Doctor of Philosophy

dissertationThe mammary gland is a branched, secretory organ that that is composed of diverse cells types. The populations that comprise the mammary epithelium include mammary stem cells, lineage-restricted progenitors, and differentiated luminal and basal cells. Breast cancer develops when one or a subset of these epithelial cells undergoes transformation, resulting in disease that can vary broadly in pathology and prognosis. For example, gene expression analysis of a large cohort of breast cancers has classified tumors into distinct subtypes, including: HER2-positive, Basal-Like, Luminal A, and Luminal B. Furthermore, hormone receptor status is also used in the clinic to classify tumors and define the course of treatment. Factors that may contribute to this broad breast cancer diversity are still unclear; however, we hypothesize that breast cancer phenotype may be influenced by intrinsic properties of the originating cell. Therefore, to determine whether specific cells types influence breast cancer pathology, the goal of this dissertation has been to develop a series of mouse models of breast cancer that can be used to target oncogene expression to distinct mammary epithelial cell (MEC) lineages. One such model was generated by infecting mouse MECs with a lentivirus expressing the polyoma virus middle T antigen oncogene, then cells were enriched for specific cell lineages using fluorescence activated cell sorting, and were orthotopically transplanted to generate tumors. Resulting tumors were classified by histology, estrogen receptor status, molecular subtype, and metastatic propensity. Our results demonstrated that each MEC population we evaluated could give rise to diverse tumor types; however, we also determined that MEC populations exhibited differences in their propensity for tumor histology, molecular subtype, and metastatic potential. Furthermore, we developed an additional approach of targeting specific gene expression to distinct MEC populations. In this system, lentiviral constructs were designed to express a specific gene after Cre-mediated recombination. Then, MECs isolated from mice that express Cre iv through cell lineage-restricted promoters were infected with the lentivirus and orthotopically transplanted or analyzed by three-dimensional culture. We validated this approach by targeting fluorescent Tomato reporter and polyoma virus middle T antigen oncogene expression to specific MEC populations in vitro and in vivo

Russia and Latin America: problems and prospective of cooperation

The article reveals the continental orientation of the geopolitics of Latin America. It shows the features of development of the Russian Far East. This region remains a promising area, but in Russian current political strategy it occupies a special place. And there is a hope for the Far Eastern region becoming a Russian Federation’s power center in the Asia-Pacific region. It is emphasized that nowadays the interests of Latin American countries and Russia coincide in several important areas. We can infer that currently it is a conducive situation for the development of relations between Russia and States in Latin America, especially in the economic sphere and in the sphere of tourism, cultural and educational exchanges. The Far East plays an important role in the development of inter-State relations between Russia and Latin America.Keywords: geopolitics, geopolitical vector, geopolitical potential, regional integration, the Far East, Latin America, the Asia-Pacific region, the development of infrastructur

Do online social networks help to get a job? A study on online social networks as a recruitment method in Russia

Introduction Online social networks play an important role in business practices and recruitment is not an exception. At the same time, there is a clear shortage of research about online social networks and their applicability as a recruitment method. Therefore this topic was chosen for this master thesis study. Objective of the Research This study aims to find out what factors make online social networks a useful tool when searching for employment and make practical recommendations on how to use social networking sites to job seekers’ advantage. The study will be geographically limited to Russia since different cultural factors can influence the choice of job search methods in different countries and in order to net out this effect one country was chosen. Methodology The multi method research approach was used in this study. Data was collected utilizing observations, online questionnaire, semi-structured interviews and secondary data. Findings and Conclusions It can be concluded that SNSs are emerging as an important recruitment method in Russia. It was found that job candidates regard online social networks as a very good way to be passively looking for a job as well as receive up to date information about job offerings. Recruiters consider online social networks to be a useful recruitment method due to large candidates’ pool, cost savings and educational benefits. The use of SNSs as recruitment method is expected to grow in the next few years

Open Source Dataset and Machine Learning Techniques for Automatic Recognition of Historical Graffiti

Machine learning techniques are presented for automatic recognition of the historical letters (XI-XVIII centuries) carved on the stoned walls of St.Sophia cathedral in Kyiv (Ukraine). A new image dataset of these carved Glagolitic and Cyrillic letters (CGCL) was assembled and pre-processed for recognition and prediction by machine learning methods. The dataset consists of more than 4000 images for 34 types of letters. The explanatory data analysis of CGCL and notMNIST datasets shown that the carved letters can hardly be differentiated by dimensionality reduction methods, for example, by t-distributed stochastic neighbor embedding (tSNE) due to the worse letter representation by stone carving in comparison to hand writing. The multinomial logistic regression (MLR) and a 2D convolutional neural network (CNN) models were applied. The MLR model demonstrated the area under curve (AUC) values for receiver operating characteristic (ROC) are not lower than 0.92 and 0.60 for notMNIST and CGCL, respectively. The CNN model gave AUC values close to 0.99 for both notMNIST and CGCL (despite the much smaller size and quality of CGCL in comparison to notMNIST) under condition of the high lossy data augmentation. CGCL dataset was published to be available for the data science community as an open source resource.Comment: 11 pages, 9 figures, accepted for 25th International Conference on Neural Information Processing (ICONIP 2018), 14-16 December, 2018 (Siem Reap, Cambodia

Raltegravir Is a Potent Inhibitor of XMRV, a Virus Implicated in Prostate Cancer and Chronic Fatigue Syndrome

Xenotropic murine leukemia-related retrovirus (XMRV) is a recently discovered retrovirus that has been linked to human prostate cancer and chronic fatigue syndrome (CFS). Both diseases affect a large fraction of the world population, with prostate cancer affecting one in six men, and CFS affecting an estimated 0.4 to 1% of the population.. We found that the retroviral integrase inhibitor, raltegravir, was potent and selective against XMRV at submicromolar concentrations, in MCF-7 and LNCaP cells, a breast cancer and prostate cancer cell line, respectively. Another integrase inhibitor, L-000870812, and two nucleoside reverse transcriptase inhibitors, zidovudine (ZDV), and tenofovir disoproxil fumarate (TDF) also inhibited XMRV replication. When combined, these drugs displayed mostly synergistic effects against this virus, suggesting that combination therapy may delay or prevent the selection of resistant viruses.If XMRV proves to be a causal factor in prostate cancer or CFS, these discoveries may allow for rational design of clinical trials

The Place and the Role of the Commonwealth of Unrecognized States in Today’s International Relations on the Post-Soviet Area

Nowadays there are four unrecognized republics (Nagorno-Karabakh, Transnistria, Abkhazia and South Ossetia) on the territory of the former Soviet Union. Together they form the Commonwealth of Unrecognized States, or “parallel CIS”. The main task of the international community is to find acceptable solutions applicable to a particular case, because each of these conflicts is unique. The problem of unrecognized states is a major geopolitical issue for Russia. Russia’s task is to convince the international community that the unrecognized states on the post-Soviet area have the right to exist. Also Russia is one of the main forces that stimulates the resolving of these conflicts. The US and the EU can’t allow Russia be the only leader on the post-Soviet area because it means the growing influence of Russia, which is extremely disadvantageous from a geopolitical point of view. Therefore, the main strategic direction of the policy of the Western countries regarded to the countries of the Commonwealth of Unrecognized States is to support anti-Russian sentiment

От «Черного квадрата» до «Черного зеркала»: современное искусство в поисках света

A hundred years of history of contemporary art, notionally from the picturesque «Black Square» artwork by Malevich (1915) to the British TV series «Black Mirror» by Brooker (2011) and Ruben Östlund’s film «The Square» (2017) is in the focus of this study. The aim is to analyze the axiological foundations of modern art. Relevance of the chosen discourse is due, firstly, it’s enduring importance, and, secondly, major advances in the Architectonics of Culture – from the latest technologies as a factor of cultural development to mental perversions generated by those technologies. Formal, existential and institutional values are highlighted, basing on analysis of the proposed artworks as main axiological tags in current art practices. The formal ones serve to carry the value of novelty, conformity to modern technological platforms, the second – existential – a hardly compliable mix of tolerance and individuality (in terms of compliance with privacy), the third – values of authentication and multiplicativity. As the result of the study, the conclusion has been made that, despite the ironic pathos of postmodernism, art still remains a search space for new value configurations that represent the actual cultural architectonicsВ фокусе исследовательского внимания – сто лет истории современного искусства, условно – от живописной работы «Черный квадрат» Малевича (1915) до британского сериала «Черное зеркало» Брукера (2011) и фильма «Квадрат» Эстлунда (2017). Целью является анализ аксиологических оснований современного искусства. Актуальность избранного дискурса обусловлена, во‑первых, его непреходящей значимостью, во‑вторых, серьезными подвижками в архитектонике культуры – от новейших технологий как фактора культурного развития до порождаемых ими ментальных перверсий. На основании анализа предложенных произведений в качестве основных аксиомаркеров в области актуальных художественных практик выделены формальные, экзистенциальные и институциональные ценности. К первым предлагается отнести ценности новизны, соответствия современным технологическим платформам, ко вторым – сложно соблюдаемый микст толерантности и индивидуальности (в части соблюдения privacy), к третьим – ценности подлинности и мультипликативности. Делается вывод о том, что, несмотря на иронический пафос постмодерна, искусство все равно остается пространством поисков новых ценностных конфигураций, репрезентирующих актуальную культурную архитектоник

ДОСЛІДЖЕННЯ КОРОТКИХ РУКОПИСНИХ ЗАПИСІВ, ВИКОНАНИХ ОСОБАМИ ПОХИЛОГО ТА СТАРЕЧОГО ВІКУ

Nowadays, the objects of forensic handwriting analysis are often become short handwritten records of elderly people and senile. The study of such records is one of the most difficult when conducting handwriting examination. This is due to the nature of this object, which is often subjected to changes due to insufficient written practice, influence of age-related changes in the body or conditions common for the elderly people and senile, frequent execution of short handwritten records in unusual conditions, and sometimes with the help of other people, limitations in the studied graphic material. The article attempts to substantiate and systematize theoretical knowledge on the study of short handwritten records executed by elderly and senile people through analyzing the literature and forensic practice on the study of this type of objects, establishing individual patterns of handwriting, explaining the nature of diagnostic signs occurrence, determining the structure of the process for solving the mentioned tasks. Cases from practice and related problematic aspects of solving identification and diagnostic tasks are considered. The main characteristics of impaired ability (sensory, amnestic and motor aphasia) to write are given. Literature sources are analyzed, which consider the physiological mechanisms of the formation of writing skills and the features of their changes due to various conditions in elderly and senile people. Handwriting can undergo changes owing to aging of the body. Disorder of hand-eye coordination, conditions of the musculoskeletal system, nervous system, circulatory disorders, inherent for elderly and senile people, affect the stability of handwriting features. Testaments, contracts of sale and donation, bank documents are often signed by people of elderly and senile age shortly before death resulting from a serious long illness after experiencing such conditions as stroke or myocardial infarction. It is the aging of the body that is accompanied by deterioration in the state of health, impaired vision, muscle weakness, depletion of the nervous system, decreased mobility of the musculoskeletal system and impaired blood circulation. Features of writing motor skill functioning in the elderly and senile people lead to a slowdown in the tempo of movement, decrease in their amplitude and speed, decrease in the plasticity of movements. The correct ratio of such signs as proficiency and coordination of movements is of great importance. In addition, short handwritten records executed by the elderly and senile people contain a limited amount of graphic material. At the moment of executing a short recording, even under normal conditions, the performer needs a certain adaptation to a situation, which can not be performed while rare or occasional execution of a single short record. Therefore, the stability of a skill while executing short recording has an increased spread, and selective variability has low thresholds.У статті зроблено спробу обґрунтувати й систематизувати теоре-тичні знання щодо дослідження коротких рукописних записів, виконаних особами похилого та старечого віку, шляхом аналізу літератури й екс-пертної практики щодо дослідження подібного виду об’єктів, визначення окремих закономірностей почерку і пояснення природи виникнення діагностичних ознак, а також шляхом визначення структури процесу розв­’язання зазначеного завдання. Наведено основні характеристики порушень здатності писати — сенсорної, амнестичної й моторної афазії. Проаналізо-вано літературні джерела, у яких розглянуто фізіологічні механізми фор-мування навичок письма й особливості їх змін за різних захворювань в осіб похилого та старечого віку. Розглянуто випадки з експертної практики та пов’язані з цим проблемні аспекти розв’язання ідентифікаційних і діагно-стичних завдань

INTEGRATIVE MUSICAL PSYCHOLOGY

Introduction. In recent decades, diverse scientific directions have been actively developed at the interface between various fields of knowledge, including social sciences and humanities. Interdisciplinary research provides a high-quality “unification” of achievements of different sciences and gains fundamental value, since they allow full information on this or that studied subject or phenomenon to be received and options of optimum solutions for difficult research tasks to be obtained. However, there are two problem zones in an integrative trend of knowledge – ontological and epistemological origin.The aim of the research was to reveal the potential of interdisciplinary research and integration of diverse directions from several disciplines by the example of musical psychology. Methodology and research methods. The provisions of the system-integrative approach and the concept of “meta-individual world” (MIW) were employed. The MIW theory justifies the heterogeneous, multi-qualitative, multi-determined nature of poly-systems. Results and scientific novelty. The subject field of musical psychology is outlined and characterised. It is shown that now it is shattered into multi-directional components from the field of psychology and musicology, which links are poorly articulated. The reason is not only in heterogeneity of basic psychological and musicological concepts, but also in the discrepancy of ontological status of objects and objects of two key structural components of the sphere under discussion. Nevertheless, there is urgent necessity for their cross-disciplinary integration and elimination of epistemological dualism in the development of scientific industry. The theoretical and logical grounds for the introduction of the concepts of  “musicological” and “psychological” musical psychology are obviously provided. Differences between them are shown: if the first is turned to a piece of music, then the second – to mentality of a composer and a musician. However, they generate unequal phenomenology and lie outside to each other, although they move in the opposite direction. Therefore, the need for creation of integrative musical psychology (IMP) as psychogenetics, psychophysiology, ethnopsychology or behavioural geography is recognised. As the integrative prototype, it is proposed to use the concept of MIW, which supports the pluralistic view on IMP, i.e. IMP considers individuality (personality, mentality, consciousness) and world (external realities, social groups, culture, art) in a coherent manner. The authors proposed the idea of musical psychology transcendence – bidirectional transitions from one its subject field to another. The main point of existence of such transitions consists in the emergence of the phenomena of otherness as the form (way) of overcoming gaps between subject areas of “psychological” and “musicological” musical psychology. The present research concretises and justifies the ways of formation and development of IMP and contributes to the methodology of social sciences and humanities.Practical significance. The research materials are of practical importance for education of graduates of musical and art specialties. In the teaching and educational process, it is necessary to use the potential of two aspects of musical psychology, but not separately, in order to form and develop in students the skills of transcendental perception and analysis of pieces of music. Введение. В последние десятилетия в науке, в том числе в ее общественно-гуманитарной области, активно развиваются направления на стыке различных отраслей знания. Междисциплинарные исследования, благодаря которым происходит качественное соединение достижений разных наук, приобретают фундаментальное значение, поскольку они позволяют получить максимально полные сведения о том или ином изучаемом предмете либо явлении и найти варианты оптимальных решений для сложных исследовательских задач. Однако в интегративном тренде знаний обнаруживаются, по крайней мере, две проблемные зоны – онтологического и эпистемологического происхождения. Цель исследования, которому посвящена статья, – раскрыть на примере музыкальной психологии потенциал междисциплинарного исследования и интеграции разнокачественных образований из нескольких дисциплин. Методология и методики. В работе использовались положения системно-интегративного подхода к изучению человека и концепции «метаиндивидуального мира» (МИМ), базирующейся на представлениях о гетерогенной, многокачественной, многодетерминированной природе полисистем. Результаты и научная новизна. Очерчено и охарактеризовано предметное поле музыкальной психологии. Показано, что в настоящее время оно раздроблено на разнонаправленные составляющие из области психологии и музыкознания, связи между которыми слабо артикулированы. Причина заключается не только в разнородности базовых психологических и музыковедческих понятий, но и в несовпадении онтологического статуса объектов и предметов двух ключевых структурных компонентов обсуждаемой сферы. Вместе с тем явственно ощущается потребность их междисциплинарной интеграции и устранения эпистемологического дуализма в развитии научной отрасли. Впервые теоретически и логически сформулированы основания для введения понятий «музыковедческой» и «психоведческой» музыкальных психологий. Показаны различия между ними: если первая обращена к собственно музыкальному произведению, то вторая – к психике композитора и музыканта. И хотя они порождают неодинаковые феноменологии и внеположны друг другу, но движутся во встречном направлении. Поэтому акцентируется необходимость построения интегративной музыкальной психологии (ИМП) по типу психогенетики, психофизиологии, этнопсихологии или поведенческой географии. В качестве интеграционного прототипа предлагается концепция МИМ, которая допускает плюралистический взгляд на ИМП и в которой индивидуальность (личность, психика, сознание) и мир (внешние реалии, социальные группы, культура, искусство) рассматриваются в едином ключе. Выдвигается идея трансцендентности музыкальной психологии – двунаправленных переходов из одного ее предметного поля в другое. Главный смысл наличия таких переходов состоит в появлении феноменов инобытия как формы (способа) преодоления разрывов между предметными областями «психоведческой»и «музыковедческой» музыкальной психологии. Изложенное исследование конкретизирует пути становления и укрепления ИМП и вносит свою лепту в методологию гуманитарно-общественных наук в целом. Практическая значимость. Материалы публикации имеют важное прикладное значение для подготовки выпускников музыкальных и искусствоведческих специальностей. В учебно-воспитательном процессе следует использовать потенциал двух аспектов музыкальной психологии совместно, а не по отдельности, формируя и развивая у студентов умения и навыки трансцендентного восприятия и анализа музыкальных произведений