Correlation Integral and Frequency Analysis of Cardiovascular Functions

To study the dynamics of the cardiovascular system several cardiovascular functions are measured at different sites of the human body. Measured time series of peripheral blood flow, respiration, electrical activity of the heart (ECG), and instantaneous heart rate (IHR) derived from the ECG are analysed in time and frequency domains and in phase space. Correlation integrals are calculated for the original signals and their surrogates. The auto and crosscorrelation functions and the Fourier spectra are also presented. All measured data of the physiological origin are corrupted by noise. To some extent they also contain non-stationarities. Therefore, the correlation integral is first analysed on numerically generated quasi-periodic time series and the effect of added noise is studied. The scale that is corrupted by noise is also analytically examined. An upper dimension which may reliably be estimated is evaluated. The results presented suggest that the calculated correlation integral cannot be used as a quantitative characterization of an attractor reconstructed from measured time series. Hence, only the relative qualitative differences between slopes of the correlation integral of measured time series and their surrogates are analysed. For all measured time series the slopes of their correlation integrals differ from those of their surrogates suggesting deterministic nature of the system that governs cardiovascular dynamics. It is also shown that all time series contain the same five characteristic peaks in their frequency spectra.     

Revealing oscillators calculation of the dimension of attractors

The monitoring of various natural phenomena yields data sets sustaining the dynamics of usually very complex systems. The question then is: how to reveal the characteristics and the nature of a system? In approaching this question, the calculation of the dimension of its attractor may give an indication of its complexity. The present review is an account of the analyses of the calculation of attractor dimension. Various quasi-periodic systems with different degrees of freedom are simulated and, by adding noise and nonstationarity, experimental conditions are mimicked. By increasing the complexity of the system an overestimation of attractor dimension is profound, even on noise-free signals. The presented analysis points out that for experimental data sets, resulting from systems already having more than one degree of freedom, the calculated value of attractor dimension cannot be used to determine whether the system dynamics is chaotic. It may be firmly determined whether it is deterministic or not, since in the case of a deterministic system its surrogate has a higher dimension than the original signal.     

Chemistry towards Biology—Instruct: Snapshot

The knowledge of interactions between different molecules is undoubtedly the driving force of all contemporary biomedical and biological sciences. Chemical biology/biological chemistry has become an important multidisciplinary bridge connecting the perspectives of chemistry and biology to the study of small molecules/peptidomimetics and their interactions in biological systems. Advances in structural biology research, in particular linking atomic structure to molecular properties and cellular context, are essential for the sophisticated design of new medicines that exhibit a high degree of druggability and very importantly, druglikeness. The authors of this contribution are outstanding scientists in the field who provided a brief overview of their work, which is arranged from in silico investigation through the characterization of interactions of compounds with biomolecules to bioactive materials.     

Fraxetin Interacts Additively with Cisplatin and Mitoxantrone,Antagonistically with Docetaxel in Various Human Melanoma Cell Lines—An Isobolographic Analysis

Malignant melanoma is a skin cancer characterized by rapid development, poor prognosis and high mortality. Due to the frequent drug resistance and/or early metastases in melanoma, new therapeutic methods are urgently needed. The study aimed at assessing the cytotoxic and antiproliferative effects of scoparone and fraxetin in vitro, when used alone and in combination with three cytostatics: cisplatin, mitoxantrone, and docetaxel in four human melanoma cell lines. Our experiments showed that scoparone in the concentration range tested up to 200 µM had no significant effect on the viability of human malignant melanoma (therefore, it was not possible to evaluate it in combination with other cytostatics), while fraxetin inhibited cell proliferation with IC₅₀ doses in the range of 32.42–73.16 µM, depending on the cell line. Isobolographic analysis allowed for the assessment of the interactions between the studied compounds. Importantly, fraxetin was not cytotoxic to normal keratinocytes (HaCaT) and melanocytes (HEMa-LP), although it slightly inhibited their viability at high concentrations. The combination of fraxetin with cisplatin and mitoxantrone showed the additive interaction, which seems to be a promising direction in melanoma therapy. Unfortunately, the combination of fraxetin with docetaxel may not be beneficial due to the antagonistic antiproliferative effect of both drugs used in the mixture.     

Mixture Effects of Tryptophan Intestinal Microbial Metabolites on Aryl Hydrocarbon Receptor Activity

Aryl hydrocarbon receptor (AHR) plays pivotal roles in intestinal physiology and pathophysiology. Intestinal AHR is activated by numerous dietary, endogenous, and microbial ligands. Whereas the effects of individual compounds on AHR are mostly known, the effects of real physiological mixtures occurring in the intestine have not been studied. Using reporter gene assays and RT-PCR, we evaluated the combinatorial effects (3520 combinations) of 11 microbial catabolites of tryptophan (MICTs) on AHR. We robustly (n = 30) determined the potencies and relative efficacies of single MICTs. Synergistic effects of MICT binary mixtures were observed between low- or medium-efficacy agonists, in particular for combinations of indole-3-propionate and indole-3-lactate. Combinations comprising highly efficacious agonists such as indole-3-pyruvate displayed rather antagonist effects, caused by saturation of the assay response. These synergistic effects were confirmed by RT-PCR as CYP1A1 mRNA expression. We also tested mimic multicomponent and binary mixtures of MICTs, prepared based on the metabolomic analyses of human feces and colonoscopy aspirates, respectively. In this case, AHR responsiveness did not correlate with type of diet or health status, and the indole concentrations in the mixtures were determinative of gross AHR activity. Future systematic research on the synergistic activation of AHR by microbial metabolites and other ligands is needed.     

Combined Drying of Apple Cubes by Using of Heat Pump,Vacuum-Microwave,and Intermittent Techniques

Apple cubes of 15 mm were dried naturally without adding any chemical preservative using various drying methods namely intermittent hot air–dehumidified air drying with cyclic temperature profile and step-up temperature profile, heat-pump-assisted (HP) drying, convective vacuum-microwave (C/VM) drying, and heat pump vacuum-microwave (HP/VM) drying. The drying kinetics of apple samples dehydrated by different methods was divided into characteristic drying periods and fitted with empirical models, which gave high value of determination coefficient. The application of C/VM in drying of fruits gave the shortest drying time compared to other drying methods (about 50 % of the total drying time). The drying time was affected by effective diffusivity ranging from 3.522?×?10^?8 to 1.431?×?10^?6 m²/min depending on the drying technique used. It was found that combined drying which apply vacuum microwave (C/VM, HP/VM) gave the lowest values in hardness and chewiness. In addition, HP/VM drying gave the highest retained total polyphenol content, antioxidant activity, and the best appearance quality.     

Synthesis of Demissidine Analogues from Tigogenin via Imine Intermediates

A five-step transformation of a spiroketal side chain of tigogenin into an indolizidine system present in solanidane alkaloids such as demissidine and solanidine was elaborated. The key intermediate in the synthesis was spiroimine 3 readily obtained from tigogenin by its RuO₄ oxidation to 5,6-dihydrokryptogenin followed by amination with aluminum amide generated in situ from DIBAlH and ammonium chloride. The mild reduction of spiroimine to a 26-hydroxy-dihydropyrrole derivative and subsequent mesylation resulted in the formation of 25-epidemissidinium salt or 23-sulfone depending on reaction conditions.