1,134,245 research outputs found

    Measles virus causes immunogenic cell death in human melanoma

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    Oncolytic viruses (OV) are promising treatments for cancer, with several currently undergoing testing in randomised clinical trials. Measles virus (MV) has not yet been tested in models of human melanoma. This study demonstrates the efficacy of MV against human melanoma. It is increasingly recognised that an essential component of therapy with OV is the recruitment of host anti-tumour immune responses, both innate and adaptive. MV-mediated melanoma cell death is an inflammatory process, causing the release of inflammatory cytokines including type-1 interferons and the potent danger signal HMGB1. Here, using human in vitro models, we demonstrate that MV enhances innate antitumour activity, and that MV-mediated melanoma cell death is capable of stimulating a melanoma-specific adaptive immune response

    The colored Jones function is q-holonomic

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    A function of several variables is called holonomic if, roughly speaking, it is determined from finitely many of its values via finitely many linear recursion relations with polynomial coefficients. Zeilberger was the first to notice that the abstract notion of holonomicity can be applied to verify, in a systematic and computerized way, combinatorial identities among special functions. Using a general state sum definition of the colored Jones function of a link in 3-space, we prove from first principles that the colored Jones function is a multisum of a q-proper-hypergeometric function, and thus it is q-holonomic. We demonstrate our results by computer calculations.Comment: Published by Geometry and Topology at http://www.maths.warwick.ac.uk/gt/GTVol9/paper29.abs.htm

    Using dissolved oxygen concentrations to determine mixed layer depths in the Bellingshausen Sea

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    Concentrations of oxygen (O<sub>2</sub>) and other dissolved gases in the oceanic mixed layer are often used to calculate air-sea gas exchange fluxes. The mixed layer depth (<i>z</i><sub>mix</sub>) may be defined using criteria based on temperature or density differences to a reference depth near the ocean surface. However, temperature criteria fail in regions with strong haloclines such as the Southern Ocean where heat, freshwater and momentum fluxes interact to establish mixed layers. Moreover, the time scales of air-sea exchange differ for gases and heat, so that <i>z</i><sub>mix</sub> defined using oxygen may be different than <i>z</i><sub>mix</sub> defined using temperature or density. Here, we propose to define an O<sub>2</sub>-based mixed layer depth, <i>z</i><sub>mix</sub>(O<sub>2</sub>), as the depth where the relative difference between the O<sub>2</sub> concentration and a reference value at a depth equivalent to 10 dbar equals 0.5 %. This definition was established by analysis of O<sub>2</sub> profiles from the Bellingshausen Sea (west of the Antarctic Peninsula) and corroborated by visual inspection. Comparisons of <i>z</i><sub>mix</sub>(O<sub>2</sub>) with <i>z</i><sub>mix</sub> based on potential temperature differences, i.e., <i>z</i><sub>mix</sub>(0.2 °C) and <i>z</i><sub>mix</sub>(0.5 °C), and potential density differences, i.e., <i>z</i><sub>mix</sub>(0.03 kg m<sup>−3</sup>) and <i>z</i><sub>mix</sub>(0.125 kg m<sup>−3</sup>), showed that <i>z</i><sub>mix</sub>(O<sub>2</sub>) closely follows <i>z</i><sub>mix</sub>(0.03 kg m<sup>−3</sup>). Further comparisons with published <i>z</i><sub>mix</sub> climatologies and <i>z</i><sub>mix</sub> derived from World Ocean Atlas 2005 data were also performed. To establish <i>z</i><sub>mix</sub> for use with biological production estimates in the absence of O<sub>2</sub> profiles, we suggest using <i>z</i><sub>mix</sub>(0.03 kg m<sup>−3</sup>), which is also the basis for the climatology by de Boyer Montégut et al. (2004)

    Determination of cellular strains by combined atomic force microscopy and finite element modeling

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    Many organs adapt to their mechanical environment as a result of physiological change or disease. Cells are both the detectors and effectors of this process. Though many studies have been performed in vitro to investigate the mechanisms of detection and adaptation to mechanical strains, the cellular strains remain unknown and results from different stimulation techniques cannot be compared. By combining experimental determination of cell profiles and elasticities by atomic force microscopy with finite element modeling and computational fluid dynamics, we report the cellular strain distributions exerted by common whole-cell straining techniques and from micromanipulation techniques, hence enabling their comparison. Using data from our own analyses and experiments performed by others, we examine the threshold of activation for different signal transduction processes and the strain components that they may detect. We show that modulating cell elasticity, by increasing the F-actin content of the cytoskeleton, or cellular Poisson ratio are good strategies to resist fluid shear or hydrostatic pressure. We report that stray fluid flow in some substrate-stretch systems elicits significant cellular strains. In conclusion, this technique shows promise in furthering our understanding of the interplay among mechanical forces, strain detection, gene expression, and cellular adaptation in physiology and disease

    Synthesis and characterisation of Fe<sub>6</sub> and Fe<sub>12</sub> clusters using bicine

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    Reaction of bicine {BicH3, N,N-bis(2-hydroxyethyl)glycine} with an Fe(III) oxo-centered pivalate triangle in MeCN in the presence of Et&lt;sub&gt;2&lt;/sub&gt;NH yields [Et&lt;sub&gt;2&lt;/sub&gt;NH&lt;sub&gt;2&lt;/sub&gt;]&lt;sub&gt;2&lt;/sub&gt;[Fe&lt;sub&gt;6&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;(OH)&lt;sub&gt;2&lt;/sub&gt;(Bic)&lt;sub&gt;2&lt;/sub&gt;(O&lt;sub&gt;2&lt;/sub&gt;CCMe&lt;sub&gt;3&lt;/sub&gt;)&lt;sub&gt;8&lt;/sub&gt;], which possesses an S = 5 ground state. Changing the base to NaOMe produces [Fe&lt;sub&gt;12&lt;/sub&gt;O&lt;sub&gt;4&lt;/sub&gt;(Bic)&lt;sub&gt;4&lt;/sub&gt;(HBic)&lt;sub&gt;4&lt;/sub&gt;(O&lt;sub&gt;2&lt;/sub&gt;CCMe&lt;sub&gt;3&lt;/sub&gt;)&lt;sub&gt;8&lt;/sub&gt;], which contains two Fe6 units bridged by the carboxylate arms from the bicine ligands. The complex displays strong antiferromagnetic coupling leading to an S = 0 ground state

    Electrical and physical characterization of the Al<sub>2</sub>O<sub>3</sub>/ <i>p</i>-GaSb interface for 1%, 5%, 10%, and 22% (NH<sub>4</sub>)<sub>2</sub>S surface treatments

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    In this work, the impact of ammonium sulfide ((NH&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt;S) surface treatment on the electrical passivation of the Al&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt;/ &lt;i&gt;p&lt;/i&gt;-GaSb interface is studied for varying sulfide concentrations. Prior to atomic layer deposition of Al&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt;, GaSb surfaces were treated in 1%, 5%, 10%, and 22% (NH&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt;S solutions for 10 min at 295 K. The smallest stretch-out and flatband voltage shifts coupled with the largest capacitance swing, as indicated by capacitance-voltage (&lt;i&gt;CV&lt;/i&gt;) measurements, were obtained for the 1% treatment. The resulting interface defect trap density (&lt;i&gt;D&lt;/i&gt;&lt;sub&gt;it&lt;/sub&gt;) distribution showed a minimum value of 4 x 10&lt;sup&gt;12&lt;/sup&gt; cm&lt;sup&gt;-2&lt;/sup&gt;eV&lt;sup&gt;-1&lt;/sup&gt; at &lt;i&gt;E&lt;/i&gt;&lt;sub&gt;v&lt;/sub&gt; + 0.27 eV. Transmission electron microscopy and atomic force microscopy examination revealed the formation of interfacial layers and increased roughness at the Al&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt;/ &lt;i&gt;p&lt;/i&gt;-GaSb interface of samples treated with 10% and 22% (NH&lt;sub&gt;4&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt;S. In combination, these effects degrade the interface quality as reflected in the &lt;i&gt;CV&lt;/i&gt; characteristics

    X-ray absorption spectroscopy systematics at the tungsten L-edge

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    A series of mononuclear six-coordinate tungsten compounds spanning formal oxidation states from 0 to +VI, largely in a ligand environment of inert chloride and/or phosphine, has been interrogated by tungsten L-edge X-ray absorption spectroscopy. The L-edge spectra of this compound set, comprised of [W&lt;sup&gt;0&lt;/sup&gt;(PMe&lt;sub&gt;3&lt;/sub&gt;)&lt;sub&gt;6&lt;/sub&gt;], [W&lt;sup&gt;II&lt;/sup&gt;Cl&lt;sub&gt;2&lt;/sub&gt;(PMePh&lt;sub&gt;2&lt;/sub&gt;)&lt;sub&gt;4&lt;/sub&gt;], [W&lt;sup&gt;III&lt;/sup&gt;Cl&lt;sub&gt;2&lt;/sub&gt;(dppe)&lt;sub&gt;2&lt;/sub&gt;][PF&lt;sub&gt;6&lt;/sub&gt;] (dppe = 1,2-bis(diphenylphosphino)ethane), [W&lt;sup&gt;IV&lt;/sup&gt;Cl&lt;sub&gt;4&lt;/sub&gt;(PMePh&lt;sub&gt;2&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt;], [W&lt;sup&gt;V&lt;/sup&gt;(NPh)Cl&lt;sub&gt;3&lt;/sub&gt;(PMe&lt;sub&gt;3&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt;], and [W&lt;sup&gt;VI&lt;/sup&gt;Cl&lt;sub&gt;6&lt;/sub&gt;] correlate with formal oxidation state and have usefulness as references for the interpretation of the L-edge spectra of tungsten compounds with redox-active ligands and ambiguous electronic structure descriptions. The utility of these spectra arises from the combined correlation of the estimated branching ratio (EBR) of the L&lt;sub&gt;3,2&lt;/sub&gt;-edges and the L&lt;sub&gt;1&lt;/sub&gt; rising-edge energy with metal Z&lt;sub&gt;eff&lt;/sub&gt;, thereby permitting an assessment of effective metal oxidation state. An application of these reference spectra is illustrated by their use as backdrop for the L-edge X-ray absorption spectra of [W&lt;sup&gt;IV&lt;/sup&gt;(mdt)&lt;sub&gt;2&lt;/sub&gt;(CO)&lt;sub&gt;2&lt;/sub&gt;] and [W&lt;sup&gt;IV&lt;/sup&gt;(mdt)&lt;sub&gt;2&lt;/sub&gt;(CN)&lt;sub&gt;2&lt;/sub&gt;]&lt;sup&gt;2–&lt;/sup&gt; (mdt&lt;sup&gt;2–&lt;/sup&gt; = 1,2-dimethylethene-1,2-dithiolate), which shows that both compounds are effectively W&lt;sup&gt;IV&lt;/sup&gt; species. Use of metal L-edge XAS to assess a compound of uncertain formulation requires: 1) Placement of that data within the context of spectra offered by unambiguous calibrant compounds, preferably with the same coordination number and similar metal ligand distances. Such spectra assist in defining upper and/or lower limits for metal Z&lt;sub&gt;eff&lt;/sub&gt; in the species of interest; 2) Evaluation of that data in conjunction with information from other physical methods, especially ligand K-edge XAS; 3) Increased care in interpretation if strong π-acceptor ligands, particularly CO, or π-donor ligands are present. The electron-withdrawing/donating nature of these ligand types, combined with relatively short metal-ligand distances, exaggerate the difference between formal oxidation state and metal Z&lt;sub&gt;eff&lt;/sub&gt; or, as in the case of [W&lt;sup&gt;IV&lt;/sup&gt;(mdt)&lt;sub&gt;2&lt;/sub&gt;(CO)&lt;sub&gt;2&lt;/sub&gt;], add other subtlety by modulating the redox level of other ligands in the coordination sphere

    Gallium oxide and gadolinium gallium oxide insulators on Si &#948;-doped GaAs/AlGaAs heterostructures

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    Test devices have been fabricated on two specially grown GaAs/AlGaAs wafers with 10 nm thick gate dielectrics composed of either Ga&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt; or a stack of Ga&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt; and Gd&lt;sub&gt;0.25&lt;/sub&gt;Ga&lt;sub&gt;0.15&lt;/sub&gt;O&lt;sub&gt;0.6&lt;/sub&gt;. The wafers have two GaAs transport channels either side of an AlGaAs barrier containing a Si delta-doping layer. Temperature dependent capacitance-voltage (C-V) and current-voltage (I-V) studies have been performed at temperatures between 10 and 300 K. Bias cooling experiments reveal the presence of DX centers in both wafers. Both wafers show a forward bias gate leakage that is by a single activated channel at higher temperatures and by tunneling at lower temperatures. When Gd&lt;sub&gt;0.25&lt;/sub&gt;Ga&lt;sub&gt;0.15&lt;/sub&gt;O&lt;sub&gt;0.6&lt;/sub&gt; is included in a stack with 1 nm of Ga&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt; at the interface, the gate leakage is greatly reduced due to the larger band gap of the Gd&lt;sub&gt;0.25&lt;/sub&gt;Ga&lt;sub&gt;0.15&lt;/sub&gt;O&lt;sub&gt;0.6&lt;/sub&gt; layer. The different band gaps of the two oxides result in a difference in the gate voltage at the onset of leakage of ~3 V. However, the inclusion of Gd&lt;sub&gt;0.25&lt;/sub&gt;Ga&lt;sub&gt;0.15&lt;/sub&gt;O&lt;sub&gt;0.6&lt;/sub&gt; in the gate insulator introduces many oxide states (&#8804;4.70��10&lt;sup&gt;12&lt;/sup&gt; cm&lt;sup&gt;�2&lt;/sup&gt;). Transmission electron microscope images of the interface region show that the growth of a Gd&lt;sub&gt;0.25&lt;/sub&gt;Ga&lt;sub&gt;0.15&lt;/sub&gt;O&lt;sub&gt;0.6&lt;/sub&gt; layer on Ga&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt; disturbs the well ordered Ga&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt;/GaAs interface. We therefore conclude that while including Gd&lt;sub&gt;0.25&lt;/sub&gt;Ga&lt;sub&gt;0.15&lt;/sub&gt;O&lt;sub&gt;0.6&lt;/sub&gt; in a dielectric stack with Ga&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt; is necessary for use in device applications, the inclusion of Gd decreases the quality of the Ga&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;3&lt;/sub&gt;/GaAs interface and near interface region by introducing roughness and a large number of defect states

    HREM studies of intergrowths in Sr2[Srn-1TinO3n+1] Ruddlesden-Popper phases synthesized by mechanochemical activation

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    A mechanochemical activation route has been applied in order to obtain the &lt;i&gt;n&lt;/i&gt;=1–4 and &#8734; members of the Sr&lt;sub&gt;2&lt;/sub&gt;[Sr&lt;sub&gt;n&lt;/sub&gt;&lt;sub&gt;−1&lt;/sub&gt;Ti&lt;sub&gt;n&lt;/sub&gt;O&lt;sub&gt;3n+1&lt;/sub&gt;] Ruddlesden– Popper series from different (&lt;i&gt;n&lt;/i&gt;+1)SrO:nTiO&lt;sub&gt;2&lt;/sub&gt; mixtures. The mechanosynthesis of SrTiO&lt;sub&gt;3&lt;/sub&gt; and Sr&lt;sub&gt;2&lt;/sub&gt;TiO&lt;sub&gt;4&lt;/sub&gt; was observed during the milling process from the initial stoichiometric mixture, but in the cases of the &lt;i&gt;n&lt;/i&gt;=2–4 members, a subsequent thermal treatment was needed. The synthesis protocol of Sr&lt;sub&gt;3&lt;/sub&gt;Ti&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;7&lt;/sub&gt; has been greatly improved and this compound can be isolated as a single, crystalline phase after annealing at 800&#176;C. In the case of Sr&lt;sub&gt;4&lt;/sub&gt;Ti&lt;sub&gt;3&lt;/sub&gt;O&lt;sub&gt;10&lt;/sub&gt; and Sr&lt;sub&gt;5&lt;/sub&gt;Ti&lt;sub&gt;4&lt;/sub&gt;O&lt;sub&gt;13&lt;/sub&gt;, the formation temperature was also decreased, but members with &lt;i&gt;n&lt;/i&gt;=3 and 4 could not be isolated. Detailed investigations using electron microscopy methods (TEM, HREM and SAED) were carried out in the samples corresponding to &lt;i&gt;n&lt;/i&gt;=2–4. Although a single ordered Sr&lt;sub&gt;3&lt;/sub&gt;Ti&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;7&lt;/sub&gt; structure is dominant in the sample corresponding to &lt;i&gt;n&lt;/i&gt;=2, a few intergrowths of other Ruddlesden–Popper phases were observed. In the cases of &lt;i&gt;n&lt;/i&gt;=3 and 4, the intergrowths of Ruddlesden–Popper phases are more frequent than in the &lt;i&gt;n&lt;/i&gt;=2 composition and are randomly distributed in the sample. The more frequent occurrence of such stacking faults, with increasing &lt;i&gt;n&lt;/i&gt; value, leads to a somewhat disordered layer stacking sequence
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