Protein-based materials, toward a new level of structural control

Through billions of years of evolution nature has created and refined structural proteins for a wide variety of specific purposes. Amino acid sequences and their associated folding patterns combine to create elastic, rigid or tough materials. In many respects, nature’s intricately designed products provide challenging examples for materials scientists, but translation of natural structural concepts into bio-inspired materials requires a level of control of macromolecular architecture far higher than that afforded by conventional polymerization processes. An increasingly important approach to this problem has been to use biological systems for production of materials. Through protein engineering, artificial genes can be developed that encode protein-based materials with desired features. Structural elements found in nature, such as β-sheets and α-helices, can be combined with great flexibility, and can be outfitted with functional elements such as cell binding sites or enzymatic domains. The possibility of incorporating non-natural amino acids increases the versatility of protein engineering still further. It is expected that such methods will have large impact in the field of materials science, and especially in biomedical materials science, in the future

Individualisation of Mycophenolate Mofetil Therapy: Explaining variability in mycophenolic acid pharmacokinetics and introducing therapeutic

The prodrug mycophenolate mofetil contains the active compound mycophenolic acid (MPA), which has immunosuppressive properties. It is used to prevent acute rejection after solid organ transplantation. In renal transplantation, the dose recommendation for mycophenolate mofetil is 1000 mg twice daily for adult patients. This fixed dose strategy for mycophenolate mofetil is remarkable in the field of transplantation as most other immunosuppressive drugs are used in an individualised dose, often based on drug concentration measurements. During the use of mycophenolate mofetil in the past ten years, data have become available which provide four reasons to question the justification of a fixed mycophenolate mofetil dose. The first reason is the existence of a concentration-effect relationship: the risk for acute rejection is lower when exposure to MPA is higher. This has led to the adoption of a target exposure range for MPA area-under-the-curve (AUC0-12) values of 30 to 60 mg*h/L. The second reason is the large between-patient variability in MPA pharmacokinetics, reported to be more than 10-fold for MPA AUC0-12. The third reason is that MPA exposure increases over time after transplantation despite a fixed dose. Finally, exposure to MPA is significantly influenced by the use of several other drugs. The result of these four factors is that with the use of a standard dose of mycophenolate mofetil, an important subset of renal transplant recipients will have MPA exposure outside the target range, and may therefore be at risk for acute rejection or toxicity. Individualisation of the mycophenolate mofetil dose is likely to improve exposure to MPA and may optimise clinical outcome. The aim of this thesis was to develop recommendations about when and how to individualise the mycophenolate mofetil dose. Two hypotheses in this regard were addressed, formulated in c

Territorial Factors in a Globalised Art World?

In comparison to other disciplines of high culture, the visual arts seem to be the most suitable to internationalise (cf. Crane, 1992; Janssen, Kuipers & Verboord, 2008). The global diffusion of visual art works, for example, is far less complex than that of the performing arts, which entails an impressive transportation operation of both goods – instruments, sets, costumes – and the actors involved, such as orchestra musicians, theatre company actors or dancers. The global distribution of literature, meanwhile, is easier to achieve than is the case for the visual arts, yet language obstacles manifestly hinder its internationalisation (Heilbron, 1999; Janssen, 2009; Sapiro, 2010). Indeed, the only way to overcome such hurdles is when the author provides a translation of the work, or when the reader learns the foreign language in which it is written (De Swaan, 2001). This is similar in the case of theatre plays or the cinema (Hofstede, 2000). On the other hand, the visual language is deemed to be universal and is unhindered by these issues. In short, while the internationalisation of other domains demands different kinds of investment, the visual arts seem to have the best conditions for artists to conquer the world

Standaardnederlands, de sleutel tot integratie in Vlaanderen? Over de uitdagingen van niet-standaardtaal voor NT2-leerders in Vlaanderen

Flanders strongly encourages newcomers to take language courses to learn the official language, on the assumption that certified competence in Dutch will enhance integration. However, in Dutch L2-education the focus lies on Standard Dutch, and this contrasts to everyday spoken encounters in Flanders, where Standard Dutch is rarely used. Despite the perceived importance of learning the official language of the host society, the attested contrast between policy and language reality has up to now not been given much attention. In this publication we go into the results of a linguistic-ethnographic study conducted with language learners living in East-Flanders. We show that non-standard Dutch used by L1-speakers of Dutch sometimes causes comprehension difficulties in their interactions with the language learners. Based on interactional and interview data, we reflect on the question if L2-education should pay more attention to non-standard Dutch in class

Artificial cells: synthetic compartments with life-like functionality and adaptivity

Cells are highly advanced microreactors that form the basis of all life. Their fascinating complexity has inspired scientists to create analogs from synthetic and natural components using a bottom-up approach. The ultimate goal here is to assemble a fully man-made cell that displays functionality and adaptivity as advanced as that found in nature, which will not only provide insight into the fundamental processes in natural cells but also pave the way for new applications of such artificial cells.In this Account, we highlight our recent work and that of others on the construction of artificial cells. First, we will introduce the key features that characterize a living system; next, we will discuss how these have been imitated in artificial cells. First, compartmentalization is crucial to separate the inner chemical milieu from the external environment. Current state-of-the-art artificial cells comprise subcompartments to mimic the hierarchical architecture of eukaryotic cells and tissue. Furthermore, synthetic gene circuits have been used to encode genetic information that creates complex behavior like pulses or feedback. Additionally, artificial cells have to reproduce to maintain a population. Controlled growth and fission of synthetic compartments have been demonstrated, but the extensive regulation of cell division in nature is still unmatched.Here, we also point out important challenges the field needs to overcome to realize its full potential. As artificial cells integrate increasing orders of functionality, maintaining a supporting metabolism that can regenerate key metabolites becomes crucial. Furthermore, life does not operate in isolation. Natural cells constantly sense their environment, exchange (chemical) signals, and can move toward a chemoattractant. Here, we specifically explore recent efforts to reproduce such adaptivity in artificial cells. For instance, synthetic compartments have been produced that can recruit proteins to the membrane upon an external stimulus or modulate their membrane composition and permeability to control their interaction with the environment. A next step would be the communication of artificial cells with either bacteria or another artificial cell. Indeed, examples of such primitive chemical signaling are presented. Finally, motility is important for many organisms and has, therefore, also been pursued in synthetic systems. Synthetic compartments that were designed to move in a directed, controlled manner have been assembled, and directed movement toward a chemical attractant is among one of the most life-like directions currently under research.Although the bottom-up construction of an artificial cell that can be truly considered “alive” is still an ambitious goal, the recent work discussed in this Account shows that this is an active field with contributions from diverse disciplines like materials chemistry and biochemistry. Notably, research during the past decade has already provided valuable insights into complex synthetic systems with life-like properties. In the future, artificial cells are thought to contribute to an increased understanding of processes in natural cells and provide opportunities to create smart, autonomous, cell-like materials.<br/

Feminism in Flux : Indigenous Rights Activism and the Evolution of Feminism in New South Wales, 1930-1960

From the 1930s in Australia, white female voices of protest regarding Indigenous affairs were prominent. While undoubtedly emerging from philanthropic concerns, this thesis argues that more can be elicited from white women’s interest in Indigenous affairs. My focus is feminist organisations in Sydney between 1930 and 1960 where Indigenous affairs were continually a part of a ‘progressive’ feminist agenda which in the period shifted to the left of the political spectrum. A feminist interest in Indigenous rights is used to illustrate the radicalisation of feminism from the conservatism of the 1930s to the antecedents of the politics of female liberation in the 1950s