Role of the adducin family genes in human essential hypertension

OBJECTIVE: In both humans and rats, polymorphisms of the alpha adducin (ADD1) gene are involved in renal sodium handling, essential hypertension and some of its organ complications. Adducin functions within cells as a heterodimer composed of various combinations of three subunits that are coded by three genes (ADD1, 2, 3) each located on a different chromosome. DESIGN: These characteristics provide the biochemical basis for investigating epistatic interactions among these loci. METHODS: We examined the three adducin gene polymorphisms and their association with ambulatory blood pressure (ABPM) and with plasma levels of renin activity (PRA), endogenous ouabain (EO), in 512 newly discovered and never-treated hypertensive patients. RESULTS: Relative to carriers of the wild type (Gly/Gly) ADD1 gene, patients carrying the mutated Trp ADD1 allele had higher blood pressure (systolic blood pressure (SBP) 143.2 +/- 1.0 versus 140.6 +/- 0.6 mmHg P = 0.027 and diastolic blood pressure (DBP) 94.2 +/- 0.77 versus 92.3 +/- 0.5 mmHg, P = 0.03), lower PRA and EO, consistent with the hypothesis of the renal sodium retaining effect of the Trp allele. Polymorphisms in the ADD2 and ADD3 genes taken alone were not associated with these variables. However, the differences in SBP and DBP between the two ADD1 genotypes were greatest in carriers of the ADD3 G allele (around + 8 mmHg). The significance of the interaction between ADD1 and ADD3 ranged between P = 0.020 to P = 0.006 according to the genetic model applied. CONCLUSIONS: The interaction of ADD1 and ADD3 gene variants in humans is statistically associated with variation in blood pressure, suggesting the presence of epistatic effects among these loci

RF and Mechanical Design of the ITER Ion Cyclotron Resonance Frequency Antenna

The ITER Ion Cyclotron Resonance Frequency antenna must couple 20 MW at an antenna-plasma spacing of ∼ 15 cm for pulse lengths up to 1000 s at frequencies from 40 MHz to 55 MHz, using matching components mounted outside of the torus to allow powering through fast (sub-ms) changes in loading during Edge Localised Modes (ELM's) by the use of either 3dB couplers or a conjugate-T configuration. The chosen design comprises a port plug supporting a close-packed array of 24 straps which are connected in triplets to eight feed transmission lines. Rear sections of the antenna are removable from the rear of the port plug, to allow damaged windows or diagnostics to be replaced, and much of the interior comprises radiation shielding material. The RF specification poses substantial challenges. Computer modelling has been used to maximise the coupled power and/or reduce electric field strength for the straps, feeders and transmission lines, and is now being extended to minimise power loadings caused by sheath effects. The use of closely-spaced straps leads to significant levels of inter-strap mutual coupling that complicates the matching algorithm. Arc detection is also a key issue for this antenna, as recent JET and Tore Supra results have highlighted the need for parallel development of arc detection and ELM-tolerant systems. The mechanical design challenges lie even further beyond the range of present experience. Given the long pulse length, the thermal design dominates much of the detailed mechanical design as peak RF currents of 1 - 2 kA will result in high thermal loads; a situation exacerbated by the power loading from the plasma. Resilience to disruption forces has required the design of RF windows that can transmit the forces on the central RF conductors to the port plug structure. The requirement that the rear transmission line section is removable considerably increases the complexity of the mechanical layout. Achievement of the required level of radiation shielding is challenging, given the need to both maintain the water/steel fraction close to the optimum value and to keep the total antenna weight below 45 tonnes. This paper details the RF and mechanical design features proposed for the antenna and outlines the manner in which the wider EU programme will feed into the design proces