R&D on co-working transport schemes in Geant4

A research and development (R&D) project related to the extension of the Geant4 toolkit has been recently launched to address fundamental methods in radiation transport simulation. The project focuses on simulation at different scales in the same experimental environment; this problem requires new methods across the current boundaries of condensed-random-walk and discrete transport schemes. The new developments have been motivated by experimental requirements in various domains, including nanodosimetry, astronomy and detector developments for high energy physics applications.Comment: To be published in the Proceedings of the CHEP (Computing in High Energy Physics) 2009 conferenc

A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

Using hiCLIP to identify RNA duplexes that interact with a specific RNA-binding protein

The structure of RNA molecules has a critical role in regulating gene expression, largely through influencing their interactions with RNA-binding proteins (RBPs). RNA hybrid and individual-nucleotide resolution UV cross-linking and immunoprecipitation (hiCLIP) is a transcriptome-wide method of monitoring these interactions by identifying RNA duplexes bound by a specific RBP. The hiCLIP protocol consists of the following steps: in vivo cross-linking of RBPs to their bound RNAs; partial RNA digestion and purification of RNA duplexes interacting with the specific RBP using immunoprecipitation; ligation of the two arms of RNA duplexes via a linker; reverse transcription; cDNA library amplification; and finally high-throughput DNA sequencing. Mapping of the sequenced arms to a reference transcriptome identifies the exact locations of duplexes. hiCLIP data can directly identify all types of RNA duplexes bound by RBPs, including those that are challenging to predict computationally, such as intermolecular and long-range intramolecular duplexes. Moreover, the use of an adaptor that links the two arms of the RNA duplex permits hiCLIP to unambiguously identify the duplexes. Here we describe in detail the procedure for a hiCLIP experiment and the subsequent streamlined data analysis with an R package, 'hiclipr' (https://github.com/luslab/hiclipr/). Preparation of the library for high-throughput DNA sequencing takes ∼7 d and the basic bioinformatic pipeline takes 1 d

Bayesian analysis of data: reconstruction of track structure at 100% detection efficiency for a track-nanodosimetric counter

An algorithmic reconstruction of the probability distribution of ionisation cluster-size formation from measurements performed with detectors having a non-uniform sensitive volume is presented. From such a data analysis, ionisation spectra, which correspond to a detection efficiency of 100%, are extracted for the track-nanodosimetric counter at L.N.L.-I.N.F.N

Simulation of the measured ionisation-cluster distributions of alpha-particles in nanometric volumes of propane

In the last years, the probability of the formation of ionisation clusters by primary alpha particles at 5.4 MeV in nanometric volumes of propane (20.6 and 24.0 nm in a material of density 1.0 g cm(-3)) was studied experimentally and by Monte Carlo simulation. Calculations were performed taking into account the single electron detection efficiency of the track-nanodosimetric counter, which was estimated on the base of Monte Carlo calculations of electron transport inside the detector. Now a new evaluation of the efficiency has been performed, pointing out a value lower than previously estimated. Besides, the efficiency of the counter in resolving temporally the collected electrons has been calculated, together with its effect on the measured distribution. On the base of these evaluations, a new comparison has been performed between measurements and calculations, pointing out a better agreement than previously reported