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61.
Stefan Strobl Peter Supancic Tanja Lube Robert Danzer 《Journal of the European Ceramic Society》2012,32(8):1491-1501
The Newman and Raju formula for the stress intensity factor of a semi-elliptical surface crack loaded in uniaxial tension or in bending has been developed about 30 years ago using an FE-analysis for several geometric parameters and fitting an empirical equation to the data points. The Poisson's ratio analyzed was 0.3.In this paper a reassessment of the Newman and Raju formula is made, where all relevant geometric parameters of crack and specimen and the Poisson's ratio are considered. The deviations of the old formula from the new results are up to 21%, if the full range of Poisson's ratio is taken into account. Furthermore the influence of the crack-surface intersection angle is discussed.The results of this work are important for more precise fracture toughness measurements in brittle materials and give a practical guidance for appropriate specimen preparation for fracture toughness measurements, which is also considered here. 相似文献
62.
Contemporary urban policies in various liberal democracies are purposefully crafted to foster both economic efficiency and social justice. For Barel (1989), achieving these directives constitutes a ‘paradox’. Yet, as argued here, this paradox is not new. Rather, it is rooted in liberalism, which, in turn, shapes mainstream planning practices and modes of government. This paper therefore turns to the ‘ethico-politics’ of planning in order to demonstrate how the City of Johannesburg articulates its economic growth and social responsibility policies. It is proposed that unless planners challenge the often unquestioned liberal norms of planning, entrenched norms will continue to obscure alternative possibilities. 相似文献
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Spatial planning has been the subject of critique within the South African context, particularly the disconnect between the intentions of spatial plans and land use decision-making. The City of Cape Town uses a land use assessment mechanism called the Package of Plans, originally developed for the assessment of the Victoria and Alfred Waterfront development, which based on the hierarchical nature of the approach, can provide a link between strategic spatial planning and land use decision-making. Although the mechanism was developed for a specific purpose over 20 years ago, it has not been reviewed within the current spatial planning and land use legislative context. The paper reviews the Package of Plans within this current context and discusses the role it can play in linking spatial planning and land use management within the Cape Town context (and perhaps elsewhere). In so doing, it raises particular questions regarding the role of the mechanism within the City of Cape Town and ways its implementation could be improved. 相似文献
66.
Silke Corall Tamas Haraszti Tanja Bartoschik Joachim Pius Spatz Thomas Ludwig Elisabetta Ada Cavalcanti-Adam 《Computational Mechanics》2014,53(3):499-510
Cell migration is a crucial event for physiological processes, such as embryonic development and wound healing, as well as for pathological processes, such as cancer dissemination and metastasis formation. Cancer cell migration is a result of the concerted action of matrix metalloproteinases (MMPs), expressed by cancer cells to degrade the surrounding matrix, and integrins, the transmembrane receptors responsible for cell binding to matrix proteins. While it is known that cell-microenvironment interactions are essential for migration, the role of the physical state of such interactions remains still unclear. In this study we investigated human fibrosarcoma cell migration in two-dimensional (2D) and three-dimensional (3D) fibronectin (FN) microenvironments. By using antibody blocking approach and cell-binding site mutation, we determined that $\upalpha _{5}\upbeta _{1}$ -integrin is the main mediator of fibrosarcoma cell migration in 2D FN, whereas in 3D fibrillar FN, the binding of $\upalpha _{5}\upbeta _{1}$ - and $\upalpha _\mathrm{v}\upbeta _{3}$ -integrins is not necessary for cell movement in the fibrillar network. Furthermore, while the general inhibition of MMPs with GM6001 has no effect on cell migration in both 2D and 3D FN matrices, we observed opposing effect after targeted silencing of a membrane-bound MMP, namely MT1-MMP. In 2D fibronectin, silencing of MT1-MMP results in decreased migration speed and loss of directionality, whereas in 3D FN matrices, cell migration speed is increased and integrin-mediated signaling for actin dynamics is promoted. Our results suggest that the fibrillar nature of the matrix governs the migratory behavior of fibrosarcoma cells. Therefore, to hinder migration and dissemination of diseased cells, matrix molecules should be directly targeted, rather than specific subtypes of receptors at the cell membrane. 相似文献
67.
Armando Rodríguez-Alfonso Astrid Heck Yasser Bruno Ruiz-Blanco Andrea Gilg Ludger Stndker Seah Ling Kuan Tanja Weil Elsa Sanchez-Garcia Sebastian Wiese Jan Münch Mirja Harms 《International journal of molecular sciences》2022,23(23)
Advanced derivatives of the Endogenous Peptide Inhibitor of CXCR4 (EPI-X4) have shown therapeutic efficacy upon topical administration in animal models of asthma and dermatitis. Here, we studied the plasma stability of the EPI-X4 lead compounds WSC02 and JM#21, using mass spectrometry to monitor the chemical integrity of the peptides and a functional fluorescence-based assay to determine peptide function in a CXCR4-antibody competition assay. Although mass spectrometry revealed very rapid disappearance of both peptides in human plasma within seconds, the functional assay revealed a significantly higher half-life of 9 min for EPI-X4 WSC02 and 6 min for EPI-X4 JM#21. Further analyses demonstrated that EPI-X4 WSC02 and EPI-X4 JM#21 interact with low molecular weight plasma components and serum albumin. Albumin binding is mediated by the formation of a disulfide bridge between Cys10 in the EPI-X4 peptides and Cys34 in albumin. These covalently linked albumin–peptide complexes have a higher stability in plasma as compared with the non-bound peptides and retain the ability to bind and antagonize CXCR4. Remarkably, chemically synthesized albumin-EPI-X4 conjugates coupled by non-breakable bonds have a drastically increased plasma stability of over 2 h. Thus, covalent coupling of EPI-X4 to albumin in vitro before administration or in vivo post administration may significantly increase the pharmacokinetic properties of this new class of CXCR4 antagonists. 相似文献
68.
Synthesis and Biological Evaluation of Papain‐Family Cathepsin L‐Like Cysteine Protease Inhibitors Containing a 1,4‐Benzodiazepine Scaffold as Antiprotozoal Agents 下载免费PDF全文
Dr. Roberta Ettari Dr. Andrea Pinto Dr. Lucia Tamborini Dr. Ilenia C. Angelo Prof. Silvana Grasso Prof. Maria Zappalà Dr. Natale Capodicasa Dr. Laura Yzeiraj Dr. Esther Gruber Dr. Makoah N. Aminake Dr. Gabriele Pradel Prof. Tanja Schirmeister Prof. Carlo De Micheli Prof. Paola Conti 《ChemMedChem》2014,9(8):1817-1825
Novel papain‐family cathepsin L‐like cysteine protease inhibitors endowed with antitrypanosomal and antimalarial activity were developed, through an optimization study of previously developed inhibitors. In the present work, we studied the structure–activity relationships of these derivatives, with the aim to develop new analogues with a simplified and more synthetically accessible structure and with improved antiparasitic activity. The structure of the model compounds was significantly simplified by modifying or even eliminating the side chain appended at the C3 atom of the benzodiazepine scaffold. In addition, a simple methylene spacer of appropriate length was inserted between the benzodiazepine ring and the 3‐bromoisoxazoline moiety. Several rhodesain and falcipain‐2 inhibitors displaying single‐digit micromolar or sub‐micromolar antiparasitic activity against one or both parasites were identified, with activities that were one order of magnitude more potent than the model compounds. 相似文献
69.
Elektronische Agenten können auf sämtlichen Stufen elektronischer Geschäftsprozesse eingesetzt werden, wodurch die Transaktionskosten gesenkt und der elektronische Geschäftsverkehr insgesamt beschleunigt und vereinfacht wird (vgl. [30], S. 548). 相似文献
70.
Natalija Dj Polovic Rada V Pjanovic Lidija M Burazer Sava J Velickovic Ratko M Jankov Tanja D Cirkovic Velickovic 《Journal of the science of food and agriculture》2009,89(1):8-14
BACKGROUND: It is thought that food sensitisers must be able to reach the intestine in order to sensitise patients. Pectin is a gel‐forming plant polysaccharide that can protect allergens from in vivo gastric digestion and in vitro pepsin digestion. The aim of this study was to examine if pectin gel formed in the acidic environment of the stomach can protect labile allergen from in vitro gastrointestinal digestion. RESULTS: Pectin forms a gel in the acidic conditions of gastric fluid up to a concentration of 1.0 ± 0.14 g L?1. Four allergenic fruits (kiwi, cherry, apple and banana) form gels in the same manner at the dilutions 14.8 ± 0.4; 8.4 ± 0.2, 9.4 ± 0.35 and 29.1 ± 0.2, respectively. The time necessary for dissolution of 50 g L?1 pectin gel in intestinal fluid was found to be 70 ± 0.2 min. Pectin gel formed in situ was able to protect Act c 1 from pepsin digestion for 1 h and from further intestinal digestion for one additional hour. CONCLUSION: Pectin gel in an acidic environment protects Act c 1 from pepsin digestion and dissolves slowly in the slightly basic environment of the intestine allowing the survival of fruit allergen for additional time and possible interaction with the gut immune system. Copyright © 2008 Society of Chemical Industry 相似文献