Nanoparticle-Based Magnetic Resonance Imaging on Tumor-Associated Macrophages and Inflammation

The inflammatory response, mediated by tissue-resident or newly recruited macrophages, is an underlying pathophysiological condition for many diseases, including diabetes, obesity, neurodegeneration, atherosclerosis, and cancer. Paradoxically, inflammation is a double-edged sword in oncology. Macrophages are, generally speaking, the major drivers of inflammatory insult. For many solid tumors, high density of cells expressing macrophage-associated markers have generally been found in association with a poor clinical outcome, characterized by inflamed microenvironment, a high level of dissemination and resistance to conventional chemotherapies. On another hand, radiation treatment also triggers an inflammatory response in tumors (often referred to as pseudoprogression), which can be associated with a positive treatment response. As such, non-invasive imaging of cancer inflammation and tumor-associated macrophages (TAMs) provides a revolutionary diagnostic tool and monitoring strategy for anti-inflammatory, immuno- and radiotherapies. Recently, quantitative T2-weighted magnetic resonance imaging (qT2wMRI), using injection of superparamagnetic iron oxide nanoparticles (SPIONs), has been reported for the assessment of TAMs non-invasively in animal models and in human trials. The SPIONs are magnetic resonance imaging (MRI) contrast agents that significantly decrease T2 MR relaxation times in inflamed tissues due to the macrophage-specific uptake and retention. It has been shown that macrophage-populated tumors and metastases will accumulate iron oxide nanoparticles and decrease T2-relaxation time that will result in a negative (dark) contrast in qT2wMRI. Non-invasive imaging of TAMs using SPION holds a great promise for staging the inflammatory microenvironment of primary and metastatic tumors as well monitoring the treatment response of cancer patients treated with radiation and immunotherapy

Metabolic Imaging to Assess Treatment Response to Cytotoxic and Cytostatic Agents

For several decades, cytotoxic chemotherapeutic agents were considered the basis of anti-cancer treatment for patients with metastatic tumors. A decrease in tumor burden, assessed by volumetric computed tomography (CT) and magnetic resonance imaging (MRI), according to the Response Evaluation Criteria in Solid Tumors (RECIST), was considered as a radiological response to cytotoxic chemotherapies. In addition to RECIST-based dimensional measurements, a metabolic response to cytotoxic drugs can be assessed by positron emission tomography (PET) using 18F-fluoro-thymidine (FLT) as a radioactive tracer for drug-disrupted DNA synthesis. The decreased 18FLT-PET uptake is often seen concurrently with increased apparent diffusion coefficients (ADC) by diffusion weighted imaging (DWI) due to chemotherapy-induced changes in tumor cellularity. Recently, the discovery of molecular origins of tumorogenesis led to the introduction of novel signal transduction inhibitors (STIs). STIs are targeted cytostatic agents; their effect is based on a specific biological inhibition with no immediate cell death. As such, tumor size is not anymore a sensitive end-point for a treatment response to STIs; novel physiological imaging end-points are desirable. For receptor tyrosine kinase inhibitors as well as modulators of the downstream signaling pathways, an almost immediate inhibition in glycolytic activity (the Warburg effect) and phospholipid turnover (the Kennedy pathway) has been seen by metabolic imaging in the first 24 hours of treatment. The quantitative imaging end-points by magnetic resonance spectroscopy (MRS) and metabolic PET (including 18F-fluoro-deoxy-glucose, FDG, and total choline) provide an early treatment response to targeted STIs, before a reduction in tumor burden can be seen

Impact of infrastructure on socio-economic development of Russian regions: methodology and analysis

Relevance. Regional infrastructure development directly affects economic growth, social development and the quality of life. To identify the key areas of infrastructure development in Russian regions, it is necessary to develop a methodological approach to the analysis of the impact of infrastructure on socio-economic development, which determines the relevance of this study.Research objective. This study aims to improve the methodology of assessment of the role infrastructure plays in the socio-economic development of Russian regions.Data and methods. The analysis relies on a system of general and integral, static and dynamic indicators used to assess the current state and dynamics of infrastructure in regions. The analysis takes into account the structural and functional features of infrastructure. The proposed methodology comprises methods for obtaining comparative estimates of regional infrastructure development, which can be applied to compile regional rankings. The study also uses methods of econometric and K-means cluster analysis.Results.  A comparative analysis of the infrastructure development of Russian regions allowed us to assess the infrastructural potential of these regions, the discrepancies in infrastructure development and compare the infrastructure-related characteristics of the leading lagging regions. The results of econometric analysis as well as cluster analysis of regions based on general and integral dynamic indicators are discussed.Conclusions. The methodological approach proposed by the authors has been tested by using the data on Russian regions. The analysis has revealed the most typical problems faced by Russian regions. These problems should be taken into account in strategic decision- and policy-making

Cultural code in controlling stereotypes of mass consciousness

The article is concerned with the problem of interrelation between mental dynamics of mass subject and functions of cultural code in the context of modern media environment. The urgency of researching a hidden control mechanism through background knowledge and mass consciousness stereotypes is determined by the fact that modern global information and communication networks transform and destabilize the sociocultural semantic space in its historically developed order. The methodology of analyzing control of mass consciousness stereotypes is based on integration of sociocultural, semiotic, communicative aspects of studying properties of cultural code in the mass media theory. It is emphasized that code control of an individual’s mentality dynamics is exercised anonymously. Knowledge of the reality where implicit instructions for an immediate perception of the world play a special role naturally forms stereotyped practices of understanding and action that are not reflected in everyday life. Codes set a certain limit of perception of events and their evaluation, catalyze a predicted stereotyped reaction. Cultural codes based on sign-oriented symbols form a semantic matrix that communicates basic orientation in the physical and sociocultural space to an individual’s subconsciousness. This invisible framework, determinated by a sign-oriented form, ensures transmission of a socially significant meaning that is necessary for mutual understanding of people, social control of their actions and thinking. The tendency to dominate functional and adaptive rationality in the media environment is accompanied by a transformation of the world perception stereotype, erosion of semantic boundaries between the real and the virtual, the subjective and the objective.peer-reviewe

Promotion of Environmentally Friendly Products

The promotion of natural products in the modern world is becoming more and more relevant and increases the environmental literacy of society. The article discusses the tools of environmental marketing in the activities of companies and the importance of environmentally friendly products in people’s lives. The author conducts a survey of consumers using a survey, and based on the results, a Scandinavian market map is compiled, which helps determine the position of the manufacturer of natural ice cream «Clean Line» among competitors.Продвижение натуральных продуктов в современном мире всё больше становится актуальным и повышает экологическую грамотность общества. В статье рассматриваются инструменты экологического маркетинга в деятельности компаний и важность экологически чистых продуктов в жизни людей. Автором проводится исследование потребителей с помощью опроса, а также на основе результатов составляется скандинавская карта рынка, которая помогает определить позиции компании-производителя натурального мороженного «Чистая линия» среди конкурентов

Contract as economical and legal design

In article on the basis of the analysis of works of the Russian and foreign scientists-lawyers, experts lawyers, and also economists the contract research as economical and legal design is conducted. The contract as an economical and legal design represents the special economical and legal mechanism regulator mediating economic activity, designed to provide legal satisfaction of economic interests, certain subjects, formed by the elements interconnected and coordinated among them.It is revealed that such economical and legal design consists both from legal, and from economic elements. It is formed of the following obligatory and necessary elements: (1) legal procedure of coordination of terms of the contract, (2) form of the contract, (3) term, (4) subjective rights and legal obligations of the parties, (5) valid economic contents of the contract. The list of the designated elements of the contract is open and depends on complexity of the most economical and legal design and a type of the bilateral or multilateral civil transaction.The nature of its legal communications exerts impact on an economical and legal orientation of a design of the contract. In turn features of contractual communications affect achievement of the legal purposes.It is proved that the contract as an economical and legal design has to be always filled with economic sense. It is shown that lack of the valid economic sense of the contract is considered by law-enforcement practice therefore leads to adverse legal effects

Computational reconstruction of tissue-specific metabolic models: application to human liver metabolism

The first computational approach for the rapid generation of genome-scale tissue-specific models from a generic species model.A genome scale model of human liver metabolism, which is comprehensively tested and validated using cross-validation and the ability to carry out complex hepatic metabolic functions.The model's flux predictions are shown to correlate with flux measurements across a variety of hormonal and dietary conditions, and are successfully used to predict biomarker changes in genetic metabolic disorders, both with higher accuracy than the generic human model