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

The pancreatic beta cell surface proteome

The pancreatic beta cell is responsible for maintaining normoglycaemia by secreting an appropriate amount of insulin according to blood glucose levels. The accurate sensing of the beta cell extracellular environment is therefore crucial to this endocrine function and is transmitted via its cell surface proteome. Various surface proteins that mediate or affect beta cell endocrine function have been identified, including growth factor and cytokine receptors, transporters, ion channels and proteases, attributing important roles to surface proteins in the adaptive behaviour of beta cells in response to acute and chronic environmental changes. However, the largely unknown composition of the beta cell surface proteome is likely to harbour yet more information about these mechanisms and provide novel points of therapeutic intervention and diagnostic tools. This article will provide an overview of the functional complexity of the beta cell surface proteome and selected surface proteins, outline the mechanisms by which their activity may be modulated, discuss the methods and challenges of comprehensively mapping and studying the beta cell surface proteome, and address the potential of this interesting subproteome for diagnostic and therapeutic applications in human disease

The role of reasoning ability in university students’ cognitive and metacognitive skill development

This chapter addresses the relationship between university students’ cognitive and metacognitive aspects of learning, focusing on the role of reasoning ability in the development of cognitive and metacognitive skills. The chapter reports on a three-wave longitudinal study of over 2,000 university students in England in which self-report measures of cognitive and meta-cognitive skill were vomplemented by a test of reasoning ability. Th is test and its administration is described in detail before hypotheses about the relationship between reasoning ability and the cognitive and metacognitive aspects of learning are respectively explored. Results suggest a complex set of relationships, with weaker than expected associations. Potential explanations for these findings are discussed

Designing Feedback for Impact

This chapter focuses on influences, affordances and challenges for teachers in designing for (and identifying) feedback impact. We propose four key questions that need to be asked: Do learners know the purpose of feedback and their role(s) in it? Can learners make sense of the information? Can learners take action? What effects should we be looking for? We then explore strategies that have been shown to be valuable in designing feedback that makes a difference. These are organised according to three important considerations: creating opportunities for effective feedback; developing learner and teacher capacities; and looking for effects. We finish the chapter by taking a step back and considering the implications at the programme and institutional levels in cultivating feedback that makes a difference