A simple model for DNA elution from filters

DNA chain scission, induced both in vitro and in vivo by various agents, is an event of great biological relevance. The damage is currently evaluated by empirical membrane separation techniques; the results are quite reproducible and the sensitivity higher than 1 single strand break per 10(9) Daltons. We outline a simple theory of the filtration of coiled macrosolutes, having a random size distribution, through porous membranes, considered as being in quasi-steady flow. The basic transport equation Jj = cj (1 - sigma)Jv is solved by considering that the value of sigma j, the reflection coefficient of component j, (1 less than or equal to j less than or equal to N), is given by (1 - KjRj), where Kj is the partition constant between pore and solution, a function of the conformational entropy loss of the coil, and Rj accounts for the frictional force experienced by a particle moving along the pore. The problem of evaluating the volume Vs filled up with solute has been approached according to a simplified theory of the excluded volume for flexible polymers; the result is Vs = sigma nj4/3 pi(rGj)3 where rGj is the jth radius of gyration. The solution of the resulting set of N differential equations gives nj, the number of molecules of component j remaining on the filter, as a function of the elution volume V. The theory demonstrates that the process is governed by the average dimensions of the coil, so affording a universal calibration of filter elution methods, in excellent agreement with the experiments.     

Blood flow: Theory,effective viscosity and effects of particle distribution

A study is made of blood flow by assuming that the blood constitutes a suspension of cells in plasma instead of a simple homogeneous fluid. A macroscopic theory governing the motion of plasma in a plasma-cell system is derived from the local volume averaging method for a system without mass transfer between the phases, and its characteristic length is much larger than the size of the cells. The equations governing the motion of the local averaged fluid quantities include one additional term in the equation of motion and two additional terms in the energy equation. These terms represent, respectively, the force exerted upon the fluid by the particles, and the rate of heat transfer and work kone upon the fluid by the particles. The theory is applied to obtain the effective viscosity as the explicit function of the volume concentration of the cells by assuming that the cells behave like rigid spherical particles with slip-collision, and the plasma is an compressible Newtonian fluid. Comparison with existing experimental results shows a good agreement. The theory is also used to obtain the effects of cell distribution upon the overall effective viscosity in a circular tube. The quantitative result shows that there is a decrease in overall effective viscosity as the concentration of cells increases toward the center of the tube, and the overall effective viscosity is smaller than the flow with evenly distributed cells.     

Interaction cutoff effect on ruggedness of protein-protein energy landscape

The concept of the energy landscape is important for better understanding of protein-protein interactions and for designing adequate docking procedures. The intermolecular landscape has a rugged terrain that impedes search procedures. Its inherent ruggedness is related to the conformational characteristics of the molecules and to the form of the potential function--more rugged for short-range potentials and less rugged for "soft," typically long-range potentials. Our study determined that the landscape ruggedness is further substantially exacerbated by truncation of the potentials. This additional ruggedness appears below certain critical interaction ranges that depend on the form of the potential. The theoretical model describing the cutoff effect on the landscape ruggedness is confirmed by the energy calculation on a dataset of protein-protein complexes. The negative effect of the potentials cutoff is well known. However, revealing its physical basis in terms of the energy landscape is important for better understanding of intermolecular interactions.     

Formation of a cylindrical ion beam in the field of an axisymmetric system of ring currents at a low Hall current

A study is made of the structure of an accelerating layer with a closed Hall current and the geometry of an ion beam in an external magnetic field created by an arbitrary axisymmetric system of ring currents under conditions such that the Hall current can be ignored. It is shown that the ion trajectories are perpendicular to the magnetron cutoff surface for electrons and that the cathode plasma boundary coincides with a magnetic field line. A magnetic field configuration is found in which the cutoff surface is a plane surface perpendicular to the axis of the system. It is shown that, for a small ratio of the gyroradius of the electrons (in terms of the maximum energy acquired by them in the layer) to the characteristic size of the structure, such a configuration provides sufficient means to ensure the formation of slightly converging ion beams or those that are essentially parallel to the system axis.     

Optimization of an ultra-fast silicon detector for proton and carbon beams using GEANT4 Monte Carlo toolkit

AimThe purpose of this study was to investigate the crosstalk effects between adjacent pixels in a thin silicon detector with 50 um thickness.BackgroundThere are some limitations in the applications of detectors in hadron therapy. So it is necessary to have a detector with concurrent excellent time and resolution. In this work, the GEANT4 toolkit was applied to estimate the best value for energy cutoff in the thin silicon detector in order to optimize the detector.Materials and MethodsGEANT4 toolkit was applied to simulate the transport and interactions of particles. Calculations were performed for a thin silicon detector (2 cm × 2 cm×0.005 cm) irradiated by proton and carbon ion beams. A two-dimensional array of silicon pixels in the x-y plane with 100 um × 100 um × 50 um dimensions build the whole detector. In the end, the ROOT package is used to interpret and analyze the resultsResultsIt is seen that by the presence of energy cutoff, pixels with small deposited energy are ignored. The best values for energy cutoff are 0.01 MeV and 0.7 MeV for proton and carbon ion beams, respectively. By applying these energy cutoff values, efficiency and purity values are maximized and also minimum output errors are achieved.ConclusionsThe results are reasonable, good and useful to optimize the geometry of future silicon detectors in order to be used as beam monitoring in hadron therapy applications.     

Continuum reaction field calculation of dielectric constant and vapor pressures for water and carbon disulfide.

Continuum reaction field theory is applied to calculations of dielectric constant, contribution of intermolecular interactions to the free energy of a liquid, and heat of vaporization. Introduction of repulsive interactions and the use of one adjustable parameter, the free volume, enables prediction of vapor pressures. The calculations are illustrated for a simple nonpolar liquid, carbon disulfide, and for liquid water. It is shown that when Onsager's equation is rearranged to a quadratic equation, and a recently found value of the polarizability is employed, its solutions for liquid water yield good agreement with experimental values throughout the whole temperature range. The decrease of the dielectric constant with temperature is essentially linear with the inverse of absolute temperature, but there is additional significant decrease due to the decrease of density with temperature. The relatively high value of the heat of vaporization of liquid water is expressed in terms of large dipolar interaction of a water molecule with the environment, which is due to polarization effects.     

Concepts of microdosimetry

This is the first part of an investigation of microdosimetric concepts relevant to numerical calculations. The definitions of the microdosimetric quantities are reviewed and formalized, and some additional conventions are adopted. The common interpretation of the quantities in terms of energy imparted to spherical sites is contrasted with their interpretation as the result of a diffusing process applied to the initial spatial pattern of energy transfers in the irradiated medium.     

Biphasic regulation in ligand-receptor interactions

A model is examined in which an excess of activator may inhibit the response in a ligand-receptor interaction. The equation accounts for biphasic responses in which an effector stimulates the response at low concentrations and then inhibits the response at higher concentrations, towards a limit that can be higher, identical or lower than the initial value. Reciprocal features could be observed according to the values of the involved parameters. A maximum 7 dimensions can be found in the space of the parameters of the equation which is of the simple form: v = (A + B + C). Sn/(H + Sn).     

The growth of lung volumes affected by physical performance capacity in boys and girls during childhood and adolescence

The paper concerns a longitudinal study of the relationship between growth in lung functions in terms of forced vital capacity and forced expiratory volume in 1 s, and the development of maximal aerobic power during the age span from 8-18 years of age. The growth curves of anatomical dimensions for boys and girls were similar to those previously established for Northern European children. The growth in lung volume ended later than the growth in body height. It was found that the growth in lung volume was entirely due to growth in body dimensions, with no additional effect of changes in the development of physical performance capacity.     

The dimerization of ferrihaems. II. Equilibrium and kinetic studies of mesoferrihaem dimerization.

Spectrophotometric data have been determined for mesoferrihaem at several pH values and over a range of concentration covering four orders of magnitude. The data reveal a dimerization process according to the equation 2 monomer in equilibrium dimer + H+, analogous to earlier findings for deuteroferrihaem and protoferrihaem. The value of K (defined as K = [dimer] [H+]/[monomer]2) was found to be 6.92.10(-2). This is close to the value for deuteroferrihaem but much less than that for protoferrihaem. This is interpreted in terms of possible additional bonding between the delocalized electron systems in protoferrihaem dimers relative to those of mesoferrihaem and deuteroferrihaem. Rate constants for dimerization were determined by temperature-jump spectrophotometry. The pH dependence of the rate constants is explained in terms of two distinct pathways for the dimerization process. These involve either direct reaction between two undissociated monomer molecules or alternatively an initial acid dissociation of a monomer molecule followed by reaction between an undissociated and dissociated molecule.     

Spectral analysis of inert gas elimination data: resolution limits

A new method of analyzing inert gas data for recovery of the pulmonary ventilation-perfusion ration (VA/Q) distribution is proposed. It is shown that the conventional inert gas elimination equation takes the form of a convolution integral, and the relationship between VA/Q distribution and inert gas elimination resembles that of a noncausal low-pass filter with infinite zero-frequency gain. With the use of this formulation, characteristic features of VA/Q distribution may be represented in the frequency domain in terms of the corresponding energy spectrum. It is shown that the lack of resolution associated with finite data samples and measurement error is caused by distortions in the high-frequency contents of the resulting VA/Q distribution. With six inert gases, the technique cannot resolve a log SD less than 0.21 decade and a modal separation less than 0.87 decade. In the presence of measurement error, the degree of resolution is even less. It is suggested that for maximum resolution the number of discrete and duplicate data samples should be chosen so that the resulting noise and sampling cutoff frequencies are approximately equal.     

Salt-Dependent Folding Energy Landscape of RNA Three-Way Junction

RNAs are highly negatively charged chain molecules. Metal ions play a crucial role in RNA folding stability and conformational changes. In this work, we employ the recently developed tightly bound ion (TBI) model, which accounts for the correlation between ions and the fluctuation of ion distributions, to investigate the ion-dependent free energy landscape for the three-way RNA junction in a 16S rRNA domain. The predicted electrostatic free energy landscape suggests that 1), ion-mediated electrostatic interactions cause an ensemble of unfolded conformations narrowly populated around the maximally extended structure; and 2), Mg²⁺ ion-induced correlation effects help bring the helices to the folded state. Nonelectrostatic interactions, such as noncanonical interactions within the junctions and between junctions and helix stems, might further limit the conformational diversity of the unfolded state, resulting in a more ordered unfolded state than the one predicted from the electrostatic effect. Moreover, the folded state is predominantly stabilized by the coaxial stacking force. The TBI-predicted folding stability agrees well with the experimental measurements for the different Na⁺ and Mg²⁺ ion concentrations. For Mg²⁺ solutions, the TBI model, which accounts for the Mg²⁺ ion correlation effect, gives more improved predictions than the Poisson-Boltzmann theory, which tends to underestimate the role of Mg²⁺ in stabilizing the folded structure. Detailed control tests indicate that the dominant ion correlation effect comes from the charge-charge Coulombic correlation rather than the size (excluded volume) correlation between the ions. Furthermore, the model gives quantitative predictions for the ion size effect in the folding energy landscape and folding cooperativity.     

Microdosimetry of rat alveolar type II cells irradiated with alpha particles from 239PuO2

The alveolar type II cell is one of the critical cells for radiation damage in the lungs after inhalation of radioactive aerosols. With the aid of a Quantimet-970 image analyzer and a VAX-11/780 computer, we calculated the radiation dose to rat alveolar type II cells from alpha particles emitted by 239PuO2. A series of dosimetric parameters for type II cells, including track length distribution, linear energy transfer (LET), values of the specific energy for a single hit of a spherical target (z1), cellular dose, hit number, and their spatial distributions were calculated. By comparing the volume density of type II cells and lung tissue with energy deposited in alveolar type II cells, we found that the energy deposited per unit volume of type II cells was larger than that of lung tissue excluding type II cells. The z1 for spherical targets and the LET across type II cells were less than those in lung tissue excluding type II cells. The age of the rat and damage to lung by inhalation may significantly influence some of the parameters. The neoplastic transformation probability for type II cells is also discussed. The results suggest that the type II cell is an important target cell in the rat lung for exposure to inhaled 239PuO2.     

RF tumor ablation with internally cooled electrodes and saline infusion: what is the optimal location of the saline infusion?

Background

Radiofrequency ablation (RFA) of tumors by means of internally cooled electrodes (ICE) combined with interstitial infusion of saline may improve clinical results. To date, infusion has been conducted through outlets placed on the surface of the cooled electrode. However, the effect of infusion at a distance from the electrode surface is unknown. Our aim was to assess the effect of perfusion distance (PD) on the coagulation geometry and deposited power during RFA using ICE.

Methods

Experiments were performed on excised bovine livers. Perfusion distance (PD) was defined as the shortest distance between the infusion outlet and the surface of the ICE. We considered three values of PD: 0, 2 and 4 mm. Two sets of experiments were considered: 1) 15 ablations of 10 minutes (n ≥ 4 for each PD), in order to evaluate the effect of PD on volume and diameters of coagulation; and 2) 20 additional ablations of 20 minutes. The effect of PD on deposited power and relative frequency of uncontrolled impedance rises (roll-off) was evaluated using the results from the two sets of experiments (n ≥ 7 for each PD). Comparisons between PD were performed by analysis of variance or Kruskal-Wallis test. Additionally, non-linear regression models were performed to elucidate the best PD in terms of coagulation volume and diameter, and the occurrence of uncontrolled impedance rises.

Results

The best-fit least square functions were always obtained with quadratic curves where volume and diameters of coagulation were maximum for a PD of 2 mm. A thirty per cent increase in volume coagulation was observed for this PD value compared to other values (P < 0.05). Likewise, the short coagulation diameter was nearly twenty five per cent larger for a 2 mm PD than for 0 mm. Regarding deposited power, the best-fit least square function was obtained by a quadratic curve with a 2 mm PD peak. This matched well with the higher relative frequency of uncontrolled impedance rises for PD of 0 and 4 mm.

Conclusion

Saline perfusion at around 2 mm from the electrode surface while using an ICE in RFA improves deposition of energy and enlarges coagulation volume.     

Modeling the electrophoresis of lysozyme. II. Inclusion of ion relaxation.

In this work, boundary element methods are used to model the electrophoretic mobility of lysozyme over the pH range 2-6. The model treats the protein as a rigid body of arbitrary shape and charge distribution derived from the crystal structure. Extending earlier studies, the present work treats the equilibrium electrostatic potential at the level of the full Poisson-Boltzmann (PB) equation and accounts for ion relaxation. This is achieved by solving simultaneously the Poisson, ion transport, and Navier-Stokes equations by an iterative boundary element procedure. Treating the equilibrium electrostatics at the level of the full rather than the linear PB equation, but leaving relaxation out, does improve agreement between experimental and simulated mobilities, including ion relaxation improves it even more. The effects of nonlinear electrostatics and ion relaxation are greatest at low pH, where the net charge on lysozyme is greatest. In the absence of relaxation, a linear dependence of mobility and average polyion surface potential, (lambda zero)s, is observed, and the mobility is well described by the equation [formula: see text] where epsilon 0 is the dielectric constant of the solvent, and eta is the solvent viscosity. This breaks down, however, when ion relaxation is included and the mobility is less than predicted by the above equation. Whether or not ion relaxation is included, the mobility is found to be fairly insensitive to the charge distribution within the lysozyme model or the internal dielectric constant.     

Myocardial stress equations: fiberstresses of the prolate spheroid

There are occasions in physiological research and medical practice where it is desirable to estimate the average fiberstress in a chamber wall, knowing only the pressure and dimensions. Because the contribution of a strained wall element to pressure depends on its location whereas its contribution to average stress is independent of location, an equation of this kind must involve an assumption about the stress distribution. When applied to a particular chamber, it will give an exact result only if the chamber's stress distribution is in some sense like that of the model for which the equation was derived. Since the fibers of biological chambers are continually being deposited and resorbed, they tend to exhibit similar stretches under the average conditions of the chamber. To the extent that this is so, P = (2/3) sigma v ln V0/Vc, is the best simple fiberstress equation for biological chambers. (P = transmural pressure, sigma v = volume-averaged fiberstress, V0 = volume enclosed by outside surface, Vc = cavity volume). It expresses the pressure-dimension-average-fiberstress relation of a chamber of any shape whose stresses exhibit the simplest possible distribution. One can add a term to the right side to account for the influence of stress profile complexities. That term takes the form of a moment whose value is zero at one state of distension. This "stress moment" expresses the unequal weighting of complexities on the two sides of the midwall isobar. Judging from the sarcomere length profile of the left ventricular wall, the stress moment is zero and the average fiberstress equation above is exact for average developed stress (without a second term) when cavity volume is somewhere near end-diastolic. Moreover, the departures from the relation (the effects of stress moment) are small so long as the inner and outer stresses do not differ by a factor greater than two.     

Sulfuryl transfer catalyzed by phosphokinases.

Adenosine 5'-sulfatopyrophosphate is a substrate for nucleoside diphosphate kinase. The reaction appears to proceed through a ping-pong mechanism analogous to the physiological reaction involving ATP, presumably by way of a sulfohistidine intermediate. Unlike the phosphoryl transfer reactions, the corresponding sulfuryl transfers catalyzed by nucleoside diphosphate kinase do not have a strict divalent metal requirement. The estimated rate constants for the metal- and nonmetal-catalyzed sulfuryl transfers differ by less than an order of magnitude and are approximately 1000-fold slower than the corresponding phosphate transfers. These results suggest that the role of the metal ion in nucleoside diphosphate kinase is to coordinate the alpha, beta-phosphates of the substrate. Sulfuryl and phosphoryl transfer probably occur through dissociative transition states.     

An Equation to Estimate the Concentration of Serum Apolipoprotein B

Background

Several large prospective studies have demonstrated that apolipoprotein B (apoB) has greater value in predicting cardiovascular risk than any other lipid measurements. Currently, however, serum apoB levels are not routinely measured, because of the additional cost. The aim of this study was to develop an equation to estimate apoB from conventional lipid measurements including total cholesterol, HDL cholesterol, and triglycerides.

Methods

Data from a total of 78,127 subjects (47,057 men and 31,070 women), aged 15 to 88 years (mean age 41.8 years) were reviewed to develop an apoB equation. Additional datasets from the same institution and the NHANES obtained in 2007–2008 were used for internal (n = 73,445) and external validation (n = 3,097), respectively.

Results

We developed an apoB equation based on a linear regression model that contains total cholesterol, triglycerides, and HDL cholesterol as terms (model 1). To more precisely estimate the serum apoB level, we adjusted mode1 1 using a cutoff serum triglyceride value of 270 mg/dl (model 2). Model 2 showed more randomly distributed residuals in patients with diabetes, atherogenic dyslipidemia, and those taking lipid-lowering agents than model 1. The residuals in the development, internal validation, and external validation datasets were also randomly distributed around 0 with no clear trends.

Conclusion

The new equation we developed to estimate serum apoB concentrations is accurate and can be used in diverse subgroups of patients including those with diabetes, atherogenic dyslipidemia, and those taking lipid-lowering agents.     

Comparison of discrete models of charge transfer in thin membranes. I. Stationary regime]

The model of the ion transport through thin membranes is discussed. It is assumed that there exist some steps of the ion transfer in the membrane volume. Theory of absolute rate of processes is used to derive an equation for stationary transmembrane flow. As a result the thory parameters are connected with the form of potential energy curve of permeable ions into the membrane phase.     

Electrodiffusion of ions approaching the mouth of a conducting membrane channel.

The movement of ions in the aqueous medium as they approach the mouth (radius a) of a conducting membrane channel is analyzed. Starting with the Nernst-Planck and Poisson equations, we derive a nonlinear integrodifferential equation for the electric potential, phi(r), a less than or equal to r less than infinity. The formulation allows deviations from charge neutrality and dependence of phi(r) on ion flux. A numerical solution is obtained by converting the equation to an integral equation that is solved by an iterative method for an assumed mouth potential, combined with a shooting method to adjust the mouth potential until the numerical solution agrees with an asymptotic expansion of the potential at r-a much greater than lambda (lambda = Debye length). Approximate analytic solutions are obtained by assuming charge neutrality (Läuger, 1976) and by linearizing. The linear approximation agrees with the exact solution under most physiological conditions, but the charge-neutrality solution is only valid for r much greater than lambda and thus cannot be used unless a much greater than lambda. Families of curves of ion flux vs. potential drop across the electrolyte, phi(infinity)-phi (a), and of permeant ion density at the channel mouth, n1(a), vs. flux are obtained for different values of a/lambda and S = a d phi/dr(a). If a much greater than lambda and S = O, the maximum flux (which is approached when n1(a)----0) is reduced by 50% compared to the value predicted by the charge-neutrality solution. Access resistance is shown to be a factor a/[2 (a + lambda)] times the published formula (Hille, 1968), which was derived without including deviations from charge neutrality and ion density gradients and hence does not apply when there is no counter-ion current. The results are applied to an idealized diffusion-limited channel with symmetric electrolytes. For S = O, the current/voltage curves saturate at a value dependent on a/lambda; for S greater than O, they increase linearly for large voltage.