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排序方式: 共有498条查询结果,搜索用时 15 毫秒
1.
Wei Peng Henriette S. de Bruijn Timo L. M. ten Hagen Go M. van Dam Jan L. N. Roodenburg Kristian Berg Max J. H. Witjes Dominic J. Robinson 《Photochemistry and photobiology》2020,96(3):708-717
Targeted photodynamic therapy (PDT) in head/neck cancer patients with a conjugate of the anti-epidermal growth factor receptor (EGFR) antibody, Cetuximab and a phthalocyanine photosensitizer IR700DX is under way, but the exact mechanisms of action are still not fully understood. In this study, the EGFR-overexpressing human head/neck OSC-19-luc2-cGFP tumor with transfected GFP gene was used in a skin-fold window chamber model in BALB/c nude mice. The uptake and localization of the conjugate in the tumor and its surrounding normal tissues were studied by an intravital confocal laser scanning microscopy with image analyses. The tumor was also irradiated with 690 nm laser light 24 h after conjugate administration. The vascular and tumor responses were examined by morphological evaluation and immunohistochemistry (IHC). The amount of conjugate in the tumor peaked at 24–48 h after injection. Image analyses of colocalization correlation parameters demonstrated a high fraction of the conjugate IR700DX colocalized in the GFP-expressing tumor cells. PDT-treated tumors showed extensive necrotic/apoptotic destruction with little vascular damage, while IHC showed no HIF-1α expression and decreased EGFR and Ki67 expression with activated caspase-3 overexpression, indicating a direct killing of tumor cells through both necrotic and apoptotic cell death. 相似文献
2.
Design and Synthesis of High‐Affinity Dimeric Inhibitors Targeting the Interactions between Gephyrin and Inhibitory Neurotransmitter Receptors 下载免费PDF全文
Dr. Hans Michael Maric Vikram Babu Kasaragod Dr. Linda Haugaard‐Kedström Dr. Torben Johann Hausrat Prof. Dr. Matthias Kneussel Prof. Dr. Hermann Schindelin Prof. Dr. Kristian Strømgaard 《Angewandte Chemie (International ed. in English)》2015,54(2):490-494
Gephyrin is the central scaffolding protein for inhibitory neurotransmitter receptors in the brain. Here we describe the development of dimeric peptides that inhibit the interaction between gephyrin and these receptors, a process which is fundamental to numerous synaptic functions and diseases of the brain. We first identified receptor‐derived minimal gephyrin‐binding peptides that displayed exclusive binding towards native gephyrin from brain lysates. We then designed and synthesized a series of dimeric ligands, which led to a remarkable 1220‐fold enhancement of the gephyrin affinity (KD=6.8 nM ). In X‐ray crystal structures we visualized the simultaneous dimer‐to‐dimer binding in atomic detail, revealing compound‐specific binding modes. Thus, we defined the molecular basis of the affinity‐enhancing effect of multivalent gephyrin inhibitors and provide conceptually novel compounds with therapeutic potential, which will allow further elucidation of the gephyrin–receptor interplay. 相似文献
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Anne Techen Sylvia Czapla Kristian Möllnitz Dennis Budach Pablo Wessig Michael U. Kumke 《Helvetica chimica acta》2013,96(11):2046-2067
Fluorescence probes consisting of well‐established fluorophores in combination with rigid molecular rods based on spirane‐type structures were investigated with respect to their fluorescence properties under different solvent conditions. The attachment of the dyes was accomplished by 1,3‐dipolar cycloaddition between alkynes and azides (‘click’ reaction) and is a prime example for a novel class of sensor constructs. Especially, the attachment of two (different) fluorophores on opposite sides of the molecular rods paves the way to new sensor systems with less bulky (compared to the conventional DNA‐ or protein‐based concepts), nevertheless rigid spacer constructs, e.g., for FRET‐based sensing applications. A detailed photophysical characterization was performed in MeOH (and in basic H2O/MeOH mixtures) for i) rod constructs containing carboxyfluorescein, ii) rod constructs containing carboxyrhodamine, iii) rod constructs containing both carboxyfluorescein and carboxyrhodamine, and iv) rod constructs containing both pyrene and perylene parts. For each dye (pair), two rod lengths with different numbers of spirane units were synthesized and investigated. The rod constructs were characterized in ensemble as well as single‐molecule fluorescence experiments with respect to i) specific rod? dye and ii) dye? dye interactions. In addition to MeOH and MeOH/NaOH, the rod constructs were also investigated in micellar systems, which were chosen as a simplified model for membranes. 相似文献
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Nonlinear Dynamics - Two types of constitutive equations consisting of instantaneous and power type hereditary contributions are proposed in order to model generalized capacitor (inductor). The... 相似文献
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In this work, we investigate the impact of mobility changes due to flow reversals from co-current to counter-current flow on the displacement performance of water alternating gas (WAG) injection processes. In WAG processes, the injected gas will migrate toward the top of the formation while the injected water will migrate toward the bottom of the formation. The segregation of gas, oil and water phases will result in counter-current flow occurring in the vertical direction in some portions of the reservoir during the displacement process. Previous experimental and theoretical studies of counter-current flow have shown that the relative mobility of each of the phases in a porous medium is considerably less when counter-current flow prevails as compared to co-current flow settings. A reduction of the relative permeability in the vertical direction results in a dynamic anisotropy in phase mobilities. This effect has, to the best of our knowledge, not previously been considered in the modeling and simulation of WAG processes. A new flow model that accounts for flow reversals in the vertical direction has been implemented and tested in a three-phase compositional reservoir simulator. In order to investigate the impact of flow reversals, results from the new flow model are compared to cases where counter-current flow effects on the phase mobilities are ignored. A range of displacement settings, covering relevant slug sizes, have been investigated to gauge the impact of mobility reductions due to flow reversals. Significant differences, in terms of saturation distribution, producing GOR and oil recovery, are observed between the conventional flow model (ignoring mobility reductions due to counter-current flow) and the proposed new model that accounts for reductions in phase mobility during counter-current flow. Accordingly, we recommend that an explicit representation of flow transitions between co-current and counter-current flow (and the related impact on phase mobilities) should be considered to ensure accurate and optimal design of WAG injection processes. 相似文献
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Nuttapol Risangud Thomas R. Congdon Daniel J. Keddie Paul Wilson Kristian Kempe David M. Haddleton 《Journal of polymer science. Part A, Polymer chemistry》2016,54(17):2698-2705
The synthesis of two types of isocyanate side chain containing copolymers, poly(methyl methacrylate‐co‐isocyanatoethyl methacrylate) (P(MMA‐co‐IEM)) and poly(benzyl methacrylate‐co‐isocyanatoethyl methacrylate) (P(BnMA‐co‐IEM)), which were synthesized by Cu(0)‐mediated radical polymerization, is reported. Polymerization proceeded to high conversion giving polymers of relatively narrow molar mass distributions. The incorporation of the bulky aromatic groups in the latter copolymer rendered it sufficiently stable toward hydrolysis and enabled the isolation of the product and its characterization by 1H and 13C NMR, and FTIR spectroscopy and SEC. Both P(MMA‐co‐IEM) and P(BnMA‐co‐IEM) were functionalized with dibutylamine, octylamine, and (R)‐(+)‐α‐methylbenzyl‐amine, which further proved the successful incorporation of the isocyanate groups. Furthermore, P(BnMA‐co‐IEM) was used for the fabrication of liquid core microcapsules via oil‐in‐water interfacial polymerization with diethylenetriamine as crosslinker. The particles obtained were in the size range of 10–90 µm in diameter independent of the composition of copolymer. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2698–2705 相似文献
10.
Analyse von Protease‐Inhibitor‐Interaktionen unter Nutzung evolvierbarer tricyclischer Microviridine