Modelling the Density-Driven Discharge of Sandstone Blocks

The density-driven discharge of salt-laden sandstone blocks has been studied to provide a knowledge basis for the prediction of the contaminant release of abandoned mines when they are flooded. To this end the results of a model experiment, of simplified analytical models and of numerical simulations in 1D, 2D and 3D have been analysed. Simple analytical functions have been found which approximately describe the time-dependent discharge of salt mass at complete saturation. They depend on the material parameters, the dimensions and the outflow geometry of the blocks. The discharge through the basal face is described well by an exponential behaviour. If the outflow occurs solely through the lateral block faces an algebraic function has been fitted to the simulated curves. In this case similarities to directed transport models of statistical physics have been pointed out. The results facilitate the superposition of discharge functions for single sandstone blocks to yield the discharge behaviour of the whole mine.     

Synthesis of diastereomeric,deoxy and ring-expanded sulfone analogues of aigialomycin D

Several analogues of the fungal natural product aigialomycin D (AmD) have been synthesised. These include the stereoisomer 5′R,6′S-AmD, 2,4-di-deoxyAmD, 1′,2′,7′,8′-tetrahydroAmD and a 15-membered macrocyclic sulfone. Growth inhibitory activities of these compounds against the HL-60 leukaemic cell line were measured. The ring-expanded sulfone and tetrahydro-analogue were found to have similar IC₅₀ values to the natural product, whereas the 5′R,6′S-stereoisomer was inactive. Energy minimisation of AmD and the synthesised analogues resulted in a range of lowest energy conformers, from planar, open arrangements of the macrocycle in AmD and tetrahydroAmD to bent, L-shaped structures for the sulfone. The synthesis of methyl orsellinate was investigated and optimised as part of this work. A stereodivergent route to both enantiomers of the diol fragment from d-ribose was also achieved.     

UA62784 Is a cytotoxic inhibitor of microtubules, not CENP-E

A recent screen for compounds that selectively targeted pancreatic cancer cells isolated UA62784. We found that UA62784 inhibits microtubule polymerization in?vitro. UA62784 interacts with tubulin dimers ten times more potently than colchicine, vinblastine, or nocodazole. Competition experiments revealed that UA62784 interacts with tubulin at or near the colchicine-binding site. Nanomolar doses of UA62784 promote the accumulation of mammalian cells in mitosis, due to aberrant mitotic spindles, as shown by immunofluorescence and live cell imaging. Treatment of cancerous cell lines with UA62784 is lethal, following activation of apoptosis signaling. By monitoring mitotic spindle perturbations and apoptosis, we found that the effects of UA62784 and of some known microtubule-depolymerizing drugs are additive. Finally, high content screening of H2B-GFP HeLa cells revealed that low doses of UA62784 and vinblastine potentiate each other to inhibit proliferation.     

About de Smit��s question on flatness

Let ${\varphi : A \rightarrow B}$ be a flat morphism of Artin local rings with the same embedding dimension. Denote by ${\mathfrak{m}_A}$ the maximal ideal of A. Bart de Smit asked whether any finite B-module that is A-flat is B-flat. We prove the conjecture in embedding dimension one or two. In embedding dimension n, we prove the conjecture under an additional assumption on ${B/\mathfrak{m}_{A}B}$ .     

Mechanism of YF3 nanoparticle formation in reverse micelles

This article reports an investigation of the mechanism of YF(3) nanoparticle formation in two variants of the reverse microemulsion precipitation method. These two variants involve the addition of F(-), either as a microemulsion or directly as an aqueous solution, to Y(3+) dispersed in nonionic reverse micelles. The two methods yield amorphous and single-crystal nanoparticles, respectively. The kinetics of reagent mixing are studied by (19)F NMR and colorimetric model reactions, and the particle growth is monitored by TEM. Mixing and nucleation are shown to occur within seconds to minutes whereas particle growth continues for 4 to 48 h, depending on the particle type. Moreover, the growth rate remains constant during most of the growth period, indicating that Ostwald ripening is the most probable growth mechanism. The single-emulsion method also produces a minority amorphous population that exhibits significantly different growth kinetics, attributed to a coagulation mechanism. Secondary growth experiments, involving the addition of precursor ions to mature particles, have been conducted to evaluate the relative importance of nucleation and the competitive growth of existing particle populations. The key differences between the two methods reside in the nucleation step. In the case of the classical method, nucleation occurs upon intermicellar collisions and under conditions of comparable concentrations of Y(3+) and F(-). This method generates more numerous stable nuclei and smaller particles. In the single-microemulsion method, nucleation occurs in the presence of excess F(-) through the interaction of Y(3+)-containing micelles with microdroplets of aqueous F(-). These conditions lead to the formation of crystalline particles and a wider size distribution of unstable nuclei.     

Photoinduced Charge Transfer in a Conformational Switching Chlorin Dimer–Azafulleroid in Polar and Nonpolar Media

In the present study, a biomimetic reaction center model, that is, a molecular triad consisting of a chlorin dimer and an azafulleroid, is synthesized and its photophysical properties are studied in comparison with the corresponding molecular dyad, which consists only of a chlorin monomer and an azafulleroid. As evidenced by ¹H NMR, UV/Vis, and fluorescence spectroscopy, the chlorin dimer–azafulleroid folds in nonpolar media into a C₂‐symmetric geometry through hydrogen bonding, resulting in appreciable electronic interactions between the chlorins, whereas in polar media the two chlorins diverge from contact. Femtosecond transient absorption spectroscopy studies reveal longer charge‐separated states for the chlorin dimer–azafulleroid; ≈1.6 ns in toluene, compared with the lifetime of ≈0.9 ns for the corresponding chlorin monomer–azafulleroid in toluene. In polar media, for example, benzonitrile, similar charge‐separated states are observed, but the lifetimes are inevitably shorter: 65 and 73 ps for the dimeric and monomeric chlorin–azafulleroids, respectively. Nanosecond transient absorption and singlet oxygen phosphorescence studies corroborate that in toluene, the charge‐separated state decays indirectly via the triplet excited state to the ground state, whereas in benzonitrile, direct recombination to the ground state is observed. Complementary DFT studies suggest two energy‐minima conformations, that is, a folded chlorin dimer–azafulleroid, which is present in nonpolar media, and another conformation in polar media, in which the two hydrophobic chlorins wrap the azafulleroid. Inspection of the frontier molecular orbitals shows that in the folded conformation, the HOMO on each chlorin is equivalent and is shared owing to partial π–π overlap, resulting in delocalization of the conjugated π electrons, whereas the wrapped conformation lacks this stabilization. As such, the longer charge‐separated lifetime for the dimer is rationalized by both the electron donor–acceptor separation distance and the stabilization of the radical cation through delocalization. The chlorin folding seems to change the photophysical properties in a manner similar to that observed in the chlorophyll dimer in natural photosynthetic reaction centers.     

MALDI-TOF-MS Directly Combined with TLC: A Review of the Current State

Thin-layer chromatography (TLC) is a widely used, fast and inexpensive method for separating complex mixtures. Unfortunately, the quality of achievable separation represents only one side. An additional problem is the unambiguous assignment of the obtained spots to defined compounds. Clear identification of spots is often not possible by common staining methods and comparison with a known reference compound. Therefore, further analytical techniques are mostly required for further structural elucidation. Mass spectrometry (MS) is a suitable method due to its high sensitivity. In particular, matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) MS is a modern soft-ionization technique that may be easily combined with TLC. This review summarizes the so far available knowledge about direct TLC–MALDI combination and gives an overview about different molecule classes that have already been successfully analyzed by this approach. This review critically summarizes the capabilities and limitations of the direct MALDI–TLC combination and highlights in particular the problems related to sample preparation and instrumentation.     

Blood Compatibility of Multilayered Polyelectrolyte Films Containing Immobilized Gold Nanoparticles

Surface material functionalization including layer‐by‐layer (LbL) polyelectrolyte films with incorporated nanoparticles is a growing field with a wide range of biomedical applications: drug reservoirs, medical devices, or tissue engineering. In parallel, gold nanoparticles (AuNPs) can be grafted by drugs and sensitive molecules using simple protocols. This study shows that AuNP behavior is modified when they are entrapped into three partner LbL films in comparison to the colloidal solution. A polycationic (polyallylamine hydrochloride (PAH)) and a polyanionic (polyacrylic acid (PAA)) polymer is used to build films based on three cycles ((PAH/AuNP/PAA)₃). To investigate the interaction with biomolecules and cells, three different films are developed changing the outer layer (either PAH or AuNP or PAA) with the same number of AuNP deposit. The best biocompatibility is observed with a polyacrylic acid outer layer. Due to the high capacity of drug grafting on gold nanoparticles, the results seem promising for the development of nanostructured biomedical devices.     

Testing statistical significance of multivariate time series analysis techniques for epileptic seizure prediction

Nonlinear time series analysis techniques have been proposed to detect changes in the electroencephalography dynamics prior to epileptic seizures. Their applicability in practice to predict seizure onsets is hampered by the present lack of generally accepted standards to assess their performance. We propose an analytic approach to judge the prediction performance of multivariate seizure prediction methods. Statistical tests are introduced to assess patient individual results, taking into account that prediction methods are applied to multiple time series and several seizures. Their performance is illustrated utilizing a bivariate seizure prediction method based on synchronization theory.