The site of synthesis of the iron-sulfur subunits of the flavoprotein and iron-protein fractions of human NADH dehydrogenase

The site of synthesis of the iron-sulfur subunits of the flavoprotein and iron-protein fractions of the human respiratory chain NADH dehydrogenase has been investigated to test the possibility that any of them is synthesized in mitochondria. For this purpose, antibodies specific for individual subunits of the bovine enzyme, which cross- reacted with the homologous human subunits in immunoblot assays, were tested against HeLa cell mitochondrial proteins labeled in vivo with [35S]methionine in the absence or presence of inhibitors of mitochondrial or cytoplasmic protein synthesis. The results clearly indicated that all the iron-sulfur subunits of the flavoprotein and iron-protein fractions of human complex I are synthesized in the cytosol and are, therefore, encoded in nuclear genes

Giant Stark effect in the emission of single semiconductor quantum dots

We study the quantum-confined Stark effect in single InAs/GaAs quantum dots embedded within a AlGaAs/GaAs/AlGaAs quantum well. By significantly increasing the barrier height we can observe emission from a dot at electric fields of -500 kV/cm, leading to Stark shifts of up to 25 meV. Our results suggest this technique may enable future applications that require self-assembled dots with transitions at the same energy

Unification in the Description Logic EL

The Description Logic EL has recently drawn considerable attention since, on the one hand, important inference problems such as the subsumption problem are polynomial. On the other hand, EL is used to define large biomedical ontologies. Unification in Description Logics has been proposed as a novel inference service that can, for example, be used to detect redundancies in ontologies. The main result of this paper is that unification in EL is decidable. More precisely, EL-unification is NP-complete, and thus has the same complexity as EL-matching. We also show that, w.r.t. the unification type, EL is less well-behaved: it is of type zero, which in particular implies that there are unification problems that have no finite complete set of unifiers.Comment: 31page

Unique structural properties associated with mouse prion Δ105-125 protein

Murine prion protein deleted for residues 105-125 is intrinsically neurotoxic and mediates a TSE-like phenotype in transgenic mice. Equivalent and overlapping deletions were expressed in E.coli, purified and analyzed. Among mutants spanning the region 95-135, a construct lacking solely residues 105-125 had distinct properties when compared with the full-length prion protein 23-231 or other deletions. This distinction was also apparent followed expression in eukaryotic cells. Unlike the full-length protein, all deletion mutants failed to bind to synthetic membranes in vitro. These data suggest a novel structure for the 105-125 deleted variant that may relate to its biological propertie

Budget impact of adding ivabradine to standard of care in patients with chronic systolic heart failure in the United States

BACKGROUND: Heart failure (HF) costs $21 billion annually in direct health care costs, 80 OBJECTIVE: To estimate the budget impact of ivabradine from a U.S. commercial payer perspective. METHODS: A budget impact model estimated the per-member-per month (PMPM) impact of introducing ivabradine to existing formularies by comparing a reference scenario (SoC) and a new drug scenario (ivabradine + SoC) in hypothetical 1 million-member commercial and Medicare Advantage plans. In both scenarios, U.S. claims data were used for the reference cumulative annual rates of hospitalizations (HF, non-HF cardiovascular [CV], and non-CV), and hospitalization rates were adjusted using SHIFT data. The model controlled for mortality risk using SHIFT and U.S. life table data, and hospitalization costs were obtained from U.S. claims data: HF-related =$37,507; non-HF CV = $28,951; and non-CV =$17,904. The annualized wholesale acquisition cost of ivabradine was $4,500, with baseline use for this new drug at 2 RESULTS: Based on the approved U.S. indication, approximately 2,000 commercially insured patients from a 1 million-member commercial plan were eligible to receive ivabradine. Ivabradine resulted in a PMPM cost savings of$0.01 and $0.04 in years 1 and 3 of the core model, respectively. After including the acquisition price for ivabradine, the model showed a decrease in total costs in the commercial ($991,256 and $474,499, respectively) and Medicare populations ($13,849,262 and $4,280,291, respectively) in year 1. This decrease was driven by ivabradine’s reduction in hospitalization rates. For the core model, the estimated pharmacy-only PMPM in year 1 was$0.01 for the commercial population and $0.24 for the Medicare Advantage population. CONCLUSIONS: Adding ivabradine to SoC led to lower average annual treatment costs. The negative PMPM budget impact indicates that ivabradine is an affordable option for U.S. payers

Impacts of composition and beta irradiation on phase separation in multiphase amorphous calcium borosilicates

Borosilicate glasses for nuclear waste applications are limited in waste loading by the precipitation of water-soluble molybdates. In order to increase storage efficiency, new compositions are sought out that trap molybdenum in a water-durable CaMoO4 crystalline phase. Factors affecting CaMoO4 combination and glass-in-glass phase separation in calcium borosilicate systems as a function of changing [MoO3] and [B2O3] are examined in this study in order to understand how competition for charge balancers affects phase separation. It further examines the influence of radiation damage on structural modifications using 0.77 to 1.34 GGy of 2.5 MeV electron radiation that replicates inelastic collisions predicted to occur over long-term storage. The resulting microstructure of separated phases and the defect structure were analyzed using electron microscopy, XRD, Raman and EPR spectroscopy prior to and post irradiation. Synthesized calcium borosilicates are observed to form an unusual heterogeneous microstructure composed of three embedded amorphous phases with a solubility limit ~ 2.5 mol% MoO3. Increasing [B2O3] increased the areas of immiscibility and order of (MoO4)2 − anions, while increasing [MoO3] increased both the phase separation and crystallization temperature resulting in phases closer to metastable equilibrium, and initiated clustered crystallization for [MoO3] > 2.5 mol%. β-irradiation was found to have favorable properties in amorphous systems by creating structural disorder and defect assisted ion migration that thus prevented crystallization. It also increased reticulation in the borosilicate network through 6-membered boroxyl ring and Si ring cleavage to form smaller rings and isolated units. This occurred alongside an increased reduction of Mo6 + with dose that can be correlated to molybdenum solubility. In compositions with existing CaMoO4 crystallites, radiation caused a scattering effect, though the crystal content remained unchanged. Therefore β-irradiation can preferentially prevent crystallization in calcium borosilicates for [MoO3] < 2.5 mol%, but has a smaller impact on systems with existing CaMoO4 crystallites

Tunable Indistinguishable Photons From Remote Quantum Dots

Single semiconductor quantum dots have been widely studied within devices that can apply an electric field. In the most common system, the low energy offset between the InGaAs quantum dot and the surrounding GaAs material limits the magnitude of field that can be applied to tens of kVcm^-1, before carriers tunnel out of the dot. The Stark shift experienced by the emission line is typically 1 meV. We report that by embedding the quantum dots in a quantum well heterostructure the vertical field that can be applied is increased by over an order of magnitude whilst preserving the narrow linewidths, high internal quantum efficiencies and familiar emission spectra. Individual dots can then be continuously tuned to the same energy allowing for two-photon interference between remote, independent, quantum dots