Reasons for action

Reasons for action are considerations in the light of which we act. But just what is it that we attribute to a person when we credit her with a good reason? What sort of entity is on our minds when we deliberate about what we have reason to do? This book examines this question and evaluates a number of approaches to the philosophy of reasons, including normative realism, psychologism and Humeanism. The second half of the book contains the defense of a theory of reasons influenced by the writings of Wilfrid Sellars and Robert Brandom. This theory is further developed in relation to a number of recent topics in action theory, including the Guise of the Good thesis, internalism and the normativity of reasons

Widening the Methodological Lens on the Investigation of Diversity in the Transition to Higher Education: A Discussion

This discussion addresses the methodological approaches used in the special issue on student transitions and diversity. We provide an overview of how the different papers contribute to methodological development in the field, in particular by their use of advanced multi-factor analyses and accounting for diversity in student transitions at several levels. The discussion touches upon challenges concerning (a) the distinction of analytical levels, (b) different conceptualisations and operationalisations of diversity and (c) the types of data collection methodologies. We conclude by discussing future steps to widen the methodological lens in transition research

Reasons for action

Reasons for action are considerations in the light of which we act. But just what is it that we attribute to a person when we credit her with a good reason? What sort of entity is on our minds when we deliberate about what we have reason to do? This book examines this question and evaluates a number of approaches to the philosophy of reasons, including normative realism, psychologism and Humeanism. The second half of the book contains the defense of a theory of reasons influenced by the writings of Wilfrid Sellars and Robert Brandom. This theory is further developed in relation to a number of recent topics in action theory, including the Guise of the Good thesis, internalism and the normativity of reasons

Scalable numerical approach for the steady-state ab initio laser theory

We present an efficient and flexible method for solving the non-linear lasing equations of the steady-state ab initio laser theory. Our strategy is to solve the underlying system of partial differential equations directly, without the need of setting up a parametrized basis of constant flux states. We validate this approach in one-dimensional as well as in cylindrical systems, and demonstrate its scalability to full-vector three-dimensional calculations in photonic-crystal slabs. Our method paves the way for efficient and accurate simulations of lasing structures which were previously inaccessible.Comment: 17 pages, 8 figure

Multimodal imaging of pancreatic beta cells in vivo by targeting transmembrane protein 27 (TMEM27)

Aims/hypothesis: Non-invasive diagnostic tools specific for pancreatic beta cells will have a profound impact on our understanding of the pathophysiology of metabolic diseases such as diabetes. The objective of this study was to use molecular imaging probes specifically targeting beta cells on human samples and animal models using state-of-the-art imaging modalities (fluorescence and PET) with preclinical and clinical perspective. Methods: We generated a monoclonal antibody, 8/9-mAb, targeting transmembrane protein 27 (TMEM27; a surface N-glycoprotein that is highly expressed on beta cells), compared its expression in human and mouse pancreas, and demonstrated beta cell-specific binding in both. In vivo imaging was performed in mice with subcutaneous insulinomas overexpressing the human TMEM27 gene, or transgenic mice with beta cell-specific hTMEM27 expression under the control of rat insulin promoter (RIP-hTMEM27-tg), using fluorescence and radioactively labelled antibody, followed by tissue ex vivo analysis and fluorescence microscopy. Results: Fluorescently labelled 8/9-mAb showed beta cell-specific staining on human and mouse pancreatic sections. Real-time PCR on islet cDNA indicated about tenfold higher expression of hTMEM27 in RIP-hTMEM27-tg mice than in humans. In vivo fluorescence and PET imaging in nude mice with insulinoma xenografts expressing hTMEM27 showed high 8/9-mAb uptake in tumours after 72h. Antibody homing was also observed in beta cells of RIP-hTMEM27-tg mice by in vivo fluorescence imaging. Ex vivo analysis of intact pancreas and fluorescence microscopy in beta cells confirmed these findings. Conclusions/interpretation: hTMEM27 constitutes an attractive target for in vivo visualisation of pancreatic beta cells. Studies in mouse insulinoma models and mice expressing hTMEM27 demonstrate the feasibility of beta cell-targeted in vivo imaging, which is attractive for preclinical investigations and holds potential in clinical diagnostic

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research