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This paper is devoted to the development of an innovative Matlab software, dedicated to the numerical analysis of two-dimensional elliptic problems, by means of the probabilistic approach. This approach combines features of the Monte Carlo random walk method with discretization and approximation techniques, typical for meshless methods. It allows for determination of an approximate solution of elliptic equations at the specified point (or group of points), without a necessity to generate large system of equations for the entire problem domain. While the procedure is simple and fast, the final solution may suffer from both stochastic and discretization errors. The attached Matlab software is based on several original author’s concepts. It permits the use of arbitrarily irregular clouds of nodes, non-homogeneous right-hand side functions, mixed type of boundary conditions as well as variable material coefficients (of anisotropic materials). The paper is illustrated with results of analysis of selected elliptic problems, obtained by means of this software.

© 2014, Springer-Verlag Berlin Heidelberg. Opportunistic oral infections caused by Candida albicans are frequent problems in immunocompromised patients. Management of such infections is limited due to the low number of antifungal drugs available, their relatively high toxicity and the emergence of antifungal resistance. Given these issues, our investigations have focused on novel derivatives of the antifungal antibiotic Nystatin A1, generated by modifications at the amino group of this molecule. The aims of this study were to evaluate the antifungal effectiveness and host cell toxicity of these new compounds using an in vitro model of oral candidosis based on a reconstituted human oral epithelium (RHOE). Initial studies employing broth microdilution, revealed that against planktonic C. albicans, Nystatin A1had lower minimal inhibitory concentration than novel derivatives. However, Nystatin A1was also markedly more toxic against human keratinocyte cells. Interestingly, using live/dead staining to assess C.albicans and tissue cell viability after RHOE infection, Nystatin A1derivatives were more active against Candida with lower toxicity to epithelial cells than the parent drug. Lactate dehydrogenase activity released by the RHOE indicated a fourfold reduction in tissue damage when certain Nystatin derivatives were used compared with Nystatin A1. Furthermore, compared with Nystatin A1, colonisation of the oral epithelium by C. albicans was notably reduced by the new polyenes. In the absence of antifungal agents, confocal laser scanning microscopy showed that C. albicans extensively invaded the RHOE. However, the presence of the novel derivatives greatly reduced or totally prevented this fungal invasion.

Meshless Finite Difference Method (MFDM) is nowadays a powerful engineering tool for numerical analysis of boundary value problems. Nowadays, its computational capabilities are not fully used mainly due to the lack of suitable commercial software. This paper briefly presents current state-of-the-art of the MFDM solution approach as well as deals with the selected computational aspects of the MFDM. A set of Matlab functions written by the author is attached to the paper. Techniques for generation of nodes, MFD stars, formulas, equations as well as local approximation technique and numerical integration schemes are discussed there.

This work is devoted to some recent developments in the Higher Order Approximation introduced to the Meshless Finite Difference Method (MFDM), and its application to the solution of boundary value problems in mechanics. In the MFDM, approximation of the sought function is described in terms of nodes rather than by means of any imposed structure like elements, regular meshes etc. Therefore, the MFDM, using arbitrarily irregular clouds of nodes using the Moving Weighted Least Squares (MWLS) approximation falls into the category of the Meshless Methods (MM). The MFDM, dating to early seventies, is one of the oldest and possibly the most developed one. In this paper considered are some techniques which lead to improvement of the MFDM solution�s quality. The main objective of this paper is the presentation and overview of new ideas and the development of the Higher Order solution approach in the MFDM provided by correction terms, preceded by a brief information about the current state-of-the art of this method. The main concept of the Higher Order Approximation (HOA) used here, is based on consideration of additional terms in the local Taylor expansion of the sought function. It shall be demonstrated that such a move may essentially improve, in many ways, efficiency and solution quality of the Higher Order MFDM. The Higher Order correction terms may be applied in many aspects of the MFDM solution approach. Among them one may distinguish the a-posteriori error estimation as well as adaptive solution process with multigrid strategy. Moreover, in the present work considered are: computational implementation of the Higher Order MFDM algorithms, examination of the above mentioned aspects using 1D and 2D benchmark tests, as well as an application of the Higher Order MFDM solution approach to selected boundary value problems in mechanics.

Two genes, LYS21 and LYS22, encoding isoforms of homocitrate synthase, an enzyme catalysing the first committed step in the lysine biosynthetic pathway, were disrupted in Candida albicans using the SAT1 flipper strategy. The double null lys21Δ/lys22Δ mutant lacked homocitrate synthase activity and exhibited lysine auxotrophy in minimal media that could be fully rescued by the addition of 0.5-0.6 mM L: -lysine. On the other hand, its virulence in vivo in the model of disseminated murine candidiasis appeared identical to that of the mother, wild-type strain. These findings strongly question a possibility of exploitation of homocitrate synthase and possibly also other enzymes of the lysine biosynthetic pathway as targets in chemotherapy of disseminated fungal infections.

The 3' part of the glucosamine-6-phosphate synthase gene from Histoplasma capsulatum was PCR amplified using degenerate primers designed from the known glucosamine-6-phosphate synthase gene sequences, cloned and sequenced. The computer analysis of the 676 bp sequence revealed the presence of two introns. The identities of the deduced amino acid sequence to the corresponding Saccharomyces cerevisiae and Candida albicans fragment are 65 and 63.8%, respectively.

The mycelial (M) form of Candida albicans is more sensitive to the action of the antibiotic tetaine than the yeast (Y) form. Tetaine, at low concentrations about 1 microgram/ml also inhibits Y-M transition. It causes severe deformation of cells, agglutination and inhibits septum formation in the yeast forms. Tetaine action is reversed by dipeptides in both forms and by tripeptides in M form. N-acetyl glucosamine is a powerful antagonist of tetaine action on both morphological forms. Tetaine action on mycelial forms is slightly antagonised by N-acetyl mannosamine and very powerfully by glutamine.

The antibiotic tetaine inhibits in Candida albicans the biosynthesis of two important cell wall constituents, chitin and mannoprotein. This effect is a consequence of inactivation of the enzyme glucosamine-6-phosphate synthetase. Due to the lack of glucosamine-6-phosphate the effective secretion of mannoprotein enzymes, acid phosphatase and invertase, by Candida albicans spheroplasts is inhibited. In the presence of tetaine, probably a modified mannoprotein, lacking a branched polymannan, is synthesized. The antibiotic action decreases the viability of Candida albicans cells, especially that of mycelial forms of this fungus.