Photosensitization of human skin cell lines by ATMPn (9-acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene) in vitro: mechanism of action

9-Acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene (ATMPn) is a promising new photosensitizer characterized by high absorption around 640 nm and high singlet oxygen yield. To study the mechanism of action in vitro we have investigated uptake, intracellular localization, cell survival and ultrastructural changes following photodynamic treatment in human cell lines derived from the skin (SCL1 and SCL2, squamous cell carcinoma; HaCaT keratinocytes; N1 fibroblasts). Using flow cytometry we have determined the cellular fluorescence as a marker for the uptake of ATMPn after incubation for 60 min. Co-staining with ATMPn and fluorescent dyes specific for cell organelles reveals an intracellular localization of ATMPn in lysosomes. Following irradiation using an incoherent light source (580-740 nm) and a light fluence of 24 J cm-2, phototoxicity is determined by means of the 3-4.5 dimethylthiazol-2,5 diphenyl tetrazolium bromide (MTT) assay. For all cell lines ATMPn concentrations above 15 nM yield a significant phototoxic effect. The 50% effective concentration, EC50, for SCL1 cells is 11.2 +/- 2.9 nM ATMPn. ATMPn uptake and phototoxicity are more effective for HaCaT and SCL1 as compared to SCL2 and N1 cells. Growth curves confirmed the results of the MTT assay. Because of the high lysosomal accumulation of ATMPn, already low photosensitizer concentrations without dark toxicity yield a high photodynamic effect. Immunofluorescence and electron microscopy reveal damage to tonofilaments, plasma membrane and mitochondria, indicating a mechanism unrelated to apoptosis. A dose yielding complete cell killing, as needed for oncological indications, might lead to necrosis, whereas lower sub-lethal doses result in induction of apoptosis.     

Convergence analysis of high-order time-splitting pseudo-spectral methods for rotational Gross–Pitaevskii equations

A convergence analysis of time-splitting pseudo-spectral methods adapted for time-dependent Gross–Pitaevskii equations with additional rotation term is given. For the time integration high-order exponential operator splitting methods are studied, and the space discretization relies on the generalized-Laguerre–Fourier spectral method with respect to the $(x,y)$ -variables as well as the Hermite spectral method in the $z$ -direction. Essential ingredients in the stability and error analysis are a general functional analytic framework of abstract nonlinear evolution equations, fractional power spaces defined by the principal linear part, a Sobolev-type inequality in a curved rectangle, and results on the asymptotical distribution of the nodes and weights associated with Gauß–Laguerre quadrature. The obtained global error estimate ensures that the nonstiff convergence order of the time integrator and the spectral accuracy of the spatial discretization are retained, provided that the problem data satisfy suitable regularity requirements. A numerical example confirms the theoretical convergence estimate.     

Modified defect correction algorithms for ODEs. Part II: Stiff initial value problems

As shown in part I of this paper and references therein, the classical method of Iterated Defect Correction (IDeC) can be modified in several nontrivial ways, extending the flexibility and range of applications of this approach. The essential point is an adequate definition of the defect, resulting in a significantly more robust convergence behavior of the IDeC iteration, in particular, for nonequidistant grids. The present part II is devoted to the efficient high-order integration of stiff initial value problems. By means of model problem investigation and systematic numerical experiments with a set of stiff test problems, our new versions of defect correction are systematically evaluated, and further algorithmic measures are proposed for the stiff case. The performance of the different variants under consideration is compared, and it is shown how strong coupling between non-stiff and stiff components can be successfully handled. AMS subject classification 65L05 Supported by the Austrian Research Fund (FWF) grant P-15030.     

Bindungstheoretische Untersuchungen von Bor-Phosphor-Wasserstoff-Verbindungen mit semiempirischen SCF-Verfahren

The applicability of theCNDO/2 method for compounds containing boron, phosphorus and hydrogen is tested, comparing the results with ab initio calculations. Good agreement is found for most data; for P–H bonds, however, some methodical artefacts are found, leading to erroneous results, especially in regard to charge densities. An imperfect parametrization of phosphorus is supposed to be responsible for these artefacts.Calculations were performed for a recently prepared compound, -phosphinodiborane, and one possible isomer, in their respectiveCNDO minimum geometries. The energies obtained lead to the same predictions about their relative stability as is found experimentally.Bonding is discussed by means of localized molecular orbitals, and the hybridization model, frequently used for such species, is tested critically.     

Proteome profiling of keratinocytes transforming to malignancy

To shed light on the multistep process of squamous cell carcinoma development and the underlying pathologic mechanisms, we performed comparative proteome analysis of keratinocytes, keratinocytes stimulated with Il‐1beta, and A431 epidermoid carcinoma cells. Fractionation of the cells into supernatant, nucleus, and cytoplasm was followed by protein separation, proteolytic digest, and nano‐LC separation, and fragmentation using an ion trap mass spectrometer. Specific bioinformatics tools were used to generate a list of keratinocyte‐specific proteins. Ninety percent of these proteins were found to be upregulated in keratinocytes versus the A431 cells. Classification of the identified proteins by biologic function and gene set enrichment analysis revealed that keratinocytes produced more proteins involved in cell differentiation, cell adhesion, cell junction, calcium ion, calmodulin binding, cytoskeleton organization, and cytokinesis, whereas A431 produced more proteins involved in cell cycle checkpoint, cell cycle process, RNA processing and transport, DNA damage and repair, RNA and DNA binding, and chromatin remodeling. The protein signatures of A431 and normal keratinocytes treated with IL‐1beta showed marked similarity, confirming that inflammation is an important step in malignant transformation in nonmelanoma skin cancer. Thus, proteome profiling and bioinformatic processing may support the understanding of the underlying mechanisms, with the potential to facilitate development of early biomarkers and patient‐tailored therapy.     

Modified Defect Correction Algorithms for ODEs. Part I: General Theory

The well-known method of Iterated Defect Correction (IDeC) is based on the following idea: Compute a simple, basic approximation and form its defect w.r.t. the given ODE via a piecewise interpolant. This defect is used to define an auxiliary, neighboring problem whose exact solution is known. Solving the neighboring problem with the basic discretization scheme yields a global error estimate. This can be used to construct an improved approximation, and the procedure can be iterated. The fixed point of such an iterative process corresponds to a certain collocation solution. We present a variety of modifications to this algorithm. Some of these have been proposed only recently, and together they form a family of iterative techniques, each with its particular advantages. These modifications are based on techniques like defect quadrature (IQDeC), defect interpolation (IPDeC), and combinations thereof. We investigate the convergence on locally equidistant and nonequidistant grids and show how superconvergent approximations can be obtained. Numerical examples illustrate our considerations. The application to stiff initial value problems will be discussed in Part II of this paper.     

Iterative diagonalization in augmented plane wave based methods in electronic structure calculations

Due to the increased computer power and advanced algorithms, quantum mechanical calculations based on Density Functional Theory are more and more widely used to solve real materials science problems. In this context large nonlinear generalized eigenvalue problems must be solved repeatedly to calculate the electronic ground state of a solid or molecule. Due to the nonlinear nature of this problem, an iterative solution of the eigenvalue problem can be more efficient provided it does not disturb the convergence of the self-consistent-field problem. The blocked Davidson method is one of the widely used and efficient schemes for that purpose, but its performance depends critically on the preconditioning, i.e. the procedure to improve the search space for an accurate solution. For more diagonally dominated problems, which appear typically for plane wave based pseudopotential calculations, the inverse of the diagonal of (H ? ES) is used. However, for the more efficient “augmented plane wave + local-orbitals” basis set this preconditioning is not sufficient due to large off-diagonal terms caused by the local orbitals. We propose a new preconditioner based on the inverse of (H ? λS) and demonstrate its efficiency for real applications using both, a sequential and a parallel implementation of this algorithm into our WIEN2k code.     

Synthese und Struktur von assoziiertem μ-Phosphinodiboran und von phosphorsubstituierten Derivaten

Associated -phosphinodiborane, (-H₂PB₂H₅) _n , is formed in the reaction of H₂P(BH₃)₂Na with HCl in diethyl ether solution at –96°C. The formation of B–H–B bridges is demonstrated by IR and¹¹B-NMR spectra. (-H₂PB₂H₅) _n decomposes thermally to diborane and polymeric phosphinoborane analogous to -H₂NB₂H₅. Other phosphorus substituted -phosphinodiboranes associated via B–H–B bridges are formed in the reaction of the salts (CH₃)PH(BH₃)₂Li, (CH₃)₂P(BH₃)₂Li, andPhPH(BH₃)₂Li with HCl.

---

---

Mit 6 Abbildungen

---

Herrn Professor Dr.E. Hayek zum 70. Geburtstag gewidmet.     

An approximate eigensolver for self-consistent field calculations

In this paper, we give a comprehensive error analysis for an approximate solution method for the generalized eigenvalue problems arising for instance in the context of electronic structure computations based on density functional theory. The solution method has been demonstrated to excel as compared to established solvers in both computational effort and scaling for parallelization. Here we estimate the improvement provided by our proposed subspace method starting from the initial approximations for instance provided in the course of the self-consistent field iteration, showing that in general the approximation quality is improved by our method to yield sufficiently accurate eigenvalues.