Solving problems of clustering and classification of cancer diseases based on DNA methylation data

The article deals with the problem of diagnosis of oncological diseases based on the analysis of DNA methylation data using algorithms of cluster analysis and supervised learning. The groups of genes are identified, methylation patterns of which significantly change when cancer appears. High accuracy is achieved in classification of patients impacted by different cancer types and in identification if the cell taken from a certain tissue is aberrant or normal. With method of cluster analysis two cancer types are highlighted for which the hypothesis was confirmed stating that among the people affected by certain cancer types there are groups with principally different methylation pattern

Dinosaur trackways from the Upper Cretaceous Nichkesai Formation near Mayluu Suu City, Southern Tien Shan Mountains, north-western Kyrgyzstan

Trackways provide essential data on the biogeographic distribution, locomotion and behaviour of dinosaurs. Cretaceous dinosaur trackways are abundant in the Americas, Europe, North Africa and East Asia, but are less well documented in Central Asia despite extensive exposure of Cretaceous terrestrial sedimentary rocks in the region. Here we report the presence of bipedal, tridactyl dinosaur trackways near the city of Mayluu Suu, Jalal Abad Oblast, north-western Kyrgyzstan, the first discovery of dinosaur trace fossils within the country. The trackways are situated on a steep slope uncovered by a landslide around the year 2000 in a highly landslide-affected area. Photogrammetry is used to digitally analyse and conserve the trace fossils. We infer a shoreface setting for the trackways based on the locality sedimentology, discuss the identity of the track makers and highlight the potential for future trackway discovery in the area. This discovery contributes vital data to an otherwise sparse record on the spatio-temporal distribution of dinosaurs in Kyrgyzstan, and to the dinosaur trackway record of Central Asia

Railway-induced ground vibrations – a review of vehicle effects

This paper is a review of the effect of vehicle characteristics on ground- and track borne-vibrations from railways. It combines traditional theory with modern thinking and uses a range of numerical analysis and experimental results to provide a broad analysis of the subject area. First, the effect of different train types on vibration propagation is investigated. Then, despite not being the focus of this work, numerical approaches to vibration propagation modelling within the track and soil are briefly touched upon. Next an in-depth discussion is presented related to the evolution of numerical models, with analysis of the suitability of various modelling approaches for analysing vehicle effects. The differences between quasi-static and dynamic characteristics are also discussed with insights into defects such as wheel/rail irregularities. Additionally, as an appendix, a modest database of train types are presented along with detailed information related to their physical attributes. It is hoped that this information may provide assistance to future researchers attempting to simulate railway vehicle vibrations. It is concluded that train type and the contact conditions at the wheel/rail interface can be influential in the generation of vibration. Therefore, where possible, when using numerical approach, the vehicle should be modelled in detail. Additionally, it was found that there are a wide variety of modelling approaches capable of simulating train types effects. If non-linear behaviour needs to be included in the model, then time domain simulations are preferable, however if the system can be assumed linear then frequency domain simulations are suitable due to their reduced computational demand

Application of the bacteriophage Mu-driven system for the integration/amplification of target genes in the chromosomes of engineered Gram-negative bacteria—mini review

The advantages of phage Mu transposition-based systems for the chromosomal editing of plasmid-less strains are reviewed. The cis and trans requirements for Mu phage-mediated transposition, which include the L/R ends of the Mu DNA, the transposition factors MuA and MuB, and the cis/trans functioning of the E element as an enhancer, are presented. Mini-Mu(LR)/(LER) units are Mu derivatives that lack most of the Mu genes but contain the L/R ends or a properly arranged E element in cis to the L/R ends. The dual-component system, which consists of an integrative plasmid with a mini-Mu and an easily eliminated helper plasmid encoding inducible transposition factors, is described in detail as a tool for the integration/amplification of recombinant DNAs. This chromosomal editing method is based on replicative transposition through the formation of a cointegrate that can be resolved in a recombination-dependent manner. (E-plus)- or (E-minus)-helpers that differ in the presence of the trans-acting E element are used to achieve the proper mini-Mu transposition intensity. The systems that have been developed for the construction of stably maintained mini-Mu multi-integrant strains of Escherichia coli and Methylophilus methylotrophus are described. A novel integration/amplification/fixation strategy is proposed for consecutive independent replicative transpositions of different mini-Mu(LER) units with “excisable” E elements in methylotrophic cells

Northern Eurasia Future Initiative (NEFI): facing the challenges and pathways of global change in the 21st century

During the past several decades, the Earth system has changed significantly, especially across Northern Eurasia. Changes in the socio-economic conditions of the larger countries in the region have also resulted in a variety of regional environmental changes that can have global consequences. The Northern Eurasia Future Initiative (NEFI) has been designed as an essential continuation of the Northern Eurasia Earth Science Partnership Initiative (NEESPI), which was launched in 2004. NEESPI sought to elucidate all aspects of ongoing environmental change, to inform societies and, thus, to better prepare societies for future developments. A key principle of NEFI is that these developments must now be secured through science-based strategies co-designed with regional decision makers to lead their societies to prosperity in the face of environmental and institutional challenges. NEESPI scientific research, data, and models have created a solid knowledge base to support the NEFI program. This paper presents the NEFI research vision consensus based on that knowledge. It provides the reader with samples of recent accomplishments in regional studies and formulates new NEFI science questions. To address these questions, nine research foci are identified and their selections are briefly justified. These foci include: warming of the Arctic; changing frequency, pattern, and intensity of extreme and inclement environmental conditions; retreat of the cryosphere; changes in terrestrial water cycles; changes in the biosphere; pressures on land-use; changes in infrastructure; societal actions in response to environmental change; and quantification of Northern Eurasia's role in the global Earth system. Powerful feedbacks between the Earth and human systems in Northern Eurasia (e.g., mega-fires, droughts, depletion of the cryosphere essential for water supply, retreat of sea ice) result from past and current human activities (e.g., large scale water withdrawals, land use and governance change) and potentially restrict or provide new opportunities for future human activities. Therefore, we propose that Integrated Assessment Models are needed as the final stage of global change assessment. The overarching goal of this NEFI modeling effort will enable evaluation of economic decisions in response to changing environmental conditions and justification of mitigation and adaptation efforts

DNA aptamers for as analytical tools for the quantitative analysis of DNA-dealkylating enzymes.

The AlkB family of oxygenases catalyze the removal of alkyl groups from nucleic acid substrates in an iron and 2-oxoglutarate-dependent manner and have roles including in DNA repair. To understand the biological functions of these DNA-dealkylating enzymes it is desirable to measure their expression levels in vitro and in vivo in complex biological matrixes. Quantitative analyses of the enzymes require affinity probes capable of binding AlkB family members selectively and with high affinity. Here we report that DNA aptamers can serve as efficient affinity probes for quantitative detection of such enzymes in vitro. Nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM) was applied as a general tool for: (i) selection of DNA aptamers, (ii) characterization of binding parameters for the aptamers, and (iii) quantitative detection of the target in an aptamer-based affinity analysis. The selected aptamers have a range of K(d) values between 20 and 240nM. The aptamers enabled accurate quantitative analysis of AlkB even in the presence of the Escherichia coli cell lysate. Aptamers can likely be developed for other nucleic acid repair enzymes. They may also be developed for use in in vitro and potentially in vivo studies of known nucleic acid-modifying enzymes including for functional analysis