144 research outputs found
A point process framework for modeling electrical stimulation of the auditory nerve
Model-based studies of auditory nerve responses to electrical stimulation can
provide insight into the functioning of cochlear implants. Ideally, these
studies can identify limitations in sound processing strategies and lead to
improved methods for providing sound information to cochlear implant users. To
accomplish this, models must accurately describe auditory nerve spiking while
avoiding excessive complexity that would preclude large-scale simulations of
populations of auditory nerve fibers and obscure insight into the mechanisms
that influence neural encoding of sound information. In this spirit, we develop
a point process model of the auditory nerve that provides a compact and
accurate description of neural responses to electric stimulation. Inspired by
the framework of generalized linear models, the proposed model consists of a
cascade of linear and nonlinear stages. We show how each of these stages can be
associated with biophysical mechanisms and related to models of neuronal
dynamics. Moreover, we derive a semi-analytical procedure that uniquely
determines each parameter in the model on the basis of fundamental statistics
from recordings of single fiber responses to electric stimulation, including
threshold, relative spread, jitter, and chronaxie. The model also accounts for
refractory and summation effects that influence the responses of auditory nerve
fibers to high pulse rate stimulation. Throughout, we compare model predictions
to published physiological data and explain differences in auditory nerve
responses to high and low pulse rate stimulation. We close by performing an
ideal observer analysis of simulated spike trains in response to sinusoidally
amplitude modulated stimuli and find that carrier pulse rate does not affect
modulation detection thresholds.Comment: 1 title page, 27 manuscript pages, 14 figures, 1 table, 1 appendi
Simple, Fast and Accurate Implementation of the Diffusion Approximation Algorithm for Stochastic Ion Channels with Multiple States
The phenomena that emerge from the interaction of the stochastic opening and
closing of ion channels (channel noise) with the non-linear neural dynamics are
essential to our understanding of the operation of the nervous system. The
effects that channel noise can have on neural dynamics are generally studied
using numerical simulations of stochastic models. Algorithms based on discrete
Markov Chains (MC) seem to be the most reliable and trustworthy, but even
optimized algorithms come with a non-negligible computational cost. Diffusion
Approximation (DA) methods use Stochastic Differential Equations (SDE) to
approximate the behavior of a number of MCs, considerably speeding up
simulation times. However, model comparisons have suggested that DA methods did
not lead to the same results as in MC modeling in terms of channel noise
statistics and effects on excitability. Recently, it was shown that the
difference arose because MCs were modeled with coupled activation subunits,
while the DA was modeled using uncoupled activation subunits. Implementations
of DA with coupled subunits, in the context of a specific kinetic scheme,
yielded similar results to MC. However, it remained unclear how to generalize
these implementations to different kinetic schemes, or whether they were faster
than MC algorithms. Additionally, a steady state approximation was used for the
stochastic terms, which, as we show here, can introduce significant
inaccuracies. We derived the SDE explicitly for any given ion channel kinetic
scheme. The resulting generic equations were surprisingly simple and
interpretable - allowing an easy and efficient DA implementation. The algorithm
was tested in a voltage clamp simulation and in two different current clamp
simulations, yielding the same results as MC modeling. Also, the simulation
efficiency of this DA method demonstrated considerable superiority over MC
methods.Comment: 32 text pages, 10 figures, 1 supplementary text + figur
The what and where of adding channel noise to the Hodgkin-Huxley equations
One of the most celebrated successes in computational biology is the
Hodgkin-Huxley framework for modeling electrically active cells. This
framework, expressed through a set of differential equations, synthesizes the
impact of ionic currents on a cell's voltage -- and the highly nonlinear impact
of that voltage back on the currents themselves -- into the rapid push and pull
of the action potential. Latter studies confirmed that these cellular dynamics
are orchestrated by individual ion channels, whose conformational changes
regulate the conductance of each ionic current. Thus, kinetic equations
familiar from physical chemistry are the natural setting for describing
conductances; for small-to-moderate numbers of channels, these will predict
fluctuations in conductances and stochasticity in the resulting action
potentials. At first glance, the kinetic equations provide a far more complex
(and higher-dimensional) description than the original Hodgkin-Huxley
equations. This has prompted more than a decade of efforts to capture channel
fluctuations with noise terms added to the Hodgkin-Huxley equations. Many of
these approaches, while intuitively appealing, produce quantitative errors when
compared to kinetic equations; others, as only very recently demonstrated, are
both accurate and relatively simple. We review what works, what doesn't, and
why, seeking to build a bridge to well-established results for the
deterministic Hodgkin-Huxley equations. As such, we hope that this review will
speed emerging studies of how channel noise modulates electrophysiological
dynamics and function. We supply user-friendly Matlab simulation code of these
stochastic versions of the Hodgkin-Huxley equations on the ModelDB website
(accession number 138950) and
http://www.amath.washington.edu/~etsb/tutorials.html.Comment: 14 pages, 3 figures, review articl
Pharmacokinetics of isoflavones, daidzein and genistein, after ingestion of soy beverage compared with soy extract capsules in postmenopausal Thai women
BACKGROUND: Isoflavones from soybeans may provide some beneficial impacts on postmenopausal health. The purpose of this study was to compare the pharmacokinetics and bioavailability of plasma isoflavones (daidzein and genistein) after a single dose of orally administered soy beverage and soy extract capsules in postmenopausal Thai women. METHODS: We conducted a randomized two-phase crossover pharmacokinetic study in 12 postmenopausal Thai women. In the first phase, each subject randomly received either 2 soy extract capsules (containing daidzin : genistin = 7.79 : 22.57 mg), or soy beverage prepared from 15 g of soy flour (containing daidzin : genistin = 9.27 : 10.51 mg). In the second phase, the subjects received an alternative preparation in the same manner after a washout period of at least 1 week. Blood samples were collected immediately before and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24 and 32 h after administration of the soy preparation in each phase. Plasma daidzein and genistein concentrations were determined by using high performance liquid chromatography (HPLC). The pharmacokinetic parameters of daidzein and genistein, i.e. maximal plasma concentration (C(max)), time to maximal plasma concentration (T(max)), area under the plasma concentration-time curve (AUC) and half-life (t(1/2)), were estimated using the TopFit version 2.0 software with noncompartmental model analysis. RESULTS: There were no significant differences in the mean values of C(max)/dose, AUC(0–32)/dose, AUC(0-∝)/dose, T(max), and t(1/2 )of genistein between both preparations. For pharmacokinetic parameters of daidzein, the mean values of C(max)/dose, T(max), and t(1/2 )did not significantly differ between both preparations. Nonetheless, the mean AUC(0–32)/dose and AUC(0-∝)/dose after administration of soy extract capsules were slightly (but significantly, p < 0.05) higher than those of soy beverage. CONCLUSION: The bioavailability of daidzein, which was adjusted for the administered dose (AUC/dose), following a single oral administration of soy beverage was slightly (but significantly) less than that of soy extract capsules, whereas, the bioavailability adjusted for administered dose of genistein from both soy preparations were comparable. The other pharmacokinetic parameters of daidzein and genistein, including C(max )adjusted for the dose, T(max )and t(1/2), were not different between both soy preparations
Citizenship Education and Liberalism: A State of the Debate Analysis 1990–2010
What kind of citizenship education, if any, should schools in liberal societies promote? And what ends is such education supposed to serve? Over the last decades a respectable body of literature has emerged to address these and related issues. In this state of the debate analysis we examine a sample of journal articles dealing with these very issues spanning a twenty-year period with the aim to analyse debate patterns and developments in the research field. We first carry out a qualitative analysis where we design a two-dimensional theoretical framework in order to systematise the various liberal debate positions, and make us able to study their justifications, internal tensions and engagements with other positions. In the ensuing quantitative leg of the study we carry out a quantitative bibliometric analysis where we weigh the importance of specific scholars. We finally discuss possible merits and flaws in the research field, as evidenced in and by the analysis
The Resource Curse and Rentier States in the Caspian Region : A Need for Context Analysis
Although much attention is paid to the Caspian region with regard to energy issues, the domestic
consequences of the region’s resource production have so far constituted a neglected field of research.
A systematic survey of the latest research trends in the economic and political causalities of
the resource curse and of rentier states reveals that there is a need for context analysis. In reference
to this, the paper traces any shortcomings and promising approaches in the existent body of literature
on the Caspian region. Following on from this, the paper then proposes a new approach; specifically,
one in which any differences and similarities in the context conditions are captured. This
enables a more precise exploration of the exact ways in which they form contemporary post-Soviet
Caspian rentier states.Obwohl der Region am Kaspischen Meer im Zuge von Energiediskursen große Aufmerksamkeit zuteil
wird, stellen die innerstaatlichen Folgen der Ressourcenproduktion in der Region ein bislang
vernachlässigtes Forschungsfeld dar. Ein systematischer Überblick über die jüngsten Forschungstrends
zu wirtschaftlichen und politischen Kausalzusammenhängen des Ressourcenfluchs und zu
Rentierstaaten offenbart die Notwendigkeit von Kontextanalysen. Hierauf Bezug nehmend, analysiert
der Aufsatz sowohl die Mängel als auch viel versprechende Ansätze in der betreffenden Literatur
zur Region am Kaspischen Meer. Der Aufsatz stellt letztendlich einen neuen Ansatz vor, der
Unterschiede und Gemeinsamkeiten in den Kontextbedingungen erfasst, um zu erforschen, wie diese
die gegenwärtigen post-sowjetischen Rentierstaaten in der Region am Kaspischen Meer tatsächlich
prägen
- …