Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause.

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1

Thermodynamic properties of pulverized coal during rapid heating devolatilization processes

The thermodynamic properties of coal under conditions of rapid heating have been determined using a combination of UTRC facilities including a proprietary rapid heating rate differential thermal analyzer (RHR-DTA), a microbomb calorimeter (MBC), an entrained flow reactor (EFR), an elemental analyzer (EA), and a FT-IR. The total heat of devolatilization, was measured for a HVA bituminous coal (PSOC 1451D, Pittsburgh No. 8) and a LV bituminous coal (PSOC 1516D, Lower Kittaning). For the HVA coal, the contributions of each of the following components to the overall heat of devolatilization were measured: the specific heat of coal/char during devolatilization, the heat of thermal decomposition of the coal, the specific heat capacity of tars, and the heat of vaporization of tars. Morphological characterization of coal and char samples was performed at the University of Pittsburgh using a PC-based image analysis system, BET apparatus, helium pcynometer, and mercury porosimeter. The bulk density, true density, CO{sub 2} surface area, pore volume distribution, and particle size distribution as a function of extent of reaction are reported for both the HVA and LV coal. Analyses of the data were performed to obtain the fractal dimension of the particles as well as estimates for the external surface area. The morphological data together with the thermodynamic data obtained in this investigation provides a complete database for a set of common, well characterized coal and char samples. This database can be used to improve the prediction of particle temperatures in coal devolatilization models. Such models are used both to obtain kinetic rates from fundamental studies and in predicting furnace performance with comprehensive coal combustion codes. Recommendations for heat capacity functions and heats of devolatilization for the HVA and LV coals are given. Results of sample particle temperature calculations using the recommended thermodynamic properties are provided