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Biomedical subjects

M H Holmes

Publications and source records attributed to M H Holmes.

At least 19 recordsLinked to original sources
PubMed2001

DNA sequence quality trimming and vector removal.

MOTIVATION: Most sequence comparison methods assume that the data being compared are trustworthy, but this is not the case with raw DNA sequences obtained from automatic sequencing machines. Nevertheless, sequence comparisons need to be done on them in order to remove vector splice sites and contaminants. This step is necessary before other genomic data processing stages can be carried out, such as fragment assembly or EST clustering. A specialized tool is therefore needed to solve this apparent dilemma. RESULTS: We have designed and implemented a program that specifically addresses the problem. This program, called LUCY, has been in use since 1998 at The Institute for Genomic Research (TIGR). During this period, many rounds of experience-driven modifications were made to LUCY to improve its accuracy and its ability to deal with extremely difficult input cases. We believe we have finally obtained a useful program which strikes a delicate balance among the many issues involved in the raw sequence cleaning problem, and we wish to share it with the research community. AVAILABILITY: LUCY is available directly from TIGR (http://www.tigr.org/softlab). Academic users can download LUCY after accepting a free academic use license. Business users may need to pay a license fee to use LUCY for commercial purposes. CONTACT: Questions regarding the quality assessment module of LUCY should be directed to Michael Holmes (mholmes@tigr.org). Questions regarding other aspects of LUCY should be directed to Hui-Hsien Chou (hhchou@iastate.edu).

Algorithms↗
PubMed1997

A mathematical approximation for the solution of a static indentation test.

The classical contact problem of the indentation of a thin compressible linear elastic layer bonded to a rigid substrate is considered. Closed-form mathematical approximations of the deformation are presented for the cases of plane indentation by a rectangular block and three dimensional indentation by a plane-ended (axisymmetric) cylinder. The approximations are analyzed in the context of a static indentation test by comparison of applied load values to those obtained using a classical integral transform solution. In the case of plane indentation, the mathematical and classical predictions agree to within 2% relative error for aspect ratios between 0.1 and 1.0 and apparent Poisson ratio between 0.0 and 0.3. Comparisons for the axisymmetric case indicate a similar pattern. The main advantage of the new approach is that it yields closed-form approximations of the static indentation solution which can also capture the essential singular behavior.

Animals↗
PubMed1994

A note on modeling mechano-chemical transduction with an application to a skin receptor.

Strain-sensitive (also called stretch-sensitive) ionic channels are thought to be present in various mechanoreceptors. The gating of these channels is precipitated by mechanical strains, as opposed to the usual activation processes of changes in membrane potential or other ligands. Below we present a class of models for the strain-activated mechanism, compare our approach to one of Sachs and Lecar (1991) and apply the gating mechanism to a model of a specific mechanoreceptor, namely a Pacinian corpuscle neurite model. The simulation experiment suggests the activation energy of the channel depends linearly, rather than nonlinearly, on the (hoop) strain in the receptor membrane.

Animals↗
PubMed1992

An analysis of the squeeze-film lubrication mechanism for articular cartilage.

An asymptotic analysis of a lubrication problem is presented for a model of articular cartilage and synovial fluid under the squeeze-film condition. This model is based upon the following constitutive assumptions: (1) articular cartilage is a linear porous-permeable biphasic material filled with a linearly viscous fluid (i.e. Newtonian fluid); (2) synovial fluid is also a linearly viscous fluid. The geometry of the problem is defined by assuming that (1) cartilage is a uniform layer of thickness H; (2) synovial fluid is a very thin layer compared to H; (3) the radius R of the load-supporting area (or the effective radius of curvature of joint surface, Ri) is large compared to H. Squeeze-film action is generated in the lubricant by a step loading function applied onto the two bearing surfaces. The model assumptions and the material properties yield two small parameters in the mathematical formulation. Based on these two small parameters, two coupled nonlinear partial differential equations were derived from an asymptotic analysis of the problem: one for the lubricant (analogous to the Reynolds equation) and one for the cartilage. For known properties of normal cartilage, our calculations show: (1) the cartilage layer deforms to enlarge the load-supporting area; (2) cartilage deformation acts to reduce the lateral fluid speed in the lubricant, thus prolonging the squeeze-film time which ranges from 1 to 10 s; (3) lubricant fluid in the gap is forced from the central high-pressure region into cartilage, and expelled from the tissue at the low-pressure periphery of the load-bearing region; and (4) tensile hoop stress exists at the cartilage surface despite the compressive squeeze-film loading condition. This hoop stress results directly from the radial flow of the interstitial fluid in the cartilage layer.

Biomechanical Phenomena↗
PubMed1991

Identification, sequence, and expression of the gene encoding the second-largest subunit of the vaccinia virus DNA-dependent RNA polymerase.

The gene, rpo 132, encoding the second-largest subunit of the vaccinia virus DNA-dependent RNA polymerase was identified and sequenced. Two complementary approaches, involving antiserum to purified vaccinia virus RNA polymerase, were used to locate the rpo 132 gene. One method involved the screening of a lambda gt11 library of vaccinia virus genome fragments and the other was based on the immunoprecipitation and polyacrylamide gel electrophoresis of the in vitro translation products of mRNA that hybridized to immobilized vaccinia virus DNA. The deduced open reading frame of the rpo 132 gene predicted a polypeptide of 1164 amino acid residues with sequence similarities to the second-largest RNA polymerase subunits of eubacteria, archaebacteria, and eukaryotes as well as to other poxviruses. Transcriptional analyses indicated that rpo 132 has both early and late RNA start sites and is expressed throughout infection.

Amino Acid Sequence↗
PubMed1990

The nonlinear characteristics of soft gels and hydrated connective tissues in ultrafiltration.

A one-dimensional ultrafiltration problem of fluid flow through a soft permeable tissue or gel under high pressure and compressive strain is solved. A finite deformation biphasic theory is used to model the behavior of the soft porous permeable solid matrix. This theory includes a Helmholtz free energy function which depends on the three principal invariants (I, II, III) of the right Cauchy-Green tensor and which satisfies the Baker-Ericksen inequalities on the principal stresses and strains. The dependence of the porosity phi f and the solidity phi s on deformation is deduced and a generalization of the exponential strain-dependent functional form for the permeability, k = k0 exp (M epsilon), of Lai and Mow (Biorheology 103, 111-123, 1980) is proposed. In this one-dimensional problem, we show that the dependence of the permeability on phi f, phi s, and III is equivalent to its dependence on hydration as proposed by Fatt and Goldstick (J. Colloid Sci. 20, 962-988, 1965). The exact solution of the ultrafiltration problem is derived and asymptotic and numerical methods are used to evaluate it. For high pressures and finite strains, the solution provides some surprising effects. The theory predicts that a material starting with a homogeneous porosity will have a strongly non-homogeneous porosity throughout the column during ultrafiltration. The resulting change in pore size through the filtration column may be very important in understanding its filtration characteristics. It is also found that there is a long delay time, up to 10 to 15 min, before the filtration velocity reaches an equilibrium. In filtration experiments where the rate of mass transport across the tissue or column of gel is important, sufficient time must be allowed for the steady state to be reached.

Animals↗
PubMed1989

Boundary conditions at the cartilage-synovial fluid interface for joint lubrication and theoretical verifications.

The objective of this study is to establish and verify the set of boundary conditions at the interface between a biphasic mixture (articular cartilage) and a Newtonian or non-Newtonian fluid (synovial fluid) such that a set of well-posed mathematical problems may be formulated to investigate joint lubrication problems. A "pseudo-no-slip" kinematic boundary condition is proposed based upon the principle that the conditions at the interface between mixtures or mixtures and fluids must reduce to those boundary conditions in single phase continuum mechanics. From this proposed kinematic boundary condition, and balances of mass, momentum and energy, the boundary conditions at the interface between a biphasic mixture and a Newtonian or non-Newtonian fluid are mathematically derived. Based upon these general results, the appropriate boundary conditions needed in modeling the cartilage-synovial fluid-cartilage lubrication problem are deduced. For two simple cases where a Newtonian viscous fluid is forced to flow (with imposed Couette or Poiseuille flow conditions) over a porous-permeable biphasic material of relatively low permeability, the well known empirical Taylor slip condition may be derived using matched asymptotic analysis of the boundary layer at the interface.

Cartilage, Articular↗
PubMed1988

Three-dimensional acoustic waves in the ear canal and their interaction with the tympanic membrane.

The long and slender geometry of the ear canal supports an infinite number of cross-sectional acoustic modes. The lower mode(s) travel along the length of the ear canal, while the higher modes are trapped near the ends of the canal. Many of these waves are introduced as a result of the complex vibrational shape of the eardrum. A three-dimensional mathematical model of the ear canal is formulated that includes this acoustic interaction. The coupled system is solved using matched asymptotic expansions that take advantage of the small slenderness ratio. This solution in the ear canal is in the form of a series of modes, the first being the plane-wave solution. As an illustrative example, the analysis is applied to a geometry that partially represents the ear canal and eardrum of a cat. The results indicate that the plane-wave solution is supplemented by multidimensional trapped modes at low frequencies and by a limited number of traveling waves at high frequencies. The magnitude of these higher modes generally increases with frequency and can significantly influence the acoustic coupling of the ear.

Acoustic Stimulation↗
PubMed1987

Frequency discrimination in the mammalian cochlea: theory versus experiment.

A three-dimensional hydroelastic model for the motion in the cochlea is analyzed for the case of a pure-tone forcing. It is shown to agree well with experiment, including moderate intensity tuning curves and the frequency map, for a variety of mammals. In doing this, the parameters that are needed for each animal are geometric; thus the theory is easy to apply. The analysis also indicates that the fluid viscosity is the dominant dissipation mechanism, at least for moderate to high frequencies.

Animals↗
PubMed1986

A nonlinear model for transduction in hair cells.

Based on the experimental observations of the mechano-electrical transduction in hair cells, we formulate a model of the receptor potential utilizing a simple model circuit and ideas of stretch activation that have been developed for other mechanoreceptors. The stereociliary displacement-response relation is developed based on the cilia crosslinking, thus incorporating notions of bidirectional sensitivity, asymmetry, saturation, and adaptation into the model. We then give some simulation results involving periodic stimuli to the hair bundle as well as current stimuli of study latency behavior and other qualitative properties of the model.

Animals↗
PubMed1986

Behaviour of a model for the synapse of an auditory receptor cell.

The purpose of this paper is to formulate a dynamical model of an auditory hair-cell synapse, coupled to a model of the hair cell's receptor potential through intracellular calcium concentration. The synaptic model includes a mechanism for auditory nerve discharge, which allows for the determination of the afferent nerve's firing rate from stimulation of the receptor cell's hair bundle. We show that the synaptic model has a periodic solution under certain conditions, given a constant current stimulus. We also show that the firing rate undergoes adaptation.

Adaptation, Physiological↗
PubMed1986

Finite deformation of soft tissue: analysis of a mixture model in uni-axial compression.

The dynamic finite deformational behavior of a biphasic model for soft hydrated tissue is examined. In the case of uni-axial confined compression the displacement and stress fields are derived for steady-state permeation, creep, and stress-relaxation. It is shown how to use the results of this analysis to obtain the constitutive relations, as well as the associated material parameters, from the corresponding experiments. It is also shown that the solutions from the theory go much farther, giving a detailed account of the deformation and interaction of the fluid and solid phases in the tissue.

Animals↗
PubMed1986

A fibrous dynamic continuum model of the tympanic membrane.

The geometry and anisotropic ultrastructure of the tympanic membrane are used in combination with curvilinear shell equations to formulate a general continuum model describing its dynamic behavior. Primary terms appearing in the model are associated with shell membrane restoring forces, bending-type structural damping, and transverse inertia. Since the model is based extensively on the physical characteristics of the membrane, it is relatively easy to account for differences between species as well as pathological conditions. The fibrous structure and cone-shaped geometry, readily apparent in mammalian eardrums, introduce several small parameters into the model that are exploited in order to construct a closed-form asymptotic solution. The solution includes the coupling to the three-dimensional motion of the ossicular chain and it includes the frequency-dependent pressure distribution in the auditory canal. When applied to the cat eardrum, this asymptotic solution is shown to reproduce a large manifold of experimentally observed frequency and excitation-dependent vibrational shapes. In addition to the shapes, transient amplitude and phase data for the cat are reproduced.

Animals↗
PubMed1985

Singular perturbation analysis of the nonlinear, flow-dependent compressive stress relaxation behavior of articular cartilage.

The dominant mechanism giving rise to the viscoelastic response of articular cartilage during compression is the nonlinear diffusive interaction of the fluid and solid phases of the tissue as they flow relative to one another. The present study is concerned with the role of this interaction under uniaxial stress relaxation in compression. The model is a biphasic mixture of fluid and solid which incorporates the strain-dependent permeability found earlier from permeation experiments. When a ramp-displacement is imposed on the articular surface, simple, but accurate, asymptotic approximations are derived for the deformation and stress fields in the tissue for slow and moderately fast rates of compression. They are shown to agree very well with experiment and they provide a simple means for determining the material parameters. Moreover, they lead to important insights into the role of the flow-dependent viscoelastic nature of articular cartilage and other hydrated biological tissues.

Cartilage, Articular↗
PubMed1984

Fluid transport and mechanical properties of articular cartilage: a review.

This review is aimed at unifying our understanding of cartilage viscoelastic properties in compression, in particular the role of compression-dependent permeability in controlling interstitial fluid flow and its contribution to the observed viscoelastic effects. During the previous decade, it was shown that compression causes the permeability of cartilage to drop in a functional manner described by k = ko exp (epsilon M) where ko and M were defined as intrinsic permeability parameters and epsilon is the dilatation of the solid matrix (epsilon = tr delta u). Since permeability is inversely related to the diffusive drag coefficient of relative fluid motion with respect to the porous solid matrix, the measured load-deformation response of the tissue must therefore also depend on the non-linearly permeable nature of the tissue. We have summarized in this review our understanding of this non-linear phenomenon. This understanding of these flow-dependent viscoelastic effects are put into the historical perspective of a comprehensive literature review of earlier attempts to model the compressive viscoelastic properties of articular cartilage.

Biological Transport↗
PubMed1984

Cochlear mechanics: analysis for a pure tone.

A three-dimensional hydroelastic model of the cochlea is analyzed, in which the fluid is viscous and the basilar membrane is an inhomogeneous orthotropic elastic plate. After the solution is obtained using a multiple-scale approximation, comparison is made with experiment for the human cochlea.

Basilar Membrane↗