2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011

Great flights by great snipes: long and fast non-stop migration over benign habitats

Migratory land birds perform extreme endurance flights when crossing ecological barriers, such as deserts, oceans and ice-caps. When travelling over benign areas, birds are expected to migrate by shorter flight steps, since carrying the heavy fuel loads needed for long non-stop flights comes at considerable cost. Here, we show that great snipes Gallinago media made long and fast nonstop flights (4300-6800 km in 48-96 h), not only over deserts and seas but also over wide areas of suitable habitats, which represents a previously unknown migration strategy among land birds. Furthermore, the great snipes achieved very high ground speeds (15-27 ms(-1)), which was not an effect of strong tailwind support, and we know of no other animal that travels this rapidly over such a long distance. Our results demonstrate that some migratory birds are prepared to accept extreme costs of strenuous exercise and large fuel loads, even when stopover sites are available along the route and there is little tailwind assistance. A strategy of storing a lot of energy before departure, even if migration is over benign habitats, may be advantageous owing to differential conditions of fuel deposition, predation or infection risk along the migration route

Targeted Covalent Inhibition of Plasmodium FK506 Binding Protein 35

FK506-binding protein 35, FKBP35, has been implicated as an essential malarial enzyme. Rapamycin and FK506 exhibit antiplasmodium activity in cultured parasites. However, due to the highly conserved nature of the binding pockets of FKBPs and the immunosuppressive properties of these drugs, there is a need for compounds that selectively inhibit FKBP35 and lack the undesired side effects. In contrast to human FKBPs, FKBP35 contains a cysteine, C106, adjacent to the rapamycin binding pocket, providing an opportunity to develop targeted covalent inhibitors of Plasmodium FKBP35. Here, we synthesize inhibitors of FKBP35, show that they directly bind FKBP35 in a model cellular setting, selectively covalently modify C106, and exhibit antiplasmodium activity in blood-stage cultured parasites

Targeted Covalent Inhibition of Plasmodium FK506 Binding Protein 35

FK506-binding protein 35, FKBP35, has been implicated as an essential malarial enzyme. Rapamycin and FK506 exhibit antiplasmodium activity in cultured parasites. However, due to the highly conserved nature of the binding pockets of FKBPs and the immunosuppressive properties of these drugs, there is a need for compounds that selectively inhibit FKBP35 and lack the undesired side effects. In contrast to human FKBPs, FKBP35 contains a cysteine, C106, adjacent to the rapamycin binding pocket, providing an opportunity to develop targeted covalent inhibitors of Plasmodium FKBP35. Here, we synthesize inhibitors of FKBP35, show that they directly bind FKBP35 in a model cellular setting, selectively covalently modify C106, and exhibit antiplasmodium activity in blood-stage cultured parasites.Broad Institute (SPARC Grant)Broad Institute (Broad Next10)Bill & Melinda Gates Foundation (OPP1158199 and OPP1162467

Do Trading and Power Operations Mix? The Case of Constellation Energy Group 2008

Constellation Energy has been a leading performer in the merchant power business since 2001. In addition to its legacy utility, Baltimore Gas and Electric, Constellation is a merchant generator and a wholesale power marketer serving the load of utilities as well as industrial, commercial and retail customers. Constellation has developed sophisticated risk management capabilities and a large trading operation in electric power and related commodities. In a recent reorganization, Constellation gave its trading operations greater organizational independence and prominence. It also increased the scale of its proprietary trading, and used its trading operation as the tool for expanded investments into upstream natural gas and coal and international freight. In August and September of 2008, Constellation experienced a major liquidity crisis that saw its stock price fall by nearly three-quarters. In an emergency search for cash, it was forced to agree to sell itself at the low price. This paper reviews Constellation’s history and the specific events precipitating its liquidity crisis. It then places Constellation’s strategy vis-à-vis its commodity trading operations in the context of the larger history of commodity trading operations and discusses the key financial and strategic questions posed by Constellation’s crisis.Massachusetts Institute of Technology. Center for Energy and Environmental Policy Research

Double Take

The Polity data are widely used to explore the causes and consequences of democratic authority patterns. These data often have been used uncritically. The authors explore some of the theoretical and empirical characteristics of these data. They show how the analytical composition of the well-known democracy and autocracy scores is not upheld by an empirical analysis of the component measurements and demonstrate that democracy, as measured by the Polity indicators, is fundamentally a reflection of decisional constraints on the chief executive. The recruitment and participation dimensions are shown to be empirically extraneous despite their centrality in democratic theory. The authors conclude that it is a mistake to overlook the categorical nature of these data and that an analysis of the constituent authority patterns is likely to be fruitful for the democratic peace and democratization literature