DECENTRALIZATION: ECONOMICS, FINANCE AND ENVIRONMENTAL SAFETY

In the article considered the implementation problem an effective organizational and economic mechanism (algorithm) and ensuring the safety of the process of decentralization of management of natural resources is considered as an organized transfer of powers from the sphere of state management to water, land, forest and mineral resources to territorial communities. The concept of the mechanism of ensuring the security of the decentralization process in the system of management of natural resources with the participation of local communities is proposed

A PROMISING MECHANISM FOR FINANCING THE NATIONAL ECONOMY, SECURITY AND DEFENSE OF UKRAINE

The principles of the permanent financing of necessities of state development, national safety and defensive due to forming of legal institute of civil property on natural resources and mechanisms of the sovereign financing by receivabless from natural rent are grounded here. The description of sovereign fund and fund of civil dividends as institutes of accumulation of state facilities and management of assets is given here

Systematic dissection of regulatory motifs in 2000 predicted human enhancers using a massively parallel reporter assay

Genome-wide chromatin annotations have permitted the mapping of putative regulatory elements across multiple human cell types. However, their experimental dissection by directed regulatory motif disruption has remained unfeasible at the genome scale. Here, we use a massively parallel reporter assay (MPRA) to measure the transcriptional levels induced by 145-bp DNA segments centered on evolutionarily conserved regulatory motif instances within enhancer chromatin states. We select five predicted activators (HNF1, HNF4, FOXA, GATA, NFE2L2) and two predicted repressors (GFI1, ZFP161) and measure reporter expression in erythroleukemia (K562) and liver carcinoma (HepG2) cell lines. We test 2104 wild-type sequences and 3314 engineered enhancer variants containing targeted motif disruptions, each using 10 barcode tags and two replicates. The resulting data strongly confirm the enhancer activity and cell-type specificity of enhancer chromatin states, the ability of 145-bp segments to recapitulate both, the necessary role of regulatory motifs in enhancer function, and the complementary roles of activator and repressor motifs. We find statistically robust evidence that (1) disrupting the predicted activator motifs abolishes enhancer function, while silent or motif-improving changes maintain enhancer activity; (2) evolutionary conservation, nucleosome exclusion, binding of other factors, and strength of the motif match are predictive of enhancer activity; (3) scrambling repressor motifs leads to aberrant reporter expression in cell lines where the enhancers are usually inactive. Our results suggest a general strategy for deciphering cis-regulatory elements by systematic large-scale manipulation and provide quantitative enhancer activity measurements across thousands of constructs that can be mined to develop predictive models of gene expression.National Institutes of Health (U.S.) (Grant HG004037)National Institutes of Health (U.S.) (Grant HG004037-S1

Targeted next-generation sequencing of a cancer transcriptome enhances detection of sequence variants and novel fusion transcripts

Combining next-generation sequencing with capture of sequences from a relevant subset of a transcriptome produces an enhanced view of this subse

Hybrid selection for sequencing pathogen genomes from clinical samples

We have adapted a solution hybrid selection protocol to enrich pathogen DNA in clinical samples dominated by human genetic material. Using mock mixtures of human and Plasmodium falciparum malaria parasite DNA as well as clinical samples from infected patients, we demonstrate an average of approximately 40-fold enrichment of parasite DNA after hybrid selection. This approach will enable efficient genome sequencing of pathogens from clinical samples, as well as sequencing of endosymbiotic organisms such as Wolbachia that live inside diverse metazoan phyla

Rapid dissection and model-based optimization of inducible enhancers in human cells using a massively parallel reporter assay

Learning to read and write the transcriptional regulatory code is of central importance to progress in genetic analysis and engineering. Here we describe a massively parallel reporter assay (MPRA) that facilitates the systematic dissection of transcriptional regulatory elements. In MPRA, microarray-synthesized DNA regulatory elements and unique sequence tags are cloned into plasmids to generate a library of reporter constructs. These constructs are transfected into cells and tag expression is assayed by high-throughput sequencing. We apply MPRA to compare >27,000 variants of two inducible enhancers in human cells: a synthetic cAMP-regulated enhancer and the virus-inducible interferon-β enhancer. We first show that the resulting data define accurate maps of functional transcription factor binding sites in both enhancers at single-nucleotide resolution. We then use the data to train quantitative sequence-activity models (QSAMs) of the two enhancers. We show that QSAMs from two cellular states can be combined to design enhancer variants that optimize potentially conflicting objectives, such as maximizing induced activity while minimizing basal activity.National Human Genome Research Institute (U.S.) (grant R01HG004037)National Science Foundation (U.S.) ((NSF) grant PHY-0957573)National Science Foundation (U.S.) (NSF grant PHY-1022140)Broad Institut

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Ensuring the Stability of Economic Systems in Conditions of Market Variability and Increasing Threats and Risks

The article aims to develop a comprehensive methodological basis for the study and justification of four-level homeostatic mechanisms for controlling the stability of control systems in the “new normal” conditions, which is implemented in accordance with the author's concept of sustainable management. The article describes and details the features of the main types of homeostasis of control systems (evolutionary, structural, stable, systemic homeostasis), their hierarchical cyclic-closed relationship and their specific and predictive capabilities to provide administrative properties. This is substantiated and disclosed by determining: a) a set of conditions for generating homeostasis and implementing the specific effect of adaptation mechanisms and, accordingly, regulators of regeneration of control systems to external and internal transformations; b) guidelines and methods for the formation of economic systems that are resistant to institutional and resource constraints, supplemented by appropriate types of management systems; c) system-forming levers to ensure the inverse relationship within the self-regulatory economic system in its adaptation to the threats and challenges of sustainable development. The article notes that the combinatorics of homeostasis control includes stabilizing, inertial, adaptive, organizational and economic, kinematic, cybernetic, anxiety, cognitive information, reparative, regenerative and other types of control. It emphasizes that a set of mechanisms to ensure the self-regulatory properties of systems should focus on maintaining their adaptability to external and internal transformations in the context of ensuring the transition to sustainable development. Given the four-level structural hierarchy of homeostatic properties, the article substantiates the possibility of ensuring adequate design of regulators for their consolidation in accordance with the priority objects of localization of the most effective management tools and measures. Prospects for further research in the field of ensuring the stability of economic systems in market volatility and growing threats and risks are associated with solving the following problems: a) the formation of a stable management system to b) create a congruent institutional environment at each stage of systemic homeostasis; c) overcoming the existing institutional and resource constraints, eliminating the dangers and risks of sustainable development of economic systems with their differentiation in accordance with the spatial characteristics of the national meta-space. Methodologically important conclusions on the consequences of project implementation (in turbulent conditions) of four stages of management of ensuring the stability of economic systems according to the dominants of homeostasis are formulated. It is confirmed that as a result of achieving homeostasis: the system not only retains the main vital parameters in the process of adaptation to operating conditions and critical changes, but also provides stabilization of activity; systemic homeostatic properties and its stabilization parameters depend on the evolutionary, structural and resistance traits acquired by the system in the previous stages of generation; for the system and its elements or processes (economic, production, natural resource, societal nature) at each point in time should determine the state of the generalized results of the evaluation of five properties and stabilization parameters (self-alignment, inertia, delay, measurements of industry and structural-logical construction) and set the concept of changing these parameters and properties over time

Peak picking NMR spectral data using non-negative matrix factorization

Background: Simple peak-picking algorithms, such as those based on lineshape fitting, perform well when peaks are completely resolved in multidimensional NMR spectra, but often produce wrong intensities and frequencies for overlapping peak clusters. For example, NOESY-type spectra have considerable overlaps leading to significant peak-picking intensity errors, which can result in erroneous structural restraints. Precise frequencies are critical for unambiguous resonance assignments. Results: To alleviate this problem, a more sophisticated peaks decomposition algorithm, based on non-negative matrix factorization (NMF), was developed. We produce peak shapes from Fourier-transformed NMR spectra. Apart from its main goal of deriving components from spectra and producing peak lists automatically, the NMF approach can also be applied if the positions of some peaks are known a priori, e.g. from consistently referenced spectral dimensions of other experiments. Conclusions: Application of the NMF algorithm to a three-dimensional peak list of the 23 kDa bi-domain section of the RcsD protein (RcsD-ABL-HPt, residues 688-890) as well as to synthetic HSQC data shows that peaks can be picked accurately also in spectral regions with strong overlap