Track structure of protons and other light ions in liquid water: applications of the LIonTrack code at the nanometer scale.

PURPOSE: The LIonTrack (Light Ion Track) Monte Carlo (MC) code for the simulation of H(+), He(2+), and other light ions in liquid water is presented together with the results of a novel investigation of energy-deposition site properties from single ion tracks. METHODS: The continuum distorted-wave formalism with the eikonal initial state approximation (CDW-EIS) is employed to generate the initial energy and angle of the electrons emitted in ionizing collisions of the ions with H2O molecules. The model of Dingfelder et al. ["Electron inelastic-scattering cross sections in liquid water," Radiat. Phys. Chem. 53, 1-18 (1998); "Comparisons of calculations with PARTRAC and NOREC: Transport of electrons in liquid water," Radiat. Res. 169, 584-594 (2008)] is linked to the general-purpose MC code PENELOPE/penEasy to simulate the inelastic interactions of the secondary electrons in liquid water. In this way, the extended PENELOPE/penEasy code may provide an improved description of the 3D distribution of energy deposits (EDs), making it suitable for applications at the micrometer and nanometer scales. RESULTS: Single-ionization cross sections calculated with the ab initio CDW-EIS formalism are compared to available experimental values, some of them reported very recently, and the theoretical electronic stopping powers are benchmarked against those recommended by the ICRU. The authors also analyze distinct aspects of the spatial patterns of EDs, such as the frequency of nearest-neighbor distances for various radiation qualities, and the variation of the mean specific energy imparted in nanoscopic targets located around the track. For 1 MeV/u particles, the C(6+) ions generate about 15 times more clusters of six EDs within an ED distance of 3 nm than H(+). CONCLUSIONS: On average clusters of two to three EDs for 1 MeV/u H(+) and clusters of four to five EDs for 1 MeV/u C(6+) could be expected for a modeling double strand break distance of 3.4 nm.

Monte Carlo dosimetry for forthcoming clinical trials in x-ray microbeam radiation therapy.

The purpose of this work is to define safe irradiation protocols in microbeam radiation therapy. The intense synchrotron-generated x-ray beam used for the treatment is collimated and delivered in an array of 50 microm-sized rectangular fields with a centre-to-centre distance between microplanes of 400 microm. The absorbed doses received by the tumour and the healthy tissues in a human head phantom have been assessed by means of Monte Carlo simulations. The identification of safe dose limits is carried out by evaluating the maximum peak and valley doses achievable in the tumour while keeping the valley doses in the healthy tissues under tolerances. As the skull receives a significant fraction of the dose, the dose limits are referred to this tissue. Dose distributions with high spatial resolution are presented for various tumour positions, skull thicknesses and interbeam separations. Considering a unidirectional irradiation (field size of 2 x 2 cm(2)) and a centrally located tumour, the largest peak and valley doses achievable in the tumour are 55 Gy and 2.6 Gy, respectively. The corresponding maximum valley doses received by the skin, bone and healthy brain are 4 Gy, 14 Gy and 7 Gy (doses in one fraction), respectively, i.e. within tolerances (5% probability of complication within 5 years).

Influence of electrodes on the photon energy deposition in CVD-diamond dosimeters studied with the Monte Carlo code PENELOPE.

A new dosimeter, based on chemical vapour deposited (CVD) diamond as the active detector material, is being developed for dosimetry in radiotherapeutic beams. CVD-diamond is a very interesting material, since its atomic composition is close to that of human tissue and in principle it can be designed to introduce negligible perturbations to the radiation field and the dose distribution in the phantom due to its small size. However, non-tissue-equivalent structural components, such as electrodes, wires and encapsulation, need to be carefully selected as they may induce severe fluence perturbation and angular dependence, resulting in erroneous dose readings. By introducing metallic electrodes on the diamond crystals, interface phenomena between high- and low-atomic-number materials are created. Depending on the direction of the radiation field, an increased or decreased detector signal may be obtained. The small dimensions of the CVD-diamond layer and electrodes (around 100 microm and smaller) imply a higher sensitivity to the lack of charged-particle equilibrium and may cause severe interface phenomena. In the present study, we investigate the variation of energy deposition in the diamond detector for different photon-beam qualities, electrode materials and geometric configurations using the Monte Carlo code PENELOPE. The prototype detector was produced from a 50 microm thick CVD-diamond layer with 0.2 microm thick silver electrodes on both sides. The mean absorbed dose to the detector's active volume was modified in the presence of the electrodes by 1.7%, 2.1%, 1.5%, 0.6% and 0.9% for 1.25 MeV monoenergetic photons, a complete (i.e. shielded) (60)Co photon source spectrum and 6, 18 and 50 MV bremsstrahlung spectra, respectively. The shift in mean absorbed dose increases with increasing atomic number and thickness of the electrodes, and diminishes with increasing thickness of the diamond layer. From a dosimetric point of view, graphite would be an almost perfect electrode material. This study shows that, for the considered therapeutic beam qualities, the perturbation of the detector signal due to charge-collecting graphite electrodes of thicknesses between 0.1 and 700 microm is negligible within the calculation uncertainty of 0.2%.

Escoliosis en el paralítico cerebral gravemente afectado / Scoliosis in seriously affected cerebral palsy subject

Objetivo. Se pretende analizar en una población de paralíticos cerebrales en edad escolar, la incidencia de desviación vertebral, sus tipos y su tratamiento. Pacientes y método. Se han revisado las historias clínicas y radiografías de los 34 paralíticos cerebrales que acuden al Centro Escolar San Germán de ASPACE Zaragoza. Se han analizado los siguientes parámetros: sexo, edad, etiología de la parálisis cerebral, diagnóstico clínico y nivel funcional, grado de retraso mental, exploración clínica y radiológica de columna de todos ellos. En la exploración radiológica se midió la existencia o no de desviaciones vertebrales en los tres planos del espacio. En los casos con escoliosis se ha estudiado además, la edad de aparición de las curvas, la existencia de oblicuidad pélvica, luxación de cadera, úlceras por decúbito, tratamientos realizados, tiempo de seguimiento y evolución de la escoliosis y se dividieron en dos grupos según la medición del índice de Cobb en el plano frontal: grupo I inferior o igual a 40° y grupo II mayor o igual a 41°, para compararlos. Resultados. Han presentado desviación vertebral 23 (67,6 por ciento), 18 (78,2 por ciento) del grupo I y 5 (21,8 por ciento) del grupo II, siendo lo más frecuente la curva única dorsolumbar con un 52,1 por ciento de los casos. La media de edad de aparición de las curvas fue de 6 años con un rango de 1 a 14 años. El tiempo de seguimiento ha sido de una media de 5 años (de 1 a 13 años).Presentaron oblicuidad pélvica 12 de ellos (52 por ciento), 13 (56,5 por ciento) luxación de cadera, y 4 (17,4 por ciento), úlceras por decúbito. La localización de las úlceras fue: dos sacras, una isquiática y en un caso se asociaban una sacra y una en región costal. Los tratamientos realizados para su escoliosis, además de fisioterapia diaria en todos ellos, ha sido asiento moldeado en 10 casos (43,5 por ciento), corsé ortopédico en tres (13 por ciento), colchón de gomaespuma para decúbito en cinco (21,7 por ciento) e intervención quirúrgica en dos (8,6 por ciento) (AU)

Calculations of electron fluence correction factors using the Monte Carlo code PENELOPE.

In electron-beam dosimetry, plastic phantom materials may be used instead of water for the determination of absorbed dose to water. A correction factor phi(water)plastic is then needed for converting the electron fluence in the plastic phantom to the fluence at an equivalent depth in water. The recommended values for this factor given by AAPM TG-25 (1991 Med. Phys. 18 73-109) and the IAEA protocols TRS-381 (1997) and TRS-398 (2000) disagree, in particular at large depths. Calculations of the electron fluence have been done, using the Monte Carlo code PENELOPE, in semi-infinite phantoms of water and common plastic materials (PMMA, clear polystyrene, A-150, polyethylene, Plastic water and Solid water (WT1)). The simulations have been carried out for monoenergetic electron beams of 6, 10 and 20 MeV, as well as for a realistic clinical beam. The simulated fluence correction factors differ from the values in the AAPM and IAEA recommendations by up to 2%, and are in better agreement with factors obtained by Ding et al (1997 Med. Phys. 24 161-76) using EGS4. Our Monte Carlo calculations are also in good accordance with phi(water)plastic values measured by using an almost perturbation-free ion chamber. The important interdependence between depth- and fluence-scaling corrections for plastic phantoms is discussed. Discrepancies between the measured and the recommended values of phi(water)plastic may then be explained considering the different depth-scaling rules used.

Comparison of Monte Carlo calculated electron slowing-down spectra generated by 60Co gamma-rays, electrons, protons and light ions.

When analysing the factors affecting the relative biological effectiveness (RBE) of different radiation qualities, it is essential to consider particularly the low-energy slowing-down electrons (around 100 eV to 1 keV) since they have the potential of inflicting severe damage to the DNA. We present a modified and extended version of the Monte Carlo code PENELOPE that enables scoring of slowing-down spectra. mean local energy imparted spectra and average intra-track nearest-neighbour energy deposition distances of the secondary electrons generated by different radiation qualities, such as electrons, photons, protons and light ions in general. The resulting spectra show that the low-linear energy transfer (LET) beams, 60Co gamma-rays and electrons with initial energies of 0.1 MeV and higher, have as expected approximately the same electron slowing-down fluence per unit dose in the biologically important low-energy interval. Consistent with the general behaviour of the RBE of low-energy electrons, protons and light ions, the low-energy electron slowing-down fluence per unit dose is larger than for low-LET beams, and it increases with decreasing initial projectile energy.

Characterization of a high-dose-rate 90Sr-90Y source for intravascular brachytherapy by using the Monte Carlo code PENELOPE.

Radiation treatment with catheter-based beta-emitter sources is currently under clinical trial to prevent restenosis. In the present paper, we address the characterization of the high-dose-rate 90Sr-90Y seeds of the Beta-Cath system supplied by Novoste Corporation, one of the commercially available sources for intravascular brachytherapy. The Monte Carlo code PENELOPE has been used to simulate the transport of electrons emitted by the encapsulated 90Sr-90Y seeds. The calculated radial dose function and anisotropy function for a single seed in water are compared with simulation results from other authors. Regarding g(r), the present result lies between the ITS3 and EGS4 curves, being somewhat closer to ITS3, while in the case of F(r, theta) some differences appear for certain angular intervals and radial distances. In order to put the observed differences into perspective, we have calculated radial doses for point isotropic sources in water. Our results for 0.5 and 1 MeV electrons are in good agreement with simulations using EGSnrc, and an excellent agreement is obtained with ITS for point 90Sr-90Y emitters. Dose distributions in water are calculated for source 'trains' consisting of 1, 2, 3, 4, 5, 9 and 12 seeds. The dose at the source midplane is enhanced if the number of seeds is up to 4, and saturates for trains with 5 or more seeds. We also compare the dose distribution obtained by simply adding the contributions of individual seeds with the simulation of the complete source train. It is found that both calculation procedures yield essentially the same result for distances greater than about 2 mm. Finally, the contribution of bremsstrahlung photons to the dose is briefly analysed.

Monte Carlo simulation of electron beams from an accelerator head using PENELOPE.

The Monte Carlo code PENELOPE has been used to simulate electron beams from a Siemens Mevatron KDS linac with nominal energies of 6, 12 and 18 MeV. Owing to its accuracy, which stems from that of the underlying physical interaction models, PENELOPE is suitable for simulating problems of interest to the medical physics community. It includes a geometry package that allows the definition of complex quadric geometries, such as those of irradiation instruments, in a straightforward manner. Dose distributions in water simulated with PENELOPE agree well with experimental measurements using a silicon detector and a monitoring ionization chamber. Insertion of a lead slab in the incident beam at the surface of the water phantom produces sharp variations in the dose distributions, which are correctly reproduced by the simulation code. Results from PENELOPE are also compared with those of equivalent simulations with the EGS4-based user codes BEAM and DOSXYZ. Angular and energy distributions of electrons and photons in the phase-space plane (at the downstream end of the applicator) obtained from both simulation codes are similar, although significant differences do appear in some cases. These differences, however, are shown to have a negligible effect on the calculated dose distributions. Various practical aspects of the simulations, such as the calculation of statistical uncertainties and the effect of the 'latent' variance in the phase-space file, are discussed in detail.

Do sequence repeats play an equivalent role in the choline-binding module of pneumococcal LytA amidase?

LytA amidase breaks down the N-acetylmuramoyl-l-alanine bonds in the peptidoglycan backbone of Streptococcus pneumoniae. Its polypeptide chain has two modules: the NH(2)-terminal module, responsible for the catalytic activity, and the COOH-terminal module, constructed by six tandem repeats of 20 or 21 amino acids (p1-p6) and a short COOH-terminal tail. The polypeptide chain must contain at least four repeats to efficiently anchor the autolysin to the choline residues of the cell wall. Nevertheless, the catalytic efficiency decreases by 90% upon deletion of the final tail. The structural implications of deleting step by step the two last (p5 and p6) repeats and the final COOH-tail and their effects on choline-amidase interactions have been examined by comparing four truncated mutants with LytA amidase by means of different techniques. Removal of this region has minor effects on secondary structure content but significantly affects the stability of native conformations. The last 11 amino acids and the p5 repeat stabilize the COOH-terminal module; each increases the module transition temperature by about 6 degrees C. Moreover, the p5 motif also seems to participate, in a choline-dependent way, in the stabilization of the NH(2)-terminal module. The effects of choline binding on the thermal stability profile of the mutant lacking the p5 repeat might reflect a cooperative pathway providing molecular communication between the choline-binding module and the NH(2)-terminal region. The three sequence motives favor the choline-amidase interaction, but the tail is an essential factor in the monomer <--> dimer self-association equilibrium of LytA and its regulation by choline. The final tail is required for preferential interaction of choline with LytA dimers and for the existence of different sets of choline-binding sites. The p6 repeat scarcely affects the amidase stability but could provide the proper three-dimensional orientation of the final tail.

Practical aspects of Monte Carlo simulation of charged particle transport: mixed algorithms and variance reduction techniques.

This paper is concerned with the practical implementation of Monte Carlo simulation methods for charged particle transport. The emphasis is on light particles (electrons and positrons) because of the larger scattering and energy straggling effects. Differential cross sections (DCS) for the various interaction mechanisms are described. As the average number of interactions along the particle track increases with the initial energy, detailed simulation becomes unfeasible at high energies. We can then rely on mixed simulation algorithms: hard events (i.e. individual interactions with angular deflection or energy loss larger than given cutoff values) are sampled from the DCS whereas soft events are simulated by means of a multiple scattering approach. Too frequently, the statistical uncertainty of analogue simulation (i.e. strict simulation of the physical interaction process) is found to be so large that results are meaningless. This problem can be partially solved by applying simple variance reduction techniques.

Biochemical and conformational characterisation of HSP-3, a stallion seminal plasma protein of the cysteine-rich secretory protein (CRISP) family.

HSP-3 is a member of the cysteine-rich secretory protein (CRISP) family from stallion seminal plasma. We report a large-scale purification protocol for native HSP-3. This protein is a non-glycosylated polypeptide chain with a pI of 8-9 and an isotope-averaged molecular mass of 24987 +/- 3 Da. The molecular mass of HSP-3, determined by equilibrium sedimentation, is 26 kDa, showing that the protein exists in solution as a monomer. The concentration of HSP-3 in the seminal plasma of different stallions ranged from 0.3 to 1.3 mg/ml. On average, 0.9-9 million HSP-3 molecules/cell coat the postacrosomal and mid-piece regions of an ejaculated, washed stallion spermatozoon, suggesting a role in sperm physiology. Conformational characterisation of purified HSP-3 was assessed by combination of circular dichroism and Fourier-transform infrared spectroscopies and differential scanning microcalorimetry. Based on secondary structure assignment, HSP-3 may belong to the alpha+beta class of proteins. Thermal denaturation of HSP-3 is irreversible and follows a non-two state transition characterised by a Tm of 64 degrees C, an enthalpy change of 75 kcal/mol, and a van 't Hoff enthalpy of 184 kcal/mol. Analysis of the spectroscopic and calorimetric data indicates the occurrence of aggregation of denatured HSP-3 molecules and suggests the monomer as the cooperative unfolding unit.

Detour factors in water and plastic phantoms and their use for range and depth scaling in electron-beam dosimetry.

Average penetration depths and detour factors of 1-50 MeV electrons in water and plastic materials have been computed by means of analytical calculation, within the continuous-slowing-down approximation and including multiple scattering, and using the Monte Carlo codes ITS and PENELOPE. Results are compared to detour factors from alternative definitions previously proposed in the literature. Different procedures used in low-energy electron-beam dosimetry to convert ranges and depths measured in plastic phantoms into water-equivalent ranges and depths are analysed. A new simple and accurate scaling method, based on Monte Carlo-derived ratios of average electron penetration depths and thus incorporating the effect of multiple scattering, is presented. Data are given for most plastics used in electron-beam dosimetry together with a fit which extends the method to any other low-Z plastic material. A study of scaled depth-dose curves and mean energies as a function of depth for some plastics of common usage shows that the method improves the consistency and results of other scaling procedures in dosimetry with electron beams at therapeutic energies.

sbmC, a stationary-phase induced SOS Escherichia coli gene, whose product protects cells from the DNA replication inhibitor microcin B17.

Microcin B17 (MccB17) is a ribosomally synthesized peptide antibiotic of 43 amino acids that induces double-strand breaking of DNA in a DNA gyrase-dependent reaction. As a consequence, the SOS regulon is induced and massive DNA degradation occurs. In this work we have characterized an Escherichia coli gene, sbmC, that in high copy number determines high cell resistance to MccB17. sbmC encodes a cytoplasmic polypeptide of 157 amino acids (M(r), 18,095) that has been visualized in SDS-polyacrylamide gels. The gene is located at min 44 of the E. coli genetic map, close to the sbcB gene. sbmC expression is induced by DNA-damaging agents and, also, by the entry of cells into the stationary growth phase. A G-->T transversion at the fifth nucleotide of the quasicanonical LexA-box preceding the gene makes recA cells 16-fold more resistant to exogenous MccB17. The gene product, SbmC, also blocks MccB17 export from producing cells. Altogether, our results suggest that SbmC recognizes and sequesters MccB17 in a reversible way.

Uso del benfluorex en pacientes hiperlipidémicos ecuatorianos: estudio cooperativo multicéntrico / Use of benfluorex in hyperlipidemic ecuadorian patients: multicentric and cooperative study

El benfluorex, un hipolipemiante ampliamente conocido, ha demostrado, mediante un estudio abierto en una muestra ecuatoriana, sus propiedades al hacer descender los niveles de colesterol total, triglicéridos y LDL-C en forma significativa e incrementar los niveles del HDL-C también significativamente. Todo esto redunda en la disminución del riesgo aterosclerótico

Effect of Somatostatin on TSH levels in non-toxic sporadic goiter.

Somatostatin (SS-14; growth hormone-release inhibiting hormone) was infused into eight patients with non-toxic sporadic goiter and into eleven normal control subjects. Each patient was given 150 microgram(s) of somatostatin as an intravenous bolus and 350 microgram(s) by infusion over a period of 60 minutes. Somatostatin did not lower the basal TSH levels as compared to the pre-infusion levels in this type of goiter, but produced a decrease in the TSH response to TRH during and after the infusion.