Calculations of heavy-ion track structure

A Monte Carlo model is presented to study details of the energy deposition inside tracks of heavy charged particles in water vapor. The input data for most of the calculations based on the binary encounter approximation are double-differential cross sections for electron emission after heavy-ion impact. The paths of the liberated electrons are simulated, taking into account elastic scattering, ionization, and excitation. Each basic interaction of an electron or heavy ion is treated individually. Radial dose distributions and specific energy deposition are calculated for projectiles from protons to uranium in the energy range from one to several hundred megaelectron volts per unified atomic mass unit. Good agreement with measurements in tissue-equivalent gas and propane is obtained for light and medium-heavy projectiles, whereas for heavy projectiles such as uranium, deviations around a factor of 2–3 are observed.     

Mathematical modeling of gas-dynamic and radiative processes in experiments with the use of laser and heavy-ion beams

Results are presented from theoretical and experimental studies of gas-dynamic and radiative processes in the plasma that is planned to be used in future experiments on the stopping of fast heavy-ion beams. These experiments are aimed at measuring the enhanced (as compared to cold substance) plasma stopping power. To reliably interpret the experimental results, it is necessary to create a hydrodynamically stable homogeneous plasma with a uniform temperature and a lifetime exceeding the transit time of the heavy-ion beam (3–5 ns). The method for calculating plasma gas-dynamic characteristics with allowance for radiative heat transfer is described. The specific features of the so-called ion model of plasma, which is used to calculate plasma radiative characteristics, are discussed. The emission spectrum formed as a result of conversion of laser radiation into X-rays and the subsequent passing through a triacetate cellulose (C₁₂H₁₆O₈) target is calculated. The simulated spectrum of transmitted radiation satisfactorily agrees with experimental data.     

Microdosimetric measurements and estimation of human cell survival for heavy-ion beams

The microdosimetric spectra for high-energy beams of photons and proton, helium, carbon, neon, silicon and iron ions (LET = 0.5-880 keV/microm) were measured with a spherical-walled tissue-equivalent proportional counter at various depths in a plastic phantom. Survival curves for human tumor cells were also obtained under the same conditions. Then the survival curves were compared with those estimated by a microdosimetric model based on the spectra and the biological parameters for each cell line. The estimated alpha terms of the liner-quadratic model with a fixed beta value reproduced the experimental results for cell irradiation for ion beams with LETs of less than 450 keV/microm, except in the region near the distal peak.     

Mapping interaction forces with the atomic force microscope.

Force curves were recorded as the sample was raster-scanned under the tip. This opens new opportunities for imaging with the atomic force microscope: several characteristics of the samples can be measured simultaneously, for example, topography, adhesion forces, elasticity, van der Waals, and electrostatic interactions. The new opportunities are illustrated by images of several characteristics of thin metal films, aggregates of lysozyme, and single molecules of DNA.     

Terminal maturation of megakaryocytes and platelet production by hematopoietic stem cells irradiated with heavy-ion beams

Hematopoietic processes, especially megakaryocytopoiesis and thrombopoiesis, are highly sensitive to high-linear energy transfer (LET) radiations such as heavy-ion beams that have greater biological effects than low-LET radiation. This study examined the terminal maturation of megakaryocytes and platelet production derived from hematopoietic stem cells irradiated with heavy-ion beams. CD34(+) cells derived from human placental/umbilical cord blood were exposed to monoenergetic carbon-ion beams (LET = 50 keV/μm) and then cultured in a serum-free medium supplemented with thrombopoietin and interleukin-3. There was no significant difference in megakaryocyte-specific markers between nonirradiated control and irradiated cells. Expression of Tie-2, a receptor that acts in early hematopoiesis, showed a significant 1.31-fold increase after 2 Gy irradiation compared to control cells on day 7. There was a significant increase in Tie-2 mRNA expression. In addition, the expression of other mRNAs, such as PECAM1, SELP and CD44, was also significantly increased in cells irradiated with heavy-ion beams. However, the adherent function of platelets derived from the irradiated cells showed no difference from that in the controls. These results clarify that the functions of megakaryocytopoiesis and thrombopoiesis derived from hematopoietic stem/progenitor cells irradiated with heavy-ion beams are similar to those in the unirradiated cells, although heavy-ion beams affect the expression of genes associated with cellular adhesion.     

Imaging biological structures with the cryo atomic force microscope.

It has long been recognized that one of the major limitations in biological atomic force microscopy (AFM) is the softness of most biological samples, which are easily deformed or damaged by the AFM tip, because of the high pressure in the contact area, especially from the very sharp tips required for high resolution. Another is the molecular motion present at room temperature due to thermal fluctuation. Using an AFM operated in liquid nitrogen vapor (cryo-AFM), we demonstrate that cryo-AFM can be applied to a large variety of biological samples, from immunoglobulins to DNA to cell surfaces. The resolution achieved with cryo-AFM is much improved when compared with AFM at room temperature with similar specimens, and is comparable to that of cryo-electron microscopy on randomly oriented macromolecules. We will also discuss the technical problems that remain to be solved for achieving even higher resolution with cryo-AFM and other possible applications of this novel technique.     

Energy balance in the interaction of intense high-temperature plasma flows with solid targets

The energy balance in the interaction of intense (W≈7 MW/cm², Q≈130 J/cm²) flows of a high-temperature (T _e+T _i≈0.7 keV deuterium plasma with targets made of different materials (graphite, tungsten, copper, etc.) is studied experimentally. It is shown that radiation plays a decisive role in the interaction energy balance: a plasma layer arising near the surface of the eroded target reemits most of the plasma-flow energy into the surrounding space. No more than 50 J/cm² reaches the surface. Then, this energy is expended primarily on the target heating and only a small fraction (less than 3 J/cm²) is spent on the evaporation of the target surface layer. It is shown that, for targets made of high-Z materials, the energy reaching the surface is transferred predominantly by radiation.     

Electrostatic interaction in atomic force microscopy

In atomic force microscopy, the stylus experiences an electrostatic force when imaging in aqueous medium above a charged surface. This force has been calculated numerically with continuum theory for a silicon nitrite or silicon oxide stylus. For comparison, the Van der Waals force was also calculated. In contrast to the Van der Waals attraction, the electrostatic force is repulsive. At a distance of 0.5 nm the electrostatic force is typically 10^-12-10^-10 N and thus comparable in strength to the Van der Waals force. The electrostatic force increases with increasing surface charge density and decreases roughly exponentially with distance. It can be reduced by imaging in high salt concentrations. Below surface potentials of ≈50 mV, a simple analytical approximation of the electrostatic force is described.     

Probing tethered targets of a single biomolecular complex with atomic force microscopy

DNA origami shows tremendous promise as templates for the assembly of nano‐components and detection of molecular recognition events. So far, the method of choice for evaluating these structures has been atomic force microscopy (AFM), a powerful tool for imaging nanoscale objects. In most cases, tethered targets on DNA origami have proven to be highly effective samples for investigation. Still, while maximal assembly of the nanostructures might benefit from the greatest flexibility in the tether, AFM imaging requires a sufficient stability of the adsorbed components. The balance between the tether flexibility and sample stability is a major, poorly understood, concern in such studies. Here, we investigated the dependence of the tethering length on molecular capture events monitored by AFM. In our experiments, single biotin molecules were attached to DNA origami templates with various linker lengths of thymidine nucleotides, and their interaction with streptavidin was observed with AFM. Our results show that the streptavidin‐biotin complexes are easily detected with short tethered lengths, and that their morphological features clearly change with the tethering length. We identify the functionally useful tether lengths for these investigations, which are also expected to prove useful in the construction and further application of DNA origami in bio‐nanotechnology studies. Copyright © 2013 John Wiley & Sons, Ltd.     

Stretched DNA structures observed with atomic force microscopy.

Double-stranded DNA molecules are occasionally found that appear to be straightened and stretched in atomic force microscope (AFM) images. Usually pBS+ plasmid and lambda DNA show relaxed structures with bends and kinks along the strands and have measured contour lengths consistent to about 5-7%; they also appear not to cross over each other, except in very high concentrations. The anomalous molecules observed here, compared with the majority of molecules in the preparation, show contour lengths increased by as much as 80% and have measured heights of about half that of normal relaxed DNA. Some molecules also appear to be in transition between stretched and relaxed forms. These observations are consistent with an uncoiling of the DNA helix without breakage of the covalent bonds in the deoxyribose-phosphate backbone.     

Structure-reactivity relationships for electrophilic sugars in interaction with nucleophilic biological targets

The global electrophilicity index that incorporates electrostatic and polarizability contributions shows a quantitative correlation with antiviral and cytotoxic activities of electrophilic sugars. The model is applied to a series of compounds that behave as Michael acceptors in interaction with biological nucleophilic targets.     

An effective method for detection and analysis of DNA damage induced by heavy-ion beams

We have developed an efficient system to detect and analyze DNA mutations induced by heavy-ion beams in Arabiopsis thaliana. In this system, a stable transgenic Arabidopsis line that constitutively expresses a yellow fluorescent protein (YFP) by a single-copy gene at a genomic locus was constructed and irradiated with heavy-ion beams. The YFP gene is a target of mutagenesis, and its loss of function or expression can easily be detected by the disappearance of YFP signals in planta under microscopy. With this system, a (12)C(6+)-induced mutant with single deletion and multiple base changes was isolated.     

Chiral interaction in protein structures

A new mode of interaction, to be termed chiral interaction, is proposed between chiral molecules such as proteins and polar solvents (H₂O). Such a mode of interaction is well-recognized for macroscopic chiral devices, such as windmills or electric cells, and various media, such as wind or electrolyte. This mode of interaction requires several structural ingredients, all possessed by proteins, and its source is in ionic motion in the solvent. Such an interaction exists only for chiral objects or molecules and therefore possesses several peculiar and uncommon features, which may be of special biological significance. From a thermodynamical viewpoint this phenomenon is non-ergodic and time-irreversible, and therefore does not obey the principle of detailed balance. The energy content of this interaction is rather small and therefore it is to be regarded as a subthermal organization. Chiral interaction appears in the form of an intrinsic flow of perturbation or currents throughout the molecule and hence it is not easily observable. Two experiments are proposed for its observation. One is direct and the other is based on an assumption that couples chiral interaction with enzymatic activity. A model is proposed that links this interaction with the natural selection of the L-enantiomer of amino acids via the magnetic field of the earth. Several structural and other properties may obtain biological significance via the concept of chiral interaction. It is conjectured that chiral interaction may play a significant role in the control of protein activity.     

Selective prediction of interaction sites in protein structures with THEMATICS

Background  

Methods are now available for the prediction of interaction sites in protein 3D structures. While many of these methods report high success rates for site prediction, often these predictions are not very selective and have low precision. Precision in site prediction is addressed using Theoretical Microscopic Titration Curves (THEMATICS), a simple computational method for the identification of active sites in enzymes. Recall and precision are measured and compared with other methods for the prediction of catalytic sites.     

Formation of multiply charged ions in the interaction of laser radiation with targets of various densities

Mass, charge, and energy spectra of multiply charged ions in a plasma formed by laser heating of Ho₂O₃ and Y₂O₃ targets of various densities are investigated. The features of the formation of multiply charged oxygen and holmium (yttrium) ions at fairly low ion energies (≤50 eV) are examined. It is found that, for oxygen ions, Z _max is achieved at low target densities, whereas, for holmium (yttrium) ions, it is achieved at high target densities. It is suggested that these features are related mainly to nonequilibrium ionization processes in the plasma.