22,107 research outputs found
Eredoctoraat prof. mr. Geert Corstens
No full textOn October 17, 2023, during the 100th Dies Natalis of Radboud University, Geert Corstens received an honorary doctorate from Radboud University. This honorary doctorate was awarded to him because of his tireless efforts for a strong, fair and equal constitutional state. This edition includes the laudation of honorary supervisor Roel Schutgens, the acceptance speech of Geert Corstens and the Van der Grint lecture given by Geert Corstens during the week of the Dies Natalis.
Geert Corstens was president of the Supreme Court of the Netherlands from 2008 to 2014. Immediately after his appointment, he was known for his assertive attitude towards the political apparatus. The independence of the constitutional state should not be threatened by the wishes and needs of politicians and other outsiders, Corstens believed. He has also made a formidable contribution to public-oriented communication and explanation of the rule of law. Corstens also wrote, among other things, the books Our constitutional state and The judge seizes power: And other misconceptions about the democratic constitutional state to promote general communication about rights and democracy in the Netherlands. Corstens is also the author of the standard work Dutch criminal procedural law and was professor of criminal law at Radboud University from 1982 to 1995
Chemoenzymatic Synthesis of Heparan Sulfate Oligosaccharides having Domain Structures
No full textHeparan sulfate (HS) can interact with various proteins that mediate various biological processes. The biosynthesis of HS is incomplete leading to molecular diversity to obtain well-defined compounds from natural sources difficultly. There is data to support that the domain structures of HS can regulate protein binding, however, such a binding mode has been difficult to probe because of a lack of methodologies to prepare well-defined HS oligosaccharides having domain structures. A chemoenzymatic methodology is described that can provide well-defined HS mimetics that have multiple NS domains separated by NA domains of different length. It is based on the chemical synthesis of a sulfated HS oligosaccharide that enzymatically could be extended by GlcA-GlcNAc moieties and a terminal GlcNAc-6N3 moiety. The reducing end of HS oligosaccharide could be functionalized by an alkyne moiety and the resulting compound could be coupled with the afore GlcNAc-6N3 HS oligosaccharide by CuAAC reaction to give compounds having two NS domains separated by an NA domain. The process of enzymatic NA introduction and click reaction could be repeated to give mimetics having three sulfated domains. SPR competition studies indicate that the length of NA domain influences the binding of chemokines CXCL8 and CCL5 in complex manners. We prepared heparin mimetics by head-to-tail CuAAC-mediated coupling of a sulfate oligosaccharide having an alkyne at the reducing end and azide moiety at the nonreducing end. By repeating the process of enzymatically introducing an azido containing GlcNAc moiety and chemically attachment of an anomeric alkyne containing moiety followed by CuAAC mediated coupling, well-defined multimeric compounds could be prepared composed of as many as 27 monosaccharides. We examined mono-, di-, tri-, and tetravalent heparin mimetics for their ability to inhibit the binding of the spike of SARS-CoV-2 to immobilized heparin. It was found that increasing the number of repeating units resulted in large increases in inhibitory potential and a tetravalent compound had similar potency compared to heparin. Similar inhibition was observed for the binding of trimeric RBD to Vero cells. The data support that well-defined heparin mimetics can be developed to inhibit the attachment of SARS-CoV-2 to the target cell. We described a modular synthetic methodology that can provide libraries of HS oligosaccharide bearing glucosamine residues modified by N-acetyl and N-sulfate moieties. It was found that the amino protecting groups trifluoromethylphenyl-methanimine and azide, as well as the hydroxyl protection by Lev, TDS, Alloc and Fmoc allow for selective manipulation of functionalities in the synthesis of high complex HS oligosaccharides. The microarray studies highlight key requirements of chemokines to engage with HS. The methodology will make it possible to prepare panels of compounds for structure-activity relationship investigations for a better understanding the biology of HS and provide the possibility to assemble HS oligosaccharides having NS and NA domains chemically. In summary, we have developed efficient methodology for the synthesis of HS derivatives of unprecedented complexity. Although further developments are needed to access the immense complexity found in natural HS, we were able to capture the domain architecture of HS in synthetic oligosaccharides
Dimensionalizing Cultures: The Hofstede Model in Context
No full textThis article describes briefly the Hofstede model of six dimensions of national cultures: Power Distance, Uncertainty Avoidance, Individualism/Collectivism, Masculinity/Femininity, Long/Short Term Orientation, and Indulgence/Restraint. It shows the conceptual and research efforts that preceded it and led up to it, and once it had become a paradigm for comparing cultures, research efforts that followed and built on it. The article stresses that dimensions depend on the level of aggregation; it describes the six entirely different dimensions found in the Hofstede et al. (2010) research into organizational cultures. It warns against confusion with value differences at the individual level. It concludes with a look ahead in what the study of dimensions of national cultures and the position of countries on them may still bring
Combinatorial Biosynthesis of Complex Carbohydrates
No full textThis chapter contains sections titled:
Introduction
Combinatorial Enzymatic and Chemoenzymatic Synthesis of Glycoconjugates
Combinatorial Enzymatic and Chemoenzymatic Synthesis of Oligosaccharides
Whole Cells as Catalysts for the Synthesis of Oligosaccharides
Generating Homogeneously Modified Bacterial Polysaccharides by Metabolic Pathway Engineering
Conclusion
Acknowledgments
Reference
Modern approaches to the synthesis of diverse classes of oligosaccharides
No full textThrough diverse oligosaccharide examples of what today constitutes a complex target, this thesis details four total synthetic oligosaccharide projects. Each project emphasizes the importance of scalable delivery of required monosaccharide building blocks, selection of most optimal synthetic routes, and rational, experience-based choice of protecting groups so that even the most fragile functionalities can be preserved. Special attention is also devoted to the so-called “hybrid” synthesis, whereby chemical and enzymatic approaches are combined together to step-economically deliver the products. Finally, it is shown which types of complex oligosaccharides have reached the state of enzyme-catalyzed assembly, and the ones that are not
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