On maximum norm contractivity of second order damped single step methods

In this paper we consider A(θ)-stable finite difference methods for numerical solutions of dissipative partial differential equations of parabolic type. Combining two rational approximation methods with different orders of accuracy, where the lower order method is applied n ₀ times (n ₀ fixed) at each time step, we prove the existence of a second order method which is contractive for all time steps. Moreover, we shed light on the conditions on the lower order method which are sufficient (and sometimes necessary) to obtain the optimal order of accuracy. For the one-dimensional heat equation we construct a family of numerical methods which are contractive in the maximum norm for all values of the discretization parameters. We also present numerical examples to illustrate our results. Received: May 2002 / Accepted: January 2003     

The ring transformations of 1,2,3,4-diepoxybutane (2,2′-bioxirane) catalysed by various aluminosilicates

The transformations of a molecule containing two adjacent epoxide rings, 2,2-bioxirane that is, were studied over various acidic aluminosilicates (HZSM-5, HY-FAU, AlMCM-41), for the first time, In the 373–473 K temperature range, in a pulse reactor, a ring-opening–ring-enlargment reaction producing furan only occured over the zeolites and it was the predominant reaction on AlMCM-41 as well. The driving force of this transformation route is water formation via elimination from 2,2-bioxirane. Suprising is the lack of the mono- or dialdehyde, the would-be products of the cleavage of the sterically more hindered C–O bonds – an acid-catalysed reaction typical for alkyl-substituted oxiranes.     

The behaviour of the multi-layer perceptron and the support vector regression learning methods in the prediction of NO and NO2 concentrations in Szeged, Hungary

The main aim of this paper is to predict NO and NO₂ concentrations 4 days in advance by comparing two artificial intelligence learning methods, namely, multi-layer perceptron and support vector machines, on two kinds of spatial embedding of the temporal time series. Hourly values of NO and NO₂ concentrations, as well as meteorological variables were recorded in a cross-road monitoring station with heavy traffic in Szeged, in order to build a model for predicting NO and NO₂ concentrations several hours in advance. The prediction of NO and NO₂ concentrations was performed partly on the basis of their past values, and partly on the basis of temperature, humidity and wind speed data. Since NO can be predicted more accurately, its values were considered primarily when forecasting NO₂. Time series prediction can be interpreted in a way that is suitable for artificial intelligence learning. Two effective learning methods, namely, multi-layer perceptron and support vector regression are used to provide efficient non-linear models for NO and NO₂ time series predictions. Multi-layer perceptron is widely used to predict these time series, but support vector regression has not yet been applied for predicting NO and NO₂ concentrations. Three commonly used linear algorithms were considered as references: 1-day persistence, average of several day persistence and linear regression. Based on the good results of the average of several day persistence, a prediction scheme was introduced, which forms weighted averages instead of simple ones. The optimization of these weights was performed with linear regression in linear case and with the learning methods mentioned in non-linear case. Concerning the NO predictions, the non-linear learning methods give significantly better predictions than the reference linear methods. In the case of NO₂, the improvement of the prediction is considerable, however, it is less notable than for NO.     

Synthesis and Cell Growth Inhibitory Activity of Six Non-glycosaminoglycan-Type Heparin-Analogue Trisaccharides

The design and synthesis of heparin mimetics with high anticancer activity but no anticoagulant activity is an important task in medicinal chemistry. Herein, we present the efficient synthesis of five Glc-GlcA-Glc-sequenced and one Glc-IdoA-Glc-sequenced non-glycosaminoglycan, heparin-related trisaccharides with various sulfation/sulfonylation and methylation patterns. The cell growth inhibitory effects of the compounds were tested against four cancerous human cell lines and two non-cancerous cell lines. Two d -glucuronate-containing tetra-O-sulfated, partially methylated trisaccharides displayed remarkable and selective inhibitory effects on the growth of ovary carcinoma (A2780) and melanoma (WM35) cells. Methyl substituents on the glucuronide unit proved to be detrimental, whereas acetyl substituents were beneficial to the cytostatic activity of the sulfated derivatives.     

First genetically verified occurrence of Ligula pavlovskii outside its native range and characteristics of its infection in Neogobius fluviatilis

In this study, we provide the first genetically verified distribution record beyond its native range of Ligula pavlovskii, a high-impact endoparasite of Ponto-Caspian gobies. According to parasitological surveys, ligulosis was detected for the first time in monkey goby individuals collected from Lake Balaton in 2004, 34 years after the first record of monkey goby in the lake. During a Lake Balaton survey in 2018, we detected tapeworms in 44.4% of the sampled monkey gobies. This prevalence is about two to ten times higher than it was reported from within the native range of the fish hosts. The same survey revealed an uneven spatial distribution of the ligulosis in the monkey gobies inhabiting different shoreline sections of the lake. We assume that the occurrence and recent distribution data of this high-impact endoparasite may provide useful information for potential biocontrol measures of invasive Ponto-Caspian gobies in the future.     

Ultra-trace Analysis of Enantiomeric Impurities in Proteinogenic N-Fmoc-Amino-acid Samples on Cinchona Alkaloid-based Chiral Stationary Phases

The enantiomeric purity of N_α-Fmoc-protected amino acids is crucial from the viewpoint of peptide synthesis; therefore, a sensitive high-performance liquid chromatographic protocol was developed for the identification and quantification of enantiomeric impurities of commercially available N_α-Fmoc-protected amino acids on Cinchona alkaloid quinine- and quinidine-based weak anion exchanger-type chiral stationary phases. In the course of the evaluation of the chiral chromatographic method, the effect of the mobile phase composition, nature, and concentration of different additives were optimized. The specific phenomenon that quinine- and quinidine-based chiral stationary phases behave as pseudo-enantiomers permits that the sequence of elution of the enantiomers might be reversed by simple column switching. This is quite advantageous as regards the separation of the minor component in the presence of the major one. The method developed permits detection of less than 0.01 % enantiomeric impurity in the presence of the major enantiomer.     

Investigation of the Antiproliferative Properties of Natural Sesquiterpenes from Artemisia asiatica and Onopordum acanthium on HL-60 Cells in Vitro

Plants and plant extracts play a crucial role in the research into novel antineoplastic agents. Four sesquiterpene lactones, artecanin (1), 3β-chloro-4α,10α-dihydroxy-1α,2α-epoxy-5α,7αH-guaia-11(13)-en-12,6α-olide (2), iso-seco-tanapartholide 3-O-methyl ether (3) and 4β,15-dihydro-3-dehydrozaluzanin C (4), were isolated from two traditionally used Asteraceae species (Onopordum acanthium and Artemisia asiatica). When tested for antiproliferative action on HL-60 leukemia cells, these compounds exhibited reasonable IC₅₀ values in the range 3.6–13.5 μM. Treatment with the tested compounds resulted in a cell cycle disturbance characterized by increases in the G1 and G2/M populations, while there was a decrease in the S phase. Additionally, 1–3 elicited increases in the hypodiploid (subG1) population. The compounds elicited concentration-dependent chromatin condensation and disruption of the membrane integrity, as revealed by Hoechst 33258–propidium staining. Treatment for 24 h resulted in significant increases in activity of caspases-3 and -9, indicating that the tested sesquiterpenes induced the mitochondrial pathway of apoptosis. The proapoptotic properties of the sesquiterpene lactones were additionally demonstrated withannexin V staining. Compounds 1 and 2 increased the Bax/Bcl-2 expression and decreased the expressions of CDK1 and cyclin B2, as determined at the mRNA level by means of RT-PCR. These experimental results indicate that sesquiterpene lactones may be regarded as potential starting structures for the development of novel anticancer agents.     

Role of the Blood-Brain Barrier in the Formation of Brain Metastases

The majority of brain metastases originate from lung cancer, breast cancer and malignant melanoma. In order to reach the brain, parenchyma metastatic cells have to transmigrate through the endothelial cell layer of brain capillaries, which forms the morphological basis of the blood-brain barrier (BBB). The BBB has a dual role in brain metastasis formation: it forms a tight barrier protecting the central nervous system from entering cancer cells, but it is also actively involved in protecting metastatic cells during extravasation and proliferation in the brain. The mechanisms of interaction of cancer cells and cerebral endothelial cells are largely uncharacterized. Here, we provide a comprehensive review on our current knowledge about the role of junctional and adhesion molecules, soluble factors, proteolytic enzymes and signaling pathways mediating the attachment of tumor cells to brain endothelial cells and the transendothelial migration of metastatic cells. Since brain metastases represent a great therapeutic challenge, it is indispensable to understand the mechanisms of the interaction of tumor cells with the BBB in order to find targets of prevention of brain metastasis formation.     

The Irritant Effects of Pharmaceutically Applied Surfactants

Dermal or transdermal medication may lead to irritant contact dermatitis. However, little information is available on the irritant effect of surfactants which are applied in topical formulations. Our aim was to examine the irritant effect of the most frequent compounds in topical products. A murine model was applied. The following compounds were examined: sodium lauryl sulphate (SLS), polyethoxylated (40EO) hydrogenated castor oil and sucrose laurate. SLS led to severe erythema, increase in transepidermal water loss (TEWL) and induced necrosis and accumulation of neutrophylic granulocytes and lymphocytes. Exposure to sucrose laurate resulted in an elevation of TEWL, but histology did not reveal impairment of the skin structure. Application of polyethoxylated (40EO) hydrogenated castor oil was not accompanied by tissue damage. Special attention should be paid to the irritant effect of SLS. Polyethoxylated (40EO) hydrogenated castor oil seems to be a non-irritant agent and sucrose laurate is also a promising candidate for application in topical preparations.