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Natural gas is widely considered to be an environmentally cleaner fuel than coal because it does not produce detrimental by-products such as sulfur, mercury, ash and particulates and because it provides twice the energy per unit of weight with half the carbon footprint during combustion. These points are not in dispute. However, in their recent publication in Climatic Change Letters, Howarth et al. (2011) report that their life-cycle evaluation of shale gas drilling suggests that shale gas has a larger GHG footprint than coal and that this larger footprint "undercuts the logic of its use as a bridging fuel over the coming decades". We argue here that their analysis is seriously flawed in that they significantly overestimate the fugitive emissions associated with unconventional gas extraction, undervalue the contribution of "green technologies" to reducing those emissions to a level approaching that of conventional gas, base their comparison between gas and coal on heat rather than electricity generation (almost the sole use of coal), and assume a time interval over which to compute the relative climate impact of gas compared to coal that does not capture the contrast between the long residence time of CO 2 and the short residence time of methane in the atmosphere. High leakage rates, a short methane GWP, and comparison in terms of heat content are the inappropriate bases upon which Howarth et al. ground their claim that gas could be twice as bad as coal in its greenhouse impact. Using more reasonable leakage rates and bases of comparison, shale gas has a GHG footprint that is half and perhaps a third that of coal.

Type II diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular, renal, neurologic, and retinal complications. While several drugs are currently prescribed to treat type II diabetes, their efficacy is limited by mechanism-related side effects (weight gain, hypoglycemia, gastrointestinal distress), inadequate efficacy for use as monotherapy, and the development of tolerance to the agents. Consequently, combination therapies are frequently employed to effectively regulate blood glucose levels. We have focused on the mitochondrial sodium-calcium exchanger (mNCE) as a novel target for diabetes drug discovery. We have proposed that inhibition of the mNCE can be used to regulate calcium flux across the mitochondrial membrane, thereby enhancing mitochondrial oxidative metabolism, which in turn enhances glucose-stimulated insulin secretion (GSIS) in the pancreatic beta-cell. In this paper, we report the facile synthesis of benzothiazepines and derivatives by S-alkylation using 2-aminobenzhydrols. The syntheses of other bicyclic analogues based on benzothiazepine, benzothiazecine, benzodiazecine, and benzodiazepine templates are also described. These compounds have been evaluated for their inhibition of mNCE activity, and the results from the structure-activity relationship (SAR) studies are discussed.

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