Biomedical subjects

C S Peskin

Publications and source records attributed to C S Peskin.

8 recordsLinked to original sources

PubMed1992

What drives the translocation of proteins?

We propose that protein translocation across membranes is driven by biased random thermal motion. This "Brownian ratchet" mechanism depends on chemical asymmetries between the cis and trans sides of the membrane. Several mechanisms could contribute to rectifying the thermal motion of the protein, such as binding and dissociation of chaperonins to the translocating chain, chain coiling induced by pH and/or ionic gradients, glycosylation, and disulfide bond formation. This helps explain the robustness and promiscuity of these transport systems.

Biological Transport↗

PubMed1992

Cardiac fluid dynamics.

The heart is modeled as a system of elastic and/or contractile fibers immersed in a viscous incompressible fluid. Simulated heart walls and valves are constructed by arranging the fibers according to an idealized version of the actual distribution of muscle fibers in the heart walls and collagen fibers in the valve leaflets. Then the combined motion of the fluid-fiber system is predicted through the numerical solution of its coupled equations of motion. Fluid equations are solved by a finite difference method on a fixed, regular computational lattice. Fiber points move freely through this lattice without being constrained to lie at the lattice intersections. Communication between fibers and fluid involves interpolation of the fluid velocity to the fiber points and the spreading of the fiber forces to the computational lattice of the fluid. Both of these operations make use of a smoothed approximation to the Dirac delta function. The entire method is suitable for implementation on vector, parallel, or parallel-vector hardware. Applications include the investigation of normal cardiac function, the simulation of disease processes affecting the mechanical function of the heart or its valves, and the computer-assisted design of prosthetic cardiac valves.

Aortic Valve↗

PubMed1990

The derivation and verification of a non-stationary, optimal smoothing filter for nuclear medicine image data.

A non-stationary optimal smoothing filter for digital nuclear medicine image data, degraded by Poisson noise, has been derived and applied to temporal simulated and clinical gated blood pool study (GBPS) data. The derived filter is automatically calculated from a large group (library) of similar GBPS which are representative of all studies acquired according to the same protocol in a defined patient population (the ensemble). The filter is designed to minimize the mean-square difference between the filtered data and the true image values; it provides an optimal trade-off between noise reduction and signal degradation for members of the ensemble. The filter is evaluated using a computer simulated ensemble of GBPS. Libraries of Poisson-degraded and non-degraded studies were generated. Libraries of up to 400 Poisson-degraded simulated studies were used to estimate optimal temporal filters that, when applied to Poisson-degraded members of the ensemble not included in the libraries, reduced the mean-square error in the raw data by 65%. When the non-degraded studies were used instead to compute the optimal filter values, the corresponding reduction in the error was 83%. Libraries of previously acquired clinical GBPS were then used to estimate optimal temporal filters for an ensemble of similarly acquired studies. These filters were subsequently applied to studies of 13 patients (not in the original libraries) who received multiple sequential repeat studies. Comparisons of both the filtered and raw data to averages of the repeat studies demonstrated that optimal filters calculated from 400 and 800 clinical studies reduced the mean-square error in the clinical data by 56% and 63% respectively.

Filtration↗

PubMed1990

A C version of Fourier-derived affinity spectrum analysis (FASA) to resolve binding heterogeneity.

The computer program described in this paper facilitates resolution of binding affinity heterogeneity by transforming binding curve data (bound versus free) into affinity spectra (density versus affinity). The original program, written in FORTRAN, is extended and presented here in the language C. New applications include an ability to transform competition curves into affinity spectra and to evaluate the effects of sampling and experimental error on spectrum analysis. We propose that this program be incorporated in the routine evaluation of binding systems.

Binding, Competitive↗

PubMed1989

Hemodynamics in transposition of the great arteries with comparison to ventricular septal defect.

This paper uses a mathematical model of the circulations to study the hemodynamics of transposition of the great arteries (TGA) with comparison to ventricular septal defect (VSD). Computer experiments are conducted to determine the influence of the defect conductance and the pulmonary vascular conductance on the pulsatile pressures, flows, and oxygen concentrations of the circulation. In particular, the model is used to determine the waveform of the (possibly bidirectional) shunt through the ventricular and atrial septal defects. The results of the computer experiments consist of two parts. The first set of experiments is devoted to the comparison of VSD and TGA with a ventricular septal defect. The results are theoretical in the sense that most parameters have been fixed at the same levels. In each case TGA is represented by changing the connection of the chambers and reversing the compliance of the two ventricles. In the second set of experiments we attempt to simulate conditions clinically observed in a variety of cases of TGA. In each case we use clinical observations to infer parameters as the input to the model. We find that the model (with appropriate choice of parameters) generally exhibits blood pressure, blood flows and oxygen concentrations similar to the clinical observations. As a byproduct of these computer experiments we predict the effects of changing the pulmonary conductance. The comparison between TGA and VSD shows that as the defect conductance increases, the systemic oxygen concentrations decrease in VSD and increase in TGA. Even at large defect conductance, the two conditions remain distinct, however, since the mixing of the right and left ventricular blood pools is incomplete. This phenomenon of incomplete mixing sets quantitative limits on the benefits that can be achieved by surgical enlargement of the defect. A result of this study that may be useful in the management of TGA patients with a ventricular septal defect is the finding that there is a value of the pulmonary conductance that maximizes the effective flow and hence the systemic oxygen concentrations. The optimal pulmonary conductance is approximately equal to the systemic conductance when the defect is large.

Computer Simulation↗

PubMed1988

Light adaptation in the turtle retina: embedding a parametric family of linear models in a single nonlinear model.

A method for constructing nonlinear models for light adaptation in the retina is introduced. The components of the models are linear filters and static (instantaneous) nonlinear elements configured in a feedback arrangement. The signals in the models are combined through algebraic addition or multiplication. We apply the method to model light adaptation measured in turtle horizontal cells. Given a particular wiring diagram for the components, the functional forms of the static nonlinearities and frequency responses of the linear filters are determined by constraining the model to give temporal frequency responses (linear regime behavior) consistent with a family of linear feedback models which has been shown to provide a good description of adaptation in these cells. Two particular models, quite different in structure, are presented. Each model responds to perturbations around a mean light level as a feedback circuit in which the gain (strength) of feedback is adjusted to be proportional to the mean light level, but neither model has a separate pathway for measuring the mean light level. Thus, each of these nonlinear models embeds an entire family of linear models parametric in mean light level. Harmonic distortion in the responses of these models to sinusoidal input is found to be qualitatively consistent with physiological data. An alternative class of nonlinear models in which feedback gain is set by a separate slow pathway which tracks the mean light level is ruled out on the basis of its incorrect steady-state input-output behavior. The methods presented can be used to develop specific physical models for light adaptation based on the chemical kinetics of phototransduction or on nonlinear neural feedback. The relevance of the nonlinear models and construction techniques to modeling phototransduction is discussed.

Adaptation, Ocular↗

PubMed1988

A "give" in tension and sarcomere dynamics in cardiac muscle relaxation.

Isometric relaxation in cardiac sarcomeres is characterised by an early, very slow phase of tension fall which is terminated by a 'give' in tension. A 'give' which occurs during relaxation in cardiac muscle can not be attributed to decrease in myofilament overlap. After the 'give' asynchronous motion occurs between sarcomeres, but the duration and extent of their displacement is limited. Intriguingly, the effect of isotonic displacements on the early fall in the velocity of sarcomere shortening indicates that an internal resistance increases near the peak of contraction. The complex shape of the sarcomere's complete force-velocity relation, with lengthening motions in particular, was consistent with an idealized model of cross-bridge cycling. The sarcomere's resistance to stretch is high at low velocity, but it diminishes to reveal yielding at larger velocities. Relative to tension, the resistance to yielding does not decrease during relaxation, and it may actually increase. The decay of isometric tension after a controlled stretch also slows during relaxation. Consequently, cycling slows in those cross-bridges which form (or persist but produce less force) later in contraction. Changes in cross-bridge properties may restrict sarcomere shortening, prolong activation, but promote a disequilibrium which favors rapid relaxation in cardiac muscle.

Animals↗

PubMed1978

The aortic sinus vortex.

This paper describes an analytic and a numerical method for the aortic sinus problem. Both methods are based on the dynamics of point vortices, and both exploit a particular conformal mapping from a model aortic sinus to the upper half plane. The analytic description is based on an isolated point vortex in equilibrium with a free stream. This inviscid model is used to study the stability of the aortic sinus vortex and to elucidate the mechanism of aortic valve closure, but it cannot be used to study the formation of the sinus vortex and it gives a somewhat incorrect picture of the flow pattern. These difficulties are overcome by the introduction of a numerical method for the aortic sinus problem with fluid viscosity. We use Chorin's vortex method combined with conformal mapping. The conformal mapping approach gives an explicit formula for the vortex velocities and it resolves the singularities associated with the corners of the domain. This method is then used to study the formation of the sinus vortex and to confirm the predictions of the point vortex model with respect to the role of the vortex in valve closure.

Animals↗