217 research outputs found

    Use of a proof assistant as a learning tool in an introductory logic course for computer science undergraduates

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    27 W 2.1 µm OPCPA system for coherent soft X-ray generation operating at 10 kHz

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    © 2020 Optical Society of America. Users may use, reuse, and build upon the article, or use the article for text or data mining, so long as such uses are for non-commercial purposes and appropriate attribution is maintained. All other rights are reserved.We developed a high power optical parametric chirped-pulse amplification (OPCPA) system at 2.1 µm harnessing a 500 W Yb:YAG thin disk laser as the only pump and signal generation source. The OPCPA system operates at 10 kHz with a single pulse energy of up to 2.7 mJ and pulse duration of 30 fs. The maximum average output power of 27 W sets a new record for an OPCPA system in the 2 µm wavelength region. The soft X-ray continuum generated through high harmonic generation with this driver laser can extend to around 0.55 keV, thus covering the entire water window (284 eV - 543 eV). With a repetition rate still enabling pump-probe experiments on solid samples, the system can be used for many applications.EC/H2020/654148/EU/The Integrated Initiative of European Laser Research Infrastructures/LASERLAB-EUROP

    Promoter hypermethylation of the phosphatase DUSP22 mediates PKA-dependent TAU phosphorylation and CREB activation in Alzheimer's disease

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    Genetic screening in Alzheimer's disease (AD) has identified only a handful of genes that are mutated in the disorder. Thus, for a very large proportion of patients, the biology of their disease is poorly understood. Epigenetic alterations may provide an explanation in these cases. Using DNA methylation profiles of human hippocampus from controls and patients, we have identified the presence of promoter hypermethylation of the dual-specificity phosphatase 22 (DUSP22) gene in AD. DUSP22 is a likely candidate gene for involvement in the pathogenesis of the disorder since, as we demonstrate here, it inhibits PKA activity and thereby determines TAU phosphorylation status and CREB signaling

    The function of tcf3 in medaka embryos: efficient knockdown with pePNAs

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    Background: The application of antisense molecules, such as morpholino oligonucleotides, is an efficient method of gene inactivation in vivo. We recently introduced phosphonic ester modified peptide nucleic acids (PNA) for in vivo loss-of-function experiments in medaka embryos. Here we tested novel modifications of the PNA backbone to knockdown the medaka tcf3 gene. Results: A single tcf3 gene exists in the medaka genome and its inactivation strongly affected eye development of the embryos, leading to size reduction and anophthalmia in severe cases. The function of Tcf3 strongly depends on co-repressor interactions. We found interactions with Groucho/Tle proteins to be most important for eye development. Using a dominant negative approach for combined inactivation of all groucho/tle genes also resulted in eye phenotypes, as did interference with three individual tle genes. Conclusions: Our results show that side chain modified PNAs come close to the knockdown efficiency of morpholino oligonucleotides in vivo. A single medaka tcf3 gene combines the function of the two zebrafish paralogs hdl and tcf3b. In combination with Groucho/Tle corepressor proteins Tcf3 acts in anterior development and is critical for eye formation

    Fast Direct Multiple Shooting Algorithms for Optimal Robot Control

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    International audienceIn this overview paper, we first survey numerical approaches to solve nonlinear optimal control problems, and second, we present our most recent algorithmic developments for real-time optimization in nonlinear model predictive control. In the survey part, we discuss three direct optimal control approaches in detail: (i) single shooting, (ii) collocation, and (iii) multiple shooting, and we specify why we believe the direct multiple shooting method to be the method of choice for nonlinear optimal control problems in robotics. We couple it with an efficient robot model generator and show the performance of the algorithm at the example of a five link robot arm. In the real-time optimization part, we outline the idea of nonlinear model predictive control and the real-time challenge it poses to numerical optimization. As one solution approach, we discuss the real-time iteration scheme
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