Peptaibol-Containing Extracts of Trichoderma atroviride and the Fight against Resistant Microorganisms and Cancer Cells

Fighting resistance to antibiotics and chemotherapeutics has brought bioactive peptides to the fore. Peptaibols are short α-aminoisobutyric acid-containing peptides produced by Trichoderma species. Here, we studied the production of peptaibols by Trichoderma atroviride O1 and evaluated their antibacterial and anticancer activity against drug-sensitive and multidrug-resistant bacterium and cancer cell lines. This was substantiated by an analysis of the activity of the peptaibol synthetase-encoding gene. Atroviridins, 20-residue peptaibols were detected using MALDI-TOF mass spectrometry. Gram-positive bacteria were susceptible to peptaibol-containing extracts of T. atroviride O1. A synergic effect of extract constituents was possible, and the biolo-gical activity of extracts was pronounced in/after the peak of peptaibol synthetase activity. The growth of methicillin-resistant Staphylococcus aureus was reduced to just under 10% compared to the control. The effect of peptaibol-containing extracts was strongly modulated by the lipoteichoic acid and only slightly by the horse blood serum present in the cultivation medium. Peptaibol-containing extracts affected the proliferation of human breast cancer and human ovarian cancer cell lines in a 2D model, including the multidrug-resistant sublines. The peptaibols influenced the size and compactness of the cell lines in a 3D model. Our findings indicate the molecular basis of peptaibol production in T. atroviride O1 and the potential of its peptaibol-containing extracts as antimicrobial/anticancer agents.     

Bioanalysis of drugs and their metabolites by chiral electromigration techniques (2010–2020)

The further development and application of capillary electromigration techniques for the enantioselective determination of drugs and their metabolites in body fluids, tissues, and in vitro preparations during the 2010 to 2020 time period continued to proof their usefulness and attractiveness in bioanalysis. This review discusses the principles and important aspects of capillary electrophoresis- based chiral drug bioassays, provides a survey of the assays reported during the past 10 years and presents an overview of the key achievements encountered in that time period. For systems with charged chiral selectors, special attention is paid on assays that feature field-amplified sample injection to enable the determination of ppb levels of analytes and optimized online incubation procedures for the rapid assessment of a metabolic pathway. Applications discussed encompass the pharmacokinetics of drug enantiomers in vivo and in vitro, the impact of inhibitors on metabolic steps, the elucidation of the stereoselectivity of drug metabolism in vivo and in vitro, and drug enantiomers in toxicological, forensic, and doping analysis.     

Scenarios for Multistage Stochastic Programs

A major issue in any application of multistage stochastic programming is the representation of the underlying random data process. We discuss the case when enough data paths can be generated according to an accepted parametric or nonparametric stochastic model. No assumptions on convexity with respect to the random parameters are required. We emphasize the notion of representative scenarios (or a representative scenario tree) relative to the problem being modeled.     

Stability Properties of a Bond Portfolio Management Problem

The bond portfolio management problem is formulated as a multiperiod two-stage or multistage stochastic program based on interest rate scenarios. These scenarios depend on the available market data, on the applied estimation and sampling techniques, etc., and are used to evaluate coefficients of the resulting large scale mathematical program. The aim of the contribution is to analyze stability and sensitivity of this program on small changes of the coefficients – the (scenario dependent) values of future interest rates and prices. We shall prove that under sensible assumptions, the scenario subproblems are stable linear programs and that also the optimal first-stage decisions and the optimal value of the considered stochastic program possess acceptable continuity properties.     

Matrix effects in (ultra)trace analysis of pesticide residues in food and biotic matrices

If one has to determine multiple residues of modern pesticides and/or other groups of (semi)polar and/or thermally unstable contaminants with a wide range of physico-chemical properties within a single analytical run, it can be complicated to obtain low limits of quantitation (LOQ), good precision as well as relevant trueness of results for all the target analytes. Matrix components, which are unavoidably present in analyzed samples (even after the thorough clean-up step), may be responsible for miscellaneous adverse affects impairing different stages of the GC and/or LC determinative step. In this review, the nature of various types of matrix effects are discussed together with suggestions for prevention, reduction and/or compensation of their occurrence when determining troublesome analytes in foods and other complex biotic matrices.     

The fluorescence properties and NMR analysis of protopine and allocryptopine

The fluorescence properties of protopine and allocryptopine in aqueous and organic environments are described for the first time. The fluorescence of alkaloids and their pH-dependent interconversion to cationic forms (transannular interaction) were studied using steady-state and time-resolved fluorescence techniques. For the analysis of tricyclic base and cis/trans tetracyclic cations of the alkaloids, NMR and X-ray crystallography were used.     

Optimal managing of forest structure using data simulated optimal control

We analyze the deterministic infinite time horizon optimal control model aimed to determine optimal areas forested by particular tree species in Drahanska highlands in the Czech Republic. Facing the limitations in original data available we suggest a simulation technique to generate valid full scope data and to estimate correct underlaying functions. The simulation procedure, based on the experts suggestions and comments, is described in detail and the economic interpretations of the assumptions made are provided. Subsequently, we develop the optimal control model given the nonlinear cost and revenue functions and find its analytical solution. The results obtained are discussed with respect to forestry practice and further application of our model. The presented approach intends to be a valid basement for further thorough study of related dynamical decision problems in the Czech forestry business.     

Stereoselective determination of drugs and metabolites in body fluids,tissues and microsomal preparations by capillary electrophoresis (2000–2010)

During the past two decades, chiral capillary electrophoresis (CE) emerged as a promising, effective and economic approach for the enantioselective determination of drugs and their metabolites in body fluids, tissues and in vitro preparations. This review discusses the principles and important aspects of CE-based chiral bioassays, provides a survey of the assays developed during the past 10 years and presents an overview of the key achievements encountered in that time period. Applications discussed encompass the pharmacokinetics of drug enantiomers in vivo and in vitro, the elucidation of the stereoselectivity of drug metabolism in vivo and in vitro, and bioanalysis of drug enantiomers of toxicological, forensic and doping interest. Chiral CE was extensively employed for research purposes to investigate the stereoselectivity associated with hydroxylation, dealkylation, carboxylation, sulfoxidation, N-oxidation and ketoreduction of drugs and metabolites. Enantioselective CE played a pivotal role in many biomedical studies, thereby providing new insights into the stereoselective metabolism of drugs in different species which might eventually lead to new strategies for optimization of pharmacotherapy in clinical practice.     

Robustness of optimal portfolios under risk and stochastic dominance constraints

Solutions of portfolio optimization problems are often influenced by a model misspecification or by errors due to approximation, estimation and incomplete information. The obtained results, recommendations for the risk and portfolio manager, should be then carefully analyzed. We shall deal with output analysis and stress testing with respect to uncertainty or perturbations of input data for static risk constrained portfolio optimization problems by means of the contamination technique. Dependence of the set of feasible solutions on the probability distribution rules out the straightforward construction of convexity-based global contamination bounds. Results obtained in our paper [Dupa?ová, J., & Kopa, M. (2012). Robustness in stochastic programs with risk constraints. Annals of Operations Research, 200, 55–74.] were derived for the risk and second order stochastic dominance constraints under suitable smoothness and/or convexity assumptions that are fulfilled, e.g. for the Markowitz mean–variance model. In this paper we relax these assumptions having in mind the first order stochastic dominance and probabilistic risk constraints. Local bounds for problems of a special structure are obtained. Under suitable conditions on the structure of the problem and for discrete distributions we shall exploit the contamination technique to derive a new robust first order stochastic dominance portfolio efficiency test.