760 research outputs found
Adaptive response and enlargement of dynamic range
Many membrane channels and receptors exhibit adaptive, or desensitized,
response to a strong sustained input stimulus, often supported by protein
activity-dependent inactivation. Adaptive response is thought to be related to
various cellular functions such as homeostasis and enlargement of dynamic range
by background compensation. Here we study the quantitative relation between
adaptive response and background compensation within a modeling framework. We
show that any particular type of adaptive response is neither sufficient nor
necessary for adaptive enlargement of dynamic range. In particular a precise
adaptive response, where system activity is maintained at a constant level at
steady state, does not ensure a large dynamic range neither in input signal nor
in system output. A general mechanism for input dynamic range enlargement can
come about from the activity-dependent modulation of protein responsiveness by
multiple biochemical modification, regardless of the type of adaptive response
it induces. Therefore hierarchical biochemical processes such as methylation
and phosphorylation are natural candidates to induce this property in signaling
systems.Comment: Corrected typos, minor text revision
Pediatric stroke and transcranial direct current stimulation: methods for rational individualized dose optimization
Background: Transcranial direct current stimulation (tDCS) has been investigated mainly in adults and doses may not be appropriate in pediatric applications. In perinatal stroke where potential applications are promising, rational adaptation of dosage for children remains under investigation. Objective: Construct child-specific tDCS dosing parameters through case study within a perinatal stroke tDCS safety and feasibility trial. Methods: 10-year-old subject with a diagnosis of presumed perinatal ischemic stroke and hemiparesis was identified. T1 magnetic resonance imaging (MRI) scans used to derive computerized model for current flow and electrode positions. Workflow using modeling results and consideration of dosage in previous clinical trials was incorporated. Prior ad hoc adult montages vs. de novo optimized montages provided distinct risk benefit analysis. Approximating adult dose required consideration of changes in both peak brain current flow and distribution which further tradeoff between maximizing efficacy and adding safety factors. Electrode size, position, current intensity, compliance voltage, and duration were controlled independently in this process. Results: Brain electric fields modeled and compared to values previously predicted models (Datta et al., 2011; Minhas et al., 2012). Approximating conservative brain current flow patterns and intensities used in previous adult trials for comparable indications, the optimal current intensity established was 0.7 mA for 10 min with a tDCS C3/C4 montage. Specifically 0.7 mA produced comparable peak brain current intensity of an average adult receiving 1.0 mA. Electrode size of 5 Ă— 7 cm2 with 1.0 mA and low-voltage tDCS was employed to maximize tolerability. Safety and feasibility confirmed with subject tolerating the session well and no serious adverse events. Conclusion: Rational approaches to dose customization, with steps informed by computational modeling, may improve guidance for pediatric stroke tDCS trials
Interlayer Registry Determines the Sliding Potential of Layered Metal Dichalcogenides: The case of 2H-MoS2
We provide a simple and intuitive explanation for the interlayer sliding
energy landscape of metal dichalcogenides. Based on the recently introduced
registry index (RI) concept, we define a purely geometrical parameter which
quantifies the degree of interlayer commensurability in the layered phase of
molybdenum disulphide (2HMoS2). A direct relation between the sliding energy
landscape and the corresponding interlayer registry surface of 2H-MoS2 is
discovered thus marking the registry index as a computationally efficient means
for studying the tribology of complex nanoscale material interfaces in the
wearless friction regime.Comment: 13 pages, 7 figure
Stochastic Resonance in Ion Channels Characterized by Information Theory
We identify a unifying measure for stochastic resonance (SR) in voltage
dependent ion channels which comprises periodic (conventional), aperiodic and
nonstationary SR. Within a simplest setting, the gating dynamics is governed by
two-state conductance fluctuations, which switch at random time points between
two values. The corresponding continuous time point process is analyzed by
virtue of information theory. In pursuing this goal we evaluate for our
dynamics the tau-information, the mutual information and the rate of
information gain. As a main result we find an analytical formula for the rate
of information gain that solely involves the probability of the two channel
states and their noise averaged rates. For small voltage signals it simplifies
to a handy expression. Our findings are applied to study SR in a potassium
channel. We find that SR occurs only when the closed state is predominantly
dwelled. Upon increasing the probability for the open channel state the
application of an extra dose of noise monotonically deteriorates the rate of
information gain, i.e., no SR behavior occurs.Comment: 10 pages, 2 figures, to appear in Phys. Rev.
Density-dependence of functional development in spiking cortical networks grown in vitro
During development, the mammalian brain differentiates into specialized
regions with distinct functional abilities. While many factors contribute to
functional specialization, we explore the effect of neuronal density on the
development of neuronal interactions in vitro. Two types of cortical networks,
dense and sparse, with 50,000 and 12,000 total cells respectively, are studied.
Activation graphs that represent pairwise neuronal interactions are constructed
using a competitive first response model. These graphs reveal that, during
development in vitro, dense networks form activation connections earlier than
sparse networks. Link entropy analysis of dense net- work activation graphs
suggests that the majority of connections between electrodes are reciprocal in
nature. Information theoretic measures reveal that early functional information
interactions (among 3 cells) are synergetic in both dense and sparse networks.
However, during later stages of development, previously synergetic
relationships become primarily redundant in dense, but not in sparse networks.
Large link entropy values in the activation graph are related to the domination
of redundant ensembles in late stages of development in dense networks. Results
demonstrate differences between dense and sparse networks in terms of
informational groups, pairwise relationships, and activation graphs. These
differences suggest that variations in cell density may result in different
functional specialization of nervous system tissue in vivo.Comment: 10 pages, 7 figure
Amelioration of bleomycin-induced lung fibrosis in hamsters by dietary supplementation with taurine and niacin: biochemical mechanisms.
Interstitial pulmonary fibrosis induced by intratracheal instillation of bleomycin (BL) involves an excess production of reactive oxygen species, unavailability of adequate levels of NAD and ATP to repair the injured pulmonary epithelium, and an overexuberant lung collagen reactivity followed by deposition of highly cross-linked mature collagen fibrils resistant to enzymatic degradation. In the present study, we have demonstrated that dietary supplementation with taurine and niacin offered almost complete protection against the lung fibrosis in a multidose BL hamster model. The mechanisms for the protective effect of taurine and niacin are multifaceted. These include the ability of taurine to scavenge HOCl and stabilize the biomembrane; niacin's ability to replenish the BL-induced depletion of NAD and ATP; and the combined effect of taurine and niacin to suppress all aspects of BL-induced increases in the lung collagen reactivity, a hallmark of interstitial pulmonary fibrosis. It was concluded from the data presented at this Conference that the combined treatment with taurine and niacin, which offers a multipronged approach, will have great therapeutic potential in the intervention of the development of chemically induced interstitial lung fibrosis in animals and humans
Wavelength-Selective Switch with Direct Few Mode Fiber Integration
The first realization of a wavelength-selective switch (WSS) with direct integration of few mode fibers (FMF) is fully described. The freespace optics FMF-WSS dynamically steers spectral information-bearing beams containing three spatial modes from an input port to one of nine output ports using a phase spatial light modulator. Sources of mode dependent losses (MDL) are identified, analytically analyzed and experimentally confirmed on account of different modal sensitivities to fiber coupling in imperfect imaging and at spectral channel edges due to mode clipping. These performance impacting effects can be reduced by adhering to provided design guidelines, which scale in support of higher spatial mode counts. The effect on data transmission of cascaded passband filtering and MDL build-up is experimentally investigated in detail
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