Mikhail I. Bogachev

Improved El Niño forecasting by cooperativity detection

Although anomalous episodic warming of the eastern equatorial Pacific, dubbed El Niño by Peruvian fishermen, has major (and occasionally devastating) impacts around the globe, robust forecasting is still limited to about 6 mo ahead. A significant extension of the prewarning time would be instrumental for avoiding some of the worst damages such as harvest failures in developing countries. Here we introduce a unique avenue toward El Niño prediction based on network methods, inspecting emerging teleconnections. Our approach starts from the evidence that a large-scale cooperative mode—linking the El Niño basin (equatorial Pacific corridor) and the rest of the ocean—builds up in the calendar year before the warming event. On this basis, we can develop an efficient 12-mo forecasting scheme, i.e., achieve some doubling of the early-warning period. Our method is based on high-quality observational data available since 1950 and yields hit rates above 0.5, whereas false-alarm rates are below 0.1.

Very early warning of next El Niño

The most important driver of climate variability is the El Niño Southern Oscillation, which can trigger disasters in various parts of the globe. Despite its importance, conventional forecasting is still limited to 6 mo ahead. Recently, we developed an approach based on network analysis, which allows projection of an El Niño event about 1 y ahead. Here we show that our method correctly predicted the absence of El Niño events in 2012 and 2013 and now announce that our approach indicated (in September 2013 already) the return of El Niño in late 2014 with a 3-in-4 likelihood. We also discuss the relevance of the next El Niño to the question of global warming and the present hiatus in the global mean surface temperature.

Statistics of return intervals between long heartbeat intervals and their usability for online prediction of disorders

We study the statistics of return intervals between large heartbeat intervals (above a certain threshold Q) in 24 h records obtained from healthy subjects. We find that both the linear and the nonlinear long-term memory inherent in the heartbeat intervals lead to power-laws in the probability density function PQ(r) of the return intervals. As a consequence, the probability WQ(t; Δt) that at least one large heartbeat interval will occur within the next Δt heartbeat intervals, with an increasing elapsed number of intervals t after the last large heartbeat interval, follows a power-law. Based on these results, we suggest a method of obtaining a priori information about the occurrence of the next large heartbeat interval, and thus to predict it. We show explicitly that the proposed method, which exploits long-term memory, is superior to the conventional precursory pattern recognition technique, which focuses solely on short-term memory. We believe that our results can be straightforwardly extended to obtain more reliable predictions in other physiological signals like blood pressure, as well as in other complex records exhibiting multifractal behaviour, e.g. turbulent flow, precipitation, river flows and network traffic.

Universal Internucleotide Statistics in Full Genomes: A Footprint of the DNA Structure and Packaging?

Uncovering the fundamental laws that govern the complex DNA structural organization remains challenging and is largely based upon reconstructions from the primary nucleotide sequences. Here we investigate the distributions of the internucleotide intervals and their persistence properties in complete genomes of various organisms from Archaea and Bacteria to H. Sapiens aiming to reveal the manifestation of the universal DNA architecture. We find that in all considered organisms the internucleotide interval distributions exhibit the same -exponential form. While in prokaryotes a single -exponential function makes the best fit, in eukaryotes the PDF contains additionally a second -exponential, which in the human genome makes a perfect approximation over nearly 10 decades. We suggest that this functional form is a footprint of the heterogeneous DNA structure, where the first -exponential reflects the universal helical pitch that appears both in pro- and eukaryotic DNA, while the second -exponential is a specific marker of the large-scale eukaryotic DNA organization.

Universality in the precipitation and river runoff

For characterizing the inherent dynamical structure of precipitation and river runoffs, we study in representative seasonally detrended records the durations τ where the record is below a given threshold Q. When keeping the return period RQ of the threshold fixed, we find that the probability density function (PDF) of these durations shows universal features when scaled with the average duration τ. For both types of data the scaling function can be approximated by a Γ-distribution, but also a description by the corresponding PDF of long-term correlated records is possible. The parameters of the PDF depend on the kind of data (precipitation or river runoff) and on RQ but neither on the climate nor on the hydrological details of the location of the record.

Analysis of blood pressure-heart rate feedback regulation under non-stationary conditions: beyond baroreflex sensitivity

The feedback regulation of blood pressure and heart rate is an important indicator of human autonomic function usually assessed by baroreflex sensitivity (BRS). We suggest a new method yielding a higher temporal resolution than standard BRS methods. Our approach is based on a regression analysis of the first differences of inter-heartbeat intervals and blood pressure values. Data are recorded from 23 patients with hypertension and sleep apnoea, 22 patients with diabetes mellitus and 23 healthy subjects. Using the proposed method for 3 min data segments, we obtain average regression coefficients of 9.1 and 3.5 ms mmHg(-1) for healthy subjects in supine and orthostatic positions, respectively. In patients with hypertension, we find them to be 3.8 and 2.6 ms mmHg(-1). The diabetes patients with and without autonomic neuropathy are characterized by 3.1 and 6.1 ms mmHg(-1) in the supine position compared with 1.7 and 3.3 ms mmHg(-1) in the orthostatic position. The results are highly correlated with conventional BRS measures; we find r > 0.9 for the dual sequence method. Therefore, we suggest that the new method can quantify BRS. It is superior in distinguishing healthy subjects from patients both in supine and orthostatic positions for short-term recordings. It is suitable for non-stationary data and has good reproducibility. Besides, we cannot exclude that other regulatory mechanisms than BRS may also contribute to the regression coefficients between the first differences.

Inhibition of biofilm formation in Bacillus subtilis by new halogenated furanones.

Gram-positive bacteria can cause various infections including hospital-acquired infections. While in the biofilm, the resistance of bacteria to both antibiotics and the human immune system is increased causing difficulties in the treatment. Bacillus subtilis, a non-pathogenic Gram-positive bacterium, is widely used as a model organism for studying biofilm formation. Here we investigated the effect of novel synthesized chloro- and bromo-containing 2(5H)-furanones on biofilm formation by B. subtilis. Mucobromic acid (3,4-dibromo-5-hydroxy-2(5H)-furanone) and the two derivatives of mucochloric acid (3,4-dichloro-5-hydroxy-2(5H)-furanone)—F8 and F12—were found to inhibit the growth and to efficiently prevent biofilm formation by B. subtilis. Along with the low production of polysaccharide matrix and repression of the eps operon, strong repression of biofilm-related yqxM also occurred in the presence of furanones. Therefore, our data confirm that furanones affect significantly the regulatory pathway(s) leading to biofilm formation. We propose that the global regulator, Spo0A, is one of the potential putative cellular targets for these compounds.

New Derivatives of Pyridoxine Exhibit High Antibacterial Activity against Biofilm-Embedded Staphylococcus Cells.

Opportunistic bacteria Staphylococcus aureus and Staphylococcus epidermidis often form rigid biofilms on tissues and inorganic surfaces. In the biofilm bacterial cells are embedded in a self-produced polysaccharide matrix and thereby are inaccessible to biocides, antibiotics, or host immune system. Here we show the antibacterial activity of newly synthesized cationic biocides, the quaternary ammonium, and bisphosphonium salts of pyridoxine (vitamin B6) against biofilm-embedded Staphylococci. The derivatives of 6-hydroxymethylpyridoxine were ineffective against biofilm-embedded S. aureus and S. epidermidis at concentrations up to 64 μg/mL, although all compounds tested exhibited low MICs (2 μg/mL) against planktonic cells. In contrast, the quaternary ammonium salt of pyridoxine (N,N-dimethyl-N-((2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)methyl)octadecan-1-aminium chloride (3)) demonstrated high biocidal activity against both planktonic and biofilm-embedded bacteria. Thus, the complete death of biofilm-embedded S. aureus and S. epidermidis cells was obtained at concentrations of 64 and 16 μg/mL, respectively. We suggest that the quaternary ammonium salts of pyridoxine are perspective to design new synthetic antibiotics and disinfectants for external application against biofilm-embedded cells.

Targeting microbial biofilms using Ficin, a nonspecific plant protease

Biofilms, the communities of surface-attached bacteria embedded into extracellular matrix, are ubiquitous microbial consortia securing the effective resistance of constituent cells to environmental impacts and host immune responses. Biofilm-embedded bacteria are generally inaccessible for antimicrobials, therefore the disruption of biofilm matrix is the potent approach to eradicate microbial biofilms. We demonstrate here the destruction of Staphylococcus aureus and Staphylococcus epidermidis biofilms with Ficin, a nonspecific plant protease. The biofilm thickness decreased two-fold after 24 hours treatment with Ficin at 10 μg/ml and six-fold at 1000 μg/ml concentration. We confirmed the successful destruction of biofilm structures and the significant decrease of non-specific bacterial adhesion to the surfaces after Ficin treatment using confocal laser scanning and atomic force microscopy. Importantly, Ficin treatment enhanced the effects of antibiotics on biofilms-embedded cells via disruption of biofilm matrices. Pre-treatment with Ficin (1000 μg/ml) considerably reduced the concentrations of ciprofloxacin and bezalkonium chloride required to suppress the viable Staphylococci by 3 orders of magnitude. We also demonstrated that Ficin is not cytotoxic towards human breast adenocarcinoma cells (MCF7) and dog adipose derived stem cells. Overall, Ficin is a potent tool for staphylococcal biofilm treatment and fabrication of novel antimicrobial therapeutics for medical and veterinary applications.

Superstatistical model of bacterial DNA architecture

Understanding the physical principles that govern the complex DNA structural organization as well as its mechanical and thermodynamical properties is essential for the advancement in both life sciences and genetic engineering. Recently we have discovered that the complex DNA organization is explicitly reflected in the arrangement of nucleotides depicted by the universal power law tailed internucleotide interval distribution that is valid for complete genomes of various prokaryotic and eukaryotic organisms. Here we suggest a superstatistical model that represents a long DNA molecule by a series of consecutive ~150 bp DNA segments with the alternation of the local nucleotide composition between segments exhibiting long-range correlations. We show that the superstatistical model and the corresponding DNA generation algorithm explicitly reproduce the laws governing the empirical nucleotide arrangement properties of the DNA sequences for various global GC contents and optimal living temperatures. Finally, we discuss the relevance of our model in terms of the DNA mechanical properties. As an outlook, we focus on finding the DNA sequences that encode a given protein while simultaneously reproducing the nucleotide arrangement laws observed from empirical genomes, that may be of interest in the optimization of genetic engineering of long DNA molecules.