4,442 research outputs found

    YB-1 dependent oncolytic adenovirus efficiently inhibits tumor growth of glioma cancer stem like cells

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    Background: The brain cancer stem cell (CSC) model describes a small subset of glioma cells as being responsible for tumor initiation, conferring therapy resistance and tumor recurrence. In brain CSC, the PI3-K/AKT and the RAS/mitogen activated protein kinase (MAPK) pathways are found to be activated. In consequence, the human transcription factor YB-1, knowing to be responsible for the emergence of drug resistance and driving adenoviral replication, is phosphorylated and activated. With this knowledge, YB-1 was established in the past as a biomarker for disease progression and prognosis. This study determines the expression of YB-1 in glioblastoma (GBM) specimen in vivo and in brain CSC lines. In addition, the capacity of Ad-Delo3-RGD, an YB-1 dependent oncolytic adenovirus, to eradicate CSC was evaluated both in vitro and in vivo. Methods: YB-1 expression was investigated by immunoblot and immuno-histochemistry. In vitro, viral replication as well as the capacity of Ad-Delo3-RGD to replicate in and, in consequence, to kill CSC was determined by real-time PCR and clonogenic dilution assays. In vivo, Ad-Delo3-RGD-mediated tumor growth inhibition was evaluated in an orthotopic mouse GBM model. Safety and specificity of Ad-Delo3-RGD were investigated in immortalized human astrocytes and by siRNA-mediated downregulation of YB-1. Results: YB-1 is highly expressed in brain CSC lines and in GBM specimen. Efficient viral replication in and virus-mediated lysis of CSC was observed in vitro. Experiments addressing safety aspects of Ad-Delo3-RGD showed that (i) virus production in human astrocytes was significantly reduced compared to wild type adenovirus (Ad-WT) and (ii) knockdown of YB-1 significantly reduced virus replication. Mice harboring othotopic GBM developed from a temozolomide (TMZ)-resistant GBM derived CSC line which was intratumorally injected with Ad-Delo3-RGD survived significantly longer than mice receiving PBS-injections or TMZ treatment. Conclusion: The results of this study supported YB-1 based virotherapy as an attractive therapeutic strategy for GBM treatment which will be exploited further in multimodal treatment concepts

    ΔNp63α a key factor of epithelial differentiation controls the activity of YB-1 oncoprotein: potential implications in carcinogenesis

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    My thesis unveils a novel protein-protein association involving ΔNp63αand YB-1 and a mechanism through which a factor essential for epithelial development and differentiation can control the activity of an oncoprotein

    Yb<sup>3+</sup>-Yb<sup>3+</sup> cooperative upconversion in oxyfluoride glass and glass ceramics

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    Yb 3+-doped oxyfluoride glasses and glass ceramics containing KZnF 3 nanocrystals were obtained by melt-quenching. Under excitation of a 980 nm laser, a strong blue emission from Yb 3+-Yb 3+ cooperative upconversion was observed in the glass sample, which increased by five times in glass ceramics after heat treatment for 20 h. The photoluminescence mechanism and sample properties were investigated by X-ray diffraction, transmission electron microscopy, fluorescent lifetime, absorption and emission spectra. The size of KZnF 3 nanocrystals is in the range 5 nm–20 nm, making the glass ceramic samples highly transparent. The STEM-EDS measurements indicate that the distribution of Yb is consistent with that of the KZnF 3 nanocrystals. Fluroide phase provides a low-phonon-energy environment for Yb 3+-Yb 3+ ion pairs, which facilitates an intense fluorescent blue emission in the KZnF 3 crystal lattice. Both theoretical and experimental results demonstrate that Yb 3+-doped oxyfluoride glasses and glass ceramics containing KZnF 3 nanocrystals are promising materials for blue upconversion emission. </p

    High energy mode-locked Yb-doped fiber laser with Bi2Te3 deposited on tapered-fiber

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    The report presents the high energy mode-locking operation in an all-normal-dispersion Yb-doped mode-locked fiber laser based on evanescent field interaction with tapered fiber deposited with Bi2Te3 topological insulator. Different from most of solution processing methods, Bi2Te3 film is deposited on the tapered fiber by pulsed laser deposition (PLD) technology. In this way, it can bring less non-saturable losses and contact to the fiber better. By incorporating this novel fiber-taper Bi2Te3 saturable absorber into Yb-doped fiber laser cavity, a.repetition rate of 6.2 MHz mode-locked fiber laser is achieved. The maximum single pulse energy of 2 nJ is obtained. The results indicate that fiber-taper Bi2Te3 saturable absorber possesses potentiality for high power mode-locked fiber laser applications. (C) 2017 Elsevier GmbH. All rights reserved.</p

    Near infrared photoluminescence from Yb,Al Co-implanted SiO2 films on silicon

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    Intense room-temperature near infrared (NIR) photoluminescence (980 nm and 1032 nm) is observed from Yb,Al co-implanted SiO2 films on silicon. The optical transitions occur between the F-2(5/2) and F-2(7/2) levels of Yb3+ in SiO2. The additional Al-implantation into SiO2 films can effectively improve the concentration quenching effect of Yb3+ in SiO2. Photoluminescence exitation sprectroscopy shows that the NIR photoluminescence is due to the non-radiative energy transfer from Al-implantation-induced non-bridging oxygen hole defects in SiO2 to Yb3+ in the Yb-related luminescent complexes. It is believed that the defect-mediated luminscence of rare-earth ions in SiO2 is very effective

    Yb-doped femtosecond lasers and their frequency doubling

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    Ultralow threshold, compact and highly efficient femtosecond lasers based on Yb³⁺-doped potassium yttrium tungstate (Yb:KYW) and Yb³⁺-doped vanadium yttrium oxide (Yb:YVO 4 ) have been demonstrated within this PhD-research project. For a continuous wave unmode-locked Yb:KYW laser a threshold as low as 101 mW was obtained with a slope efficiency of 74%. By employing a single prism for dispersion control, the laser was tunable between 1012 nm to 1069 nm. When operated in the mode-locked regime, this laser produced transform-limited pulses having durations of 210 fs at a central wavelength of 1044 nm. Stable mode locking was observed for an optimised incident pulse fluence on the SESAM between 140 μJ/cm² to 160 μJ/cm² which was 2-3 times higher than the designed energy pulse fluence of the SESAM (70 μJ/cm²). The employment of several combinations of chirped mirror designs for control of intracavity group velocity dispersion led to excellent results. The threshold for mode locking was satisfied for a pump power of 255 mW where the slope efficiency was measured to be 62%. This is the most efficient SESAM-assisted femtosecond laser yet reported and the highest optical-to-optical efficiency of 37% is exceptional. Transform-limited pulses with durations as short as 90 fs were produced in a spectral region centred on 1052 nm. The success of this research thus represents a good foundation on which to design and build more compact configurations that will incorporate just one chirped mirror for dispersion compensation. A relatively high nonlinear refractive index, n₂ , of 15 x 10⁻¹⁶ cm²/W was measured in Yb:YVO₄ and this affords particular potential for this candidate material in Kerr-lens mode locking. In fact, for operation in the femtosecond domain, the threshold power was 190 mW with a slope efficiency of 26% and near-transform-limited pulses as short as 61fs were generated at a centre wavelength of 1050 nm. The main objectives in developing this type of laser relate to a demonstration of high peak power operation in thin disc laser configurations. The deployment of a diode-pumped Yb:KYW femtosecond laser as a pump source for frequency doubling in a periodically-poled LiTaO₃ crystal was realised. The maximum realized output power of 150 mW corresponded to an impressive second harmonic conversion efficiency of 43%. 225-fs duration green pulses (centred at 525 nm) were generated under the condition of strong focusing in the nonlinear crystal

    Yb-doped passively mode-locked fiber laser with Bi2Te3-deposited

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    In this study we present an all-normal-dispersion Yb-doped fiber laser passively mode-locked with topological insulator (Bi2Te3) saturable absorber. The saturable absorber device is fabricated by depositing Bi2Te3 on a tapered fiber through using pulsed laser deposition (PLD) technology, which can give rise to less non-saturable losses than most of the solution processing methods. Owing to the long interaction length, Bi2Te3 is not exposed to high optical power, which allows the saturable absorber device to work in a high power regime. The modulation depth of this kind of saturable absorber is measured to be 10%. By combining the saturable absorber device with Yb-doped fiber laser, a mode-locked pulse operating at a repetition rate of 19.8 MHz is achieved. The 3-dB spectral width and pulse duration are measured to be 1.245 nm and 317 ps, respectively

    Towards the tumble resistant microlight

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    The tumble mode is a pitching departure from controlled flight which leads to a pitch autorotation that is generally unrecoverable – resulting in vertical ground impact, usually preceded by in-flight breakup (the mechanism for which, surprisingly, can sometimes prevent loss of life). This was identified in work led by the British Microlight Aircraft Association beginning in 1997 as a response to a number of fatal accidents in Rogallo winged microlight aeroplanes, although the tumble is also known to occur to hang-gliders. This paper explains how this class of aeroplane is controlled, and how it has been found that they can enter the tumble mode. The mechanism by which the tumble can be entered is described. This has led to work showing how flight testing can be used to establish and demonstrate resistance to tumble entry – particularly important with increasing number of very high performance flexwings. These flight tests will be explained, together with the significance of the results. Recent accident investigation work has also shown a new mechanism of tumble entry, through partial failure of the A-frame structure and the pitch-trimmer mechanism. Also described is a possible relevance to well known historical accidents to flying wing aeroplanes– specifically the YB-49 and dH-108, and discovered data on the characteristics of the BKB-1flying wing glider; are also described

    Tunable Yb-doped fiber amplified spontaneous emission source

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    Tunable narrow-linewidth operation of an Yb-doped fiber amplified-spontaneous-emission (ASE) source is reported. The source yielded 135mW output at 1040nm and could be tuned from 1034nm to 1084nm. The prospects for improvement in performance are considered

    High-energy Q-switched Yb-doped fiber laser based on WS2 film saturable absorber

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    An all-fiber high-energy Q-switched Yb-doped fiber laser using WS2 film as the saturable absorber (SA) is demonstrated. The highest single pulse energy of 56.50 nJ and the shortest pulse width of 1.0 &mu;s were achieved. &copy; OSA 2016.</p
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