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Cooling the dark energy camera instrument
DECam, camera for the Dark Energy Survey (DES), is undergoing general design and component testing. For an overview see DePoy, et al in these proceedings. For a description of the imager, see Cease, et al in these proceedings. The CCD instrument will be mounted at the prime focus of the CTIO Blanco 4m telescope. The instrument temperature will be 173K with a heat load of 113W. In similar applications, cooling CCD instruments at the prime focus has been accomplished by three general methods. Liquid nitrogen reservoirs have been constructed to operate in any orientation, pulse tube cryocoolers have been used when tilt angles are limited and Joule-Thompson or Stirling cryocoolers have been used with smaller heat loads. Gifford-MacMahon cooling has been used at the Cassegrain but not at the prime focus. For DES, the combined requirements of high heat load, temperature stability, low vibration, operation in any orientation, liquid nitrogen cost and limited space available led to the design of a pumped, closed loop, circulating nitrogen system. At zenith the instrument will be twelve meters above the pump/cryocooler station. This cooling system expected to have a 10,000 hour maintenance interval. This paper will describe the engineering basis including the thermal model, unbalanced forces, cooldown time, the single and two-phase flow model
Ion Channel Regulation in the Pathophysiology of Atrial Fibrillation: Using Mathematical Modeling as a Predictive Tool for Cardiac Disease
Cycle length restitution in sinoatrial node cells: a theory for understanding spontaneous action potential dynamics.
Normal heart rhythm (sinus rhythm) is governed by the sinoatrial node, a specialized and highly heterogeneous collection of spontaneously active myocytes in the right atrium. Sinoatrial node dysfunction, characterized by slow and/or asynchronous pacemaker activity and even failure, is associated with cardiovascular disease (e.g. heart failure, atrial fibrillation). While tremendous progress has been made in understanding the molecular and ionic basis of automaticity in sinoatrial node cells, the dynamics governing sinoatrial nodel cell synchrony and overall pacemaker function remain unclear. Here, a well-validated computational model of the mouse sinoatrial node cell is used to test the hypothesis that sinoatrial node cell dynamics reflect an inherent restitution property (cycle length restitution) that may give rise to a wide range of behavior from regular periodicity to highly complex, irregular activation. Computer simulations are performed to determine the cycle length restitution curve in the computational model using a newly defined voltage pulse protocol. The ability of the restitution curve to predict sinoatrial node cell dynamics (e.g., the emergence of irregular spontaneous activity) and susceptibility to termination is evaluated. Finally, ionic and tissue level factors (e.g. ion channel conductances, ion concentrations, cell-to-cell coupling) that influence restitution and sinoatrial node cell dynamics are explored. Together, these findings suggest that cycle length restitution may be a useful tool for analyzing cell dynamics and dysfunction in the sinoatrial node
The cycle length restitution curve.
<p>(<b>A–B</b>) Simulated spontaneous action potentials during a protocol to determine the cycle length restitution curve. A 10-ms stimulus is applied with varying amplitude at the maximum diastolic potential to accelerate or delay the subsequent spontaneous action potential. Time between 2<sup>nd</sup> and 1<sup>st</sup> APs following perturbation (CL<sub>2</sub>) is then plotted as a function of time between 1<sup>st</sup> perturbed and steady-state APs (CL<sub>1</sub>). (<b>C</b>) CL restitution curves for control (<i>black</i>), low [Na<sup>+</sup>]<sub>o</sub> (<i>red</i>) and <i>I<sub>Kr</sub></i> block (<i>gray</i>). Note that low [Na<sup>+</sup>]<sub>o</sub> results in a curve with an abrupt transition from a relatively flat region to a very steep region (maximal slope >>−1 indicated by <i>arrow</i>; <i>dashed line</i> has slope of −1 for reference).</p
Termination of spontaneous activity in the one-dimensional fiber model.
<p>(<b>A</b>) [Na<sup>+</sup>]<sub>o</sub> or (<b>B</b>) <i>g<sub>Kr</sub></i> was decreased in a stepwise fashion under normal coupling conditions (<i>black</i>) and with uniform gap junction uncoupling (twofold increase in gap junction resistance, <i>gray</i>) to reduce electrotonic loading of sinoatrial node cells. Termination of spontaneous activity occurs earlier in the fiber than in the single cell as [Na<sup>+</sup>]<sub>o</sub> decreases, preceded by irregular activation and long runs (up to 20 sec) of skipped beats. Furthermore, uniform gap junctional uncoupling (<i>gray</i>) delays termination. In contrast, termination is delayed in the fiber relative to the single as <i>g<sub>Kr</sub></i> is decreased (gradual decline) and uncoupling accelerates termination.</p
Termination modes of spontaneous activity in a mathematical model of the mouse sinoatrial node cell.
<p>(<b>A</b>) Irregular activation and periodic skipped beat runs are apparent prior to termination as [Na<sup>+</sup>]<sub>o</sub> is decreased stepwise from 70 mM to 58 mM. (<b>B</b>) In contrast, a gradual decline in regular activity occurs as <i>g<sub>Kr</sub></i> is decreased from 0.37 to 0.31 times its control value. (<b>C-E</b>) Representative spontaneous action potentials under (<b>C</b>) control conditions, and during stepwise decrease in (<b>D</b>) [Na<sup>+</sup>]<sub>o</sub> and (<b>E</b>) <i>g<sub>Kr</sub></i> (corresponding time periods marked by <i>red bars</i> in panels <b>A</b> and <b>B</b>).</p
Ionic mechanism for irregular SAN activity with long pauses.
<p>(<b>A</b>) Simulated spontaneous APs and (<b>B</b>) [Na<sup>+</sup>]<sub>i</sub> from a single SAN cell subjected to low [Na<sup>+</sup>]<sub>o</sub> (100 mM) and constant, low amplitude (0.0077 µA/µF) bias current stimulation. During AP firing, [Na<sup>+</sup>]<sub>i</sub> rises until a threshold is reached (∼6.98 mM) at which point spontaneous activation terminates and [Na<sup>+</sup>]<sub>i</sub> slowly falls until a second threshold is reached (∼5.91 mM) and the pattern repeats. Clamping [Na<sup>+</sup>]<sub>i</sub> to the termination threshold (<i>red line</i> in <b>A</b> and <b>B</b>, clamp applied at time point labeled <i>b</i>) results in complete termination of activity, while clamping to the recovery threshold (<i>gray line</i>) eliminates the skipped beat runs resulting in regular periodic activity. (<b>C</b>) The CL restitution curve was determined for the model with low [Na<sup>+</sup>]<sub>o</sub> and bias current stimulation just after onset of regular periodic activity (<i>black line</i>, determined at time point labeled <i>a</i> in panels <b>A</b> and <b>B</b>) or prior to onset of skipped beat run (red line, determined at point marked <i>b</i>). [Na<sup>+</sup>]<sub>i</sub> was then reset to the low threshold value and restitution was determined again at the same time point (<i>gray line</i>). The restitution curve from the control model (normal [Na<sup>+</sup>]<sub>o</sub>, no bias current) is shown for reference (<i>black line</i>). Dashed line denotes a slope of −1. [Na<sup>+</sup>]<sub>i</sub> alters the slope of the restitution curve with much steeper slope at higher [Na<sup>+</sup>]<sub>i</sub>.</p
A graphical method for understanding the relationship between spontaneous SAN activity and restitution.
<p>Simulated spontaneous APs are shown in <i>top</i> of each panel with schematic representation of corresponding restitution curve in <i>bottom</i>. The identity line may be superimposed on the restitution curve to create a return map for tracking CL dynamics in response to a perturbation (<i>arrows</i> demonstrate iterative response to perturbation from fixed point, defined as intersection of return map with identity line). (<b>A</b>) Regular periodic activity (control model) occurs when restitution slope is shallow (slope >−1). Perturbation from steady-state results in eventual return to stable fixed point. (<b>B</b>) 2:2 periodic behavior (APs correspond to control model with bias current  = 0.0274 mA/mF) results from a monophasic curve with a slope equal to the critical value of −1 (in this example, CL stably alternates between 306 ms and 283 ms). (<b>C</b>) Higher dimensional periodic activity (e.g. 4:4) and skipped beats may result from a multiphasic curve with regions of steep slope (<−1) (APs correspond to [Na<sup>+</sup>]<sub>o</sub> = 63 mM), (<b>D</b>) irregular activity with long skipped beat runs may occur in instances where the CL restitution curve experiences an abrupt transition from a shallow region (slope<−1) to a very steep region (slope>>−1) (APs are shown for [Na<sup>+</sup>]<sub>o</sub> = 100 mM, bias current  = 0.0077 µA/µF). Schematic curves and corresponding return map trajectory are shown as spontaneous activity progresses from time point <i>a</i> (onset of activity) to <i>b</i> (just before termination). In this case, dynamic changes in [Na<sup>+</sup>]<sub>i</sub> may produce intermittent long skipped beat runs by shifting the curve and altering its slope.</p