Analysis of low-energy electron track structure in liquid water

An implementation is presented of interaction cross sections for non-relativistic electron track structure simulations. The model, incorporating liquid-phase cross sections for inelastic interactions and improved algorithms for elastic scattering, is applied to Monte Carlo simulation of the track structure of low-energy electrons. Benchmark distributions and mean values are presented for several measures of penetration distances that characterize the general physical extent of the track structure. The results indicate that, except for the last approximately 500 eV of energy loss, electron tracks have a quasi-linear character; this suggests that a major part of an electron track may be reasonably described by a lineal-energy-like characterization.     

On protein partitioning in two-phase aqueous polymer systems.

The partitioning of proteins between the coexisting phases of two-phase aqueous polymer systems reflects an intricate and delicate balance of interactions between proteins, polymers, salts and water. Experimental investigations have suggested that a large number of factors influence protein partitioning, including the types of polymers, their molecular weight and concentration; the protein sizes, conformation and composition; salt type and concentration, and solution pH; and the presence of ligands attached to the polymer which may interact with surface sites of the protein. Complementary modelling attempts have been successful in illuminating several molecular-level mechanisms influencing protein partitioning using lattice-model techniques, viral expansions and a scaling-thermodynamic approach. In spite of these experimental and modelling approaches, many of the physical phenomena associated with these complex systems are not well understood. Notably, the precise nature of the protein-polymer interactions and the potent effect of inorganic salts on the partitioning of proteins in these systems remains poorly understood.     

The consideration of biological effectiveness of low energy protons using biophysical modeling of the effects induced by exposure of V79 cells

We have applied Monte Carlo track structure simulations to estimate relative biological effectiveness (RBE) of low-energy protons using biophysical modelling of radiation effects induced by exposure of V79 cells growing in mono-layer. The microscopic energy deposition in cell nucleus and sub-nucleus volumes was investigated in order to understand the reasons of enhanced biological effectiveness near Bragg peak. Theoretical estimations of RBE based on frequency/dose average lineal energy and calculated yields of initial DNA breaks were collated with experimental RBE_M data. It was found: (1) dose average lineal energy for whole cell nucleus as a function of proton energy shows a distinct peak at 550 keV; (2) the peak values for subnucleus volumes are large compared with the whole cell nucleus; (3) the yield of complex DNA breaks correlates with experimental RBE_M data.     

Chemical and physical microenvironments at the Viking landing sites

Summary Physical and chemical considerations permit the division of the near-surface regolith on Mars into at least six zones of distinct microenvironments. The zones are euphotic, duricrust/peds, tempofrost, permafrost, endolithic, and interfacial/transitional. Microenvironments vary significantly in temperature extremes, mean temperature, salt content, relative pressure of water vapor, UV and visible light irradiance, and exposure to ionizing radiation events (100 Mrad) and oxidative molecular species. From what is known of the chemistry of the atmossphere and regolith fines (soil), limits upon the aqueous chemistry of soil pastesmay be estimated. Heat of wetting could reach 45 cal/g dry soil; initial pH is indeterminate between 1 and 10; ionic strength and salinity are predicted to be extremely high; freezing point depression is inadequate to provide quantities of liquid water except in special cases. The prospects for biotic survival are grim by terrestrial standards, but the extremes of biological resiliency are inaccessible to evaluation. Second-generation in situ experiments which will better define Martian microenvironments are clearly possible. Antarctic dry valleys are approximations to Martian conditions, but deviate significantly by at least half-a-dozen criteria.     

Biophysical mechanism of radiation damage to mammalian cells by X- and gamma-rays

Published information on the reproductive death in mammalian cells irradiated by a wide range of X- and gamma-ray energies has been re-analysed to extract intrinsic efficiencies of damage for the secondary electrons in transient equilibrium. On a log-log plot, a linear dependence on the track average l.e.t. and the average specific primary ionization is found, indicating that either serves as a good quality parameter. The soft X-ray data are consistent with this conclusion. Upon comparison with data for fast heavy ion irradiations, the average specific primary ionization is shown to be applicable independently of radiation type whereas track average l.e.t. is not. Furthermore it is revealed that electrons are most damaging near the end of their range but their efficiency is only about 10-20 per cent of that of fast ions at the same quality, possibly due to the influence of multiple scatter on the electron penetration depth. It is deduced that, for the dose rates involved, the damage by electrons is predominantly by intra-track action and not inter-track action. The results are consistent with the suggestion that optimum damage occurs when the mean free path between ionizations is equivalent to the strand separation in the double-stranded DNA.     

Sonochemical free radical formation in aqueous solutions

The phenomena of stable and transient acoustic cavitation in liquids exposed to ultrasound are briefly explained. The role of micronuclei, resonant bubble size, and rectified diffusion in the initiation of transient cavitation is reviewed. In aqueous solutions transient cavitation initially generates hydrogen atoms and hydroxyl radicals that may recombine to form hydrogen and H2O2 or may react with solutes in the gas phase, at the gas-liquid boundary, or in the bulk of the solution. The analogies and differences between sonochemistry and ionizing radiation chemistry are explored. The use of spin trapping and electron spin resonance to conclusively identify hydrogen atoms and hydroxyl radicals and to detect cavitation produced by continuous wave and by pulsed ultrasound is described in detail.     

Quantitative modelling of DNA damage using Monte Carlo track structure method

This paper presents data on modelling of DNA damage induced by electrons, protons and alpha-particles to provide an insight into factors which determine the biological effectiveness of radiations of high and low linear energy transfer (LET). These data include the yield of single- and double-strand breaks (ssb, dsb) and base damage in a cellular environment. We obtain a ratio of 4–15 for ssb:dsb for solid and cellular DNA and a preliminary ratio of about 2 for base damage to strand breakage. Data are also given on specific characteristics of damage at the DNA level in the form of clustered damage of varying complexity, that challenge the repair processes and if not processed adequately could lead to the observed biological effects. It is shown that nearly 30% of dsb are of complex form for low-LET radiation, solely by virtue of additional breaks, rising to about 70% for high-LET radiation. Inclusion of base damage increases the complex proportion to about 60% and 90% for low- and high-LET radiation, respectively. The data show a twofold increase in frequencies of complex dsb from low-LET radiation when base damage is taken into account. It is shown that most ssb induced by high-LET radiation have associated base damages, and also a substantial proportion is induced by low-energy electrons. Received: 20 September 1998 / Accepted in revised form: 15 December 1998     

Enhancement of the biological effectiveness of low-energy quantum radiation. Microdosimetric basis for a selective radiation effect on chromosome material in cells

Microdosimetric data are presented indicating the possibility of a selective action of ionizing radiation on the chromosomal material of cells using low-energy electrons and photoelectrons formed, as the result of the photoeffect, on the incorporated or native atoms inside DNA upon irradiation with low-energy quantum radiation ("X-activating" effect). A presumed biological effectiveness of the "X-activating" effect on B-16 melanocarcinoma, with bromine and iodine incorporated into the DNA molecule, was estimated.     

A polymer, random walk model for the size-distribution of large DNA fragments after high linear energy transfer radiation

DNA double-strand breaks (DSBs) produced by densely ionizing radiation are not located randomly in the genome: recent data indicate DSB clustering along chromosomes. Stochastic DSB clustering at large scales, from >100 Mbp down to <0.01 Mbp, is modeled using computer simulations and analytic equations. A random-walk, coarse-grained polymer model for chromatin is combined with a simple track structure model in Monte Carlo software called DNAbreak and is applied to data on alpha-particle irradiation of V-79 cells. The chromatin model neglects molecular details but systematically incorporates an increase in average spatial separation between two DNA loci as the number of base-pairs between the loci increases. Fragment-size distributions obtained using DNAbreak match data on large fragments about as well as distributions previously obtained with a less mechanistic approach. Dose-response relations, linear at small doses of high linear energy transfer (LET) radiation, are obtained. They are found to be non-linear when the dose becomes so large that there is a significant probability of overlapping or close juxtaposition, along one chromosome, for different DSB clusters from different tracks. The non-linearity is more evident for large fragments than for small. The DNAbreak results furnish an example of the RLC (randomly located clusters) analytic formalism, which generalizes the broken-stick fragment-size distribution of the random-breakage model that is often applied to low-LET data. Received: 19 July 1999 / Accepted in revised form: 10 December 1999     

Monte Carlo simulation of DNA strand-break induction in supercoiled plasmid pBR322 DNA from indirect effects

We present a new Monte Carlo simulation code system (DBREAK) of the detailed events that occur when ionizing radiation interacts with water and DNA molecules. The model treats the initial energy deposition by radiation, the formation of chemically active species, subsequent diffusion-controlled chemical reactions, and induction of DNA strand breaks. DBREAK assumes one-hit single-strand break (SSB) and two-hit double-strand break (DSB) mechanisms. A high-resolution model of plasmid DNA structure has been introduced. The calculated results are compared with the results of previously performed experiments of the same type. Under aerobic conditions, 89.4% of the DNA damage was attributed to OH-radical and 10.5% and 0.1% to e^– _aq and H, respectively. We also compared the differences between liquid-water track structure and gas-phase-water track structure. The calculated yield of SSBs by liquid-water track structure exceeded that of gas-phase-water track structure by a factor of 1.2. Received: 13 February 1997 / Accepted in revised form: 26 August 1997     

Low-energy electrons inside active DNA models: A tool to elucidate the radiation action mechanisms

To postulate radiation action mechanisms and to test them by Monte Carlo simulation, a complex computer model was developed consisting of major components for the generation of a radiation spectrum, biomolecular structures, and electron track structures in liquid water. As the radiation source¹²⁵I is employed here; it is an excellent test radiation due to its exactly localized position in the DNA molecule and high biological toxicity as a consequence of the emission of short-ranging Auger electrons. A linear DNA plasmid model (Pomplun 1991) which can actively respond to radical attack (Terrissol and Pomplun 1994) has been modified into a nucleosome model representing the double-helix of DNA with 146 basepairs and more than 9000 atoms surrounding the histones. The introduction of this new target structure allows a more realistic simulation of cellular conditions. Using the model's decay accumulation aspect, the situation of many break and survival experiments can be approximated and the influence of several cellular parameters tested. As a first step, a correlation between the size of energy depositions and strand-break patterns was sought.     

A Monte–Carlo step-by-step simulation code of the non-homogeneous chemistry of the radiolysis of water and aqueous solutions. Part I: theoretical framework and implementation

The importance of the radiolysis of water in irradiation of biological systems has motivated considerable theoretical and experimental work in the radiation chemistry of water and aqueous solutions. In particular, Monte–Carlo simulations of radiation track structure and non-homogeneous chemistry have greatly contributed to the understanding of experimental results in radiation chemistry of heavy ions. Actually, most simulations of the non-homogeneous chemistry are done using the Independent Reaction Time (IRT) method, a very fast technique. The main limitation of the IRT method is that the positions of the radiolytic species are not calculated as a function of time, which is needed to simulate the irradiation of more complex systems. Step-by-step (SBS) methods, which are able to provide such information, have been used only sparsely because these are time consuming in terms of calculation. Recent improvements in computer performance now allow the regular use of the SBS method in radiation chemistry. In the present paper, the first of a series of two, the SBS method is reviewed in detail. To these ends, simulation of diffusion of particles and chemical reactions in aqueous solutions is reviewed, and implementation of the program is discussed. Simulation of model systems is then performed to validate the adequacy of stepwise diffusion and reaction schemes. In the second paper, radiochemical yields of simulated radiation tracks calculated by the SBS program in different conditions of LET, pH, and temperature are compared with results from the IRT program and experimental data.     

Basic aspects of photon transport through matter with respect to track structure formation

After a short summary of the most important physical aspects of photon interaction with matter and of the main elements of photon transport simulation, some basic features of photon tracks in liquid water are discussed. These include the statistical distribution of the number of photon interactions caused during the complete photon slow-down, the corresponding mean value, the distance distribution of photon interactions, and the spectral distribution of secondary electrons or, which is the same, the spectral distribution of the start energy of secondary electron tracks. The latter distribution can easily be interpreted in terms of the track entity concept of Mozumder and Magee, which, therefore, proves to be the most natural concept of track structure analysis in the case of photon irradiation. Received: 20 September 1998 / Accepted in revised form: 30 April 1999     

Calculation on spectrum of direct DNA damage induced by low-energy electrons including dissociative electron attachment

In this work, direct DNA damage induced by low-energy electrons (sub-keV) is simulated using a Monte Carlo method. The characteristics of the present simulation are to consider the new mechanism of DNA damage due to dissociative electron attachment (DEA) and to allow determining damage to specific bases (i.e., adenine, thymine, guanine, or cytosine). The electron track structure in liquid water is generated, based on the dielectric response model for describing electron inelastic scattering and on a free-parameter theoretical model and the NIST database for calculating electron elastic scattering. Ionization cross sections of DNA bases are used to generate base radicals, and available DEA cross sections of DNA components are applied for determining DNA-strand breaks and base damage induced by sub-ionization electrons. The electron elastic scattering from DNA components is simulated using cross sections from different theoretical calculations. The resulting yields of various strand breaks and base damage in cellular environment are given. Especially, the contributions of sub-ionization electrons to various strand breaks and base damage are quantitatively presented, and the correlation between complex clustered DNA damage and the corresponding damaged bases is explored. This work shows that the contribution of sub-ionization electrons to strand breaks is substantial, up to about 40–70%, and this contribution is mainly focused on single-strand break. In addition, the base damage induced by sub-ionization electrons contributes to about 20–40% of the total base damage, and there is an evident correlation between single-strand break and damaged base pair A–T.     

Electron spectra and the RBE of X rays

For an assessment of the possible difference in effectiveness between mammography X rays and conventional X rays, the energy and LET spectra of the released electrons are examined. At photon energies below 20 keV and above 100 keV, the energy of the electrons increases with increasing photon energy, which implies that higher-energy photons produce less densely ionizing radiation and are therefore somewhat less effective per unit dose. However, in the intermediate energy range from 20 keV to 100 keV-the range that is relevant to medical diagnostics-the change from the photoelectric effect to the Compton effect causes a transient decrease of electron energies. The ionization density is therefore similar for 200 kVp X rays and 30 kVp mammography X rays, and the distributions of dose in LET suggest an RBE of 30 kVp mammography X rays compared to 200 kVp X rays of up to 1.3. This is in line with an earlier assessment by Brenner and Amols in terms of microdosimetric data, but it is strongly at variance with a recent claim that X rays for mammography are about four times more effective at small doses than conventional X rays and that they cause a correspondingly greater risk for breast cancer. Since LET need not be the only relevant factor, general response functions are examined here that specify-at low dose-the effect per electron of initial energy E and account, for example, for a particular role of the electron range. It is shown that, with any response per electron track that is a nondecreasing function of its starting energy, the low-dose RBE of the mammography X rays relative to the 200 kVp X rays must be substantially less than 2. The Auger electron that accompanies most photoelectrons, but only a minority of the Compton electrons, may increase the effectiveness of the mammography X rays somewhat, but it cannot explain the reported high values of the RBE.     

Structure-guided forcefield optimization

Accurate modeling of biomolecular systems requires accurate forcefields. Widely used molecular mechanics (MM) forcefields obtain parameters from experimental data and quantum chemistry calculations on small molecules but do not have a clear way to take advantage of the information in high-resolution macromolecular structures. In contrast, knowledge-based methods largely ignore the physical chemistry of interatomic interactions, and instead derive parameters almost exclusively from macromolecular structures. This can involve considerable double counting of the same physical interactions. Here, we describe a method for forcefield improvement that combines the strengths of the two approaches. We use this method to improve the Rosetta all-atom forcefield, in which the total energy is expressed as the sum of terms representing different physical interactions as in MM forcefields and the parameters are tuned to reproduce the properties of macromolecular structures. To resolve inaccuracies resulting from possible double counting of interactions, we compare distribution functions from low-energy modeled structures to those from crystal structures. The structural and physical bases of the deviations between the modeled and reference structures are identified and used to guide forcefield improvements. We describe improvements resolving double counting between backbone hydrogen bond interactions and Lennard-Jones interactions in helices; between sidechain-backbone hydrogen bonds and the backbone torsion potential; and between the sidechain torsion potential and Lennard-Jones interactions. Discrepancies between computed and observed distributions are also used to guide the incorporation of an explicit Cα-hydrogen bond in β sheets. The method can be used generally to integrate different sources of information for forcefield improvement.     

Peptide conjugates as tools for the study of biological signal transduction

Today, many biological phenomena are being investigated and understood in molecular detail, and organic chemistry is increasingly being directed towards biological phenomena. This review is intended to highlight this interplay of organic chemistry and biology, using biological signal transduction as an example. Lipo-, glyco-, phospho- and nucleoproteins play key roles in the processes whereby chemical signals are passed across cell membranes and further to the cell nucleus. For the study of the biological phenomena associated with these protein conjugates, structurally well-defined peptides containing the characteristic linkage region of the peptide backbone with the lipid, the carbohydrate or the phosphoric acid ester can provide valuable tools. The multi-functionality and pronounced acid- and base-lability of such compounds renders their synthesis a formidable challenge to conventional organic synthesis. However, the recent development of enzymatic protecting groups, provides one of the central techniques which, when coupled with classic chemical synthesis, can provide access to these complex and sensitive biologically relevant peptide conjugates under particularly mild conditions and with high selectivity.     

Dispersal and transient dynamics in metapopulations

Abstract Recent studies of spatially explicit metapopulation models have shown the existence of complex transient behaviour (supertransients and mesotransients) characterized by spontaneous changes in the system's dynamics after thousands or hundreds of generations, respectively. Their detection in simple ecological models has been taken as evidence that transient dynamics may be common in nature. In this study, we explore the generality of these phenomena in a simple one‐dimensional spatially explicit metapopulation model. We investigate how frequently supertransient behaviour emerges in relation to the shape and type of the dispersal kernel used (normal and Laplace), system size, boundary conditions and how sensitive they are to initial conditions. Our results show that supertransients are rare, are heavily affected by initial conditions and occur for a small set of dispersal parameter values, which vary according to kernel type, system size, and boundary conditions. Similarly, mesotransients emerge over a very narrow range of dispersal parameter values and are rare under all circumstances. Thus, transient dynamics are not likely to be either common or widespread in simple models of ecological systems.     

Thermalization of subexcitation electrons in solid water

We present the results of our Monte Carlo simulations of the slowing down and thermalization of subexcitation (E less than 7.4 eV) electrons in solid water. The scattering cross sections used in the simulations were obtained in another study from the analysis of electron-impact experiments performed on thin ice films deposited on a metal substrate at 14 K. The procedure by which these cross sections were determined is tested with our simulation code and is shown to be satisfactory. We find an average electron thermalization distance of approximately 13 nm, which is larger than what is usually assumed (2-7 nm) in models describing the diffusion-controlled track reactions which occur after 10(-12) s in irradiated liquid water. As for our calculated average thermalization time, it is of the order of 10(-13) s, in good agreement with experimental observations. To show the progression of the thermalization process, we give the distributions of slowing-down distances and times obtained for different stages of this process. The possibility that the subexcitation electrons undergo a dissociative attachment to water molecules is considered and its consequences on the initial yield of various chemical species are discussed. In particular, this dissociative attachment could provide a new explanation for the origin of the unscavengeable initial yield of molecular hydrogen.     

Pulse radiolysis studies of some aza analogues of nucleic acid components

The technique of pulse radiolysis has been utilized to study the reactions of some aza analogues of nucleic acid components with hydrated electrons and OH radicals. The absorption spectra of the transient free radical adducts which result from these reactions and their decay kinetics were determined. The 5-aza analogues gave similar results to those of pyrimidine bases. The 6-aza analogues also showed similar kinetics, however, transient spectra were different. The presence of the sugar moiety in these aza analogues changed the rate law of the OH adduct transient decay from second order to first order kinetics. This finding may have implications for the understanding of the radiation chemistry of DNA.