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  • Proceedings of the National Academy of Sciences of the United States of America
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  • 1
    In: Proceedings of the National Academy of Sciences of the United States, March 14, 2000, Vol.97(6), p.2785
    Description: We are developing assays for noninvasive, quantitative imaging of reporter genes with positron emission tomography (PET), for application both in animal models and in human gene therapy. We report here a method to improve the detection of lower levels of PET reporter gene expression by utilizing a mutant herpes simplex virus type I thymidine kinase (HSV1-sr39tk) as a PET reporter gene. The HSV1-sr39tk mutant was identified from a library of site-directed mutants. Accumulation (net uptake) of the radioactively labeled substrates [8-[sup.3]H]penciclovir (8-[sup.3]H]PCV), and 8-[[sup.18]F]fluoro-penciclovir (FPCV) in C6 rat glioma cells expressing HSV1-sr39tk is increased by a factor of [approximately equals] 2.0 when compared with C6 cells expressing wild-type HSV1-tk. The increased imaging sensitivity of HSV1-sr39tk when FPCV is used is also demonstrated in vivo both with tumor cells stably transfected with either HSV1-tk or HSV1-sr39tk, and after hepatic delivery of HSV1-tk or HSV1-sr39tk by using adenoviral vectors. The use of HSV1-sr39tk as a PET reporter gene and FPCV as a PET reporter probe results in significantly enhanced sensitivity for imaging reporter gene expression in vivo.
    Keywords: Herpes Simplex Virus -- Genetic Aspects ; Positron Emission Tomography -- Usage ; Gene Therapy -- Research ; Gene Expression -- Analysis
    ISSN: 0027-8424
    E-ISSN: 10916490
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  • 2
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 23 March 2010, Vol.107(12), pp.5329-5333
    Description: The most general investigation and exploitation of light-induced processes require simultaneous control over spatial and temporal properties of the electromagnetic field on a femtosecond time and nanometer length scale. Based on the combination of polarization pulse shaping and time-resolved two-photon photoemission electron microscopy, we demonstrate such control over nanoscale spatial and ultrafast temporal degrees of freedom of an electromagnetic excitation in the vicinity of a nanostructure. The time-resolved cross-correlation measurement of the local photo-emission yield reveals the switching of the nanolocalized optical near-field distribution with a lateral resolution well below the diffraction limit and a temporal resolution on the femtosecond time scale. In addition, successful adaptive spatiotemporal control demonstrates the flexibility of the method. This flexible simultaneous control of temporal and spatial properties of nanophotonic excitations opens new possibilities to tailor and optimize the light-matter interaction in spectroscopic methods as well as in nanophotonic applications.
    Keywords: Applied sciences -- Engineering -- Mechanical engineering ; Applied sciences -- Materials science -- Materials ; Physical sciences -- Physics -- Microphysics ; Physical sciences -- Physics -- Microphysics ; Physical sciences -- Physics -- Fundamental forces ; Physical sciences -- Physics -- Fundamental forces ; Applied sciences -- Engineering -- Optical engineering ; Environmental studies -- Environmental quality -- Environmental degradation ; Applied sciences -- Electronics -- Electronics engineering ; Physical sciences -- Physics -- Mechanics
    ISSN: 00278424
    E-ISSN: 10916490
    Library Location Call Number Volume/Issue/Year Availability
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