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51.
Introducing Glycolinkers for the Functionalization of Cytotoxic Drugs and Applications in Antibody–Drug Conjugation Chemistry
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Dr. Filip S. Ekholm Henna Pynnönen Anja Vilkman Virve Pitkänen Dr. Jari Helin Juhani Saarinen Tero Satomaa 《ChemMedChem》2016,11(22):2501-2505
Antibody–drug conjugates (ADCs) are promising alternatives to naked antibodies for selective drug‐delivery applications and treatment of diseases such as cancer. Construction of ADCs relies upon site‐selective, efficient and mild conjugation technologies. The choice of a chemical linker is especially important, as it affects the overall properties of the ADC. We envisioned that hydrophilic bifunctional chemical linkers based on carbohydrates would be a useful class of derivatization agents for the construction of linker–drug conjugates and ADCs. Herein we describe the synthesis of carbohydrate‐based derivatization agents, glycolinker–drug conjugates featuring the tubulin inhibitor monomethyl auristatin E and an ADC based on an anti‐EGFR antibody. In addition, an initial in vitro cytotoxicity evaluation of the individual components and the ADC is provided against EGFR‐positive cancer cells. 相似文献
52.
53.
Andreja Žužić Filip Car Jelena Macan Vesna Tomašić Andreja Gajović 《International Journal of Applied Ceramic Technology》2022,19(5):2891-2904
Strontium-doped lanthanum manganites, La1-xSrxMnO3 (LSMO), are promising and affordable catalysts for oxidative degradation of volatile organic compounds. LSMO catalysts (x = 0, .1, .2, and .3) were prepared by the citrate-nitrate autocombustion (CNA) and coprecipitation synthesis. The phase composition was confirmed by X-ray diffraction and Rietveld refinement analysis, while the oxygen content was determined by Mohr's salt permanganate titration. Morphology and porosity of prepared catalysts was correlated to catalytic oxidation of benzene, toluene, ethylbenzene and o-xylene. It was observed that both synthesis methods yielded catalysts of similar average pore size diameter and specific surface area, but the pore size distribution differed: CNA-prepared catalysts had a multimodal pore size distribution, while the coprecipitated ones had a single maximum at 4 nm. Catalysts prepared by the CNA method have shown a higher catalytic activity in the temperature range 373–723 K, as the presence of Mn3+/Mn4+ mixed valences increased their reducibility. 相似文献
54.
Vilko Mandić Emilija Tkalčec Stanislav Kurajica 《Journal of the American Ceramic Society》2014,97(7):2264-2271
Monophasic gel with stoichiometric 3Al2O3·2SiO2 composition and gels with 0.99, 1.96, and 2.91 mol% La2O3 added were sol–gel derived. The crystallization path, structure evolution, microstructure, and morphology of calcined premullite powders and sintered ceramic bodies have been investigated as a function of La2O3 content and sintering temperature. In addition to mullite, spinel phase at about 980°C, and α‐alumina at above 1000°C were determined; however, neither La2O3 nor La‐related compounds had crystallized. The La2O3 predominately incorporated into the glassy phase, enhanced with La2O3 level, which affected both mullite structure and composition, as confirmed by electron microscopy, Rietveld structure refinement, determination of unit cell parameters, electron microscopy, and achieved density of the sintered bodies. Increased thermal treatment changes the alumina/silica ratio in mullite (towards 3:2 below 1200°C, and toward 2:1 above), and decreases the mullite/amorphous ratio. Sintered dense ceramic bodies revealed a positive densification effect and increased sinterability as a result of the lanthanum‐induced increase in glassy phase. 相似文献
55.
Polymeric nanocapsules are attractive devices with a number of potential applications. In the present contribution we describe a method for nanocapsule preparation which is based on the formation of nanosized templates (mesoglobules, prepared from thermo-responsive poly(methoxydiethyleneglycol methacrylate)s, PDEGMA). These mesoglobules were coated with a cross-linked shell formed by pseudo-seeded radical polymerization of either N-isopropylacrylamide or 2-hydroxyethylmethacrylate in the presence of a cross-linking agent. Dissolution and removal of templates were achieved by extensive dialysis against water at temperatures below the LCST of PDEGMA. The obtained nanocapsules were visualized by transmission electron microscopy and their dimensions were determined by dynamic light scattering. The differences in the morphology of the nanocapsules were attributed to the different structures of the cross-linked membranes. 相似文献
56.
Richard E. Lyon Natallia Safronava James G. Quintiere Stanislav I. Stoliarov Richard N. Walters Sean Crowley 《火与材料》2014,38(2):264-278
Five material properties commonly used to describe the fire behavior of solids were evaluated as sole explanatory variables for four small‐scale fire tests with pass/fail outcomes by using a physically based probabilistic (phlogistic) burning model. The phlogistic model describes the likelihood of passing vertical Bunsen burner tests and a regulatory heat release rate test reasonably well over a wide range of material properties, as deduced from the correlation coefficient and mean deviation of the predicted and measured values. Of the thermal, combustion, and fire properties examined, the best predictors of the likelihood of passing the fire tests of this study were the heat of combustion of the sample, the heat release capacity, and the heat release parameter. The relative merits and drawbacks of qualitative (threshold) and quantitative (probabilistic) approaches to predicting fire test results using thermal and combustion properties are discussed. Published 2013. This article is a U.S. Government work and is in the public domain in the USA. 相似文献
57.
Mark Portnoi Paul Anthony Haigh Thomas JM acdonald Filip Ambroz Ivan PParkin Izzat Darwazeh loannis Papakonstantinou 《光:科学与应用(英文版)》2021,10(1):29-40
Luminescent solar concentrators(LSCs)have recently emerged as a promising receiver technology in free-space optical communications due to their inherent ability to collect light from a wide field-of-view and concentrate it into small areas,thus leading to high optical gains.Several high-speed communication systems integrating LSCs in their detector blocks have already been demonstrated,with the majority of efforts so far being devoted to maximising the received optical power and the system's field-of-view.However,LSCs may pose a severe bottleneck on the bandwidth of such communication channels due to the comparably slow timescale of the fluorescence events involved,a situation further aggravated by the inherent reabsorption in these systems,and yet,an in-depth study into such dynamic effects remains absent in the field.To fill this gap,we have developed a comprehensive analytical solution that delineates the fundamental bandwidth limits of LSCs as optical detectors in arbitrary free-space optical links,and establishes their equivalence with simple RC low-pass electrical circuits.Furthermore,we demonstrate a time-domain Monte Carlo simulation platform,an indispensable tool in the multiparameter optimisation of LSC-based receiver systems.Our work offers vital insight into LSC system dynamic behaviour and paves the way to evaluate the technology for a wide range of applications,including visible light communications,high-speed video recording,and real-time biological imaging,to name a few. 相似文献
58.
Bernarda Majc Anamarija Habi
Metka Novak Ana Rotter Andrej Por
nik Jernej Mlakar Vera
upunski Ura Pe
ar Fonovi Damijan Knez Nace Zidar Stanislav Gobec Janko Kos Tamara Lah Turnek Anja Pilar Barbara Breznik 《International journal of molecular sciences》2022,23(3)
Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Understanding GBM pathobiology and discovering novel therapeutic targets are critical to finding efficient treatments. Upregulation of the lysosomal cysteine carboxypeptidase cathepsin X has been linked to immune dysfunction and neurodegenerative diseases, but its role in cancer and particularly in GBM progression in patients is unknown. In this study, cathepsin X expression and activity were found to be upregulated in human GBM tissues compared to low-grade gliomas and nontumor brain tissues. Cathepsin X was localized in GBM cells as well as in tumor-associated macrophages and microglia. Subsequently, potent irreversible (AMS36) and reversible (Z7) selective cathepsin X inhibitors were tested in vitro. Selective cathepsin X inhibitors decreased the viability of patient-derived GBM cells as well as macrophages and microglia that were cultured in conditioned media of GBM cells. We next examined the expression pattern of neuron-specific enzyme γ-enolase, which is the target of cathepsin X. We found that there was a correlation between high proteolytic activity of cathepsin X and C-terminal cleavage of γ-enolase and that cathepsin X and γ-enolase were colocalized in GBM tissues, preferentially in GBM-associated macrophages and microglia. Taken together, our results on patient-derived material suggest that cathepsin X is involved in GBM progression and is a potential target for therapeutic approaches against GBM. 相似文献
59.
Wojciech H. Bednarek Filip Ciesielczyk Majka Odalanowska Dominik Paukszta Adam Piasecki 《Polymer Engineering and Science》2020,60(8):1856-1865
The activity of isotactic polypropylene (iPP) nucleating additives during shear flow of composite materials is still not entirely explained. In current work the sol-gel method was employed to synthesize MgO·SiO2 filler, surface-modified with trivalent lanthanum. The crystallization of commercial iPP in the presence of 0.5% by weight La3+ modified or unmodified silicates was analyzed. The wide angle X-ray scattering analysis proved that the presence of even small amount of filler influences significantly on supermolecular structure of iPP. The results of microscope observations confirmed that the lanthanum-modified filler shows the nucleating ability for iPP. In that case a significant reduction of crystallization induction time was noticed. The investigation of iPP crystallization in composites after shear treatment confirmed that the increase of shear rate reduces the nucleating ability of additives. Moreover, the flow of filler particles during shearing may impede the shear-induced crystallization phenomenon. 相似文献
60.
James W. Palko Ali Sayir Stanislav V. Sinogeikin Waltraud M. Kriven Jay D. Bass 《Journal of the American Ceramic Society》2002,85(8):2005-2012
Directionally solidified mullite fibers have been grown by the laser-heated, float-zone method from starting materials with a nominal composition of 3Al2 O3 ·2SiO2 . The fibers used in this study have large single-crystal regions with composition 2.5Al2 O3 ·SiO2 and (001) fiber axis orientation. The complete elastic tensor of these samples has been determined by Brillouin spectroscopy at room temperature and elevated temperatures up to 1200°C. Isotropic moduli (bulk, shear, and Young's) have been calculated using the Voigt–Reuss–Hill averaging scheme. The room-temperature values obtained are K VRH = 173.5 ± 6.9 GPa, G VRH = 88.0 ± 3.5 GPa, E VRH = 225.9 ± 9.0 GPa. All moduli show gradual, linear decreases with temperature. The temperature derivatives obtained for the equivalent, isotropic moduli are d K VRH /d T =−17.5 ± 2.5 MPa/°C, d G VRH /d T =−8.8 ± 1.4 MPa/°C, d E VRH /d T =−22.6 ± 2.8 MPa/°C. Substantial differences between bulk properties calculated from the single–crystal measurements in this study and the properties reported in the literature for polycrystalline sintered mullite are identified, indicating the importance of factors such as microstructure, intergranular phases, and composition to the elasticity of mullite ceramics. 相似文献