Ryan Miller

Combined neprilysin and renin-angiotensin system inhibition for the treatment of heart failure.

Neprilysin is an enzyme that contributes to the breakdown of the biologically active natriuretic peptides and several other vasoactive compounds. Inhibiting neprilysin has been a therapeutic target for several compounds that have been tested in cardiovascular disease, including ecadotril, candoxatril, omapatrilat, and LCZ696. Although ecadotril, candoxatril, and omapatrilat were initially tested in hypertension and/or heart failure, lack of efficacy and side effects led to discontinuation of their development. LCZ696 (sacubitril valsartan) is a first-in-class angiotensin receptor neprilysin inhibitor that has been developed for use in heart failure. This compound is composed of 2 molecular moieties in a single crystalline complex-the angiotensin receptor blocker valsartan and a neprilysin inhibitor prodrug-and has now been tested in hypertension, in a phase 2 trial in heart failure with preserved ejection fraction, and has demonstrated greater efficacy than enalapril in a phase 3 trial in heart failure with reduced ejection fraction. Its ability to inhibit the renin-angiotensin-aldosterone axis and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease.

Schottky's conjecture on multiplication of field enhancement factors

Of great interest to high power microwave, millimeter wave to terahertz sources, x-ray tubes, electrons guns, etc., is the electric field enhancement obtained from sharp emitting structures fabricated by various microfabrication methods. In this paper, we use conformal mapping to investigate the field enhancement of several rectilinear geometries, including a single rectangular ridge, a trapezoidal ridge, and their superposition, i.e., one ridge on top of another. We show that the composite field enhancement factor of the double ridge with a microprotrusion on top of a macroprotrusion is dominated by the product of the individual protrusions’ field enhancement factors over a very wide range of geometric aspect ratios, as conjectured by Schottky. Simplified scaling laws are proposed. Significant deviation from Schottky’s product rule occurs almost exclusively when the half-width of the macroprotrusion is less than the height of the microprotrusion. Accurate expressions of the divergent electric field near ...

Antibody responses to influenza vaccine in pre‐and post‐lung transplant patients

Although pre‐transplant immunization is routinely recommended, this recommendation is based on little data. The primary objective of this study was to compare antibody responses in lung transplant patients who received influenza vaccine before the transplant, within the first six months of transplant, between 13 and 60 months post‐transplant, and 110 months or beyond transplant.

Field enhancement on knife-edge cathodes

We extend the analysis of single rectangular-ridge field enhancement to the case of a double ridge.

High Current Density Advanced Cold Cathode Experiments

We report the design, construction and initial operation of an advanced, high-current-density, field emission cathode facility. The facility is designed to examine the nanophysics of field emission from advanced Al, Ni, C, CsI, Mo, and other material cathodes that operate in the 1-1000 A/cm2 regime. Operation is designed for UHV vacuum (10-10 Torr) with bake-out provisions up to temperatures of 450 C for several days to eliminate any residual water vapor or other contaminants. Three pumps are used to achieve UHV vacuum. The first is a Varian scroll pump, working from atmospheric pressure to 10-3 Torr. Then, a Varian turbo pump is used to reduce the pressure from -3 Torr to-8 Torr, with an all-metal bakeable right 90-degree angle valve to cut off the turbo pump from the whole system after pumping. Finally, a 250L/S, VacIon pump brings the whole system to -8 Torr with 450 C baking