Photodynamic therapy of human glioma spheroids using 5-aminolevulinic acid

The response of human glioma spheroids to 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) is investigated. A two-photon fluorescence microscopy technique is used to show that human glioma cells readily convert ALA to protoporphyrin IX throughout the entire spheroid volume. The central finding of this study is that the response of human glioma spheroids to ALA-mediated PDT depends not only on the total fluence, but also on the rate at which the fluence is delivered. At low fluences (< or = 50 J cm-2), lower fluence rates are more effective. At a fluence of 50 J cm-2, near-total spheroid kill is observed at fluence rates of as low as 10 mW cm-2. The fluence rate effect is not as pronounced at higher fluences (> 50 J cm-2), where a favorable response is observed throughout the range of fluence rates investigated. The clinical implications of these findings are discussed.     

Unsteady flow through in-vitro models of the glottis

The unsteady two-dimensional flow through fixed rigid in vitro models of the glottis is studied in some detail to validate a more accurate model based on the prediction of boundary-layer separation. The study is restricted to the flow phenomena occurring within the glottis and does not include effects of vocal-fold movement on the flow. Pressure measurements have been carried out for a transient flow through a rigid scale model of the glottis. The rigid model with a fixed geometry driven by an unsteady pressure is used in order to achieve a high accuracy in the specification of the geometry of the glottis. The experimental study is focused on flow phenomena as they might occur in the glottis, such as the asymmetry of the flow due to the Coanda effect and the transition to turbulent flow. It was found that both effects need a relatively long time to establish themselves and are therefore unlikely to occur during the production of normal voiced speech when the glottis closes completely during part of the oscillation cycle. It is shown that when the flow is still laminar and symmetric the prediction of the boundary-layer model and the measurement of the pressure drop from the throat of the glottis to the exit of the glottis agree within 40%. Results of the boundary-layer model are compared with a two-dimensional vortex-blob method for viscous flow. The difference between the results of the simpiflied boundary-layer model and the experimental results is explained by an additional pressure difference between the separation point and the far field within the jet downstream of the separation point. The influence of the movement of the vocal folds on our conclusions is still unclear.     

A MICROSPECTROFLUOROMETRIC STUDY OF PORPHYRIN-PHOTOSENSITIZED SINGLE LIVING CELLS— I. MEMBRANE ALTERATIONS

Microspectrofluorometry on single living cells reveals that the primary effects of porphyrin-photosensitization on membranes results in the production of fluorescent lipofuscin-like pigments implying important lipid photoperoxidation. These fluorescent products (_max 450 nm) can also be formed in the dark after the irradiation of the cell. Their formation is abolished not only by crocetin and Tigason, two long-chain polyenes, but also by chloroquine. The latter, although a lysosomotropic drug, cannot inhibit the photosensitized permeation of lysosomal membranes which occurs at the beginning of the irradiation as shown by the splitting of fluorogenic substrates by lysosomal proteinases or by β-galactosidase when added before or after irradiation.     

Self-sustained oscillations in pipe systems with multiple deep side branches: Prediction and reduction by detuning

Flow-induced pulsations are frequently observed in pipe networks. In the present work we focus on the case of flow-induced pulsations in a pipe system composed of six equally spaced deep closed side branches. These pulsations are self-sustained aeroacoustic oscillations driven by the instability of the flow along the closed branches. The prediction of pulsations in such complex systems has not yet been proved to be possible, indeed the methods proposed in the literature have only been applied to relatively simple geometries, mainly single or double side branch systems. We propose a prediction model of the self-sustained oscillations in multiple deep side branch systems. This has been established by means of an analytical model for the acoustic wave propagation in which a semi-analytical source model is included. Detuning of the acoustic resonator is often considered as a possible remedial measure to suppress pulsations. Although this countermeasure appears to be very effective for double side branch systems in cross configuration, its effectiveness has never been assessed for different geometries. The effectiveness of the length-detuning on the six side branch system appear to be limited and depends on the upstream and downstream acoustic boundary conditions of the main pipe.     

Photosystem II activity and turnover of the D1 protein are impaired in the psbA Y112L mutant of Synechocystis PCC6803 sp.

Site-directed psbA mutants at the tyrosine Y112 position have been generated in Synechocystis PCC6803 cells. The mutation Y112F does not affect photosystem II (PSII) activity as compared with control 4 delta 1K cells. However, the Y112L mutant exhibits a photosynthetically impaired phenotype. PSII activity is not detectable in this mutant when grown at 30 mumol photons m-2 s-1, while low levels of the D1 and D2 proteins and oxygen evolution activity are present in the mutant cells grown at a low light intensity (0.5-1 mumol m-2 s-1). The recombination of the QB-/S2,3 states of PSII in the Y112L mutant cells as detected by thermoluminescence (TL) is altered. The TL signal emission maximum of these cells due to charge recombination of the S2,3/QB- occurs at 20 degrees C as compared to 35-40 degrees C for the wild-type cells, indicating a possible change in the S2,3/Yz equilibrium. The Y112L mutant cells are rapidly photoinactivated and impaired in the recovery of the PSII activity. These results suggest that replacement of the aromatic residue at position Y112 by a hydrophobic amino acid may alter the function of the donor-side activity and affects the degradation and replacement of the PSII core proteins.     

On whistling of pipes with a corrugated segment: Experiment and theory

Corrugated pipes are commonly used because of their local rigidity combined with global flexibility. The flow through such a pipe can induce strong whistling tones, which is an environmental nuisance and can be a threat to the mechanical integrity of the system. This paper considers the use of a composite pipe: a shorter corrugated pipe segment embedded between smooth pipe segments. Such a pipe retains some flexibility, while the acoustical damping in the smooth pipe reduces whistling tones. Whistling is the result of coherent vortex shedding at the cavities in the wall. This vortex shedding is synchronized by longitudinal acoustic waves traveling along the pipe. The acoustic waves trigger the vortex shedding, which reinforces the acoustic field for a critical range of the Strouhal number values. A linear theory for plane wave propagation and the sound production is proposed, which allows a prediction of the Mach number at the threshold of whistling in such pipes. A semi-empirical approach is chosen to determine the sound source in this model. This source corresponds to a fluctuating force acting on the fluid as a consequence of the vortex shedding. The functional form of the Strouhal number dependency of the dimensionless sound source amplitude is based on numerical simulations. The magnitude of the source and the Strouhal number range in which it can drive whistling are determined by matching the model to results for a specific corrugated pipe segment length. This semi-empirical source model is then applied to composite pipes with different corrugated segment lengths. In addition, the effect of inlet acoustical convective losses due to flow separation is considered. The Mach number at the threshold of whistling is predicted within a factor 2.     

Effect of Pr-Ca substitution on the transport and magnetic behavior of LaMnO3 perovskite

The effect of simultaneous substitution of a fluctuating cation and a divalent cation in LaMnO₃ perovskite modifies the properties of the material to exhibit large valence colossal magnetoresistance (CMR) effect. A good example of these properties is (La_1−2x Pr _x Ca _x )MnO₃ (LPCMO) type CMR material. In this communication it is reported that, with the increase in x (for x=0.1, 0.15, 0.2), the T _c varies between 100 and 120 K with improvisation in metal-insulator transition. Interestingly, resistance increases with x from few hundred ohms to few kilo ohms with corresponding decrease in the unit cell volume. The results of the studies using X-ray diffraction (XRD), electrical resistivity, magnetoresistance and ac susceptibility measurements on LPCMO samples for understanding the structural, transport and magnetic properties are discussed in detail.     

Upper and lower bounds for graph-diameter problems with application to record allocation

This paper studies three graph problems with parameters n, the number of nodes, e, the number of edges, and k, the diameter of the graph. Given any two of these three parameters, the problem is to construct a directed graph which minimizes or maximizes the third. The first problem has its origin in a recent study of record allocation in a paged computer system. It is shown how to construct graphs that are optimal for all three problems in some cases and are asymptotically optimal for other cases. The solution of the second problem answers a question raised by Berge in “The Theory of Graphs and its Application,” 1962.     

Lossless compression of chemical fingerprints using integer entropy codes improves storage and retrieval

Many modern chemoinformatics systems for small molecules rely on large fingerprint vector representations, where the components of the vector record the presence or number of occurrences in the molecular graphs of particular combinatorial features, such as labeled paths or labeled trees. These large fingerprint vectors are often compressed to much shorter fingerprint vectors using a lossy compression scheme based on a simple modulo procedure. Here, we combine statistical models of fingerprints with integer entropy codes, such as Golomb and Elias codes, to encode the indices or the run lengths of the fingerprints. After reordering the fingerprint components by decreasing frequency order, the indices are monotone-increasing and the run lengths are quasi-monotone-increasing, and both exhibit power-law distribution trends. We take advantage of these statistical properties to derive new efficient, lossless, compression algorithms for monotone integer sequences: monotone value (MOV) coding and monotone length (MOL) coding. In contrast to lossy systems that use 1024 or more bits of storage per molecule, we can achieve lossless compression of long chemical fingerprints based on circular substructures in slightly over 300 bits per molecule, close to the Shannon entropy limit, using a MOL Elias Gamma code for run lengths. The improvement in storage comes at a modest computational cost. Furthermore, because the compression is lossless, uncompressed similarity (e.g., Tanimoto) between molecules can be computed exactly from their compressed representations, leading to significant improvements in retrival performance, as shown on six benchmark data sets of druglike molecules.     

Studies of the protein and the energy metabolism in man during a wintering in Antarctica

During the 29th Soviet Antarctic Expedition in Novolazarevskaya from March 1984 to March 1985, the protein and energy metabolisms were studied in six expeditioners from the German Democratic Republic. The investigations were carried out at the beginning of the expedition (May), during the polar night (July) and during the polar day (December). The effect of a special stress situation (sledge trek in April 1984) was investigated in one subject. The stable nitrogen isotope (15)N was used to study the protein metabolism. The assessment of the energy metabolism was based on the oxygen consumption, which was determined by means of a spirograph. In addition, the vital capacity, the breath minute volume, the blood pressure, etc. were measured. The following results were obtained: During the polar night, the utilisation of the dietary proteins and the whole body protein synthesis calculated by means of the (15)N excretion of the total nitrogen in urine were greater (73.6±0.9 % and 3.48±0.17?g protein d(-1)?kg(-1), n=3) than the respective values during the polar day (69.7±1.2, p<0.05, n=3 and 3.05±0.07, p<0.05, n=3) and at the beginning of the expedition (69.6±1.4, p<0.02, n=5 and 2.81±0.09, p<0.01, n=5). The lowest values (58.0 % and 2.43?g protein d(-1)?kg(-1)) were obtained in the subject after the trek. The resting metabolic rate (in kJ?d(-1)?m(-2)) was decreased during the polar night (45.6±5.0, n=4) in comparison with the polar day (61.5±11.3, n=3) and the beginning of the expedition (52.3±9.6, n=4) with p<0.01 in both cases.