Molecular chaperones facilitate the correct folding of other proteins under physiological and stress conditions. Recently it has become evident that various co‐chaperone proteins regulate the cellular functions of these chaperones, particularly Hsp70 and Hsp90. Hop is one of the most extensively studied co‐chaperones that is able to directly associate with both Hsp70 and Hsp90. The current dogma proposes that Hop functions primarily as an adaptor that directs Hsp90 to Hsp70‐client protein complexes in the cytoplasm. However, recent evidence suggests that Hop (...) can also modulate the chaperone activities of these Hsps, and that it is not dedicated to Hsp70 and Hsp90. While the co‐chaperone function of Hop within the cytoplasm has been extensively studied, its association with nuclear complexes and prion proteins remains to be elucidated. This article will review the structural features of Hop, and the evidence that its biological function is considerably broader than previously envisaged. BioEssays 26:1058–1068, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Self‐renewal and differentiation of stem cells are tightly regulated processes subject to intrinsic and extrinsic signals. Molecular chaperones and co‐chaperones, especially heat shock proteins (Hsp), are ubiquitous molecules involved in the modulation of protein conformational and complexation states. The function of Hsp, which are typically associated with stress response and tolerance, is well characterized in differentiated cells, while their role in stem cells remains unclear. It appears that embryonic stem cells exhibit increased stress tolerance and concomitant high levels of chaperone (...) expression. This review critically evaluates stem cell research from a molecular chaperone perspective. Furthermore, we propose a model of chaperone‐modulated self‐renewal in mouse embryonic stem cells. (shrink)

The purpose of the article is the analysis of the causes of the systemic crisis that hit modern civilization through the description of its main structures, identifying the relationship between its elements, assessments of their heuristic potential. This will open up opportunities for finding ways to resolve this crisis, new directions of civilizational development. Theoretical basis of the research are the systems analysis, socio-philosophical and philosophical-anthropological approaches as well as the analysis of scientific developments in the field of global studies. (...) Originality lies in the fact that this article is the first to show the connection between the main structural elements of human civilization as a system. Change in one of the parameters leads to a change in all the others, together with a change in civilization as a whole. Conclusions. The reason for the deep crisis that hit modern civilization is its imbalance as a system. The most important elements of this system are population size, resources and technology, and the core is consciousness in its individual and collective forms. The perception, processing, and use of information, which is a defining civilizational resource, as well as the stability of the entire system depend on the state of consciousness. Consciousness, based on old, obsolete principles and stereotypes, is unable to cope with the most acute challenges of time. New consciousness, since it is formed, will mark the transition to a new theoretical picture of the world and a model of human behavior, in which people will act, driven by proven knowledge, and not willfulness and prejudice. The idea of forming a productive information environment where the ideas of constructiveness and creative work will dominate rather than consumerism and destruction, as is the case at present, must become the categorical imperative of the new consciousness. (shrink)

The concept of interpretation is applicable to any forms of knowledge, including systems of religious knowledge, designing the ideal model of the subject of religious veneration. The author analyzes the epistemological features of theology as a form of spiritual culture, its formation in ancient culture. It is shown that the epistemological basis for overcoming mythological consciousness was the decentralization of thinking, i.e. development of the ability of consciousness in the construction of the image, the picture of the world to correct (...) the position of the subject, to take into account the relativity of the reference system, from the standpoint of which the subject perceives the object and transforms it into an operational system of thinking. Decentration of thinking provided the overcoming of the subjective mental boundaries of the field, giving the thinking nature of universality. Historical stages and moments of this process - the transformation of mythology into forms of folk art, mythopoetic epic, in the form of religious consciousness. In line with such transformations of archaic consciousness, cultural and historical prerequisites of theology emergence were formed. They are represented in mythopoetic art, ancient mythography, early traditions of critical and rationalistic interpretation of the myth, etc. The article shows the formation of allegorical theology, which became possible in the era of individualization of artistic creativity, when the visible was the difference between the motive and the purpose of activity, creative idea and its embodiment, figuratively-poetic and rationally-conceptual ways of reflecting the world, when the image of reality and its personal meaning began to be realized as different States of consciousness. The main function of any theology is the interpretation of abstract models of the subject of religious veneration. (shrink)

The aim of this study was to explore the existence of moral distress among nurses in Lilongwe District of Malawi. Qualitative research was conducted in selected health institutions of Lilongwe District in Malawi to assess knowledge and causes of moral distress among nurses and coping mechanisms and sources of support that are used by morally distressed nurses. Data were collected from a purposive sample of 20 nurses through in-depth interviews using a semi-structured interview guide. Thematic analysis of qualitative data was (...) used. The results show that nurses, irrespective of age, work experience and tribe, experienced moral distress related to patient/nursing care. The major distressing factors were inadequate resources and lack of respect from patients, guardians, peers and bosses. Nurses desire teamwork and ethics committees in their health institutions as a means of controlling and preventing moral distress. There is a need for creation of awareness for nurses to recognize and manage moral distress, thus optimizing their ability to provide quality and uncompromised nursing care. (shrink)

BackgroundThe potential contribution of community engagement to addressing ethical challenges for international biomedical research is well described, but there is relatively little documented experience of community engagement to inform its development in practice. This paper draws on experiences around community engagement and informed consent during a genetic cohort study in Kenya to contribute to understanding the strengths and challenges of community engagement in supporting ethical research practice, focusing on issues of communication, the role of field workers in 'doing ethics' on (...) the ground and the challenges of community consultation.MethodsThe findings are based on action research methods, including analysis of community engagement documentation and the observations of the authors closely involved in their development and implementation. Qualitative and quantitative content analysis has been used for documentation of staff meetings and trainings, a meeting with 24 community leaders, and 40 large public and 70 small community group meetings. Meeting minutes from a purposive sample of six community representative groups have been analysed using a thematic framework approach.ResultsField workers described challenges around misunderstandings about research, perceived pressure for recruitment and challenges in explaining the study. During consultation, leaders expressed support for the study and screening for sickle cell disease. In community meetings, there was a common interpretation of research as medical care. Concerns centred on unfamiliar procedures. After explanations of study procedures to leaders and community members, few questions were asked about export of samples or the archiving of samples for future research.ConclusionsCommunity engagement enabled researchers to take account of staff and community opinions and issues during the study and adapt messages and methods to address emerging ethical challenges. Field workers conducting informed consent faced complex issues and their understanding, attitudes and communication skills were key influences on ethical practice. Community consultation was a challenging concept to put into practice, illustrating the complexity of assessing information needs and levels of deliberation that are appropriate to a given study. (shrink)

The importance of communities in strengthening the ethics of international collaborative research is increasingly highlighted, but there has been much debate about the meaning of the term ‘community’ and its specific normative contribution. We argue that ‘community’ is a contingent concept that plays an important normative role in research through the existence of morally significant interplay between notions of community and individuality. We draw on experience of community engagement in rural Kenya to illustrate two aspects of this interplay: (i) that (...) taking individual informed consent seriously involves understanding and addressing the influence of communities in which individuals’ lives are embedded; (ii) that individual participation can generate risks and benefits for communities as part of the wider implications of research. We further argue that the contingent nature of a community means that defining boundaries is generally a normative process itself, with ethical implications. Community engagement supports the enactment of normative roles; building mutual understanding and trust between researchers and community members have been important goals in Kilifi, requiring a broad range of approaches. Ethical dilemmas are continuously generated as part of these engagement activities, including the risks of perverse outcomes related to existing social relations in communities and conditions of ‘half knowing’ intrinsic to processes of developing new understandings. (shrink)

The purpose is to identify common and distinctive features of concepts and methodology of the problem of subject within different discourses, implicitly or explicitly relevant to the definition of "clinical" mode of human existence. The research methodology combines techniques of discourse analysis and basic principles of historical and philosophical studies. Originality of the research lies in definition of the clinical philosophical discourse as a special communicative process, where utterances not only focus on disease syndromes, and reveal phenomenology of inner experience (...) of a pathological self, but also structure a certain type of sociality. Clinical discourse represents the space where the patient is treated not as a subject but as an object of disease. Ontology of clinical discourse prevails over ontology of disease, since its structures determine the notion of disease as such. Categorization of the disease, the idea of disease as a phenomenon subdued to professional authority leads to the idea of the need for patient’s isolation from the natural environment and removing him to special social institutions. The clinicist doctrines share the intention to reduce the patient’s self to its bodily dimension, while ignoring social determinants of psychological deviations. Conclusions of the study are summarized in the following positions: the current clinical discourse is based on the positivist-biological trend in humanitarian knowledge and it is the basis for the production and reproduction of medical and pharmaceutical repressive ideology; criticism of philosophical clinical discourse opens the possibility of overcoming the dominance of purely clinicist discourse; such a transformation is possible only after a paradigm shift in understanding the category of subject. (shrink)

This article is devoted to the study of the peculiarities of the functioning of the connection between the brain and the body, the analysis of possible disturbances in the transmission of information impulses from the brain to the body and consideration of the causes of distortion and defects in the implementation of this connection. The specifics of the connection between the brain and the body are considered from the point of view of various areas: neurophysiological, anatomical, psychological. Examples of communication (...) distortion and reasons for incorrect transmission of the reaction are given. An analysis of all possible factors influencing the implementation of the connection under consideration is carried out, various types of violations are listed, and methods for correcting these violations are also presented. The result of this study is the structuring of information about the functioning of the connection between the brain and the body, consideration of all special cases of defectiveness of this connection and an explanation of the reasons for their occurrence. The article will be of practical benefit to specialists in the field of neurobiology. (shrink)

Purpose. The article deals with the problem of mutual perception of individuals, which implies the analysis of the anthropological prerequisites for the study of interpersonal communication. The work emphasizes the need to identify the gnoseological lacuna of the possibility and relevance of knowing someone else’s "I". As well as the need to point out implicit metaphysical attitudes, universal for many worldviews, which are implicitly included in the theory of personal communication. Theoretical basis. The author proceeds from the logical consequences of (...) the evolutionary premise in anthropology. He compares the psychophysical goals of the interpersonal communication task with its ideological theory, monitors the impossibility of the realizing the communication level declared in the consciousness. As an opposite evolutionary premise, the author cites the postulates of the "philosophy of dialogue" by F. Rosenzweig, F. Ebner, M. Buber, and others. The correlation of these philosophical positions reveals the inconsistency of materialistic reduction in anthropology. Originality. The author identifies four levels of communication: background, obstacle, function and dialogue. He represents the rationale for the fact that the first three levels do not need the existence of an individual "I". The first three levels leave the existential "I" unnecessary and therefore unclaimed. The philosophy of dialogue with the Other raises an equally important question about the conditions for the possibility of a metaphysical continuum in ontology, and in turn, suggests the acceptance of a philosophical premise about God as the space of subjectivity in the "I-You" dialogue. Conclusions. Philosophical understanding of the communication of two existential "I" demanded in communication is possible only within the framework of religious discourse. The phenomenal consciousness can enter into communication with a specific other phenomenal consciousness only when there is a metaphysical space between them, allowing for the possibility of communication of such a level. The materialistic conditioning by the human evolutionary needs in all its conceivable forms produces a reduction of the communicative inquiry, which makes the mutual perception of the two "I" impossible. In this psychophysiological anthropological model, there is no space for the possibility of a dialogue of individuals. (shrink)

In this paper, we use Saaty's Eigenvector Method and the Power Method as well as Ω=1, 2, ⋯ , 9, 1/2, 1/3, ⋯ , 1/9} and Ω-={1,2, ⋯ ,9,1, 1/2, ⋯ ,1/9} as the sets from which the pairwise comparison judgments are assigned at random to examine the variation in the values determined for the mean random consistency index. By extensive simulation analysis, we found that both methods produce the same values for the mean random consistency random index. Also, we (...) found that the reason for producing two different sets of values is the use of Ω vs. Ω- and not the selection of the Power Method vs. Saaty's Eigenvector Method. (shrink)

В монографии рассматривается соотношение индивидуальных и универсальных начал в праве как эффективное средство решения многих правовых проблем, как руководство в законодательной и судебной деятельности.

The achievements of modern cybernetics and mathematical logic are of much importance to an understanding of the nature of the thinking process. One of the principal tasks which these branches of knowledge set themselves is a study of the laws of thought with the aid of exact mathematical methods and modeling techniques. It goes without saying that neither cybernetics nor mathematical logic can pretend to offer a complete explanation of so complex a process as that of thinking. The physiological aspect, (...) which relates to the fact that life is the specific form of existence of proteins, is outside the framework of cybernetics and especially of mathematical logic. Likewise, cybernetics and logic do not and cannot replace the social sciences in explaining the specifics of the social aspect of the thinking process. (shrink)

The problem of the electromagnetic coupling for spin-3/2 particles is discussed. Following supergravity and some previous researches in the field of classical supersymmetric particles, we found that the electromagnetic coupling must not obey a minimal coupling in the sense of coupling the electromagnetic potential, but some kind of an electromagnetic field strength.

The structural-parametric synthesis of neural networks of deep learning, in particular convolutional neural networks used in image processing, is considered. The classification of modern architectures of convolutional neural networks is given. It is shown that almost every convolutional neural network, depending on its topology, has unique blocks that determine its essential features, Residual block, Inception module, ResNeXt block. It is stated the problem of structural-parametric synthesis of convolutional neural networks, for the solution of which it is proposed to use a (...) genetic algorithm. The genetic algorithm is used to effectively overcome a large search space: on the one hand, to generate possible topologies of the convolutional neural network, namely the choice of specific blocks and their locations in the structure of the convolutional neural network, and on the other hand to solve the problem of structural-parametric synthesis of convolutional neural network of selected topology. The most significant parameters of the convolutional neural network are determined. An encoding method is proposed that allows to repre- sent each network structure in the form of a string of fixed length in binary format. After that, several standard genetic operations were identified, i.e. selection, mutation and crossover, which eliminate weak individuals of the previous generation and use them to generate competitive ones. An example of solving this problem is given, a database of patients with thyroid disease was used as a training sample. (shrink)

When Introduction à la méthode de Léonard de Vinci was published, Valéry was not yet twenty-four. The period during which he wrote this work, as well as Soirée avec M. Teste, which appeared a year later, was extremely important in his biography, for it defined the principal trends of his thought for decades to come. After a twenty-year period of silence and retirement, there appeared his small volume La Jeune Parque, the collection Charmes, Album de vers anciens, and his Socratic (...) dialogues, all of which won him fame. The reader became aware of a brilliant stylist producing essays most abundant in number and themes, an acute analyst of culture in crisis, of the human community, mind, and morals, and the author of notebooks kept for many years in which he appears, as, among other things, a forerunner of the most diverse ideas in the realm of linguistics, psychology, information theory, aesthetic theory, and the like. Finally, there was to be the posthumous publication of Mon Faust, which, in the mind of the more perceptive reader, markedly emphasizes and sharpens the tragic aspects of Valéry's personality and consciousness of the world, for he is still today sometimes presented as a kind of causeur of high society, a cold master of "manufactured" poetry, an overly brilliant dilettante blinded by science or, at the very best, an utterly academic classicist in the category of those who are as dead as Bossuet or Boileau. All that was still in the future. However, it was precisely in these early works that, with all the fire of youth and maximalism of thought, he formulated ideas that must be central to the attention of those who wish to discover the system of Paul Valéry. (shrink)

В монографии проводится системный анализ социальной философия одного из самых значительных отечественных социальных мыслителей Б. Н. Чичерина. Для читателей, интересующихся историей отечественной социально-философской мысли.

The article proposes a methodological scheme, on the one hand, describing the process of the formation of a new reality, which can later be constituted as an object (cognition or ideal), on the other hand, including logical “stops” interpreted as schemes, concepts and metaphors. The author presents a point of view on the distinction between the scheme and the concept of A. P. Ogurtsov, as well as his study of the development of metaphor in political discourse. On the material of (...) the reconstruction of Plato's “Feast” and some statements of philosophers, the concepts of schema, concept and metaphor are characterized. It is argued that within the framework of the Aristotelian and Cartesian traditions of thinking, metaphors can be eliminated, and in creativity they are an integral element of any work. (shrink)

In the article, I analyze the current situation in the field of teaching philosophy and also other social sciences and humanities. The point is that in higher school, under various pretexts, many departments and philosophy councils are closed, hours for teaching philosophical courses and seminars are reduced. Teachers of philosophy and other disciplines in higher education, in addition to being overwhelmed, have to spend a lot of time on unnecessary reporting, which for the most part does not reflect the essence (...) of the matter. The policy of education officials and their belief in the need for such reporting and reduction of hours are critically reviewed. I show that in addition to the well-known functions of philosophy, teaching philosophy is of crucial importance today is due to three important circumstances: we live, firstly, in a period of double transition and, secondly, in a period of an anthropological crisis and a crisis of reality, thirdly, due to a crisis of morality and ethics. Only philosophy, based on the methodology, as well as the humanities and social sciences can comprehend modern conditions. The question is about a new start to the practice of teaching philosophy. I propose to introduce a temporary moratorium on the compilation of new teaching programs and start a broad discussion in the philosophical and pedagogical community of the goals and content of the teaching of philosophy. In this regard, I offer my own understanding of the problems and the essence of the teaching of philosophy. I also share my personal experience in teaching philosophy, which includes lecturing and organizing the creative work of small groups of students. (shrink)