Breadboard RL10-2B low-thrust operating mode (second iteration) test report

Cryogenic rocket engines requiring a cooling process to thermally condition the engine to operating temperature can be made more efficient if cooling propellants can be burned. Tank head idle and pumped idle modes can be used to burn propellants employed for cooling, thereby providing useful thrust. Such idle modes required the use of a heat exchanger to vaporize oxygen prior to injection into the combustion chamber. During December 1988, Pratt and Whitney conducted a series of engine hot firing demonstrating the operation of two new, previously untested oxidizer heat exchanger designs. The program was a second iteration of previous low thrust testing conducted in 1984, during which a first-generation heat exchanger design was used. Although operation was demonstrated at tank head idle and pumped idle, the engine experienced instability when propellants could not be supplied to the heat exchanger at design conditions

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

Functional interaction between angiotensin II receptor type 1 and chemokine (C-C Motif) receptor 2 with implications for chronic kidney disease

Understanding functional interactions between G protein-coupled receptors is of great physiological and pathophysiological importance. Heteromerization provides one important potential mechanism for such interaction between different signalling pathways via macromolecular complex formation. Previous studies suggested a functional interplay between angiotensin II receptor type 1 (AT1) and Chemokine (C-C motif) Receptor 2 (CCR2). However the molecular mechanisms are not understood. We investigated AT1-CCR2 functional interaction [i]in vitro[/i] using bioluminescence resonance energy transfer in HEK293 cells and [i]in vivo[/i] using subtotal-nephrectomized rats as a well-established model for chronic kidney disease. Our data revealed functional heteromers of these receptors resulting in CCR2-Gαi1 coupling being sensitive to AT1 activation, as well as apparent enhanced β-arrestin2 recruitment with agonist co-stimulation that is synergistically reversed by combined antagonist treatment. Moreover, we present [i]in vivo[/i] findings where combined treatment with AT1- and CCR2-selective inhibitors was synergistically beneficial in terms of decreasing proteinuria, reducing podocyte loss and preventing renal injury independent of blood pressure in the subtotal-nephrectomized rat model. Our findings further support a role for G protein-coupled receptor functional heteromerization in pathophysiology and provide insights into previous observations indicating the importance of AT1-CCR2 functional interaction in inflammation, renal and hypertensive disorders