Arctic Transformations: Multinational Companies Facing the New Challenges of Sustainable Development

What is the impact of the ongoing transformations in the Arctic region – global warming, socio-economic and institutional changes – on internationalization in the Arctic and the activities of multinational companies in the polar regions of the Arctic countries? What is the role of multinational companies in the sustainable development of these regions, including the ensuring of the welfare of the northerners? The article attempts to answer these questions and discuss new approaches to the problem of sustainable development in the Arctic region with its extremely vulnerable and severe nature, large reserves of natural resources, unique human potential, dynamically developing economy, infrastructure and active involvement in the world economy. The main emphasis is on the assessing of the social component in the triangle of the interrelated priorities of sustainable development  – social, environmental and economic. The analysis showed that the consequences of systemic transformations form a new context for the activities of multinational companies, which have to adapt their corporate strategies to the Arctic specifics. The northern regions are actively involved in internationalization; a significant part of their GRP is produced by enterprises controlled by multinational companies. Assessments of the role of multinational companies for the local population and sustainable development are mixed. Such companies help to modernize the economy and infrastructure, create jobs, place orders with local producers, and develop human potential. In a number of countries, the control of the local population over the activities of multinational corporations (USA, Canada) is strengthening. At the same time, serious social and economic imbalances arise, including social disproportions and stratification of the population, as well as challenges for traditional activities and nature. The contribution of the Arctic regions to the world economy is almost five times higher than their share in the world population. Obtaining a social license from the northerners, implementing corporate social responsibility is becoming a popular instrument used by multinational companies to support their activities in the Arctic. The interaction between the state and multinational companies is strengthening, and the forms of state regulation of the access to natural resources and infrastructure are being diversified. The study is based on the analysis of the practices of foreign Arctic countries, rich in mineral and energy resources – the USA, Canada and Norway; their approaches and practices may be of interest to Russia and its northern regions. In conclusion, new scientific concepts of adaptive governance of sustainable development and its inclusiveness in the context of the interaction between transforming natural and social systems in the Arctic are summarized

Citation of Mass Media Resources in Social Network

The role of social networks in the formation of collective behaviour and a sustainable point of view/position regarding the information events or facts is studied herein. The purpose of the study is to analyse the reaction of the users of popular social networks, expressed in quotations and responses to the messages of mass media resources. A statistical measure of interest in the media news is identified through unique messages from queries on the topic. The approach used is aimed at improving the scientific argumentation on the assumption of a direct relationship between these phenomena. The empirical evaluation is carried out according to the data obtained from the Russian segment of social networks. The trends in the distribution of media content in social media and social networks are revealed using structural and correlation analysis. It is determined that the publications in online media correlate directly with the activities of social networks and are caused by the release of one or another information event. The results of the study also convincingly point out that the importance of the media resources, expanding due to the integration of social networks, increases, while the classical model of online media (media edition as own website) is gradually losing popularity and audience

Dimethyl 11,13-dimethyl-16-[1,2-bis­(methoxy­carbon­yl)ethen­yl]-12-oxo-16,17-dioxa-18-aza­hexa­cyclo­[7.5.1.11,4.16,9.110,14.05,15]octa­deca-2,7-diene-2,3-dicarboxyl­ate

The title compound, C27H29NO11, is a product of the tandem ‘domino’ Diels–Alder reaction. The mol­ecule comprises a fused hexa­cyclic system containing four five-membered rings (two dihydro­furan and two tetra­hydro­furan) in the usual envelope conformations and two six-membered rings (tetra­hydro­pyridinone and piperidine) adopting slightly flattened boat and chair conformations, respectively. The dispositions of the carboxyl­ate substituents relative to each other are determined by both steric reasons and inter­molecular C—H⋯O hydrogen bonding and attractive anti­parallel C=O⋯C=O inter­actions [C⋯O = 2.995 (2) Å]

Modeling Energy-Efficient Consumption at Industrial Enterprises

A possibility to reduce costs incurred in both product manufacturing and energy consumption constitutes energy-efficient consumption at industrial enterprises. Manufacturers operating in various economic sectors adopt similar conceptual models of energy consumption, which allows developing a universal solution for modeling such processes. The central problem of modeling lies in finding an adequate objective function based on a sufficient set of parameters and characteristics of the efficiency of an enterprise's power circuit. The article justifies the performance indicators of industrial enterprises' power supply systems. The literature review proves that economic feasibility of energy efficiency is especially obvious if a massive modernization program is implemented. The estimates produced indicate that the largest portion of the potential energy savings is attributed to implementation of energy-saving projects in industrial buildings and other structures. We present a mathematical model designed to perform a comparative analysis of technical and economic features of two modernization scenarios of the heat and power supply system of an industrial enterprise circuit. Performing a simulation calculation based on performance aspects of Russian companies, the paper outlines the advantages of integrated modernization and analyzes the influence of various factors. The results reveal that there is an inverse correlation between specific heat consumption of buildings under thermal modernization and the length of the thermal network. As specific energy consumption in the thermal modernization scenario increases, the payback period for capital investments decreases. The effect of this dynamics is virtually proportional. Compared with total costs for various heat sources, the share of capital costs differs significantly; however, the share of running costs is dominant for all types of units. At the same time, the length of an enterprise's heat circuit weakly affects the payback period of capital costs. Keywords: Energy efficiency; Industrial enterprise; Thermal modernization; Energy modeling. JEL Classifications: Q43, L95, L97 DOI: https://doi.org/10.32479/ijeep.737

Methyl (9aR*,10S*,11R*,13aS*,13bS*)-9-oxo-6,7,9,9a,10,11-hexa­hydro-5H,13bH-11,13a-ep­oxy­pyrrolo­[2′,1′:3,4][1,4]diazepino[2,1-a]isoindole-10-carboxyl­ate

The title compound, C17H18N2O4, is the methyl ester of the adduct of intra­molecular Diels–Alder reaction between maleic anhydride and 1-(2-fur­yl)-2,3,4,5-tetra­hydro-1H-pyrrolo­[1,2-a][1,4]diazepine. The mol­ecule comprises a fused penta­cyclic system containing four five-membered rings (viz. pyrrole, 2-pyrrolidinone, tetra­hydro­furan and dihydro­furan) and one seven-membered ring (1,4-diazepane). The pyrrole ring is approximately planar (r.m.s. deviation = 0.003 Å) while the 2-pyrrolidinone, tetra­hydro­furan and dihydro­furan five-membered rings have the usual envelope conformations. The central seven-membered diazepane ring adopts a boat conformation. In the crystal, mol­ecules are bound by weak inter­molecular C—H⋯O hydrogen-bonding inter­actions into zigzag chains propagating in [010]. In the crystal packing, the chains are stacked along the a axis

Abnormal methylation of PRDM16 and PTPRN2 genes in chorionic villi in miscarriage

Relevance. Abnormal epigenetic regulation of genes responsible for the development of the embryo and placenta is associated with many pregnancy pathologies. Aim. The aim of this work was to analyze the prevalence of abnormal methylation of the PRDM16 and PTPRN2 genes in chorionic villi of spontaneous abortions with normal karyotype and with the most frequent aneuploidies (trisomy 16 and monosomy X). Materials and Methods. The methylation profile was evaluated using targeted bisulfite massive parallel sequencing in chorionic villi of induced abortions (n = 10), spontaneous abortions with normal karyotype (n = 39), trisomy 16 (n = 17) and monosomy X (n = 20) and peripheral blood lymphocytes of healthy volunteers (n = 6). Results and Discussion. In analyzed genes, differential methylation of individual CpG sites was found in chorionic villi of spontaneous abortions. Despite the absence of significant differences between the groups in the average level of methylation in analyzed gene regions, abnormal methylation of the PRDM16 and PTPRN2 genes were detected for 33 % and 5 % of spontaneous abortions, respectively, indicating a high incidence of epigenetic abnormalities in these genes in the chorionic villi of spontaneous abortions. The level of methylation of the PRDM16 gene significantly correlated with the level of methylation of the retrotransposon LINE-1, which indicates the generalized nature of methylation disorders in spontaneous abortions. Finally, the level of methylation of the PTPRN2 gene depended on the age of mothers of spontaneous abortions with monosomy X, which raises the question of the influence of maternal factors on the methylation profile in this group of spontaneous abortions. Conclusion. The results indicate that epigenetic disorders of the PRDM16 gene may be associated with spontaneous termination of pregnancy in the first trimester

LINE-1 retrotransposon methylation in chorionic villi of first trimester miscarriages with aneuploidy

Purpose High frequency of aneuploidy in meiosis and cleavage stage coincides with waves of epigenetic genome reprogramming that may indicate a possible association between epigenetic mechanisms and aneuploidy occurrence. This study aimed to assess the methylation level of the long interspersed repeat element 1 (LINE-1) retrotransposon in chorionic villi of first trimester miscarriages with a normal karyotype and aneuploidy. Methods The methylation level was assessed at 19 LINE-1 promoter CpG sites in chorionic villi of 141 miscarriages with trisomy of chromosomes 2, 6, 8-10, 13-15, 16, 18, 20-22, and monosomy X using massive parallel sequencing. Results The LINE-1 methylation level was elevated statistically significant in chorionic villi of miscarriages with both trisomy (45.2 +/- 4.3%) and monosomy X (46.9 +/- 4.2%) compared with that in induced abortions (40.0 +/- 2.4%) (p < 0.00001). The LINE-1 methylation levels were specific for miscarriages with different aneuploidies and significantly increased in miscarriages with trisomies 8, 14, and 18 and monosomy X (p < 0.05). The LINE-1 methylation level increased with gestational age both for group of miscarriages regardless of karyotype (R = 0.21, p = 0.012) and specifically for miscarriages with trisomy 16 (R = 0.48, p = 0.007). LINE-1 methylation decreased with maternal age in miscarriages with a normal karyotype (R = - 0.31, p = 0.029) and with trisomy 21 (R = - 0.64, p = 0.024) and increased with paternal age for miscarriages with trisomy 16 (R = 0.38, p = 0.048) and monosomy X (R = 0.73, p = 0.003). Conclusion Our results indicate that the pathogenic effects of aneuploidy in human embryogenesis can be supplemented with significant epigenetic changes in the repetitive sequences

Novel Photosensitizers Trigger Rapid Death of Malignant Human Cells and Rodent Tumor Transplants via Lipid Photodamage and Membrane Permeabilization

BACKGROUND: Apoptotic cascades may frequently be impaired in tumor cells; therefore, the approaches to circumvent these obstacles emerge as important therapeutic modalities. METHODOLOGY/PRINCIPAL FINDINGS: Our novel derivatives of chlorin e(6), that is, its amide (compound 2) and boronated amide (compound 5) evoked no dark toxicity and demonstrated a significantly higher photosensitizing efficacy than chlorin e(6) against transplanted aggressive tumors such as B16 melanoma and M-1 sarcoma. Compound 5 showed superior therapeutic potency. Illumination with red light of mammalian tumor cells loaded with 0.1 µM of 5 caused rapid (within the initial minutes) necrosis as determined by propidium iodide staining. The laser confocal microscopy-assisted analysis of cell death revealed the following order of events: prior to illumination, 5 accumulated in Golgi cysternae, endoplasmic reticulum and in some (but not all) lysosomes. In response to light, the reactive oxygen species burst was concomitant with the drop of mitochondrial transmembrane electric potential, the dramatic changes of mitochondrial shape and the loss of integrity of mitochondria and lysosomes. Within 3-4 min post illumination, the plasma membrane became permeable for propidium iodide. Compounds 2 and 5 were one order of magnitude more potent than chlorin e(6) in photodamage of artificial liposomes monitored in a dye release assay. The latter effect depended on the content of non-saturated lipids; in liposomes consisting of saturated lipids no photodamage was detectable. The increased therapeutic efficacy of 5 compared with 2 was attributed to a striking difference in the ability of these photosensitizers to permeate through hydrophobic membrane interior as evidenced by measurements of voltage jump-induced relaxation of transmembrane current on planar lipid bilayers. CONCLUSIONS/SIGNIFICANCE: The multimembrane photodestruction and cell necrosis induced by photoactivation of 2 and 5 are directly associated with membrane permeabilization caused by lipid photodamage

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores

No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest