177 research outputs found
Local symmetries in gauge theories in a finite-dimensional setting
It is shown that the correct mathematical implementation of symmetry in the
geometric formulation of classical field theory leads naturally beyond the
concept of Lie groups and their actions on manifolds, out into the realm of Lie
group bundles and, more generally, of Lie groupoids and their actions on fiber
bundles. This applies not only to local symmetries, which lie at the heart of
gauge theories, but is already true even for global symmetries when one allows
for fields that are sections of bundles with (possibly) non-trivial topology
or, even when these are topologically trivial, in the absence of a preferred
trivialization.Comment: 23 page
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Taking the lag out of jet lag through model-based schedule design
Travel across multiple time zones results in desynchronization of environmental time cues and the sleep–wake schedule from their normal phase relationships with the endogenous circadian system. Circadian misalignment can result in poor neurobehavioral performance, decreased sleep efficiency, and inappropriately timed physiological signals including gastrointestinal activity and hormone release. Frequent and repeated transmeridian travel is associated with long-term cognitive deficits, and rodents experimentally exposed to repeated schedule shifts have increased death rates. One approach to reduce the short-term circadian, sleep–wake, and performance problems is to use mathematical models of the circadian pacemaker to design countermeasures that rapidly shift the circadian pacemaker to align with the new schedule. In this paper, the use of mathematical models to design sleep–wake and countermeasure schedules for improved performance is demonstrated. We present an approach to designing interventions that combines an algorithm for optimal placement of countermeasures with a novel mode of schedule representation. With these methods, rapid circadian resynchrony and the resulting improvement in neurobehavioral performance can be quickly achieved even after moderate to large shifts in the sleep–wake schedule. The key schedule design inputs are endogenous circadian period length, desired sleep–wake schedule, length of intervention, background light level, and countermeasure strength. The new schedule representation facilitates schedule design, simulation studies, and experiment design and significantly decreases the amount of time to design an appropriate intervention. The method presented in this paper has direct implications for designing jet lag, shift-work, and non-24-hour schedules, including scheduling for extreme environments, such as in space, undersea, or in polar regions
Optimal stimulus shapes for neuronal excitation
The work is made available under the Creative Commons CC0 public domain dedication. The definitive version was published in PLoS Computational Biology 7 (2011): e1002089, doi:10.1371/journal.pcbi.1002089.An important problem in neuronal computation is to discern how features of stimuli control the timing of action potentials. One aspect of this problem is to determine how an action potential, or spike, can be elicited with the least energy cost, e.g., a minimal amount of applied current. Here we show in the Hodgkin & Huxley model of the action potential and in experiments on squid giant axons that: 1) spike generation in a neuron can be highly discriminatory for stimulus shape and 2) the optimal stimulus shape is dependent upon inputs to the neuron. We show how polarity and time course of post-synaptic currents determine which of these optimal stimulus shapes best excites the neuron. These results are obtained mathematically using the calculus of variations and experimentally using a stochastic search methodology. Our findings reveal a surprising complexity of computation at the single cell level that may be relevant for understanding optimization of signaling in neurons and neuronal networks.This work was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 and NIH grant R01 HL718884 to DP. DBF is an AFOSR Young Investigator (FA 9550-08-01-0076)
A mechanism for robust circadian timekeeping via stoichiometric balance
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102189/1/msb201262.reviewer_comments.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102189/2/msb201262.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102189/3/msb201262-sup-0001.pd
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