62 research outputs found

    Selective gene silencing by viral delivery of short hairpin RNA

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    RNA interference (RNAi) technology has not only become a powerful tool for functional genomics, but also allows rapid drug target discovery and in vitro validation of these targets in cell culture. Furthermore, RNAi represents a promising novel therapeutic option for treating human diseases, in particular cancer. Selective gene silencing by RNAi can be achieved essentially by two nucleic acid based methods: i) cytoplasmic delivery of short double-stranded (ds) interfering RNA oligonucleotides (siRNA), where the gene silencing effect is only transient in nature, and possibly not suitable for all applications; or ii) nuclear delivery of gene expression cassettes that express short hairpin RNA (shRNA), which are processed like endogenous interfering RNA and lead to stable gene down-regulation. Both processes involve the use of nucleic acid based drugs, which are highly charged and do not cross cell membranes by free diffusion. Therefore, in vivo delivery of RNAi therapeutics must use technology that enables the RNAi therapeutic to traverse biological membrane barriers in vivo. Viruses and the vectors derived from them carry out precisely this task and have become a major delivery system for shRNA. Here, we summarize and compare different currently used viral delivery systems, give examples of in vivo applications, and indicate trends for new developments, such as replicating viruses for shRNA delivery to cancer cells

    Status of the Superconducting Soft X-ray Free-Electron Laser FLASH at DESY

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    FLASH, the free-electron laser (FEL) user facility at DESY, deliverers high brilliance XUV and soft x-ray FEL radiation for photon experiments since summer 2005.In 2014 and 2015 a second beamline, FLASH2, has been commissioned in parallel to user operation at FLASH1.FLASH's superconducting linac can produce bunch trains of up to 800 bunches within a 0.8 ms RF flat top at a repetition rate of 10 Hz.In standard operation during 2017 FLASH supplied up to 500 bunches in two bunch trains with independent fill patterns and compression schemes.Since mid 2017 initial commissioning of a third experimental beamline, accommodating the FLASHForward plasma wakefield acceleration experiment, has started.We report on the highlights of the FLASH operation in 2017/2018

    Status of the Superconductig Soft X-Ray Free-Electron Laser User Facility FLASHat DESY

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    FLASH, the free electron laser user facility at DESY (Hamburg, Germany), delivers high brilliance XUV and soft X-ray FEL radiation to photon experiments with different parameters at two undulator beamlines simultaneously. FLASH’s superconducting linac can produce bunch trains of up to 800 bunches within a 0.8ms RF flat top at a repetition rate of 10Hz. In standard operation during 2018, FLASH supplied up to 500 bunches in two bunch trains with independent fill patterns and compression schemes to each of the two beamlines. In 2018 first successful plasma accelerating experiments could be reported by the FLASHForward plasma wakefield acceleration experiment situated in a third beamline. We report on the highlights of FLASH operation in 2018/2019

    Status of the Soft X-Ray Free Electron Laser FLASH

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    The superconducting free-electron laser user facility FLASH at DESY in Hamburg, routinely produces several thousand photon pulses per second. The operational parameters cover a wavelength range from 90 nm down to 4 nm with pulse energies from several μ\muJ up to 1 mJ and with pulse durations of several hundred fs down to a few fs. The FLASH injector and linac drives two undulator beam lines (FLASH1, FLASH2) and therefore FLASH is capable of serving 2 independent experiments with photon pulse (sub-) trains of several 100 bunches at the full train repetition frequency of 10 Hz.We summarize here the highlights of the user operation at FLASH1/2 and the study program (machine development and FEL optimization) of the FLASH facility

    Experience with Multi-Beam and Multi-Beamline FEL-Operation

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    DESY’s free-electron laser FLASH provides soft X-ray pulses for scientific usersat wavelengths down to 4 nm simultaneously in two undulator beamlines. They are drivenby a common linear superconducting accelerator with a beam energy of up to 1.25 GeV. Thesuperconducting technology allows the acceleration of electron bunch trains of several hundredbunches with a spacing of 1 microsecond or more and a repetition rate of 10Hz. A fast kickerseptumsystem directs one part of the bunch train to FLASH1 and the other part to FLASH2keeping the full 10Hz repetition rate for both. The unique setup of FLASH allows independentFEL pulse parameters for both beamlines. In April 2016, simultaneous operation of FLASH1and FLASH2 for external users started. This paper reports on our operating experience withthis type of multi-beam, multi-beamline set-up

    Status of the Soft X-Ray Free Electron Laser FLASH

    No full text
    The superconducting free-electron laser user facility FLASH at DESY in Hamburg, routinely produces several thousand photon pulses per second. The operational parameters cover a wavelength range from 90 nm down to 4 nm with pulse energies from several μ\muJ up to 1 mJ and with pulse durations of several hundred fs down to a few fs. The FLASH injector and linac drives two undulator beam lines (FLASH1, FLASH2) and therefore FLASH is capable of serving 2 independent experiments with photon pulse (sub-) trains of several 100 bunches at the full train repetition frequency of 10 Hz.We summarize here the highlights of the user operation at FLASH1/2 and the study program (machine development and FEL optimization) of the FLASH facility
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