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At least 811 records · Page 45Linked to original sources

PubMed1988

A theory of blood flow in skeletal muscle.

A theoretical analysis of blood flow in the microcirculation of skeletal muscle is provided. The flow in the microvessels of this organ is quasi steady and has a very low Reynolds number. The blood is non-Newtonian and the blood vessels are distensible with viscoelastic properties. A formulation of the problem is provided using a viscoelastic model for the vessel wall which was recently derived from measurements in the rat spinotrapezius muscle (Skalak and Schmid-Schönbein, 1986b). Closed form solutions are derived for several physiologically important cases, such as perfusion at steady state, transient and oscillatory flows. The results show that resting skeletal muscle has, over a wide range of perfusion pressures an almost linear pressure-flow curve. At low flow it exhibits nonlinearities. Vessel distensibility and the non-Newtonian properties of blood both have a strong influence on the shape of the pressure-flow curve. During oscillatory flow the muscle exhibits hysteresis. The theoretical results are in qualitative agreement with experimental observations.

Animals↗

PubMed1981

Digital solution of cochlear mechanics problems.

Several advantages are incurred when the greater part of the solution to a cochlear mechanics problem is carried out with an analytical method. Many cochlear mechanics problems can be formulated in such a way that they require solution of a specific integral equation in terms of the Fourier transform W(k) of the BM velocity w(x). An analytical solution for W(k) is possible for a certain class of impedance functions. In this paper it is shown how the Fourier transformation to the x domain can be carried out without producing aliasing errors. The impedance function Z(x) must be made periodic in x. For a particular choice of this function, one which puts the main emphasis on BM resonance, the solution to the integral equation can be found from a simple recurrence relation between the spectral components Wn of w(x). The method is illustrated for typical one-, two-, and three-dimensional cochlea models. It is proven that in the region of resonance for (nondigital) solution method published earlier produces nearly equivalent results. The digital method has a much wider scope of application.

Biomechanical Phenomena↗

PubMed1992

Two-sensor power measurements in lossy ducts.

Theory and measurements of the use of two adjacent pressure sensors to measure acoustic power flow of a simple harmonic sound wave in a duct are presented. This theory differs from the usual intensity-times-area formulation of this problem by including the phase shift between pressure gradient and velocity, which is caused by viscous drag on the gas at the duct wall. For high standing-wave ratios, the power obtained by this method differs significantly from the product of mid-duct intensity and duct area. These measurements confirm the method to an accuracy of 5%, even at high amplitudes where the acoustic flow is turbulent and the theory might not necessarily be valid.

Acoustics↗

PubMed2000

Three-dimensional numerical modeling for global cochlear dynamics.

A hybrid analytical-numerical model using Galerkin approximation to variational equations has been developed for predicting global cochlear responses. The formulation provides a flexible framework capable of incorporating morphologically based mechanical models of the cochlear partition and realistic geometry. The framework is applied for a simplified model with an emphasis on application of hybrid methods for three-dimensional modeling. The resulting formulation is modular, where matrices representing fluid and cochlear partition are constructed independently. Computational cost is reduced using two methods, a modal-finite-element method and a boundary element-finite-element method. The first uses a cross-mode expansion of fluid pressure (2.5D model) and the second uses a waveguide Green's-function-based boundary element method (BEM). A novel wave number approach to the boundary element formulation for interior problem results in efficient computation of the finite-element matrix. For the two methods a convergence study is undertaken using a simplified passive structural model of cochlear partition. It is shown that basilar membrane velocity close to best place is influenced by fluid and structural discretization. Cochlear duct pressure fields are also shown demonstrating the 3D nature of pressure near best place.

Auditory Perception↗

PubMed2000

Acoustic scattering by baffled flexible surfaces: the discrete optical theorem

The optical theorem for acoustic scattering by baffled membranes and plates relates the total cross section of the scattered field, the directivity factor in the specular direction, and the energy dissipated by the structure. It is basically a statement of conservation of power. In this paper it is demonstrated that the discrete formulation of these problems, obtained by a Galerkin approximation, exactly satisfies the optical theorem. This discrete relationship holds regardless of the choice of basis functions and the size of the truncated system N. Thus, the adherence of the approximate numerical results to the power conservation law does not necessarily imply its accuracy.

Journal Article↗

PubMed2000

Effects of thermal diffusion on sound attenuation in evaporating and condensing gas-vapor mixtures in tubes

An investigation of sound propagation in an air-water vapor mixture contained in a cylindrical tube with wet walls was recently presented [Raspet et al., J. Acoust. Soc. Am. 105, 65-73 (1999)]. The formulation of the problem paralleled the "low reduced frequency method" of Tijdeman [J. Sound Vib. 39, 1-33 (1975)]. It was pointed out that a term of reduced frequency order had been neglected in the radial component of the diffusion equation [G. Swift, personal communication (1999)]. This term represents the additional mass diffusion driven by the temperature gradient, or Soret effect, and is proportional to the thermal diffusion ratio. The solution for the complex wave number of the acoustic mode with this additional term is presented here. Numerically calculated predictions for the air-water vapor mixture show little change in acoustic attenuation due to the coupling. Therefore, a description of the acoustic attenuation where the viscous, thermal, and diffusion processes are decoupled is adequate for the specific case previously discussed by Raspet et al.

Journal Article↗

PubMed2004

Multiplexing schemes for generic SNP genotyping assays.

A generic genotyping assay utilizes a fixed set of reagents, which is independent of the actual target sample, to determine all present alleles. An example is the interrogation of several amplicons spanning polymorphic sites using an all k-mer array. Due to the high cost associated with a genotyping experiment, it is desirable to design a set of experiments, which maximizes the number of SNPs that can be genotyped in parallel per assay. In this study we investigate algorithmic approaches for optimally multiplexing SNP genotyping using generic assays. We devise a graph theoretic formulation of the problem and use it to derive an approximation algorithm for the problem, and several practical heuristics. We apply our methods to simulated and real data, for evaluating the multiplexing rates afforded by generic techniques. The results on real human data show the practicality of generic approaches for genotyping, allowing, e.g., the genotyping of 5000 SNPs using four all 7-mer arrays.

Algorithms↗

PubMed2001

Quality control in manufacturing oligo arrays: a combinatorial design approach.

The advent of the DNA microarray technology has brought with it the exciting possibility of simultaneously observing the expression levels of all genes in an organism. One such microarray technology, called "oligo arrays", manufactures short single strands of DNA (called probes) onto a glass surface using photolithography. An altered or missed step in such a manufacturing protocol can adversely affect all probes using this failed step, and is in general impossible to disentangle from experimental variation when using such a defective array. The idea of designing special quality control probes to detect a failed step was first formulated by Hubbell and Pevzner. We consider an alternative formulation of this problem and use a combinatorial design approach to solve it. Our results improve over prior work in guaranteeing coverage of all protocol steps and in being able to tolerate a greater number of unreliable probe intensities.

Combinatorial Chemistry Techniques↗

PubMed2003

Computational assignment of protein backbone NMR peaks by efficient bounding and filtering.

NMR resonance assignment is one of the key steps in solving an NMR protein structure. The assignment process links resonance peaks to individual residues of the target protein sequence, providing the prerequisite for establishing intra- and inter-residue spatial relationships between atoms. The assignment process is tedious and time-consuming, which could take many weeks. Though there exist a number of computer programs to assist the assignment process, many NMR labs are still doing the assignments manually to ensure quality. This paper presents a new computational method based on the combination of a suite of algorithms for automating the assignment process, particularly the process of backbone resonance peak assignment. We formulate the assignment problem as a constrained weighted bipartite matching problem. While the problem, in the most general situation, is NP-hard, we present an efficient solution based on a branch-and-bound algorithm with effective bounding techniques using two recently introduced approximation algorithms. We also devise a greedy filtering algorithm for reducing the search space. Our experimental results on 70 instances of (pseudo) real NMR data derived from 14 proteins demonstrate that the new solution runs much faster than a recently introduced (exhaustive) two-layer algorithm and recovers more correct peak assignments than the two-layer algorithm. Our result demonstrates that integrating different algorithms can achieve a good tradeoff between backbone assignment accuracy and computation time.

Algorithms↗

PubMed2005

An optimization method for the identification of minimal sets of discriminating gene markers: application to cultivar identification in wheat.

A potentially large number of molecular markers are available for identifying genotypes in various species. For wheat, cultivar identity is an important determinant for end-use segregation and for payment of end-point royalties and grower premiums. A number of dominant DNA markers, that give either a positive or negative response, have been developed previously for wheat cultivar identification. This paper gives a method for identifying minimal marker sets for a given cultivar group, for example those grown in a specific geographical zone. It is based on an integer linear programming formulation of the problem, and can find all minimal marker sets for the group if required. The paper then describes the production of two software packages, GGDS and GGIP, that incorporate this methodology. Various practical issues are also discussed. These packages enable the rapid selection of minimal marker sets for the efficient discrimination of any sample set where the marker responses of the samples are known. They are already being used by the Australian wheat industry.

Algorithms↗

PubMed2005

A statistical framework for haplotype block inference.

The existence of haplotype blocks transmitted from parents to offspring has been suggested recently. This has created an interest in the inference of the block structure and length. The motivation is that haplotype blocks that are characterized well will make it relatively easier to quickly map all the genes carrying human diseases. To study the inference of haplotype block systematically, we propose a statistical framework. In this framework, the optimal haplotype block partitioning is formulated as the problem of statistical model selection; missing data can be handled in a standard statistical way; population strata can be implemented; block structure inference/hypothesis testing can be performed; prior knowledge, if present, can be incorporated to perform a Bayesian inference. The algorithm is linear in the number of loci, instead of NP-hard for many such algorithms. We illustrate the applications of our method to both simulated and real data sets.

Algorithms↗

PubMed1992

On the design and interpretation of experiments to elucidate albumin-dependent hepatic uptake.

The liver's apparently anomalous extraction of organic anions tightly bound to albumin continues to provoke controversy and confusion. Decisive experiments have proved difficult to design, and mathematical models have usually been constructed to defend one or another putative mechanism to the exclusion of others. To stimulate more decisive experiments and as an aid to interpreting those already reported, we discuss a general formulation of the problem that predicts the clearance pattern to be expected when facilitated dissociation and codiffusion are joint determinants of the uptake flux. The results provide an approach to modeling the various mechanisms by which the concentration of bound ligand at the cell surface could be a driving force for uptake. Further we present new calculations to clarify the interpretation of net ligand clearance when the removal of free ligand is the result of bidirectional fluxes into and out of an unstirred sink. Applied to a previously published comparison of the uptake performances of hepatocytes and polyethylene, the new calculations support the inference that facilitated dissociation of albumin-palmitate complexes occurs at or near the hepatocyte surface.

Animals↗

PubMed1977

A numerical method for fitting compartmental models directly to tracer data.

A numerical method is presented for obtaining the exchange rates of a metabolic compartmental system, working directly from the time course of tracer activity and excretion after bolus injection. The conventional mathematical formulation of this problem, in terms of sums of exponential functions, is bypassed, enabling implementation of the method in a short computer program. An important by-product of the method is a set of variance-covariance estimates for the fitted parameters. The method is tested on "classic" data, both simulated and real. Its capabilities and limitations are demonstrated, and the strategy of its effective application is discussed.

Humans↗

PubMed1981

Modeling and identification of metabolic systems.

Introductory principles of physiological systems analysis by computer simulation or computation are introduced. The problems of model formulation, identification, and validation are examined. Selected guidelines for successful modeling are suggested, and examples of such applications in the field of endocrinology and metabolism are given.

Animals↗

PubMed2004

The size of the chi-square test for the Hardy-Weinberg law.

Many scientific problems can be formulated in terms of a statistical model indexed by parameters, only some of which are of scientific interest and the other parameters, called nuisance parameters, are not of interest in themselves. For testing the Hardy-Weinberg law, a relation among genotype and allele probabilities is of interest and allele probabilities are of no interest and now nuisance parameters. In this paper we investigate how the size (the maximum of the type I error rate over the nuisance parameter space) of the chi-square test for the Hardy-Weinberg law is affected by the nuisance parameters. Whether the size is well controlled or not under the nominal level has been frequently investigated as basic components of statistical tests. The size represents the type I error rate at the worst case. We prove that the size is always greater than the nominal level as the sample size increases. Extensive computations show that the size of the chi-squared test (worst type I error rate over the nuisance parameter space) deviates more upwardly from the nominal level as the sample size gets larger. The value at which the maximum of the type I error rate was found moves closer to the edges of the the nuisance parameter space with increasing sample size. An exact test is recommended as an alternative when the type I error is inflated.

Alleles↗

PubMed2002

Computational capacity of an odorant discriminator: the linear separability of curves.

We introduce and study an artificial neural network inspired by the probabilistic receptor affinity distribution model of olfaction. Our system consists of N sensory neurons whose outputs converge on a single processing linear threshold element. The system's aim is to model discrimination of a single target odorant from a large number p of background odorants within a range of odorant concentrations. We show that this is possible provided p does not exceed a critical value p(c) and calculate the critical capacity alpha(c) = p(c)/N. The critical capacity depends on the range of concentrations in which the discrimination is to be accomplished. If the olfactory bulb may be thought of as a collection of such processing elements, each responsible for the discrimination of a single odorant, our study provides a quantitative analysis of the potential computational properties of the olfactory bulb. The mathematical formulation of the problem we consider is one of determining the capacity for linear separability of continuous curves, embedded in a large-dimensional space. This is accomplished here by a numerical study, using a method that signals whether the discrimination task is realizable, together with a finite-size scaling analysis.

Algorithms↗

PubMed2000

Risk-benefit decision making for treatment of depression during pregnancy.

OBJECTIVE: The Committee on Research on Psychiatric Treatments of the American Psychiatric Association identified treatment of major depression during pregnancy as a priority area for improvement in clinical management. The goal of this article was to assist physicians in optimizing treatment plans for childbearing women. METHOD: The authors' work group developed a decision-making model designed to structure the information delivered to pregnant women in the context of the risk-benefit discussion. Perspectives of forensic and decision-making experts were incorporated. RESULTS: The model directs the psychiatrist to structure the problem through diagnostic formulation and identification of treatment options for depression. Reproductive toxicity in five domains (intrauterine fetal death, physical malformations, growth impairment, behavioral teratogenicity, and neonatal toxicity) is reviewed for the potential somatic treatments. The illness (depression) also is characterized by symptoms of somatic dysregulation that compromise health during pregnancy. The patient actively participates and provides her evaluation of the acceptability of the various treatments and outcomes. Her capacity to participate in this process provides evidence of competence to consent. Included in the decision-making process are the patient's significant others and obstetrical physician. The process is ongoing, with the need for incorporation of additional data as the pregnancy and treatment response progress. CONCLUSIONS: The conceptual model provides structure to a process that is frequently stressful for both patients and psychiatrists. By applying the model, clinicians will ensure that critical aspects of the risk-benefit discussion are included in their care of pregnant women.

Adult↗

PubMed1985

Wild analysis.

Contemporary debates over psychoanalytic theory and practice warrant a reconsideration of the concept of wild analysis. Freud's initial formulation of the problem, subsequent developments in the Freudian conventions, and the work of Melanie Klein, Kohut, and Gill are compared in order to bring out different conceptions of interpretation that is wild, sound, or too tame. These different conceptions are system-bound. Moral implications of Klein's, Kohut's, and Gill's critiques and alternative systems are taken up.

Anxiety Disorders↗