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Biomedical subjects

Y Rabin

Publications and source records attributed to Y Rabin.

At least 19 recordsLinked to original sources
PubMed2004

Metastable network model of protein transport through nuclear pores.

To reconcile the observed selectivity and the high rate of translocation of cargo-importin complexes through nuclear pores, we propose that the core of the nuclear pore complex is blocked by a metastable network of phenylalanine and glycine nucleoporins. Although the network arrests the unfacilitated passage of objects larger than its mesh size, cargo-importin complexes act as catalysts that reduce the free energy barrier between the cross-linked and the dissociated states of the Nups, and open the network. Using Brownian dynamics simulations we calculate the distribution of passage times through the network for inert particles and cargo-importin complexes of different sizes and discuss the implications of our results for experiments on translocation of proteins through the nuclear pore complex.

Active Transport, Cell Nucleus↗
PubMed2001

Fluctuating elastic rings: statics and dynamics.

We study the effects of thermal fluctuations on elastic rings. Analytical expressions are derived for correlation functions of Euler angles, mean-square distance between points on the ring contour, radius of gyration, and probability distribution of writhe fluctuations. Since fluctuation amplitudes diverge in the limit of vanishing twist rigidity, twist elasticity is essential for the description of fluctuating rings. We discover a crossover from a small scale regime in which the filament behaves as a straight rod, to a large scale regime in which spontaneous curvature is important and twist rigidity affects the spatial configurations of the ring. The fluctuation-dissipation relation between correlation functions of Euler angles and response functions, is used to study the deformation of the ring by external forces. The effects of inertia and dissipation on the relaxation of temporal correlations of writhe fluctuations, are analyzed using Langevin dynamics.

Algorithms↗
PubMed2001

Kinetics and mechanism of DNA uptake into the cell nucleus.

Gene transfer to eukaryotic cells requires the uptake of exogenous DNA into the cell nucleus. Except during mitosis, molecular access to the nuclear interior is limited to passage through the nuclear pores. Here we demonstrate the nuclear uptake of extended linear DNA molecules by a combination of fluorescence microscopy and single-molecule manipulation techniques, using the latter to follow uptake kinetics of individual molecules in real time. The assays were carried out on nuclei reconstituted in vitro from extracts of Xenopus eggs, which provide both a complete complement of biochemical factors involved in nuclear protein import, and unobstructed access to the nuclear pores. We find that uptake of DNA is independent of ATP or GTP hydrolysis, but is blocked by wheat germ agglutinin. The kinetics are much slower than would be expected from hydrodynamic considerations. A fit of the data to a simple model suggests femto-Newton forces and a large friction relevant to the uptake process.

Adenosine Triphosphate↗
PubMed2000

Thermal fluctuations of elastic filaments with spontaneous curvature and torsion.

We study the effects of thermal fluctuations on thin elastic filaments with spontaneous curvature and torsion. We derive analytical expressions for the orientational correlation functions and for the persistence length of helices and find that this length varies nonmonotonically with the strength of thermal fluctuations. In the weak fluctuation regime, the persistence length of a spontaneously twisted helix has three resonance peaks as a function of the twist rate. In the limit of strong fluctuations, all memory of the helical shape is lost.

Algorithms↗
PubMed2000

An elastic analysis of Listeria monocytogenes propulsion.

The bacterium Listeria monocytogenes uses the energy of the actin polymerization to propel itself through infected tissues. In steady state, it continuously adds new polymerized filaments to its surface, pushing on its tail, which is made from previously cross-linked actin filaments. In this paper we introduce an elastic model to describe how the addition of actin filaments to the tail results in the propulsive force on the bacterium. Filament growth on the bacterial surface produces stresses that are relieved at the back of the bacterium as it moves forward. The model leads to a natural competition between growth from the sides and growth from the back of the bacterium, with different velocities and strengths for each. This competition can lead to the periodic motion observed in a Listeria mutant.

Actins↗
PubMed2000

Is it reasonable to assume a uniformly distributed cooling-rate along the microslide of a directional solidification stage?

It is commonly assumed that the cooling-rate along the microslide of a directional solidification stage is uniformly distributed, an assumption which is typically applied in low cooling-rates studies. A new directional solidification stage has recently been presented, which is specified to achieve high cooling-rates of up to 1.8 x 104 degrees C min-1, where cooling-rates are still assumed to be uniformly distributed. The current study presents a closed-form solution to the temperature distribution and to the cooling-rate in the microslide. Thermal analysis shows that the cooling-rate is by no means uniformly distributed and can vary by several hundred percent along the microslide in some cases. Therefore, the mathematical solution presented in this study is essential for experimental planning of high cooling-rate experiments.

Journal Article↗
PubMed2000

Temperature-controlled microscopy for imaging living cells: apparatus, thermal analysis and temperature dependency of embryonic elongation in Caenorhabditis elegans.

A new experimental apparatus for temperature-controlled microscopy has been developed for the study of the temperature dependency of developmental processes in the nematode Caenorhabditis elegans. However, the application of this apparatus is rather general and can be used for a wide range of temperatures between - 10 and 90 degrees C. The new apparatus is easy to use, inexpensive, simple to construct, and is designed for precise temperature control of oil-immersion microscopy using epifluorescence. Thermal analysis of the experimental apparatus shows the effects of each of its components, as well as the effects of uncertainty in temperature measurements. Finally, results of this study indicate that: (i) embryos incubated and imaged at temperatures of 8 degrees C and below do not elongate; (ii) the initial elongation rate is strongly temperature-dependent between 9 and 25 degrees C.

Animals↗
PubMed2000

Fluctuating filaments: statistical mechanics of helices

We examine the effects of thermal fluctuations on thin elastic filaments with noncircular cross section and arbitrary spontaneous curvature and torsion. Analytical expressions for orientational correlation functions and for the persistence length of helices are derived, and it is found that this length varies nonmonotonically with the strength of thermal fluctuations. In the weak fluctuation regime, the local helical structure is preserved and the statistical properties are dominated by long-wavelength bending and torsion modes. As the amplitude of fluctuations is increased, the helix "melts" and all memory of intrinsic helical structure is lost. Spontaneous twist of the cross section leads to resonant dependence of the persistence length on the twist rate.

Journal Article↗
PubMed1999

Long-term follow-up post-cryosurgery in a sheep breast model.

This study constitutes the advanced stage of an ongoing project for the development of cryosurgical devices and techniques for breast cryosurgery. The current study focuses on the long-term follow-up post-cryosurgery in a sheep breast model. Results of this study indicate that the cryotreatment site in a sheep breast model cannot be identified up to 5 months post-cryosurgery by means of ultrasound, mammography, or MRI. Histology findings of this study further indicate that there is no gross or microscopic difference between lesions that have been subject to one versus three freeze/thaw cycles. Under either cryosurgical protocol, there is a main cryoinjured region that has uniform destruction of epithelium and healing scar formation and a transition zone of damaged lobules without acini, surrounded by healthy tissues. The cryoinjured region at 5 months post-cryosurgery was found to be about half the diameter of the ultrasound-imaged frozen region during the cryoprocedure. This study shows that, in terms of recovery and regeneration, surgical excision appears to have an advantage over cryosurgery, which results in a more rapid healing process. Based on observations that the cryoinjured region is no smaller than the ultrasound-imaged ice-ball and that the typical thickness of the transition zone is up to 5 mm, a conservative use of the cryosurgical device developed for the current study in an ultrasound-monitored cryoprocedure requires at least 5 mm safety margins of the frozen region radius around the target region.

Animals↗
PubMed1998

Thermal expansion measurements of frozen biological tissues at cryogenic temperatures.

Thermal expansion data are essential for analyses of cryodestruction associated with thermal stresses during cryopreservation protocols as well as during cryosurgery. The present study tests a commonly used hypothesis that the thermal expansion of frozen tissues is similar to that of pure water ice crystals. This study further provides insight into the potential effect of the presence of cryoprotectants on thermal expansion. A new apparatus for thermal strain measurements of frozen biological tissues within a cryogenic temperature range is presented. Results are presented for fresh tissue samples taken from beef muscle, chicken muscle, rabbit muscle, rabbit bone, and pig liver. Pilot studies of the effect of cryoprotectants on thermal expansion are further presented for rabbit muscle immersed in dimethyl sulphoxide (2 mols/l) and glycerol (2 mols/l), and for pig liver perfused with dimethyl sulphoxide (2 mols/l). Thermal expansion of frozen soft biological tissues was found to be similar to that of water ice crystals in the absence of cryoprotectant. Thermal expansion of the rabbit bone was found to be about one half of that of frozen soft tissues. A significant reduction in the thermal expansion at higher temperatures was observed in the presence of cryoprotectants. A rapid change of thermal strain near -100 degrees C was also observed, which is likely to be associated with the glass transition process of the cryoprotectant solutions.

Animals↗
PubMed1998

Numerical solution of the multidimensional freezing problem during cryosurgery.

A multidimensional, finite difference numerical scheme for the freezing process of biological tissues during cryosurgery is presented, which is a modification of an earlier numerical solution for inanimate materials. The tissues are treated as nonideal materials, freezing over a temperature range and possessing temperature-dependent thermophysical properties, blood perfusion, and metabolic heat generation. The numerical scheme is based on the application of an effective specific heat, substituting the intrinsic property, to include the latent heat effect within the phase transition temperature range. Results of the numerical solution were verified against an existing exact solution of a one-dimensional inverse Stefan problem in Cartesian coordinates. Results were further validated against experimental data available from the literature. The utility of the numerical solution for the design and application of cryodevices is demonstrated by parametric studies of the freezing processes around spherical and cylindrical cryoprobes. The parameters studied are the cryoprobe cooling power and the dimensions of the frozen region. Results are calculated for typical thermophysical properties of soft biological tissues, for angioma and for water.

Cell Survival↗
PubMed1997

Gross damage accumulation on frozen rabbit liver due to mechanical stress at cryogenic temperatures.

The second phase of a pilot study dealing with the mechanical response of frozen biological tissues to external compressive load is presented. This stage deals with histological observations of the damage accompanying mechanically induced permanent deformation in frozen rabbit liver. no significant gross histological damage was observed in the liver samples due to either processing the tissue in the frozen state, due to slow cooling of the liver tissues down to -20 degrees C, or due to rapid cooling of the samples down to -196 degrees C. No histological changes were observed in tissue samples that were loaded within the elastic regime, that is, below the yield strength of the material. Therefore, it is concluded that histological changes due to mechanical stresses are associated with plastic (permanent) deformations. Histological observations indicate that linear cracks which appear to have no preferred orientation develop due to mechanical stress beyond the yield strength of the frozen tissue. These cracks accumulate until final failure of the frozen tissue, when the tissue sample collapses to rubble. Based on histological observations and concepts from solid mechanics, an interaction between crack formation and irregularities in the frozen medium is suggested. Significant sources for such irregularities, in an homogeneous tissue such as the liver, are blood vessels and bile ducts. These irregularities may either initiate crack formation or, on the other hand, may also arrest propagating cracks.

Animals↗
PubMed1997

Combined solution of the inverse Stefan problem for successive freezing/thawing in nonideal biological tissues.

A new combined solution of the one-dimensional inverse Stefan problem in biological tissues is presented. The tissue is assumed to be a nonideal material in which phase transition occurs over a temperature range. The solution includes the thermal effects of blood perfusion and metabolic heat generation. The analysis combines a heat balance integral solution in the frozen region and a numerical enthalpy-based solution approach in the unfrozen region. The subregion of phase transition is included in the unfrozen region. Thermal effects of blood perfusion and metabolic heat generation are assumed to be temperature dependent and present in the unfrozen region only. An arbitrary initial condition is assumed that renders the solution useful for cryosurgical applications employing repeated freezing/thawing cycles. Very good agreement is obtained between the combined and an exact solution of a similar problem with constant thermophysical properties and a uniform initial condition. The solution indicated that blood perfusion does not appreciably affect either the shape of the temperature forcing function on the cryoprobe or the location and depth of penetration of the freezing front in peripheral tissues. It does, however, have a major influence on the freezing/thawing cycle duration, which is most pronounced during the thawing stage. The cooling rate imposed at the freezing front also has a major inverse effect on the duration of the freezing/thawing.

Blood Flow Velocity↗
PubMed1996

A new cryosurgical device for controlled freezing.

A new cryosurgical device utilizing liquid nitrogen, which is a modification of an existing commercial system, was developed. In the new computer-controlled cryodevice the temperature of the cryoprobe is controlled by means of an electrical heating element. The desired temperature-forcing function is calculated to ensure a specified constant cooling rate at the freezing front. The new device facilitates real-time data processing, and, in particular, simulation of the heat transfer processes. A series of tests was performed to study the characteristics of the cryodevice and to validate the underlying assumptions. These tests were performed using organic tissue, i.e., potatoes, as an in vivo simulating medium of biological tissue. The differences between experimental data and computed results were found to be within +/-0.5 degrees C, which falls within the uncertainty range of the experimental temperature measurements. A typical control error of the new device is within +/-0.3 degrees C, prior to the formation of the freezing front, and +/-0.6 degrees C thereafter, which is of the same order of magnitude as the uncertainty range of the temperature measurements. The new device is capable of producing maximal cooling rates of 50 degrees C/min down to temperatures of -165 degrees C and a maximal heating rate of 300 degrees C/min. The maximal cooling power of the cryoprobe, due to LN2 boiling, is 80 W; the maximal electrical heating power of the cryoprobe is 160 W. Precooling of the device requires about 30 min, and it can be operated continuously for about 3 h. Initial results of experimental in vivo cryosurgery performed on rabbit hindlimbs, including histological observations and thermal analysis, are presented in the second part of this study.

Computer Simulation↗
PubMed1996

A new cryosurgical device for controlled freezing.

A new cryosurgical device was developed in this study to facilitate examination of factors affecting the outcome of cryotreatment. Special emphasis was placed on the control of the cooling rate at the freezing front. In the new computer-controlled cryosurgical device, the controlling variable is the cryoprobe temperature, which is calculated to ensure prespecified cooling rates at the freezing front. Details of the new cryodevice, results of a validation test, and the system characteristics are presented in Part I of this study. In this part of the study initial results of 13 in vivo experimental cryotreatments, including histological observations, are presented. The in vivo pilot investigations include the normal, healthy skin and the underlying skeletal muscle of the thighs in rabbits. Using low cooling rate-controlled freezing, the new cryosurgical device is demonstrated here as an effective surgical tool. An in vivo temperature measurement technique is employed based on miniature thermocouples and X-ray images. Thermal analysis of the heat transfer in the cryotreated tissue is presented, based on the temperature measurements and on numerical heat transfer simulations. Cryotreated tissue was extracted either immediately or 4 or 7 days following the procedure. The histological observations on the skeletal muscle of the 4- and 7-day postcryoinjury were not substantially different. The effective penetration depth of the cryolesion was in the range of 5-15 mm, possibly extending up to 25 mm, depending on the specific area treated and operating parameters. The cryotreatment resulted in complete destruction of cells in the skin followed by rapid replacement by epithelial cells. Histological responses to cryotreatment of skeletal muscle were similar to those resulting from a range of traumatic episodes, e.g., crush damage. It was also found that most of the blood vessels in the cryotreated region remained intact without histological evidence of extravasation of erythrocytes.

Animals↗
PubMed1996

Analysis of Thermal Stresses around a Cryosurgical Probe

Large thermal stresses easily exceeding the tissue yield strength may develop in the frozen region around a cryosurgical probe. A new integrodifferential solution for the heat transfer problem of biological tissues freezing around a cryosurgical probe is presented in this article. This solution is suitable for cases of high Stephan numbers and for a temperature-dependent forcing function at the cryoprobe. A new solution for the thermal stresses around a cryosurgical probe is also presented, based on an elastic-perfectly plastic model. It is proposed that thermal stresses beyond the elastic limit of the frozen region may sharply increase the mechanical damage to the cell membranes due to plastic deformation. It was found that plastic deformation always starts at the cryoprobe surface; however, plastic deformation may also be formed near the freezing front at high cooling rates and large cryoprobes. It is demonstrated that under some conditions plastic deformation may occur in the entire frozen region. A parametric study to identify the best cooling protocol for maximal plastic deformation is presented.

Journal Article↗
PubMed1996

An experimental study of the mechanical response of frozen biological tissues at cryogenic temperatures.

An experimental study of the mechanical response of frozen soft biological tissues to applied compressive stresses is presented. This study is related to the mechanical stresses that develop due to the contraction of frozen tissues in cryopreservation as well as in cryosurgical procedures. The main concept in this study is that the stresses associated with the constrained contraction of the frozen tissue, i.e., due to temperature variations within the frozen tissue, can be simulated by an external mechanical load which is applied to the frozen tissue while the tissue is maintained at a uniform temperature. A new apparatus for measuring compressive stresses and strains of frozen biological tissues in cryogenic temperature range is presented. A new technique for processing the fresh biological tissue into a cylindrical frozen sample for mechanical testing is introduced. Results of compression tests on rabbit liver, kidney, and brain are presented and are compared with available data from the literature on sea ice and single ice crystals. An unusual response of frozen biological tissues to compressive stress was observed: after the initial, roughly linear elastic portion there was a series of sudden stress drops at constant strain, each followed by a linear increase of stress with strain to the next drop. This phenomenon, which is attributed to the accumulation of microcracks, broadly resembles plastic deformation, and thus provides some support for simple mechanical models invoked in theoretical studies.

Animals↗