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A tumor-selective non-lytic retroviral replicating vector (RRV), Toca 511, and an extended-release formulation of 5-fluorocytosine (5-FC), Toca FC, are currently being evaluated in clinical trials in patients with recurrent high-grade glioma (NCT01156584, NCT01470794 and NCT01985256). Tumor-selective propagation of this RRV enables highly efficient transduction of glioma cells with cytosine deaminase (CD), which serves as a prodrug activator for conversion of the anti-fungal prodrug 5-FC to the anti-cancer drug 5-fluorouracil (5-FU) directly within the infected cells. We investigated whether, in addition to its direct cytotoxic effects, 5-FU generated intracellularly by RRV-mediated CD/5-FC prodrug activator gene therapy could also act as a radiosensitizing agent. Efficient transduction by RRV and expression of CD were confirmed in the highly aggressive, radioresistant human glioblastoma cell line U87EGFRvIII and its parental cell line U87MG (U87). RRV-transduced cells showed significant radiosensitization even after transient exposure to 5-FC. This was confirmed both in vitro by a clonogenic colony survival assay and in vivo by bioluminescence imaging analysis. These results provide a convincing rationale for development of tumor-targeted radiosensitization strategies utilizing the tumor-selective replicative capability of RRV, and incorporation of radiation therapy into future clinical trials evaluating Toca 511 and Toca FC in brain tumor patients.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.icarus.2009.08.012 Byline: M. Setoh (a), A.M. Nakamura (a), P. Michel (b), K. Hiraoka (c), Y. Yamashita (a)(d), S. Hasegawa (d), N. Onose (d), K. Okudaira (d)(e) Keywords: Asteroids Abstract: Impact experiments on porous targets consisting of sintered glass beads have been performed at different impact velocities in order to investigate the disruption impact energy threshold (also called Q.sup.a) of these targets, the influence of the target compressive strength on this threshold and a scaling parameter of the degree of fragmentation that takes into account material strength. A large fraction of small bodies of our Solar System are expected to be composed of highly-porous material. Depending on their location and on the period considered during the Solar System history, these bodies collide with each other at velocities which cover a wide range of values from a few m/s to several km/s. Determining the impact response of porous bodies in both high- and low-velocity regimes is thus crucial to understand their collisional evolution over the entire Solar System history, from the early stages of planetary formation through collisional accretion at low impact velocities to the current and future stages during which impact velocities are much higher and lead to their disruption. While these problems at large scale can only be addressed directly by numerical simulations, small scale impact experiments are a necessary step which allows the understanding of the physical process itself and the determination of the small scale behavior of the material used as target. Moreover, they are crucial to validate numerical codes that can then be applied to larger scales. Sintered glass beads targets of different shapes and porosity have been built and their main material properties, in particular their compressive strength and their porosity, have been measured. The outcomes of their disruptions both at low and high impact velocities have then been analyzed. We then found that the value of Q.sup.a strongly depends on the target compressive strength. Measuring the particle velocities as a function of their distance to the impact point, we first found that the attenuation rate of the stress wave in our sintered glass bead targets does not depend on the impact velocity regime. Ejecta velocities as a function of the distance from the impact point can thus be well fitted by a power law with an exponent about -2 in both velocity regimes. We then looked for a scaling parameter that can apply to both regimes. We found that the scaling parameter PI, which is related to the initial peak pressure and to the stress wave attenuation can be used to represent the outcome in a general way. Future investigations will be performed to determine whether these results can be generalized to other kinds of porous materials. Author Affiliation: (a) Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan (b) University of Nice-Sophia Antipolis, UMR 6202 Cassiopee/CNRS, Observatoire de la CA[acute accent]te d'Azur, B.P. 4229, 06304 Nice cedex 4, France (c) Graduate School of Science and Technology, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan (d) Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency, Sagamihara, Kanagawa 229-8510, Japan (e) The University of Aizu, ikki-machi, Aizu-Wakamatsu, Fukushima 965-8580, Japan Article History: Received 20 January 2009; Revised 8 August 2009; Accepted 11 August 2009

The gas-phase affinities of methyl and ethyl cations (MCA and ECA) for rare gas atoms and N(sub 2) are measured with a pulsed electron-beam high-pressure mass spectrometer. MCA values for Ar, Xe, and Ne are in good agreement.

Pyroelectric charge response induced by instantaneous heating using YA G laser pulse (7 ns) irradiation has been measured over a 1 ns to 10 s time range for a VDF/TRFE copolymer with composition 75/25 mol%. The observed spectra exhibited two damped oscillations associated with thermal expansion in the thickness and length directions coupled with piezoelectric effects. Removing these two components revealed pyroelectric responses consisting of an instantaneous component followed by a gradually increasing component. The instantaneous component appearing in parallel with the integrated laser intensity was attributed to primary pyroelectricity whose response time was

This study aims to measure objectively and/or estimate the needs of impaired elderly persons and their families for social care services. The research was carried out in Maebashi, a medium size Japanese city. In our study, 'impaired elderly persons' included both physically and/or mentally impaired persons. In total, 693 impaired elderly persons and their families were classified according to 20 specific types of need: these 'need types' were cross-tabulated with two sets of factors: (1) Severity of impairments and (2) Difficulty of caregivers in providing the required care. A standard model of the service provision necessary for each 'need type' was established through group consultation with social care service professionals. Finally, the total amount of each service required in the city was calculated. Major findings are: (1) Our estimates indicate that 7.1 per cent of all persons 65 and over residing in Maebashi City were physically and/or mentally impaired to a certain degree. (2) Forty per cent of these elderly people were being cared for by caregivers who themselves had serious difficulties. (3) The demand for social care services in local Japanese cities is high. In order for this demand to be met a substantial expansion of both nursing home care and in-home care services is required. KEY WORDS - Need measurement, social-care services, impaired elderly people, welfare planning, family care.

Background and purpose: Cholinergic dysfunction appears to play a role in the cognitive impairment observed in Parkinson's disease and dementia with Lewy bodies. The occurrence of cholinergic dysfunction in the early stages of these conditions, however, has not been investigated. The objective of this study was to investigate cholinergic function in patients with idiopathic rapid eye movement sleep behaviour disorder (iRBD), a disorder recognized to be an early stage of both Parkinson's disease and dementia with Lewy bodies. Methods: A total of 21 patients with polysomnography‐confirmed iRBD with no evidence of parkinsonism and cognitive impairment and 10 controls underwent positron emission tomography (PET) to assess brain acetylcholinesterase levels (11C‐donepezil PET) and nigrostriatal dopaminergic function (18F‐DOPA PET). Clinical examination included the Movement Disorder Society–Unified Parkinson's Disease Rating Scale part III, Mini Mental State Examination and Montreal Cognitive Assessment. Results: The 11C‐donepezil PET was successfully performed in 17 patients with iRBD and nine controls. Compared with controls, patients with iRBD showed a mean 7.65% reduction in neocortical 11C‐donepezil levels (P = 0.005). Bilateral superior temporal cortex, occipital cortex, cingulate cortex and dorsolateral prefrontal cortex showed the most significant reductions at voxel level. Conclusion: Reduced neocortical 11C‐donepezil binding in our patients indicates cholinergic denervation and suggests that the projections from the nucleus basalis of Meynert, which supplies cholinergic innervation to the neocortex, are dysfunctional in iRBD. Longitudinal studies will clarify if these changes are predictive of future cognitive impairment in these patients. [ABSTRACT FROM AUTHOR]