Demiarcs, creaons and genons

Useful insights into the representation of natural systems can be gained by decomposing directed graphs (digraphs) into elementary components. Arcs of digraphs can be split into male demiarcs (outarcs) which leave vertices and female demiarcs (inarcs) which enter demiarcs. Likewise, a vertex can be split into an input perceiving side called the creaon and an output generating side called the genon. Digraphs can be regarded as being hierarchically organized because each vertex in a level-1 digraph can be expanded into a level-2 digraph. In general, each vertex of a level-i digraph can be expanded into a level-(i+1) digraph. Arcs of a level-i digraph can be regarded as bundles of level-(i + 1) arcs which are split at the vertex boundary. These elementary graphical components are shown to be useful for depicting input-output systems such as organisms, ecosystems and societies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24236/1/0000496.pd

Classification and Management of Wetlands in the Western Kentucky Coal Field

This is the first research report of a three-year project on wetland identification and management criteria in the western Kentucky coal field. The region is approximately 12,000 square kilometers and, due to its slight relief, contains many wetlands, some contiguous with surface coal mining operations. The overall objectives of the research project are 1) to identify, classify, and map wetlands in the western Kentucky coal field; 2) to evaluate the major biotic and abiotic factors that affect those wetlands; and 3) to develop strategies for the proper management of those wetlands. The first report of this three-year project has involved the following tasks related to wetlands in the coal fields of western Kentucky: establishment of three intensive study sites in major wetlands for identification and assessment of management impacts, sampling tripe in May, July, and September to the intensive study sites, to measure water quality and ecological structure, development of a classification specifically for wetlands in western Kentucky and an application of the classification to the three intensive study sites, and development of conceptual models of the region, watersheds, and specific ecosystems, and preliminary simulations of a wetland model. Our specific sites in western Kentucky are Cypress Creek Wetlands in Muhlenberg County, which are affected by mine drainage and channelization; Clear Creek Swamp in Hopkins County, which is affected by mine drainage and higher water levels; and Henderson Sloughs in Henderson County, which are affected by oil wells and clearing for agriculture. Preliminary analysis of field surveys demonstrates that several activities, particularly coal mining and oil \u27extraction, may affect the health of wetlands in western Kentucky. Drainage, logging, channelization, and impoundments have also caused significant alterations

In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs

Comment in Lowering the High Cost of Cancer Drugs--III. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--I. [Mayo Clin Proc. 2016] Lowering the High Cost of Cancer Drugs--IV. [Mayo Clin Proc. 2016] In Reply--Lowering the High Cost of Cancer Drugs. [Mayo Clin Proc. 2016] US oncologists call for government regulation to curb drug price rises. [BMJ. 2015

A 7-Deaza-Adenosine Analog Is a Potent and Selective Inhibitor of Hepatitis C Virus Replication with Excellent Pharmacokinetic Properties

Improved treatments for chronic hepatitis C virus (HCV) infection are needed due to the suboptimal response rates and deleterious side effects associated with current treatment options. The triphosphates of 2′-C-methyl-adenosine and 2′-C-methyl-guanosine were previously shown to be potent inhibitors of the HCV RNA-dependent RNA polymerase (RdRp) that is responsible for the replication of viral RNA in cells. Here we demonstrate that the inclusion of a 7-deaza modification in a series of purine nucleoside triphosphates results in an increase in inhibitory potency against the HCV RdRp and improved pharmacokinetic properties. Notably, incorporation of the 7-deaza modification into 2′-C-methyl-adenosine results in an inhibitor with a 20-fold-increased potency as the 5′-triphosphate in HCV RdRp assays while maintaining the inhibitory potency of the nucleoside in the bicistronic HCV replicon and with reduced cellular toxicity. In contrast, while 7-deaza-2′-C-methyl-GTP also displays enhanced inhibitory potency in enzyme assays, due to poor cellular penetration and/or metabolism, the nucleoside does not inhibit replication of a bicistronic HCV replicon in cell culture. 7-Deaza-2′-C-methyl-adenosine displays promising in vivo pharmacokinetics in three animal species, as well as an acute oral lethal dose in excess of 2,000 mg/kg of body weight in mice. Taken together, these data demonstrate that 7-deaza-2′-C-methyl-adenosine is an attractive candidate for further investigation as a potential treatment for HCV infection

Trichomonas vaginalis Antimicrobial Drug Resistance in 6 US Cities, STD Surveillance Network, 2009–2010

Such isolates should undergo drug susceptibility testing periodically to detect emerging resistance