Semi-empirical formulation of multiple scattering for Gaussian beam model of heavy charged particles stopping in tissue-like matter

Dose calculation for radiotherapy with protons and heavier ions deals with a large volume of path integrals involving a scattering power of body tissue. This work provides a simple model for such demanding applications. There is an approximate linearity between RMS end-point displacement and range of incident particles in water, empirically found in measurements and detailed calculations. This fact was translated into a simple linear formula, from which the scattering power that is only inversely proportional to residual range was derived. The simplicity enabled analytical formulation for ions stopping in water, which was designed to be equivalent with the extended Highland model and agreed with measurements within 2% or 0.02 cm in RMS displacement. The simplicity will also improve the efficiency of numerical path integrals in the presence of heterogeneity.Comment: 6 pages, 3 figures, submitted to Physics in Medicine and Biolog

Computational modeling of beam-customization devices for heavy-charged-particle radiotherapy

A model for beam customization with collimators and a range-compensating filter based on the phase-space theory for beam transport is presented for dose distribution calculation in treatment planning of radiotherapy with protons and heavier ions. Independent handling of pencil beams in conventional pencil-beam algorithms causes unphysical collimator-height dependence in the middle of large fields, which is resolved by the framework comprised of generation, transport, collimation, regeneration, range-compensation, and edge-sharpening processes with a matrix of pencil beams. The model was verified to be consistent with measurement and analytic estimation at a submillimeter level in penumbra of individual collimators with a combinational-collimated carbon-ion beam. The model computation is fast, accurate, and readily applicable to pencil-beam algorithms in treatment planning with capability of combinational collimation to make best use of the beam-customization devices.Comment: 16 pages, 5 figure

3D silicon microdosimetry and RBE study using C-12 ion of different energies

This paper presents a new version of the 3D mesa "bridge" microdosimeter comprised of an array of 4248 silicon cells fabricated on 10 µm thick silicon-on-insulator substrate. This microdosimeter has been designed to overcome limitations existing in previous generation silicon microdosimeters and it provides well-defined sensitive volumes and high spatial resolution. The charge collection characteristics of the new 3D mesa microdosimeter were investigated using the ANSTO heavy ion microprobe, utilizing 5.5 MeV He2+ ions. Measurement of microdosimetric quantities allowed for the determination of the Relative Biological Effectiveness of 290 MeV/u and 350 MeV/u 12C heavy ion therapy beams at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. The microdosimetric RBE obtained showed good agreement with the tissue-equivalent proportional counter. Utilizing the high spatial resolution of the SOI microdosimeter, the LET spectra for 70 MeV 12C+6 ions, like those present at the distal edge of 290 and 350 MeV/u beams, were obtained as the ions passed through thin layers of polyethylene film. This microdosimeter can provide useful information about the lineal energy transfer (LET) spectra downstream of the protective layers used for shielding of electronic devices for single event upset prediction

Recode-2: new design, new search tools, and many more genes

'Recoding' is a term used to describe non-standard read-out of the genetic code, and encompasses such phenomena as programmed ribosomal frameshifting, stop codon readthrough, selenocysteine insertion and translational bypassing. Although only a small proportion of genes utilize recoding in protein synthesis, accurate annotation of ‘recoded’ genes lags far behind annotation of 'standard' genes. In order to address this issue, provide a service to researchers in the field, and offer training data for developers of gene-annotation software, we have gathered together known cases of recoding within the Recode database. Recode-2 is an improved and updated version of the database. It provides access to detailed information on genes known to utilize translational recoding and allows complex search queries, browsing of recoding data and enhanced visualization of annotated sequence elements. At present, the Recode-2 database stores information on approximately 1500 genes that are known to utilize recoding in their expression—a factor of approximately three increase over the previous version of the database. Recode-2 is available at http://recode.ucc.i

A new kinetic model reveals the synergistic effect of E-, P- and A-sites on +1 ribosomal frameshifting

Programmed ribosomal frameshifting (PRF) is a process by which ribosomes produce two different polypeptides from the same mRNA. In this study, we propose three different kinetic models of +1 PRF, incorporating the effects of the ribosomal E-, P- and A-sites toward promoting efficient +1 frameshifting in Escherichia coli. Specifically, the timing of E-site tRNA dissociation is discussed within the context of the kinetic proofreading mechanism of aminoacylated tRNA (aa-tRNA) selection. Mathematical modeling using previously determined kinetic rate constants reveals that destabilization of deacylated tRNA in the E-site, rearrangement of peptidyl-tRNA in the P-site, and availability of cognate aa-tRNA corresponding to the A-site act synergistically to promote efficient +1 PRF. The effect of E-site codon:anticodon interactions on +1 PRF was also experimentally examined with a dual fluorescence reporter construct. The combination of predictive modeling and empirical testing allowed the rate constant for P-site tRNA slippage (ks) to be estimated as ks ≈1.9 s−1 for the release factor 2 (RF2) frameshifting sequence. These analyses suggest that P-site tRNA slippage is the driving force for +1 ribosomal frameshifting while the presence of a ‘hungry codon’ in the A-site and destabilization in the E-site further enhance +1 PRF in E. coli

Identification and Classification of Conserved RNA Secondary Structures in the Human Genome

The discoveries of microRNAs and riboswitches, among others, have shown functional RNAs to be biologically more important and genomically more prevalent than previously anticipated. We have developed a general comparative genomics method based on phylogenetic stochastic context-free grammars for identifying functional RNAs encoded in the human genome and used it to survey an eight-way genome-wide alignment of the human, chimpanzee, mouse, rat, dog, chicken, zebra-fish, and puffer-fish genomes for deeply conserved functional RNAs. At a loose threshold for acceptance, this search resulted in a set of 48,479 candidate RNA structures. This screen finds a large number of known functional RNAs, including 195 miRNAs, 62 histone 3′UTR stem loops, and various types of known genetic recoding elements. Among the highest-scoring new predictions are 169 new miRNA candidates, as well as new candidate selenocysteine insertion sites, RNA editing hairpins, RNAs involved in transcript auto regulation, and many folds that form singletons or small functional RNA families of completely unknown function. While the rate of false positives in the overall set is difficult to estimate and is likely to be substantial, the results nevertheless provide evidence for many new human functional RNAs and present specific predictions to facilitate their further characterization

Polyamines and cancer: old molecules, new understanding

The amino-acid-derived polyamines have long been associated with cell growth and cancer, and specific oncogenes and tumour-suppressor genes regulate polyamine metabolism. Inhibition of polyamine synthesis has proven to be generally ineffective as an anticancer strategy in clinical trials, but it is a potent cancer chemoprevention strategy in preclinical studies. Clinical trials, with well-defined goals, are now underway to evaluate the chemopreventive efficacy of inhibitors of polyamine synthesis in a range of tissues