Long-term dependence in exchange rates

The extent to which exchange rates of four major currencies against the Greek Drachma exhibit long-term dependence is investigated using a R/S analysis testing framework. We show that both classic R/S analysis and the modified R/S statistic if enhanced by bootstrapping techniques can be proven very reliable tools to this end. Our findings support persistence and long-term dependence with non-periodic cycles for the Deutsche Mark and the French Franc series. In addition a noisy chaos explanation is favored over fractional Brownian motion. On the contrary, the US Dollar and British Pound were found to exhibit a much more random behavior and lack of any long-term structure

KDM1A microenvironment, its oncogenic potential, and therapeutic significance

The lysine-specific histone demethylase 1A (KDM1A) was the first demethylase to challenge the concept of the irreversible nature of methylation marks. KDM1A, containing a flavin adenine dinucleotide (FAD)-dependent amine oxidase domain, demethylates histone 3 lysine 4 and histone 3 lysine 9 (H3K4me1/2 and H3K9me1/2). It has emerged as an epigenetic developmental regulator and was shown to be involved in carcinogenesis. The functional diversity of KDM1A originates from its complex structure and interactions with transcription factors, promoters, enhancers, oncoproteins, and tumor-associated genes (tumor suppressors and activators). In this review, we discuss the microenvironment of KDM1A in cancer progression that enables this protein to activate or repress target gene expression, thus making it an important epigenetic modifier that regulates the growth and differentiation potential of cells. A detailed analysis of the mechanisms underlying the interactions between KDM1A and the associated complexes will help to improve our understanding of epigenetic regulation, which may enable the discovery of more effective anticancer drugs

Nonlinear time-series analysis of the Greek exchange-rate market

Using concepts from the theory of chaos and nonlinear dynamical systems, a time-series analysis is performed on four major currencies against the Greek Drachma. The R/S analysis provided evidence for fractality due to noisy chaos in only two of the data series, while the BDS test showed that all four systems exhibit nonlinearity. Correlation dimension and related tests, as well as Lyapunov exponents, gave consistent results, which did not rule out the possibility of deterministic chaos for the two possibly fractal series, rejecting though the occurrence of a simple low-dimensional attractor, while the other two series seemed to have followed a behavior close to that of a random signal. SVD analysis, used to filter away noise, strongly supported the above findings and provided reliable evidence for the existence of an underlying system with a limited number of degrees-of-freedom only for those series found to exhibit fractality, while it revealed a noise domination over the remaining two. These results were further confirmed through a forecasting attempt using artificial neural networks

Biochemical, structural, and biological evaluation of tranylcypromine derivatives as inhibitors of histone demethylases LSD1 and LSD2.

LSD1 and LSD2 histone demethylases are implicated in a number of physiological and pathological processes, ranging from tumorigenesis to herpes virus infection. A comprehensive structural, biochemical, and cellular study is presented here to probe the potential of these enzymes for epigenetic therapies. This approach employs tranylcypromine as a chemical scaffold for the design of novel demethylase inhibitors. This drug is a clinically validated antidepressant known to target monoamine oxidases A and B. These two flavoenzymes are structurally related to LSD1 and LSD2. Mechanistic and crystallographic studies of tranylcypromine inhibition reveal a lack of selectivity and differing covalent modifications of the FAD cofactor depending on the enantiomeric form. These findings are pharmacologically relevant, since tranylcypromine is currently administered as a racemic mixture. A large set of tranylcypromine analogues were synthesized and screened for inhibitory activities. We found that the common evolutionary origin of LSD and MAO enzymes, despite their unrelated functions and substrate specificities, is reflected in related ligand-binding properties. A few compounds with partial enzyme selectivity were identified. The biological activity of one of these new inhibitors was evaluated with a cellular model of acute promyelocytic leukemia chosen since its pathogenesis includes aberrant activities of several chromatin modifiers. Marked effects on cell differentiation and an unprecedented synergistic activity with antileukemia drugs were observed. These data demonstrate that these LSD1/2 inhibitors are of potential relevance for the treatment of promyelocytic leukemia and, more generally, as tools to alter chromatin state with promise of a block of tumor progression

Biochemical, Structural, and Biological Evaluation of Tranylcypromine Derivatives as Inhibitors of Histone Demethylases LSD1 and LSD2

LSD1 and LSD2 histone demethylases are implicated in a number of physiological and pathological processes, ranging from tumorigenesis to herpes virus infection. A comprehensive structural, biochemical, and cellular study is presented here to probe the potential of these enzymes for epigenetic therapies. This approach employs tranylcypromine as a chemical scaffold for the design of novel demethylase inhibitors. This drug is a clinically validated antidepressant known to target monoamine oxidases A and B. These two flavoenzymes are structurally related to LSD1 and LSD2. Mechanistic and crystallographic studies of tranylcypromine inhibition reveal a lack of selectivity and differing covalent modifications of the FAD cofactor depending on the enantiomeric form. These findings are pharmacologically relevant, since tranylcypromine is currently administered as a racemic mixture. A large set of tranylcypromine analogues were synthesized and screened for inhibitory activities. We found that the common evolutionary origin of LSD and MAO enzymes, despite their unrelated functions and substrate specificities, is reflected in related ligand-binding properties. A few compounds with partial enzyme selectivity were identified. The biological activity of one of these new inhibitors was evaluated with a cellular model of acute promyelocytic leukemia chosen since its pathogenesis includes aberrant activities of several chromatin modifiers. Marked effects on cell differentiation and an unprecedented synergistic activity with antileukemia drugs were observed. These data demonstrate that these LSD1/2 inhibitors are of potential relevance for the treatment of promyelocytic leukemia and, more generally, as tools to alter chromatin state with promise of a block of tumor progression

Determinants of bronchial responsiveness in the European Community Respiratory Health Survey in Italy: evidence of an independent role of atopy, total serum IgE levels, and asthma symptoms

The aim of the analysis was to test whether total serum IgE levels, specific serum IgE levels, and asthma symptoms are independent predictors of bronchial hyperresponsiveness (BHR), after controlling for known risk factors or potential confounders. The study was carried out on a sample of 875 young adults, 20-44 years old, who took part in the European Community Respiratory Health Survey in Italy. The subjects underwent a dose-response methacholine challenge test. We also measured airway caliber as the baseline FEV1 in absolute terms and as percentage of forced vital capacity (FVC); skin wheal response to 11 common environmental allergens; and total and specific serum IgE levels to mites, molds, pets, and respiratory symptoms by means of a standardized questionnaire. Atopy (positive skin prick test and/or positive specific IgE assay), total IgE, asthma symptoms, airway caliber, and age appeared to be independent predictors of BHR. When all the other risk factors were taken into account, atopy and total IgE were associated with a threefold increase in BHR risk and thus emerged as the main determinants of BHR. The importance of symptom status as a determinant of BHR decreased remarkably after controlling for atopy and IgE: the odds ratio of current asthmatics to asymptomatic subjects decreased from 15.3 to 8.8. When controlling for symptoms and atopy, a family history of allergic diseases and early respiratory infections was not found to be associated with BHR. Both FEV1 and FEV1/FVC were strongly and inversely associated with BHR. When airway caliber was taken into account, older age was associated with decreased responsiveness, and the level of responsiveness did not differ significantly between males and females and between smokers and nonsmokers. The results from this analysis indicate that at any given age, irrespective of sex and smoking habits, total serum IgE, specific IgE, airway caliber, and asthma symptoms are the main independent factors influencing the occurrence of BHR in a young adult sampl