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      • Paclitaxel‐Loaded Polymer Nanoparticles for the Reversal of Multidrug Resistance in Breast Cancer Cells

        Lee, Yeonju,Graeser, Ralph,Kratz, Felix,Geckeler, Kurt E. WILEY‐VCH Verlag 2011 Advanced Functional Materials Vol.21 No.22

        <P><B>Abstract</B></P><P>Novel paclitaxel‐loaded polymer nanoparticles were developed for circumventing multidrug resistance (MDR) of malignant cancerous diseases, which is an unsolved clinical problem in cancer chemotherapy. In many cases, MDR is due to the intrinsic or acquired expression of an efflux pump, the P‐170 glycoprotein (P‐gp). By encapsulating paclitaxel in a water‐soluble and biocompatible synthetic polyampholyte using a solid‐state reaction the highly water‐soluble paclitaxel‐loaded nanoparticles are formed. The resulting paclitaxel nanoparticles with an average diameter of 250 nm show a significant reversal of chemoresistance in the drug‐resistant variants (MCF7/ADR, MT3/ADR) by a factor of 100 or more. The novel paclitaxel nanoparticles enter MDR breast cancer cells by adsorptive endocytosis bypassing the P‐gp, preventing the efflux of paclitaxel and thus restoring the anti‐proliferative effect of paclitaxel.</P>

      • KCI등재

        Predictive simulation for the design of robotic solution to mobility aid

        Yin ChengXin,Benali Abderraouf,Kratz Frédéric 한국CDE학회 2021 Journal of computational design and engineering Vol.8 No.6

        Maintaining substantial mobility is essential for those who suffer from reduced mobility to regain their independence in daily motion tasks. In recent years, robotic solutions to human mobility aid have been functionally verified by various applications. Moreover, with the emergence of new robots and systems, the robot design theory is also under rapid evolution. This paper proposes a methodology to enhance the design of robotic exoskeleton. The aim was to help the designer to select adequate dynamical behaviors to the development of control scheme for the human motions assisted by a robotic assistance device. The main contribution of this work resides in the proposition of optimized impedance parameters for a particular human movement via neuromusculoskeletal (NMS) modelization and predictive simulation. The technique of NMS modeling that represents the motions of human upper limb was applied to study the underlying mechanisms of human movements. Predictive simulation integrated with the NMS model was formulated and solved for generating a series of optimized human dynamic parameters. In this paper, a case study of human–robot interface has been proposed to exemplify our methodology. The modeling and simulation processes were validated with experimental tools. According to the simulated human dynamics, the optimized stiffness and damping coefficients of one degree of freedom were calculated. Results show that our methods are promising and allowed to specify the human movement for a given task, and can provide the design parameters to control scheme of a robotic exoskeleton.

      • Controlling Major Cellular Processes of Human Mesenchymal Stem Cells using Microwell Structures

        Xu, Xun,Wang, Weiwei,Kratz, Karl,Fang, Liang,Li, Zhengdong,Kurtz, Andreas,Ma, Nan,Lendlein, Andreas Wiley (John WileySons) 2014 Advanced healthcare materials Vol.3 No.12

        <P>Directing stem cells towards a desired location and function by utilizing the structural cues of biomaterials is a promising approach for inducing effective tissue regeneration. Here, the cellular response of human adipose-derived mesenchymal stem cells (hADSCs) to structural signals from microstructured substrates comprising arrays of square-shaped or round-shaped microwells is explored as a transitional model between 2D and 3D systems. Microwells with a side length/diameter of 50 관m show advantages over 10 관m and 25 관m microwells for accommodating hADSCs within single microwells rather than in the inter-microwell area. The cell morphologies are three-dimensionally modulated by the microwell structure due to differences in focal adhesion and consequent alterations of the cytoskeleton. In contrast to the substrate with 50 관m round-shaped microwells, the substrate with 50 관m square-shaped microwells promotes the proliferation and osteogenic differentiation potential of hADSCs but reduces the cell migration velocity and distance. Such microwell shape-dependent modulatory effects are highly associated with Rho/ROCK signaling. Following ROCK inhibition, the differences in migration, proliferation, and osteogenesis between cells on different substrates are diminished. These results highlight the possibility to control stem cell functions through the use of structured microwells combined with the manipulation of Rho/ROCK signaling.</P>

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        Development of a Novel Imaging Agent for Determining Albumin Uptake in Solid Tumors

        S. Daum,J. P. Magnusson,L. Pes,J. Garcia Fernandez,S. Chercheja,F. Medda,F. I. Nollmann,S. D. Koester,P. Perez Galan,A. Warnecke,K. Abu Ajaj,Felix Kratz 대한핵의학회 2019 핵의학 분자영상 Vol.53 No.3

        Purpose The purpose of this study was to investigate the albumin-binding compound 111In-C4-DTPA as an imaging agent for the detection of endogenous albumin accumulation in tumors. Methods 111In-C4-DTPA was injected in healthy nude mice for pharmacokinetic and biodistribution studies (10 min, 1, 6, 24, and 48 h, n = 4) and subsequently in tumor-bearing mice for single-photon emission computed tomography/X-ray-computed tomography (SPECT/CT) imaging studies. Four different human tumor xenograft models (LXFL529, OVXF899, MAXFTN401, and CXF2081) were implanted subcutaneously unilaterally or bilaterally (n = 4–8). After intravenous administration of 111In-C4-DTPA, SPECT/CT images were collected over 72 h at 4–6 time points. Additionally, gamma counting was performed for the blood, plasma, lungs, heart, liver, spleen, kidneys, muscle, and tumors at 72 h post-injection. Results 111In-C4-DTPA bound rapidly to circulating albumin upon injection, and the radiolabeled albumin conjugate thus formed was stable in murine and human serum. SPECT/CT images demonstrated a time-dependent uptake with a maximum of 2.7– 3.8% ID/cm3 in the tumors at approximately 24 h post-injection and mean tumor/muscle ratios in the range of 3.2–6.2 between 24 and 72 h post-injection. The kidneys and bladder were the predominant elimination organs. Gamma counting at 72 h postinjection showed 1.3–2.5% ID/g in the tumors and mean tumor/muscle ratios in the range of 4.9–9.4. Conclusion 111In-C4-DTPA bound rapidly to circulating albumin upon injection and showed time-dependent uptake in the tumors demonstrating a potential for clinical application as a companion imaging diagnostic for albumin-binding anticancer drugs.

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