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排序方式: 共有1008条查询结果,搜索用时 46 毫秒
1.
Maarten Sijm Julianna Siciliano de Araújo Alba Ramos Llorca Dr. Kristina Orrling Lydia Stiny An Matheeussen Prof. Dr. Louis Maes Prof. Dr. Iwan J. P. de Esch Dr. Maria de Nazaré Correia Soeiro Dr. Geert Jan Sterk Prof. Dr. Rob Leurs 《ChemMedChem》2019,14(18):1662-1668
Chagas disease is becoming a worldwide problem; it is currently estimated that over six million people are infected. The two drugs in current use, benznidazole and nifurtimox, require long treatment regimens, show limited efficacy in the chronic phase of infection, and are known to cause adverse effects. Phenotypic screening of an in-house library led to the identification of 2,2′-methylenebis(5-(4-bromophenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC50 value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied, ultimately leading to 2,2′-methylenebis(5-(3-bromo-4-methoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (NPD-0228) as the most potent analogue. NPD-0228 has an in vitro pIC50 value of 6.4 against intracellular amastigotes of T. cruzi and no apparent toxicity against the human MRC-5 cell line and murine cardiac cells. 相似文献
2.
Owies M. Wani Rob Verpaalen Hao Zeng Arri Priimagi Albert P. H. J. Schenning 《Advanced materials (Deerfield Beach, Fla.)》2019,31(2)
Beyond their colorful appearances and versatile geometries, flowers can self‐shape‐morph by adapting to environmental changes. Such responses are often regulated by a delicate interplay between different stimuli such as temperature, light, and humidity, giving rise to the beauty and complexity of the plant kingdom. Nature inspires scientists to realize artificial systems that mimic their natural counterparts in function, flexibility, and adaptation. Yet, many of the artificial systems demonstrated to date fail to mimic the adaptive functions, due to the lack of multi‐responsivity and sophisticated control over deformation directionality. Herein, a new class of liquid‐crystal‐network (LCN) photoactuators whose response is controlled by delicate interplay between light and humidity is presented. Using a novel deformation mechanism in LCNs, humidity‐gated photoactuation, an artificial nocturnal flower is devised that is closed under daylight conditions when the humidity level is low and/or the light level is high, while it opens in the dark when the humidity level is high. The humidity‐gated photoactuators can be fueled with lower light intensities than conventional photothermal LCN actuators. This, combined with facile control over the speed, geometry, and directionality of movements, renders the “nocturnal actuator” promising for smart and adaptive bioinspired microrobotics. 相似文献
3.
Thomas C. van den Ende Jeroen M. M. Heuts Dr. Geoffroy P. P. Gential Marten Visser Michel J. van de Graaff Dr. Nataschja I. Ho Prof. Dr. Wim Jiskoot Dr. A. Rob P. M. Valentijn Nico J. Meeuwenoord Prof. Dr. Herman S. Overkleeft Prof. Dr. Jeroen D. C. Codée Prof. Dr. Sjoerd H. van der Burg Dr. Els M. E. Verdegaal Prof. Dr. Gijsbert A. van der Marel Prof. Dr. Ferry Ossendorp Dr. Dmitri V. Filippov 《Chembiochem : a European journal of chemical biology》2021,22(7):1215-1222
Synthetic vaccines, based on antigenic peptides that comprise MHC−I and MHC-II T-cell epitopes expressed by tumors, show great promise for the immunotherapy of cancer. For optimal immunogenicity, the synthetic peptides (SPs) should be adjuvanted with suitable immunostimulatory additives. Previously, we have shown that improved immunogenicity in vivo is obtained with vaccine modalities in which an SP is covalently connected to an adjuvanting moiety, typically a ligand to Toll-like receptor 2 (TLR2). SPs were covalently attached to UPam, which is a derivative of the classic TLR2 ligand Pam3CysSK4. A disadvantage of the triply palmitoylated UPam is its high lipophilicity, which precludes universal adoption of this adjuvant for covalent modification of various antigenic peptides as it renders the synthetic vaccine insoluble in several cases. Here, we report a novel conjugatable TLR2 ligand, mini-UPam, which contains only one palmitoyl chain, rather than three, and therefore has less impact on the solubility and other physicochemical properties of a synthetic peptide. In this study, we used SPs that contain the clinically relevant neoepitopes identified in a melanoma patient who completely recovered after T-cell therapy. Homogeneous mini-UPam-SP conjugates have been prepared in good yields by stepwise solid-phase synthesis that employed a mini-UPam building block pre-prepared in solution and the standard set of Fmoc-amino acids. The immunogenicity of the novel mini-UPam-SP conjugates was demonstrated by using the cancer patient's T-cells. 相似文献
4.
Mapping of background air pollution at a fine spatial scale across the European Union 总被引:5,自引:0,他引:5
Rob Beelen Gerard Hoek Danielle Vienneau David J. Briggs 《The Science of the total environment》2009,407(6):1852-1867
Background
There is a need to understand much more about the geographic variation of air pollutants. This requires the ability to extrapolate from monitoring stations to unsampled locations. The aim was to assess methods to develop accurate and high resolution maps of background air pollution across the EU.Methods
We compared the validity of ordinary kriging, universal kriging and regression mapping in developing EU-wide maps of air pollution on a 1 × 1 km resolution. Predictions were made for the year 2001 for nitrogen dioxide (NO2), fine particles < 10 µm (PM10), ozone (O3), sulphur dioxide (SO2) and carbon monoxide (CO) using routine monitoring data in Airbase. Predictor variables from EU-wide databases were land use, road traffic, population density, meteorology, altitude, topography and distance to sea. Models were developed for the global, rural and urban scale separately. The best method to model concentrations was selected on the basis of predefined performance measures (R2, Root Mean Square Error (RMSE)).Results
For NO2, PM10 and O3 universal kriging performed better than regression mapping and ordinary kriging. Validation of the final universal kriging estimates with results from all validation sites gave R2-values and RMSE-values of 0.61 and 6.73 µg/m3 for NO2; 0.45 and 5.19 µg/m3 for PM10; and 0.70 and 7.69 µg/m3 for O3. For SO2 and CO none of the three methods was able to provide a satisfactory prediction.Conclusion
Reasonable prediction models were developed for NO2, PM10 and O3 on an EU-wide scale. Our study illustrates that it is possible to develop detailed maps of background air pollution using EU-wide databases. 相似文献5.
The socio-cultural production of architects' identities, and their professional personas, is a lively source of continuing debate. At one extreme, there is the claim to autonomy that highlights the distinctiveness of architecture and its cultural and disciplinary specificity. This view is challenged by those who emphasise architects' dependence, for acting and actions, on their embeddedness into collective, social, settings and relationships. In the paper, we consider what it may mean to be ‘autonomous of’ and ‘dependent on’ in relation to the actions of architects. There is limited specification in architectural writings about what autonomy and dependence are, and we suggest that there is a need not to discount such terms, but to reformulate them by recognising that the socially constructed self is an integral part of individual action. In this respect, we seek to amplify, and evaluate, the concept of relational autonomy that distances the notion of autonomy from individualistic, under-socialised, accounts of architects and their practices. Referring to three empirical examples of practice, we amplify this understanding by, first, outlining what a relational autonomous approach to architecture might entail, and, secondly, assessing how far it may enable a conception of the practices of architects in ways whereby, following Tony Fry's observations, they are conceived as much broader than ‘the specificity of any particular activity’ that expresses their existence. 相似文献
6.
Samuel Brando Susin Vinicius Pistor Sandro Campos Amico Luiz Antonio Ferreira Coelho Sergio Henrique Pezzin Ademir José Zattera 《应用聚合物科学杂志》2014,131(3)
With the increased interest in thermoset resin nanocomposites, it is important to understand the effects of the material on nanoscale characteristics. In this study, a curing reaction of an epoxy resin, which contained 0.25, 0.50, or 1.00 wt % of multiwalled carbon nanotubes (MWCNTs), at different heating rates was monitored by differential scanning calorimetry; cure kinetics were also evaluated to establish a relationship between crosslinking (network formation) and mechanical properties. MWCNT concentrations above 0.25 wt % favored crosslinking formation and decreased the activation energy (Ea) in the curing reaction. Examination of the kinetic mechanism suggests that the MWCNT locally restricted the spatial volume and favored the formation of nodular morphology in the resin, especially for high MWCNT concentrations. The MWCNT exhibited some entanglement in the matrix, which hindered a more pronounced effect on the mechanical properties. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39857. 相似文献
7.
Thermally sprayed coatings are often used to mitigate corrosion of offshore structures. They act as a physical barrier to the aggressive marine environment and as a sacrificial distributed anode for low carbon steel. In such environments, the severity of material degradation depends on many factors. The effect of temperature, exposure time or the presence of micro‐organisms are the focus of many studies, for example, however, the effect of the different ions present in seawater remains largely unexplored. The chemical composition of the water changes considerably depending on the location; industrial, glacial, estuarine, and so forth. In addition, when thermal spray aluminum (TSA) protects steel in seawater, calcareous matter precipitates as a result of the cathodic polarization and subsequent localized increase in pH. Therefore, understanding how ions such as magnesium (II), calcium (II), or carbonates alter the coating properties in the marine environment is important. This paper reports the experimental work carried out with TSA‐coated steel samples with defects to simulate mechanical damage or erosion of the coating. The combination of electrochemical tests and surface characterization provided evidence of the efficiency of the calcareous bilayer that forms on top of steel reducing the TSA degradation. 相似文献
8.
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10.
Fleur Deken Maaike Kleinsmann Marco Aurisicchio Kristina Lauche Rob Bracewell 《Research in Engineering Design》2012,23(3):203-218
Designing is a knowledge-intensive activity. For novice design engineers, an important means of acquiring knowledge is to consult experienced colleagues. We observed novice?Cexpert consultations as part of three engineering projects in a large aerospace company. Seven meetings were analysed in detail regarding the design activity, the content, and the form of interaction. Although the meetings were initiated for the purpose of information seeking, this process amounted to only 8% of the time compared to knowledge creation between novices and experts (47% of meeting time), and contextual information sharing (45% of meeting time). Both experts and novices were found to contribute equally and interactively to the discussion and analysis of solutions. The analysis showed how the processes alternated in the meetings. We identified tentative patterns on how these consultation processes change over the course of the design process phases. The micro-level analysis of the design activities and form of interaction provided a deeper understanding of how the consultation processes are discursively produced by the experts and novices. Finally, implications for design engineering practitioners are derived and suggestions for further research are provided. 相似文献