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.     

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.     

Existence and Non-Existence Results for Quasilinear Elliptic Exterior Problems with Nonlinear Boundary Conditions

Existence and non-existence results are established for quasilinear elliptic problems with nonlinear boundary conditions and lack of compactness. The proofs combine variational methods with the geometrical feature, due to the competition between the different growths of the nonlinearities.