The NIST Johnson Noise Thermometry System for the Determination of the Boltzmann Constant.

In preparation for the redefinition of the International System of Units (SI), five different electronic measurements of the Boltzmann constant have been performed using different Johnson noise thermometry (JNT) systems over the past seven years. In this paper, we describe in detail the JNT system and uncertainty components associated with the most recent National Institute of Standards and Technology (NIST) determination of the Boltzmann constant: k = 1.380642 9(69) × 10-23 J/K, with a relative standard uncertainty of 5.0 × 10-6 and relative offset of -4.05 × 10-6 from the Committee on Data for Science and Technology (CODATA) 2014 recommended value. We discuss the input circuits and the approach we used to match the frequency response of two noise sources. We present new measurements of the correlated noise of the 4 K on-chip resistors in the quantum-accurate, pseudorandom, voltage-noise source, which we used to estimate the correlated, frequency-dependent, nonthermal noise in our system. Finally, we contrast our system with those used in other measurements and speculate on future improvements.

Keratocyte apoptosis and not myofibroblast differentiation mark the graft/host interface at early time-points post-DSAEK in a cat model.

PURPOSE: To evaluate myofibroblast differentiation as an etiology of haze at the graft-host interface in a cat model of Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK). METHODS: DSAEK was performed on 10 eyes of 5 adult domestic short-hair cats. In vivo corneal imaging with slit lamp, confocal, and optical coherence tomography (OCT) were performed twice weekly. Cats were sacrificed and corneas harvested 4 hours, and 2, 4, 6, and 9 days post-DSAEK. Corneal sections were stained with the TUNEL method and immunohistochemistry was performed for α-smooth muscle actin (α-SMA) and fibronectin with DAPI counterstain. RESULTS: At all in vivo imaging time-points, corneal OCT revealed an increase in backscatter of light and confocal imaging revealed an acellular zone at the graft-host interface. At all post-mortem time-points, immunohistochemistry revealed a complete absence of α-SMA staining at the graft-host interface. At 4 hours, extracellular fibronectin staining was identified along the graft-host interface and both fibronectin and TUNEL assay were positive within adjacent cells extending into the host stroma. By day 2, fibronectin and TUNEL staining diminished and a distinct acellular zone was present in the region of previously TUNEL-positive cells. CONCLUSIONS: OCT imaging consistently showed increased reflectivity at the graft-host interface in cat corneas in the days post-DSAEK. This was not associated with myofibroblast differentiation at the graft-host interface, but rather with apoptosis and the development of a subsequent acellular zone. The roles of extracellular matrix changes and keratocyte cell death and repopulation should be investigated further as potential contributors to the interface optical changes.

Enhanced active cross-bridges during diastole: molecular pathogenesis of tropomyosin's HCM mutations.

Three HCM-causing tropomyosin (Tm) mutants (V95A, D175N, and E180G) were examined using the thin-filament extraction and reconstitution technique. The effects of Ca(2+), ATP, phosphate, and ADP concentrations on cross-bridge kinetics in myocardium reconstituted with each of these mutants were studied at 25°C, and compared to wild-type (WT) Tm at physiological ionic strength (200 mM). All three mutants showed significantly higher (2-3.5 fold) low Ca(2+) tension (T(LC)) and stiffness than WT at pCa 8.0. High Ca(2+) tension (T(HC)) was significantly higher for E180G than that for WT, whereas T(HC) of V95A and D175N was similar to WT; high Ca(2+) stiffness (Y(HC)) had the same trend. The Ca(2+) sensitivity of isometric force was significantly greater for V95A and E180G than for WT, whereas that of D175N remained the same as for WT; for all mutants, cooperativity was lower than for WT. Nine kinetic constants and the cross-bridge distribution were deduced using sinusoidal analysis. The number of force-generating cross bridges was similar among the D175N, E180G, and WT Tm forms, but it was significantly larger in the case of V95A than WT. We conclude that the increased number of actively cycling cross bridges at pCa 8 is the major cause of Tm mutation-related HCM pathogenesis, which may result in diastolic dysfunction. Decreased contractility (T(act)) in V95A and D175N may further contribute to the severity of myocyte hypertrophy and related prognosis of the disease.

Fabrication and mechanical properties of large-scale freestanding nanoparticle membranes.

Thin-film membranes consisting of nanoparticles are of interest in applications ranging from nanosieves to electric, magnetic, or photonic devices and sensors. However, the fabrication of large-scale membranes in a simple but controlled way has remained a challenge, due to the limited understanding of their mechanical properties. Systematic experiments on ultrathin, freestanding nanoparticle membranes of different core materials, core sizes, and capping ligands are reported. The results demonstrate that a drying-mediated self-assembly process can be used to create close-packed monolayer membranes that span holes tens of micrometers in diameter. Containing up to approximately 10(7) particles, these freely suspended layers exhibit remarkable mechanical properties with Young's moduli of the order of several GPa, independent of membrane size. Comparison of three different core-ligand combinations suggests that the membrane's elastic response is set by how tightly the ligands are bound to the particle cores and by the ligand-ligand interactions.