Chromatin accessibility mapping identifies mediators of basal transcription and retinoid-induced repression of OTX2 in medulloblastoma.

Despite an emerging understanding of the genetic alterations giving rise to various tumors, the mechanisms whereby most oncogenes are overexpressed remain unclear. Here we have utilized an integrated approach of genomewide regulatory element mapping via DNase-seq followed by conventional reporter assays and transcription factor binding site discovery to characterize the transcriptional regulation of the medulloblastoma oncogene Orthodenticle Homeobox 2 (OTX2). Through these studies we have revealed that OTX2 is differentially regulated in medulloblastoma at the level of chromatin accessibility, which is in part mediated by DNA methylation. In cell lines exhibiting chromatin accessibility of OTX2 regulatory regions, we found that autoregulation maintains OTX2 expression. Comparison of medulloblastoma regulatory elements with those of the developing brain reveals that these tumors engage a developmental regulatory program to drive OTX2 transcription. Finally, we have identified a transcriptional regulatory element mediating retinoid-induced OTX2 repression in these tumors. This work characterizes for the first time the mechanisms of OTX2 overexpression in medulloblastoma. Furthermore, this study establishes proof of principle for applying ENCODE datasets towards the characterization of upstream trans-acting factors mediating expression of individual genes.

Broadband pulse propagation with electromagnetically induced transparency: Splitting of adiabatic and nonadiabatic components

The propagation of a broadband pulse through a dense resonant medium with a narrow transparency window is considered. We show that the pulse splits into a slowly propagating adiabatic part and a fast nonadiabatic part. © 2005 Optical Society of America.

The ParaWise expert assistant - widening accessibility to efficient and scalable tool Generated OpenMP code

Despite the apparent simplicity of the OpenMP directive shared memory programming model and the sophisticated dependence analysis and code generation capabilities of the ParaWise/CAPO tools, experience shows that a level of expertise is required to produce efficient parallel code. In a real world application the investigation of a single loop in a generated parallel code can soon become an in-depth inspection of numerous dependencies in many routines. The additional understanding of dependencies is also needed to effectively interpret the information provided and supply the required feedback. The ParaWise Expert Assistant has been developed to automate this investigation and present questions to the user about, and in the context of, their application code. In this paper, we demonstrate that knowledge of dependence information and OpenMP are no longer essential to produce efficient parallel code with the Expert Assistant. It is hoped that this will enable a far wider audience to use the tools and subsequently, exploit the benefits of large parallel systems.

Accurate and efficient non-adiabatic quantum molecular dynamics approach for laser-matter interactions

A non-adiabatic quantum molecular dynamics approach for treating the interaction of matter with intense, short-duration laser pulses is developed. This approach, which is parallelized to run on massively-parallel supercomputers, is shown to be both accurate and efficient. Illustrative results are presented for harmonic generation occurring in diatomic molecules using linearly polarized laser pulses.

Beyond Ehrenfest: correlated non-adiabatic molecular dynamics

A method for introducing correlations between electrons and ions that is computationally affordable is described. The central assumption is that the ionic wavefunctions are narrow, which makes possible a moment expansion for the full density matrix. To make the problem tractable we reduce the remaining many-electron problem to a single-electron problem by performing a trace over all electronic degrees of freedom except one. This introduces both one- and two-electron quantities into the equations of motion. Quantities depending on more than one electron are removed by making a Hartree-Fock approximation. Using the first-moment approximation, we perform a number of tight binding simulations of the effect of an electric current on a mobile atom. The classical contribution to the ionic kinetic energy exhibits cooling and is independent of the bias. The quantum contribution exhibits strong heating, with the heating rate proportional to the bias. However, increased scattering of electrons with increasing ionic kinetic energy is not observed. This effect requires the introduction of the second moment.

A Novel Multimodal Interface for Improving Visually Impaired People's Web Accessibility

This paper introduces a novel interface designed to help blind and visually impaired people to explore and navigate on the Web. In contrast to traditionally used assistive tools, such as screen readers and magnifiers, the new interface employs a combination of both audio and haptic features to provide spatial and navigational information to users. The haptic features are presented via a low-cost force feedback mouse allowing blind people to interact with the Web, in a similar fashion to their sighted counterparts. The audio provides navigational and textual information through the use of non-speech sounds and synthesised speech. Interacting with the multimodal interface offers a novel experience to target users, especially to those with total blindness. A series of experiments have been conducted to ascertain the usability of the interface and compare its performance to that of a traditional screen reader. Results have shown the advantages that the new multimodal interface offers blind and visually impaired people. This includes the enhanced perception of the spatial layout of Web pages, and navigation towards elements on a page. Certain issues regarding the design of the haptic and audio features raised in the evaluation are discussed and presented in terms of recommendations for future work.

Ion-acoustic waves in a plasma consisting of adiabatic warm ions, non-isothermal electrons and a weakly relativistic electron beam: linear and higher-order nonlinear effects

The nonlinear propagation of finite amplitude ion acoustic solitary waves in a plasma consisting of adiabatic warm ions, nonisothermal electrons, and a weakly relativistic electron beam is studied via a two-fluid model. A multiple scales technique is employed to investigate the nonlinear regime. The existence of the electron beam gives rise to four linear ion acoustic modes, which propagate at different phase speeds. The numerical analysis shows that the propagation speed of two of these modes may become complex-valued (i.e., waves cannot occur) under conditions which depend on values of the beam-to-background-electron density ratio , the ion-to-free-electron temperature ratio , and the electron beam velocity v0; the remaining two modes remain real in all cases. The basic set of fluid equations are reduced to a Schamel-type equation and a linear inhomogeneous equation for the first and second-order potential perturbations, respectively. Stationary solutions of the coupled equations are derived using a renormalization method. Higher-order nonlinearity is thus shown to modify the solitary wave amplitude and may also deform its shape, even possibly transforming a simple pulse into a W-type curve for one of the modes. The dependence of the excitation amplitude and of the higher-order nonlinearity potential correction on the parameters , , and v0 is numerically investigated.

Providing Legal Information and Advice to Older People: as much a question of accessibility as affordability

No continent has as high a proportion of older people as Europe. In this paper, we report the findings of an empirical project examining the legal advice needs of older people. An important element of the project also sought information about the capacity of the internet for meeting the legal advice needs of older people. Overall our findings broadly indicate considerable failings in legal information provision for older people from more traditional advice sources. Whilst we have uncovered some examples of individualised good practice, our research in the main revealed an alarming sense of fear, mistrust, uncertainty and ambivalence among older people towards accessing legal advice. The research was funded by the Changing Ageing Partnership (CAP). We believe our findings have broad implications and applicability across Europe.

Acoustic solitary waves in dusty and/or multi-ion plasmas with cold, adiabatic, and hot constituents

Large nonlinear acoustic waves are discussed in a four-component plasma, made up of two superhot isothermal species, and two species with lower thermal velocities, being, respectively, adiabatic and cold. First a model is considered in which the isothermal species are electrons and ions, while the cooler species are positive and/or negative dust. Using a Sagdeev pseudopotential formalism, large dust-acoustic structures have been studied in a systematic way, to delimit the compositional parameter space in which they can be found, without restrictions on the charges and masses of the dust species and their charge signs. Solitary waves can only occur for nonlinear structure velocities smaller than the adiabatic dust thermal velocity, leading to a novel dust-acoustic-like mode based on the interplay between the two dust species. If the cold and adiabatic dust are oppositely charged, only solitary waves exist, having the polarity of the cold dust, their parameter range being limited by infinite compression of the cold dust. However, when the charges of the cold and adiabatic species have the same sign, solitary structures are limited for increasing Mach numbers successively by infinite cold dust compression, by encountering the adiabatic dust sonic point, and by the occurrence of double layers. The latter have, for smaller Mach numbers, the same polarity as the charged dust, but switch at the high Mach number end to the opposite polarity. Typical Sagdeev pseudopotentials and solitary wave profiles have been presented. Finally, the analysis has nowhere used the assumption that the dust would be much more massive than the ions and hence, one or both dust species can easily be replaced by positive and/or negative ions and the conclusions will apply to that plasma model equally well. This would cover a number of different scenarios, such as, for example, very hot electrons and ions, together with a mix of adiabatic ions and dust (of either polarity) or a very hot electron-positron mix, together with a two-ion mix or together with adiabatic ions and cold dust (both of either charge sign), to name but some of the possible plasma compositions.

Modelling non-adiabatic processes using correlated electron-ion dynamics

Here we survey the theory and applications of a family of methods (correlated electron-ion dynamics, or CEID) that can be applied to a diverse range of problems involving the non-adiabatic exchange of energy between electrons and nuclei. The simplest method, which is a paradigm for the others, is Ehrenfest Dynamics. This is applied to radiation damage in metals and the evolution of excited states in conjugated polymers. It is unable to reproduce the correct heating of nuclei by current carrying electrons, so we introduce a moment expansion that allows us to restore the spontaneous emission of phonons. Because of the widespread use of Non-Equilibrium Green's Functions for computing electric currents in nanoscale systems, we present a comparison of this formalism with that of CEID with open boundaries. When there is strong coupling between electrons and nuclei, the moment expansion does not converge. We thus conclude with a reworking of the CEID formalism that converges systematically and in a stable manner.