Multiple exon skipping strategies to by-pass dystrophin mutations.

Manipulation of dystrophin pre-mRNA processing offers the potential to overcome mutations in the dystrophin gene that would otherwise lead to Duchenne muscular dystrophy. Dystrophin mutations will require the removal of one or more exons to restore the reading frame and in some cases, multiple exon skipping strategies exist to restore dystrophin expression. However, for some small intra-exonic mutations, a third strategy, not applicable to whole exon deletions, may be possible. The removal of only one frame-shifting exon flanking the mutation-carrying exon may restore the reading frame and allow synthesis of a functional dystrophin isoform, providing that no premature termination codons are encountered. For these mutations, the removal of only one exon offers a simpler, cheaper and more feasible alternative approach to the dual exon skipping that would otherwise be considered. We present strategies to by-pass intra-exonic dystrophin mutations that clearly demonstrate the importance of tailoring exon skipping strategies to specific patient mutations

Editorial: crime patterns in time and space: the dynamics of crime opportunities in urban areas

The routine activity approach and associated crime pattern theory emphasise how crime emerges from spatio-temporal routines. In order to understand this crime should be studied in both space and time. However, the bulk of research into crime patterns and related activities has investigated the spatial distributions of crime, neglecting the temporal dimension. Specifically, disaggregation of crime by place and by time, for example hour of day, day of week, month of year, season, or school day versus none school day, is extremely relevant to theory. Modern data make such spatio-temporal disaggregation increasingly feasible, as exemplified in this special issue. First, much larger data files allow disaggregation of crime data into temporal and spatial slices. Second, new forms of data are generated by modern technologies, allowing innovative and new forms of analyses. Crime pattern analyses and routine activity inquiries are now able to explore avenues not previously available. The unique collection of nine papers in this thematic issue specifically examine spatio-temporal patterns of crime to; demonstrate the value of this approach for advancing knowledge in the field; consider how this informs our theoretical understanding of the manifestations of crime in time and space; to consider the prevention implications of this; and to raise awareness of the need for further spatio-temporal research into crime event

The Spin Structure of the Nucleon

We present an overview of recent experimental and theoretical advances in our understanding of the spin structure of protons and neutrons.Comment: 84 pages, 29 figure

Light-Cone Quantization and Hadron Structure

In this talk, I review the use of the light-cone Fock expansion as a tractable and consistent description of relativistic many-body systems and bound states in quantum field theory and as a frame-independent representation of the physics of the QCD parton model. Nonperturbative methods for computing the spectrum and LC wavefunctions are briefly discussed. The light-cone Fock state representation of hadrons also describes quantum fluctuations containing intrinsic gluons, strangeness, and charm, and, in the case of nuclei, "hidden color". Fock state components of hadrons with small transverse size, such as those which dominate hard exclusive reactions, have small color dipole moments and thus diminished hadronic interactions; i.e., "color transparency". The use of light-cone Fock methods to compute loop amplitudes is illustrated by the example of the electron anomalous moment in QED. In other applications, such as the computation of the axial, magnetic, and quadrupole moments of light nuclei, the QCD relativistic Fock state description provides new insights which go well beyond the usual assumptions of traditional hadronic and nuclear physics.Comment: LaTex 36 pages, 3 figures. To obtain a copy, send e-mail to [email protected]

The German Internationale Bauausstellung (IBA) and Urban Regeneration: Lessons from the IBA Emscher Park

URBAN. REGENERATION. Lessons. from. the. IBA. Emscher. Park. Philip Pinch and Neil Adams Summary The German approach of using international building exhibitions (Internationale Bauausstellung) to provide an impetus for innovation ..

The nuclear receptors of Biomphalaria glabrata and Lottia gigantea: Implications for developing new model organisms

© 2015 Kaur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedNuclear receptors (NRs) are transcription regulators involved in an array of diverse physiological functions including key roles in endocrine and metabolic function. The aim of this study was to identify nuclear receptors in the fully sequenced genome of the gastropod snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni and compare these to known vertebrate NRs, with a view to assessing the snail's potential as a invertebrate model organism for endocrine function, both as a prospective new test organism and to elucidate the fundamental genetic and mechanistic causes of disease. For comparative purposes, the genome of a second gastropod, the owl limpet, Lottia gigantea was also investigated for nuclear receptors. Thirty-nine and thirty-three putative NRs were identified from the B. glabrata and L. gigantea genomes respectively, based on the presence of a conserved DNA-binding domain and/or ligand-binding domain. Nuclear receptor transcript expression was confirmed and sequences were subjected to a comparative phylogenetic analysis, which demonstrated that these molluscs have representatives of all the major NR subfamilies (1-6). Many of the identified NRs are conserved between vertebrates and invertebrates, however differences exist, most notably, the absence of receptors of Group 3C, which includes some of the vertebrate endocrine hormone targets. The mollusc genomes also contain NR homologues that are present in insects and nematodes but not in vertebrates, such as Group 1J (HR48/DAF12/HR96). The identification of many shared receptors between humans and molluscs indicates the potential for molluscs as model organisms; however the absence of several steroid hormone receptors indicates snail endocrine systems are fundamentally different.The National Centre for the Replacement, Refinement and Reduction of Animals in Research, Grant Ref:G0900802 to CSJ, LRN, SJ & EJR [www.nc3rs.org.uk]

First Measurement of Transferred Polarization in the Exclusive e p --> e' K+ Lambda Reaction

The first measurements of the transferred polarization for the exclusive ep --> e'K+ Lambda reaction have been performed in Hall B at the Thomas Jefferson National Accelerator Facility using the CLAS spectrometer. A 2.567 GeV electron beam was used to measure the hyperon polarization over a range of Q2 from 0.3 to 1.5 (GeV/c)2, W from 1.6 to 2.15 GeV, and over the full center-of-mass angular range of the K+ meson. Comparison with predictions of hadrodynamic models indicates strong sensitivity to the underlying resonance contributions. A non-relativistic quark model interpretation of our data suggests that the s-sbar quark pair is produced with spins predominantly anti-aligned. Implications for the validity of the widely used 3P0 quark-pair creation operator are discussed.Comment: 6 pages, 4 figure

Onset of asymptotic scaling in deuteron photodisintegration

We investigate the transition from the nucleon-meson to quark-gluon description of the strong interaction using the photon energy dependence of the $d(\gamma,p)n$ differential cross section for photon energies above 0.5 GeV and center-of-mass proton angles between $30^{\circ}$ and $150^{\circ}$. A possible signature for this transition is the onset of cross section $s^{-11}$ scaling with the total energy squared, $s$, at some proton transverse momentum, $P_T$. The results show that the scaling has been reached for proton transverse momentum above about 1.1 GeV/c. This may indicate that the quark-gluon regime is reached above this momentum.Comment: Accepted by PRL; 5 pages, 2 figure