Strategies for Accelerating the Development of Catalytic Enantioselective Reactions

The development of enantioselective catalytic processes for the manufacture of chiral intermediates is a very complex endeavor and can be very time consuming and expensive. In this contribution the major issues which might lead to long development times will be discussed and strategies to deal with these problems are described. The general part is illustrated with the approach Solvias has chosen for assisting and supporting the development of enantioselective homogeneous hydrogenation processes, at the moment the most important industrial application of asymmetric catalysis. Special emphasis is given to the application of high-throughput screening (HTS) using a Symyx HiP system and the description of the Solvias portfolio of chiral ligands which makes a broad variety of diphosphine ligands available for all phases of process development from the first screening experiments to the large-scale manufacturing phase. Four case histories serve to illustrate the generic description of the development process

London and beyond: essays in honour of Derek Keene

This volume contains selected papers from a major conference held in October 2008 to celebrate the 20th anniversary of the setting up of the Centre for Metropolitan History at the IHR, and the contribution of Professor Derek Keene to the Centre, the IHR and the wider world of scholarship. 'One of the pioneer volumes in the handsomely produced new Institute of Historical Research Conference series, this book serves as a fitting tribute to one of the most influential urban historians of our time.' - Ian Archer, Urban History, May 2013

Multidisciplinary investigations of the diets of two post-medieval populations from London using stable isotopes and microdebris analysis

This paper presents the first multi-tissue study of diet in post-medieval London using both the stable light isotope analysis of carbon and nitrogen and analysis of microdebris in dental calculus. Dietary intake was explored over short and long timescales. Bulk bone collagen was analysed from humans from the Queen’s Chapel of the Savoy (QCS) (n = 66) and the St Barnabas/St Mary Abbots (SB) (n = 25). Incremental dentine analysis was performed on the second molar of individual QCS1123 to explore childhood dietary intake. Bulk hair samples (n = 4) were sampled from adults from QCS, and dental calculus was analysed from four other individuals using microscopy. In addition, bone collagen from a total of 46 animals from QCS (n = 11) and the additional site of Prescot Street (n = 35) was analysed, providing the first animal dietary baseline for post-medieval London. Overall, isotopic results suggest a largely C3-based terrestrial diet for both populations, with the exception of QCS1123 who exhibited values consistent with the consumption of C4 food sources throughout childhood and adulthood. The differences exhibited in δ15Ncoll across both populations likely reflect variations in diet due to social class and occupation, with individuals from SB likely representing wealthier individuals consuming larger quantities of animal and marine fish protein. Microdebris analysis results were limited but indicate the consumption of domestic cereals. This paper demonstrates the utility of a multidisciplinary approach to investigate diet across long and short timescales to further our understanding of variations in social status and mobility

Endothelial-to-mesenchymal transition contributes to cardiac fibrosis

Cardiac fibrosis, associated with a decreased extent of microvasculature and with disruption of normal myocardial structures, results from excessive deposition of extracellular matrix, which is mediated by the recruitment of fibroblasts. The source of these fibroblasts is unclear and specific anti-fibrotic therapies are not currently available. Here we show that cardiac fibrosis is associated with the emergence of fibroblasts originating from endothelial cells, suggesting an endothelial-mesenchymal transition (EndMT) similar to events that occur during formation of the atrioventricular cushion in the embryonic heart. Transforming growth factor-beta 1 (TGF-beta 1) induced endothelial cells to undergo EndMT, whereas bone morphogenic protein 7 (BMP-7) preserved the endothelial phenotype. The systemic administration of recombinant human BMP-7 (rhBMP-7) significantly inhibited EndMT and the progression of cardiac fibrosis in mouse models of pressure overload and chronic allograft rejection. Our findings show that EndMT contributes to the progression of cardiac fibrosis and that rhBMP-7 can be used to inhibit EndMT and to intervene in the progression of chronic heart disease associated with fibrosis