Survivin a radiogenetic promoter for glioblastoma viral gene therapy independently from CArG motifs

BACKGROUND: Radiogenetic therapy is a novel approach in the treatment of cancer, which employs genetic modification to alter the sensitivity of tumor cells to the effect of applied radiation. AIM: To select a potent radiation inducible promoter in the context of brain tumors and to investigate if CArG radio responsive motifs or other elements in the promoter nucleotide sequences can correlate to its response to radiation. METHODS: To select initial candidates for promoter inducible elements, the levels of mRNA expression of six different promoters were assessed using Quantitative RTPCR in D54 MG cells before and after radiation exposure. Recombinant Ad/reporter genes driven by five different promoters; CMV, VEGF, FLT-1, DR5 and survivin were constructed. Glioma cell lines were infected with different multiplicity of infection of the (promoter) Ad or CMV Ad. Cells were then exposed to a range of radiation (0–12 Gy) at single fraction. Fluorescent microscopy, Luc assay and X-gal staining was used to detect the level of expression of related genes. Different glioma cell lines and normal astrocytes were infected with Ad survivin and exposed to radiation. The promoters were analyzed for presence of CArG radio-responsive motifs and CCAAT box consensus using NCBI blast bioinformatics software. RESULTS: Radiotherapy increases the expression of gene expression by 1.25–2.5 fold in different promoters other than survivin after 2 h of radiation. RNA analysis was done and has shown an increase in copy number of tenfold for survivin. Most importantly cells treated with RT and Ad Luc driven by survivin promoter showed a fivefold increase in expression after 2 Gy of radiation in comparison to non-irradiated cells. Presence or absence of CArG motifs did not correlate with promoter response to radiation. Survivin with the best response to radiation had the lowest number of CCAAT box. CONCLUSION: Survivin is a selective potent radiation inducible promoter for glioblastoma viral gene therapy and this response to radiation could be independent of CArG motifs

On the exit statistics theorem of many particle quantum scattering

We review the foundations of the scattering formalism for one particle potential scattering and discuss the generalization to the simplest case of many non interacting particles. We point out that the "straight path motion" of the particles, which is achieved in the scattering regime, is at the heart of the crossing statistics of surfaces, which should be thought of as detector surfaces. We sketch a proof of the relevant version of the many particle flux across surfaces theorem and discuss what needs to be proven for the foundations of scattering theory in this context.Comment: 15 pages, 4 figures; to appear in the proceedings of the conference "Multiscale methods in Quantum Mechanics", Accademia dei Lincei, Rome, December 16-20, 200

Genomic signatures of heterokaryosis in the oomycete pathogen Bremia lactucae.

Lettuce downy mildew caused by Bremia lactucae is the most important disease of lettuce globally. This oomycete is highly variable and rapidly overcomes resistance genes and fungicides. The use of multiple read types results in a high-quality, near-chromosome-scale, consensus assembly. Flow cytometry plus resequencing of 30 field isolates, 37 sexual offspring, and 19 asexual derivatives from single multinucleate sporangia demonstrates a high incidence of heterokaryosis in B. lactucae. Heterokaryosis has phenotypic consequences on fitness that may include an increased sporulation rate and qualitative differences in virulence. Therefore, selection should be considered as acting on a population of nuclei within coenocytic mycelia. This provides evolutionary flexibility to the pathogen enabling rapid adaptation to different repertoires of host resistance genes and other challenges. The advantages of asexual persistence of heterokaryons may have been one of the drivers of selection that resulted in the loss of uninucleate zoospores in multiple downy mildews

Dissipation time and decay of correlations

We consider the effect of noise on the dynamics generated by volume-preserving maps on a d-dimensional torus. The quantity we use to measure the irreversibility of the dynamics is the dissipation time. We focus on the asymptotic behaviour of this time in the limit of small noise. We derive universal lower and upper bounds for the dissipation time in terms of various properties of the map and its associated propagators: spectral properties, local expansivity, and global mixing properties. We show that the dissipation is slow for a general class of non-weakly-mixing maps; on the opposite, it is fast for a large class of exponentially mixing systems which include uniformly expanding maps and Anosov diffeomorphisms.Comment: 26 Pages, LaTex. Submitted to Nonlinearit

The Role of Published Materials in Curriculum Development and Implementation for Secondary School Design and Technology in England and Wales

This is a postprint of an article whose final and definitive form has been published in the International Journal of Technology and Design Education. The original publication is available at www.springerlink.com.This paper discusses the ways in which teachers exploited a set of curriculum materials published as a vehicle for curriculum innovation, and the relationship between chosen modes of exploitation and teachers’ own perceptions of how the materials had ’added value’ to their teaching. The materials in question were developed by the Nuffield Design and Technology Project (’the Project’) to offer a pedagogy appropriate to the statutory curriculum for secondary school design and technology education in England and Wales (DFE/WO 1995). The Project had sought both to inform the statutory curriculum, and respond to its requirements. An earlier case study (Givens 1997) laid the foundations for the survey that is reported here. This paper focuses on the teaching of pupils aged 11–14. It finds that while most teachers made at least some use of all the various components of the publications, they were selective. While the Study Guide, which carries out a meta-cognitive dialogue with pupils, was generally underused, those teachers who did use it perceived greater value added by the materials as a whole to the quality of pupils’ work, their effectiveness in design and technology and their autonomy

The impact of hyperhidrosis on patients' daily life and quality of life : A qualitative investigation

Background: An understanding of the daily life impacts of hyperhidrosis and how patients deal with them, based on qualitative research, is lacking. This study investigated the impact of hyperhidrosis on the daily life of patients using a mix of qualitative research methods. Methods: Participants were recruited through hyperhidrosis patient support groups such as the Hyperhidrosis Support Group UK. Data were collected using focus groups, interviews and online surveys. A grounded theory approach was used in the analysis of data transcripts. Data were collected from 71 participants, out of an initial 100 individuals recruited. Results: Seventeen major themes capturing the impacts of hyperhidrosis were identified; these covered all areas of life including daily life, psychological well-being, social life, professional /school life, dealing with hyperhidrosis, unmet health care needs and physical impact. Conclusions: Psychosocial impacts are central to the overall impacts of hyperhidrosis, cutting across and underlying the limitations experienced in other areas of life.Peer reviewe

Activity driven modeling of time varying networks

Network modeling plays a critical role in identifying statistical regularities and structural principles common to many systems. The large majority of recent modeling approaches are connectivity driven. The structural patterns of the network are at the basis of the mechanisms ruling the network formation. Connectivity driven models necessarily provide a time-aggregated representation that may fail to describe the instantaneous and fluctuating dynamics of many networks. We address this challenge by defining the activity potential, a time invariant function characterizing the agents' interactions and constructing an activity driven model capable of encoding the instantaneous time description of the network dynamics. The model provides an explanation of structural features such as the presence of hubs, which simply originate from the heterogeneous activity of agents. Within this framework, highly dynamical networks can be described analytically, allowing a quantitative discussion of the biases induced by the time-aggregated representations in the analysis of dynamical processes.Comment: 10 pages, 4 figure

Vestibular Perception following Acute Unilateral Vestibular Lesions.

Little is known about the vestibulo-perceptual (VP) system, particularly after a unilateral vestibular lesion. We investigated vestibulo-ocular (VO) and VP function in 25 patients with vestibular neuritis (VN) acutely (2 days after onset) and after compensation (recovery phase, 10 weeks). Since the effect of VN on reflex and perceptual function may differ at threshold and supra-threshold acceleration levels, we used two stimulus intensities, acceleration steps of 0.5°/s(2) and velocity steps of 90°/s (acceleration 180°/s(2)). We hypothesised that the vestibular lesion or the compensatory processes could dissociate VO and VP function, particularly if the acute vertiginous sensation interferes with the perceptual tasks. Both in acute and recovery phases, VO and VP thresholds increased, particularly during ipsilesional rotations. In signal detection theory this indicates that signals from the healthy and affected side are still fused, but result in asymmetric thresholds due to a lesion-induced bias. The normal pattern whereby VP thresholds are higher than VO thresholds was preserved, indicating that any 'perceptual noise' added by the vertigo does not disrupt the cognitive decision-making processes inherent to the perceptual task. Overall, the parallel findings in VO and VP thresholds imply little or no additional cortical processing and suggest that vestibular thresholds essentially reflect the sensitivity of the fused peripheral receptors. In contrast, a significant VO-VP dissociation for supra-threshold stimuli was found. Acutely, time constants and duration of the VO and VP responses were reduced - asymmetrically for VO, as expected, but surprisingly symmetrical for perception. At recovery, VP responses normalised but VO responses remained shortened and asymmetric. Thus, unlike threshold data, supra-threshold responses show considerable VO-VP dissociation indicative of additional, higher-order processing of vestibular signals. We provide evidence of perceptual processes (ultimately cortical) participating in vestibular compensation, suppressing asymmetry acutely in unilateral vestibular lesions

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.