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51.
Structure–Activity Relationships of JMV4463, a Vectorized Cathepsin D Inhibitor with Antiproliferative Properties: The Unique Role of the AMPA‐Based Vector 下载免费PDF全文
Dr. Lubomir L. Vezenkov Clément A. Sanchez Dr. Virginie Bellet Dr. Vincent Martin Dr. Marie Maynadier Dr. Nadir Bettache Prof. Vincent Lisowski Prof. Jean Martinez Dr. Marcel Garcia Dr. Muriel Amblard Dr. Jean‐François Hernandez 《ChemMedChem》2016,11(3):302-308
Cathepsin D (CathD) is overexpressed and secreted by several solid tumors and stimulates their growth, the mechanism of which is still not understood. In this context, the pepstatin bioconjugate JMV4463 [Ac‐arg‐O2Oc‐(Val)3‐Sta‐Ala‐Sta‐(AMPA)4‐NH2; O2Oc=8‐amino‐3,6‐dioxaoctanoyl, Sta=statine, AMPA=ortho‐aminomethylphenylacetyl], containing a new kind of cell‐penetrating vector, was previously shown to exhibit potent antiproliferative effects in vitro and to delay the onset of tumors in vivo. In this study, we performed a structure–activity relationship analysis to evaluate the significance of the inhibitor and vector moieties of JMV4463. By modifying both statine residues of pepstatin we found that the antiproliferative activity is correlated with CathD inhibition, supporting a major role of the catalytic activity of intracellular CathD in cancer cell proliferation. Replacing the vector composed of four AMPA units with other vectors was found to abolish cytotoxicity, although all of the conjugates enabled pepstatin transport into cells. In addition, the AMPA4 vector must be localized at the C terminus of the bioconjugate. The unexpected importance of the vector structure and position for cytotoxic action suggests that AMPA4 enables pepstatin to inhibit the proteolysis of critical CathD substrates involved in cell proliferation via a unique mechanism of action. 相似文献
52.
Marcel Richter Yuriy Zakrevskyy Michael Eisele Nino Lomadze Svetlana Santer Regine v. Klitzing 《Polymer》2014
The contraction/swelling transition of anionic PNIPAM-co-AAA particles can be manipulated by light using interactions with cationic azobenzene-containing surfactant. In this study the influence of pH-buffers and their concentrations, the charge density (AAA content) in microgel particles as well as the spacer length of the surfactant on the complex formation between the microgel and surfactant is investigated. It is shown that the presence of pH buffer can lead to complete blocking of the interactions in such complexes and the resulting microgel contraction/swelling response. There is a clear competition between the buffer ions and the surfactant molecules interacting with microgel particles. When working in pure water solutions with fixed concentration (charge density) of microgel, the contraction/swelling of the particles is controlled only by relative concentration (charge ratio) of the surfactant and AAA groups of the microgel. Furthermore, the particle contraction is more efficient for shorter spacer length of the surfactant. The onset point of the contraction process is not affected by the surfactant hydrophobicity. This work provides new insight into the interaction between microgel particles and photo-sensitive surfactants, which offers high potential in new sensor systems. 相似文献
53.
Gerhard Heise Andreas Brner Marcel Dickmann Marina Englmaier Andreas Heiss Matthias Kemnitzer Jan Konrad Regina Moser Jrg Palm Helmut Vogt Heinz P. Huber 《Progress in Photovoltaics: Research and Applications》2015,23(10):1291-1304
In this paper, we present the selective structuring of all three patterns (P1, P2 and P3) of a monolithic interconnection of CIS (Cu(In,Ga)(S,Se)2) thin film solar cells by picosecond laser pulses at a wavelength of 1064 nm. We show results for single pulse ablation threshold values and line scribing of molybdenum films on glass (P1), CIS on molybdenum (P2) and zinc oxide on CIS (P3). The purposes of these processes are the p‐type isolation (P1), cell interconnect (P2) and n‐type isolation (P3), which are required for complete cell architecture. The half micron thick molybdenum back electrode can be structured with a process speed of more than 15 m/s at about 15 W average power without detectable residues and damage by direct induced laser ablation from the back side (P1). The CIS layer can be structured selectively down to the molybdenum at process speeds up to 1 m/s at about 15 W average power, due to the precision of direct laser ablation in the ultrashort pulse regime (P2). The ZnO front electrode layer is separated by clean trenches with straight side walls at process speeds of up to 15 m/s at about 10 W average power, as a result of indirect induced laser ablation (P3). A validation of functionality of all processes is demonstrated on CIS solar cell modules (30 × 30 cm2). By replacing one state‐of‐the‐art process by a picosecond laser process at a time, solar efficiencies could be increased for P1 and P2 and stayed on a similar level for P3. After an optimization of the patterning processes in the R&D pilot line of AVANCIS, we achieved a new record efficiency for an all‐laser‐patterned CIS solar module: 14.7% as best value for the aperture area efficiency of a 30 × 30 cm2 sized CIS module was reached. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
54.
Daniela Grimm Herbert Schulz Marcus Krüger Jos Luis Corts-Snchez Marcel Egli Armin Kraus Jayashree Sahana Thomas J. Corydon Ruth Hemmersbach Petra M. Wise Manfred Infanger Markus Wehland 《International journal of molecular sciences》2022,23(6)
Cancer is a disease exhibiting uncontrollable cell growth and spreading to other parts of the organism. It is a heavy, worldwide burden for mankind with high morbidity and mortality. Therefore, groundbreaking research and innovations are necessary. Research in space under microgravity (µg) conditions is a novel approach with the potential to fight cancer and develop future cancer therapies. Space travel is accompanied by adverse effects on our health, and there is a need to counteract these health problems. On the cellular level, studies have shown that real (r-) and simulated (s-) µg impact survival, apoptosis, proliferation, migration, and adhesion as well as the cytoskeleton, the extracellular matrix, focal adhesion, and growth factors in cancer cells. Moreover, the µg-environment induces in vitro 3D tumor models (multicellular spheroids and organoids) with a high potential for preclinical drug targeting, cancer drug development, and studying the processes of cancer progression and metastasis on a molecular level. This review focuses on the effects of r- and s-µg on different types of cells deriving from thyroid, breast, lung, skin, and prostate cancer, as well as tumors of the gastrointestinal tract. In addition, we summarize the current knowledge of the impact of µg on cancerous stem cells. The information demonstrates that µg has become an important new technology for increasing current knowledge of cancer biology. 相似文献
55.
The presence of saliva in the oral environment is relevant for several essential health processes. However, the noncontrolled early saliva interaction with biomaterials manufactured for oral rehabilitation may generate alterations in the superficial properties causing negative biological outcomes. Therefore, the present review aimed to provide a compilation of all possible physical–chemical–biological changes caused by the early saliva interaction in dental implants and materials for oral regeneration. Dental implants, bone substitutes and membranes in dentistry possess different properties focused on improving the healing process when in contact with oral tissues. The early saliva interaction was shown to impair some positive features present in biomaterials related to quick cellular adhesion and proliferation, such as surface hydrophilicity, cellular viability and antibacterial properties. Moreover, biomaterials that interacted with contaminated saliva containing specific bacteria demonstrated favorable conditions for increased bacterial metabolism. Additionally, the quantity of investigations associating biomaterials with early saliva interaction is still scarce in the current literature and requires clarification to prevent clinical failures. Therefore, clinically, controlling saliva exposure to sites involving the application of biomaterials must be prioritized in order to reduce impairment in important biomaterial properties developed for rapid healing. 相似文献
56.
Jeremy A. Nestele Anne-Katrin Rohlfing Valerie Dicenta Alexander Bild Daniela Eißler Frederic Emschermann Marcel Kremser Konstantin Krutzke Tilman E. Schffer Oliver Borst Moran Levi Netanel Korin Meinrad Paul Gawaz 《International journal of molecular sciences》2022,23(1)
Traditional antithrombotic agents commonly share a therapy-limiting side effect, as they increase the overall systemic bleeding risk. A novel approach for targeted antithrombotic therapy is nanoparticles. In other therapeutic fields, nanoparticles have enabled site-specific delivery with low levels of toxicity and side effects. Here, we paired nanotechnology with an established dimeric glycoprotein VI-Fc (GPVI-Fc) and a GPVI-CD39 fusion protein, thereby combining site-specific delivery and new antithrombotic drugs. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles, NP-BSA, NP-GPVI and NP-GPVI-CD39 were characterized through electron microscopy, atomic force measurements and flow cytometry. Light transmission aggregometry enabled analysis of platelet aggregation. Thrombus formation was observed through flow chamber experiments. NP-GPVI and NP-GPVI-CD39 displayed a characteristic surface coating pattern. Fluorescence properties were identical amongst all samples. NP-GPVI and NP-GPVI-CD39 significantly impaired platelet aggregation. Thrombus formation was significantly impaired by NP-GPVI and was particularly impaired by NP-GPVI-CD39. The receptor-coated nanoparticles NP-GPVI and the bifunctional molecule NP-GPVI-CD39 demonstrated significant inhibition of in vitro thrombus formation. Consequently, the nanoparticle-mediated antithrombotic effect of GPVI-Fc, as well as GPVI-CD39, and an additive impact of CD39 was confirmed. In conclusion, NP-GPVI and NP-GPVI-CD39 may serve as a promising foundation for a novel therapeutic approach regarding targeted antithrombotic therapy. 相似文献
57.
Esther Hontañón Marcel Rouenhoff Alfredo Azabal Emilio Ramiro Frank Einar Kruis 《Aerosol science and technology》2014,48(3):333-339
An existing differential mobility analyzer (DMA) of cylindrical electrodes and a novel DMA of rectangular plate electrodes are demonstrated for size fractionation of nanoparticles at high-aerosol flow rates in this work. The two DMAs are capable of delivering monodisperse size selected nanoparticles (SMPS σg < 1.1) at gas flow rates ranging from 200 slm to 500 slm. At an aerosol flow rate of 200 slm, the maximum attainable particle mean size is of about 20 nm for the cylindrical DMA and of nearly 50 nm for the rectangular plate DMA. The number concentration of the monodisperse nanoparticles delivered by the high-flow DMAs spans from 104 cm?3 to 106 cm?3 depending upon the particle mean size and particle size dispersion.
Copyright 2014 American Association for Aerosol Research 相似文献
58.
Solar radiation is a key factor determining electricity produced by photovoltaic (PV) systems. This paper presents a solar radiation database of Europe developed in the geographical information system, and three interactive web applications providing an access to it. The database includes monthly and yearly average values of the global irradiation on horizontal and inclined surfaces, as well as climatic parameters needed for an assessment of the potential PV electricity generation (Linke atmospheric turbidity, the ratio of diffuse to global irradiation, an optimum inclination angle of modules to maximize energy yield). In the first web application, a user may browse radiation maps and query irradiation incident on a PV module for different inclination angles. The second application simulates daily profiles of irradiance for a chosen month and module inclination and orientation. The third web application estimates electricity generation for a chosen PV configuration. It also calculates optimal inclination and orientation of a PV module for a given location. The database and the applications are accessible at http://re.jrc.cec.ev.int/pvgis/pv/imaps/imaps.htm. 相似文献
59.
Cristina Flox Javier Rubio-Garcia Raquel Nafria Reza Zamani Marcel Skoumal Teresa Andreu Jordi Arbiol Andreu Cabot Joan Ramon Morante 《Carbon》2012,50(6):2372-2374
Graphene-supported monometallic (Pt) and bimetallic (CuPt3) cubic nanocatalysts have been investigated as new positive electrode materials for improving the VO2+/VO2+ redox process occurring in the vanadium redox flow batteries (VRB). High-resolution transmission electron microscopy (HRTEM) and scanning electron microscopy (SEM) have been employed to characterize the electrodes. The presence of the CuPt3 nanocubes on graphene conferred higher electrocatalytic activity due to the much higher electroactive area compared to that obtained with the Pt nanoparticles. The electrochemical surface area of the nano-(CuPt3)-decorated graphene electrode was 105% higher compared to non-decorated graphene, being then a promising alternative for improving the VRB. 相似文献
60.
Optimization of alcohol‐free beer production by lager and cachaça yeast strains using response surface methodology 下载免费PDF全文
Cláudia Puerari Jan Strejc Angélica C. Souza Marcel Karabín Rosane F. Schwan Tomáš Brányik 《Journal of the Institute of Brewing》2016,122(1):69-75
Alcohol‐free beers (AFBs) are an attractive segment of the beer market both for the brewing industry and for consumers. While AFBs produced by arrested/limited fermentation often suffer from a lack of volatile compounds, beer flavour can be improved by yeast selection and optimization of fermentation conditions. The yeast selection strategy was demonstrated by comparing traditional lager yeast with selected cachaça yeast strains. Correspondingly, response surface methodology was used to enhance the formation of the flavour‐active volatile compounds by optimization of the fermentation conditions (original wort extract, fermentation temperature, pitching rate). Statistical analysis of the experimental data revealed the relative significance of process variables and their interactions. The developed quadratic model describing the responses of total esters and higher alcohols to changes in process variables was used to predict the ideal fermentation conditions in terms of flavour formation. The predicted conditions were experimentally verified and alternative strategies of AFB production are suggested. Copyright © 2016 The Institute of Brewing & Distilling 相似文献