Topical safety and vasoconstrictive assay-based bioequivalence of a new reformulated mometasone cream

Objectives: A new improved mometasone furoate (Elocon?) cream with an emulsification system that produces a stable emulsion has been developed. In order to register the product in various markets, it was essential to ensure the cream was topically well tolerated and that it was bioequivalent to the reference product.

Methods: Phase I clinical studies were performed to assess the local safety and tolerability upon multiple dosing of this new cream as well as to assess the single-dose bioequivalence relative to the marketed product. Bioequivalence was assessed using a vasoconstrictive assay (VCA) after a dose-duration pilot study was completed with the marketed Elocon cream.

Key findings: The new mometasone cream and its vehicle were nonirritating in healthy subjects during 21-day patch application (MCII <0.025). The positive control was moderately irritating in the same study. The pivotal VCA study enrolled 162 subjects with 105 detectors included in the analysis of bioequivalence. In the 105 detectors, the ratio (×100%) of AUEC values at ED₅₀ for test vs. standard (90% CI) was 112.91% (105.55, 120.87), within the bioequivalence criteria of (80, 125).

Conclusions: These studies supported the registration of reformulated mometasone cream in various markets.     

Covalent functionalization of zinc oxide nanowires for high sensitivity p-nitrophenol detection in biological systems

High-quality zinc oxide (ZnO) nanowires were synthesized using the atmospheric chemical vapor deposition technique and were appropriately characterized. Subsequently, the nanowire surface was covalently grafted with 1-pyrenebutyric acid (PBA) fluorophore, and surface-sensitive X-ray photoelectron spectroscopy and Fourier transform infrared-attenuated total reflectance spectroscopy were utilized to confirm the functionalization of 1-pyrenebutyric acid on the nanowire surface. Additionally, photoluminescence (PL) measurements were used to evaluate the optical behavior of pristine nanowires. Through fluorescence quenching of 1-pyrenebutyric acid by p-nitrophenol, a detection limit of 28 ppb was estimated. Based on these findings, ZnO nanowires functionalized with 1-pyrenebutyric acid are envisaged as extremely sensitive platforms for the ultra-trace detection of p-nitrophenol in biological systems.     

Efficient and scalable omniscient debugging for model transformations

This paper discusses a technique for supporting omniscient debugging for model transformations, which are used to define core operations on software and system models. Similar to software systems developed using general-purpose languages, model transformations are also subject to human error and may possess defects. Existing model-driven engineering tools provide stepwise execution to aid developers in locating and removing defects. In this paper, we describe our investigation into a technique and associated algorithms that support omniscient debugging features for model transformations. Omniscient debugging enables enhanced navigation and exploration features during a debugging session beyond those possible in a strictly stepwise execution environment. Finally, the execution time performance is comparatively evaluated against stepwise execution, and the scalability (in terms of memory usage) is empirically investigated.     

Operando infrared spectroscopy of the fuel cell membrane electrode assembly Nafion–platinum interface

The Nafion–Pt interfaces in membrane electrode assemblies of operating fuel cells were studied by operando infrared spectroscopy. The potential dependence of atop adsorbed CO peak frequencies were measured over the potential range of 0–600 mV (vs. NHE) at 60 °C. Complex Stark tuning of peak frequencies arise from a combination of potential dependent coverage effects, and changes in the extent of back-donation from the metal d-band to the renormalized 2π^∗ MO of CO_ads. The Nafion–Pt interface was studied at higher potentials (initiating at open circuit) by examining platinum reflectivity as a function of electrode potential. The oxygen reduction onset-current is coincident with the observance of a 2% step-increase in Pt reflectivity and emergence of Nafion–Pt interface spectra.     

Existentially informed HIV-related psychotherapy.

This article describes an existentially informed approach to conducting psychotherapy with individuals living with the human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS). Uses of existential concepts to guide a holistic conceptualization of the individual and illuminate core existential concerns and dilemmas in confronting HIV-related challenges are delineated. Applications of existential ideas regarding psychotherapy process and technique in HIV-related psychotherapy also are illustrated. It is concluded that existential psychotherapy offers a conceptual framework that is especially well suited to the work of psychotherapy with individuals living with HIV disease, although the approach has received only limited attention in the HIV-related psychotherapy literature. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A robust mixed integer linear programming framework for underground cut-and-fill mining production scheduling

ABSTRACT

A review of general optimization studies that have been proposed for underground mining shows that previous works lack flexibility, operability and practicality in relation to cut-and-fill mining production scheduling. This paper presents a robust mixed integer linear programming (MILP) formulation for underground cut-and-fill mining. The objective function of the model is to maximize the net present value (NPV) of the operation while meeting all mining and processing operational and technical constraints. The MILP model features stope development and extraction sequencing constraints, mining and processing tonnage fluctuation constraints, and extraction duration and active levels control constraints. These features make the model more practical and expandable. The MILP model is verified and validated with two case studies from an existing mine and the results are compared with the actual mining strategy. The comparison shows a 9% to 17% improved NPV in both case studies resulting from mining higher grades and processing less tonnes thereby generating a better cash flow.     

Application of the MAHDS Method for Multiple Alignment of Highly Diverged Amino Acid Sequences

The aim of this work was to compare the multiple alignment methods MAHDS, T-Coffee, MUSCLE, Clustal Omega, Kalign, MAFFT, and PRANK in their ability to align highly divergent amino acid sequences. To accomplish this, we created test amino acid sequences with an average number of substitutions per amino acid (x) from 0.6 to 5.6, a total of 81 sets. Comparison of the performance of sequence alignments constructed by MAHDS and previously developed algorithms using the CS and Z score criteria and the benchmark alignment database (BAliBASE) indicated that, although the quality of the alignments built with MAHDS was somewhat lower than that of the other algorithms, it was compensated by greater statistical significance. MAHDS could construct statistically significant alignments of artificial sequences with x ≤ 4.8, whereas the other algorithms (T-Coffee, MUSCLE, Clustal Omega, Kalign, MAFFT, and PRANK) could not perform that at x > 2.4. The application of MAHDS to align 21 families of highly diverged proteins (identity < 20%) from Pfam and HOMSTRAD databases showed that it could calculate statistically significant alignments in cases when the other methods failed. Thus, MAHDS could be used to construct statistically significant multiple alignments of highly divergent protein sequences, which accumulated multiple mutations during evolution.