The development of T cells and B cells from pluripotent hematopoietic precursors occurs through a stepwise narrowing of developmental potential that ends in lineage commitment. During this process, lineage-specific genes are activated asynchronously, and lineage-inappropriate genes, although initially expressed, are asynchronously turned off. These complex gene expression events are the outcome of the changes in expression of multiple transcription factors with partially overlapping roles in early lymphocyte and myeloid cell development. Key transcription factors promoting B-cell development and candidates for this (...) role in T-cell development are discussed in terms of their possible modes of action in fate determination. We discuss how a robust, stable, cell-type–specific gene expression pattern may be established in part by the interplay between endogenous transcription factors and signals transduced by cytokine receptors, and in part by the network of effects of particular transcription factors on each other. BioEssays 21:726–742, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

Cascades of transcriptional regulation are the common source of the forward drive in all developmental systems. Increases in complexity and specificity of gene expression at successive stages are based on the collaboration of varied combinations of transcription factors already expressed in the cells to turn on new genes, and the logical relationships between the transcription factors acting and becoming newly expressed from stage to stage are best visualized as gene regulatory networks. However, gene regulatory networks used in different developmental contexts (...) underlie processes that actually operate through different sets of rules, which affect the kinetics, synchronicity, and logical properties of individual network nodes. Contrasting early embryonic development in flies and sea urchins with adult mammalian hematopoietic development from stem cells, major differences are seen in transcription factor dosage dependence, the silencing or damping impacts of repression, and the impact of cellular regulatory history on the parts of the genome that are accessible to transcription factor action in a given cell type. These different features not only affect the kinds of models that can illuminate developmental mechanisms in the respective biological systems, but also reflect the evolutionary needs of these biological systems to optimize different aspects of development. (shrink)

The vertebrate immune system provides a remarkable showcase of the different ways the genome can be used to specify cellular identity and to mediate cellular function. It is arguably the leading mammalian system in which gene regulation programs that drive the acquisition of specific cell-type identities have been elucidated at the single cell level. More broadly for molecular genomics, the activation-induced gene expression pathways used in immune effector responses have provided textbook cases for fundamental elements of transcription factor assembly at (...) enhancers ; and immune system genes and gene clusters have provided key paradigms for the roles of long-range.. (shrink)

Pendant l’été 2012, les artistes Ellen Rothenberg et Délia Popa participèrent à un projet d’échange culturel avec une famille rom vivant dans une petite communauté agraire du comté de Sibiu, vieille région de Transylvanie. Le deuxième volet de ce projet comprenait une exposition des œuvres inspirées par cette expérience, dans les Galeries d’Art Contemporain du Musée National de Brukenthal, à l’automne 2013. Intitulée « Chelen Amenca (Danse avec nous) », cette exposition fut organisée par la c...

The European Union Commission’s whitepaper on Artificial Intelligence proposes shaping the emerging AI market so that it better reflects common European values. It is a master plan that builds upon the EU AI High-Level Expert Group guidelines. This article reviews the masterplan, from a culture cycle perspective, to reflect on its potential clashes with current societal, technical, and methodological constraints. We identify two main obstacles in the implementation of this plan: the lack of a coherent EU vision to drive future (...) decision-making processes at state and local levels and the lack of methods to support a sustainable diffusion of AI in our society. The lack of a coherent vision stems from not considering societal differences across the EU member states. We suggest that these differences may lead to a fractured market and an AI crisis in which different members of the EU will adopt nation-centric strategies to exploit AI, thus preventing the development of a frictionless market as envisaged by the EU. Moreover, the Commission aims at changing the AI development culture proposing a human-centred and safety-first perspective that is not supported by methodological advancements, thus taking the risks of unforeseen social and societal impacts of AI. We discuss potential societal, technical, and methodological gaps that should be filled to avoid the risks of developing AI systems at the expense of society. Our analysis results in the recommendation that the EU regulators and policymakers consider how to complement the EC programme with rules and compensatory mechanisms to avoid market fragmentation due to local and global ambitions. Moreover, regulators should go beyond the human-centred approach establishing a research agenda seeking answers to the technical and methodological open questions regarding the development and assessment of human-AI co-action aiming for a sustainable AI diffusion in the society. (shrink)

We are drowning in information, while starving for wisdom.Are the smartest people also the wisest? Not necessarily. While traditional intellectual reasoning and procedural knowledge have helped build the communities we live in, there is a growing scientific understanding that we need emotionally balanced and better-fitting prosocial frameworks for coping with the uncertainties and complexities of life and addressing new challenges of the modern world. We are now poised on the edge of a new science of wisdom.The concept of wisdom, long (...) considered the “pinnacle of insight into the human condition”, has been that of an intangible, subjective, culturally specific entity—an unscientific... (shrink)

This book discusses ways for people to handle today's bioethical issues in the context of America's history and culture--and from the perspective of various ...

While a significant literature has appeared discussing theoretical ethical concerns regarding COVID-19, particularly regarding resource prioritization, as well as a number of personal reflections on providing patient care during the early stages of the pandemic, systematic analysis of the actual ethical issues involving patient care during this time is limited. This single-center retrospective cohort mixed methods study of ethics consultations during the first surge of the COVID 19 pandemic in Massachusetts between March 15, 2020 through June 15, 2020 aim to (...) fill this gap. Results indicate that there was no significant difference in the median number of monthly consultation cases during the first COVID-19 surge compared to the same period the year prior and that the characteristics of the ethics consults during the COVID-19 surge and same period the year prior were also similar. Through inductive analysis, we identified four themes related to ethics consults during the first COVID-19 surge including (1) prognostic difficulty for COVID-19 positive patients, (2) challenges related to visitor restrictions, (3) end of life scenarios, and (4) family members who were also positive for COVID-19. Cases were complex and often aligned with multiple themes. These patient case-related sources of ethical issues were managed against the backdrop of intense systemic ethical issues and a near lockdown of daily life. Healthcare ethics consultants can learn from this experience to enhance training to be ready for future disasters. (shrink)

From February 2020, the COVID-19 pandemic led to closures of educational institutions to reduce the spread of infectious disease. This forced the U.S. education system into a massive experiment with online education. Despite conducting online bioethics education for nearly twenty years, our bioethics program, a joint endeavor of Clarkson University and Icahn School of Medicine at Mount Sinai, was not immune to this disruption because our curriculum features intensive, one-week onsite courses. Even in the face of historic disruptions, it is (...) vital to ensure minimal interruptions to teaching and assessing students to provide effective education. This paper reviews the steps we took to successfully convert the onsite components of our curriculum to a synchronous online format, and it focuses on how we preserved instruction and assessment of practical skills that comprise these courses’ core. It also explains how we fostered interactive classroom environments. (shrink)

Objective Although patients exercise greater autonomy than in the past, and shared decision making is promoted as the preferred model for doctor-patient engagement, tensions still exist in clinical practice about the primary locus of decision-making authority for complex, scarce, and resource-intensive medical therapies: patients and their surrogates, or physicians. We assessed physicians’ attitudes toward decisional authority for adult venoarterial extracorporeal membrane oxygenation (VA-ECMO), hypothesizing they would favor a medical locus. Design, Setting, Participants A survey of resident/fellow physicians and internal medicine (...) attendings at an academic medical center, May to August 2013. Measurements We used a 24-item, internet-based survey assessing physician-respondents’ demographic characteristics, knowledge, and attitudes regarding decisional authority for adult VA-ECMO. Qualitative narratives were also collected. Main Results A total of 179 physicians completed the survey (15 percent response rate); 48 percent attendings and 52 percent residents/ fellows. Only 32 percent of the respondents indicated that a surrogate’s consent should be required to discontinue VA-ECMO; 56 percent felt that physicians should have the right to discontinue VA-ECMO over a surrogate’s objection. Those who self-reported as “knowledgeable” about VA-ECMO, compared to those who did not, more frequently replied that there should not be presumed consent for VA-ECMO (47.6 percent versus 33.3 percent, p = 0.007), that physicians should have the right to discontinue VAECMO over a surrogate’s objection (76.2 percent versus 50 percent, p = 0.02) and that, given its cost, the use of VA-ECMO should be restricted (81.0 percent versus 54.4 percent, p = 0.005). Conclusions Surveyed physicians, especially those who self-reported as knowledgeable about VA-ECMO and/or were specialists in pulmonary/ critical care, favored a medical locus of decisional authority for VA-ECMO. VA-ECMO is complex, and the data may (1) reflect physicians’ hesitance to cede authority to presumably less knowledgeable patients and surrogates, (2) stem from a stewardship of resources perspective, and/or (3) point to practical efforts to avoid futility and utility disputes. Whether these results indicate a more widespread reversion to paternalism or a more circumscribed usurping of decisional authority occasioned by VA-ECMO necessitates further study. (shrink)

Wisdom is a multi-component trait that is important for mental health and well-being. In this study, we sought to understand gender differences in relative strengths in wisdom. A total of 659 individuals aged 27–103 years completed surveys including the 3-Dimensional Wisdom Scale and the San Diego Wisdom Scale. Analyses assessed gender differences in wisdom and gender’s moderating effect on the relationship between wisdom and associated constructs including depression, loneliness, well-being, optimism, and resilience. Women scored higher on average on the 3D-WS (...) but not on the SD-WISE. Women scored higher on compassion-related domains and on SD-WISE Self-Reflection. Men scored higher on cognitive-related domains and on SD-WISE Emotion Regulation. There was no impact of gender on the relationships between wisdom and associated constructs. Women and men have different relative strengths in wisdom, likely driven by sociocultural and biological factors. Tailoring wisdom interventions to individuals based on their profiles is an important next step. (shrink)

The Tennessee Supreme Court's decision in Davis v. Davis, a case that raises the question of how to allocate frozen embryos in the event of divorce, addresses many of the legal issues posed by in vitro fertilization. The decision considers the interests of the progenitors as well as of the children who may result. For example, the court held that gamete providers' discretion regarding the disposition of embryos can be limited only when their decisions would harm the children who might (...) be born. The court also made clear that efforts to seek genetic parenthood are protected only when accompanied by a desire to raise the resulting children, a conclusion that also affects other reproductive technologies. In addition to elaborating an analytic framework, the court set guidelines for resolving disputes when the couples had made no prior agreements, including holding that while the embryos are ex-utero the desire to avoid genetic parenthood almost always trumps the wish to become a parent. The well-reasoned analysis in Davis v. Davis should help shape legal and ethical discussion regarding the use of in vitro fertilization for many years to come. (shrink)

The central goal of this essay is to develop a theory of justified paternalism that will be useful in evaluating and designing paternalistic public policies. The theory is designed for a society that promotes the development of characteristics of autonomy in its members. In the opening chapter I analyze widely-held legal, familial and philosophic conceptions of paternalism, discuss the inadequacies of each of those conceptions and develop a "unified" conception of paternalism. In Chapter II I analyze what it means to (...) be "morally responsible" and base this analysis on the legal, psychological and psychiatric accounts of responsibility that inform an autonomist society. From these analyses I develop two principles which inform an autonomist society: Respect for Others and Non-Interference and discuss the restraints on justifiable paternalism entailed by them. In Chapter III I discuss the roles of voluntariness and consent in the legal, phychiatric and philosophic concepts of moral responsibility and turn to an analysis of the disappointing treatments of these concepts in traditional philosophic justifications for paternalism. I argue that "unencumbered consent" is an appropriate concept of consent to utilize in any philosophic justification for paternalism that would be consistent with the concepts of moral responsibility and autonomy and the principles of respect for others and of non-interference. Chapter IV offers a decision-theoretic model justifying acting paternalistically for others. Each of the necessary conditions for justified paternalism is drawn from the aforementioned concepts and principles. In Chapter V, I show that if Rawls is to be consistent, he must adopt a theory of paternalism similar to mine, and I argue that my theory of paternalism overcomes libertarian, utilitarian and statistical arguments against it. I then apply the theory to specific forms of paternalism including involuntary commitment and guardianship, mandatory blood transfusions, flouridation of public water supplies, mandatory motorcycle helmets and seatbelts, social security taxation, mandatory education of children and suicide intervention. A 267-entry bibliography is appended. (shrink)

Medical assistance in dying legislation in Canada followed much deliberation after the Supreme Court of Canada’s ruling in Carter v. Canada. Included in this deliberation was the Special Joint Committee on Physician Assisted Dying’s recommendation to extend MAID legislation beyond the inclusion of adults to mature minors. Children's agency is a construct advanced within childhood studies literature which entails eliciting children’s voices in order to recognise children as active participants in constructing their own childhoods. Using this framework, we consider the (...) possible extension of MAID legislation to most minors. We highlight important questions regarding how insights from children’s voices could be mobilised in the life or death context of MAID. We conclude that children’s voices have the potential to help determine their eligibility for MAID; however, incorporating children's voices in the context of MAID requires careful consideration due to the complexity of voice. (shrink)

Writing in 1999, legal ethics scholar Brad Wendel noted that “[v]ery little empirical work has been done on the moral decision making of lawyers.” Indeed, since the mid-1990s, few empirical studies have attempted to explore how attorneys deliberate about ethical dilemmas they encounter in their practice. Moreover, while past research has explored some of the ethical issues confronting lawyers practicing in certain specific areas of practice, no published data exists probing the moral mind of health care lawyers. As signaled by (...) the creation of a regular column “devoted to ethical issues arising in the practice of health law” in the Journal of Law, Medicine & Ethics, the time to address the empirical gap in the professional ethics literature is now. Accordingly, this article presents data collected from 120 health care lawyers. Presenting this population with a number of hypothetical scenarios relating to how they would respond when confronting an ethical dilemma without an obvious solution or when facing a situation in which their personal values were in tension with their professional obligations, this article represents a first step toward better understanding how lawyers who practice in health care settings understand and resolve the moral discomfort they encounter in their professional lives. (shrink)

Ellen Fox and collaborators have produced the most detailed description of healthcare ethics practices in the United States available. Some findings are shocking for anyone committed to promoting q...

Purpose. The article is aimed to substantiate the view on the phenomenon of laughter as a subject of semiotic analysis, which leads to the following tasks: to reveal the possibilities of semiotics application in the study of laughter nature; to analyze the phenomenon of laughter as a cultural and natural phenomenon, as a sign and as an attribute; to consider the place of laughter in culture, which is understood as a sign system. Theoretical basis. The semiotic approach proceeds from the (...) fact that human lives in the world of signs, all the surrounding reality can be interpreted as a sign system. The basic concept of semiotics is the concept of a sign. The theoretical basis of the article is understanding the culture as a sign-symbolic system. Laughter is considered as a phenomenon ontologically rooted in human culture. At the same time, laughter is on the edge of culture. The research is based on the work of semiotic authors, cultural researchers, and the researchers of laughter. Originality. The originality lies in the application of the semiotic method to the research of laughter phenomenon, consideration of the dialectics of natural and cultural, signedness and non-signedness, manifested in the phenomenon of laughter. Conclusions. Laughter is considered as a psychophysiological phenomenon and as a cultural phenomenon. Laughter acts as an emotional manifestation, a physiological reaction, but socially and culturally mediated. In any case, laughter indicates an emotional or cognitive state of a human. Laughter acts as a process and result of the interpretation of a sign, a reaction to a sign. Laughter is a form and a means of communication. Being a natural phenomenon, in the process of social evolution, laughter acquires signedness, is integrated by culture as a sign system, and, at the same time, maintains a connection with nature. Thus, laughter occupies an ambivalent position between nature and culture. In the phenomenon of laughter, the dual state of human is revealed. In laughter, boundaries are blurred, the unity and opposition of natural and cultural, biological and social, soul and body, thought and feeling, sign and attribute are manifested. (shrink)

Based on some materials from the A.V. Florovsky's Foundation in the Archive of the Russian Academy of Sciences, the author of the article reconstructs a little-known page from the history of academic and philosophical life of the Russian migr, that is the history of the Philosophical Society at the Russian Free University in the 1930s-1940s, including during the Nazi occupation of Czechoslovakia. It is justified that the reconstruction of the history of Russian philosophical institutions can set a new research perspective (...) that allows us to consider the history of Russian philosophy as a process of formation and development of institutionalized forms of production, reproduction and translation of philosophical knowledge, which would allow to create a new historical and philosophical cross-section of Russian thought, complementing traditional approaches to the historiography of Russian philosophy. The article reveals new aspects of the scientific activity of N.O. Lossky and I.I. Lapshin, who played a key role in the work of the Philosophical Society. In addition, the analysis of archival materials made it possible to identify and reconstruct new facts from the creative biography of such thinkers of Russian emigration as S.L. Frank, E.V. Spektorsky, B.P. Vysheslavtsev, G.V. Florovsky. Russian Free University's Philosophical Society report for 1941 is given as an appendix to the article, as well as the reconstruction of the problems of the circle for the study of the Russian national idea. It is concluded that scientific and philosophical activity at the RSU was carried out through an extensive network of scientific societies, associations, circles and seminars, which allowed developing a wide variety of issues - aesthetics, the history of Russian and Western philosophy, philosophical problems of Russian literature and history, the Russian national idea. (shrink)

Монография предназначена для специалистов в области социальной философии, социологии и истории, а также для широкого круга читателей.

Для широкого круга читателей (слушателей, аспирантов, преподавателей) интересующихся данной проблемой.

_Purpose._ The purity of consciousness in European culture has practically been turned into an abstraction. Because of this, there are so many discrepancies in understanding its nature. For Heidegger, the question of the purity of human consciousness remains open. Our purpose is to study the purity of European consciousness in the work of M. Heidegger. _Theoretical basis._ We draw on the deep foundations of existential, phenomenological, hermeneutic, religious-philosophical and postmodern Western and Eastern thought. _Originality._ While the early Heidegger was thinking (...) under the sign of Dasein, he did not hear the nature of the "pure consciousness" of human. Nevertheless, temporality for him was such a fundamental property that it determined the depth of understanding not only of being, but also of human consciousness itself (like Dasein). In this context, we begin to understand that the depth of consciousness in the concept of early Heidegger can be associated with its temporality. In fact, towards the end of "Being and Time", Heidegger, thinking more and more about the understanding of time from the horizon of being, begins to form similar ideas about understanding itself, that is, about human consciousness, in the sense that consciousness itself arises from the horizon of time (and being). What, then, is pure human consciousness the pure time? Does not this mean that the original meaning of consciousness is in its directed temporalizing. This temporalizing of consciousness of human (as a thinking being), which arises from the future, is perceived in three modes and reveals the fundamental nature of the consciousness itself (thinking is a stream of consciousness and, in such a context, directed understanding). Paraphrasing Heidegger, we say that the ontological meaning of pure human consciousness is revealed as temporality. Already after writing _Being and Time_, Heidegger thinks about the origins of the European consciousness, its comprehending from the depths (originality) of the being of European culture. _Conclusions._ The early Heidegger seeks the purity of being and, at the same time, strives more and more to understand the essence of the purity of human thinking. All of Heidegger’s work is a consistent transition from human understanding of the purity of being (Dasein) to the purity of thinking of a human himself. In this sense, there is a transformation of M. Heidegger’s consciousness from fundamental ontology (Dasein) in the early period to existential anthropology (human consciousness) in the late period. (shrink)

In his 1951 Gibbs Memorial Lecture, Kurt Gödel put forth his famous disjunction that either the power of the mind outstrips that of any machine or there are absolutely unsolvable problems. The view that there are no absolutely unsolvable problems is optimism, the view that there are such problems is pessimism. In his 1995—and, revised in 2013—Verificationism Then and Now, Per Martin-Löf presents an illustrative argument for a constructivist form of optimism. In response to that argument, Solomon Feferman points out (...) that Martin-Löf’s reasoning relies upon constructive understandings of key philosophical notions. In the vein of Feferman’s analysis, one might be object to Martin-Löf’s argument for either its reliance upon constructivist considerations, or for its appeal to non-unproblematically mathematical premises. We argue that both of these responses fall short. On one hand, to be critical of Martin-Löf’s reasoning for its constructiveness is to reject what would otherwise be a scientific advance on the basis of the assumption of constructivism’s falsehood or implausibility, which is of course uncharitable at best. On the other hand, to object to the argument for its use of non-unproblematically mathematical premises is to assume that there is some philosophically neutral mathematics, which is implausible. Martin-Löf’s argument relies upon his third law, the claim that from the impossibility of a proof of a proposition we can construct a proof of its negation. We close with a discussion of some ways in which this claim can be criticized from the constructive point of view. Specifically, we contend that Martin-Löf’s third law is incompatible with what has been called “Poincaré’s Principle of Epistemic Conservation”, the thesis that genuine increase in mathematical knowledge requires subject-specific insight. (shrink)

The study of identity crosses all disciplinary borders to address such issues as the multiple interactions of race, class, and gender in feminist, lesbian, and gay studies, postcolonialism and globalization, and the interrelation of nationalism and ethnicity in ethnic and area studies. Identities will help disrupt the cliche-ridden discourse of identity by exploring the formation of identities and problem of subjectivity. Leading scholars in literary criticism, anthropology, sociology, and philosophy explore such topics as "Gypsies" in the Western imagination, the mobilization (...) of the West in Chinese television, the lesbian identity and the woman's gaze in fashion photography, and the regulation of black women's bodies in early 20th-century urban areas. This collection of twenty articles brings together the special issue of Critical Inquiry entitled "Identities" (Summer 1992), two other previously published essays, and five previously published critical responses and rejoinders, all of which is interrogated in two new essays by Michael Gorra and Judith Butler. Contributors include Elizabeth Abel, Kwame Anthony Appiah, Akeel Bilgrami, Daniel Boyarin, Jonathan Boyarin, Judith Butler, Hazel V. Carby, Xiaomei Chen, Diana Fuss, Henry Louis Gates, Jr., Avery Gordon, Michael Gorra, Cheryl Herr, Saree S. Makdisi, Walter Benn Michaels, Christopher Newfield, Gananath Obeyesekere, Molly Anne Rothenberg, Gayatri Chakravorty Spivak, Sara Suleri, Katie Trumpener, and Joseph Valente. (shrink)

В книге большое внимание занимает рассмотрение сущностных черт самого сложностного мышления и тех возможностей, которые оно открывает при анализе процессов глобализации, проблем биоэтики, экономики, инженерной науки. Для специалистов.