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161.
Engineering linear F(ab')2 fragments for efficient production in Escherichia coli and enhanced antiproliferative activity 总被引:1,自引:0,他引:1
Zapata Gerardo; Ridgway John B. B.; Mordenti Joyce; Osaka Gary; Wong Wai Lee T.; Bennett Gregory L.; Carter Paul 《Protein engineering, design & selection : PEDS》1995,8(10):1057-1062
We developed a novel bivalent antibody fragment, the linear(L-) F(ab')2, comprising tandem repeats of a heavy chain fragmentVHCH1VHCH1 cosecreted with a light chain.Functional humanized L-F(ab')2 directed against p185HER2 wassecreted from Escherichia coli at high titer (100 mg/l) andpurified to homogeneity. The L-F(ab')2 binds two equivalentsof antigen with an apparent affinity (Kd = 0.46 nM) that iswithin 3-fold of the corresponding thioether-linked F(ab')2fragment The N-terminal site binds antigen with an affinity(Kd = 1.2 nM) that is 4-fold greater than that for the C-terminalsite, as shown by the comparison of L-F(ab')2 variants containinga single functional binding site. L-F(ab')2 has greater antiproliferativeactivity than the thioether-linked F(ab')2 against the p185HER2-overexpressingtumor cell line BT474. Linear and thioether-linked F(ab')2 havevery similar pharmacokinetic properties in normal mice, andtheir serum permanence times are respectively 7- and 8-foldlonger than the corresponding Fab fragment L-F(ab')2 offersa facile route to bivalent antibody fragments that are potentiallysuitable for clinical applications, and that may have improvedbiological activity compared with thioether-linked F(ab')2 fragments. 相似文献
162.
Murine neuroblastoma cells, N1E-115, were induced to differentiate into neuron-like cells by serum deprivation for 18 h. As previous studies have shown that the suppression of protein kinase C (PKC) activity by selective inhibitors or neutralizing antibodies induces neuroblastoma cells to differentiate, we tested the hypothesis that serum deprivation may cause a rapid loss in membrane PKC activity that occurs well before the morphological changes that are characteristic of cell differentiation. A significant reduction in particulate (membrane) PKC activity was indeed observed within 3 h of serum withdrawal when enzyme activity was measured in intact native membranes by the recently described in vitro "direct" assay. This rapid reduction in enzyme activity was confirmed by the decreased phosphorylation of the MARCKS protein, an endogenous PKC-selective substrate, in intact cells. The decrease in membrane PKC activity occurred without any loss in the amount of membrane-associated enzyme, suggesting that some factor(s) resident in neuroblastoma membranes was suppressing PKC activity. Indeed, results indicate the presence of an endogenous inhibitor of PKC tightly associated with neuroblastoma membranes. This inhibitory activity increased in the membranes of cells subjected to serum deprivation, raising the possibility that it was likely responsible for the decline in membrane PKC activity in differentiating N1E-115 cells. Preliminary characterization indicated that the inhibitory activity is a protein and is localized mainly in the membrane fraction. Thus, these results demonstrate directly that endogenous inhibitor can regulate membrane-associated PKC activity in cells and thereby modulate PKC-related neuronal functions. 相似文献
163.
Kseniia A. Sergeeva Dmitrii V. Pavlov Albert A. Seredin Eugeny V. Mitsai Aleksandr A. Sergeev Evgeny B. Modin Anastasiia V. Sokolova Tsz Chun Lau Kseniia V. Baryshnikova Mihail I. Petrov Stephen V. Kershaw Aleksandr A. Kuchmizhak Kam Sing Wong Andrey L. Rogach 《Advanced functional materials》2023,33(44):2307660
In order to advance the development of quantum emitter-based devices, it is essential to enhance light-matter interactions through coupling between semiconductor quantum dots with high quality factor resonators. Here, efficient tuning of the emission properties of HgTe quantum dots in the infrared spectral region is demonstrated by coupling them to a plasmonic metasurface that supports bound states in the continuum. The plasmonic metasurface, composed of an array of gold nanobumps, is fabricated using single-step direct laser printing, opening up new opportunities for creating exclusive 3D plasmonic nanostructures and advanced photonic devices in the infrared region. A 12-fold enhancement of the photoluminescence in the 900–1700 nm range is observed under optimal coupling conditions. By tuning the geometry of the plasmonic arrays, controllable shaping of the emission spectra is achieved, selectively enhancing specific wavelength ranges across the emission spectrum. The observed enhancement and shaping of the emission are attributed to the Purcell effect, as corroborated by systematic measurements of radiative lifetimes and optical simulations based on the numerical solution of Maxwell's equations. Moreover, coupling of the HgTe photoluminescence to high quality factor modes of the metasurface improves emission directivity, concentrating output within an ≈20° angle. 相似文献
164.
Zhifeng Jiang Zhiquan Zhang Jianli Liang Min Zhou Daobin Liu Danjun Mao Qun Zhang Wei Zhang Huaming Li Li Song Taicheng An Po Keung Wong Chun-Sing Lee 《Advanced functional materials》2023,33(29):2301785
Solar-driven CO2 reduction reaction (CO2RR) with water into carbon-neutral fuels is of great significance but remains challenging due to thermodynamic stability and kinetic inertness of CO2. Biomass-derived nitrogen-doped carbon (N-Cb) have been considered as promising earth-abundant photocatalysts for CO2RR, although their activities are not ideal and the reaction mechanism is still unclear. Herein, an efficient catalyst is developed for CO2-to-CO conversion realized on diverse N-Cb materials with hierarchical pore structures. It is demonstrated that the CO2-to-CO conversion preferentially takes place on positively charged carbon atoms next to pyridinic-N using two representatives treated pollens with the largest difference in pyridinic-N density and N content as model photocatalysts. Systematic experimental results indicate that surface local electric field originating from charge separation can be boosted by hierarchical pore structures, doped N, as well as pyridinic-N. Mechanistic studies reveal that positively charged carbon atoms next to pyridinic-N serve as active sites for CO2RR, reduce the energy barrier on the formation of CO*, and facilitate the CO2RR performance. All these benefits cooperatively contribute to treated chrysanthemum pollen catalyst exhibiting excellent CO formation rate of 203.2 µmol h−1 g−1 with 97.2% selectivity in pure water vapor. These results provide a new perspective into CO2RR on N-Cb, which shall guide the design of nature-based photocatalysts for high-performance solar-fuel generation. 相似文献
165.
Over the past decade, the call to foster computational thinking (CT) in every child has received considerable attention. However, there is little understanding of whether children are developmentally ready to think computationally and what specific CT concepts and skills can be developed at various ages. This study explored the developmental and gender differences in CT skills of 197 Grade 4–6 students (aged 9–13) before being exposed to instruction and investigated the age–gender interaction effects on their CT acquisition in an intervention combining both programming and non-programming (unplugged) activities. Results show that students' CT skills followed a developmental progression before instruction. Gender difference across ages was insignificant in conditionals, logical operators, pattern recognition and generalization skills. Additionally, students of different ages developed CT differently during the intervention, and their CT acquisition was unaffected by gender. Implications for practice and research in CT education were discussed. 相似文献
166.
Identifying and integrating patient and caregiver perspectives for clinical practice guidelines on the screening and management of infectious microorganisms in hemodialysis units
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Hilary M. Miller Allison Tong David J. Tunnicliffe Denise Campbell Jule Pinter Robert J. Commons Eugene Athan Jonathan C. Craig Nicole Gilroy Julianne Green Belinda Henderson Martin Howell Rhonda L. Stuart Carolyn van Eps Muh Geot Wong Janak de Zoysa Meg J. Jardine 《Hemodialysis international. International Symposium on Home Hemodialysis》2017,21(2):213-223
167.
Chung Yen Ang Si Yu Tan Cathleen Teh Jia Min Lee Mun Fei Eddy Wong Qiuyu Qu Li Qing Poh Menghuan Li Yuanyuan Zhang Vladimir Korzh Yanli Zhao 《Small (Weinheim an der Bergstrasse, Germany)》2017,13(7)
Responsive nanomaterials have emerged as promising candidates as drug delivery vehicles in order to address biomedical diseases such as cancer. In this work, polymer‐based responsive nanoparticles prepared by a supramolecular approach are loaded with doxorubicin (DOX) for the cancer therapy. The nanoparticles contain disulfide bonds within the polymer network, allowing the release of the DOX payload in a reducing environment within the endoplasm of cancer cells. In addition, the loaded drug can also be released under acidic environment. In vitro anticancer studies using redox and pH dual responsive nanoparticles show excellent performance in inducing cell death and apoptosis. Zebrafish larvae treated with DOX‐loaded nanoparticles exhibit an improved viability as compared with the cases treated with free DOX by the end of a 3 d treatment. Confocal imaging is utilized to provide the daily assessment of tumor size on zebrafish larva models treated with DOX‐loaded nanoparticles, presenting sustainable reduction of tumor. This work demonstrates the development of functional nanoparticles with dual responsive properties for both in vitro and in vivo drug delivery in the cancer therapy. 相似文献
168.
Yi Huang Lian Xiao Tingting An Wenxiang Lim Teckneng Wong Handong Sun 《Small (Weinheim an der Bergstrasse, Germany)》2017,13(34)
Microfluidic systems have become a superior platform for explorations of fascinating fluidic physics at microscale as well as applications in biomedical devices, chemical reactions, drug delivery, etc. Exploitations of this platform are built upon the fundamental techniques of flow visualizations. However, the currently employed fluorescent materials for microfluidic visualization are far from satisfaction, which severely hinders their widespread applications. Here fluorescent carbon nanodots are documented as a game‐changer, applicable in versatile fluidic environment for the visualization in microfluidics with unprecedented advantages. One of the fastest fluorescent imaging speeds up to 2500 frames per second under a normal contionous wave (CW) laser line is achieved by adopting carbon nanodots in microfluidics. Besides better visualizations of the fluid or interface, fluorescent carbon nanodots‐based microparticles enable quantitative studies of high speed dynamics in fluids at microscale with a more than 90% lower cost, which is inaccessible by traditionally adopted fluorescent dye based seeding particles. The findings hold profound influences to microfluidic investigations and may even lead to revolutionary changes to the relevant industries. 相似文献
169.
Zou Rui Huang Junjian Shi Junpeng Huang Lin Zhang Xuejie Wong Ka-Leung Zhang Hongwu Jin Dayong Wang Jing Su Qiang 《Nano Research》2017,10(6):2070-2082
Near-infrared (NIR) persistent-luminescence nanoparticles have emerged as a new class of background-free contrast agents that are promising for in vivo imaging.The next key roadblock is to establish a robust and controllable method for synthesizing monodisperse nanoparticles with high luminescence brightness and long persistent duration.Herein,we report a synthesis strategy involving the coating/etching of the SiO2 shell to obtain a new class of small NIR highly persistent luminescent ZnGa2O4∶Cr3+,Sn4+ (ZGOCS) nanoparticles.The optimized ZGOCS nanoparticles have an excellent size distribution of ~15 nm without any agglomeration and an NIR persistent luminescence that is enhanced by a factor of 13.5,owing to the key role of the SiO2 shell in preventing nanoparticle agglomeration after annealing.The ZGOCS nanoparticles have a signal-to-noise ratio ~3 times higher than that of previously reported ZnGa2O4∶Cr3+ (ZGC-1) nanoparticles as an NIR persistent-luminescence probe for in vivo bioimaging.Moreover,the persistent-luminescence signal from the ZGOCS nanoparticles can be repeatedly re-charged in situ with external excitation by a white lightemitting diode;thus,the nanoparticles are suitable for long-term in vivo imaging applications.Our study suggests an improved strategy for fabricating novel high-performance optical nanoparticles with good biocompatibility. 相似文献
170.