Mechanism of azole antifungal activity as determined by liquid chromatographic/mass spectrometric monitoring of ergosterol biosynthesis

A liquid chromatography/mass spectrometry (LC/MS) method for separation and characterization of ergosterol biosynthetic precursors was developed to study the effect of Posaconazole on sterol biosynthesis in fungi. Ergosterol biosynthetic precursors were characterized from their electron ionization mass spectra acquired by a normal-phase chromatography, particle beam LC/MS method. Fragment ions resulting from cleavage across the D-ring and an abundant M - 15 fragment ion were diagnostic for methyl substitution at C-4 and C-14. Comparison of the sterol profile in control and treated Candida albicans incubations showed depletion of ergosterol and accumulation of C-4 and C-14 methyl-substituted sterols following treatment with Posaconazole. These C-4 and C-14 methyl sterols are known to be incapable of sustaining cell growth. The results demonstrate that Posaconazole exerts its antifungal activity by inhibition of ergosterol biosynthesis. Furthermore, Posaconazole appears to disrupt ergosterol biosynthesis by inhibition of lanosterol 14alpha-demethylase.     

Three-Dimensional Analytical Solution for an Axisymmetric Biharmonic Problem

In this paper, we propose a method for the solution of the axisymmetric boundary value problem for a finite elastic cylinder with assigned stress and/or displacements acting on the ends and side. The technique utilizes the Love representation, which allows for reduction of the solution of the elastic problem to the search for a biharmonic function on a cylindrical domain. In the solution method suggested here, we write the Love function with a Bessel expansion and analyze in detail the conditions under which it is possible to differentiate the expansion term by term. We show that this is possible only for a restricted class of elastic solutions. In the general case, we introduce two new auxiliary functions of the z-coordinate. In this way, we obtain the general form of the axisymmetric biharmonic function, which is discussed in relation to certain specific boundary conditions applied on the side and ends of the cylinder. We obtain an exact explicit solution of practical interest for a cylinder with free ends and assigned displacements applied to the side.     

Existence of extremals for the Maz’ya and for the Caffarelli–Kohn–Nirenberg inequalities

This paper deals with some Sobolev-type inequalities with weights that were proved by Maz’ya in 1980 and by Caffarelli–Kohn–Nirenberg in 1984.     

Integration of InGaP/GaAs/Ge triple‐junction solar cells on deeply patterned silicon substrates

We report preliminary results on InGaP/InGaAs/Ge photovoltaic cells for concentrated terrestrial applications, monolithically integrated on engineered Si(001) substrates. Cells deposited on planar Ge/Si(001) epilayers, grown by plasma‐enhanced chemical vapor deposition, provide good efficiency and spectral response, despite the small thickness of the Ge epilayers and a threading dislocation density as large as 10⁷/cm². The presence of microcracks generated by the thermal misfit is compensated by a dense collection grid that avoids insulated areas. In order to avoid the excessive shadowing introduced by the use of a dense grid, the crack density needs to be lowered. Here, we show that deep patterning of the Si substrate in blocks can be an option, provided that a continuous Ge layer is formed at the top, and it is suitably planarized before the metalorganic chemical vapor deposition. The crack density is effectively decreased, despite that the efficiency is also lowered with respect to unpatterned devices. The reasons of this efficiency reduction are discussed, and a strategy for improvement is proposed and explored. Full morphological analysis of the coalesced Ge blocks is reported, and the final devices are tested under concentrated AM1.5D spectrum. Copyright © 2016 John Wiley & Sons, Ltd.     

Simultaneous Differential Pulse Voltammetric Determination of Ascorbic Acid and Caffeine in Pharmaceutical Formulations Using a Boron‐Doped Diamond Electrode

A cathodically pretreated boron‐doped diamond electrode was used for the simultaneous anodic determination of ascorbic acid (AA) and caffeine (CAF) by differential pulse voltammetry. Linear calibration curves (r=0.999) were obtained from 1.9×10^?5 to 2.1×10^?4 mol L^?1 for AA and from 9.7×10^?6 to 1.1×10^?4 mol L^?1 for CAF, with detection limits of 19 μmol L^?1 and 7.0 μmol L^?1, respectively. This method was successfully applied for the determination of AA and CAF in pharmaceutical formulations, with results equal to those obtained using a HPLC reference method.     

Photodegradation of poly(3-hydroxybutyrate)

The effect of ultraviolet radiation on the properties of poly(3-hydroxybutyrate) (PHB) was studied. The PHB investigated is produced from microbial fermentation using saccharose from sugarcane as the carbon source to the bacteria. The material was exposed to artificial UV-A radiation for 3, 6, 9 and 12 weeks. The photodegradation effect was followed by changes of molecular weight, of chemical and crystalline structures, of thermal, morphological, optical and mechanical properties, as well as of biodegradability. The experimental results showed that PHB undergoes both chain scission and crosslinking reactions, but the continuous decrease in its mechanical properties and the low amount of gel content upon UV exposure indicated that the scission reactions were predominant. Molar mass, melting temperature and crystallinity measurements for two layers of PHB samples with different depth suggested that the material has a strong degradation profile, which was attributed to its dark colour that restricted the transmission of light. Previous photodegradation initially delayed PHB biodegradability, due to the superficial increase in crystallinity seen with UV exposure. The possible reactions taking place during PHB photodegradation were presented and discussed in terms of the infrared and nuclear magnetic resonance spectra. A reference peak (internal standard) in the infrared spectra was proposed for PHB photodegradation.     

Macromolecular Diffusion in Self-Assembling Biodegradable Thermosensitive Hydrogels

Hydrogel formation triggered by a change in temperature is an attractive mechanism for in situ gelling biomaterials for pharmaceutical applications such as the delivery of therapeutic proteins. In this study, hydrogels were prepared from ABA triblock polymers having thermosensitive poly(N-(2-hydroxypropyl) methacrylamide lactate) flanking A-blocks and hydrophilic poly(ethylene glycol) B-blocks. Polymers with fixed length A blocks (~22 kDA) but differing PEG-midblock lengths (2, 4 and 10 kDa) were synthesized and dissolved in water with dilute fluorescein isothiocyanate (FITC)-labeled dextrans (70 and 500 kDA). Hydrogels encapsulating the dextrans were formed by raising the temperature. Fluorescence recovery after photobleaching (FRAP) studies showed that diffusion coefficients and mobile fractions of the dextran dyes decreased upon elevating temperatures above 25 °C. Confocal laser scanning microscopy and cryo-SEM demonstrated that hydrogel structure depended on PEG block length. Phase separation into polymer-rich and water-rich domains occurred to a larger extent for polymers with small PEG blocks compared to polymers with a larger PEG block. By changing the PEG block length and thereby the hydrogel structure, mobility of FITC-dextran could be tailored. At physiological pH the hydrogels degraded over time by ester hydrolysis, resulting in increased mobility of the encapsulated dye. Since diffusion can be controlled according to polymer design and concentration, plus temperature, these biocompatible hydrogels are attractive as potential in situ gelling biodegradable materials for macromolecular drug delivery.     

Beliefs and engagement structures: behind the affective dimension of mathematical learning

Beliefs influencing students’ mathematical learning and problem solving are structured and intertwined with larger affective and cognitive structures. This theoretical article explores a psychological concept we term an engagement structure, with which beliefs are intertwined. Engagement structures are idealized, hypothetical constructs, analogous in many ways to cognitive structures. They describe complex “in the moment” affective and social interactions as students work on conceptually challenging mathematics. We present engagement structures in a self-contained way, paying special attention to their theoretical justification and relation to other constructs. We suggest how beliefs are characteristically woven into their fabric and influence their activation. The research is based on continuing studies of middle school students in inner-city classrooms in the USA.     

Solvability of the Dirichlet Problem in W~（2,p ）for a Class of Elliptic Equations with Singular Data

We prove an existence and uniqueness result for the Dirichlet problem for a class of elliptic equations with singular data in weighted Sobolev spaces.