reduced (but not eliminated) by peptides containing the RGD sequence, which compete with native ligands for integrin bonds.There is co-variance in the magnitude of the stretch and osmotic effects; that is, individual terminals exhibiting a large stretch effect also show strong enhancement by hypertonicity, and vice versa. The stretch and osmotic enhancements also can partially occlude each other.There remain some clear-cut differences between osmotic and stretch forms of modulation: the larger range of enhancement by hypertonic solutions, the relative lack of effect of osmolarity on evoked release, and the reported higher temperature sensitivity of osmotic enhancement. Nevertheless, our data strongly implicate integrins in a significant fraction of the osmotic enhancement, possibly acting via the same mechanism as stretch modulation.

Short-term effects of beta-amyloid25-35 peptide aggregates on transmitter release in neuromuscular synapses.

PubMed

Garcia, Neus; Santafé, Manel M; Tomàs, Marta; Lanuza, Maria A; Tomàs, Josep

2008-03-01

The beta-amyloid (AB) peptide25-35 contains the functional domain of the AB precursor protein that is both required for neurotrophic effects in normal neural tissues and is involved in the neurotoxic effects in Alzheimer disease. We demonstrated the presence of the amyloid precursor protein/AB peptide in intramuscular axons, presynaptic motor nerve terminals, terminal and myelinating Schwann cells, and the postsynaptic and subsarcolemmal region in the Levator auris longus muscle of adult rats by immunocytochemistry. Using intracellular recording, we investigated possible short-term functional effects of the AB fragment (0.1-10 micromol/L) on acetylcholine release in adult and newborn motor end plates. We found no change in evoked, spontaneous transmitter release or resting membrane potential of the muscle cells. A previous block of the presynaptic muscarinic receptor subtypes and a previous block or stimulation of protein kinase C revealed no masked effect of the peptide on the regulation of transmitter release. The aggregated form of AB peptide25-35, however, interfered acutely with acetylcholine release (quantal content reduction) when synaptic activity was maintained by electric stimulation. The possible relevance of this inhibition of neurotransmission by AB peptide25-35 to the pathogenesis of Alzheimer remains to be determined.

Altered Exocytosis in Chromaffin Cells from Mouse Models of Neurodegenerative Diseases.

PubMed

de Diego, Antonio M G; García, Antonio G

2018-05-09

Chromaffin cells from the adrenal gland (CCs) have extensively been used to explore the molecular structure and function of the exocytotic machinery, neurotransmitter release and synaptic transmission. The CC is integrated in the sympathoadrenal axis that helps the body maintain homeostasis during both routine life and in acute stress conditions. This function is exquisitely controlled by the cerebral cortex and the hypothalamus. We propose the hypothesis that damage undergone by the brain during neurodegenerative diseases is also affecting the neurosecretory function of adrenal medullary CCs. In this context we review here the following themes: (i) how the discharge of catecholamines is centrally and peripherally regulated at the sympatho-adrenal axis; (ii) which are the intricacies of the amperometric techniques used to study the quantal release of single-vesicle exocytotic events; (iii) which are the alterations of the exocytotic fusion pore so far reported, in CCs of mouse models of neurodegenerative diseases; (iv) how some proteins linked to neurodegenerative pathologies affects the kinetics of exocytotic events; (v) finally we try to integrate available data into a hypothesis to explain how the centrally originated neurodegenerative diseases may alter the kinetics of single-vesicle exocytotic events in peripheral adrenal medullary CCs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Advanced model for the prediction of the neutron-rich fission product yields

NASA Astrophysics Data System (ADS)

Rubchenya, V. A.; Gorelov, D.; Jokinen, A.; Penttilä, H.; Äystö, J.

2013-12-01

The consistent models for the description of the independent fission product formation cross sections in the spontaneous fission and in the neutron and proton induced fission at the energies up to 100 MeV is developed. This model is a combination of new version of the two-component exciton model and a time-dependent statistical model for fusion-fission process with inclusion of dynamical effects for accurate calculations of nucleon composition and excitation energy of the fissioning nucleus at the scission point. For each member of the compound nucleus ensemble at the scission point, the primary fission fragment characteristics: kinetic and excitation energies and their yields are calculated using the scission-point fission model with inclusion of the nuclear shell and pairing effects, and multimodal approach. The charge distribution of the primary fragment isobaric chains was considered as a result of the frozen quantal fluctuations of the isovector nuclear matter density at the scission point with the finite neck radius. Model parameters were obtained from the comparison of the predicted independent product fission yields with the experimental results and with the neutron-rich fission product data measured with a Penning trap at the Accelerator Laboratory of the University of Jyväskylä (JYFLTRAP).

H-, He-like recombination spectra - II. l-changing collisions for He Rydberg states

NASA Astrophysics Data System (ADS)

Guzmán, F.; Badnell, N. R.; Williams, R. J. R.; van Hoof, P. A. M.; Chatzikos, M.; Ferland, G. J.

2017-01-01

Cosmological models can be constrained by determining primordial abundances. Accurate predictions of the He I spectrum are needed to determine the primordial helium abundance to a precision of <1 per cent in order to constrain big bang nucleosynthesis models. Theoretical line emissivities at least this accurate are needed if this precision is to be achieved. In the first paper of this series, which focused on H I, we showed that differences in l-changing collisional rate coefficients predicted by three different theories can translate into 10 per cent changes in predictions for H I spectra. Here, we consider the more complicated case of He atoms, where low-l subshells are not energy degenerate. A criterion for deciding when the energy separation between l subshells is small enough to apply energy-degenerate collisional theories is given. Moreover, for certain conditions, the Bethe approximation originally proposed by Pengelly & Seaton is not sufficiently accurate. We introduce a simple modification of this theory which leads to rate coefficients which agree well with those obtained from pure quantal calculations using the approach of Vrinceanu et al. We show that the l-changing rate coefficients from the different theoretical approaches lead to differences of ˜10 per cent in He I emissivities in simulations of H II regions using spectral code CLOUDY.

Multilevel Empirical Bayes Modeling for Improved Estimation of Toxicant Formulations to Suppress Parasitic Sea Lamprey in the Upper Great Lakes

USGS Publications Warehouse

Hatfield, L.A.; Gutreuter, S.; Boogaard, M.A.; Carlin, B.P.

2011-01-01

Estimation of extreme quantal-response statistics, such as the concentration required to kill 99.9% of test subjects (LC99.9), remains a challenge in the presence of multiple covariates and complex study designs. Accurate and precise estimates of the LC99.9 for mixtures of toxicants are critical to ongoing control of a parasitic invasive species, the sea lamprey, in the Laurentian Great Lakes of North America. The toxicity of those chemicals is affected by local and temporal variations in water chemistry, which must be incorporated into the modeling. We develop multilevel empirical Bayes models for data from multiple laboratory studies. Our approach yields more accurate and precise estimation of the LC99.9 compared to alternative models considered. This study demonstrates that properly incorporating hierarchical structure in laboratory data yields better estimates of LC99.9 stream treatment values that are critical to larvae control in the field. In addition, out-of-sample prediction of the results of in situ tests reveals the presence of a latent seasonal effect not manifest in the laboratory studies, suggesting avenues for future study and illustrating the importance of dual consideration of both experimental and observational data. ?? 2011, The International Biometric Society.

The QDREC web server: determining dose-response characteristics of complex macroparasites in phenotypic drug screens.

PubMed

Asarnow, Daniel; Rojo-Arreola, Liliana; Suzuki, Brian M; Caffrey, Conor R; Singh, Rahul

2015-05-01

Neglected tropical diseases (NTDs) caused by helminths constitute some of the most common infections of the world's poorest people. The etiological agents are complex and recalcitrant to standard techniques of molecular biology. Drug screening against helminths has often been phenotypic and typically involves manual description of drug effect and efficacy. A key challenge is to develop automated, quantitative approaches to drug screening against helminth diseases. The quantal dose-response calculator (QDREC) constitutes a significant step in this direction. It can be used to automatically determine quantitative dose-response characteristics and half-maximal effective concentration (EC50) values using image-based readouts from phenotypic screens, thereby allowing rigorous comparisons of the efficacies of drug compounds. QDREC has been developed and validated in the context of drug screening for schistosomiasis, one of the most important NTDs. However, it is equally applicable to general phenotypic screening involving helminths and other complex parasites. QDREC is publically available at: http://haddock4.sfsu.edu/qdrec2/. Source code and datasets are at: http://tintin.sfsu.edu/projects/phenotypicAssays.html. rahul@sfsu.edu. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Statistical Physics on the Eve of the 21st Century: in Honour of J B McGuire on the Occasion of His 65th Birthday

NASA Astrophysics Data System (ADS)

Batchelor, Murray T.; Wille, Luc T.

The Table of Contents for the book is as follows: * Preface * Modelling the Immune System - An Example of the Simulation of Complex Biological Systems * Brief Overview of Quantum Computation * Quantal Information in Statistical Physics * Modeling Economic Randomness: Statistical Mechanics of Market Phenomena * Essentially Singular Solutions of Feigenbaum- Type Functional Equations * Spatiotemporal Chaotic Dynamics in Coupled Map Lattices * Approach to Equilibrium of Chaotic Systems * From Level to Level in Brain and Behavior * Linear and Entropic Transformations of the Hydrophobic Free Energy Sequence Help Characterize a Novel Brain Polyprotein: CART's Protein * Dynamical Systems Response to Pulsed High-Frequency Fields * Bose-Einstein Condensates in the Light of Nonlinear Physics * Markov Superposition Expansion for the Entropy and Correlation Functions in Two and Three Dimensions * Calculation of Wave Center Deflection and Multifractal Analysis of Directed Waves Through the Study of su(1,1)Ferromagnets * Spectral Properties and Phases in Hierarchical Master Equations * Universality of the Distribution Functions of Random Matrix Theory * The Universal Chiral Partition Function for Exclusion Statistics * Continuous Space-Time Symmetries in a Lattice Field Theory * Quelques Cas Limites du Problème à N Corps Unidimensionnel * Integrable Models of Correlated Electrons * On the Riemann Surface of the Three-State Chiral Potts Model * Two Exactly Soluble Lattice Models in Three Dimensions * Competition of Ferromagnetic and Antiferromagnetic Order in the Spin-l/2 XXZ Chain at Finite Temperature * Extended Vertex Operator Algebras and Monomial Bases * Parity and Charge Conjugation Symmetries and S Matrix of the XXZ Chain * An Exactly Solvable Constrained XXZ Chain * Integrable Mixed Vertex Models Ftom the Braid-Monoid Algebra * From Yang-Baxter Equations to Dynamical Zeta Functions for Birational Tlansformations * Hexagonal Lattice Directed Site Animals * Direction in the Star-Triangle Relations * A Self-Avoiding Walk Through Exactly Solved Lattice Models in Statistical Mechanics

Projectile n distributions following charge transfer of Ar+ and Na+ in a Na Rydberg target

NASA Astrophysics Data System (ADS)

MacAdam, K. B.; Gray, L. G.; Rolfes, R. G.

1990-11-01

The n distributions produced by charge transfer of Ar+ and Na+ ions in a target of Na(nl) Rydberg atoms were extensively measured at intermediate velocities. The 60-2100-eV ions bombarded a laser-excited atomic-beam target. The projectiles were neutralized by capture into Rydberg states of Ar and Na and were analyzed by field ionization in an inhomogeneous-field detector whose response over states and energies was carefully mapped. The choice of initially prepared Na states, 24d, 25s, 28d, 29s, 33d, and 34s, allowed a comparison of l=0 and >=2 targets at nearly equal binding energies over a range of reduced velocity v~=0.187 to 1.95. Capture populates m sublevels broadly, not merely m~=0. Overlapping contributions from adiabatic and diabatic modes of field ionization were accommodated in the analysis, which used a maximum-entropy-principle parametric form to fit the observed final-state distributions. The peak of the distributions, nmax, shifts upward from a value less than the initial state ni to a value one to three units higher than ni at v~ between 0.7 and 0.9 and ultimately shifts downward below ni as v~ is further increased. The distributions become significantly sharper where the maximum upward shift occurs. Two ratios were defined to express the widths of final-state distributions in relative terms, one measuring the spread of orbital kinetic energy and the other the spread of Bohr-orbit velocity. By these ratios a universal behavior over energies, states, and projectile species is observed, and small differences between l=0 and >=2 targets may be seen. A theoretical understanding of the present results, which span velocities where both molecular and perturbative theories are normally used, will require a quantal formulation that models the free-ranging response that is a hallmark of the high-quantum-number limit.

Identification of unique release kinetics of serotonin from guinea-pig and human enterochromaffin cells

PubMed Central

Raghupathi, Ravinarayan; Duffield, Michael D; Zelkas, Leah; Meedeniya, Adrian; Brookes, Simon J H; Sia, Tiong Cheng; Wattchow, David A; Spencer, Nick J; Keating, Damien J

2013-01-01

The major source of serotonin (5-HT) in the body is the enterochromaffin (EC) cells lining the intestinal mucosa of the gastrointestinal tract. Despite the fact that EC cells synthesise ∼95% of total body 5-HT, and that this 5-HT has important paracrine and endocrine roles, no studies have investigated the mechanisms of 5-HT release from single primary EC cells. We have developed a rapid primary culture of guinea-pig and human EC cells, allowing analysis of single EC cell function using electrophysiology, electrochemistry, Ca2+ imaging, immunocytochemistry and 3D modelling. Ca2+ enters EC cells upon stimulation and triggers quantal 5-HT release via L-type Ca2+ channels. Real time amperometric techniques reveal that EC cells release 5-HT at rest and this release increases upon stimulation. Surprisingly for an endocrine cell storing 5-HT in large dense core vesicles (LDCVs), EC cells release 70 times less 5-HT per fusion event than catecholamine released from similarly sized LDCVs in endocrine chromaffin cells, and the vesicle release kinetics instead resembles that observed in mammalian synapses. Furthermore, we measured EC cell density along the gastrointestinal tract to create three-dimensional (3D) simulations of 5-HT diffusion using the minimal number of variables required to understand the physiological relevance of single cell 5-HT release in the whole-tissue milieu. These models indicate that local 5-HT levels are likely to be maintained around the activation threshold for mucosal 5-HT receptors and that this is dependent upon stimulation and location within the gastrointestinal tract. This is the first study demonstrating single cell 5-HT release in primary EC cells. The mode of 5-HT release may represent a unique mode of exocytosis amongst endocrine cells and is functionally relevant to gastrointestinal sensory and motor function. PMID:24099799

Wavelet Analysis of Nonstationary Fluctuations of Monte Carlo-Simulated Excitatory Postsynaptic Currents

PubMed Central

Aristizabal, F.; Glavinovic, M. I.

2003-01-01

Tracking spectral changes of rapidly varying signals is a demanding task. In this study, we explore on Monte Carlo-simulated glutamate-activated AMPA patch and synaptic currents whether a wavelet analysis offers such a possibility. Unlike Fourier methods that determine only the frequency content of a signal, the wavelet analysis determines both the frequency and the time. This is owing to the nature of the basis functions, which are infinite for Fourier transforms (sines and cosines are infinite), but are finite for wavelet analysis (wavelets are localized waves). In agreement with previous reports, the frequency of the stationary patch current fluctuations is higher for larger currents, whereas the mean-variance plots are parabolic. The spectra of the current fluctuations and mean-variance plots are close to the theoretically predicted values. The median frequency of the synaptic and nonstationary patch currents is, however, time dependent, though at the peak of synaptic currents, the median frequency is insensitive to the number of glutamate molecules released. Such time dependence demonstrates that the “composite spectra” of the current fluctuations gathered over the whole duration of synaptic currents cannot be used to assess the mean open time or effective mean open time of AMPA channels. The current (patch or synaptic) versus median frequency plots show hysteresis. The median frequency is thus not a simple reflection of the overall receptor saturation levels and is greater during the rise phase for the same saturation level. The hysteresis is due to the higher occupancy of the doubly bound state during the rise phase and not due to the spatial spread of the saturation disk, which remains remarkably constant. Albeit time dependent, the variance of the synaptic and nonstationary patch currents can be accurately determined. Nevertheless the evaluation of the number of AMPA channels and their single current from the mean-variance plots of patch or synaptic currents is not highly accurate owing to the varying number of the activatable AMPA channels caused by desensitization. The spatial nonuniformity of open, bound, and desensitized AMPA channels, and the time dependence and spatial nonuniformity of the glutamate concentration in the synaptic cleft, further reduce the accuracy of estimates of the number of AMPA channels from synaptic currents. In conclusion, wavelet analysis of nonstationary fluctuations of patch and synaptic currents expands our ability to determine accurately the variance and frequency of current fluctuations, demonstrates the limits of applicability of techniques currently used to evaluate the single channel current and number of AMPA channels, and offers new insights into the mechanisms involved in the generation of unitary quantal events at excitatory central synapses. PMID:14507683

Wavelet analysis of nonstationary fluctuations of Monte Carlo-simulated excitatory postsynaptic currents.

PubMed

Aristizabal, F; Glavinovic, M I

2003-10-01

Tracking spectral changes of rapidly varying signals is a demanding task. In this study, we explore on Monte Carlo-simulated glutamate-activated AMPA patch and synaptic currents whether a wavelet analysis offers such a possibility. Unlike Fourier methods that determine only the frequency content of a signal, the wavelet analysis determines both the frequency and the time. This is owing to the nature of the basis functions, which are infinite for Fourier transforms (sines and cosines are infinite), but are finite for wavelet analysis (wavelets are localized waves). In agreement with previous reports, the frequency of the stationary patch current fluctuations is higher for larger currents, whereas the mean-variance plots are parabolic. The spectra of the current fluctuations and mean-variance plots are close to the theoretically predicted values. The median frequency of the synaptic and nonstationary patch currents is, however, time dependent, though at the peak of synaptic currents, the median frequency is insensitive to the number of glutamate molecules released. Such time dependence demonstrates that the "composite spectra" of the current fluctuations gathered over the whole duration of synaptic currents cannot be used to assess the mean open time or effective mean open time of AMPA channels. The current (patch or synaptic) versus median frequency plots show hysteresis. The median frequency is thus not a simple reflection of the overall receptor saturation levels and is greater during the rise phase for the same saturation level. The hysteresis is due to the higher occupancy of the doubly bound state during the rise phase and not due to the spatial spread of the saturation disk, which remains remarkably constant. Albeit time dependent, the variance of the synaptic and nonstationary patch currents can be accurately determined. Nevertheless the evaluation of the number of AMPA channels and their single current from the mean-variance plots of patch or synaptic currents is not highly accurate owing to the varying number of the activatable AMPA channels caused by desensitization. The spatial nonuniformity of open, bound, and desensitized AMPA channels, and the time dependence and spatial nonuniformity of the glutamate concentration in the synaptic cleft, further reduce the accuracy of estimates of the number of AMPA channels from synaptic currents. In conclusion, wavelet analysis of nonstationary fluctuations of patch and synaptic currents expands our ability to determine accurately the variance and frequency of current fluctuations, demonstrates the limits of applicability of techniques currently used to evaluate the single channel current and number of AMPA channels, and offers new insights into the mechanisms involved in the generation of unitary quantal events at excitatory central synapses.

Development and characterization of a diamond-insulated graphitic multi electrode array realized with ion beam lithography.

PubMed

Picollo, Federico; Battiato, Alfio; Carbone, Emilio; Croin, Luca; Enrico, Emanuele; Forneris, Jacopo; Gosso, Sara; Olivero, Paolo; Pasquarelli, Alberto; Carabelli, Valentina

2014-12-30

The detection of quantal exocytic events from neurons and neuroendocrine cells is a challenging task in neuroscience. One of the most promising platforms for the development of a new generation of biosensors is diamond, due to its biocompatibility, transparency and chemical inertness. Moreover, the electrical properties of diamond can be turned from a perfect insulator into a conductive material (resistivity ~mΩ·cm) by exploiting the metastable nature of this allotropic form of carbon. A 16‑channels MEA (Multi Electrode Array) suitable for cell culture growing has been fabricated by means of ion implantation. A focused 1.2 MeV He+ beam was scanned on a IIa single-crystal diamond sample (4.5 × 4.5 × 0.5 mm3) to cause highly damaged sub-superficial structures that were defined with micrometric spatial resolution. After implantation, the sample was annealed. This process provides the conversion of the sub-superficial highly damaged regions to a graphitic phase embedded in a highly insulating diamond matrix. Thanks to a three-dimensional masking technique, the endpoints of the sub-superficial channels emerge in contact with the sample surface, therefore being available as sensing electrodes. Cyclic voltammetry and amperometry measurements of solutions with increasing concentrations of adrenaline were performed to characterize the biosensor sensitivity. The reported results demonstrate that this new type of biosensor is suitable for in vitro detection of catecholamine release.

Ultraviolet radiation cataract: dose dependence

NASA Astrophysics Data System (ADS)

Soderberg, Per G.; Loefgren, Stefan

1994-07-01

Current safety limits for cataract development after acute exposure to ultraviolet radiation (UVR) are based on experiments analyzing experimental data with a quantal, effect-no effect, dose-response model. The present study showed that intensity of forward light scattering is better described with a continuous dose-response model. It was found that 3, 30 and 300 kJ/m2UVR300nm induces increased light scattering within 6 h. For all three doses the intensity of forward light scattering was constant after 6 h. The intensity of forward light scattering was proportional to the log dose of UVR300nm. There was a slight increase of the intensity of forward light scattering on the contralateral side in animals that received 300 kJ/m2. Altogether 72 Sprague-Dawley male rats were included. Half of the rats were exposed in vivo on one side to UVR300nm. The other half was kept as a control group, receiving the same treatment as exposed rats but without delivery of UVR300nm to the eye. Subgroups of the rats received either of the three doses. Rats were sacrificed at varying intervals after the exposure. The lenses were extracted and the forward light scattering was estimated. It is concluded that intensity of forward light scattering in the lens after exposure to UVR300nm should be described with a continuous dose-reponse model.

The influence of incubation time on adenovirus quantitation in A549 cells by most probable number.

PubMed

Cashdollar, Jennifer L; Huff, Emma; Ryu, Hodon; Grimm, Ann C

2016-11-01

Cell culture based assays used to detect waterborne viruses typically call for incubating the sample for at least two weeks in order to ensure that all the culturable virus present is detected. Historically, this estimate was based, at least in part, on the length of time used for detecting poliovirus. In this study, we have examined A549 cells infected with human adenovirus type 2, and have found that a three week incubation of virus infected cells results in a higher number of detected viruses by quantal assay than what is seen after two weeks of incubation, with an average 955% increase in Most Probable Number (MPN) from 2 weeks to 3 weeks. This increase suggests that the extended incubation time is essential for accurately estimating viral titer, particularly for slow-growing viruses, UV treated samples, or samples with low titers of virus. In addition, we found that for some UV-treated samples, there was no detectable MPN at 2 weeks, but after 3 weeks, MPN values were obtained. For UV-treated samples, the average increase in MPN from 2 weeks to 3 weeks was 1401%, while untreated samples averaged a change in MPN of 674%, leading us to believe that the UV-damaged viral DNA may be able to be repaired such that viral replication then occurs. Published by Elsevier B.V.

Articulatory characteristics of Hungarian ‘transparent’ vowels

PubMed Central

Benus, Stefan; Gafos, Adamantios I.

2007-01-01

Using a combination of magnetometry and ultrasound, we examined the articulatory characteristics of the so-called ‘transparent’ vowels [iː], [i], and [eː] in Hungarian vowel harmony. Phonologically, transparent vowels are front, but they can be followed by either front or back suffixes. However, a finer look reveals an underlying phonetic coherence in two respects. First, transparent vowels in back harmony contexts show a less advanced (more retracted) tongue body posture than phonemically identical vowels in front harmony contexts: e.g. [i] in buli-val is less advanced than [i] in bili-vel. Second, transparent vowels in monosyllabic stems selecting back suffixes are also less advanced than phonemically identical vowels in stems selecting front suffixes: e.g. [iː] in ír, taking back suffixes, compared to [iː] of hír, taking front suffixes, is less advanced when these stems are produced in bare form (no suffixes). We thus argue that the phonetic degree of tongue body horizontal position correlates with the phonological alternation in suffixes. A hypothesis that emerges from this work is that a plausible phonetic basis for transparency can be found in quantal characteristics of the relation between articulation and acoustics of transparent vowels. More broadly, the proposal is that the phonology of transparent vowels is better understood when their phonological patterning is studied together with their articulatory and acoustic characteristics. PMID:18389086

Depletion of intracellular calcium stores facilitates the influx of extracellular calcium in platelet derived growth factor stimulated A172 glioblastoma cells.

PubMed

Vereb, G; Szöllösi, J; Mátyus, L; Balázs, M; Hyun, W C; Feuerstein, B G

1996-05-01

Calcium signaling in non-excitable cells is the consequence of calcium release from intracellular stores, at times followed by entry of extracellular calcium through the plasma membrane. To study whether entry of calcium depends upon the level of saturation of intracellular stores, we measured calcium channel opening in the plasma membrane of single confluent A172 glioblastoma cells stimulated with platelet derived growth factor (PDGF) and/or bradykinin (BK). We monitored the entry of extracellular calcium by measuring manganese quenching of Indo-1 fluorescence. PDGF raised intracellular calcium concentration ([Ca2+]i) after a dose-dependent delay (tdel) and then opened calcium channels after a dose-independent delay (tch). At higher doses (> 3 nM), BK increased [Ca2+]i after a tdel approximately 0 s, and tch decreased inversely with both dose and peak [Ca2+]i. Experiments with thapsigargin (TG), BK, and PDGF indicated that BK and PDGF share intracellular Ca2+ pools that are sensitive to TG. When these stores were depleted by treatment with BK and intracellular BAPTA, tdel did not change, but tch fell to almost 0 s in PDGF stimulated cells, indicating that depletion of calcium stores affects calcium channel opening in the plasma membrane. Our data support the capacitative model for calcium channel opening and the steady-state model describing quantal Ca2+ release from intracellular stores.

Presynaptic congenital myasthenic syndrome with a homozygous sequence variant in LAMA5 combines myopia, facial tics, and failure of neuromuscular transmission.

PubMed

Maselli, Ricardo A; Arredondo, Juan; Vázquez, Jessica; Chong, Jessica X; Bamshad, Michael J; Nickerson, Deborah A; Lara, Marian; Ng, Fiona; Lo, Victoria L; Pytel, Peter; McDonald, Craig M

2017-08-01

Defects in genes encoding the isoforms of the laminin alpha subunit have been linked to various phenotypic manifestations, including brain malformations, muscular dystrophy, ocular defects, cardiomyopathy, and skin abnormalities. We report here a severe defect of neuromuscular transmission in a consanguineous patient with a homozygous variant in the laminin alpha-5 subunit gene (LAMA5). The variant c.8046C>T (p.Arg2659Trp) is rare and has a predicted deleterious effect. The affected individual, who also carries a rare homozygous sequence variant in LAMA1, had muscle weakness, myopia, and facial tics. Magnetic resonance imaging of brain showed mild volume loss and periventricular T2 prolongation. Repetitive nerve stimulation revealed 50% decrement of compound muscle action potential amplitudes and 250% facilitation immediately after exercise, Endplate studies identified a profound reduction of the endplate potential quantal content and endplates with normal postsynaptic folding that were denuded or partially occupied by small nerve terminals. Expression studies revealed that p.Arg2659Trp caused decreased binding of laminin alpha-5 to SV2A and impaired laminin-521 cell-adhesion and cell projection support in primary neuronal cultures. In summary, this report describing severe neuromuscular transmission failure in a patient with a LAMA5 mutation expands the list of phenotypes associated with defects in genes encoding alpha-laminins. © 2017 Wiley Periodicals, Inc.

Quantum-Classical Correspondence Principle for Work Distributions

NASA Astrophysics Data System (ADS)

Jarzynski, Christopher; Quan, H. T.; Rahav, Saar

2015-07-01

For closed quantum systems driven away from equilibrium, work is often defined in terms of projective measurements of initial and final energies. This definition leads to statistical distributions of work that satisfy nonequilibrium work and fluctuation relations. While this two-point measurement definition of quantum work can be justified heuristically by appeal to the first law of thermodynamics, its relationship to the classical definition of work has not been carefully examined. In this paper, we employ semiclassical methods, combined with numerical simulations of a driven quartic oscillator, to study the correspondence between classical and quantal definitions of work in systems with 1 degree of freedom. We find that a semiclassical work distribution, built from classical trajectories that connect the initial and final energies, provides an excellent approximation to the quantum work distribution when the trajectories are assigned suitable phases and are allowed to interfere. Neglecting the interferences between trajectories reduces the distribution to that of the corresponding classical process. Hence, in the semiclassical limit, the quantum work distribution converges to the classical distribution, decorated by a quantum interference pattern. We also derive the form of the quantum work distribution at the boundary between classically allowed and forbidden regions, where this distribution tunnels into the forbidden region. Our results clarify how the correspondence principle applies in the context of quantum and classical work distributions and contribute to the understanding of work and nonequilibrium work relations in the quantum regime.

Capsaicin modulates acetylcholine release at the myoneural junction.

PubMed

Thyagarajan, Baskaran; Potian, Joseph G; Baskaran, Padmamalini; McArdle, Joseph J

2014-12-05

Transient receptor potential (TRP) proteins are non-selective cation channel proteins that are expressed throughout the body. Previous studies demonstrated the expression of TRP Vanilloid 1 (TRPV1), capsaicin (CAP) receptor, in sensory neurons. Recently, we reported TRPV1 expression in mouse motor nerve terminals [MNTs; (Thyagarajan et al., 2009)], where we observed that CAP protected MNTs from botulinum neurotoxin A (BoNT/A). Phrenic nerve diaphragm nerve muscle preparations (NMP) isolated from isoflurane anesthetized adult mice were analyzed for twitch tension, spontaneous (mEPCs) and nerve stimulus evoked (EPCs) acetylcholine release. When acutely applied to isolated NMP, CAP produced a concentration-dependent decline of twitch tension and produced a significant decline in the amplitude of EPCs and quantal content without any effect on the mEPCs. The suppression of nerve stimulus evoked acetylcholine release by CAP was antagonized by capsazepine (CPZ), a TRPV1 antagonist. CAP did not suppress phrenic nerve stimulus evoked acetylcholine release in TRPV1 knockout mice. Also, CAP treatment, in vitro, interfered with the localization of adapter protein 2 in cholinergic Neuro 2a cells. Wortmannin, (WMN; non-selective phosphoinositol kinase inhibitor), mimicked the effects of CAP by inhibiting the acetylcholine exocytosis. Our data suggest that TRPV1 proteins expressed at the MNT are coupled to the exo-endocytic mechanisms to regulate neuromuscular functions. Copyright © 2014 Elsevier B.V. All rights reserved.

Quantal Time Asymmetry: Mathematical Foundation and Physical Interpretation

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

Bohm, A.

2010-07-29

Time in standard quantum mechanics extends from -{infinity}t{sub 0}(Feynman (1948)). In experiments on single Ba{sup +} ions, Dehmelt and others observed this finite preparation timemore » as the ensemble of onset-times t{sub 0}{sup 1}, t{sub 0}{sup 2},...,t{sub 0}{sup n} of dark periods. How the semigroup time evolution, t{sub 0{identical_to}}0

Prediction of lethal/effective concentration/dose in the presence of multiple auxiliary covariates and components of variance

USGS Publications Warehouse

Gutreuter, S.; Boogaard, M.A.

2007-01-01

Predictors of the percentile lethal/effective concentration/dose are commonly used measures of efficacy and toxicity. Typically such quantal-response predictors (e.g., the exposure required to kill 50% of some population) are estimated from simple bioassays wherein organisms are exposed to a gradient of several concentrations of a single agent. The toxicity of an agent may be influenced by auxiliary covariates, however, and more complicated experimental designs may introduce multiple variance components. Prediction methods lag examples of those cases. A conventional two-stage approach consists of multiple bivariate predictions of, say, medial lethal concentration followed by regression of those predictions on the auxiliary covariates. We propose a more effective and parsimonious class of generalized nonlinear mixed-effects models for prediction of lethal/effective dose/concentration from auxiliary covariates. We demonstrate examples using data from a study regarding the effects of pH and additions of variable quantities 2???,5???-dichloro-4???- nitrosalicylanilide (niclosamide) on the toxicity of 3-trifluoromethyl-4- nitrophenol to larval sea lamprey (Petromyzon marinus). The new models yielded unbiased predictions and root-mean-squared errors (RMSEs) of prediction for the exposure required to kill 50 and 99.9% of some population that were 29 to 82% smaller, respectively, than those from the conventional two-stage procedure. The model class is flexible and easily implemented using commonly available software. ?? 2007 SETAC.

Gradation (approx. 10 size states) of synaptic strength by quantal addition of structural modules

PubMed Central

2017-01-01

Memory storage involves activity-dependent strengthening of synaptic transmission, a process termed long-term potentiation (LTP). The late phase of LTP is thought to encode long-term memory and involves structural processes that enlarge the synapse. Hence, understanding how synapse size is graded provides fundamental information about the information storage capability of synapses. Recent work using electron microscopy (EM) to quantify synapse dimensions has suggested that synapses may structurally encode as many as 26 functionally distinct states, which correspond to a series of proportionally spaced synapse sizes. Other recent evidence using super-resolution microscopy has revealed that synapses are composed of stereotyped nanoclusters of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and scaffolding proteins; furthermore, synapse size varies linearly with the number of nanoclusters. Here we have sought to develop a model of synapse structure and growth that is consistent with both the EM and super-resolution data. We argue that synapses are composed of modules consisting of matrix material and potentially one nanocluster. LTP induction can add a trans-synaptic nanocluster to a module, thereby converting a silent module to an AMPA functional module. LTP can also add modules by a linear process, thereby producing an approximately 10-fold gradation in synapse size and strength. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’. PMID:28093559

Gradation (approx. 10 size states) of synaptic strength by quantal addition of structural modules.

PubMed

Liu, Kang K L; Hagan, Michael F; Lisman, John E

2017-03-05

Memory storage involves activity-dependent strengthening of synaptic transmission, a process termed long-term potentiation (LTP). The late phase of LTP is thought to encode long-term memory and involves structural processes that enlarge the synapse. Hence, understanding how synapse size is graded provides fundamental information about the information storage capability of synapses. Recent work using electron microscopy (EM) to quantify synapse dimensions has suggested that synapses may structurally encode as many as 26 functionally distinct states, which correspond to a series of proportionally spaced synapse sizes. Other recent evidence using super-resolution microscopy has revealed that synapses are composed of stereotyped nanoclusters of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and scaffolding proteins; furthermore, synapse size varies linearly with the number of nanoclusters. Here we have sought to develop a model of synapse structure and growth that is consistent with both the EM and super-resolution data. We argue that synapses are composed of modules consisting of matrix material and potentially one nanocluster. LTP induction can add a trans-synaptic nanocluster to a module, thereby converting a silent module to an AMPA functional module. LTP can also add modules by a linear process, thereby producing an approximately 10-fold gradation in synapse size and strength.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'. © 2017 The Author(s).

The anatomy of choice: active inference and agency.

PubMed

Friston, Karl; Schwartenbeck, Philipp; Fitzgerald, Thomas; Moutoussis, Michael; Behrens, Timothy; Dolan, Raymond J

2013-01-01

This paper considers agency in the setting of embodied or active inference. In brief, we associate a sense of agency with prior beliefs about action and ask what sorts of beliefs underlie optimal behavior. In particular, we consider prior beliefs that action minimizes the Kullback-Leibler (KL) divergence between desired states and attainable states in the future. This allows one to formulate bounded rationality as approximate Bayesian inference that optimizes a free energy bound on model evidence. We show that constructs like expected utility, exploration bonuses, softmax choice rules and optimism bias emerge as natural consequences of this formulation. Previous accounts of active inference have focused on predictive coding and Bayesian filtering schemes for minimizing free energy. Here, we consider variational Bayes as an alternative scheme that provides formal constraints on the computational anatomy of inference and action-constraints that are remarkably consistent with neuroanatomy. Furthermore, this scheme contextualizes optimal decision theory and economic (utilitarian) formulations as pure inference problems. For example, expected utility theory emerges as a special case of free energy minimization, where the sensitivity or inverse temperature (of softmax functions and quantal response equilibria) has a unique and Bayes-optimal solution-that minimizes free energy. This sensitivity corresponds to the precision of beliefs about behavior, such that attainable goals are afforded a higher precision or confidence. In turn, this means that optimal behavior entails a representation of confidence about outcomes that are under an agent's control.

Selective depolarization of the muscle membrane in frog nerve-muscle preparations by a chromatographically purified extract of the dinoflagellate Ostreopsis lenticularis

PubMed Central

Meunier, Frédéric A; Mercado, José A; Molgó, Jordi; Tosteson, Thomas R; Escalona de Motta, Gladys

1997-01-01

The actions of a chromatographically identified extract of the marine dinoflagellate Ostreopsis lenticularis, named ostreotoxin-3 (OTX-3), were studied on frog isolated neuromuscular preparations. OTX-3 (1–10 μg ml−1) applied to cutaneous pectoris nerve-muscle preparations depolarized skeletal muscle fibres and caused spontaneous contractions. The depolarization was neither reversed by prolonged washing nor by (+)-tubocurarine. OTX-3 decreased the amplitude of miniature end plate potentials (m.e.p.ps) but did not affect their frequency. Extracellular recording of compound action potentials revealed that OTX-3 affected neither excitability nor conduction along intramuscular nerve branches. End-plate potentials (e.p.ps) elicited by nerve stimulation were reduced in amplitude by OTX-3 and even showed reversed polarity in junctions deeply depolarized by the toxin. Membrane depolarization induced by OTX-3 was decreased about 70% in muscles pretreated for 30 min with 10 μM tetrodotoxin. In contrast, muscles pretreated with 5 μM μ-conotoxin GIIIA were completely insensitive to OTX-3-induced depolarization. OTX-3 did not affect e.p.p. amplitude and the quantal content of e.p.ps in junctions in which muscle depolarization was abolished by μ-conotoxin GIIIA. OTX-3 is a novel type of sodium-channel activating toxin that discriminates between nerve and skeletal muscle membranes. PMID:9249261

Considering Risk and Resilience in Decision-Making

NASA Technical Reports Server (NTRS)

Torres-Pomales, Wilfredo

2015-01-01

This paper examines the concepts of decision-making, risk analysis, uncertainty and resilience analysis. The relation between risk, vulnerability, and resilience is analyzed. The paper describes how complexity, uncertainty, and ambiguity are the most critical factors in the definition of the approach and criteria for decision-making. Uncertainty in its various forms is what limits our ability to offer definitive answers to questions about the outcomes of alternatives in a decision-making process. It is shown that, although resilience-informed decision-making would seem fundamentally different from risk-informed decision-making, this is not the case as resilience-analysis can be easily incorporated within existing analytic-deliberative decision-making frameworks.

Naturalistic Decision Making: Implications for Design

DTIC Science & Technology

1993-04-01

Cognitive Task Analysis Decision Making Design Engineer Design System Human-Computer Interface System Development 15. NUMBER OF PAGES 182 16...people use to select a course of action. The SOAR explains how stress affects the decision making of both individuals and teams. COGNITIVE TASK ANALYSIS : This...procedures for Cognitive Task Analysis , contrasting the strengths and weaknesses of each, and showing how a Cognitive Task Analysis

Development and Characterization of a Diamond-Insulated Graphitic Multi Electrode Array Realized with Ion Beam Lithography

PubMed Central

Picollo, Federico; Battiato, Alfio; Carbone, Emilio; Croin, Luca; Enrico, Emanuele; Forneris, Jacopo; Gosso, Sara; Olivero, Paolo; Pasquarelli, Alberto; Carabelli, Valentina

2015-01-01

The detection of quantal exocytic events from neurons and neuroendocrine cells is a challenging task in neuroscience. One of the most promising platforms for the development of a new generation of biosensors is diamond, due to its biocompatibility, transparency and chemical inertness. Moreover, the electrical properties of diamond can be turned from a perfect insulator into a conductive material (resistivity ∼mΩ·cm) by exploiting the metastable nature of this allotropic form of carbon. A 16-channels MEA (Multi Electrode Array) suitable for cell culture growing has been fabricated by means of ion implantation. A focused 1.2 MeV He+ beam was scanned on a IIa single-crystal diamond sample (4.5 × 4.5 × 0.5 mm3) to cause highly damaged sub-superficial structures that were defined with micrometric spatial resolution. After implantation, the sample was annealed. This process provides the conversion of the sub-superficial highly damaged regions to a graphitic phase embedded in a highly insulating diamond matrix. Thanks to a three-dimensional masking technique, the endpoints of the sub-superficial channels emerge in contact with the sample surface, therefore being available as sensing electrodes. Cyclic voltammetry and amperometry measurements of solutions with increasing concentrations of adrenaline were performed to characterize the biosensor sensitivity. The reported results demonstrate that this new type of biosensor is suitable for in vitro detection of catecholamine release. PMID:25558992

Modeling and measurement of vesicle pools at the cone ribbon synapse: changes in release probability are solely responsible for voltage-dependent changes in release

PubMed Central

Thoreson, Wallace B.; Van Hook, Matthew J.; Parmelee, Caitlyn; Curto, Carina

2015-01-01

Post-synaptic responses are a product of quantal amplitude (Q), size of the releasable vesicle pool (N), and release probability (P). Voltage-dependent changes in presynaptic Ca2+ entry alter post-synaptic responses primarily by changing P but have also been shown to influence N. With simultaneous whole cell recordings from cone photoreceptors and horizontal cells in tiger salamander retinal slices, we measured N and P at cone ribbon synapses by using a train of depolarizing pulses to stimulate release and deplete the pool. We developed an analytical model that calculates the total pool size contributing to release under different stimulus conditions by taking into account the prior history of release and empirically-determined properties of replenishment. The model provided a formula that calculates vesicle pool size from measurements of the initial post-synaptic response and limiting rate of release evoked by a train of pulses, the fraction of release sites available for replenishment, and the time constant for replenishment. Results of the model showed that weak and strong depolarizing stimuli evoked release with differing probabilities but the same size vesicle pool. Enhancing intraterminal Ca2+ spread by lowering Ca2+ buffering or applying BayK8644 did not increase PSCs evoked with strong test steps showing there is a fixed upper limit to pool size. Together, these results suggest that light-evoked changes in cone membrane potential alter synaptic release solely by changing release probability. PMID:26541100

Lyapounov variable: Entropy and measurement in quantum mechanics

PubMed Central

Misra, B.; Prigogine, I.; Courbage, M.

1979-01-01

We discuss the question of the dynamical meaning of the second law of thermodynamics in the framework of quantum mechanics. Previous discussion of the problem in the framework of classical dynamics has shown that the second law can be given a dynamical meaning in terms of the existence of so-called Lyapounov variables—i.e., dynamical variables varying monotonically in time without becoming contradictory. It has been found that such variables can exist in an extended framework of classical dynamics, provided that the dynamical motion is suitably unstable. In this paper we begin to extend these results to quantum mechanics. It is found that no dynamical variable with the characteristic properties of nonequilibrium entropy can be defined in the standard formulation of quantum mechanics. However, if the Hamiltonian has certain well-defined spectral properties, such variables can be defined but only as a nonfactorizable superoperator. Necessary nonfactorizability of such entropy operators M has the consequence that they cannot preserve the class of pure states. Physically, this means that the distinguishability between pure states and corresponding mixtures must be lost in the case of a quantal system for which the algebra of observables can be extended to include a new dynamical variable representing nonequilibrium entropy. We discuss how this result leads to a solution of the quantum measurement problem. It is also found that the question of existence of entropy of superoperators M is closely linked to the problem of defining an operator of time in quantum mechanics. PMID:16578757

The anatomy of choice: active inference and agency

PubMed Central

Friston, Karl; Schwartenbeck, Philipp; FitzGerald, Thomas; Moutoussis, Michael; Behrens, Timothy; Dolan, Raymond J.

2013-01-01

This paper considers agency in the setting of embodied or active inference. In brief, we associate a sense of agency with prior beliefs about action and ask what sorts of beliefs underlie optimal behavior. In particular, we consider prior beliefs that action minimizes the Kullback–Leibler (KL) divergence between desired states and attainable states in the future. This allows one to formulate bounded rationality as approximate Bayesian inference that optimizes a free energy bound on model evidence. We show that constructs like expected utility, exploration bonuses, softmax choice rules and optimism bias emerge as natural consequences of this formulation. Previous accounts of active inference have focused on predictive coding and Bayesian filtering schemes for minimizing free energy. Here, we consider variational Bayes as an alternative scheme that provides formal constraints on the computational anatomy of inference and action—constraints that are remarkably consistent with neuroanatomy. Furthermore, this scheme contextualizes optimal decision theory and economic (utilitarian) formulations as pure inference problems. For example, expected utility theory emerges as a special case of free energy minimization, where the sensitivity or inverse temperature (of softmax functions and quantal response equilibria) has a unique and Bayes-optimal solution—that minimizes free energy. This sensitivity corresponds to the precision of beliefs about behavior, such that attainable goals are afforded a higher precision or confidence. In turn, this means that optimal behavior entails a representation of confidence about outcomes that are under an agent's control. PMID:24093015

Hypertonicity-induced transmitter release at Drosophila neuromuscular junctions is partly mediated by integrins and cAMP/protein kinase A

NASA Technical Reports Server (NTRS)

Suzuki, Kazuhiro; Grinnell, Alan D.; Kidokoro, Yoshiaki

2002-01-01

The frequency of quantal transmitter release increases upon application of hypertonic solutions. This effect bypasses the Ca(2+) triggering step, but requires the presence of key molecules involved in vesicle fusion, and hence could be a useful tool for dissecting the molecular process of vesicle fusion. We have examined the hypertonicity response at neuromuscular junctions of Drosophila embryos in Ca(2+)-free saline. Relative to wild-type, the response induced by puff application of hypertonic solution was enhanced in a mutant, dunce, in which the cAMP level is elevated, or in wild-type embryos treated with forskolin, an activator of adenylyl cyclase, while protein kinase A (PKA) inhibitors decreased it. The response was also smaller in a mutant, DC0, which lacks the major subunit of PKA. Thus the cAMP/PKA cascade is involved in the hypertonicity response. Peptides containing the sequence Arg-Gly-Asp (RGD), which inhibit binding of integrins to natural ligands, reduced the response, whereas a peptide containing the non-binding sequence Arg-Gly-Glu (RGE) did not. A reduced response persisted in a mutant, myospheroid, which expresses no integrins, and the response in DC0 was unaffected by RGD peptides. These data indicate that there are at lease two components in the hypertonicity response: one that is integrin mediated and involves the cAMP/PKA cascade, and another that is not integrin mediated and does not involve the cAMP/PKA cascade.

Insect haptoelectrical stimulation of Venus flytrap triggers exocytosis in gland cells.

PubMed

Scherzer, Sönke; Shabala, Lana; Hedrich, Benjamin; Fromm, Jörg; Bauer, Hubert; Munz, Eberhard; Jakob, Peter; Al-Rascheid, Khaled A S; Kreuzer, Ines; Becker, Dirk; Eiblmeier, Monika; Rennenberg, Heinz; Shabala, Sergey; Bennett, Malcolm; Neher, Erwin; Hedrich, Rainer

2017-05-02

The Venus flytrap Dionaea muscipula captures insects and consumes their flesh. Prey contacting touch-sensitive hairs trigger traveling electrical waves. These action potentials (APs) cause rapid closure of the trap and activate secretory functions of glands, which cover its inner surface. Such prey-induced haptoelectric stimulation activates the touch hormone jasmonate (JA) signaling pathway, which initiates secretion of an acidic hydrolase mixture to decompose the victim and acquire the animal nutrients. Although postulated since Darwin's pioneering studies, these secretory events have not been recorded so far. Using advanced analytical and imaging techniques, such as vibrating ion-selective electrodes, carbon fiber amperometry, and magnetic resonance imaging, we monitored stimulus-coupled glandular secretion into the flytrap. Trigger-hair bending or direct application of JA caused a quantal release of oxidizable material from gland cells monitored as distinct amperometric spikes. Spikes reminiscent of exocytotic events in secretory animal cells progressively increased in frequency, reaching steady state 1 d after stimulation. Our data indicate that trigger-hair mechanical stimulation evokes APs. Gland cells translate APs into touch-inducible JA signaling that promotes the formation of secretory vesicles. Early vesicles loaded with H + and Cl - fuse with the plasma membrane, hyperacidifying the "green stomach"-like digestive organ, whereas subsequent ones carry hydrolases and nutrient transporters, together with a glutathione redox moiety, which is likely to act as the major detected compound in amperometry. Hence, when glands perceive the haptoelectrical stimulation, secretory vesicles are tailored to be released in a sequence that optimizes digestion of the captured animal.

Light-dependent quenching of chlorophyll fluorescence in pea chloroplasts induced by adenosine 5'-triphosphate.

PubMed

Horton, P; Black, M T

1981-03-12

Addition of ATP to chloroplasts causes a reversible 25-30% decrease in chlorophyll fluorescence. This quenching is light-dependent, uncoupler insensitive but inhibited by DCMU and electron acceptors and has a half-time of 3 minutes. Electron donors to Photosystem I can not overcome the inhibitory effect of DCMU, suggesting that light activation depends on the reduced state of plastoquinone. Fluorescence emission spectra recorded at -196 degrees C indicate that ATP treatment increases the amount of excitation energy transferred to Photosystem I. Examination of fluorescence induction curves indicate that ATP treatment decreases both the initial (F0) and variable (Fv) fluorescence such that the ratio of Fv to the maximum (Fm) yield is unchanged. The initial sigmoidal phase of induction is slowed down by ATP treatment and is quenched 3-fold more than the exponential slow phase, the rate of which is unchanged. A plot of Fv against area above the induction curve was identical plus or minus ATP. Thus ATP treatment can alter quantal distribution between Photosystems II and I without altering Photosystem II-Photosystem II interaction. The effect of ATP strongly resembles in its properties the phosphorylation of the light-harvesting complex by a light activated, ATP-dependent protein kinase found in chloroplast membranes and could be the basis of physiological mechanisms which contribute to slow fluorescence quenching in vivo and regulate excitation energy distribution between Photosystem I and II. It is suggested that the sensor for this regulation is the redox state of plastoquinone.

A steady-state mechanism can account for the properties of inositol 2,4,5-trisphosphate-stimulated Ca2+ release from permeabilized L1210 cells.

PubMed Central

Loomis-Husselbee, J W; Dawson, A P

1993-01-01

We have investigated the effects of sub-maximal Ins(2,4,5)P3 concentrations on the Ca2+ permeability of the residual undischarged Ca2+ stores in electroporated or digitonin-permeabilized L1210 cells by measuring Ca(2+)-efflux rate after addition of the ATPase inhibitor thapsigargin. Low concentrations of Ins(2,4,5)P3, causing rapid discharge of a small proportion of the releasable Ca2+, result in a substantial stimulation of Ca2+ efflux after thapsigargin addition. This indicates firstly that in the absence of thapsigargin there must have been a substantial, counterbalancing, increase in rate of Ca2+ pumping, and secondly that the increased Ca2+ permeability is more consistent with a steady state than with a quantal model of Ca2+ release. Similar increases in passive Ca2+ permeability are produced by addition of concentrations of ionomycin which produce equivalent changes in Ca2+ loading to those produced by Ins(2,4,5)P3, although the time course and initial rate of Ca2+ release are very much slower. In the presence of a Ca(2+)-buffering system, the time course of Ca2+ release by Ins(2,4,5)P3 becomes superimposable on that of ionomycin, indicating that the initial rapid phase of Ins(2,4,5)P3-stimulated Ca2+ is at least partially due to positive feedback from extravesicular Ca2+. PMID:8382056

Colocalization of vesicular glutamate transporters in the rat superior olivary complex.

PubMed

Billups, Brian

Vesicular glutamate transporters (VGLUTs) are responsible for the accumulation of the excitatory neurotransmitter glutamate into synaptic vesicles. It is currently controversial whether the two isoforms found in glutamatergic neurons, VGLUT1 and VGLUT2, are present at the same synapse or have entirely complementary patterns of distribution. Using fluorescent immunohistochemistry, this study examines the colocalization of these two transporters in the rat superior olivary complex (SOC) between postnatal day (P) 5 and 29. The medial and lateral superior olives (MSO; LSO) stain for both VGLUT1 and VGLUT2 at all ages studied, with VGLUT1 levels doubling over this developmental period and VGLUT2 levels remaining unchanged. The ventral nucleus of the trapezoid body (VNTB) strongly labels only for VGLUT2, despite the fact that glutamatergic synapses are present that are formed from collaterals of axons that go on to form synapses containing both VGLUT1 and VGLUT2. Principal neurons of the medial nucleus of the trapezoid body (MNTB) are surrounded by the calyx of Held presynaptic terminal, which is large enough to allow examination of VGLUT localization within a synapse. Throughout its postnatal developmental period a single calyx synapse contains both VGLUT1 and VGLUT2. Whereas VGLUT1 levels are greatly up-regulated from P5 to P29, VGLUT2 levels remain high. As the abundance of VGLUT determines the quantal size, this up-regulation will increase excitatory postsynaptic currents (EPSCs) and have influences on synaptic physiology.

Distinction between Externally vs. Internally Guided Decision-Making: Operational Differences, Meta-Analytical Comparisons and Their Theoretical Implications

PubMed Central

Nakao, Takashi; Ohira, Hideki; Northoff, Georg

2012-01-01

Most experimental studies of decision-making have specifically examined situations in which a single less-predictable correct answer exists (externally guided decision-making under uncertainty). Along with such externally guided decision-making, there are instances of decision-making in which no correct answer based on external circumstances is available for the subject (internally guided decision-making). Such decisions are usually made in the context of moral decision-making as well as in preference judgment, where the answer depends on the subject’s own, i.e., internal, preferences rather than on external, i.e., circumstantial, criteria. The neuronal and psychological mechanisms that allow guidance of decisions based on more internally oriented criteria in the absence of external ones remain unclear. This study was undertaken to compare decision-making of these two kinds empirically and theoretically. First, we reviewed studies of decision-making to clarify experimental–operational differences between externally guided and internally guided decision-making. Second, using multi-level kernel density analysis, a whole-brain-based quantitative meta-analysis of neuroimaging studies was performed. Our meta-analysis revealed that the neural network used predominantly for internally guided decision-making differs from that for externally guided decision-making under uncertainty. This result suggests that studying only externally guided decision-making under uncertainty is insufficient to account for decision-making processes in the brain. Finally, based on the review and results of the meta-analysis, we discuss the differences and relations between decision-making of these two types in terms of their operational, neuronal, and theoretical characteristics. PMID:22403525

75 FR 18205 - Notice of Peer Review Meeting for the External Peer Review Drafts of Two Documents on Using...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-09

... Role of Risk Analysis in Decision-Making AGENCY: Environmental Protection Agency (EPA). ACTION: Notice... documents entitled, ``Using Probabilistic Methods to Enhance the Role of Risk Analysis in Decision- Making... Probabilistic Methods to Enhance the Role of Risk Analysis in Decision-Making, with Case Study Examples'' and...

Understanding medical decision making in hand surgery.

PubMed

Myers, John; McCabe, Steven J

2005-10-01

The practice of medicine takes place in an environment of uncertainty. Expected value decision making, prospect theory, and regret theory are three theories of decision making under uncertainty that may be used to help us learn how patients and physicians make decisions. These theories form the underpinnings of decision analysis and provide the opportunity to introduce the broad discipline of decision science. Because decision analysis and economic analysis are underrepresented in upper extremity surgery, the authors believe these are important areas for future research.

Models for Rational Decision Making. Analysis of Literature and Selected Bibliography. Analysis and Bibliography Series, No. 6.

ERIC Educational Resources Information Center

Hall, John S.

This review analyzes the trend in educational decision making to replace hierarchical authority structures with more rational models for decision making drawn from management science. Emphasis is also placed on alternatives to a hierarchical decision-making model, including governing models, union models, and influence models. A 54-item…

The impact of management science on political decision making

NASA Technical Reports Server (NTRS)

White, M. J.

1971-01-01

The possible impact on public policy and organizational decision making of operations research/management science (OR/MS) is discussed. Criticisms based on the assumption that OR/MS will have influence on decision making and criticisms based on the assumption that it will have no influence are described. New directions in the analysis of analysis and in thinking about policy making are also considered.

Analyses of S-Box in Image Encryption Applications Based on Fuzzy Decision Making Criterion

NASA Astrophysics Data System (ADS)

Rehman, Inayatur; Shah, Tariq; Hussain, Iqtadar

2014-06-01

In this manuscript, we put forward a standard based on fuzzy decision making criterion to examine the current substitution boxes and study their strengths and weaknesses in order to decide their appropriateness in image encryption applications. The proposed standard utilizes the results of correlation analysis, entropy analysis, contrast analysis, homogeneity analysis, energy analysis, and mean of absolute deviation analysis. These analyses are applied to well-known substitution boxes. The outcome of these analyses are additional observed and a fuzzy soft set decision making criterion is used to decide the suitability of an S-box to image encryption applications.

How Expert Pilots Think Cognitive Processes in Expert Decision Making

DTIC Science & Technology

1993-02-01

Management (CRM) This document is available to the public Advanced Qualification Program (AQP) through the National Technical Information Cognitive Task Analysis (CTA...8217 Selecting realistic EDM scenarios with critical events and performing a cognitive task analysis of novice vs. expert decision making for these events...scenarios with critical events and performing a cognitive task analysis of novice vs. expert decision making for these events is a basic requirement for

Methods for Conducting Cognitive Task Analysis for a Decision Making Task.

DTIC Science & Technology

1996-01-01

Cognitive task analysis (CTA) improves traditional task analysis procedures by analyzing the thought processes of performers while they complete a...for using these methods to conduct a CTA for domains which involve critical decision making tasks in naturalistic settings. The cognitive task analysis methods

Students' Meaning Making in Classroom Discussions: The Importance of Peer Interaction

ERIC Educational Resources Information Center

Rudsberg, Karin; Östman, Leif; Aaro Östman, Elisabeth

2017-01-01

The aim is to investigate how encounters with peers affect an individual's meaning making in argumentation about socio-scientific issues, and how the individual's meaning making influences the argumentation at the collective level. The analysis is conducted using the analytical method "transactional argumentation analysis" (TAA) which…

Static Analysis Alert Audits: Lexicon and Rules

DTIC Science & Technology

2016-11-04

collaborators • Includes a standard set of well-defined determinations for static analysis alerts • Includes a set of auditing rules to help auditors make...consistent decisions in commonly-encountered situations Different auditors should make the same determination for a given alert! Improve the quality and...scenarios • Establish assumptions auditors can make • Overall: help make audit determinations more consistent We developed 12 rules • Drew on our own

Using Cluster Analysis to Examine Husband-Wife Decision Making

ERIC Educational Resources Information Center

Bonds-Raacke, Jennifer M.

2006-01-01

Cluster analysis has a rich history in many disciplines and although cluster analysis has been used in clinical psychology to identify types of disorders, its use in other areas of psychology has been less popular. The purpose of the current experiments was to use cluster analysis to investigate husband-wife decision making. Cluster analysis was…

Students' meaning making in classroom discussions: the importance of peer interaction

NASA Astrophysics Data System (ADS)

Rudsberg, Karin; Östman, Leif; Aaro Östman, Elisabeth

2017-09-01

The aim is to investigate how encounters with peers affect an individual's meaning making in argumentation about socio-scientific issues, and how the individual's meaning making influences the argumentation at the collective level. The analysis is conducted using the analytical method "transactional argumentation analysis" (TAA) which enables in situ studies. TAA combines a transactional perspective on meaning making based on John Dewey's pragmatic philosophy with an argument analysis based on Toulmin's argument pattern. Here TAA is developed further to enable analysis that in detail clarifies the dynamic interplay between the individual and the collective—the intra- and the inter-personal dimensions—and the result of this interplay in terms of meaning making and learning. The empirical material in this study consists of a video-recorded lesson in a Swedish upper secondary school. The results show that the analysed student is influenced by peers when construing arguments, and thereby acts on others' reasoning when making meaning. Further, the results show that most of the additions made by the analysed student are taken further by peers in the subsequent discussion. This study shows how an individual's earlier experiences, knowledge and thinking contribute to the collective meaning making in the classroom.

Insect haptoelectrical stimulation of Venus flytrap triggers exocytosis in gland cells

PubMed Central

Scherzer, Sönke; Shabala, Lana; Hedrich, Benjamin; Fromm, Jörg; Bauer, Hubert; Munz, Eberhard; Jakob, Peter; Al-Rascheid, Khaled A. S.; Kreuzer, Ines; Becker, Dirk; Eiblmeier, Monika; Rennenberg, Heinz; Shabala, Sergey; Neher, Erwin; Hedrich, Rainer

2017-01-01

The Venus flytrap Dionaea muscipula captures insects and consumes their flesh. Prey contacting touch-sensitive hairs trigger traveling electrical waves. These action potentials (APs) cause rapid closure of the trap and activate secretory functions of glands, which cover its inner surface. Such prey-induced haptoelectric stimulation activates the touch hormone jasmonate (JA) signaling pathway, which initiates secretion of an acidic hydrolase mixture to decompose the victim and acquire the animal nutrients. Although postulated since Darwin’s pioneering studies, these secretory events have not been recorded so far. Using advanced analytical and imaging techniques, such as vibrating ion-selective electrodes, carbon fiber amperometry, and magnetic resonance imaging, we monitored stimulus-coupled glandular secretion into the flytrap. Trigger-hair bending or direct application of JA caused a quantal release of oxidizable material from gland cells monitored as distinct amperometric spikes. Spikes reminiscent of exocytotic events in secretory animal cells progressively increased in frequency, reaching steady state 1 d after stimulation. Our data indicate that trigger-hair mechanical stimulation evokes APs. Gland cells translate APs into touch-inducible JA signaling that promotes the formation of secretory vesicles. Early vesicles loaded with H+ and Cl− fuse with the plasma membrane, hyperacidifying the “green stomach”-like digestive organ, whereas subsequent ones carry hydrolases and nutrient transporters, together with a glutathione redox moiety, which is likely to act as the major detected compound in amperometry. Hence, when glands perceive the haptoelectrical stimulation, secretory vesicles are tailored to be released in a sequence that optimizes digestion of the captured animal. PMID:28416693

Synaptic Basis for Whisker Deprivation-Induced Synaptic Depression in Rat Somatosensory Cortex

PubMed Central

Bender, Kevin J.; Allen, Cara B.; Bender, Vanessa A.; Feldman, Daniel E.

2011-01-01

Whisker deprivation weakens excitatory layer 4 (L4) inputs to L2/3 pyramidal cells in rat primary somatosensory (S1) cortex, which is likely to contribute to whisker map plasticity. This weakening has been proposed to represent long-term depression (LTD) induced by sensory deprivation in vivo. Here, we studied the synaptic expression mechanisms for deprivation-induced weakening of L4-L2/3 inputs and assessed its similarity to LTD, which is known to be expressed presynaptically at L4-L2/3 synapses. Whisker deprivation increased the paired pulse ratio at L4-L2/3 synapses and slowed the use-dependent block of NMDA receptor currents by MK-801 [(5S,10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], indicating that deprivation reduced transmitter release probability at these synapses. In contrast, deprivation did not alter either miniature EPSC amplitude in L2/3 neurons or the amplitude of quantal L4-L2/3 synaptic responses measured in strontium, indicating that postsynaptic responsiveness was unchanged. In young postnatal day 12 (P12) rats, at least 4 d of deprivation were required to significantly weaken L4-L2/3 synapses. Similar weakening occurred when deprivation began at older ages (P20), when synapses are mostly mature, indicating that weakening is unlikely to represent a failure of synaptic maturation but instead represents a reduction in the strength of existing synapses. Thus, whisker deprivation weakens L4-L2/3 synapses by decreasing presynaptic function, similar to known LTD mechanisms at this synapse. PMID:16624936

Neurotrophic Properties, Chemosensory Responses and Neurogenic Niche of the Human Carotid Body.

PubMed

Ortega-Sáenz, Patricia; Villadiego, Javier; Pardal, Ricardo; Toledo-Aral, Juan José; López-Barneo, José

2015-01-01

The carotid body (CB) is a polymodal chemoreceptor that triggers the hyperventilatory response to hypoxia necessary for the maintenance of O(2) homeostasis essential for the survival of organs such as the brain or heart. Glomus cells, the sensory elements in the CB, are also sensitive to hypercapnia, acidosis and, although less generally accepted, hypoglycemia. Current knowledge on CB function is mainly based on studies performed on lower mammals, but the information on the human CB is scant. Here we describe the structure, neurotrophic properties, and cellular responses to hypoxia and hypoglycemia of CBs dissected from human cadavers. The adult CB parenchyma contains clusters of chemosensitive glomus (type I) and sustentacular (type II) cells as well as nestin-positive progenitor cells. This organ also expresses high levels of the dopaminotrophic glial cell line-derived neurotrophic factor (GDNF). GDNF production and the number of progenitor and glomus cells were preserved in the CBs of human subjects of advanced age. As reported for other mammalian species, glomus cells responded to hypoxia by external Ca(2+)-dependent increase of cytosolic [Ca(2+)] and quantal catecholamine release. Human glomus cells are also responsive to hypoglycemia and together the two stimuli, hypoxia and hypoglycemia, can potentiate each other's effects. The chemo-sensory responses of glomus cells are also preserved at an advanced age. Interestingly, a neurogenic niche similar to that recently described in rodents is also preserved in the adult human CB. These new data on the cellular and molecular physiology of the CB pave the way for future pathophysiological studies involving this organ in humans.

Glutamatergic drive facilitates synaptic inhibition of dorsal vagal motor neurons after experimentally induced diabetes in mice

PubMed Central

Boychuk, Carie R.

2016-01-01

The role of central regulatory circuits in modulating diabetes-associated glucose dysregulation has only recently been under rigorous investigation. One brain region of interest is the dorsal motor nucleus of the vagus (DMV), which contains preganglionic parasympathetic motor neurons that regulate subdiaphragmatic visceral function. Previous research has demonstrated that glutamatergic and GABAergic neurotransmission are independently remodeled after chronic hyperglycemia/hypoinsulinemia. However, glutamatergic circuitry within the dorsal brain stem impinges on GABAergic regulation of the DMV. The present study investigated the role of glutamatergic neurotransmission in synaptic GABAergic control of DMV neurons after streptozotocin (STZ)-induced hyperglycemia/hypoinsulinemia by using electrophysiological recordings in vitro. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) was elevated in DMV neurons from STZ-treated mice. The effect was abolished in the presence of the ionotropic glutamate receptor blocker kynurenic acid or the sodium channel blocker tetrodotoxin, suggesting that after STZ-induced hyperglycemia/hypoinsulinemia, increased glutamatergic receptor activity occurs at a soma-dendritic location on local GABA neurons projecting to the DMV. Although sIPSCs in DMV neurons normally demonstrated considerable amplitude variability, this variability was significantly increased after STZ-induced hyperglycemia/hypoinsulinemia. The elevated amplitude variability was not related to changes in quantal release, but rather correlated with significantly elevated frequency of sIPSCs in these mice. Taken together, these findings suggest that GABAergic regulation of central vagal circuitry responsible for the regulation of energy homeostasis undergoes complex functional reorganization after several days of hyperglycemia/hypoinsulinemia, including both glutamate-dependent and -independent forms of plasticity. PMID:27385796

Random Photon Absorption Model Elucidates How Early Gain Control in Fly Photoreceptors Arises from Quantal Sampling

PubMed Central

Song, Zhuoyi; Zhou, Yu; Juusola, Mikko

2016-01-01

Many diurnal photoreceptors encode vast real-world light changes effectively, but how this performance originates from photon sampling is unclear. A 4-module biophysically-realistic fly photoreceptor model, in which information capture is limited by the number of its sampling units (microvilli) and their photon-hit recovery time (refractoriness), can accurately simulate real recordings and their information content. However, sublinear summation in quantum bump production (quantum-gain-nonlinearity) may also cause adaptation by reducing the bump/photon gain when multiple photons hit the same microvillus simultaneously. Here, we use a Random Photon Absorption Model (RandPAM), which is the 1st module of the 4-module fly photoreceptor model, to quantify the contribution of quantum-gain-nonlinearity in light adaptation. We show how quantum-gain-nonlinearity already results from photon sampling alone. In the extreme case, when two or more simultaneous photon-hits reduce to a single sublinear value, quantum-gain-nonlinearity is preset before the phototransduction reactions adapt the quantum bump waveform. However, the contribution of quantum-gain-nonlinearity in light adaptation depends upon the likelihood of multi-photon-hits, which is strictly determined by the number of microvilli and light intensity. Specifically, its contribution to light-adaptation is marginal (≤ 1%) in fly photoreceptors with many thousands of microvilli, because the probability of simultaneous multi-photon-hits on any one microvillus is low even during daylight conditions. However, in cells with fewer sampling units, the impact of quantum-gain-nonlinearity increases with brightening light. PMID:27445779

Interactions between the visual and the magnetoreception system: different effects of bichromatic light regimes on the directional behavior of migratory birds.

PubMed

Wiltschko, Roswitha; Dehe, Lars; Gehring, Dennis; Thalau, Peter; Wiltschko, Wolfgang

2013-01-01

When magnetic compass orientation of migratory robins was tested, the birds proved well oriented under low intensity monochromatic light of shorter wavelengths up to 565 nm green; from 583 nm yellow onward, they were disoriented. In the present study, we tested robins under bichromatic lights composed (1) of 424 nm blue and 565 nm green and (2) of 565 nm green and 583 nm yellow at two intensities. Under dim blue-green light with a total quantal flux of ca. 8 × 10(15)quanta/sm(2), the birds were well oriented in their migratory direction by their inclination compass; under blue-green light of twice this intensity, their orientation became axial. In both cases, the magnetic directional information was mediated by the radical pair processes in the eye. When green and yellow light were combined, however, the nature of the behavior changed. Under green-yellow light of the higher intensity, the birds showed a 'fixed direction' response that was polar, no longer controlled by the normal inclination compass; under dim green-yellow light, the response became axial. Under these two light conditions, the respective directional information was mediated by the magnetite-based receptors in the skin of the upper beak. Apparently, yellow light leads to a change from one magnetoreception system to the other. How this change is effected is still unknown; it appears to reflect complex interactions between the visual and the two magnetoreception systems. Copyright © 2012 Elsevier Ltd. All rights reserved.

Glia-derived signals induce synapse formation in neurones of the rat central nervous system

PubMed Central

Nägler, Karl; Mauch, Daniela H; Pfrieger, Frank W

2001-01-01

To study the effects of glial cells on synapse formation, we established microcultures of purified rat retinal ganglion cells (RGCs) and monitored synapse (autapse) development in single neurones using electrophysiological recordings, FM1-43 labelling and immunocytochemistry.Solitary neurones grew ramifying neurites, but formed only very few and inefficient excitatory autapses, when cultured for up to 2 weeks in defined medium and in the absence of glial cells.Treatment of glia-free microcultures of RGCs with glia-conditioned medium (GCM) increased the number of autapses per neurone by up to 10-fold. This was indicated by a similar increase in the frequency of spontaneous events and the number of FM1-43-labelled functional release sites and of puncta, where pre- and postsynaptic markers colocalized.In addition, GCM treatment enhanced the efficacy of presynaptic transmitter release as indicated by lower failure rates of stimulation-induced excitatory autaptic currents, a 200-fold increase in the frequency of asynchronous release and an accelerated stimulation-induced FM1-43 destaining. Furthermore, GCM induced an increase in the quantal size.GCM affected autaptic activity not immediately, but with a delay of 24 h, and the effects on stimulation-induced autaptic currents occurred before changes in the frequency of spontaneous events indicating an early strengthening of existing autapses followed by a later increase in autapse number.The observed effects were mediated by proteinase K-sensitive factors in GCM and occurred independently of electrical activity.These results suggest that soluble glia-derived signals induce synapse formation and maturation in neurones of the central nervous system (CNS). PMID:11410625

Age-dependent synapse withdrawal at axotomised neuromuscular junctions in Wlds mutant and Ube4b/Nmnat transgenic mice

PubMed Central

Gillingwater, Thomas H; Thomson, Derek; Mack, Till G A; Soffin, Ellen M; Mattison, Richard J; Coleman, Michael P; Ribchester, Richard R

2002-01-01

Axons in WldS mutant mice are protected from Wallerian degeneration by overexpression of a chimeric Ube4b/Nmnat (Wld) gene. Expression of Wld protein was independent of age in these mice. However we identified two distinct neuromuscular synaptic responses to axotomy. In young adult Wlds mice, axotomy induced progressive, asynchronous synapse withdrawal from motor endplates, strongly resembling neonatal synapse elimination. Thus, five days after axotomy, 50–90 % of endplates were still partially or fully occupied and expressed endplate potentials (EPPs). By 10 days, fewer than 20 % of endplates still showed evidence of synaptic activity. Recordings from partially occupied junctions indicated a progressive decrease in quantal content in inverse proportion to endplate occupancy. In Wlds mice aged > 7 months, axons were still protected from axotomy but synapses degenerated rapidly, in wild-type fashion: within three days less than 5 % of endplates contained vestiges of nerve terminals. The axotomy-induced synaptic withdrawal phenotype decayed with a time constant of ∼30 days. Regenerated synapses in mature Wlds mice recapitulated the juvenile phenotype. Within 4–6 days of axotomy 30–50 % of regenerated nerve terminals still occupied motor endplates. Age-dependent synapse withdrawal was also seen in transgenic mice expressing the Wld gene. Co-expression of Wld protein and cyan fluorescent protein (CFP) in axons and neuromuscular synapses did not interfere with the protection from axotomy conferred by the Wld gene. Thus, Wld expression unmasks age-dependent, compartmentally organised programmes of synapse withdrawal and degeneration. PMID:12231635

Studies of Heavy-Ion Reactions and Transuranic Nuclei

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

Schroeder, W. Udo

2016-07-28

Studies of heavy-ion reactions and transuranic nuclei performed by the University of Rochester Nuclear Science Research Group have been successful in furthering experimental systematics and theoretical understanding of the behavior of nuclear systems excited to their limits of stability. The theoretical results explain specifically the “boiling” and “vaporization” of atomic nuclei, but are more generally applicable to isolated, quantal many-particle systems which, under thermal or mechanical stresses, all disintegrate by evaporation, via surface cluster emission, or via fission-like processes. Accompanying experimental investigations by the group have demonstrated several new types of dynamical instability of nuclei: In central, “head-on” collisions, targetmore » nuclei exhibit limited ability to stop energetic projectile nuclei and to dissipate the imparted linear momentum. Substantial matter overlap (“neck”) between projectile and target nuclei, which is observed at elevated collision energies, can be stretched considerably and break at several places simultaneously. These results provide new testing grounds for microscopic theory of the cohesion of nuclear matter. This property has remained elusive, even though the elementary nucleon-nucleon forces are well known since some time. Technical R&D has resulted in a detailed characterization of a novel plastic material, which can now be used in the design of sensitive diagnostic systems for various types of radio-activity. Innovative application of powerful laser systems has produced intense, controllable sources of exotic particle radioactivity for nuclear investigations. Several students have received their Ph.D. degree in experimental nuclear science for their work on basic nuclear research or R&D projects.« less

Differential sorting of the vesicular glutamate transporter 1 into a defined vesicular pool is regulated by light signaling involving the clock gene Period2.

PubMed

Yelamanchili, Sowmya V; Pendyala, Gurudutt; Brunk, Irene; Darna, Mahesh; Albrecht, Urs; Ahnert-Hilger, Gudrun

2006-06-09

Synaptic strength depends on the amount of neurotransmitter stored in synaptic vesicles. The vesicular transmitter content has recently been shown to be directly dependent on the expression levels of vesicular neurotransmitter transporters indicating that the transport capacity of synaptic vesicles is a critical determinant for synaptic efficacy. Using synaptic vesicles prepared from whole brain at different times of the day we now show that the amount of vesicular glutamate transporter (VGLUT) 1 undergoes strong diurnal cycling. VGLUT1 protein levels are high before the start of the light period, decline at noon, increase again before start of the dark period, and decline again at midnight. Mice kept in complete darkness showed within a 24-h period only a single peak of VGLUT1 expression in the middle of the rest phase. In contrast, mice lacking the period gene Period 2, a core component of the circadian clock, did not show any light-cycle-dependent changes of VGLUT1 levels. No other of several synaptic vesicle proteins examined underwent circadian cycling. Circadian cycling of VGLUT1 was not seen when analyzing homogenate or synaptosomes, the starting fraction for vesicle preparation. Circadian cycling of VGLUT1 was also not reflected at the mRNA level. We conclude that nerve terminals are endowed with mechanisms that regulate quantal size by changing the copy number of transporters in synaptic vesicles. A reduced amount of VGLUT1 per vesicle is probably achieved by means of selective sorting controlled by clock genes.

Shifting the Focus: Children's Image-Making Practices and Their Implications for Analysis

ERIC Educational Resources Information Center

Lomax, Helen Jayne

2012-01-01

This paper provides analytic focus on the productive and editorial contexts of children and young people's image-making, making visible its implications for the analysis of photographs. Drawing on participatory research in which children and young people worked alongside researchers to create a visual narrative of their lived experiences of…

Environmental Pollution Control Policy-Making: An Analysis of Elite Perceptions and Preferences

ERIC Educational Resources Information Center

Althoff, Phillip; Greig, William H.

1974-01-01

This article is based on an analysis of the perceptions and preferences of elite groups concerning environmental pollution control policy making. Results showed that although the groups agreed that present methods were inadequate, they were, nevertheless, unable to agree upon the nature of a future policy-making system. (MA)

End-of-Life Decision Making in Palliative Care and Recommendations of the Council of Europe: Qualitative Secondary Analysis of Interviews and Observation Field Notes.

PubMed

Martins Pereira, Sandra; Fradique, Emília; Hernández-Marrero, Pablo

2018-05-01

End-of-life decisions (ELDs) are embedded in clinical, sociocultural, political, economic, and ethical concerns. In 2014, the Council of Europe (CoE) through its Committee on Bioethics launched the "Guide on the decision-making process regarding medical treatment in end-of-life situations," aiming at improving decision-making processes and empowering professionals in making ELDs. To analyze if end-of-life decision making in palliative care (PC) is consistent with this Guide and to identify if disputed/controversial issues are part of current ELDs. Qualitative secondary analysis. Four qualitative datasets, including 44 interviews and 9 team observation field notes from previous studies with PC teams/professionals in Portugal. An analysis grid based on the abovementioned guide was created considering three dimensions: ethical and legal frameworks, decision-making process, and disputed/controversial issues. The majority of the professionals considered the ethical principle of autonomy paramount in end-of-life decision making. Justice and beneficence/nonmaleficence were also valued. Although not mentioned in the Guide, the professionals also considered other ethical principles when making ELDs, namely, responsibility, integrity, and dignity. Most of the interviewees and field notes referred to the collective interprofessional dimension of the decision-making process. Palliative sedation and the wish to hasten death were the most mentioned disputed/controversial issues. The nature, limitations, and benefits of qualitative secondary analysis are discussed. End-of-life decision-making processes made by Portuguese PC teams seem to be consistent with the guidelines of the CoE. Further research is needed about disputed/controversial issues and the actual use, effectiveness, and impact of ethical guidelines for end-of-life decision making on professionals' empowerment and for all parties involved.

Shaping Strategy: An Institutional Analysis of Decision Making in the Middle Tier

ERIC Educational Resources Information Center

Vasquez, Alejandro

2017-01-01

The intent of this single-case study was to explore the effects of a competitive environment on organizational decision making. The study examines the decision making processes that resulted in the adoption of an undergraduate business major at a traditional, middle-tier Liberal Arts College and offers an analysis of academic leaders' perspectives…

Using Propensity Score Analysis for Making Causal Claims in Research Articles

ERIC Educational Resources Information Center

Bai, Haiyan

2011-01-01

The central role of the propensity score analysis (PSA) in observational studies is for causal inference; as such, PSA is often used for making causal claims in research articles. However, there are still some issues for researchers to consider when making claims of causality using PSA results. This summary first briefly reviews PSA, followed by…

From Theory to Practice: A Quantitative Content Analysis of Adult Education's Language on Meaning Making

ERIC Educational Resources Information Center

Roessger, Kevin M.

2017-01-01

Translating theory to practice has been a historical concern of adult education. It remains unclear, though, if adult education's theoretical and epistemological focus on meaning making transcends the academy. A manifest content analysis was conducted to determine if the frequency of meaning making language differed between the field's U.S.…

Walking the Fine Line: Political Decision Making with or without Data.

ERIC Educational Resources Information Center

Merkel-Keller, Claudia

The stages of the policy process are examined and explained in terms of the decision making framework. The policy process is comprised of four stages; policy analysis, policy formation, policy decision, and political analysis. Political analysis is the performance of the market analysis needed for a decision. The political weight, rather than the…

Evaluation of EMERGE, a Medical Decision Making Aid for Analysis of Chest Pain

PubMed Central

Hudson, Donna L.; Cohen, Moses E.; Deedwania, Prakash C.; Watson, Patricia E.

1983-01-01

EMERGE, a rule-based medical decision making aid for analysis of chest pain in the emergency room, was evaluated using retrospective patient data. The analysis consisted of two phases. In the initial phase, patient cases were run in order to make minor modifications and adjustments in the criteria used for determination of admission. In the second phase, patient cases were analyzed to determine the effectiveness of the EMERGE system in arriving at the proper conclusion.

Make or Buy: An Analysis of the Impacts of 3D Printing Operations, 3D Laser Scanning Technology, and Collaborative Product Lifecycle Management on Ship Maintenance and Modernization Cost Savings

DTIC Science & Technology

2016-01-30

SPONSORED REPORT SERIES Make or Buy: An Analysis of the Impacts of 3D Printing Operations, 3D Laser Scanning Technology, and Collaborative...Report Series Make or Buy: An Analysis of the Impacts of 3D Printing Operations, 3D Laser Scanning Technology, and Collaborative Product Lifecycle...Application Areas for 3D Printing ........................................................ 36 Figure 15. Potential Applications of 3D

I feel like a scrambled egg in my head: an idiographic case study of meaning making and anger using interpretative phenomenological analysis.

PubMed

Eatough, Virginia; Smith, Jonathan A

2006-03-01

What does it feel like when one's meaning making is impoverished and threatens to break down? The aim of this study is to show how meaning making is achieved in the context of one's life and how this achievement is often a struggle for the individual. The study reports data from semi-structured interviews with a female participant, which was analysed using interpretative phenomenological analysis (IPA). This paper examines how cultural discourses and conventions are experienced and given meaning by the individual. First, the analysis demonstrates how dominant discourses are used to explain anger and aggression. These include hormones, alcohol, and the influence of past relationships on present action. Second, it examines how the participant's meaning making is often ambiguous and confused, and how she variously accepts and challenges available meanings. Finally, the analysis demonstrates how meaning making can break down and the consequences of this for the individual's sense of self.

Multiple Criteria Decision Analysis for Health Care Decision Making--An Introduction: Report 1 of the ISPOR MCDA Emerging Good Practices Task Force.

PubMed

Thokala, Praveen; Devlin, Nancy; Marsh, Kevin; Baltussen, Rob; Boysen, Meindert; Kalo, Zoltan; Longrenn, Thomas; Mussen, Filip; Peacock, Stuart; Watkins, John; Ijzerman, Maarten

2016-01-01

Health care decisions are complex and involve confronting trade-offs between multiple, often conflicting, objectives. Using structured, explicit approaches to decisions involving multiple criteria can improve the quality of decision making and a set of techniques, known under the collective heading multiple criteria decision analysis (MCDA), are useful for this purpose. MCDA methods are widely used in other sectors, and recently there has been an increase in health care applications. In 2014, ISPOR established an MCDA Emerging Good Practices Task Force. It was charged with establishing a common definition for MCDA in health care decision making and developing good practice guidelines for conducting MCDA to aid health care decision making. This initial ISPOR MCDA task force report provides an introduction to MCDA - it defines MCDA; provides examples of its use in different kinds of decision making in health care (including benefit risk analysis, health technology assessment, resource allocation, portfolio decision analysis, shared patient clinician decision making and prioritizing patients' access to services); provides an overview of the principal methods of MCDA; and describes the key steps involved. Upon reviewing this report, readers should have a solid overview of MCDA methods and their potential for supporting health care decision making. Copyright © 2016. Published by Elsevier Inc.

40 CFR 51.854 - Conformity analysis.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Federal Government taking an action subject to this subpart must make its own conformity determination... agency or develop its own analysis in order to make its conformity determination. Effective Date Note: At...

Analysis of the decision-making process of nurse managers: a collective reflection.

PubMed

Eduardo, Elizabete Araujo; Peres, Aida Maris; de Almeida, Maria de Lourdes; Roglio, Karina de Dea; Bernardino, Elizabeth

2015-01-01

to analyze the decision-making model adopted by nurses from the perspective of some decision-making process theories. qualitative approach, based on action research. Semi-structured questionnaires and seminars were conducted from April to June 2012 in order to understand the nature of decisions and the decision-making process of nine nurses in position of managers at a public hospital in Southern Brazil. Data were subjected to content analysis. data were classified in two categories: the current situation of decision-making, which showed a lack of systematization; the construction and collective decision-making, which emphasizes the need to develop a decision-making model. the decision-making model used by nurses is limited because it does not consider two important factors: the limits of human rationality, and the external and internal organizational environments that influence and determine right decisions.

Training in Decision-making Strategies: An approach to enhance students' competence to deal with socio-scientific issues

NASA Astrophysics Data System (ADS)

Gresch, Helge; Hasselhorn, Marcus; Bögeholz, Susanne

2013-10-01

Dealing with socio-scientific issues in science classes enables students to participate productively in controversial discussions concerning ethical topics, such as sustainable development. In this respect, well-structured decision-making processes are essential for elaborate reasoning. To foster decision-making competence, a computer-based programme was developed that trains secondary school students (grades 11-13) in decision-making strategies. The main research question is: does training students to use these strategies foster decision-making competence? In addition, the influence of meta-decision aids was examined. Students conducted a task analysis to select an appropriate strategy prior to the decision-making process. Hence, the second research question is: does combining decision-making training with a task analysis enhance decision-making competence at a higher rate? To answer these questions, 386 students were tested in a pre-post-follow-up control-group design that included two training groups (decision-making strategies/decision-making strategies combined with a task analysis) and a control group (decision-making with additional ecological information instead of strategic training). An open-ended questionnaire was used to assess decision-making competence in situations related to sustainable development. The decision-making training led to a significant improvement in the post-test and the follow-up, which was administered three months after the training. Long-term effects on the quality of the students' decisions were evident for both training groups. Gains in competence when reflecting upon the decision-making processes of others were found, to a lesser extent, in the training group that received the additional meta-decision training. In conclusion, training in decision-making strategies is a promising approach to deal with socio-scientific issues related to sustainable development.

Work with Us | Energy Analysis | NREL

Science.gov Websites

, and local levels; and industry use NREL analysis, data, models, and tools to make critical energy and academia make us well-positioned to help solve the most important energy challenges: Yours

Changes in Properties of Auditory Nerve Synapses following Conductive Hearing Loss.

PubMed

Zhuang, Xiaowen; Sun, Wei; Xu-Friedman, Matthew A

2017-01-11

Auditory activity plays an important role in the development of the auditory system. Decreased activity can result from conductive hearing loss (CHL) associated with otitis media, which may lead to long-term perceptual deficits. The effects of CHL have been mainly studied at later stages of the auditory pathway, but early stages remain less examined. However, changes in early stages could be important because they would affect how information about sounds is conveyed to higher-order areas for further processing and localization. We examined the effects of CHL at auditory nerve synapses onto bushy cells in the mouse anteroventral cochlear nucleus following occlusion of the ear canal. These synapses, called endbulbs of Held, normally show strong depression in voltage-clamp recordings in brain slices. After 1 week of CHL, endbulbs showed even greater depression, reflecting higher release probability. We observed no differences in quantal size between control and occluded mice. We confirmed these observations using mean-variance analysis and the integration method, which also revealed that the number of release sites decreased after occlusion. Consistent with this, synaptic puncta immunopositive for VGLUT1 decreased in area after occlusion. The level of depression and number of release sites both showed recovery after returning to normal conditions. Finally, bushy cells fired fewer action potentials in response to evoked synaptic activity after occlusion, likely because of increased depression and decreased input resistance. These effects appear to reflect a homeostatic, adaptive response of auditory nerve synapses to reduced activity. These effects may have important implications for perceptual changes following CHL. Normal hearing is important to everyday life, but abnormal auditory experience during development can lead to processing disorders. For example, otitis media reduces sound to the ear, which can cause long-lasting deficits in language skills and verbal production, but the location of the problem is unknown. Here, we show that occluding the ear causes synapses at the very first stage of the auditory pathway to modify their properties, by decreasing in size and increasing the likelihood of releasing neurotransmitter. This causes synapses to deplete faster, which reduces fidelity at central targets of the auditory nerve, which could affect perception. Temporary hearing loss could cause similar changes at later stages of the auditory pathway, which could contribute to disorders in behavior. Copyright © 2017 the authors 0270-6474/17/370323-10$15.00/0.

The use of a cognitive task analysis-based multimedia program to teach surgical decision making in flexor tendon repair.

PubMed

Luker, Kali R; Sullivan, Maura E; Peyre, Sarah E; Sherman, Randy; Grunwald, Tiffany

2008-01-01

The aim of this study was to compare the surgical knowledge of residents before and after receiving a cognitive task analysis-based multimedia teaching module. Ten plastic surgery residents were evaluated performing flexor tendon repair on 3 occasions. Traditional learning occurred between the first and second trial and served as the control. A teaching module was introduced as an intervention between the second and third trial using cognitive task analysis to illustrate decision-making skills. All residents showed improvement in their decision-making ability when performing flexor tendon repair after each surgical procedure. The group improved through traditional methods as well as exposure to our talk-aloud protocol (P > .01). After being trained using the cognitive task analysis curriculum the group displayed a statistically significant knowledge expansion (P < .01). Residents receiving cognitive task analysis-based multimedia surgical curriculum instruction achieved greater command of problem solving and are better equipped to make correct decisions in flexor tendon repair.

The Risky Shift in Policy Decision Making: A Comparative Analysis

ERIC Educational Resources Information Center

Wilpert, B.; And Others

1976-01-01

Based on analysis of data on 432 decision-makers from around the world, this study examines the decision-making phenomenon that individuals tend to move toward riskier decisions after group discussion. Findings of the analysis contradicted earlier studies, showing a consistent shift toward greater risk avoidance. Available from Elsevier Scientific…

Literature Review of the Classifications of "Needs" in Needs Analysis Theory

ERIC Educational Resources Information Center

Juan, L. I.

2014-01-01

Needs analysis makes it possible that the language course can cater to the needs of learners from different countries, different language levels and different targets. A well-established needs analysis may provide references for the policy making, curriculum design of foreign language teaching. This paper reviews the point of view of some…

40 CFR 279.55 - Analysis plan.

Code of Federal Regulations, 2013 CFR

2013-07-01

... information will be used to make this determination; (2) If sample analyses are used to make this... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Analysis plan. 279.55 Section 279.55... THE MANAGEMENT OF USED OIL Standards for Used Oil Processors and Re-Refiners § 279.55 Analysis plan...

40 CFR 279.55 - Analysis plan.

Code of Federal Regulations, 2012 CFR

2012-07-01

... information will be used to make this determination; (2) If sample analyses are used to make this... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Analysis plan. 279.55 Section 279.55... THE MANAGEMENT OF USED OIL Standards for Used Oil Processors and Re-Refiners § 279.55 Analysis plan...

40 CFR 279.55 - Analysis plan.

Code of Federal Regulations, 2014 CFR

2014-07-01

... information will be used to make this determination; (2) If sample analyses are used to make this... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Analysis plan. 279.55 Section 279.55... THE MANAGEMENT OF USED OIL Standards for Used Oil Processors and Re-Refiners § 279.55 Analysis plan...

Signal Detection Analysis of Computer Enhanced Group Decision Making Strategies

DTIC Science & Technology

2007-11-01

group decision making. 20 References American Psychological Association (2002). Ethical principles of psychologists and code of conduct. American... Creelman , C. D. (2005). Detection theory: A user’s guide (2nd ed.). Mahwah, NJ: Lawrence Erlbaum. Sorkin, R. D. (1998). Group performance depends on...the majority rule. Psychological Science, 9, 456-463. Sorkin, R. D. (2001). Signal-detection analysis of group decision making. Psychological

A Case Study of Human Resource Development Professionals' Decision Making in Vendor Selection for Employee Development: A Degrees-of-Freedom Analysis

ERIC Educational Resources Information Center

Cathcart, Stephen Michael

2016-01-01

This mixed method study examines HRD professionals' decision-making processes when making an organizational purchase of training. The study uses a case approach with a degrees of freedom analysis. The data to analyze will examine how HRD professionals in manufacturing select outside vendors human resource development programs for training,…

Decision Making Methods in Space Economics and Systems Engineering

NASA Technical Reports Server (NTRS)

Shishko, Robert

2006-01-01

This viewgraph presentation reviews various methods of decision making and the impact that they have on space economics and systems engineering. Some of the methods discussed are: Present Value and Internal Rate of Return (IRR); Cost-Benefit Analysis; Real Options; Cost-Effectiveness Analysis; Cost-Utility Analysis; Multi-Attribute Utility Theory (MAUT); and Analytic Hierarchy Process (AHP).

Patient and provider perceptions of decision making about use of epidural analgesia during childbirth: a thematic analysis.

PubMed

Goldberg, Holly Bianca; Shorten, Allison

2014-01-01

This study examines the nature of differences in perceptions of decision making between patients and providers about use of epidural analgesia during labor. Thematic analysis was used to identify patterns in written survey responses from 14 patients, 13 labor nurses, and 7 obstetrician-gynecologists. Results revealed patients attempted to place themselves in an informed role in decision making and sought respect for their decisions. Some providers demonstrated paternalism and a tendency to steer patients in the direction of their own preferences. Nurses observed various pressures on decision making, reinforcing the importance of patients being supported to make an informed choice. Differences in perceptions suggest need for improvement in communication and shared decision-making practices related to epidural analgesia use in labor.

Decision-making impairments in Parkinson's disease as a by-product of defective cost-benefit analysis and feedback processing.

PubMed

Ryterska, Agata; Jahanshahi, Marjan; Osman, Magda

2014-01-01

Studies examining decision-making in people with Parkinson's disease (PD) show impaired performance on a variety of tasks. However, there are also demonstrations that patients with PD can make optimal decisions just like healthy age-matched controls. We propose that the reason for these mixed findings is that PD does not produce a generalized impairment of decision-making, but rather affects sub-components of this process. In this review we evaluate this hypothesis by considering the empirical evidence examining decision-making in PD. We suggest that of the various stages of the decision-making process, the most affected in PD are (1) the cost-benefit analysis stage and (2) the outcome evaluation stage. We consider the implications of this proposal for research in this area.

An Evaluation on Factors Influencing Decision making for Malaysia Disaster Management: The Confirmatory Factor Analysis Approach

NASA Astrophysics Data System (ADS)

Zubir, S. N. A.; Thiruchelvam, S.; Mustapha, K. N. M.; Che Muda, Z.; Ghazali, A.; Hakimie, H.

2017-12-01

For the past few years, natural disaster has been the subject of debate in disaster management especially in flood disaster. Each year, natural disaster results in significant loss of life, destruction of homes and public infrastructure, and economic hardship. Hence, an effective and efficient flood disaster management would assure non-futile efforts for life saving. The aim of this article is to examine the relationship between approach, decision maker, influence factor, result, and ethic to decision making for flood disaster management in Malaysia. The key elements of decision making in the disaster management were studied based on the literature. Questionnaire surveys were administered among lead agencies at East Coast of Malaysia in the state of Kelantan and Pahang. A total of 307 valid responses had been obtained for further analysis. Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA) were carried out to analyse the measurement model involved in the study. The CFA for second-order reflective and first-order reflective measurement model indicates that approach, decision maker, influence factor, result, and ethic have a significant and direct effect on decision making during disaster. The results from this study showed that decision- making during disaster is an important element for disaster management to necessitate a successful collaborative decision making. The measurement model is accepted to proceed with further analysis known as Structural Equation Modeling (SEM) and can be assessed for the future research.

Quantal mEPSCs and residual glutamate: how horizontal cell responses are shaped at the photoreceptor ribbon synapse

PubMed Central

Cadetti, Lucia; Bartoletti, Theodore M.; Thoreson, Wallace B.

2012-01-01

At the photoreceptor ribbon synapse, glutamate released from vesicles at different positions along the ribbon reaches the same postsynaptic receptors. Thus, vesicles may not exert entirely independent effects. We examined whether responses of salamander retinal horizontal cells evoked by light or direct depolarization during paired recordings could be predicted by summation of individual miniature excitatory postsynaptic currents (mEPSCs). For EPSCs evoked by depolarization of rods or cones, linear convolution of mEPSCs with photoreceptor release functions predicted EPSC waveforms and changes caused by inhibiting glutamate receptor desensitization. A low-affinity glutamate antagonist, kynurenic acid (KynA), preferentially reduced later components of rod-driven EPSCs, suggesting lower levels of glutamate are present during the later sustained component of the EPSC. A glutamate-scavenging enzyme, glutamic-pyruvic transaminase, did not inhibit mEPSCs or the initial component of rod-driven EPSCs, but reduced later components of the EPSC. Inhibiting glutamate uptake with a low concentration of dl-threo-β-benzoyloxyaspartate (TBOA) also did not alter mEPSCs or the initial component of rod-driven EPSCs, but enhanced later components of the EPSC. Low concentrations of TBOA and KynA did not affect the kinetics of fast cone-driven EPSCs. Under both rod- and cone-dominated conditions, light-evoked currents (LECs) were enhanced considerably by TBOA. LECs were more strongly inhibited than EPSCs by KynA, suggesting the presence of lower glutamate levels. Collectively, these results indicate that the initial EPSC component can be largely predicted from a linear sum of individual mEPSCs, but with sustained release, residual amounts of glutamate from multiple vesicles pool together, influencing LECs and later components of EPSCs. PMID:18547244

Stochastic Simulation of Dopamine Neuromodulation for Implementation of Fluorescent Neurochemical Probes in the Striatal Extracellular Space.

PubMed

Beyene, Abraham G; McFarlane, Ian R; Pinals, Rebecca L; Landry, Markita P

2017-10-18

Imaging the dynamic behavior of neuromodulatory neurotransmitters in the extracelluar space that arise from individual quantal release events would constitute a major advance in neurochemical imaging. Spatial and temporal resolution of these highly stochastic neuromodulatory events requires concurrent advances in the chemical development of optical nanosensors selective for neuromodulators in concert with advances in imaging methodologies to capture millisecond neurotransmitter release. Herein, we develop and implement a stochastic model to describe dopamine dynamics in the extracellular space (ECS) of the brain dorsal striatum to guide the design and implementation of fluorescent neurochemical probes that record neurotransmitter dynamics in the ECS. Our model is developed from first-principles and simulates release, diffusion, and reuptake of dopamine in a 3D simulation volume of striatal tissue. We find that in vivo imaging of neuromodulation requires simultaneous optimization of dopamine nanosensor reversibility and sensitivity: dopamine imaging in the striatum or nucleus accumbens requires nanosensors with an optimal dopamine dissociation constant (K d ) of 1 μM, whereas K d s above 10 μM are required for dopamine imaging in the prefrontal cortex. Furthermore, as a result of the probabilistic nature of dopamine terminal activity in the striatum, our model reveals that imaging frame rates of 20 Hz are optimal for recording temporally resolved dopamine release events. Our work provides a modeling platform to probe how complex neuromodulatory processes can be studied with fluorescent nanosensors and enables direct evaluation of nanosensor chemistry and imaging hardware parameters. Our stochastic model is generic for evaluating fluorescent neurotransmission probes, and is broadly applicable to the design of other neurotransmitter fluorophores and their optimization for implementation in vivo.

Intestinal and peritoneal mast cells differ in kinetics of quantal release

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

Balseiro-Gomez, Santiago, E-mail: sanbalgom@alum.us.es; Ramirez-Ponce, M. Pilar, E-mail: pponce@us.es; Acosta, Jorge, E-mail: jorgealo@us.es

2016-01-15

5-hydroxytriptamine (5-HT, serotonin) storage and release in mast cell (MC) secretory granules (SG) are dependent on serglycin proteoglycans (PG). This notion is based on the studies of MC of the connective tissue subtype that predominantly contain PG of the heparin type, whereas intestinal mucosal MC, which contain predominantly chondroitin sulfate, have been poorly explored. In the present study, we addressed the possibility that PG contents may differently affect the storage and release of preformed mediators in these two MC subclasses and explain in part their different functional properties. Rat peritoneal (PMC) and intestinal mast cells (IMC) were isolated and purifiedmore » using a percoll gradient, and the efflux of 5-HT from each SG was measured by amperometric detection. IMC exhibited a ∼34% reduction in the release of 5-HT compared with PMC because of a lower number of exocytotic events, rather than a lower secretion per single exocytotic event. Amperometric spikes from IMC exhibited a slower decay phase and increased half-width but a similar ascending phase and foot parameters, indicating that the fusion pore kinetics are comparable in both MC subclasses. We conclude that both PG subtypes are equally efficient systems, directly involved in serotonin accumulation, and play a crucial role in regulating the kinetics of exocytosis from SG, providing specific secretory properties for the two cellular subtypes. - Highlights: • We improved a method for isolating and purifying IMC. • There was a reduction in total serotonin release in IMC with respect to PMC. • This decrease was not due to less secretion per quantum but a lower number of exocytotic events. • There was also a deceleration of exocytosis in IMC with respect to PMC.« less

Radiation Pneumopathy in the Rat After Intravenous Application of {sup 188}Re-Labeled Microspheres

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

Liepe, Knut; Faulhaber, Diana; Wunderlich, Gerd

2011-10-01

Purpose: To determine the dose dependence and kinetics of pneumopathy after systemic administration of rhenium-188 ({sup 188}Re)-labeled microspheres in a rat model. Methods and Materials: {sup 188}Re-microspheres were injected intravenously into adult Wistar rats (n = 54, age, 8 {+-} 2 months). The rats were divided into 6 groups according to the intended absorbed dose in the lung (maximum 60 Gy). Gamma camera scans were used to estimate the individual whole lung doses. One control group (n = 5) received nonlabeled microspheres. The breathing rate was measured before and weekly after the treatment using whole body plethysmography until 24 weeks.more » An increase in the breathing rate by 20% compared with the individual pretreatment control value was defined as the quantal endpoint for dose-effect analyses. Results: A biphasic increase in the breathing rate was observed. The first impairment of lung function occurred in Weeks 3-6. For late changes, the interval to onset was clearly dose dependent and was 17 weeks (10-30 Gy) and 10 weeks (50-60 Gy), respectively. The incidence of the response was highly dependent on the estimated lung dose. The median effective dose for an early and late response was virtually identical (19.9 {+-} 0.6 Gy and 20.4 {+-} 3.1 Gy, respectively). A significant correlation was found between the occurrence of an early and a late effect in the same rat, suggesting a strong consequential component. Conclusions: The effects of radiolabeled microspheres can be studied longitudinally in a rat model, using changes in the breathing rate as the functional, clinically relevant response. The isoeffective doses from the present study using radionuclide administration and those from published investigations of homogeneous external beam radiotherapy are almost similar.« less

PSD-95 and PSD-93 Play Critical but Distinct Roles in Synaptic Scaling Up and Down

PubMed Central

Sun, Qian; Turrigiano, Gina G.

2011-01-01

Synaptic scaling stabilizes neuronal firing through the homeostatic regulation of postsynaptic strength, but the mechanisms by which chronic changes in activity lead to bidirectional adjustments in synaptic AMPAR abundance are incompletely understood. Further, it remains unclear to what extent scaling up and scaling down utilize distinct molecular machinery. PSD-95 is a scaffold protein proposed to serve as a binding “slot” that determines synaptic AMPAR content, and synaptic PSD-95 abundance is regulated by activity, raising the possibility that activity-dependent changes in the synaptic abundance of PSD-95 or other MAGUKs drives the bidirectional changes in AMPAR accumulation during synaptic scaling. We found that synaptic PSD-95 and SAP102 (but not PSD-93) abundance were bidirectionally regulated by activity, but these changes were not sufficient to drive homeostatic changes in synaptic strength. Although not sufficient, the PSD-95-MAGUKs were necessary for synaptic scaling, but scaling up and down were differentially dependent on PSD-95 and PSD-93. Scaling down was completely blocked by reduced or enhanced PSD-95, through a mechanism that depended on the PDZ1/2 domains. In contrast scaling up could be supported by either PSD-95 or PSD-93 in a manner that depended on neuronal age, and was unaffected by a superabundance of PSD-95. Taken together, our data suggest that scaling up and down of quantal amplitude is not driven by changes in synaptic abundance of PSD-95-MAGUKs, but rather that the PSD-95 MAGUKs serve as critical synaptic organizers that utilize distinct protein-protein interactions to mediate homeostatic accumulation and loss of synaptic AMPAR. PMID:21543610

Calcium Signalling through Ligand-Gated Ion Channels such as P2X1 Receptors in the Platelet and other Non-Excitable Cells.

PubMed

Mahaut-Smith, Martyn P; Taylor, Kirk A; Evans, Richard J

2016-01-01

Ligand-gated ion channels on the cell surface are directly activated by the binding of an agonist to their extracellular domain and often referred to as ionotropic receptors. P2X receptors are ligand-gated non-selective cation channels with significant permeability to Ca(2+) whose principal physiological agonist is ATP. This chapter focuses on the mechanisms by which P2X1 receptors, a ubiquitously expressed member of the family of ATP-gated channels, can contribute to cellular responses in non-excitable cells. Much of the detailed information on the contribution of P2X1 to Ca(2+) signalling and downstream functional events has been derived from the platelet. The underlying primary P2X1-generated signalling event in non-excitable cells is principally due to Ca(2+) influx, although Na(+) entry will also occur along with membrane depolarization. P2X1 receptor stimulation can lead to additional Ca(2+) mobilization via a range of routes such as amplification of G-protein-coupled receptor-dependent Ca(2+) responses. This chapter also considers the mechanism by which cells generate extracellular ATP for autocrine or paracrine activation of P2X1 receptors. For example cytosolic ATP efflux can result from opening of pannexin anion-permeable channels or following damage to the cell membrane. Alternatively, ATP stored in specialised secretory vesicles can undergo quantal release via the process of exocytosis. Examples of physiological or pathophysiological roles of P2X1-dependent signalling in non-excitable cells are also discussed, such as thrombosis and immune responses.

Quantal concept of T-cell activation: adhesion domains as immunological synapses

NASA Astrophysics Data System (ADS)

Sackmann, Erich

2011-06-01

Adhesion micro-domains (ADs) formed during encounters of lymphocytes with antigen-presenting cells (APC) mediate the genetic expression of quanta of cytokines interleukin-2 (IL-2). The IL-2-induced activation of IL-2 receptors promotes the stepwise progression of the T-cells through the cell cycle, hence their name, immunological synapses. The ADs form short-lived reaction centres controlling the recruitment of activators of the biochemical pathway (the kinases Lck and ZAP) while preventing the access of inhibitors (phosphatase CD45) through steric repulsion forces. CD45 acts as the generator of adhesion domains and, through its role as a spacer protein, also as the promoter of the reaction. In a second phase of T-cell-APC encounters, long-lived global reaction spaces (called supramolecular activation complexes (SMAC)) form by talin-mediated binding of the T-cell integrin (LFA-1) to the counter-receptor ICAM-1, resulting in the formation of ring-like tight adhesion zones (peripheral SMAC). The ADs move to the centre of the intercellular adhesion zone forming the central SMAC, which serve in the recycling of the AD. We propose that cell stimulation is triggered by integrating the effect evoked by the short-lived adhesion domains. Similar global reaction platforms are formed by killer cells to destruct APC. We present a testable mechanical model showing that global reaction spaces (SMAC or dome-like contacts between cytotoxic cells and APC) form by self-organization through delayed activation of the integrin-binding affinity and stabilization of the adhesion zones by F-actin recruitment. The mechanical stability and the polarization of the adhering T-cells are mediated by microtubule-actin cross-talk.

An electrophysiological study on the effects of Pa-1G (a phospholipase A(2)) from the venom of king brown snake, Pseudechis australis, on neuromuscular function.

PubMed

Fatehi, M; Rowan, E G; Harvey, A L

2002-01-01

The effects of Pa-1G, a phospholipase A(2) (PLA(2)) from the venom of the Australian king brown snake (Pseudechis australis) were determined on the release of acetylcholine, muscle resting membrane potential and motor nerve terminal action potential at mouse neuromuscular junction. Intracellular recording from endplate regions of mouse triangularis sterni nerve-muscle preparations revealed that Pa-1G (800 nM) significantly reduced the amplitude of endplate potentials within 10 min exposure. The quantal content of endplate potentials was decreased to 58+/-6% of control after 30 min exposure to 800 nM Pa-1G. The toxin also caused a partial depolarisation of mouse muscle fibres within 60 min exposure. Extracellular recording of action potentials at motor nerve terminals showed that Pa-1G reduced the waveforms associated with both sodium and potassium conductances. To investigate whether this was a direct or indirect effect of the toxin on these ionic currents, whole cell patch clamp experiments were performed using human neuroblastoma (SK-N-SH) cells and B82 mouse fibroblasts stably transfected with rKv1.2. Patch clamp recording experiments confirmed that potassium currents sensitive to alpha-dendrotoxin recorded from B82 cells and sodium currents in SK-N-SH cells were not affected by the toxin. Since neither facilitation of acetylcholine release at mouse neuromuscular junction nor depression of potassium currents in B82 cells has been observed, the apparent blockade of potassium currents at mouse motor nerve endings induced by the toxin is unlikely to be due to a selective block of potassium channels.

Determination of wave-function functionals: The constrained-search variational method

NASA Astrophysics Data System (ADS)

Pan, Xiao-Yin; Sahni, Viraht; Massa, Lou

2005-09-01

In a recent paper [Phys. Rev. Lett. 93, 130401 (2004)], we proposed the idea of expanding the space of variations in variational calculations of the energy by considering the approximate wave function ψ to be a functional of functions χ , ψ=ψ[χ] , rather than a function. A constrained search is first performed over all functions χ such that the wave-function functional ψ[χ] satisfies a physical constraint or leads to the known value of an observable. A rigorous upper bound to the energy is then obtained via the variational principle. In this paper we generalize the constrained-search variational method, applicable to both ground and excited states, to the determination of arbitrary Hermitian single-particle operators as applied to two-electron atomic and ionic systems. We construct analytical three-parameter ground-state functionals for the H- ion and the He atom through the constraint of normalization. We present the results for the total energy E , the expectations of the single-particle operators W=∑irin , n=-2,-1,1,2 , W=∑iδ(ri) , and W=∑iδ(ri-r) , the structure of the nonlocal Coulomb hole charge ρc(rr') , and the expectations of the two particle operators u2,u,1/u,1/u2 , where u=∣ri-rj∣ . The results for all the expectation values are remarkably accurate when compared with the 1078-parameter wave function of Pekeris, and other wave functions that are not functionals. We conclude by describing our current work on how the constrained-search variational method in conjunction with quantal density-functional theory is being applied to the many-electron case.

Nucleus reticularis neurons mediate diverse inhibitory effects in thalamus.

PubMed

Cox, C L; Huguenard, J R; Prince, D A

1997-08-05

Detailed information regarding the contribution of individual gamma-aminobutyric acid (GABA)-containing inhibitory neurons to the overall synaptic activity of single postsynaptic cells is essential to our understanding of fundamental elements of synaptic integration and operation of neuronal circuits. For example, GABA-containing cells in the thalamic reticular nucleus (nRt) provide major inhibitory innervation of thalamic relay nuclei that is critical to thalamocortical rhythm generation. To investigate the contribution of individual nRt neurons to the strength of this internuclear inhibition, we obtained whole-cell recordings of unitary inhibitory postsynaptic currents (IPSCs) evoked in ventrobasal thalamocortical (VB) neurons by stimulation of single nRt cells in rat thalamic slices, in conjunction with intracellular biocytin labeling. Two types of monosynaptic IPSCs could be distinguished. "Weak" inhibitory connections were characterized by a significant number of postsynaptic failures in response to presynaptic nRt action potentials and relatively small IPSCs. In contrast, "strong" inhibition was characterized by the absence of postsynaptic failures and significantly larger unitary IPSCs. By using miniature IPSC amplitudes to infer quantal size, we estimated that unitary IPSCs associated with weak inhibition resulted from activation of 1-3 release sites, whereas stronger inhibition would require simultaneous activation of 5-70 release sites. The inhibitory strengths were positively correlated with the density of axonal swellings of the presynaptic nRt neurons, an indicator that characterizes different nRt axonal arborization patterns. These results demonstrate that there is a heterogeneity of inhibitory interactions between nRt and VB neurons, and that variations in gross morphological features of axonal arbors in the central nervous system can be associated with significant differences in postsynaptic response characteristics.

Cholesterol-Independent Effects of Methyl-β-Cyclodextrin on Chemical Synapses

PubMed Central

Ormerod, Kiel G.; Coorssen, Jens R.; Mercier, A. Joffre

2012-01-01

The cholesterol chelating agent, methyl-β-cyclodextrin (MβCD), alters synaptic function in many systems. At crayfish neuromuscular junctions, MβCD is reported to reduce excitatory junctional potentials (EJPs) by impairing impulse propagation to synaptic terminals, and to have no postsynaptic effects. We examined the degree to which physiological effects of MβCD correlate with its ability to reduce cholesterol, and used thermal acclimatization as an alternative method to modify cholesterol levels. MβCD impaired impulse propagation and decreased EJP amplitude by 40% (P<0.05) in preparations from crayfish acclimatized to 14°C but not from those acclimatized to 21°C. The reduction in EJP amplitude in the cold-acclimatized group was associated with a 49% reduction in quantal content (P<0.05). MβCD had no effect on input resistance in muscle fibers but decreased sensitivity to the neurotransmitter L-glutamate in both warm- and cold-acclimatized groups. This effect was less pronounced and reversible in the warm-acclimatized group (90% reduction in cold, P<0.05; 50% reduction in warm, P<0.05). MβCD reduced cholesterol in isolated nerve and muscle from cold- and warm-acclimatized groups by comparable amounts (nerve: 29% cold, 25% warm; muscle: 20% cold, 18% warm; P<0.05). This effect was reversed by cholesterol loading, but only in the warm-acclimatized group. Thus, effects of MβCD on glutamate-sensitivity correlated with its ability to reduce cholesterol, but effects on impulse propagation and resulting EJP amplitude did not. Our results indicate that MβCD can affect both presynaptic and postsynaptic properties, and that some effects of MβCD are unrelated to cholesterol chelation. PMID:22590538

Exocytosis of ATP From Astrocytes Modulates Phasic and Tonic Inhibition in the Neocortex

PubMed Central

Rasooli-Nejad, Seyed; Andrew, Jemma; Haydon, Philip G.; Pankratov, Yuriy

2014-01-01

Communication between neuronal and glial cells is important for many brain functions. Astrocytes can modulate synaptic strength via Ca2+-stimulated release of various gliotransmitters, including glutamate and ATP. A physiological role of ATP release from astrocytes was suggested by its contribution to glial Ca2+-waves and purinergic modulation of neuronal activity and sleep homeostasis. The mechanisms underlying release of gliotransmitters remain uncertain, and exocytosis is the most intriguing and debated pathway. We investigated release of ATP from acutely dissociated cortical astrocytes using “sniff-cell” approach and demonstrated that release is vesicular in nature and can be triggered by elevation of intracellular Ca2+ via metabotropic and ionotropic receptors or direct UV-uncaging. The exocytosis of ATP from neocortical astrocytes occurred in the millisecond time scale contrasting with much slower nonvesicular release of gliotransmitters via Best1 and TREK-1 channels, reported recently in hippocampus. Furthermore, we discovered that elevation of cytosolic Ca2+ in cortical astrocytes triggered the release of ATP that directly activated quantal purinergic currents in the pyramidal neurons. The glia-driven burst of purinergic currents in neurons was followed by significant attenuation of both synaptic and tonic inhibition. The Ca2+-entry through the neuronal P2X purinoreceptors led to phosphorylation-dependent down-regulation of GABAA receptors. The negative purinergic modulation of postsynaptic GABA receptors was accompanied by small presynaptic enhancement of GABA release. Glia-driven purinergic modulation of inhibitory transmission was not observed in neurons when astrocytes expressed dn-SNARE to impair exocytosis. The astrocyte-driven purinergic currents and glia-driven modulation of GABA receptors were significantly reduced in the P2X4 KO mice. Our data provide a key evidence to support the physiological importance of exocytosis of ATP from astrocytes in the neocortex. PMID:24409095

Prevalence of Influenza A(H1N1)pdm09 Virus Resistant to Oseltamivir in Shiraz, Iran, During 2012 - 2013.

PubMed

Khodadad, Nastaran; Moattari, Afagh; Shamsi Shahr Abadi, Mahmoud; Kadivar, Mohammad Rahim; Sarvari, Jamal; Tavakoli, Forough; Pirbonyeh, Neda; Emami, Amir

2015-08-01

Oseltamivir has been used as a drug of choice for the prophylaxis and treatment of human influenza A(H1N1)pdm09 infection across the world. However, the most frequently identified oseltamivir resistant virus, influenza A(H1N1)pdm09, exhibit the H275Y substitution in NA gene. This study aimed to determine the prevalence and phylogenetic relationships of oseltamivir resistance in influenza A(H1N1)pdm09 viruses isolated in Shiraz, Iran. Throat swab samples were collected from 200 patients with influenza-like disease from December 2012 until February 2013. A total of 77 influenza A(H1N1)pdm09 positive strains were identified by real-time polymerase chain reaction (PCR). Oseltamivir resistance was detected using quantal assay and nested-PCR method. The NA gene sequencing was conducted to detect oseltamivir-resistant mutants and establish the phylogeny of the prevalent influenza variants. Our results revealed that A(H1N1)pdm09 viruses present in these samples were susceptible to oseltamivir, and contained 5 site specific mutations (V13G, V106I, V241I, N248D, and N369K) in NA gene. These mutations correlated with increasing expression and enzymatic activity of NA protein in the influenza A(H1N1)pdm09 viruses, which were closely related to a main influenza A(H1N1)pdm09 cluster isolated around the world. A(H1N1)pdm09 viruses, identified in this study in Shiraz, Iran, contained 5 site specific mutations and were susceptible to oseltamivir.

Factorizing the motion sensitivity function into equivalent input noise and calculation efficiency.

PubMed

Allard, Rémy; Arleo, Angelo

2017-01-01

The photopic motion sensitivity function of the energy-based motion system is band-pass peaking around 8 Hz. Using an external noise paradigm to factorize the sensitivity into equivalent input noise and calculation efficiency, the present study investigated if the variation in photopic motion sensitivity as a function of the temporal frequency is due to a variation of equivalent input noise (e.g., early temporal filtering) or calculation efficiency (ability to select and integrate motion). For various temporal frequencies, contrast thresholds for a direction discrimination task were measured in presence and absence of noise. Up to 15 Hz, the sensitivity variation was mainly due to a variation of equivalent input noise and little variation in calculation efficiency was observed. The sensitivity fall-off at very high temporal frequencies (from 15 to 30 Hz) was due to a combination of a drop of calculation efficiency and a rise of equivalent input noise. A control experiment in which an artificial temporal integration was applied to the stimulus showed that an early temporal filter (generally assumed to affect equivalent input noise, not calculation efficiency) could impair both the calculation efficiency and equivalent input noise at very high temporal frequencies. We conclude that at the photopic luminance intensity tested, the variation of motion sensitivity as a function of the temporal frequency was mainly due to early temporal filtering, not to the ability to select and integrate motion. More specifically, we conclude that photopic motion sensitivity at high temporal frequencies is limited by internal noise occurring after the transduction process (i.e., neural noise), not by quantal noise resulting from the probabilistic absorption of photons by the photoreceptors as previously suggested.

Mechanisms of efferent-mediated responses in the turtle posterior crista.

PubMed

Holt, Joseph C; Lysakowski, Anna; Goldberg, Jay M

2006-12-20

To study the cellular mechanisms of efferent actions, we recorded from vestibular-nerve afferents close to the turtle posterior crista while efferent fibers were electrically stimulated. Efferent-mediated responses were obtained from calyx-bearing (CD, calyx and dimorphic) afferents and from bouton (B) afferents distinguished by their neuroepithelial locations into BT units near the torus and BM units at intermediate sites. The spike discharge of CD units is strongly excited by efferent stimulation, whereas BT and BM units are inhibited, with BM units also showing a postinhibitory excitation. Synaptic activity was recorded intracellularly after spikes were blocked. Responses of BT/BM units to single efferent shocks consist of a brief depolarization followed by a prolonged hyperpolarization. Both components reflect variations in hair-cell quantal release rates and are eliminated by pharmacological antagonists of alpha9/alpha10 nicotinic receptors. Blocking calcium-dependent SK potassium channels converts the biphasic response into a prolonged depolarization. Results can be explained, as in other hair-cell systems, by the sequential activation of alpha9/alpha10 and SK channels. In BM units, the postinhibitory excitation is based on an increased rate of hair-cell quanta and depends on the preceding inhibition. There is, in addition, an efferent-mediated, direct depolarization of BT/BM and CD fibers. In CD units, it is the exclusive efferent response. Nicotinic antagonists have different effects on hair-cell efferent actions and on the direct depolarization of CD and BT/BM units. Ultrastructural studies, besides confirming the efferent innervation of type II hair cells and calyx endings, show that turtle efferents commonly contact afferent boutons terminating on type II hair cells.

Hippocampal distribution of vesicular glutamate transporter 1 in patients with temporal lobe epilepsy.

PubMed

van der Hel, W Saskia; Verlinde, Suzanne A M W; Meijer, Dimphna H M; de Wit, Marina; Rensen, Marije G; van Gassen, Koen L I; van Rijen, Peter C; van Veelen, Cees W M; de Graan, Pierre N E

2009-07-01

Vesicular glutamate transporters (VGLUTs) are responsible for loading synaptic vesicles with glutamate, determining the phenotype of glutamatergic neurons, and have been implicated in the regulation of quantal size and presynaptic plasticity. We analyzed VGLUT subtype expression in normal human hippocampus and tested the hypothesis that alterations in VGLUT expression may contribute to long-term changes in glutamatergic transmission reported in patients with temporal lobe epilepsy (TLE). VGLUT immunohistochemistry, immunofluorescence, in situ hybridization, Western blotting, and quantitative polymerase chain reaction (qPCR) were performed on biopsies from TLE patients without (non-HS) and with hippocampal sclerosis (HS) and compared to autopsy controls and rat hippocampus. VGLUT1 expression was compared with synaptophysin, neuropeptide Y (NPY), and Timm's staining. VGLUT1 was the predominant VGLUT in human hippocampus and appeared to be localized to presynaptic glutamatergic terminals. In non-HS hippocampi, VGLUT1 protein levels were increased compared to control and HS hippocampi in all subfields. In HS hippocampi VGLUT1 expression was decreased in subfields with severe neuronal loss, but strongly up-regulated in the dentate gyrus, characterized by mossy fiber sprouting. VGLUT1 is used as marker for glutamatergic synapses in the human hippocampus. In HS hippocampi VGLUT1 up-regulation in the dentate gyrus probably marks new glutamatergic synapses formed by mossy fiber sprouting. Our data indicate that non-HS patients have an increased capacity to store glutamate in vesicles, most likely due to an increase in translational processes or upregulation of VGLUT1 in synapses from afferent neurons outside the hippocampus. This up-regulation may increase glutamatergic transmission, and thus contribute to increased extracellular glutamate levels and hyperexcitability.

A Decision Making Analysis of Persuasive Argumentation and the Choice Shift Effect

ERIC Educational Resources Information Center

Vinokur, Amiram; And Others

1975-01-01

A subjective expected utility (SEU) decision-making analysis was performed on the content of arguments generated by subjects privately or during group discussion in response to choice-dilemmas shown to shift toward risk and caution. (Editor)

Incorporating uncertainty regarding applicability of evidence from meta-analyses into clinical decision making.

PubMed

Kriston, Levente; Meister, Ramona

2014-03-01

Judging applicability (relevance) of meta-analytical findings to particular clinical decision-making situations remains challenging. We aimed to describe an evidence synthesis method that accounts for possible uncertainty regarding applicability of the evidence. We conceptualized uncertainty regarding applicability of the meta-analytical estimates to a decision-making situation as the result of uncertainty regarding applicability of the findings of the trials that were included in the meta-analysis. This trial-level applicability uncertainty can be directly assessed by the decision maker and allows for the definition of trial inclusion probabilities, which can be used to perform a probabilistic meta-analysis with unequal probability resampling of trials (adaptive meta-analysis). A case study with several fictitious decision-making scenarios was performed to demonstrate the method in practice. We present options to elicit trial inclusion probabilities and perform the calculations. The result of an adaptive meta-analysis is a frequency distribution of the estimated parameters from traditional meta-analysis that provides individually tailored information according to the specific needs and uncertainty of the decision maker. The proposed method offers a direct and formalized combination of research evidence with individual clinical expertise and may aid clinicians in specific decision-making situations. Copyright © 2014 Elsevier Inc. All rights reserved.

XMM-Newton Science Analysis Software: How to Bring New Technologies to Long-life Satellite Missions

NASA Astrophysics Data System (ADS)

Ibarra, A.; Calle, I.; Gabriel, C.; Salgado, J.; Osuna, P.

2009-09-01

We present here the beta version of the Remote Interface to SAS Analysis (RISA), a web service-based system that allows users the analysis of XMM-Newton data making use of all of the existing SAS functionalities. RISA takes advantage of GRID architecture to run SAS, achieving high performance in resource management. We are also making the SAS remote analysis compatible with present and future VO standards.

Multicriteria decision analysis: Overview and implications for environmental decision making

USGS Publications Warehouse

Hermans, Caroline M.; Erickson, Jon D.; Erickson, Jon D.; Messner, Frank; Ring, Irene

2007-01-01

Environmental decision making involving multiple stakeholders can benefit from the use of a formal process to structure stakeholder interactions, leading to more successful outcomes than traditional discursive decision processes. There are many tools available to handle complex decision making. Here we illustrate the use of a multicriteria decision analysis (MCDA) outranking tool (PROMETHEE) to facilitate decision making at the watershed scale, involving multiple stakeholders, multiple criteria, and multiple objectives. We compare various MCDA methods and their theoretical underpinnings, examining methods that most realistically model complex decision problems in ways that are understandable and transparent to stakeholders.

Word Problems and Make-Believe: Using Frame Analysis and Ethnomethodology to Explore Aspects of the Culture of Schooling

ERIC Educational Resources Information Center

Benincasa, Luciana

2017-01-01

The paper applies Goffman's frame analysis and ethnomethodology to student performance on mathematical word problems. In educational research, frame analysis has usually been limited to primary frames. Instead, in this paper I focus on the kind of secondary frame that Goffman calls 'utilitarian make-believe'. The data consist of a fragment of…

Using the Situated Clinical Decision-Making framework to guide analysis of nurses' clinical decision-making.

PubMed

Gillespie, Mary

2010-11-01

Nurses' clinical decision-making is a complex process that holds potential to influence the quality of care provided and patient outcomes. The evolution of nurses' decision-making that occurs with experience has been well documented. In addition, literature includes numerous strategies and approaches purported to support development of nurses' clinical decision-making. There has been, however, significantly less attention given to the process of assessing nurses' clinical decision-making and novice clinical educators are often challenged with knowing how to best support nurses and nursing students in developing their clinical decision-making capacity. The Situated Clinical Decision-Making framework is presented for use by clinical educators: it provides a structured approach to analyzing nursing students' and novice nurses' decision-making in clinical nursing practice, assists educators in identifying specific issues within nurses' clinical decision-making, and guides selection of relevant strategies to support development of clinical decision-making. A series of questions is offered as a guide for clinical educators when assessing nurses' clinical decision-making. The discussion presents key considerations related to analysis of various decision-making components, including common sources of challenge and errors that may occur within nurses' clinical decision-making. An exemplar illustrates use of the framework and guiding questions. Implications of this approach for selection of strategies that support development of clinical decision-making are highlighted. Copyright © 2010 Elsevier Ltd. All rights reserved.

Path Analysis Examining Self-Efficacy and Decision-Making Performance on a Simulated Baseball Task

ERIC Educational Resources Information Center

Hepler, Teri J.; Feltz, Deborah L.

2012-01-01

The purpose of this study was to examine the relationship between decision-making self-efficacy and decision-making performance in sport. Undergraduate students (N = 78) performed 10 trials of a decision-making task in baseball. Self-efficacy was measured before performing each trial. Decision-making performance was assessed by decision speed and…

Decision Styles and Rationality: An Analysis of the Predictive Validity of the General Decision-Making Style Inventory

ERIC Educational Resources Information Center

Curseu, Petru Lucian; Schruijer, Sandra G. L.

2012-01-01

This study investigates the relationship between the five decision-making styles evaluated by the General Decision-Making Style Inventory, indecisiveness, and rationality in decision making. Using a sample of 102 middle-level managers, the results show that the rational style positively predicts rationality in decision making and negatively…

Benefit-Risk Analysis for Decision-Making: An Approach.

PubMed

Raju, G K; Gurumurthi, K; Domike, R

2016-12-01

The analysis of benefit and risk is an important aspect of decision-making throughout the drug lifecycle. In this work, the use of a benefit-risk analysis approach to support decision-making was explored. The proposed approach builds on the qualitative US Food and Drug Administration (FDA) approach to include a more explicit analysis based on international standards and guidance that enables aggregation and comparison of benefit and risk on a common basis and a lifecycle focus. The approach is demonstrated on six decisions over the lifecycle (e.g., accelerated approval, withdrawal, and traditional approval) using two case studies: natalizumab for multiple sclerosis (MS) and bedaquiline for multidrug-resistant tuberculosis (MDR-TB). © 2016 American Society for Clinical Pharmacology and Therapeutics.

Principal Component Analysis: A Method for Determining the Essential Dynamics of Proteins

PubMed Central

David, Charles C.; Jacobs, Donald J.

2015-01-01

It has become commonplace to employ principal component analysis to reveal the most important motions in proteins. This method is more commonly known by its acronym, PCA. While most popular molecular dynamics packages inevitably provide PCA tools to analyze protein trajectories, researchers often make inferences of their results without having insight into how to make interpretations, and they are often unaware of limitations and generalizations of such analysis. Here we review best practices for applying standard PCA, describe useful variants, discuss why one may wish to make comparison studies, and describe a set of metrics that make comparisons possible. In practice, one will be forced to make inferences about the essential dynamics of a protein without having the desired amount of samples. Therefore, considerable time is spent on describing how to judge the significance of results, highlighting pitfalls. The topic of PCA is reviewed from the perspective of many practical considerations, and useful recipes are provided. PMID:24061923

Principal component analysis: a method for determining the essential dynamics of proteins.

PubMed

David, Charles C; Jacobs, Donald J

2014-01-01

It has become commonplace to employ principal component analysis to reveal the most important motions in proteins. This method is more commonly known by its acronym, PCA. While most popular molecular dynamics packages inevitably provide PCA tools to analyze protein trajectories, researchers often make inferences of their results without having insight into how to make interpretations, and they are often unaware of limitations and generalizations of such analysis. Here we review best practices for applying standard PCA, describe useful variants, discuss why one may wish to make comparison studies, and describe a set of metrics that make comparisons possible. In practice, one will be forced to make inferences about the essential dynamics of a protein without having the desired amount of samples. Therefore, considerable time is spent on describing how to judge the significance of results, highlighting pitfalls. The topic of PCA is reviewed from the perspective of many practical considerations, and useful recipes are provided.

Neural systems analysis of decision making during goal-directed navigation.

PubMed

Penner, Marsha R; Mizumori, Sheri J Y

2012-01-01

The ability to make adaptive decisions during goal-directed navigation is a fundamental and highly evolved behavior that requires continual coordination of perceptions, learning and memory processes, and the planning of behaviors. Here, a neurobiological account for such coordination is provided by integrating current literatures on spatial context analysis and decision-making. This integration includes discussions of our current understanding of the role of the hippocampal system in experience-dependent navigation, how hippocampal information comes to impact midbrain and striatal decision making systems, and finally the role of the striatum in the implementation of behaviors based on recent decisions. These discussions extend across cellular to neural systems levels of analysis. Not only are key findings described, but also fundamental organizing principles within and across neural systems, as well as between neural systems functions and behavior, are emphasized. It is suggested that studying decision making during goal-directed navigation is a powerful model for studying interactive brain systems and their mediation of complex behaviors. Copyright © 2011. Published by Elsevier Ltd.

Workshop on Aeronautical Decision Making (ADM). Volume 1. Executive Summary

DTIC Science & Technology

1992-08-01

expert and novice pilots when a real decision was required. Aeronautical Decision Making (ADM), Crew Resource Management (CRM), Advanced Qualification Program (AQP), Cognitive Task Analysis (CTA), Expert Decision Making (EDM)

Accuracy of intuition in clinical decision-making among novice clinicians.

PubMed

Price, Amanda; Zulkosky, Kristen; White, Krista; Pretz, Jean

2017-05-01

To assess the reliance on intuitive and analytical approaches during clinical decision-making among novice clinicians and whether that reliance is associated with accurate decision-making. Nurse educators and managers tend to emphasize analysis over intuition during clinical decision-making though nurses typically report some reliance on intuition in their practice. We hypothesized that under certain conditions, reliance on intuition would support accurate decision-making, even among novices. This study utilized an experimental design with clinical complication (familiar vs. novel) and decision phase (cue acquisition, diagnosis and action) as within-subjects' factors, and simulation role (observer, family, auxiliary nurse and primary nurse) as between-subjects' factor. We examined clinical decision-making accuracy among final semester pre-licensure nursing students in a simulation experience. Students recorded their reasoning about emerging clinical complications with their patient during two distinct points in the simulation; one point involved a familiar complication and the other a relatively novel complication. All data were collected during Spring 2015. Although most participants relied more heavily on analysis than on intuition, use of intuition during the familiar complication was associated with more accurate decision-making, particularly in guiding attention to relevant cues. With the novel complication, use of intuition appeared to hamper decision-making, particularly for those in an observer role. Novice clinicians should be supported by educators and nurse managers to note when their intuitions are likely to be valid. Our findings emphasize the integrated nature of intuition and analysis in clinical decision-making. © 2016 John Wiley & Sons Ltd.

Shared decision-making in the paediatric field: a literature review and concept analysis.

PubMed

Park, Eun Sook; Cho, In Young

2017-09-13

The concept of shared decision-making is poorly defined and often used interchangeably with related terms. The aim of this study was to delineate and clarify the concept of shared decision-making in the paediatric field. Rodgers and Knafl's evolutionary concept analysis was used to delineate and clarify the concept. Following a search of the CINAHL, PubMed and MEDLINE databases and online journals between 1995 and 2016, we included a total of 42 articles that referred to shared decision-making in the paediatric field. The attributes included active participation of the three: parents, children and health professionals; collaborative partnership; reaching a compromise; and common goal for child's health. Antecedents were existing several options with different possible outcomes; substantial decisional conflict; recognising child's health situations that decision-making is needed; and willingness to participate in decision-making. Finally, the consequences included decreased decisional conflict; mutual empowerment; improved child health status; and improved quality of paediatric health care. This study provides a theoretical understanding of the concept of shared decision-making in the paediatric field; furthermore, by integrating this concept into paediatric practice, it may help to reduce the gap between theory and practice. The analysis could also provide nursing researchers with insight into paediatric decision-making and establish a foundation to develop future interventions and situation-specific theory for promoting high-quality decision-making in the paediatric field. © 2017 Nordic College of Caring Science.

Sourdough microbial community dynamics: An analysis during French organic bread-making processes.

PubMed

Lhomme, Emilie; Urien, Charlotte; Legrand, Judith; Dousset, Xavier; Onno, Bernard; Sicard, Delphine

2016-02-01

Natural sourdoughs are commonly used in bread-making processes, especially for organic bread. Despite its role in bread flavor and dough rise, the stability of the sourdough microbial community during and between bread-making processes is debated. We investigated the dynamics of lactic acid bacteria (LAB) and yeast communities in traditional organic sourdoughs of five French bakeries during the bread-making process and several months apart using classical and molecular microbiology techniques. Sourdoughs were sampled at four steps of the bread-making process with repetition. The analysis of microbial density over 68 sourdough/dough samples revealed that both LAB and yeast counts changed along the bread-making process and between bread-making runs. The species composition was less variable. A total of six LAB and nine yeast species was identified from 520 and 1675 isolates, respectively. The dominant LAB species was Lactobacillus sanfranciscensis, found for all bakeries and each bread-making run. The dominant yeast species changed only once between bread-making processes but differed between bakeries. They mostly belonged to the Kazachstania clade. Overall, this study highlights the change of population density within the bread-making process and between bread-making runs and the relative stability of the sourdough species community during bread-making process. Copyright © 2014 Elsevier Ltd. All rights reserved.

Decision curve analysis for assessing the usefulness of tests for making decisions to treat: an application to tests for prodromal psychosis.

PubMed

Pulleyblank, Ryan; Chuma, Jefter; Gilbody, Simon M; Thompson, Carl

2013-09-01

For a test to be considered useful for making treatment decisions, it is necessary that making treatment decisions based on the results of the test be a preferable strategy to making treatment decisions without the test. Decision curve analysis is a framework for assessing when a test would be expected to be useful, which integrates evidence of a test's performance characteristics (sensitivity and specificity), condition prevalence among at-risk patients, and patient preferences for treatment. We describe decision curve analysis generally and illustrate its potential through an application to tests for prodromal psychosis. Clinical psychosis is often preceded by a prodromal phase, but not all those with prodromal symptoms proceed to develop full psychosis. Patients identified as at risk for developing psychosis may be considered for proactive treatment to mitigate development of clinically defined psychosis. Tests exist to help identify those at-risk patients most likely to develop psychosis, but it is uncertain when these tests would be considered useful for making proactive treatment decisions. We apply decision curve analysis to results from a systematic review of studies investigating clinical tests for predicting the development of psychosis in at-risk populations, and present resulting decision curves that illustrate when the tests may be expected to be useful for making proactive treatment decisions.

Scientists' sense making when hypothesizing about disease mechanisms from expression data and their needs for visualization support.

PubMed

Mirel, Barbara; Görg, Carsten

2014-04-26

A common class of biomedical analysis is to explore expression data from high throughput experiments for the purpose of uncovering functional relationships that can lead to a hypothesis about mechanisms of a disease. We call this analysis expression driven, -omics hypothesizing. In it, scientists use interactive data visualizations and read deeply in the research literature. Little is known, however, about the actual flow of reasoning and behaviors (sense making) that scientists enact in this analysis, end-to-end. Understanding this flow is important because if bioinformatics tools are to be truly useful they must support it. Sense making models of visual analytics in other domains have been developed and used to inform the design of useful and usable tools. We believe they would be helpful in bioinformatics. To characterize the sense making involved in expression-driven, -omics hypothesizing, we conducted an in-depth observational study of one scientist as she engaged in this analysis over six months. From findings, we abstracted a preliminary sense making model. Here we describe its stages and suggest guidelines for developing visualization tools that we derived from this case. A single case cannot be generalized. But we offer our findings, sense making model and case-based tool guidelines as a first step toward increasing interest and further research in the bioinformatics field on scientists' analytical workflows and their implications for tool design.

Scientists’ sense making when hypothesizing about disease mechanisms from expression data and their needs for visualization support

PubMed Central

2014-01-01

A common class of biomedical analysis is to explore expression data from high throughput experiments for the purpose of uncovering functional relationships that can lead to a hypothesis about mechanisms of a disease. We call this analysis expression driven, -omics hypothesizing. In it, scientists use interactive data visualizations and read deeply in the research literature. Little is known, however, about the actual flow of reasoning and behaviors (sense making) that scientists enact in this analysis, end-to-end. Understanding this flow is important because if bioinformatics tools are to be truly useful they must support it. Sense making models of visual analytics in other domains have been developed and used to inform the design of useful and usable tools. We believe they would be helpful in bioinformatics. To characterize the sense making involved in expression-driven, -omics hypothesizing, we conducted an in-depth observational study of one scientist as she engaged in this analysis over six months. From findings, we abstracted a preliminary sense making model. Here we describe its stages and suggest guidelines for developing visualization tools that we derived from this case. A single case cannot be generalized. But we offer our findings, sense making model and case-based tool guidelines as a first step toward increasing interest and further research in the bioinformatics field on scientists’ analytical workflows and their implications for tool design. PMID:24766796

Importance and pitfalls of molecular analysis to parasite epidemiology.

PubMed

Constantine, Clare C

2003-08-01

Molecular tools are increasingly being used to address questions about parasite epidemiology. Parasites represent a diverse group and they might not fit traditional population genetic models. Testing hypotheses depends equally on correct sampling, appropriate tool and/or marker choice, appropriate analysis and careful interpretation. All methods of analysis make assumptions which, if violated, make the results invalid. Some guidelines to avoid common pitfalls are offered here.

Contrasting models of driver behaviour in emergencies using retrospective verbalisations and network analysis.

PubMed

Banks, Victoria A; Stanton, Neville A

2015-01-01

Automated assistance in driving emergencies aims to improve the safety of our roads by avoiding or mitigating the effects of accidents. However, the behavioural implications of such systems remain unknown. This paper introduces the driver decision-making in emergencies (DDMiEs) framework to investigate how the level and type of automation may affect driver decision-making and subsequent responses to critical braking events using network analysis to interrogate retrospective verbalisations. Four DDMiE models were constructed to represent different levels of automation within the driving task and its effects on driver decision-making. Findings suggest that whilst automation does not alter the decision-making pathway (e.g. the processes between hazard detection and response remain similar), it does appear to significantly weaken the links between information-processing nodes. This reflects an unintended yet emergent property within the task network that could mean that we may not be improving safety in the way we expect. This paper contrasts models of driver decision-making in emergencies at varying levels of automation using the Southampton University Driving Simulator. Network analysis of retrospective verbalisations indicates that increasing the level of automation in driving emergencies weakens the link between information-processing nodes essential for effective decision-making.

The role of economic evaluation in the decision-making process of family physicians: design and methods of a qualitative embedded multiple-case study

PubMed Central

Lessard, Chantale; Contandriopoulos, André-Pierre; Beaulieu, Marie-Dominique

2009-01-01

Background A considerable amount of resource allocation decisions take place daily at the point of the clinical encounter; especially in primary care, where 80 percent of health problems are managed. Ignoring economic evaluation evidence in individual clinical decision-making may have a broad impact on the efficiency of health services. To date, almost all studies on the use of economic evaluation in decision-making used a quantitative approach, and few investigated decision-making at the clinical level. An important question is whether economic evaluations affect clinical practice. The project is an intervention research study designed to understand the role of economic evaluation in the decision-making process of family physicians (FPs). The contributions of the project will be from the perspective of Pierre Bourdieu's sociological theory. Methods/design A qualitative research strategy is proposed. We will conduct an embedded multiple-case study design. Ten case studies will be performed. The FPs will be the unit of analysis. The sampling strategies will be directed towards theoretical generalization. The 10 selected cases will be intended to reflect a diversity of FPs. There will be two embedded units of analysis: FPs (micro-level of analysis) and field of family medicine (macro-level of analysis). The division of the determinants of practice/behaviour into two groups, corresponding to the macro-structural level and the micro-individual level, is the basis for Bourdieu's mode of analysis. The sources of data collection for the micro-level analysis will be 10 life history interviews with FPs, documents and observational evidence. The sources of data collection for the macro-level analysis will be documents and 9 open-ended, focused interviews with key informants from medical associations and academic institutions. The analytic induction approach to data analysis will be used. A list of codes will be generated based on both the original framework and new themes introduced by the participants. We will conduct within-case and cross-case analyses of the data. Discussion The question of the role of economic evaluation in FPs' decision-making is of great interest to scientists, health care practitioners, managers and policy-makers, as well as to consultants, industry, and society. It is believed that the proposed research approach will make an original contribution to the development of knowledge, both empirical and theoretical. PMID:19210787

How to use multi-criteria decision analysis methods for reimbursement decision-making in healthcare: a step-by-step guide.

PubMed

Diaby, Vakaramoko; Goeree, Ron

2014-02-01

In recent years, the quest for more comprehensiveness, structure and transparency in reimbursement decision-making in healthcare has prompted the research into alternative decision-making frameworks. In this environment, multi-criteria decision analysis (MCDA) is arising as a valuable tool to support healthcare decision-making. In this paper, we present the main MCDA decision support methods (elementary methods, value-based measurement models, goal programming models and outranking models) using a case study approach. For each family of methods, an example of how an MCDA model would operate in a real decision-making context is presented from a critical perspective, highlighting the parameters setting, the selection of the appropriate evaluation model as well as the role of sensitivity and robustness analyses. This study aims to provide a step-by-step guide on how to use MCDA methods for reimbursement decision-making in healthcare.

An integrated, ethically driven environmental model of clinical decision making in emergency settings.

PubMed

Wolf, Lisa

2013-02-01

To explore the relationship between multiple variables within a model of critical thinking and moral reasoning. A quantitative descriptive correlational design using a purposive sample of 200 emergency nurses. Measured variables were accuracy in clinical decision-making, moral reasoning, perceived care environment, and demographics. Analysis was by bivariate correlation using Pearson's product-moment correlation coefficients, chi square and multiple linear regression analysis. The elements as identified in the integrated ethically-driven environmental model of clinical decision-making (IEDEM-CD) corrected depict moral reasoning and environment of care as factors significantly affecting accuracy in decision-making. The integrated, ethically driven environmental model of clinical decision making is a framework useful for predicting clinical decision making accuracy for emergency nurses in practice, with further implications in education, research and policy. A diagnostic and therapeutic framework for identifying and remediating individual and environmental challenges to accurate clinical decision making. © 2012, The Author. International Journal of Nursing Knowledge © 2012, NANDA International.

Attitudes towards poverty, organizations, ethics and morals: Israeli social workers' shared decision making.

PubMed

Levin, Lia; Schwartz-Tayri, Talia

2017-06-01

Partnerships between service users and social workers are complex in nature and can be driven by both personal and contextual circumstances. This study sought to explore the relationship between social workers' involvement in shared decision making with service users, their attitudes towards service users in poverty, moral standards and health and social care organizations' policies towards shared decision making. Based on the responses of 225 licensed social workers from health and social care agencies in the public, private and third sectors in Israel, path analysis was used to test a hypothesized model. Structural attributions for poverty contributed to attitudes towards people who live in poverty, which led to shared decision making. Also, organizational support in shared decision making, and professional moral identity, contributed to ethical behaviour which led to shared decision making. The results of this analysis revealed that shared decision making may be a scion of branched roots planted in the relationship between ethics, organizations and Stigma. © 2016 The Authors. Health Expectations Published by John Wiley & Sons Ltd.

What To Do, What To Do? Determining a Course of Action at the Operational Level of War

DTIC Science & Technology

1992-05-18

and making choices can expand the limits of human rationality . 5 Where decisions involve the lives of soldiers and the future of nations, any edge or...ANALYSIS 15. N5Iu,,3E•a -r PAGES115 OPERATIONAL DECISION - MAKING MISSION ANALYSIS 115 COURSE OF ACTION SELECTION STAFF ESTIMATES I1. SECUlPIT... decision - making procedures for the operational level of war. These doctrinal procedures are found in emerging joint doctrine. For these procedures to be

An Interpretative Phenomenological Analysis of Sense-Making by Department of Defense Employees

ERIC Educational Resources Information Center

Harrison, John L., Sr.

2011-01-01

The purpose of this qualitative, phenomenological study was to explore the perceptions and lived experiences of Department of Defense (DOD) civilian employees to identify how their personal sense-making affects their coaching of adult students. The author used an interpretative phenomenological analysis (IPA) method involving personal interviews…

Demonstrating Empathy: A Phenomenological Study of Instructional Designers Making Instructional Strategy Decisions for Adult Learners

ERIC Educational Resources Information Center

Vann, Linda S.

2017-01-01

Instructional designers are tasked with making instructional strategy decisions to facilitate achievement of learning outcomes as part of their professional responsibilities. While the instructional design process includes learner analysis, that analysis alone does not embody opportunities to assist instructional designers with demonstrations of…

Vygotsky's Analysis of Children's Meaning Making Processes

ERIC Educational Resources Information Center

Mahn, Holbrook

2012-01-01

Vygotsky's work is extensive and covers many aspects of the development of children's meaning-making processes in social and cultural contexts. However, his main focus is on the examination of the unification of speaking and thinking processes. His investigation centers on the analysis of the entity created by this unification--an internal…

A Unified Framework for Monetary Theory and Policy Analysis.

ERIC Educational Resources Information Center

Lagos, Ricardo; Wright, Randall

2005-01-01

Search-theoretic models of monetary exchange are based on explicit descriptions of the frictions that make money essential. However, tractable versions of these models typically make strong assumptions that render them ill suited for monetary policy analysis. We propose a new framework, based on explicit micro foundations, within which macro…

Analysis in Motion Initiative – Summarization Capability

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

Arendt, Dustin; Pirrung, Meg; Jasper, Rob

2017-06-22

Analysts are tasked with integrating information from multiple data sources for important and timely decision making. What if sense making and overall situation awareness could be improved through visualization techniques? The Analysis in Motion initiative is advancing the ability to summarize and abstract multiple streams and static data sources over time.

A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Multiple Myeloma.

PubMed

Raju, G K; Gurumurthi, Karthik; Domike, Reuben; Kazandjian, Dickran; Landgren, Ola; Blumenthal, Gideon M; Farrell, Ann; Pazdur, Richard; Woodcock, Janet

2018-01-01

Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analysis. In this work, a quantitative benefit-risk analysis approach captures regulatory decision-making about new drugs to treat multiple myeloma (MM). MM assessments have been based on endpoints such as time to progression (TTP), progression-free survival (PFS), and objective response rate (ORR) which are different than benefit-risk analysis based on overall survival (OS). Twenty-three FDA decisions on MM drugs submitted to FDA between 2003 and 2016 were identified and analyzed. The benefits and risks were quantified relative to comparators (typically the control arm of the clinical trial) to estimate whether the median benefit-risk was positive or negative. A sensitivity analysis was demonstrated using ixazomib to explore the magnitude of uncertainty. FDA approval decision outcomes were consistent and logical using this benefit-risk framework. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Despite Best Intentions: A Critical Analysis of Social Justice Leadership and Decision Making

ERIC Educational Resources Information Center

DeMatthews, David E.; Mungal, Angus Shiva; Carrola, Paul A.

2015-01-01

The purpose of this article is to explore the relationship between social justice leadership and organizational decision making in order to make recommendations for how principals can make more socially just decisions in difficult school contexts. This article begins with a discussion of social justice leadership, facets and theories associated…

Path Analysis on Educational Fiscal Decision-Making Mechanism in China

ERIC Educational Resources Information Center

Zhao, Hongbin; Sun, Baicai

2007-01-01

In China's current educational fiscal decision making, problems are as follows: no law to trust or not abiding by available laws, absence of equity and efficiency, as well as the standardization of decision-making procedures. It is necessary to set up effective fiscal decision-making mechanism in education and rationally devise reliable paths.

Multi-Metric Sustainability Analysis

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

Cowlin, Shannon; Heimiller, Donna; Macknick, Jordan

2014-12-01

A readily accessible framework that allows for evaluating impacts and comparing tradeoffs among factors in energy policy, expansion planning, and investment decision making is lacking. Recognizing this, the Joint Institute for Strategic Energy Analysis (JISEA) funded an exploration of multi-metric sustainability analysis (MMSA) to provide energy decision makers with a means to make more comprehensive comparisons of energy technologies. The resulting MMSA tool lets decision makers simultaneously compare technologies and potential deployment locations.

The financial crisis and the European Parliament: An analysis of the Two-Pack legislation

PubMed Central

Roger, Léa; Otjes, Simon

2017-01-01

The left–right line of conflict has been the dominant dimension of decision-making in the European Parliament since 1979. A pro-/anti-European Union integration dimension is of secondary importance. Limited evidence exists on the conditions under which these different dimensions matter. This study examines parliamentary decision-making about the so-called Two-Pack, which moved responsibilities about budgetary decision-making to the European Commission. The article uses in-depth interviews, textual analysis of committee debates and roll call voting analysis in order to determine which lines of conflict matter at which stage of decision-making. The evidence indicates that left–right division is dominant in the informal stage preceding committee debates, while both the pro-/anti-European Union and the left/right dimensions matter during the committee stage, whereas for plenary votes, the pro-/anti-European Union dimension is crucial. PMID:29187803

The financial crisis and the European Parliament: An analysis of the Two-Pack legislation.

PubMed

Roger, Léa; Otjes, Simon; van der Veer, Harmen

2017-12-01

The left-right line of conflict has been the dominant dimension of decision-making in the European Parliament since 1979. A pro-/anti-European Union integration dimension is of secondary importance. Limited evidence exists on the conditions under which these different dimensions matter. This study examines parliamentary decision-making about the so-called Two-Pack, which moved responsibilities about budgetary decision-making to the European Commission. The article uses in-depth interviews, textual analysis of committee debates and roll call voting analysis in order to determine which lines of conflict matter at which stage of decision-making. The evidence indicates that left-right division is dominant in the informal stage preceding committee debates, while both the pro-/anti-European Union and the left/right dimensions matter during the committee stage, whereas for plenary votes, the pro-/anti-European Union dimension is crucial.

Evaluating Utility in Diagnostic Decision Making.

ERIC Educational Resources Information Center

Harber, Jean R.

1981-01-01

The utility of the procedures special educators apply in making decisions about the identification of handicapped individuals has not been thoroughly studied. The paper examines the utility of diagnostic decision making from the perspective of receiver operating curve analysis. (Author)

Atlas-guided volumetric diffuse optical tomography enhanced by generalized linear model analysis to image risk decision-making responses in young adults.

PubMed

Lin, Zi-Jing; Li, Lin; Cazzell, Mary; Liu, Hanli

2014-08-01

Diffuse optical tomography (DOT) is a variant of functional near infrared spectroscopy and has the capability of mapping or reconstructing three dimensional (3D) hemodynamic changes due to brain activity. Common methods used in DOT image analysis to define brain activation have limitations because the selection of activation period is relatively subjective. General linear model (GLM)-based analysis can overcome this limitation. In this study, we combine the atlas-guided 3D DOT image reconstruction with GLM-based analysis (i.e., voxel-wise GLM analysis) to investigate the brain activity that is associated with risk decision-making processes. Risk decision-making is an important cognitive process and thus is an essential topic in the field of neuroscience. The Balloon Analog Risk Task (BART) is a valid experimental model and has been commonly used to assess human risk-taking actions and tendencies while facing risks. We have used the BART paradigm with a blocked design to investigate brain activations in the prefrontal and frontal cortical areas during decision-making from 37 human participants (22 males and 15 females). Voxel-wise GLM analysis was performed after a human brain atlas template and a depth compensation algorithm were combined to form atlas-guided DOT images. In this work, we wish to demonstrate the excellence of using voxel-wise GLM analysis with DOT to image and study cognitive functions in response to risk decision-making. Results have shown significant hemodynamic changes in the dorsal lateral prefrontal cortex (DLPFC) during the active-choice mode and a different activation pattern between genders; these findings correlate well with published literature in functional magnetic resonance imaging (fMRI) and fNIRS studies. Copyright © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

A method for studying decision-making by guideline development groups.

PubMed

Gardner, Benjamin; Davidson, Rosemary; McAteer, John; Michie, Susan

2009-08-05

Multidisciplinary guideline development groups (GDGs) have considerable influence on UK healthcare policy and practice, but previous research suggests that research evidence is a variable influence on GDG recommendations. The Evidence into Recommendations (EiR) study has been set up to document social-psychological influences on GDG decision-making. In this paper we aim to evaluate the relevance of existing qualitative methodologies to the EiR study, and to develop a method best-suited to capturing influences on GDG decision-making. A research team comprised of three postdoctoral research fellows and a multidisciplinary steering group assessed the utility of extant qualitative methodologies for coding verbatim GDG meeting transcripts and semi-structured interviews with GDG members. A unique configuration of techniques was developed to permit data reduction and analysis. Our method incorporates techniques from thematic analysis, grounded theory analysis, content analysis, and framework analysis. Thematic analysis of individual interviews conducted with group members at the start and end of the GDG process defines discrete problem areas to guide data extraction from GDG meeting transcripts. Data excerpts are coded both inductively and deductively, using concepts taken from theories of decision-making, social influence and group processes. These codes inform a framework analysis to describe and explain incidents within GDG meetings. We illustrate the application of the method by discussing some preliminary findings of a study of a National Institute for Health and Clinical Excellence (NICE) acute physical health GDG. This method is currently being applied to study the meetings of three of NICE GDGs. These cover topics in acute physical health, mental health and public health, and comprise a total of 45 full-day meetings. The method offers potential for application to other health care and decision-making groups.

A correlational study between signature, writing abilities and decision-making capacity among people with initial cognitive impairment.

PubMed

Renier, M; Gnoato, F; Tessari, A; Formilan, M; Busonera, F; Albanese, P; Sartori, G; Cester, A

2016-06-01

Some clinical conditions, including dementia, compromise cognitive functions involved in decision-making processes, with repercussions on the ability to subscribe a will. Because of the increasing number of aged people with cognitive impairment there is an acute and growing need for decision-making capacity evidence-based assessment. Our study investigates the relationship between writing abilities and cognitive integrity to see if it is possible to make inferences on decision-making capacity through handwriting analysis. We also investigated the relationship between signature ability and cognitive integrity. Thirty-six participants with diagnosis of MCI and 38 participants with diagnosis of initial dementia were recruited. For each subject we collected two samples of signature-an actual and a previous one-and an extract of spontaneous writing. Furthermore, we administered a neuropsychological battery to investigate cognitive functions involved in decision-making. We found significant correlations between spontaneous writing indexes and neuropsychological test results. Nonetheless, the index of signature deterioration does not correlate with the level of cognitive decline. Our results suggest that a careful analysis of spontaneous writing can be useful to make inferences on decision-making capacity, whereas great caution should be taken in attributing validity to handwritten signature of subjects with MCI or dementia. The analysis of spontaneous writing can be a reliable aid in cases of retrospective evaluation of cognitive integrity. On the other side, the ability to sign is not an index of cognitive integrity.

Lifecycle analysis for automobiles: Uses and limitations

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

Gaines, L.; Stodolsky, F.

There has been a recent trend toward the use of lifecycle analysis (LCA) as a decision-making tool for the automotive industry. However, the different practitioners` methods and assumptions vary widely, as do the interpretations put on the results. The lack of uniformity has been addressed by such groups as the Society of Environmental Toxicology and Chemistry (SETAC) and the International Organization for Standardization (ISO), but standardization of methodology assures neither meaningful results nor appropriate use of the results. This paper examines the types of analysis that are possible for automobiles, explains possible pitfalls to be avoided, and suggests ways thatmore » LCA can be used as part of a rational decision-making procedure. The key to performing a useful analysis is identification of the factors that will actually be used in making the decision. It makes no sense to analyze system energy use in detail if direct financial cost is to be the decision criterion. Criteria may depend on who is making the decision (consumer, producer, regulator). LCA can be used to track system performance for a variety of criteria, including emissions, energy use, and monetary costs, and these can have spatial and temporal distributions. Because optimization of one parameter is likely to worsen another, identification of trade-offs is an important function of LCA.« less

Paraconsistent Annotated Logic in Viability Analysis: an Approach to Product Launching

NASA Astrophysics Data System (ADS)

Romeu de Carvalho, Fábio; Brunstein, Israel; Abe, Jair Minoro

2004-08-01

In this paper we present an application of the Para-analyzer, a logical analyzer based on the Paraconsistent Annotated Logic Pτ, introduced by Da Silva Filho and Abe in the decision-making systems. An example is analyzed in detail showing how uncertainty, inconsistency and paracompleteness can be elegantly handled with this logical system. As application for the Para-analyzer in decision-making, we developed the BAM — Baricenter Analysis Method. In order to make the presentation easier, we present the BAM applied in the viability analysis of product launching. Some of the techniques of Paraconsistent Annotated Logic have been applied in Artificial Intelligence, Robotics, Information Technolgy (Computer Sciences), etc..

Impaired decision-making and brain shrinkage in alcoholism.

PubMed

Le Berre, A-P; Rauchs, G; La Joie, R; Mézenge, F; Boudehent, C; Vabret, F; Segobin, S; Viader, F; Allain, P; Eustache, F; Pitel, A-L; Beaunieux, H

2014-03-01

Alcohol-dependent individuals usually favor instant gratification of alcohol use and ignore its long-term negative consequences, reflecting impaired decision-making. According to the somatic marker hypothesis, decision-making abilities are subtended by an extended brain network. As chronic alcohol consumption is known to be associated with brain shrinkage in this network, the present study investigated relationships between brain shrinkage and decision-making impairments in alcohol-dependent individuals early in abstinence using voxel-based morphometry. Thirty patients performed the Iowa Gambling Task and underwent a magnetic resonance imaging investigation (1.5T). Decision-making performances and brain data were compared with those of age-matched healthy controls. In the alcoholic group, a multiple regression analysis was conducted with two predictors (gray matter [GM] volume and decision-making measure) and two covariates (number of withdrawals and duration of alcoholism). Compared with controls, alcoholics had impaired decision-making and widespread reduced gray matter volume, especially in regions involved in decision-making. The regression analysis revealed links between high GM volume in the ventromedial prefrontal cortex, dorsal anterior cingulate cortex and right hippocampal formation, and high decision-making scores (P<0.001, uncorrected). Decision-making deficits in alcoholism may result from impairment of both emotional and cognitive networks. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

An Analysis of Activities in Preschool Settings. Final Report.

ERIC Educational Resources Information Center

Berk, Laura E.

This research was aimed at an analysis of classroom activities which make up educational programs for young children. Its broad purpose was to analyze systematically and to make comparisons among six preschool programs in order to describe the patterns of activity settings used; the objectives activity settings were designed to reach from the…

An Integrative Framework for the Analysis of Multiple and Multimodal Representations for Meaning-Making in Science Education

ERIC Educational Resources Information Center

Tang, Kok-Sing; Delgado, Cesar; Moje, Elizabeth Birr

2014-01-01

This paper presents an integrative framework for analyzing science meaning-making with representations. It integrates the research on multiple representations and multimodal representations by identifying and leveraging the differences in their units of analysis in two dimensions: timescale and compositional grain size. Timescale considers the…

The Role of Signifier Differences, Associations, and Combinations in Creative Digital Video Composing: Making Meaning with Gestures, Objects, Actions, and Speech

ERIC Educational Resources Information Center

Ranker, Jason

2017-01-01

This article presents an analysis of a digital video created by a student (age 13) in a classroom setting. Since sign functioning is a key focus in theories of meaning making as it occurs through language and through other modes, my analysis focuses on the relations between signifiers as they are inscribed in her video. This analysis explores new…

The use of economic evaluations in NHS decision-making: a review and empirical investigation.

PubMed

Williams, I; McIver, S; Moore, D; Bryan, S

2008-04-01

To determine the extent to which health economic information is used in health policy decision-making in the UK, and to consider factors associated with the utilisation of such research findings. Major electronic databases were searched up to 2004. A systematic review of existing reviews on the use of economic evaluations in policy decision-making, of health and non-health literature on the use of economic analyses in policy making and of studies identifying actual or perceived barriers to the use of economic evaluations was undertaken. Five UK case studies of committees from four local and one national organisation [the Technology Appraisal Committee of the National Institute for Health and Clinical Excellence (NICE)] were conducted. Local case studies were augmented by documentary analysis of new technology request forms and by workshop discussions with members of local decision-making committees. The systematic review demonstrated few previous systematic reviews of evidence in the area. At the local level in the NHS, it was an exception for economic evaluation to inform technology coverage decisions. Local decision-making focused primarily on evidence of clinical benefit and cost implications. And whilst information on implementation was frequently requested, cost-effectiveness information was rarely accessed. A number of features of the decision-making environment appeared to militate against emphasis on cost-effectiveness analysis. Constraints on the capacity to generate, access and interpret information, led to a minor role for cost-effectiveness analysis in the local decision-making process. At the national policy level in the UK, economic analysis was found to be highly integrated into NICE's technology appraisal programme. Attitudes to economic evaluation varied between committee members with some significant disagreement and extraneous factors diluted the health economics analysis available to the committee. There was strong evidence of an ordinal approach to consideration of clinical effectiveness and cost-effectiveness information. Some interviewees considered the key role of a cost-effectiveness analysis to be the provision of a framework for decision-making. Interviewees indicated that NICE makes use of some form of cost-effectiveness threshold but expressed concern about its basis and its use in decision-making. Frustrations with the appraisal process were expressed in terms of the scope of the policy question being addressed. Committee members raised concerns about lack of understanding of the economic analysis but felt that a single measure of benefit, e.g. the quality-adjusted life-year, was useful in allowing comparison of disparate health interventions and in providing a benchmark for later decisions. The importance of ensuring that committee members understood the limitations of the analysis was highlighted for model-based analyses. This study suggests that research is needed into structures, processes and mechanisms by which technology coverage decisions can and should be made in healthcare. Further development of 'resource centres' may be useful to provide independent published analyses in order to support local decision-makers. Improved methods of economic analyses and of their presentation, which take account of the concerns of their users, are needed. Finally, the findings point to the need for further assessment of the feasibility and value of a formal process of clarification of the objectives that we seek from investments in healthcare.

Centralized Analysis of Local Data, With Dollars and Lives on the Line: Lessons From The Home Radon Experience

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

Price, PhillipN.; Gelman, Andrew

2014-11-24

In this chapter we elucidate four main themes. The first is that modern data analyses, including "Big Data" analyses, often rely on data from different sources, which can present challenges in constructing statistical models that can make effective use of all of the data. The second theme is that although data analysis is usually centralized, frequently the final outcome is to provide information or allow decision-making for individuals. Third, data analyses often have multiple uses by design: the outcomes of the analysis are intended to be used by more than one person or group, for more than one purpose. Finally,more » issues of privacy and confidentiality can cause problems in more subtle ways than are usually considered; we will illustrate this point by discussing a case in which there is substantial and effective political opposition to simply acknowledging the geographic distribution of a health hazard. A researcher analyzes some data and learns something important. What happens next? What does it take for the results to make a difference in people's lives? In this chapter we tell a story - a true story - about a statistical analysis that should have changed government policy, but didn't. The project was a research success that did not make its way into policy, and we think it provides some useful insights into the interplay between locally-collected data, statistical analysis, and individual decision making.« less

The goal of making friends for youth with disabilities: creating a goal menu.

PubMed

Gerhardt, S; McCallum, A; McDougall, C; Keenan, S; Rigby, P

2015-11-01

Clinicians working with youth with disabilities have acknowledged making friends as a commonly identified client goal. Clinicians find this goal difficult to address, as there are no measures that provide a breakdown of making friends into functional steps. In addition, research on friendship has traditionally focused on characteristics and quality of friendships rather than the friend-making process as a whole. A goal menu, comprised of a variety of steps that address the goal of making friends, would provide guidance to clinicians challenged with this goal in practice. To develop an understanding of the friend-making process as a first step towards the development of a goal menu for the goal of making friends. A literature review, youth focus group and expert clinician semi-structured interviews and consultation were used to generate a comprehensive data set. Established qualitative methods were used to sort and group the data into categories. A thematic analysis of the categories was performed. Analysis revealed four themes integral to the friend-making process: person factors influencing friend-making, making friend-making a priority, opportunity for friend-making and motivation to make friends. An additional theme identified as occasionally involved in the process was a little bit of luck in making friends. The themes generated by this research indicate that actionable target areas exist for the somewhat abstract notion of friend-making and the authors recommend that clinicians explore beyond person factors when addressing the goal of making friends. As a next step, the identified themes will provide the foundation for a goal menu, ultimately enabling clinicians to address the goal of making friends in a more efficient and effective manner. © 2015 John Wiley & Sons Ltd.

Risky decision making in Attention-Deficit/Hyperactivity Disorder: A meta-regression analysis.

PubMed

Dekkers, Tycho J; Popma, Arne; Agelink van Rentergem, Joost A; Bexkens, Anika; Huizenga, Hilde M

2016-04-01

ADHD has been associated with various forms of risky real life decision making, for example risky driving, unsafe sex and substance abuse. However, results from laboratory studies on decision making deficits in ADHD have been inconsistent, probably because of between study differences. We therefore performed a meta-regression analysis in which 37 studies (n ADHD=1175; n Control=1222) were included, containing 52 effect sizes. The overall analysis yielded a small to medium effect size (standardized mean difference=.36, p<.001, 95% CI [.22, .51]), indicating that groups with ADHD showed more risky decision making than control groups. There was a trend for a moderating influence of co-morbid Disruptive Behavior Disorders (DBD): studies including more participants with co-morbid DBD had larger effect sizes. No moderating influence of co-morbid internalizing disorders, age or task explicitness was found. These results indicate that ADHD is related to increased risky decision making in laboratory settings, which tended to be more pronounced if ADHD is accompanied by DBD. We therefore argue that risky decision making should have a more prominent role in research on the neuropsychological and -biological mechanisms of ADHD, which can be useful in ADHD assessment and intervention. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gender and internet consumers' decision-making.

PubMed

Yang, Chyan; Wu, Chia-Chun

2007-02-01

The purpose of this research is to provide managers of shopping websites information regarding consumer purchasing decisions based on the Consumer Styles Inventory (CSI). According to the CSI, one can capture what decision-making styles online shoppers use. Furthermore, this research also discusses the gender differences among online shoppers. Exploratory factor analysis (EFA) was used to understand the decision-making styles and discriminant analysis was used to distinguish the differences between female and male shoppers. The result shows that there are differences in purchasing decisions between online female and male Internet users.

A Multimethod Analysis of Shared Decision-Making in Hospice Interdisciplinary Team Meetings Including Family Caregivers

PubMed Central

Washington, Karla T.; Oliver, Debra Parker; Gage, L. Ashley; Albright, David L.; Demiris, George

2015-01-01

Background Much of the existing research on shared decision-making in hospice and palliative care focuses on the provider-patient dyad; little is known about shared decision-making that is inclusive of family members of patients with advanced disease. Aim We sought to describe shared decision-making as it occurred in hospice interdisciplinary team meetings that included family caregivers as participants using video-conferencing technology. Design We conducted a multimethod study in which we used content and thematic analysis techniques to analyze video-recordings of hospice interdisciplinary team meetings (n = 100), individual interviews of family caregivers (n = 73) and hospice staff members (n = 78), and research field notes. Setting/participants Participants in the original studies from which data for this analysis were drawn were hospice family caregivers and staff members employed by one of five different community-based hospice agencies located in the Midwestern United States. Results Shared decision-making occurred infrequently in hospice interdisciplinary team meetings that included family caregivers. Barriers to shared decision-making included time constraints, communication skill deficits, unaddressed emotional needs, staff absences, and unclear role expectations. The hospice philosophy of care, current trends in health care delivery, the interdisciplinary nature of hospice teams, and the designation of a team leader/facilitator supported shared decision-making. Conclusions The involvement of family caregivers in hospice interdisciplinary team meetings using video-conferencing technology creates a useful platform for shared decision-making; however, steps must be taken to transform family caregivers from meeting attendees to shared decision-makers. PMID:26281854

A multimethod analysis of shared decision-making in hospice interdisciplinary team meetings including family caregivers.

PubMed

Washington, Karla T; Oliver, Debra Parker; Gage, L Ashley; Albright, David L; Demiris, George

2016-03-01

Much of the existing research on shared decision-making in hospice and palliative care focuses on the provider-patient dyad; little is known about shared decision-making that is inclusive of family members of patients with advanced disease. We sought to describe shared decision-making as it occurred in hospice interdisciplinary team meetings that included family caregivers as participants using video-conferencing technology. We conducted a multimethod study in which we used content and thematic analysis techniques to analyze video-recordings of hospice interdisciplinary team meetings (n = 100), individual interviews of family caregivers (n = 73) and hospice staff members (n = 78), and research field notes. Participants in the original studies from which data for this analysis were drawn were hospice family caregivers and staff members employed by one of five different community-based hospice agencies located in the Midwestern United States. Shared decision-making occurred infrequently in hospice interdisciplinary team meetings that included family caregivers. Barriers to shared decision-making included time constraints, communication skill deficits, unaddressed emotional needs, staff absences, and unclear role expectations. The hospice philosophy of care, current trends in healthcare delivery, the interdisciplinary nature of hospice teams, and the designation of a team leader/facilitator supported shared decision-making. The involvement of family caregivers in hospice interdisciplinary team meetings using video-conferencing technology creates a useful platform for shared decision-making; however, steps must be taken to transform family caregivers from meeting attendees to shared decision-makers. © The Author(s) 2015.

The illusion of handy wins: Problem gambling, chasing, and affective decision-making.

PubMed

Nigro, Giovanna; Ciccarelli, Maria; Cosenza, Marina

2018-01-01

Chasing losses is a behavioral marker and a diagnostic criterion for gambling disorder. It consists in continuing gambling to recoup previous losses. Although chasing has been recognized playing a central role in gambling disorder, research on this topic is relatively scarce, and it remains unclear whether chasing affects decision-making in behavioral tasks in which participants gain or loss some money. Even if several studies found that the more the gambling involvement, the poorer the decision-making, to date no research investigated the role of chasing in decision-making. The study aimed to first investigate the relation between chasing and decision-making in adult gamblers. One hundred and four VLT players were administered the South Oaks Gambling Screen (SOGS), a computerized task measuring chasing, and the Iowa Gambling Task (IGT). Correlation analysis showed that the higher the SOGS scores, the higher the propensity to chase, and the poorer the decision-making performance. Regression analysis revealed that chasing propensity and gambling severity predicted IGT performance. Mediation analysis indicated that the association between gambling severity and poor decision-making is mediated by chasing. Gambling severity was assessed by means of a self-report measure. The generalizability of findings is limited, since the study focused only on VLT players. This study provides the first evidence that chasing, along with gambling severity, affects decision-making, at least in behavioral tasks involving money. Since chasers and non-chasers could be two different sub-types of gamblers, treatment protocols should take into account the additive role of chasing in gambling disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

Language Policy-Making in the Free State: An Analysis of Language Policy Activities between 1994 and 2007

ERIC Educational Resources Information Center

Mathebula, Nikiwe; du Plessis, Theodorus

2010-01-01

This paper critically describes the process of language policy-making in the Free State province of South Africa since 1994, based on an adapted version of the "streams approach" to policy-making. Three policy-making phases are identified, namely a first phase under the Free State Provincial Language Committee; a second phase under the…

Averse to Initiative: Risk Management’s Effect on Mission Command

DTIC Science & Technology

2017-05-25

military decision making process (MDMP). Other changes to structure reveal administrative and safety risk information (i.e. personal operated vehicle... decision making , it requires commanders to have the capacity to make an informed , intuitive decision . Uncertainty...analysis. His situation required him to embrace uncertainty, and exercise an informed intuition to make a risk decision to create opportunity

Hospice decision making: diagnosis makes a difference.

PubMed

Waldrop, Deborah P; Meeker, Mary Ann

2012-10-01

This study explored the process of decision making about hospice enrollment and identified factors that influence the timing of that decision. This study employed an exploratory, descriptive, cross-sectional design and was conducted using qualitative methods. In-depth in-person semistructured interviews were conducted with 36 hospice patients and 55 caregivers after 2 weeks of hospice care. The study was guided by Janis and Mann's conflict theory model (CTM) of decision making. Qualitative data analysis involved a directed content analysis using concepts from the CTM. A model of hospice enrollment decision making is presented. Concepts from the CTM (appraisal, surveying and weighing the alternatives, deliberations, adherence) were used as an organizing framework to illustrate the dynamics. Distinct differences were found by diagnosis (cancer vs. other chronic illness, e.g., heart and lung diseases) during the pre-encounter phase or before the hospice referral but no differences emerged during the post-encounter phase. Differences in decision making by diagnosis suggest the need for research about effective means for tailored communication in end-of-life decision making by type of illness. Recognition that decision making about hospice admission varies is important for clinicians who aim to provide person-centered and family-focused care.

Meaning Making through Multiple Modalities in a Biology Classroom: A Multimodal Semiotics Discourse Analysis

ERIC Educational Resources Information Center

Jaipal, Kamini

2010-01-01

The teaching of science is a complex process, involving the use of multiple modalities. This paper illustrates the potential of a multimodal semiotics discourse analysis framework to illuminate meaning-making possibilities during the teaching of a science concept. A multimodal semiotics analytical framework is developed and used to (1) analyze the…

Food Purchase Decision-Making Typologies of Women with Non-Insulin-Dependent Diabetes Mellitus.

ERIC Educational Resources Information Center

Miller, Carla; Warland, Rex; Achterberg, Cheryl

1997-01-01

Food selection is a key factor in the nutritional management of diabetes. Criteria that influence point-of-purchase decision making in women with non-insulin-dependent diabetes mellitus were identified. Four types of shoppers were distinguished from interviews; cluster analysis was used to confirm the analysis. Usefulness in patient education is…

Citizen Participation in Politics: The Role of the Jury

ERIC Educational Resources Information Center

Jacobsohn, Gary J.

1977-01-01

Investigates the manner in which petit juries participate in the formulation of public policy. Of central concern is the nature of jury policy-making, involving analysis of ways in which such policy-making is manifested, and the description of a conceptual framework for political analysis of the jury. For journal availability, see SO 505 536.…

Cost Analysis of Instructional Technology.

ERIC Educational Resources Information Center

Johnson, F. Craig; Dietrich, John E.

Although some serious limitations in the cost analysis technique do exist, the need for cost data in decision making is so great that every effort should be made to obtain accurate estimates. This paper discusses the several issues which arise when an attempt is made to make quality, trade-off, or scope decisions based on cost data. Three methods…

Analysis of a bubble deformation process in a microcapsule by shock waves for developing DDS

NASA Astrophysics Data System (ADS)

Tamagawa, Masaaki; Morimoto, Kenshi

2012-09-01

This paper describes development of DDS (drug delivery systems) microcapsule using underwater shock waves, especially (1) making polymer microcapsules including a bubble and analysis of a bubble deformation process in a polymer capsule by pressure wave, (2) making liposome microcapsules with different elastic membrane and disintegration tests by ultrasonic waves.

Decision-Making, Information Communication Technology, and Data Analysis by School Leaders about Student Achievement

ERIC Educational Resources Information Center

Akoma, Ahunna Margaux

2012-01-01

This case study of one school district examined how school leaders use student performance data and technology-based data analysis tools to engage in data-informed decision-making for continuous improvement. School leaders in this context included leaders at the district, school, and classroom levels. An extensive literature review provided the…

Dynamics of individual perceptual decisions

PubMed Central

Clark, Torin K.; Lu, Yue M.; Karmali, Faisal

2015-01-01

Perceptual decision making is fundamental to a broad range of fields including neurophysiology, economics, medicine, advertising, law, etc. Although recent findings have yielded major advances in our understanding of perceptual decision making, decision making as a function of time and frequency (i.e., decision-making dynamics) is not well understood. To limit the review length, we focus most of this review on human findings. Animal findings, which are extensively reviewed elsewhere, are included when beneficial or necessary. We attempt to put these various findings and data sets, which can appear to be unrelated in the absence of a formal dynamic analysis, into context using published models. Specifically, by adding appropriate dynamic mechanisms (e.g., high-pass filters) to existing models, it appears that a number of otherwise seemingly disparate findings from the literature might be explained. One hypothesis that arises through this dynamic analysis is that decision making includes phasic (high pass) neural mechanisms, an evidence accumulator and/or some sort of midtrial decision-making mechanism (e.g., peak detector and/or decision boundary). PMID:26467513

Decision Making in Nursing Practice: A Concept Analysis.

PubMed

Johansen, Mary L; O'Brien, Janice L

2016-01-01

The study aims to gain an understanding of the concept of decision making as it relates to the nurse practice environment. Rodgers' evolutionary method on concept analysis was used as a framework for the study of the concept. Articles from 1952 to 2014 were reviewed from PsycINFO, Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), JSTOR, PubMed, and Science Direct. Findings suggest that decision making in the nurse practice environment is a complex process, integral to the nursing profession. The definition of decision making, and the attributes, antecedents, and consequences, are discussed. Contextual factors that influence the process are also discussed. An exemplar is presented to illustrate the concept. Decision making in the nurse practice environment is a dynamic conceptual process that may affect patient outcomes. Nurses need to call upon ways of knowing to make sound decisions and should be self-reflective in order to develop the process further in the professional arena. The need for further research is discussed. © 2015 Wiley Periodicals, Inc.

Iranian Nurses’ Status in Policymaking for Nursing in Health System: A Qualitative Content Analysis

PubMed Central

Cheraghi, Mohammad Ali; Ghiyasvandian, Shahrzad; Aarabi, Akram

2015-01-01

Presence of nurses in policy making will result improvement of nursing practice, and increase qualification of patients’ care, but still few nurses are involved in policy debates and health reforms and their status in policy making for nursing is not clear. The aim of this study was to elucidate Iranian nurses’ status in policy making for nursing in health system. This is a qualitative study. Using purposive sampling 22 participants were interviewed to gain deep understanding from the phenomenon of status of nurses in policy making. Of these 2 were not nurses but the members of Iran’s council for health policy making. Data were analyzed by employing conventional content analysis. Nurses’ status in policy making declared base on the implications of three main themes including “the policy making framework”, “perceived status of nurses in policy making”, and “the manner of nurses’ participation in policy making”. The conclusion of the present study is that Policy making for nursing is a subcategory of Iran’s macro health policies. What made the status of nurses more efficient in policy making for nursing was their practice and rate of participation in the appointed positions and the society. Results of this study represented major points of weakness in nursing policies and some recommendations for modifications. PMID:26089996

A Benefit-Risk Analysis Approach to Capture Regulatory Decision-Making: Non-Small Cell Lung Cancer.

PubMed

Raju, G K; Gurumurthi, K; Domike, R; Kazandjian, D; Blumenthal, G; Pazdur, R; Woodcock, J

2016-12-01

Drug regulators around the world make decisions about drug approvability based on qualitative benefit-risk analyses. There is much interest in quantifying regulatory approaches to benefit and risk. In this work the use of a quantitative benefit-risk analysis was applied to regulatory decision-making about new drugs to treat advanced non-small cell lung cancer (NSCLC). Benefits and risks associated with 20 US Food and Drug Administration (FDA) decisions associated with a set of candidate treatments submitted between 2003 and 2015 were analyzed. For benefit analysis, the median overall survival (OS) was used where available. When not available, OS was estimated based on overall response rate (ORR) or progression-free survival (PFS). Risks were analyzed based on magnitude (or severity) of harm and likelihood of occurrence. Additionally, a sensitivity analysis was explored to demonstrate analysis of systematic uncertainty. FDA approval decision outcomes considered were found to be consistent with the benefit-risk logic. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Physics faculty beliefs and values about the teaching and learning of problem solving. II. Procedures for measurement and analysis

NASA Astrophysics Data System (ADS)

Henderson, Charles; Yerushalmi, Edit; Kuo, Vince H.; Heller, Kenneth; Heller, Patricia

2007-12-01

To identify and describe the basis upon which instructors make curricular and pedagogical decisions, we have developed an artifact-based interview and an analysis technique based on multilayered concept maps. The policy capturing technique used in the interview asks instructors to make judgments about concrete instructional artifacts similar to those they likely encounter in their teaching environment. The analysis procedure alternatively employs both an a priori systems view analysis and an emergent categorization to construct a multilayered concept map, which is a hierarchically arranged set of concept maps where child maps include more details than parent maps. Although our goal was to develop a model of physics faculty beliefs about the teaching and learning of problem solving in the context of an introductory calculus-based physics course, the techniques described here are applicable to a variety of situations in which instructors make decisions that influence teaching and learning.

Multi-criteria decision making to support waste management: A critical review of current practices and methods.

PubMed

Goulart Coelho, Lineker M; Lange, Liséte C; Coelho, Hosmanny Mg

2017-01-01

Solid waste management is a complex domain involving the interaction of several dimensions; thus, its analysis and control impose continuous challenges for decision makers. In this context, multi-criteria decision-making models have become important and convenient supporting tools for solid waste management because they can handle problems involving multiple dimensions and conflicting criteria. However, the selection of the multi-criteria decision-making method is a hard task since there are several multi-criteria decision-making approaches, each one with a large number of variants whose applicability depends on information availability and the aim of the study. Therefore, to support researchers and decision makers, the objectives of this article are to present a literature review of multi-criteria decision-making applications used in solid waste management, offer a critical assessment of the current practices, and provide suggestions for future works. A brief review of fundamental concepts on this topic is first provided, followed by the analysis of 260 articles related to the application of multi-criteria decision making in solid waste management. These studies were investigated in terms of the methodology, including specific steps such as normalisation, weighting, and sensitivity analysis. In addition, information related to waste type, the study objective, and aspects considered was recorded. From the articles analysed it is noted that studies using multi-criteria decision making in solid waste management are predominantly addressed to problems related to municipal solid waste involving facility location or management strategy.

My Lived Experiences Are More Important Than Your Probabilities: The Role of Individualized Risk Estimates for Decision Making about Participation in the Study of Tamoxifen and Raloxifene (STAR).

PubMed

Holmberg, Christine; Waters, Erika A; Whitehouse, Katie; Daly, Mary; McCaskill-Stevens, Worta

2015-11-01

Decision-making experts emphasize that understanding and using probabilistic information are important for making informed decisions about medical treatments involving complex risk-benefit tradeoffs. Yet empirical research demonstrates that individuals may not use probabilities when making decisions. To explore decision making and the use of probabilities for decision making from the perspective of women who were risk-eligible to enroll in the Study of Tamoxifen and Raloxifene (STAR). We conducted narrative interviews with 20 women who agreed to participate in STAR and 20 women who declined. The project was based on a narrative approach. Analysis included the development of summaries of each narrative, and thematic analysis with developing a coding scheme inductively to code all transcripts to identify emerging themes. Interviewees explained and embedded their STAR decisions within experiences encountered throughout their lives. Such lived experiences included but were not limited to breast cancer family history, a personal history of breast biopsies, and experiences or assumptions about taking tamoxifen or medicines more generally. Women's explanations of their decisions about participating in a breast cancer chemoprevention trial were more complex than decision strategies that rely solely on a quantitative risk-benefit analysis of probabilities derived from populations In addition to precise risk information, clinicians and risk communicators should recognize the importance and legitimacy of lived experience in individual decision making. © The Author(s) 2015.

FRAMEWORK FOR ENVIRONMENTAL DECISION-MAKING, FRED: A TOOL FOR ENVIRONMENTALLY-PREFERABLE PURCHASING

EPA Science Inventory

In support of the Environmentally Preferable Purchasing Program of the US EPA, the Systems Analysis Branch has developed a decision-making tool based on life cycle assessment. This tool, the Framework for Responsible Environmental Decision-making or FRED streamlines LCA by choosi...

The effect of uncertainties in distance-based ranking methods for multi-criteria decision making

NASA Astrophysics Data System (ADS)

Jaini, Nor I.; Utyuzhnikov, Sergei V.

2017-08-01

Data in the multi-criteria decision making are often imprecise and changeable. Therefore, it is important to carry out sensitivity analysis test for the multi-criteria decision making problem. The paper aims to present a sensitivity analysis for some ranking techniques based on the distance measures in multi-criteria decision making. Two types of uncertainties are considered for the sensitivity analysis test. The first uncertainty is related to the input data, while the second uncertainty is towards the Decision Maker preferences (weights). The ranking techniques considered in this study are TOPSIS, the relative distance and trade-off ranking methods. TOPSIS and the relative distance method measure a distance from an alternative to the ideal and antiideal solutions. In turn, the trade-off ranking calculates a distance of an alternative to the extreme solutions and other alternatives. Several test cases are considered to study the performance of each ranking technique in both types of uncertainties.

Web-based visual analysis for high-throughput genomics

PubMed Central

2013-01-01

Background Visualization plays an essential role in genomics research by making it possible to observe correlations and trends in large datasets as well as communicate findings to others. Visual analysis, which combines visualization with analysis tools to enable seamless use of both approaches for scientific investigation, offers a powerful method for performing complex genomic analyses. However, there are numerous challenges that arise when creating rich, interactive Web-based visualizations/visual analysis applications for high-throughput genomics. These challenges include managing data flow from Web server to Web browser, integrating analysis tools and visualizations, and sharing visualizations with colleagues. Results We have created a platform simplifies the creation of Web-based visualization/visual analysis applications for high-throughput genomics. This platform provides components that make it simple to efficiently query very large datasets, draw common representations of genomic data, integrate with analysis tools, and share or publish fully interactive visualizations. Using this platform, we have created a Circos-style genome-wide viewer, a generic scatter plot for correlation analysis, an interactive phylogenetic tree, a scalable genome browser for next-generation sequencing data, and an application for systematically exploring tool parameter spaces to find good parameter values. All visualizations are interactive and fully customizable. The platform is integrated with the Galaxy (http://galaxyproject.org) genomics workbench, making it easy to integrate new visual applications into Galaxy. Conclusions Visualization and visual analysis play an important role in high-throughput genomics experiments, and approaches are needed to make it easier to create applications for these activities. Our framework provides a foundation for creating Web-based visualizations and integrating them into Galaxy. Finally, the visualizations we have created using the framework are useful tools for high-throughput genomics experiments. PMID:23758618

Safety Assessment of Dangerous Goods Transport Enterprise Based on the Relative Entropy Aggregation in Group Decision Making Model

PubMed Central

Wu, Jun; Li, Chengbing; Huo, Yueying

2014-01-01

Safety of dangerous goods transport is directly related to the operation safety of dangerous goods transport enterprise. Aiming at the problem of the high accident rate and large harm in dangerous goods logistics transportation, this paper took the group decision making problem based on integration and coordination thought into a multiagent multiobjective group decision making problem; a secondary decision model was established and applied to the safety assessment of dangerous goods transport enterprise. First of all, we used dynamic multivalue background and entropy theory building the first level multiobjective decision model. Secondly, experts were to empower according to the principle of clustering analysis, and combining with the relative entropy theory to establish a secondary rally optimization model based on relative entropy in group decision making, and discuss the solution of the model. Then, after investigation and analysis, we establish the dangerous goods transport enterprise safety evaluation index system. Finally, case analysis to five dangerous goods transport enterprises in the Inner Mongolia Autonomous Region validates the feasibility and effectiveness of this model for dangerous goods transport enterprise recognition, which provides vital decision making basis for recognizing the dangerous goods transport enterprises. PMID:25477954

Safety assessment of dangerous goods transport enterprise based on the relative entropy aggregation in group decision making model.

PubMed

Wu, Jun; Li, Chengbing; Huo, Yueying

2014-01-01

Safety of dangerous goods transport is directly related to the operation safety of dangerous goods transport enterprise. Aiming at the problem of the high accident rate and large harm in dangerous goods logistics transportation, this paper took the group decision making problem based on integration and coordination thought into a multiagent multiobjective group decision making problem; a secondary decision model was established and applied to the safety assessment of dangerous goods transport enterprise. First of all, we used dynamic multivalue background and entropy theory building the first level multiobjective decision model. Secondly, experts were to empower according to the principle of clustering analysis, and combining with the relative entropy theory to establish a secondary rally optimization model based on relative entropy in group decision making, and discuss the solution of the model. Then, after investigation and analysis, we establish the dangerous goods transport enterprise safety evaluation index system. Finally, case analysis to five dangerous goods transport enterprises in the Inner Mongolia Autonomous Region validates the feasibility and effectiveness of this model for dangerous goods transport enterprise recognition, which provides vital decision making basis for recognizing the dangerous goods transport enterprises.

Data warehouse model design technology analysis and research

NASA Astrophysics Data System (ADS)

Jiang, Wenhua; Li, Qingshui

2012-01-01

Existing data storage format can not meet the needs of information analysis, data warehouse onto the historical stage, the data warehouse is to support business decision making and the creation of specially designed data collection. With the data warehouse, the companies will all collected information is stored in the data warehouse. The data warehouse is organized according to some, making information easy to access and has value. This paper focuses on the establishment of data warehouse and analysis, design, data warehouse, two barrier models, and compares them.

A Statistical Analysis of the Effect of the Navy’s Tuition Assistance Program: Do Distance Learning Classes Make a Difference?

DTIC Science & Technology

2010-03-01

ANALYSIS OF THE EFFECT OF THE NAVY’S TUITION ASSISTANCE PROGRAM : DO DISTANCE LEARNING CLASSES MAKE A DIFFERENCE? by Jeremy P. McLaughlin March...TYPE AND DATES COVERED Master’s Thesis 4. TITLE AND SUBTITLE A Statistical Analysis of the Effect of the Navy’s Tuition Assistance Program : Do...200 words) This thesis analyzes the impact of participation in the Navy’s Tuition Assistance (TA) program on the retention of first-term Navy

Decision Making Analysis: Critical Factors-Based Methodology

DTIC Science & Technology

2010-04-01

the pitfalls associated with current wargaming methods such as assuming a western view of rational values in decision - making regardless of the cultures...Utilization theory slightly expands the rational decision making model as it states that “actors try to maximize their expected utility by weighing the...items to categorize the decision - making behavior of political leaders which tend to demonstrate either a rational or cognitive leaning. Leaders

Couple decision making and use of cultural scripts in Malawi.

PubMed

Mbweza, Ellen; Norr, Kathleen F; McElmurry, Beverly

2008-01-01

To examine the decision-making processes of husband and wife dyads in matrilineal and patrilineal marriage traditions of Malawi in the areas of money, food, pregnancy, contraception, and sexual relations. Qualitative grounded theory using simultaneous interviews of 60 husbands and wives (30 couples). Data were analyzed according to the guidelines of simultaneous data collection and analysis. The analysis resulted in development of core categories and categories of decision-making process. Data matrixes were used to identify similarities and differences within couples and across cases. Most couples reported using a mix of final decision-making approaches: husband-dominated, wife-dominated, and shared. Gender based and nongender based cultural scripts provided rationales for their approaches to decision making. Gender based cultural scripts (husband-dominant and wife-dominant) were used to justify decision-making approaches. Non-gender based cultural scripts (communicating openly, maintaining harmony, and children's welfare) supported shared decision making. Gender based cultural scripts were used in decision making more often among couples from the district with a patrilineal marriage tradition and where the husband had less than secondary school education and was not formally employed. Nongender based cultural scripts to encourage shared decision making can be used in designing culturally tailored reproductive health interventions for couples. Nurses who work with women and families should be aware of the variations that occur in actual couple decision-making approaches. Shared decision making can be used to encourage the involvement of men in reproductive health programs.

Early Design Energy Analysis Using Building Information Modeling Technology

DTIC Science & Technology

2011-11-01

building, (a) floor plan and (b) 3D image. ....................................... 50 Figure 28. Comparison of different energy estimates...when they make the biggest impact on building life-cycle costs. Traditionally, most building energy analyses have been conducted late in design, by...complete energy analysis. This method enables project teams to make energy conscious decisions early in design when they impact building life-cycle

Analysis of Decision Making Skills for Large Scale Disaster Response

DTIC Science & Technology

2015-08-21

Capability to influence and collaborate Compassion Teamwork Communication Leadership Provide vision of outcome / set priorities Confidence, courage to make...project evaluates the viability of expanding the use of serious games to augment classroom training, tabletop and full scale exercise, and actual...training, evaluation, analysis, and technology ex- ploration. Those techniques have found successful niches, but their wider applicability faces

Aspects of First Year Statistics Students' Reasoning When Performing Intuitive Analysis of Variance: Effects of Within- and Between-Group Variability

ERIC Educational Resources Information Center

Trumpower, David L.

2015-01-01

Making inferences about population differences based on samples of data, that is, performing intuitive analysis of variance (IANOVA), is common in everyday life. However, the intuitive reasoning of individuals when making such inferences (even following statistics instruction), often differs from the normative logic of formal statistics. The…

Nursing Faculty Decision Making about Best Practices in Test Construction, Item Analysis, and Revision

ERIC Educational Resources Information Center

Killingsworth, Erin Elizabeth

2013-01-01

With the widespread use of classroom exams in nursing education there is a great need for research on current practices in nursing education regarding this form of assessment. The purpose of this study was to explore how nursing faculty members make decisions about using best practices in classroom test construction, item analysis, and revision in…

A Grounded Theory Approach to the Development of a Framework for Researching Children's Decision-Making Skills within Design and Technology Education

ERIC Educational Resources Information Center

Mettas, Alexandros; Norman, Eddie

2011-01-01

This paper discusses the establishment of a framework for researching children's decision-making skills in design and technology education through taking a grounded theory approach. Three data sources were used: (1) analysis of available literature; (2) curriculum analysis and interviews with teachers concerning their practice in relation to their…

Advanced Productivity Analysis Methods for Air Traffic Control Operations

DTIC Science & Technology

1976-12-01

Routine Work ............................... 37 4.2.2. Surveillance Work .......................... 40 4.2.3. Conflict Prcessing Work ................... 41...crossing and overtake conflicts) includes potential- conflict recognition, assessment, and resolution decision making and A/N voice communications...makers to utilize £ .quantitative and dynamic analysis as a tool for decision - making. 1.1.3 Types of Simulation Models Although there are many ways to

21 CFR 312.84 - Risk-benefit analysis in review of marketing applications for drugs to treat life-threatening and...

Code of Federal Regulations, 2010 CFR

2010-04-01

... making the final decision on approvability. As part of this evaluation, consistent with the statement of.... (b) In making decisions on whether to grant marketing approval for products that have been the... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Risk-benefit analysis in review of marketing...

Graduate Education in Risk Analysis for Food, Agriculture, and Veterinary Medicine: Challenges and Opportunities

ERIC Educational Resources Information Center

Correia, Ana-Paula; Wolt, Jeffrey D.

2010-01-01

The notion of risk in relation to food and food production has heightened the need to educate students to effectively deal with risk in relation to decision making from a science-based perspective. Curricula and related materials were developed and adopted to support graduate learning opportunities in risk analysis and decision making as applied…

Decision-Making Phenomena Described by Expert Nurses Working in Urban Community Health Settings.

ERIC Educational Resources Information Center

Watkins, Mary P.

1998-01-01

Expert community health nurses (n=28) described crucial clinical situations. Content analysis revealed that decision making was both rational and intuitive. Eight themes were identified: decision-making focus, type, purpose, decision-maker characteristics, sequencing of events, data collection methods, facilitators/barriers, and decision-making…

A Critical Analysis of HRD Evaluation Models from a Decision-Making Perspective

ERIC Educational Resources Information Center

Holton, Elwood F., III; Naquin, Sharon

2005-01-01

HRD evaluation models are recommended for use by organizations to improve decisions made about HRD interventions. However, the organizational decision-making literature has been virtually ignored by evaluation researchers. In this article, we review the organizational decision-making literature and critically review HRD evaluation research through…

School-Based Decision Making: A Principal-Agent Perspective.

ERIC Educational Resources Information Center

Ferris, James M.

1992-01-01

A principal-agent framework is used to examine potential gains in educational performance and potential threats to public accountability that school-based decision-making proposals pose. Analysis underscores the need to tailor the design of decentralized decision making to the sources of poor educational performance and threats to school…

Modelling elderly cardiac patients decision making using Cognitive Work Analysis: identifying requirements for patient decision aids.

PubMed

Dhukaram, Anandhi Vivekanandan; Baber, Chris

2015-06-01

Patients make various healthcare decisions on a daily basis. Such day-to-day decision making can have significant consequences on their own health, treatment, care, and costs. While decision aids (DAs) provide effective support in enhancing patient's decision making, to date there have been few studies examining patient's decision making process or exploring how the understanding of such decision processes can aid in extracting requirements for the design of DAs. This paper applies Cognitive Work Analysis (CWA) to analyse patient's decision making in order to inform requirements for supporting self-care decision making. This study uses focus groups to elicit information from elderly cardiovascular disease (CVD) patients concerning a range of decision situations they face on a daily basis. Specifically, the focus groups addressed issues related to the decision making of CVD in terms of medication compliance, pain, diet and exercise. The results of these focus groups are used to develop high level views using CWA. CWA framework decomposes the complex decision making problem to inform three approaches to DA design: one design based on high level requirements; one based on a normative model of decision-making for patients; and the third based on a range of heuristics that patients seem to use. CWA helps in extracting and synthesising decision making from different perspectives: decision processes, work organisation, patient competencies and strategies used in decision making. As decision making can be influenced by human behaviour like skills, rules and knowledge, it is argued that patients require support to different types of decision making. This paper also provides insights for designers in using CWA framework for the design of effective DAs to support patients in self-management. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Are Sex Effects on Ethical Decision-Making Fake or Real? A Meta-Analysis on the Contaminating Role of Social Desirability Response Bias.

PubMed

Yang, Jianfeng; Ming, Xiaodong; Wang, Zhen; Adams, Susan M

2017-02-01

A meta-analysis of 143 studies was conducted to explore how the social desirability response bias may influence sex effects on ratings on measures of ethical decision-making. Women rated themselves as more ethical than did men; however, this sex effect on ethical decision-making was no longer significant when social desirability response bias was controlled. The indirect questioning approach was compared with the direct measurement approach for effectiveness in controlling social desirability response bias. The indirect questioning approach was found to be more effective.

Decision-making in rectal and colorectal cancer: systematic review and qualitative analysis of surgeons' preferences.

PubMed

Broc, Guillaume; Gana, Kamel; Denost, Quentin; Quintard, Bruno

2017-04-01

Surgeons are experiencing difficulties implementing recommendations not only owing to incomplete, confusing or conflicting information but also to the increasing involvement of patients in decisions relating to their health. This study sought to establish which common factors including heuristic factors guide surgeons' decision-making in colon and rectal cancers. We conducted a systematic literature review of surgeons' decision-making factors related to colon and rectal cancer treatment. Eleven of 349 identified publications were eligible for data analyses. Using the IRaMuTeQ (Interface of R for the Multidimensional Analyses of Texts and Questionnaire), we carried out a qualitative analysis of the significant factors collected in the studies reviewed. Several validation procedures were applied to control the robustness of the findings. Five categories of factors (i.e. patient, surgeon, treatment, tumor and organizational cues) were found to influence surgeons' decision-making. Specifically, all decision criteria including biomedical (e.g. tumor information) and heuristic (e.g. surgeons' dispositional factors) criteria converged towards the factor 'age of patient' in the similarity analysis. In the light of the results, we propose an explanatory model showing the impact of heuristic criteria on medical issues (i.e. diagnosis, prognosis, treatment features, etc.) and thus on decision-making. Finally, the psychosocial complexity involved in decision-making is discussed and a medico-psycho-social grid for use in multidisciplinary meetings is proposed.

How have systematic priority setting approaches influenced policy making? A synthesis of the current literature.

PubMed

Kapiriri, Lydia; Razavi, Donya

2017-09-01

There is a growing body of literature on systematic approaches to healthcare priority setting from various countries and different levels of decision making. This paper synthesizes the current literature in order to assess the extent to which program budgeting and marginal analysis (PBMA), burden of disease & cost-effectiveness analysis (BOD/CEA), multi-criteria decision analysis (MCDA), and accountability for reasonableness (A4R), are reported to have been institutionalized and influenced policy making and practice. We searched for English language publications on health care priority setting approaches (2000-2017). Our sources of literature included PubMed and Ovid databases (including Embase, Global Health, Medline, PsycINFO, EconLit). Of the four approaches PBMA and A4R were commonly applied in high income countries while BOD/CEA was exclusively applied in low income countries. PBMA and BOD/CEA were most commonly reported to have influenced policy making. The explanations for limited adoption of an approach were related to its complexity, poor policy maker understanding and resource requirements. While systematic approaches have the potential to improve healthcare priority setting; most have not been adopted in routine policy making. The identified barriers call for sustained knowledge exchange between researchers and policy-makers and development of practical guidelines to ensure that these frameworks are more accessible, applicable and sustainable in informing policy making. Copyright © 2017 Elsevier B.V. All rights reserved.

Shared decision-making - Rhetoric and reality: Women's experiences and perceptions of adjuvant treatment decision-making for breast cancer.

PubMed

Mahmoodi, Neda; Sargeant, Sally

2017-01-01

This interview-based study uses phenomenology as a theoretical framework and thematic analysis to challenge existing explanatory frameworks of shared decision-making, in an exploration of women's experiences and perceptions of shared decision-making for adjuvant treatment in breast cancer. Three themes emerged are as follows: (1) women's desire to participate in shared decision-making, (2) the degree to which shared decision-making is perceived to be shared and (3) to what extent are women empowered within shared decision-making. Studying breast cancer patients' subjective experiences of adjuvant treatment decision-making provides a broader perspective on patient participatory role preferences and doctor-patient power dynamics within shared decision-making for breast cancer.

Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR Task Force on Indirect Treatment Comparisons Good Research Practices: part 1.

PubMed

Jansen, Jeroen P; Fleurence, Rachael; Devine, Beth; Itzler, Robbin; Barrett, Annabel; Hawkins, Neil; Lee, Karen; Boersma, Cornelis; Annemans, Lieven; Cappelleri, Joseph C

2011-06-01

Evidence-based health-care decision making requires comparisons of all relevant competing interventions. In the absence of randomized, controlled trials involving a direct comparison of all treatments of interest, indirect treatment comparisons and network meta-analysis provide useful evidence for judiciously selecting the best choice(s) of treatment. Mixed treatment comparisons, a special case of network meta-analysis, combine direct and indirect evidence for particular pairwise comparisons, thereby synthesizing a greater share of the available evidence than a traditional meta-analysis. This report from the ISPOR Indirect Treatment Comparisons Good Research Practices Task Force provides guidance on the interpretation of indirect treatment comparisons and network meta-analysis to assist policymakers and health-care professionals in using its findings for decision making. We start with an overview of how networks of randomized, controlled trials allow multiple treatment comparisons of competing interventions. Next, an introduction to the synthesis of the available evidence with a focus on terminology, assumptions, validity, and statistical methods is provided, followed by advice on critically reviewing and interpreting an indirect treatment comparison or network meta-analysis to inform decision making. We finish with a discussion of what to do if there are no direct or indirect treatment comparisons of randomized, controlled trials possible and a health-care decision still needs to be made. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

DOD Financial Management: Effect of Continuing Weaknesses on Management and Operations and Status of Key Challenges

DTIC Science & Technology

2014-05-13

the information needed to effectively (1) manage its assets, (2) assess program performance and make budget decisions , (3) make cost- effective ... decision making, including the information needed to effectively (1) manage its assets, (2) assess program performance and make budget decisions , (3...incorporating key elements of a comprehensive management approach , such as a complete analysis of the return on investment, quantitatively -defined goals

Characterizing uncertain sea-level rise projections to support investment decisions.

PubMed

Sriver, Ryan L; Lempert, Robert J; Wikman-Svahn, Per; Keller, Klaus

2018-01-01

Many institutions worldwide are considering how to include uncertainty about future changes in sea-levels and storm surges into their investment decisions regarding large capital infrastructures. Here we examine how to characterize deeply uncertain climate change projections to support such decisions using Robust Decision Making analysis. We address questions regarding how to confront the potential for future changes in low probability but large impact flooding events due to changes in sea-levels and storm surges. Such extreme events can affect investments in infrastructure but have proved difficult to consider in such decisions because of the deep uncertainty surrounding them. This study utilizes Robust Decision Making methods to address two questions applied to investment decisions at the Port of Los Angeles: (1) Under what future conditions would a Port of Los Angeles decision to harden its facilities against extreme flood scenarios at the next upgrade pass a cost-benefit test, and (2) Do sea-level rise projections and other information suggest such conditions are sufficiently likely to justify such an investment? We also compare and contrast the Robust Decision Making methods with a full probabilistic analysis. These two analysis frameworks result in similar investment recommendations for different idealized future sea-level projections, but provide different information to decision makers and envision different types of engagement with stakeholders. In particular, the full probabilistic analysis begins by aggregating the best scientific information into a single set of joint probability distributions, while the Robust Decision Making analysis identifies scenarios where a decision to invest in near-term response to extreme sea-level rise passes a cost-benefit test, and then assembles scientific information of differing levels of confidence to help decision makers judge whether or not these scenarios are sufficiently likely to justify making such investments. Results highlight the highly-localized and context dependent nature of applying Robust Decision Making methods to inform investment decisions.

Characterizing uncertain sea-level rise projections to support investment decisions

PubMed Central

Lempert, Robert J.; Wikman-Svahn, Per; Keller, Klaus

2018-01-01

Many institutions worldwide are considering how to include uncertainty about future changes in sea-levels and storm surges into their investment decisions regarding large capital infrastructures. Here we examine how to characterize deeply uncertain climate change projections to support such decisions using Robust Decision Making analysis. We address questions regarding how to confront the potential for future changes in low probability but large impact flooding events due to changes in sea-levels and storm surges. Such extreme events can affect investments in infrastructure but have proved difficult to consider in such decisions because of the deep uncertainty surrounding them. This study utilizes Robust Decision Making methods to address two questions applied to investment decisions at the Port of Los Angeles: (1) Under what future conditions would a Port of Los Angeles decision to harden its facilities against extreme flood scenarios at the next upgrade pass a cost-benefit test, and (2) Do sea-level rise projections and other information suggest such conditions are sufficiently likely to justify such an investment? We also compare and contrast the Robust Decision Making methods with a full probabilistic analysis. These two analysis frameworks result in similar investment recommendations for different idealized future sea-level projections, but provide different information to decision makers and envision different types of engagement with stakeholders. In particular, the full probabilistic analysis begins by aggregating the best scientific information into a single set of joint probability distributions, while the Robust Decision Making analysis identifies scenarios where a decision to invest in near-term response to extreme sea-level rise passes a cost-benefit test, and then assembles scientific information of differing levels of confidence to help decision makers judge whether or not these scenarios are sufficiently likely to justify making such investments. Results highlight the highly-localized and context dependent nature of applying Robust Decision Making methods to inform investment decisions. PMID:29414978

Development of a special-purpose test surface guided by uncertainty analysis - Introduction of a new uncertainty analysis step

NASA Technical Reports Server (NTRS)

Wang, T.; Simon, T. W.

1988-01-01

Development of a recent experimental program to investigate the effects of streamwise curvature on boundary layer transition required making a bendable, heated and instrumented test wall, a rather nonconventional surface. The present paper describes this surface, the design choices made in its development and how uncertainty analysis was used, beginning early in the test program, to make such design choices. Published uncertainty analysis techniques were found to be of great value; but, it became clear that another step, one herein called the pre-test analysis, would aid the program development. Finally, it is shown how the uncertainty analysis was used to determine whether the test surface was qualified for service.

Reward-related decision making in eating and weight disorders: A systematic review and meta-analysis of the evidence from neuropsychological studies.

PubMed

Wu, Mudan; Brockmeyer, Timo; Hartmann, Mechthild; Skunde, Mandy; Herzog, Wolfgang; Friederich, Hans-Christoph

2016-02-01

Eating disorders (EDs) and overweight/obesity (OW/OB) are serious public health concerns that share common neuropsychological features and patterns of disturbed eating. Reward-related decision making as a basic neurocognitive function may trans-diagnostically underlie both pathological overeating and restricted eating. The present meta-analysis synthesizes the evidence from N=82 neuropsychological studies for altered reward-related decision making in all ED subtypes, OW and OB. The overall effect sizes for the differences between currently-ill ED patients and OW/OB people and controls were Hedge's g=-0.49 [CI: -0.63; -0.35], and Hedge's g=-0.39 [CI: -0.53; -0.25], respectively. Decision making was found to be altered to similar degrees in all ED subtypes and OB. Effect sizes, however, diverged for the different measures of decision making. Adolescents appear to be less affected than adults. When foods were used as rewarding stimuli, decision making was found to be intact in OB. The findings support that altered general reward-related decision making is a salient neuropsychological factor across eating and weight disorders in adulthood. Copyright © 2015 Elsevier Ltd. All rights reserved.

Improving lip wrinkles: lipstick-related image analysis.

PubMed

Ryu, Jong-Seong; Park, Sun-Gyoo; Kwak, Taek-Jong; Chang, Min-Youl; Park, Moon-Eok; Choi, Khee-Hwan; Sung, Kyung-Hye; Shin, Hyun-Jong; Lee, Cheon-Koo; Kang, Yun-Seok; Yoon, Moung-Seok; Rang, Moon-Jeong; Kim, Seong-Jin

2005-08-01

The appearance of lip wrinkles is problematic if it is adversely influenced by lipstick make-up causing incomplete color tone, spread phenomenon and pigment remnants. It is mandatory to develop an objective assessment method for lip wrinkle status by which the potential of wrinkle-improving products to lips can be screened. The present study is aimed at finding out the useful parameters from the image analysis of lip wrinkles that is affected by lipstick application. The digital photograph image of lips before and after lipstick application was assessed from 20 female volunteers. Color tone was measured by Hue, Saturation and Intensity parameters, and time-related pigment spread was calculated by the area over vermilion border by image-analysis software (Image-Pro). The efficacy of wrinkle-improving lipstick containing asiaticoside was evaluated from 50 women by using subjective and objective methods including image analysis in a double-blind placebo-controlled fashion. The color tone and spread phenomenon after lipstick make-up were remarkably affected by lip wrinkles. The level of standard deviation by saturation value of image-analysis software was revealed as a good parameter for lip wrinkles. By using the lipstick containing asiaticoside for 8 weeks, the change of visual grading scores and replica analysis indicated the wrinkle-improving effect. As the depth and number of wrinkles were reduced, the lipstick make-up appearance by image analysis also improved significantly. The lip wrinkle pattern together with lipstick make-up can be evaluated by the image-analysis system in addition to traditional assessment methods. Thus, this evaluation system is expected to test the efficacy of wrinkle-reducing lipstick that was not described in previous dermatologic clinical studies.

Topic-Focused Analysis of Verbal Interaction in a Case of Integrative Therapy with a Young Woman Presenting with Symptoms of Depression

ERIC Educational Resources Information Center

Reichelt, Sissel; Skjerve, Jan; McLeod, John

2017-01-01

It is increasingly recognised that single-case analysis makes a valuable contribution to the evidence base for psychotherapy, alongside other methodologies. Such analyses make it possible to investigate the unfolding process of change in therapy, and develop an understanding of change factors that contribute to outcome. One of the key challenges…

A Topical Trajectory on Survival: An Analysis of Link-Making in a Sequence of Lessons on Evolution

ERIC Educational Resources Information Center

Rocksén, Miranda; Olander, Clas

2017-01-01

This study explores the concept of link-making in relation to communicative strategies applied in the teaching and studying of biological evolution. The analysis focused on video recordings of 11 lessons on biological evolution conducted in a Swedish 9th grade class of students aged 15 years. It reveals how the teacher and students connected…

Perspectives about Living on the Horns of Dilemmas: An Analysis of Gender Factors Related to Superintendent Decision-Making and Problem-Solving

ERIC Educational Resources Information Center

Polka, Walter S.; Litchka, Peter R.; Calzi, Frank F.; Denig, Stephen J.; Mete, Rosina E.

2014-01-01

The major focus of this paper is a gender-based analysis of school superintendent decision-making and problem-solving as well as an investigation of contemporary leadership dilemmas. The findings are based on responses from 258 superintendents of K-12 school districts in Delaware, Maryland, New Jersey, New York, and Pennsylvania collected over a…

Human Information Behavior, Coping, and Decision-Making in the Context of a Personal Crisis: An Interpretative Phenomenological Analysis of the Voices of Birthmothers on Relinquishing a Child for Adoption

ERIC Educational Resources Information Center

Clemens, Rachael Annette

2017-01-01

This qualitative and interpretive inquiry explores the information behavior of birthmothers surrounding the processes of decision-making, coping, and living with the act of child relinquishment to adoption. An interpretative phenomenological analysis methodology is used to reveal the phenomenon as experienced by eight birthmothers, women who…

Examining a Reader's Meaning-Making Process of Picture Books Using Eye Movement Miscue Analysis

ERIC Educational Resources Information Center

Liwanag, Maria Perpetua Socorro U.; Martens, Prisca; Martens, Ray; Pelatti, Christina Yeager

2017-01-01

The goal of this case study was to examine a second grader's reading of picture books using eye movement miscue analysis as a method to further understand reading as a meaning-making process. Two picture books with different relationships (e.g., enhanced and counterpoint) were selected because they elicit varied ways of presenting meaning and thus…

Development of an intervention to support patients and clinicians with advanced lung cancer when considering systematic anticancer therapy: protocol for the PACT study.

PubMed

Anagnostou, Despina; Sivell, Stephanie; Noble, Simon; Lester, Jason; Byrne, Anthony; Sampson, Catherine; Longo, Mirella; Nelson, Annmarie

2017-07-12

Patient-centred care is essential to the delivery of healthcare; however, this necessitates direct patient involvement in clinical decision-making and can be challenging for patients diagnosed with advanced non-small cell lung cancer where there may be misunderstanding of the extent of disease, prognosis and aims of treatment. In this context, decisions are complex and there is a need to balance the risks and benefits, including treatment with palliative intent. The aim of the PACT study is to identify the information and decision support needs of patients, leading to the development of an intervention to support patients with advanced lung cancer when considering treatment options. PACT is a five-stage, multimethod and multicentre study. Participants : Patients and health professionals will be recruited from three health boards. Methods : Non-participant observation of multidisciplinary team meetings (n=12) will be used to determine patients' allocation to treatment pathways (stage I). Non-participant observation of patient-clinician consultations (n=20-30) will be used to explore communication of treatment options and decision-making. Extent of participation in decision-making will be assessed using the Observing Patient Involvement in Shared Decision-Making tool. Interviews with patients (stage III) and their clinicians (stage IV) will explore the perception of treatment options and involvement in decision-making. Based on stages I-IV, an expert consensus meeting will finalise the content and format of the intervention. Cognitive interviews with patients will then determine the face validity of the intervention (stage V). Analysis : analysis will be according to data type and research question and will include mediated discourse analysis, thematic analysis, framework analysis and interpretative phenomenological analysis. Ethical approval has been granted. The study findings will contribute to and promote shared and informed decision-making in the best interest of patients and prudent healthcare. We therefore aim to disseminate results via relevant respiratory, oncology and palliative care journals and conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Perceived risks around choice and decision making at end-of-life: a literature review.

PubMed

Wilson, F; Gott, M; Ingleton, C

2013-01-01

the World Health Organization identifies meeting patient choice for care as central to effective palliative care delivery. Little is known about how choice, which implies an objective balancing of options and risks, is understood and enacted through decision making at end-of-life. to explore how perceptions of 'risk' may inform decision-making processes at end-of-life. an integrative literature review was conducted between January and February 2010. Papers were reviewed using Hawker et al.'s criteria and evaluated according to clarity of methods, analysis and evidence of ethical consideration. All literature was retained as background data, but given the significant international heterogeneity the final analysis specifically focused on the UK context. the databases Medline, PsycINFO, Assia, British Nursing Index, High Wire Press and CINAHL were explored using the search terms decision*, risk, anxiety, hospice and palliative care, end-of-life care and publication date of 1998-2010. thematic analysis of 25 papers suggests that decision making at end-of-life is multifactorial, involving a balancing of risks related to caregiver support; service provider resources; health inequalities and access; challenges to information giving; and perceptions of self-identity. Overall there is a dissonance in understandings of choice and decision making between service providers and service users. the concept of risk acknowledges the factors that shape and constrain end-of-life choices. Recognition of perceived risks as a central factor in decision making would be of value in acknowledging and supporting meaningful decision making processes for patients with palliative care needs and their families.

The utilisation of health research in policy-making: concepts, examples and methods of assessment

PubMed Central

Hanney, Stephen R; Gonzalez-Block, Miguel A; Buxton, Martin J; Kogan, Maurice

2003-01-01

The importance of health research utilisation in policy-making, and of understanding the mechanisms involved, is increasingly recognised. Recent reports calling for more resources to improve health in developing countries, and global pressures for accountability, draw greater attention to research-informed policy-making. Key utilisation issues have been described for at least twenty years, but the growing focus on health research systems creates additional dimensions. The utilisation of health research in policy-making should contribute to policies that may eventually lead to desired outcomes, including health gains. In this article, exploration of these issues is combined with a review of various forms of policy-making. When this is linked to analysis of different types of health research, it assists in building a comprehensive account of the diverse meanings of research utilisation. Previous studies report methods and conceptual frameworks that have been applied, if with varying degrees of success, to record utilisation in policy-making. These studies reveal various examples of research impact within a general picture of underutilisation. Factors potentially enhancing utilisation can be identified by exploration of: priority setting; activities of the health research system at the interface between research and policy-making; and the role of the recipients, or 'receptors', of health research. An interfaces and receptors model provides a framework for analysis. Recommendations about possible methods for assessing health research utilisation follow identification of the purposes of such assessments. Our conclusion is that research utilisation can be better understood, and enhanced, by developing assessment methods informed by conceptual analysis and review of previous studies. PMID:12646071

New Insights into the Organization, Recombination, Expression and Functional Mechanism of Low Molecular Weight Glutenin Subunit Genes in Bread Wheat

PubMed Central

Fan, Huajie; Sun, Jiazhu; Zhang, Zhongjuan; Qin, Huanju; Li, Bin; Hao, Shanting; Li, Zhensheng; Wang, Daowen; Zhang, Aimin; Ling, Hong-Qing

2010-01-01

The bread-making quality of wheat is strongly influenced by multiple low molecular weight glutenin subunit (LMW-GS) proteins expressed in the seeds. However, the organization, recombination and expression of LMW-GS genes and their functional mechanism in bread-making are not well understood. Here we report a systematic molecular analysis of LMW-GS genes located at the orthologous Glu-3 loci (Glu-A3, B3 and D3) of bread wheat using complementary approaches (genome wide characterization of gene members, expression profiling, proteomic analysis). Fourteen unique LMW-GS genes were identified for Xiaoyan 54 (with superior bread-making quality). Molecular mapping and recombination analyses revealed that the three Glu-3 loci of Xiaoyan 54 harbored dissimilar numbers of LMW-GS genes and covered different genetic distances. The number of expressed LMW-GS in the seeds was higher in Xiaoyan 54 than in Jing 411 (with relatively poor bread-making quality). This correlated with the finding of higher numbers of active LMW-GS genes at the A3 and D3 loci in Xiaoyan 54. Association analysis using recombinant inbred lines suggested that positive interactions, conferred by genetic combinations of the Glu-3 locus alleles with more numerous active LMW-GS genes, were generally important for the recombinant progenies to attain high Zeleny sedimentation value (ZSV), an important indicator of bread-making quality. A higher number of active LMW-GS genes tended to lead to a more elevated ZSV, although this tendency was influenced by genetic background. This work provides substantial new insights into the genomic organization and expression of LMW-GS genes, and molecular genetic evidence suggesting that these genes contribute quantitatively to bread-making quality in hexaploid wheat. Our analysis also indicates that selection for high numbers of active LMW-GS genes can be used for improvement of bread-making quality in wheat breeding. PMID:20975830

Aneurysmal subarachnoid hemorrhage prognostic decision-making algorithm using classification and regression tree analysis.

PubMed

Lo, Benjamin W Y; Fukuda, Hitoshi; Angle, Mark; Teitelbaum, Jeanne; Macdonald, R Loch; Farrokhyar, Forough; Thabane, Lehana; Levine, Mitchell A H

2016-01-01

Classification and regression tree analysis involves the creation of a decision tree by recursive partitioning of a dataset into more homogeneous subgroups. Thus far, there is scarce literature on using this technique to create clinical prediction tools for aneurysmal subarachnoid hemorrhage (SAH). The classification and regression tree analysis technique was applied to the multicenter Tirilazad database (3551 patients) in order to create the decision-making algorithm. In order to elucidate prognostic subgroups in aneurysmal SAH, neurologic, systemic, and demographic factors were taken into account. The dependent variable used for analysis was the dichotomized Glasgow Outcome Score at 3 months. Classification and regression tree analysis revealed seven prognostic subgroups. Neurological grade, occurrence of post-admission stroke, occurrence of post-admission fever, and age represented the explanatory nodes of this decision tree. Split sample validation revealed classification accuracy of 79% for the training dataset and 77% for the testing dataset. In addition, the occurrence of fever at 1-week post-aneurysmal SAH is associated with increased odds of post-admission stroke (odds ratio: 1.83, 95% confidence interval: 1.56-2.45, P < 0.01). A clinically useful classification tree was generated, which serves as a prediction tool to guide bedside prognostication and clinical treatment decision making. This prognostic decision-making algorithm also shed light on the complex interactions between a number of risk factors in determining outcome after aneurysmal SAH.

Strategic Decision-Making by Deans in Academic Health Centers: A Framework Analysis

ERIC Educational Resources Information Center

Keeney, Brianne

2012-01-01

This study examines strategic decision-making at the college level in relation to seven theoretical frames. Strategic decisions are those made by top executives, have wide-ranging influence throughout the organization, affect the long-term future of the organization, and are connected to the external environment. The seven decision-making frames…

Improving IT Portfolio Management Decision Confidence Using Multi-Criteria Decision Making and Hypervariate Display Techniques

ERIC Educational Resources Information Center

Landmesser, John Andrew

2014-01-01

Information technology (IT) investment decision makers are required to process large volumes of complex data. An existing body of knowledge relevant to IT portfolio management (PfM), decision analysis, visual comprehension of large volumes of information, and IT investment decision making suggest Multi-Criteria Decision Making (MCDM) and…

Decision-Making Models in a Tunisian University: Towards a Framework for Analysis

ERIC Educational Resources Information Center

Khefacha, I.; Belkacem, L.

2014-01-01

This study investigates how decisions are made in Tunisian public higher education establishments. Some factors are identified as having a potentially significant impact on the odds that the decision-making process follows the characteristics of one of the most well known decision-making models: collegial, political, bureaucratic or anarchical…

Child Protection Decision Making: A Factorial Analysis Using Case Vignettes

ERIC Educational Resources Information Center

Stokes, Jacqueline; Schmidt, Glen

2012-01-01

This study explored decision making by child protection social workers in the province of British Columbia, Canada. A factorial survey method was used in which case vignettes were constructed by randomly assigning a number of key characteristics associated with decision making in child protection. Child protection social workers (n = 118) assessed…

Influence of dorsolateral prefrontal cortex and ventral striatum on risk avoidance in addiction: a mediation analysis.

PubMed

Yamamoto, Dorothy J; Woo, Choong-Wan; Wager, Tor D; Regner, Michael F; Tanabe, Jody

2015-04-01

Alterations in frontal and striatal function are hypothesized to underlie risky decision making in drug users, but how these regions interact to affect behavior is incompletely understood. We used mediation analysis to investigate how prefrontal cortex and ventral striatum together influence risk avoidance in abstinent drug users. Thirty-seven abstinent substance-dependent individuals (SDI) and 43 controls underwent fMRI while performing a decision-making task involving risk and reward. Analyses of a priori regions-of-interest tested whether activity in dorsolateral prefrontal cortex (DLPFC) and ventral striatum (VST) explained group differences in risk avoidance. Whole-brain analysis was conducted to identify brain regions influencing the negative VST-risk avoidance relationship. Right DLPFC (RDLPFC) positively mediated the group-risk avoidance relationship (p < 0.05); RDLPFC activity was higher in SDI and predicted higher risk avoidance across groups, controlling for SDI vs. Conversely, VST activity negatively influenced risk avoidance (p < 0.05); it was higher in SDI, and predicted lower risk avoidance. Whole-brain analysis revealed that, across group, RDLPFC and left temporal-parietal junction positively (p ≤ 0.001) while right thalamus and left middle frontal gyrus negatively (p < 0.005) mediated the VST activity-risk avoidance relationship. RDLPFC activity mediated less risky decision making while VST mediated more risky decision making across drug users and controls. These results suggest a dual pathway underlying decision making, which, if imbalanced, may adversely influence choices involving risk. Modeling contributions of multiple brain systems to behavior through mediation analysis could lead to a better understanding of mechanisms of behavior and suggest neuromodulatory treatments for addiction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Influence of dorsolateral prefrontal cortex and ventral striatum on risk avoidance in addiction: a mediation analysis*

PubMed Central

Yamamoto, Dorothy J.; Woo, Choong-Wan; Wager, Tor D.; Regner, Michael F.; Tanabe, Jody

2015-01-01

Background Alterations in frontal and striatal function are hypothesized to underlie risky decision-making in drug users, but how these regions interact to affect behavior is incompletely understood. We used mediation analysis to investigate how prefrontal cortex and ventral striatum together influence risk avoidance in abstinent drug users. Method Thirty-seven abstinent substance-dependent individuals (SDI) and 43 controls underwent fMRI while performing a decision-making task involving risk and reward. Analyses of a priori regions-of-interest tested whether activity in dorsolateral prefrontal cortex (DLPFC) and ventral striatum (VST) explained group differences in risk avoidance. Whole-brain analysis was conducted to identify brain regions influencing the negative VST-risk avoidance relationship. Results Right DLPFC (RDLPFC) positively mediated the group-risk avoidance relationship (p < 0.05); RDLPFC activity was higher in SDI and predicted higher risk avoidance across groups, controlling for SDI vs. controls. Conversely, VST activity negatively influenced risk avoidance (p < 0.05); it was higher in SDI, and predicted lower risk avoidance. Whole-brain analysis revealed that, across group, RDLPFC and left temporal-parietal junction positively (p ≤ 0.001) while right thalamus and left middle frontal gyrus negatively (p < 0.005) mediated the VST activity-risk avoidance relationship. Conclusion RDLPFC activity mediated less risky decision-making while VST mediated more risky decision-making across drug users and controls. These results suggest a dual pathway underlying decision-making, which, if imbalanced, may adversely influence choices involving risk. Modeling contributions of multiple brain systems to behavior through mediation analysis could lead to a better understanding of mechanisms of behavior and suggest neuromodulatory treatments for addiction. PMID:25736619

Bearing Procurement Analysis Method by Total Cost of Ownership Analysis and Reliability Prediction

NASA Astrophysics Data System (ADS)

Trusaji, Wildan; Akbar, Muhammad; Sukoyo; Irianto, Dradjad

2018-03-01

In making bearing procurement analysis, price and its reliability must be considered as decision criteria, since price determines the direct cost as acquisition cost and reliability of bearing determine the indirect cost such as maintenance cost. Despite the indirect cost is hard to identify and measured, it has high contribution to overall cost that will be incurred. So, the indirect cost of reliability must be considered when making bearing procurement analysis. This paper tries to explain bearing evaluation method with the total cost of ownership analysis to consider price and maintenance cost as decision criteria. Furthermore, since there is a lack of failure data when bearing evaluation phase is conducted, reliability prediction method is used to predict bearing reliability from its dynamic load rating parameter. With this method, bearing with a higher price but has higher reliability is preferable for long-term planning. But for short-term planning the cheaper one but has lower reliability is preferable. This contextuality can give rise to conflict between stakeholders. Thus, the planning horizon needs to be agreed by all stakeholder before making a procurement decision.

[A SWOT (strengths, weaknesses, opportunities, threats) analysis of the current immunization program in Zhejiang Province].

PubMed

He, Han-Qing; Ling, Luo-Ya; Xu, Xu-Qing

2009-02-01

To know the status of Immunization program in Zhejiang Province. The investigation on immunization program in zhejiang province was conducted, and the SWOT analysis was corducted to make a comprehensive evaluation. 11 cities, 22 counties and 44 towns were investigated in this study, and the current immunization program in Zhejiang province were explored by SWOT analysis. The SWOT Matrix, includes SO (strength-opportunity), ST (strength-threat), WO (weakness-opportunity) and WT (weakness-threat) can apply to make optimal strategy for the development of expanded program on immunization.

Group decision-making techniques for natural resource management applications

USGS Publications Warehouse

Coughlan, Beth A.K.; Armour, Carl L.

1992-01-01

This report is an introduction to decision analysis and problem-solving techniques for professionals in natural resource management. Although these managers are often called upon to make complex decisions, their training in the natural sciences seldom provides exposure to the decision-making tools developed in management science. Our purpose is to being to fill this gap. We present a general analysis of the pitfalls of group problem solving, and suggestions for improved interactions followed by the specific techniques. Selected techniques are illustrated. The material is easy to understand and apply without previous training or excessive study and is applicable to natural resource management issues.

Internet suicide in Japan: a qualitative content analysis of a suicide bulletin board.

PubMed

Ikunaga, Ai; Nath, Sanjay R; Skinner, Kenneth A

2013-04-01

Netto shinju, or Internet group suicide, is a contemporary form of Japanese suicide where strangers connect on the Internet and make plans to commit suicide together. In the past decade, numerous incidents have occurred whereby young Japanese make contact on the Internet, exchange tips on suicide methods, and make plans to meet offline for group/individual suicide. A systematic qualitative content/thematic analysis of online communications posted on a popular Japanese suicide bulletin board yielded a textured, thematic understanding of this phenomenon. Themes identified reflected Shneidman's theory of suicide but with an emphasis on interpersonal concerns that are embedded in Japanese culture.

Uncertainty Estimation Cheat Sheet for Probabilistic Risk Assessment

NASA Technical Reports Server (NTRS)

Britton, Paul T.; Al Hassan, Mohammad; Ring, Robert W.

2017-01-01

"Uncertainty analysis itself is uncertain, therefore, you cannot evaluate it exactly," Source Uncertain Quantitative results for aerospace engineering problems are influenced by many sources of uncertainty. Uncertainty analysis aims to make a technical contribution to decision-making through the quantification of uncertainties in the relevant variables as well as through the propagation of these uncertainties up to the result. Uncertainty can be thought of as a measure of the 'goodness' of a result and is typically represented as statistical dispersion. This paper will explain common measures of centrality and dispersion; and-with examples-will provide guidelines for how they may be estimated to ensure effective technical contributions to decision-making.

Lognormal Uncertainty Estimation for Failure Rates

NASA Technical Reports Server (NTRS)

Britton, Paul T.; Al Hassan, Mohammad; Ring, Robert W.

2017-01-01

"Uncertainty analysis itself is uncertain, therefore, you cannot evaluate it exactly," Source Uncertain. Quantitative results for aerospace engineering problems are influenced by many sources of uncertainty. Uncertainty analysis aims to make a technical contribution to decision-making through the quantification of uncertainties in the relevant variables as well as through the propagation of these uncertainties up to the result. Uncertainty can be thought of as a measure of the 'goodness' of a result and is typically represented as statistical dispersion. This presentation will explain common measures of centrality and dispersion; and-with examples-will provide guidelines for how they may be estimated to ensure effective technical contributions to decision-making.

TACIT: An open-source text analysis, crawling, and interpretation tool.

PubMed

Dehghani, Morteza; Johnson, Kate M; Garten, Justin; Boghrati, Reihane; Hoover, Joe; Balasubramanian, Vijayan; Singh, Anurag; Shankar, Yuvarani; Pulickal, Linda; Rajkumar, Aswin; Parmar, Niki Jitendra

2017-04-01

As human activity and interaction increasingly take place online, the digital residues of these activities provide a valuable window into a range of psychological and social processes. A great deal of progress has been made toward utilizing these opportunities; however, the complexity of managing and analyzing the quantities of data currently available has limited both the types of analysis used and the number of researchers able to make use of these data. Although fields such as computer science have developed a range of techniques and methods for handling these difficulties, making use of those tools has often required specialized knowledge and programming experience. The Text Analysis, Crawling, and Interpretation Tool (TACIT) is designed to bridge this gap by providing an intuitive tool and interface for making use of state-of-the-art methods in text analysis and large-scale data management. Furthermore, TACIT is implemented as an open, extensible, plugin-driven architecture, which will allow other researchers to extend and expand these capabilities as new methods become available.

Conceptualizing surrogate decision making at end of life in the intensive care unit using cognitive task analysis.

PubMed

Dionne-Odom, J Nicholas; Willis, Danny G; Bakitas, Marie; Crandall, Beth; Grace, Pamela J

2015-01-01

Surrogate decision makers (SDMs) face difficult decisions at end of life (EOL) for decisionally incapacitated intensive care unit (ICU) patients. To identify and describe the underlying psychological processes of surrogate decision making for adults at EOL in the ICU. Qualitative case study design using a cognitive task analysis interviewing approach. Participants were recruited from October 2012 to June 2013 from an academic tertiary medical center's ICU located in the rural Northeastern United States. Nineteen SDMs for patients who had died in the ICU completed in-depth semistructured cognitive task analysis interviews. The conceptual framework formulated from data analysis reveals that three underlying, iterative, psychological dimensions (gist impressions, distressing emotions, and moral intuitions) impact an SDM's judgment about the acceptability of either the patient's medical treatments or his or her condition. The framework offers initial insights about the underlying psychological processes of surrogate decision making and may facilitate enhanced decision support for SDMs. Copyright © 2015 Elsevier Inc. All rights reserved.

[The influence of meaning making following stressful life experiences on change of self-concept].

PubMed

Horita, Ryo; Sugie, Masashi

2013-10-01

As interest in meaning making following stressful life experiences continues to grow, it is important to clarify the features and functions of the meaning- making process. We examined the influence of meaning making following stressful life experiences on change of self-concept. In two studies, university students selected their most stressful life experience and completed the Assimilation and Accommodation of Meaning Making Scale. In Study 1, 235 university students also completed questionnaires regarding post-traumatic growth and positive change of the sense of identity following their stressful life experience. The results of covariance structure analysis indicated that accommodation promoted a positive change of self-concept. In Study 2, 199 university students completed questionnaires regarding change of self-concept and emotion as a positive or negative change following stressful life experiences. The results of covariance structure analysis indicated that accommodation promoted a positive change, similar to the results of Study 1. In addition, accommodation also promoted negative change. However, assimilation did not promote positive change but did restrain negative change.

An EGR performance evaluation and decision-making approach based on grey theory and grey entropy analysis

PubMed Central

2018-01-01

Exhaust gas recirculation (EGR) is one of the main methods of reducing NOX emissions and has been widely used in marine diesel engines. This paper proposes an optimized comprehensive assessment method based on multi-objective grey situation decision theory, grey relation theory and grey entropy analysis to evaluate the performance and optimize rate determination of EGR, which currently lack clear theoretical guidance. First, multi-objective grey situation decision theory is used to establish the initial decision-making model according to the main EGR parameters. The optimal compromise between diesel engine combustion and emission performance is transformed into a decision-making target weight problem. After establishing the initial model and considering the characteristics of EGR under different conditions, an optimized target weight algorithm based on grey relation theory and grey entropy analysis is applied to generate the comprehensive evaluation and decision-making model. Finally, the proposed method is successfully applied to a TBD234V12 turbocharged diesel engine, and the results clearly illustrate the feasibility of the proposed method for providing theoretical support and a reference for further EGR optimization. PMID:29377956

An EGR performance evaluation and decision-making approach based on grey theory and grey entropy analysis.

PubMed

Zu, Xianghuan; Yang, Chuanlei; Wang, Hechun; Wang, Yinyan

2018-01-01

Exhaust gas recirculation (EGR) is one of the main methods of reducing NOX emissions and has been widely used in marine diesel engines. This paper proposes an optimized comprehensive assessment method based on multi-objective grey situation decision theory, grey relation theory and grey entropy analysis to evaluate the performance and optimize rate determination of EGR, which currently lack clear theoretical guidance. First, multi-objective grey situation decision theory is used to establish the initial decision-making model according to the main EGR parameters. The optimal compromise between diesel engine combustion and emission performance is transformed into a decision-making target weight problem. After establishing the initial model and considering the characteristics of EGR under different conditions, an optimized target weight algorithm based on grey relation theory and grey entropy analysis is applied to generate the comprehensive evaluation and decision-making model. Finally, the proposed method is successfully applied to a TBD234V12 turbocharged diesel engine, and the results clearly illustrate the feasibility of the proposed method for providing theoretical support and a reference for further EGR optimization.

The Development and Validation of a Generic Instrument, QoDoS, for Assessing the Quality of Decision Making.

PubMed

Donelan, Ronan; Walker, Stuart; Salek, Sam

2016-01-01

The impact of decision-making during the development and the regulatory review of medicines greatly influences the delivery of new medicinal products. Currently, there is no generic instrument that can be used to assess the quality of decision-making. This study describes the development of the Quality of Decision-Making Orientation Scheme QoDoS(©) instrument for appraising the quality of decision-making. Semi-structured interviews about decision-making were carried out with 29 senior decision makers from the pharmaceutical industry (10), regulatory authorities (9) and contract research organizations (10). The interviews offered a qualified understanding of the subjective decision-making approach, influences, behaviors and other factors that impact such processes for individuals and organizations involved in the delivery of new medicines. Thematic analysis of the transcribed interviews was carried out using NVivo8® software. Content validity was carried out using qualitative and quantitative data by an expert panel, which led to the developmental version of the QoDoS. Further psychometric evaluations were performed, including factor analysis, item reduction, reliability testing and construct validation. The thematic analysis of the interviews yielded a 94-item initial version of the QoDoS(©) with a 5-point Likert scale. The instrument was tested for content validity using a panel of experts for language clarity, completeness, relevance and scaling, resulting in a favorable agreement by panel members with an intra-class correlation coefficient value of 0.89 (95% confidence interval = 0.56, 0.99). A 76-item QoDoS(©) (version 2) emerged from content validation. Factor analysis produced a 47-item measure with four domains. The 47-item QoDoS(©) (version 3) showed high internal consistency (n = 120, Cronbach's alpha = 0.89), high reproducibility (n = 20, intra-class correlation = 0.77) and a mean completion time of 10 min. Reliability testing and construct validation was successfully performed. The QoDoS(©) is both reliable and valid for use. It has the potential for extensive use in medicines development by both the pharmaceutical industry and regulatory authorities. The QoDoS(©) can be used to assess the quality of decision-making and to inform decision makers of the factors that influence decision-making.

An Instructional Management Guide to Cost Effective Decision Making,

DTIC Science & Technology

1974-01-01

Journal , 1968, 34. United States Congress. To improve learning. Report by the Commission on Instructional Technology of the Commis- sion on Education...of cost-benefit analysis and cost-effectiveness analysis has been recognized in public and private education. It was reported by the Commission on...instructional decision-making, however, is a more formidable task. One difficulty is that although much has been reported on the advantages of

Physics and Analysis at a Hadron Collider - Making Measurements (3/3)

ScienceCinema

Glenzinski, Douglas

2018-02-26

This is the third lecture of three which together discuss the physics of hadron colliders with an emphasis on experimental techniques used for data analysis. This third lecture discusses techniques important for analyses making a measurement (e.g. determining a cross section or a particle property such as its mass or lifetime) using some CDF top-quark analyses as specific examples. The lectures are aimed at graduate students.

Decision-Making in National Security Affairs: Toward a Typology.

DTIC Science & Technology

1985-06-07

decisional model, and thus provide the necessary linkage between observation and application of theory in explaining and/or predicting policy decisions . r...examines theories and models of decision -making processes from an interdisciplinary perspective, with a view toward deriving means by which the behavior of...processes, game theory , linear programming, network and graph theory , time series analysis, and the like. The discipline of decision analysis is a relatively

Multi-criteria decision analysis for health technology assessment in Canada: insights from an expert panel discussion.

PubMed

Diaby, Vakaramoko; Goeree, Ron; Hoch, Jeffrey; Siebert, Uwe

2015-02-01

Multi-criteria decision analysis (MCDA), a decision-making tool, has received increasing attention in recent years, notably in the healthcare field. For Canada, it is unclear whether and how MCDA should be incorporated into the existing health technology assessment (HTA) decision-making process. To facilitate debate on improving HTA decision-making in Canada, a workshop was held in conjunction with the 8th World Congress on Health Economics of the International Health Economics Association in Toronto, Canada in July 2011. The objective of the workshop was to discuss the potential benefits and challenges related to the use of MCDA for HTA decision-making in Canada. This paper summarizes and discusses the recommendations of an expert panel convened at the workshop to discuss opportunities and concerns with reference to the implementation of MCDA in Canada.

Prolegomenon to the Analysis of Nondecision Making.

ERIC Educational Resources Information Center

Mann, Dale

Non-decision-making is about how things come about in the absence of conscious choice. It is defined as a decision that stops a challenge to existing values or attempts to prevent something from reaching the stage of formal or overt decision-making. The common denominator is the suppression of wider participation in the formation of public policy.…

Leadership Style, Decision Context, and the Poliheuristic Theory of Decision Making: An Experimental Analysis

ERIC Educational Resources Information Center

Keller, Jonathan W.; Yang, Yi Edward

2008-01-01

The poliheuristic (PH) theory of decision making has made important contributions to our understanding of political decision making but remains silent about certain key aspects of the decision process. Specifically, PH theory contends that leaders screen out politically unacceptable options, but it provides no guidance on (1) the crucial threshold…

"You Can't Have a Cake unless It's Written Down": Semiotic Activity and Authentic Learning in Play as a Potential Tool for Analysis.

ERIC Educational Resources Information Center

Cook, Deirdre M.

2001-01-01

Explores young children's mark-making in a domestic play setting. Suggests mark-making indicates aspects of the relationship between semiotic and conceptual development. Focuses on contexts in which mark-making occurs and on the authenticity of the learning events in which children participate. (DLH)

"Black Magic" and "Gold Dust": The Epistemic and Political Uses of Evidence Tools in Public Health Policy Making

ERIC Educational Resources Information Center

Stewart, Ellen; Smith, Katherine E.

2015-01-01

Concerns about the limited influence of research on decision making have prompted the development of tools intended to mediate evidence for policy audiences. This article focuses on three examples, prominent in public health: impact assessments; systematic reviews; and economic decision-making tools (cost-benefit analysis and scenario modelling).…

Swift and Smart Decision Making: Heuristics that Work

ERIC Educational Resources Information Center

Hoy, Wayne K.; Tarter, C. J.

2010-01-01

Purpose: The aim of this paper is to examine the research literature on decision making and identify and develop a set of heuristics that work for school decision makers. Design/methodology/approach: This analysis is a synthesis of the research on decision-making heuristics that work. Findings: A set of nine rules for swift and smart decision…

Child Care Decision Making: Understanding Priorities and Processes Used by Low-Income Families in Minnesota

ERIC Educational Resources Information Center

Forry, Nicole; Isner, Tabitha K.; Daneri, Maria P.; Tout, Kathryn

2014-01-01

Research Findings: Few studies have described parents' child care decision-making process, yet understanding how parents make child care choices is fundamental to developing effective services to promote the selection of high-quality care. This study used latent profile analysis to distinguish subgroups of low-income parents identified as having…

The Matter of New Media Making: An Intra-Action Analysis of Adolescents Making a Digital Book Trailer

ERIC Educational Resources Information Center

Ehret, Christian; Hollett, Ty; Jocius, Robin

2016-01-01

Representational logic cannot account for the entanglements of all that matters in making new media: feeling bodies, vibrant matter, feeling bodies and vibrant matter all moving and at different rates. In the currently shifting communicative landscape, where mobile technologies are the primary means for youths' digital production, all this…

Towards a Dialogic Understanding of Children's Art-Making Process

ERIC Educational Resources Information Center

Kim, Hyunsu

2018-01-01

This article is intended to identify the complex process of children's art making by bringing new methodologies into the analysis of children's pictures. This article analyses the art-making process of a selected drawing by a five-year-old boy. The study builds on previous findings regarding children's verbal discourses during the art-making…

Monitoring of human brain functions in risk decision-making task by diffuse optical tomography using voxel-wise general linear model

NASA Astrophysics Data System (ADS)

Lin, Zi-Jing; Li, Lin; Cazzell, Marry; Liu, Hanli

2013-03-01

Functional near-infrared spectroscopy (fNIRS) is a non-invasive imaging technique which measures the hemodynamic changes that reflect the brain activity. Diffuse optical tomography (DOT), a variant of fNIRS with multi-channel NIRS measurements, has demonstrated capability of three dimensional (3D) reconstructions of hemodynamic changes due to the brain activity. Conventional method of DOT image analysis to define the brain activation is based upon the paired t-test between two different states, such as resting-state versus task-state. However, it has limitation because the selection of activation and post-activation period is relatively subjective. General linear model (GLM) based analysis can overcome this limitation. In this study, we combine the 3D DOT image reconstruction with GLM-based analysis (i.e., voxel-wise GLM analysis) to investigate the brain activity that is associated with the risk-decision making process. Risk decision-making is an important cognitive process and thus is an essential topic in the field of neuroscience. The balloon analogue risk task (BART) is a valid experimental model and has been commonly used in behavioral measures to assess human risk taking action and tendency while facing risks. We have utilized the BART paradigm with a blocked design to investigate brain activations in the prefrontal and frontal cortical areas during decision-making. Voxel-wise GLM analysis was performed on 18human participants (10 males and 8females).In this work, we wish to demonstrate the feasibility of using voxel-wise GLM analysis to image and study cognitive functions in response to risk decision making by DOT. Results have shown significant changes in the dorsal lateral prefrontal cortex (DLPFC) during the active choice mode and a different hemodynamic pattern between genders, which are in good agreements with published literatures in functional magnetic resonance imaging (fMRI) and fNIRS studies.

Compiler analysis for irregular problems in FORTRAN D

NASA Technical Reports Server (NTRS)

Vonhanxleden, Reinhard; Kennedy, Ken; Koelbel, Charles; Das, Raja; Saltz, Joel

1992-01-01

We developed a dataflow framework which provides a basis for rigorously defining strategies to make use of runtime preprocessing methods for distributed memory multiprocessors. In many programs, several loops access the same off-processor memory locations. Our runtime support gives us a mechanism for tracking and reusing copies of off-processor data. A key aspect of our compiler analysis strategy is to determine when it is safe to reuse copies of off-processor data. Another crucial function of the compiler analysis is to identify situations which allow runtime preprocessing overheads to be amortized. This dataflow analysis will make it possible to effectively use the results of interprocedural analysis in our efforts to reduce interprocessor communication and the need for runtime preprocessing.

Development of computer-assisted instruction application for statistical data analysis android platform as learning resource

NASA Astrophysics Data System (ADS)

Hendikawati, P.; Arifudin, R.; Zahid, M. Z.

2018-03-01

This study aims to design an android Statistics Data Analysis application that can be accessed through mobile devices to making it easier for users to access. The Statistics Data Analysis application includes various topics of basic statistical along with a parametric statistics data analysis application. The output of this application system is parametric statistics data analysis that can be used for students, lecturers, and users who need the results of statistical calculations quickly and easily understood. Android application development is created using Java programming language. The server programming language uses PHP with the Code Igniter framework, and the database used MySQL. The system development methodology used is the Waterfall methodology with the stages of analysis, design, coding, testing, and implementation and system maintenance. This statistical data analysis application is expected to support statistical lecturing activities and make students easier to understand the statistical analysis of mobile devices.

Consultant psychiatrists’ experiences of and attitudes towards shared decision making in antipsychotic prescribing, a qualitative study

PubMed Central

2014-01-01

Background Shared decision making represents a clinical consultation model where both clinician and service user are conceptualised as experts; information is shared bilaterally and joint treatment decisions are reached. Little previous research has been conducted to assess experience of this model in psychiatric practice. The current project therefore sought to explore the attitudes and experiences of consultant psychiatrists relating to shared decision making in the prescribing of antipsychotic medications. Methods A qualitative research design allowed the experiences and beliefs of participants in relation to shared decision making to be elicited. Purposive sampling was used to recruit participants from a range of clinical backgrounds and with varying length of clinical experience. A semi-structured interview schedule was utilised and was adapted in subsequent interviews to reflect emergent themes. Data analysis was completed in parallel with interviews in order to guide interview topics and to inform recruitment. A directed analysis method was utilised for interview analysis with themes identified being fitted to a framework identified from the research literature as applicable to the practice of shared decision making. Examples of themes contradictory to, or not adequately explained by, the framework were sought. Results A total of 26 consultant psychiatrists were interviewed. Participants expressed support for the shared decision making model, but also acknowledged that it was necessary to be flexible as the clinical situation dictated. A number of potential barriers to the process were perceived however: The commonest barrier was the clinician’s beliefs regarding the service users’ insight into their mental disorder, presented in some cases as an absolute barrier to shared decision making. In addition factors external to the clinician - service user relationship were identified as impacting on the decision making process, including; environmental factors, financial constraints as well as societal perceptions of mental disorder in general and antipsychotic medication in particular. Conclusions This project has allowed identification of potential barriers to shared decision making in psychiatric practice. Further work is necessary to observe the decision making process in clinical practice and also to identify means in which the identified barriers, in particular ‘lack of insight’, may be more effectively managed. PMID:24886121

Initiating decision-making conversations in palliative care: an ethnographic discourse analysis.

PubMed

Bélanger, Emmanuelle; Rodríguez, Charo; Groleau, Danielle; Légaré, France; Macdonald, Mary Ellen; Marchand, Robert

2014-01-01

Conversations about end-of-life care remain challenging for health care providers. The tendency to delay conversations about care options represents a barrier that impedes the ability of terminally-ill patients to participate in decision-making. Family physicians with a palliative care practice are often responsible for discussing end-of-life care preferences with patients, yet there is a paucity of research directly observing these interactions. In this study, we sought to explore how patients and family physicians initiated decision-making conversations in the context of a community hospital-based palliative care service. This qualitative study combined discourse analysis with ethnographic methods. The field research lasted one year, and data were generated through participant observation and audio-recordings of consultations. A total of 101 consultations were observed longitudinally between 18 patients, 6 family physicians and 2 pivot nurses. Data analysis consisted in exploring the different types of discourses initiating decision-making conversations and how these discourses were affected by the organizational context in which they took place. The organization of care had an impact on decision-making conversations. The timing and origin of referrals to palliative care shaped whether patients were still able to participate in decision-making, and the decisions that remained to be made. The type of decisions to be made also shaped how conversations were initiated. Family physicians introduced decision-making conversations about issues needing immediate attention, such as symptom management, by directly addressing or eliciting patients' complaints. When decisions involved discussing impending death, decision-making conversations were initiated either indirectly, by prompting the patients to express their understanding of the disease and its progression, or directly, by providing a justification for broaching a difficult topic. Decision-making conversations and the initiation thereof were framed by the organization of care and the referral process prior to initial encounters. While symptom management was taken for granted as part of health care professionals' expected role, engaging in decisions regarding preparation for death implicitly remained under patients' control. This work makes important clinical contributions by exposing the rhetorical function of family physicians' discourse when introducing palliative care decisions.

Consultant psychiatrists' experiences of and attitudes towards shared decision making in antipsychotic prescribing, a qualitative study.

PubMed

Shepherd, Andrew; Shorthouse, Oliver; Gask, Linda

2014-05-01

Shared decision making represents a clinical consultation model where both clinician and service user are conceptualised as experts; information is shared bilaterally and joint treatment decisions are reached. Little previous research has been conducted to assess experience of this model in psychiatric practice. The current project therefore sought to explore the attitudes and experiences of consultant psychiatrists relating to shared decision making in the prescribing of antipsychotic medications. A qualitative research design allowed the experiences and beliefs of participants in relation to shared decision making to be elicited. Purposive sampling was used to recruit participants from a range of clinical backgrounds and with varying length of clinical experience. A semi-structured interview schedule was utilised and was adapted in subsequent interviews to reflect emergent themes.Data analysis was completed in parallel with interviews in order to guide interview topics and to inform recruitment. A directed analysis method was utilised for interview analysis with themes identified being fitted to a framework identified from the research literature as applicable to the practice of shared decision making. Examples of themes contradictory to, or not adequately explained by, the framework were sought. A total of 26 consultant psychiatrists were interviewed. Participants expressed support for the shared decision making model, but also acknowledged that it was necessary to be flexible as the clinical situation dictated. A number of potential barriers to the process were perceived however: The commonest barrier was the clinician's beliefs regarding the service users' insight into their mental disorder, presented in some cases as an absolute barrier to shared decision making. In addition factors external to the clinician - service user relationship were identified as impacting on the decision making process, including; environmental factors, financial constraints as well as societal perceptions of mental disorder in general and antipsychotic medication in particular. This project has allowed identification of potential barriers to shared decision making in psychiatric practice. Further work is necessary to observe the decision making process in clinical practice and also to identify means in which the identified barriers, in particular 'lack of insight', may be more effectively managed.

Decision making measured by the Iowa Gambling Task in alcohol use disorder and gambling disorder: a systematic review and meta-analysis.

PubMed

Kovács, Ildikó; Richman, Mara J; Janka, Zoltán; Maraz, Aniko; Andó, Bálint

2017-12-01

Gambling disorder (GD) and alcohol use disorder (AD) have similar features, such as elevated impulsivity and decision-making deficits, which are directly linked to relapse and poor therapeutic outcomes. Our aim was to assess decision-making characteristics in GD and AD patients compared to healthy controls (HC) based on one of the most frequently used measures of decision-making: the Iowa Gambling Task (IGT). In our systematic literature search of three databases, we identified 1198 empirical articles that mentioned decision-making deficits with the use of the IGT in patients diagnosed with either AD or GD. Possible effects were calculated using meta-analysis. In the end, 17 studies (including 1360 participants) were suitable for inclusion in the meta-analysis reporting data for 23 group contrasts. The random effects estimate indicated impaired IGT performance in both AD patients (N=500; d=-0.581, CI:-89.5<δ<-26.6%) and an even greater deficit in GD patients (N=292; d=-1.034, CI:-156.1<δ<50.7%) compared to HCs. Sampling variances were calculated for both AD (v 1 =0.0056) and GD groups (v 2 =0.0061), from which the z-score was calculated (z=-21.0785; p<0.05), which indicates a statistically significant difference between AD and GD groups. No significant moderating effects of age, gender or education were found. There is enough evidence to support that decision-making deficit associated with addictive disorders, and that the deficit is more expressed in gambling disorder than in alcohol use disorder. Impaired decision-making plays an important part in poor therapeutic outcomes, thus provides a promising opportunity for cognitive intervention. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Women's Decision-Making Autonomy on Infant's Birth Weight in Rural Bangladesh

PubMed Central

Sharma, Arpana

2013-01-01

Background. Low birth weight (LBW), an outcome of maternal undernutrition, is a major public health concern in Bangladesh where the problem is most prominent. Women's decision-making autonomy is likely an important factor influencing maternal and child health outcomes. The aim of the study was to assess the effect of women's decision-making autonomy on infant's birth weight (BW). Methods. The study included data of 2175 enrolled women (14–45 years of age) from the Maternal and Infant Nutritional Intervention in Matlab (MINIMat-study) in Bangladesh. Pearson's chi-square test, analysis of covariance (ANCOVA), and logistic regression analysis were applied at the collected data. Results. Women with lowest decision-making autonomy were significantly more likely to have a low birth weight (LBW) child, after controlling for maternal age, education (woman's and her husband's), socioeconomic status (SES) (odds ratio (OR) = 1.4; 95% confidence interval (CI) 1.0, 1.8). BW was decreased significantly among women with lowest decision making autonomy after adjusting for all confounders. Conclusion. Women's decision-making autonomy has an independent effect on BW and LBW outcome. In addition, there is a need for further exploration to identify sociocultural attributes and gender related determinants of women decision-making autonomy in this study setting. PMID:24575305

The Role of Health Care Provider and Partner Decisional Support in Patients' Cancer Treatment Decision-Making Satisfaction.

PubMed

Palmer-Wackerly, Angela L; Krieger, Janice L; Rhodes, Nancy D

2017-01-01

Cancer patients rely on multiple sources of support when making treatment decisions; however, most research studies examine the influence of health care provider support while the influence of family member support is understudied. The current study fills this gap by examining the influence of health care providers and partners on decision-making satisfaction. In a cross-sectional study via an online Qualtrics panel, we surveyed cancer patients who reported that they had a spouse or romantic partner when making cancer treatment decisions (n = 479). Decisional support was measured using 5-point, single-item scales for emotional support, informational support, informational-advice support, and appraisal support. Decision-making satisfaction was measured using Holmes-Rovner and colleagues' (1996) Satisfaction With Decision Scale. We conducted a mediated regression analysis to examine treatment decision-making satisfaction for all participants and a moderated mediation analysis to examine treatment satisfaction among those patients offered a clinical trial. Results indicated that partner support significantly and partially mediated the relationship between health care provider support and patients' decision-making satisfaction but that results did not vary by enrollment in a clinical trial. This study shows how and why decisional support from partners affects communication between health care providers and cancer patients.

Development of a Shared Decision Making coding system for analysis of patient-healthcare provider encounters

PubMed Central

Clayman, Marla L.; Makoul, Gregory; Harper, Maya M.; Koby, Danielle G.; Williams, Adam R.

2012-01-01

Objectives Describe the development and refinement of a scheme, Detail of Essential Elements and Participants in Shared Decision Making (DEEP-SDM), for coding Shared Decision Making (SDM) while reporting on the characteristics of decisions in a sample of patients with metastatic breast cancer. Methods The Evidence-Based Patient Choice instrument was modified to reflect Makoul and Clayman’s Integrative Model of SDM. Coding was conducted on video recordings of 20 women at the first visit with their medical oncologists after suspicion of disease progression. Noldus Observer XT v.8, a video coding software platform, was used for coding. Results The sample contained 80 decisions (range: 1-11), divided into 150 decision making segments. Most decisions were physician-led, although patients and physicians initiated similar numbers of decision-making conversations. Conclusion DEEP-SDM facilitates content analysis of encounters between women with metastatic breast cancer and their medical oncologists. Despite the fractured nature of decision making, it is possible to identify decision points and to code each of the Essential Elements of Shared Decision Making. Further work should include application of DEEP-SDM to non-cancer encounters. Practice Implications: A better understanding of how decisions unfold in the medical encounter can help inform the relationship of SDM to patient-reported outcomes. PMID:22784391

The membrane current of single rod outer segments.

PubMed

Baylor, D A; Lamb, T D; Yau, K W

1979-03-01

1. Outer segments of individual rods in the retina of the toad, Bufo marinus, were drawn into a glass pipette to record the membrane current. 2. Light flashes evoked transient outward currents. The peak response amplitude was related to flash intensity by a Michaelis equation with half-saturating intensity about 1 photon mum-2. 3. The saturating response amplitude ranged up to 27 pA and corresponded closely to complete suppression of the steady inward current present in darkness. 4. For a given cell the saturating response amplitude varied linearly with the length of outer segment within the pipette. This is consistent with a uniform density of light-sensitive channels and negligible gradient of membrane potential along the outer segment. 5. Responses to bright flashes never showed the relaxation from an initial peak seen previously in intracellular voltage recordings, suggesting that the conductance change responsible for the relaxation does not occur in the outer segment. 6. Responses to local illumination of only the recorded outer segment were very similar to those obtained with diffuse light at the same intensity, indicating that peripheral rods made little contribution to the responses. 7. The spectral sensitivity of 'red' rods was consistent with a retinal1-based pigment with lambda max = 498 +/- 2 nm. 8. The kinetics of the response were consistent with four stages of delay affecting action of the internal transmitter. Responses were faster at the basal end of the outer segment than at the distal tip. 9. Background light reduced the sensitivity to a superposed dim test flash and shortened the time course of the response, indicating that adapting light modifies the kinetics and gain of the transduction mechanism within the outer segment. 10. Responses to dim lights exhibited pronounced fluctuations which are attributed in the succeeding paper (Baylor, Lamb & Yau, 1979) to the quantal nature of light.

Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro.

PubMed

Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C; Mennerick, Steven

2015-08-05

Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (-astrocyte) within the same culture dish. -Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal action potentials to synaptic terminals. GABA transmission was not disrupted. The disruption did not involve detectable morphological changes to axons of glutamate neurons. Our work identifies a developmental role for astrocytes in the temporal precision of excitatory signals. Copyright © 2015 the authors 0270-6474/15/3511105-13$15.00/0.

A closed-loop model of the respiratory system: focus on hypercapnia and active expiration.

PubMed

Molkov, Yaroslav I; Shevtsova, Natalia A; Park, Choongseok; Ben-Tal, Alona; Smith, Jeffrey C; Rubin, Jonathan E; Rybak, Ilya A

2014-01-01

Breathing is a vital process providing the exchange of gases between the lungs and atmosphere. During quiet breathing, pumping air from the lungs is mostly performed by contraction of the diaphragm during inspiration, and muscle contraction during expiration does not play a significant role in ventilation. In contrast, during intense exercise or severe hypercapnia forced or active expiration occurs in which the abdominal "expiratory" muscles become actively involved in breathing. The mechanisms of this transition remain unknown. To study these mechanisms, we developed a computational model of the closed-loop respiratory system that describes the brainstem respiratory network controlling the pulmonary subsystem representing lung biomechanics and gas (O2 and CO2) exchange and transport. The lung subsystem provides two types of feedback to the neural subsystem: a mechanical one from pulmonary stretch receptors and a chemical one from central chemoreceptors. The neural component of the model simulates the respiratory network that includes several interacting respiratory neuron types within the Bötzinger and pre-Bötzinger complexes, as well as the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) representing the central chemoreception module targeted by chemical feedback. The RTN/pFRG compartment contains an independent neural generator that is activated at an increased CO2 level and controls the abdominal motor output. The lung volume is controlled by two pumps, a major one driven by the diaphragm and an additional one activated by abdominal muscles and involved in active expiration. The model represents the first attempt to model the transition from quiet breathing to breathing with active expiration. The model suggests that the closed-loop respiratory control system switches to active expiration via a quantal acceleration of expiratory activity, when increases in breathing rate and phrenic amplitude no longer provide sufficient ventilation. The model can be used for simulation of closed-loop control of breathing under different conditions including respiratory disorders.

Glycine transporters GlyT1 and GlyT2 are differentially modulated by glycogen synthase kinase 3β.

PubMed

Jiménez, Esperanza; Núñez, Enrique; Ibáñez, Ignacio; Zafra, Francisco; Aragón, Carmen; Giménez, Cecilio

2015-02-01

Inhibitory glycinergic neurotransmission is terminated by the specific glycine transporters GlyT1 and GlyT2 which actively reuptake glycine from the synaptic cleft. GlyT1 is associated with both glycinergic and glutamatergic pathways, and is the main regulator of the glycine levels in the synapses. GlyT2 is the main supplier of glycine for vesicle refilling, a process that is vital to preserve the quantal glycine content in synaptic vesicles. Therefore, to control glycinergic neurotransmission efficiently, GlyT1 and GlyT2 activity must be regulated by diverse neuronal and glial signaling pathways. In this work, we have investigated the possible functional modulation of GlyT1 and GlyT2 by glycogen synthase kinase 3 (GSK3β). This kinase is involved in mood stabilization, neurodegeneration and plasticity at excitatory and inhibitory synapses. The co-expression of GSK3β with GlyT1 or GlyT2 in COS-7 cells and Xenopus laevis oocytes, leads to inhibition and stimulation of GlyT1 and GlyT2 activities, respectively, with a decrease of GlyT1, and an increase in GlyT2 levels at the plasma membrane. The specificity of these changes is supported by the antagonism exerted by a catalytically inactive form of the kinase and through inhibitors of GSK3β such as lithium chloride and TDZD-8. GSK3β also increases the incorporation of 32Pi into GlyT1 and decreases that of GlyT2. The pharmacological inhibition of the endogenous GSK3β in neuron cultures of brainstem and spinal cord leads to an opposite modulation of GlyT1 and GlyT2.Our results suggest that GSK3β is important for stabilizing and/or controlling the expression of functional GlyTs on the neural cell surface. Copyright © 2014 Elsevier Ltd. All rights reserved.

Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro

PubMed Central

Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C.

2015-01-01

Neuron–astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (−astrocyte) within the same culture dish. −Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. SIGNIFICANCE STATEMENT Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal action potentials to synaptic terminals. GABA transmission was not disrupted. The disruption did not involve detectable morphological changes to axons of glutamate neurons. Our work identifies a developmental role for astrocytes in the temporal precision of excitatory signals. PMID:26245971

Type specificity of complement-fixing antibody against herpes simplex virus type 2 AG-4 early antigen in patients with asymptomatic infection.

PubMed Central

Sherlock, C H; Ashley, R L; Shurtleff, M L; Mack, K D; Corey, L

1986-01-01

We evaluated the type specificity of complement-fixing (CF) antibody against the AG-4 early antigen of herpes simplex virus (HSV) type 2 (HSV-2) by comparing a commercial AG-4 CF kit (Simplex-2; Gene Link Australia, Inc., Princeton, N.J.) with quantal microneutralization (MN) and absorption-Western blotting in testing sera from patients with and without a history of genital herpes. Sera characterized as HSV type 1 (HSV-1) or HSV-2 positive or negative by MN were selected and tested by CF, and those with discordant results were further analyzed for specific antibodies by absorption with HSV-1 or HSV-2 antigen and Western blotting with heterologous HSV proteins. A total of 34 of 42 (81%) sera HSV-2 positive by MN, 19 of 43 (44%) sera HSV-1 positive by MN, and 0 of 19 sera negative by MN were positive by CF. Absorption-Western blotting showed that 12 of 18 (67%) sera HSV-1 positive by MN but positive by CF had no HSV-2-specific antibody and that all 7 sera HSV-2 positive by MN but negative by CF had HSV-2-specific antibody. When MN and absorption-Western blotting data were combined to analyze patients with no history of genital herpes, 7 of 19 (37%) with no HSV-2-specific antibody were positive by CF, and 7 of 27 (26%) with HSV-2-specific antibody were negative by CF. The positive and negative predictive values for the CF test were 78 and 75%, respectively, in this group. The presence of antibody to the HSV AG-4 antigen does not discriminate sufficiently between HSV-1- and HSV-2-infected patients to be of value in predicting HSV-2 infection in the absence of symptomatic disease. Images PMID:3023439

A critical comparison of the current view of Ca signaling with the novel concept of F-actin-based Ca signaling.

PubMed

Lange, Klaus; Gartzke, Joachim

2006-01-01

A detailed comparative survey on the current idea of Ca signaling and the alternative concept of F-actin-based Ca signaling is given. The two hypotheses differ in one central aspect - the mechanism of Ca storage. The current theory rests on the assumption of Ca-accumulating vesicles derived from the endoplasmic/ sarcoplasmic reticulum, which are equipped with an ATP-dependent Ca pump and IP3- or ryanodine-sensitive Ca-release channels/receptors. The alternative hypothesis proceeds from the idea of Ca storage at the high-affinity binding sites of F-actin subunits. Several prominent features of Ca signaling, which are not adequately described by the current concept, are inherent properties of the F-actin system and its dynamic state of treadmilling. F-actin is the only known biological Ca-binding system that has been proven by in vitro experiments to work within the physiological range of Ca concentrations and the only system that meets all necessary conditions to function as receptor-operated Ca store and as a coupling device between the Ca store and the store-operated Ca influx pathway. The most important properties of Ca signaling, such as store-channel coupling, quantal Ca release, spiking and oscillations, biphasic and "phasic" uptake kinetics, and Ca-induced Ca release, turn out to be systematic features of the new concept but remain unexplained by the classical vesicle storage hypothesis. A number of novel findings, specifically recent reports about direct effects of actin-specific toxins on Ca stores, have strengthened the new concept. The concept of F-actin-based Ca signaling combined with the notion of microvillar regulation of ion and substrate fluxes opens new aspects and far-reaching consequences, not only for cellular Ca signaling but also for various other cell functions, and represents an opportunity to connect several fields of cell physiology on the basis of a common mechanism.

Adenosine receptors and muscarinic receptors cooperate in acetylcholine release modulation in the neuromuscular synapse.

PubMed

Santafe, M M; Priego, M; Obis, T; Garcia, N; Tomàs, M; Lanuza, M A; Tomàs, J

2015-07-01

Adenosine receptors (ARs) are present in the motor terminals at the mouse neuromuscular junction. ARs and the presynaptic muscarinic acetylcholine receptors (mAChRs) share the functional control of the neuromuscular junction. We analysed their mutual interaction in transmitter release modulation. In electrophysiological experiments with unaltered synaptic transmission (muscles paralysed by blocking the voltage-dependent sodium channel of the muscle cells with μ-conotoxin GIIIB), we found that: (i) a collaborative action between different AR subtypes reduced synaptic depression at a moderate activity level (40 Hz); (ii) at high activity levels (100 Hz), endogenous adenosine production in the synaptic cleft was sufficient to reduce depression through A1 -type receptors (A1 Rs) and A2 A-type receptors (A2 A Rs); (iii) when the non-metabolizable 2-chloroadenosine (CADO) agonist was used, both the quantal content and depression were reduced; (iv) the protective effect of CADO on depression was mediated by A1 Rs, whereas A2 A Rs seemed to modulate A1 Rs; (v) ARs and mAChRs absolutely depended upon each other for the modulation of evoked and spontaneous acetylcholine release in basal conditions and in experimental conditions with CADO stimulation; (vi) the purinergic and muscarinic mechanisms cooperated in the control of depression by sharing a common pathway although the purinergic control was more powerful than the muscarinic control; and (vii) the imbalance of the ARs created by using subtype-selective and non-selective inhibitory and stimulatory agents uncoupled protein kinase C from evoked transmitter release. In summary, ARs (A1 Rs, A2 A Rs) and mAChRs (M1 , M2 ) cooperated in the control of activity-dependent synaptic depression and may share a common protein kinase C pathway. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Adenosine A₁ and A₂A receptor-mediated modulation of acetylcholine release in the mice neuromuscular junction.

PubMed

Garcia, Neus; Priego, Mercedes; Obis, Teresa; Santafe, Manel M; Tomàs, Marta; Besalduch, Nuria; Lanuza, M Angel; Tomàs, Josep

2013-07-01

Immunocytochemistry shows that purinergic receptors (P1Rs) type A1 and A2A (A1 R and A2 A R, respectively) are present in the nerve endings at the P6 and P30 Levator auris longus (LAL) mouse neuromuscular junctions (NMJs). As described elsewhere, 25 μm adenosine reduces (50%) acetylcholine release in high Mg(2+) or d-tubocurarine paralysed muscle. We hypothesize that in more preserved neurotransmission machinery conditions (blocking the voltage-dependent sodium channel of the muscle cells with μ-conotoxin GIIIB) the physiological role of the P1Rs in the NMJ must be better observed. We found that the presence of a non-selective P1R agonist (adenosine) or antagonist (8-SPT) or selective modulators of A1 R or A2 A R subtypes (CCPA and DPCPX, or CGS-21680 and SCH-58261, respectively) does not result in any changes in the evoked release. However, P1Rs seem to be involved in spontaneous release (miniature endplate potentials MEPPs) because MEPP frequency is increased by non-selective block but decreased by non-selective stimulation, with A1 Rs playing the main role. We assayed the role of P1Rs in presynaptic short-term plasticity during imposed synaptic activity (40 Hz for 2 min of supramaximal stimuli). Depression is reduced by micromolar adenosine but increased by blocking P1Rs with 8-SPT. Synaptic depression is not affected by the presence of selective A1 R and A2 A R modulators, which suggests that both receptors need to collaborate. Thus, A1 R and A2 A R might have no real effect on neuromuscular transmission in resting conditions. However, these receptors can conserve resources by limiting spontaneous quantal leak of acetylcholine and may protect synaptic function by reducing the magnitude of depression during repetitive activity. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Excitation-transcription coupling via calcium/calmodulin-dependent protein kinase/ERK1/2 signaling mediates the coordinate induction of VGLUT2 and Narp triggered by a prolonged increase in glutamatergic synaptic activity.

PubMed

Doyle, Sukhjeevan; Pyndiah, Slovénie; De Gois, Stéphanie; Erickson, Jeffrey D

2010-05-07

Homeostatic scaling of glutamatergic and GABAergic transmission is triggered by prolonged alterations in synaptic neuronal activity. We have previously described a presynaptic mechanism for synaptic homeostasis and plasticity that involves scaling the level of vesicular glutamate (VGLUT1) and gamma-aminobutyric acid (GABA) (VGAT) transporter biosynthesis. These molecular determinants of vesicle filling and quantal size are regulated by neuronal activity in an opposite manner and bi-directionally. Here, we report that a striking induction of VGLUT2 mRNA and synaptic protein is triggered by a prolonged increase in glutamatergic synaptic activity in mature neocortical neuronal networks in vitro together with two determinants of inhibitory synaptic strength, the neuronal activity-regulated pentraxin (Narp), and glutamate decarboxylase (GAD65). Activity-dependent induction of VGLUT2 and Narp exhibits a similar intermediate-early gene response that is blocked by actinomycin D and tetrodotoxin, by inhibitors of ionotropic glutamate receptors and L-type voltage-gated calcium channels, and is dependent on downstream signaling via calmodulin, calcium/calmodulin-dependent protein kinase (CaMK) and extracellular signal-regulated kinase 1/2 (ERK1/2). The co-induction of VGLUT2 and Narp triggered by prolonged gamma-aminobutyric acid type A receptor blockade is independent of brain-derived nerve growth factor and TrkB receptor signaling. VGLUT2 protein induction occurs on a subset of cortically derived synaptic vesicles in excitatory synapses on somata and dendritic processes of multipolar GABAergic interneurons, recognized sites for the clustering of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate glutamate receptors by Narp. We propose that VGLUT2 and Narp induction by excitation-transcription coupling leads to increased glutamatergic transmission at synapses on GABAergic inhibitory feedback neurons as part of a coordinated program of Ca(2+)-signal transcription involved in mechanisms of homeostatic plasticity after prolonged hyperactivity.

Draft of a general stochastic theory of cancer and its possible experimental verification with monoclonal multiplication of repairing and immunological systems.

PubMed

Agrell, U

1986-07-01

A general stochastic theory of cancer is outlined by applying to cancer the laws of quantum mechanics instead of the laws of traditional physics, especially with regard to the concept of cause. This theory is combined with the evolutionary theory on the one hand and the mutation theory of aging/death of multicellular beings consisting of somatic cells on the other. The cancer theory centers around the phenomenon of DNA mutating randomly by quantal steps. Because of mutations in the DNA in general as well as in the special DNA which codes for the DNA repairing systems the body is permeated in the course of time - via increasing losses of information in the DNA - with increasingly altered proteins which is observed as aging process. From this process of entropy the concept of the cancer cell is deduced: When the losses of information in a certain cell and also in the repairing and immunological systems have random concordances, cancer as a type of antigens comes into existence. Here the concept of CONCORDANCE OF "BLURRING" is introduced. This CONCORDANCE OF "BLURRING" occurs randomly approximately once among three times 60 000 billion cells, i.e. three human beings. The so-called "oncogenes" are integrated into this theory. It is proposed to test this theory using monozygotic twins both suffering from cancer: By injecting monoclonally multiplied immunological systems, eventually also repair-systems, from the respective other twin, the proposition is that the cancer would be cured in both twins. If this critical experiment is successful, one can cure human beings suffering from cancer by the same procedure, using those systems of their relatives. This treatment would cure the cancer to the extent to which there is a genetic correspondence in the sections of genes coding for these systems.

First On-Site Data Analysis System for Subaru/Suprime-Cam

NASA Astrophysics Data System (ADS)

Furusawa, Hisanori; Okura, Yuki; Mineo, Sogo; Takata, Tadafumi; Nakata, Fumiaki; Tanaka, Manobu; Katayama, Nobuhiko; Itoh, Ryosuke; Yasuda, Naoki; Miyazaki, Satoshi; Komiyama, Yutaka; Utsumi, Yousuke; Uchida, Tomohisa; Aihara, Hiroaki

2011-03-01

We developed an automated on-site quick analysis system for mosaic CCD data of Suprime-Cam, which is a wide-field camera mounted at the prime focus of the Subaru Telescope, Mauna Kea, Hawaii. The first version of the data-analysis system was constructed, and started to operate in general observations. This system is a new function of observing support at the Subaru Telescope to provide the Subaru user community with an automated on-site data evaluation, aiming at improvements of observers' productivity, especially in large imaging surveys. The new system assists the data evaluation tasks in observations by the continuous monitoring of the characteristics of every data frame during observations. The evaluation results and data frames processed by this system are also useful for reducing the data-processing time in a full analysis after an observation. The primary analysis functions implemented in the data-analysis system are composed of automated realtime analysis for data evaluation and on-demand analysis, which is executed upon request, including mosaicing analysis and flat making analysis. In data evaluation, which is controlled by the organizing software, the database keeps track of the analysis histories, as well as the evaluated values of data frames, including seeing and sky background levels; it also helps in the selection of frames for mosaicing and flat making analysis. We examined the system performance and confirmed an improvement in the data-processing time by a factor of 9 with the aid of distributed parallel data processing and on-memory data processing, which makes the automated data evaluation effective.

Decision-making process of Kala Azar care: results from a qualitative study carried out in disease endemic areas of Nepal

PubMed Central

2013-01-01

Background Analysis of consumer decision making in the health sector is a complex process of comparing feasible alternatives and evaluating the levels of satisfaction associated with the relevant options. This paper makes an attempt to understand how and why consumers make specific decisions, what motivates them to adopt a specific health intervention, and what features they find attractive in each of the options. Method The study used a descriptive-explanatory design to analyze the factors determining the choices of healthcare providers. Information was collected through focus group discussions and in-depth interviews. Results The results suggest that the decision making related to seeking healthcare for Kala Azar (KA) treatment is a complex, interactive process. Patients and family members follow a well-defined road map for decision making. The process of decision making starts from the recognition of healthcare needs and is then modified by a number of other factors, such as indigenous knowledge, healthcare alternatives, and available resources. Household and individual characteristics also play important roles in facilitating the process of decision making. The results from the group discussions and in-depth interviews are consistent with the idea that KA patients and family members follow the rational approach of weighing the costs against the benefits of using specific types of medical care. Conclusion The process of decision making related to seeking healthcare follows a complex set of steps and many of the potential factors affect the decision making in a non-linear fashion. Our analysis suggests that it is possible to derive a generalized road map of the decision-making process starting from the recognition of healthcare needs, and then modifying it to show the influences of indigenous knowledge, healthcare alternatives, and available resources. PMID:23849617

Decision-making process of Kala Azar care: results from a qualitative study carried out in disease endemic areas of Nepal.

PubMed

Adhikari, Shiva Raj; Supakankunti, Siripen; Khan, M Mahmud

2013-07-12

Analysis of consumer decision making in the health sector is a complex process of comparing feasible alternatives and evaluating the levels of satisfaction associated with the relevant options. This paper makes an attempt to understand how and why consumers make specific decisions, what motivates them to adopt a specific health intervention, and what features they find attractive in each of the options. The study used a descriptive-explanatory design to analyze the factors determining the choices of healthcare providers. Information was collected through focus group discussions and in-depth interviews. The results suggest that the decision making related to seeking healthcare for Kala Azar (KA) treatment is a complex, interactive process. Patients and family members follow a well-defined road map for decision making. The process of decision making starts from the recognition of healthcare needs and is then modified by a number of other factors, such as indigenous knowledge, healthcare alternatives, and available resources. Household and individual characteristics also play important roles in facilitating the process of decision making. The results from the group discussions and in-depth interviews are consistent with the idea that KA patients and family members follow the rational approach of weighing the costs against the benefits of using specific types of medical care. The process of decision making related to seeking healthcare follows a complex set of steps and many of the potential factors affect the decision making in a non-linear fashion. Our analysis suggests that it is possible to derive a generalized road map of the decision-making process starting from the recognition of healthcare needs, and then modifying it to show the influences of indigenous knowledge, healthcare alternatives, and available resources.

GSFC VLBI Analysis center

NASA Technical Reports Server (NTRS)

Gordon, David; Ma, Chopo; MacMillan, Dan; Petrov, Leonid; Baver, Karen

2005-01-01

This report presents the activities of the GSFC VLBI Analysis Center during 2004. The GSFC Analysis Center analyzes all IVS sessions, makes regular IVS submissions of data and analysis products, and performs research and software development activities aimed at improving the VLBI technique.

GSFC VLBI Analysis Center

NASA Technical Reports Server (NTRS)

Gordon, David; Ma, Chopo; MacMillan, Dan; Gipson, John; Bolotin, Sergei; Le Bail, Karine; Baver, Karen

2013-01-01

This report presents the activities of the GSFC VLBI Analysis Center during 2012. The GSFC VLBI Analysis Center analyzes all IVS sessions, makes regular IVS submissions of data and analysis products, and performs research and software development aimed at improving the VLBI technique.

Skill Transfer and Virtual Training for IND Response Decision-Making: Analysis of Decision-Making Skills for Large Scale Incidents

DTIC Science & Technology

2016-01-01

issues comes from the Fukushima Daiichi nuclear disaster (2011). The local medical health professional on staff at the U.S. embassy in Tokyo was not...distribution unlimited. This page intentionally left blank. iii EXECUTIVE SUMMARY An improvised nuclear device (IND...from the phase one analysis are as follows : • There is strong consistency in both the key decisions and underlying skills emphasized by emergency

Analysis of Ordinary Public Fund and Its Impact on the Quality of Academic Programs in the Higher Education in the Subsystem of the Polytechnic Universities in Mexico

ERIC Educational Resources Information Center

Monroy, Pedro Salazar; Arcos-Vega, José L.; Garcia, Juan J. Sevilla

2017-01-01

In 2015, there was the need of making this study to determine the efficient and effectiveness management for making decisions in respect to the ordinary fund allocations and their impact on the quality of the academic programs into the Polytechnic engineering universities in Mexico. This analysis is very important for providing essential evidence…

Elementary and Advanced Computer Projects for the Physics Classroom and Laboratory

DTIC Science & Technology

1992-12-01

are SPF/PC, MS Word, n3, Symphony, Mathematics, and FORTRAN. The authors’ programs assist data analysis in particular laboratory experiments and make...assist data analysis in particular laboratory experiments and make use of the Monte Carlo and other numerical techniques in computer simulation and...the language of science and engineering in industry and government laboratories (alth..4h C is becoming a powerful competitor ). RM/FORTRAN (cost $400

Escalation research: Providing new frontiers for applying behavior analysis to organizational behavior

PubMed Central

Goltz, Sonia M.

2000-01-01

Decision fiascoes such as escalation of commitment, the tendency of decision makers to “throw good money after bad,” can have serious consequences for organizations and are therefore of great interest in applied research. This paper discusses the use of behavior analysis in organizational behavior research on escalation. Among the most significant aspects of behavior-analytic research on escalation is that it has indicated that both the patterns of outcomes that decision makers have experienced for past decisions and the patterns of responses that they make are critical for understanding escalation. This research has also stimulated the refinement of methods by researchers to better assess decision making and the role reinforcement plays in it. Finally, behavior-analytic escalation research has not only indicated the utility of reinforcement principles for predicting more complex human behavior but has also suggested some additional areas for future exploration of decision making using behavior analysis. PMID:22478347

Standardization of crash analysis in Florida.

DOT National Transportation Integrated Search

2012-03-01

Crash analysis assists agencies in determining : appropriate roadway or intersection improvements : or countermeasures that can make travel on : roadways safer. Crash analysis examines many : aspects of travel and can involve specialists : from enfor...

Geospatial Data Sciences | Energy Analysis | NREL

Science.gov Websites

, demographics, and the earth's physical geography to provide the foundation for energy analysis and decision -making. Photo of two people discussing a map. Geospatial Analysis Our geographic information system

Development of Decision Making in School-Aged Children and Adolescents: Evidence from Heart Rate and Skin Conductance Analysis

ERIC Educational Resources Information Center

Crone, Eveline A.; van der Molen, Maurits W.

2007-01-01

Age differences in decision making indicate that children fail to anticipate outcomes of their decisions. Using heart rate and skin conductance analyses, we tested whether developmental changes in decision making are associated with (a) a failure to process outcomes of decisions, or (b) a failure to anticipate future outcomes of decisions.…

The Process of Making Meaning: The Interplay between Teachers' Knowledge of Mathematical Proofs and Their Classroom Practices

ERIC Educational Resources Information Center

Paddack, Megan

2009-01-01

The purpose of this study was to investigate and describe how middle school mathematics teachers "make meaning" of proofs and the process of proving in the context of their classroom practices. A framework of "making meaning," created by the researcher, guided the data collection and analysis phases of the study. This framework…

On the Road to Empowerment: A Comprehensive Analysis of Teacher Involvement in Decision Making Processes.

ERIC Educational Resources Information Center

Murray, David R.; And Others

Within the arena of public school reform, teacher empowerment and participation in the decision making process at the building level are of paramount importance. A collaborative team of teacher educators and public school staff was assembled to assess various perceptions of site-based decision making throughout Georgia. A random sample of 400…

Schools and Data: The Educator's Guide for Using Data to Improve Decision Making

ERIC Educational Resources Information Center

Creighton, Theodore B.

2006-01-01

Since the first edition of "Schools and Data", the No Child Left Behind Act has swept the country, and data-based decision making is no longer an option for educators. Today's educational climate makes it imperative for all schools to collect data and use statistical analysis to help create clear goals and recognize strategies for…

The Foci of In-Action Professional Judgement and Decision-Making in High-Level Adventure Sports Coaching Practice

ERIC Educational Resources Information Center

Collins, Loel; Collins, Dave

2017-01-01

This article continues a theme of previous investigations by the authors and examines the focus of in-action reflection as a component of professional judgement and decision-making (PJDM) processes in high-level adventure sports coaching. We utilised a thematic analysis approach to investigate the decision-making practices of a sample of…

Expanding Learning in the Workplace: Making More of Individual and Organisational Potential. A NIACE Policy Discussion Paper.

ERIC Educational Resources Information Center

Unwin, Lorna; Fuller, Alison

Ways of expanding workplace learning in the United Kingdom by making better use of individual and organizational potential were examined. The analysis focused on the following issues: ways of fostering, improving, and increasing learning in the workplace; ways of enhancing access to and participation in workplace learning; ways of making workplace…

Variations in Decision-Making Approach to Tertiary Teaching: A Case Study in Vietnam

ERIC Educational Resources Information Center

Nguyen, Thanh Tien

2016-01-01

Although the question of what to teach and how to teach has received much attention from the literature, little was known about the way in which academics in teaching groups make decision on what and how to teach. This paper reports an analysis of variations in the decision-making approach to tertiary teaching through academics' practices of…

Genetic Factors of Individual Differences in Decision Making in Economic Behavior: A Japanese Twin Study using the Allais Problem.

PubMed

Shikishima, Chizuru; Hiraishi, Kai; Yamagata, Shinji; Ando, Juko; Okada, Mitsuhiro

2015-01-01

Why does decision making differ among individuals? People sometimes make seemingly inconsistent decisions with lower expected (monetary) utility even when objective information of probabilities and reward are provided. It is noteworthy, however, that a certain proportion of people do not provide anomalous responses, choosing the alternatives with higher expected utility, thus appearing to be more "rational." We investigated the genetic and environmental influences on these types of individual differences in decision making using a classical Allais problem task. Participants were 1,199 Japanese adult twins aged 20-47. Univariate genetic analysis revealed that approximately a third of the Allais problem response variance was explained by genetic factors and the rest by environmental factors unique to individuals and measurement error. The environmental factor shared between families did not contribute to the variance. Subsequent multivariate genetic analysis clarified that decision making using the expected utility theory was associated with general intelligence and that the association was largely mediated by the same genetic factor. We approach the mechanism underlying two types of "rational" decision making from the perspective of genetic correlations with cognitive abilities.