The formation of a highly condensed chromosome structure (heterochromatin) in a region of a eukaryotic chromosome can inactivate the genes within that region. Genetic studies using the fruitfly Drosophila melanogaster have identified several essential genes which influence the formation of heterochromatin. My purpose in this review is to summarize some recent work on the genetics of heterochromatin assembly in Drosophila and a recent model for how chromosomal proteins may interact to form a heterochromatic structure.

Eukaryotes organize certain chromosomal intervals into domains capable of si lencing most genes. Examples of silencing domains include the HML/HMR loci and subtelomeric chromatin in yeast, the Barr body X chromosome in mammals, and the pericentric heterochromatin of Drosophila. Silencing chromatin is often correlated with more regularized nucleosomal array than that found in active chromatin, and transcriptional activators appear to be missing from their target sites in silent chromatin. In Drosophila, gene silencing by heterochromatin is often variegated, indicating that a (...) gene may escape silencing in some cells. In a recent study, Ahmad and Henikoff(1) show that a yeast activator can compete successfully with Drosophila heterochromatic silencing factors for target sites in DNA. This competition, together with developmental change in the stability of heterochromatin itself, decides the transcriptional state for a gene subject to heterochromatin repression. BioEssays 23:767–771, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Most tissues contain cells capable of the self‐renewal and differentiation necessary to maintain tissue and organ integrity. These somatic stem cells are generally thought to have limited developmental potential. The mechanisms that restrict cell fate decisions in somatic stem cells are only now being understood. This understanding will be important in the clinical exploitation of adult stem cells in tissue repair and replacement. Experiments performed over fifty years ago in Drosophila showed that developmental restriction could be relaxed in the proliferating (...) larval cells that are destined to form the adult fly integument. This phenomenon, called transdetermination, can serve as a model for mechanisms of stem‐cell commitment. A recent publication1 sheds new light on the mechanism of transdetermination by demonstrating that loss of homeotic gene silencing leads to increased frequency of transdetermination. In addition, the authors link a specific signaling pathway induced by tissue regeneration to the relaxation of homeotic gene silencing. The data identify key mechanisms that control developmental homeostasis and cell fate restriction that could be manipulated to make somatic stem‐cell engineering possible. BioEssays 28: 574–577, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Entirely faithful to Boethius' Latin; Relihan's translation makes the philosophy of the Consolation intelligible to readers; it gives equal weight to the poetry--in fact, Relihan's metrical translation of Boethius' _metro_ are themselves contributions of the first moment to Boethian studies. Boethius finally has a translator equal to his prodigious talents and his manifold vision. --Joseph Pucci, Brown University.

The Roman philosopher Boethius is best known for the _Consolation of Philosophy_, one of the most frequently cited texts in medieval literature. In the _Consolation_, an unnamed Boethius sits in prison awaiting execution when his muse Philosophy appears to him. Her offer to teach him who he truly is and to lead him to his heavenly home becomes a debate about how to come to terms with evil, freedom, and providence. The conventional reading of the _Consolation_ is that it is (...) a defense of pagan philosophy; nevertheless, many readers who accept this basic argument find that the ending is ambiguous and that Philosophy has not, finally, given the prisoner the comfort she had promised. In _The Prisoner's Philosophy_, Joel C. Relihan delivers a genuinely new reading of the _Consolation_. He argues that it is a Christian work dramatizing not the truths of philosophy as a whole, but the limits of pagan philosophy in particular. He views it as one of a number of literary experiments of late antiquity, taking its place alongside Augustine's _Confessions_ and _Soliloquies_ as a spiritual meditation, as an attempt by Boethius to speak objectively about the life of the mind and its relation to God. Relihan discerns three fundamental stories intertwined in the _Consolation_: an ironic retelling of Plato's _Crito,_ an adaptation of Lucian's _Jupiter Confutatus,_ and a sober reduction of _Job_ to a quiet dialogue in which the wounded innocent ultimately learns wisdom in silence. Relihan's claim that Boethius's text was written as a Menippean satire does not rest merely on identifying a mixture of disparate literary influences on the text, or on the combination of verse and prose or of fantasy and morality. More important, Relihan argues, Boethius deliberately dramatizes the act of writing about systematic knowledge in a way that calls into question the value of that knowledge. Philosophy's attempt to lead an exile to God's heaven is rejected; the exile comes to accept the value of the phenomenal world, and theology replaces philosophy to explain the place of human beings in the order of the world. Boethius Christianizes the genre of Menippean satire, and his _Consolation_ is a work about humility and prayer. _“Acknowledging that the _Consolation of Philosophy_ is ‘over-familiar and under-read,’ Joel Relihan puts to the side old bromides about the work and instead pays careful attention to the narrative Boethius constructs, grounding his readings in the contexts the work cultivates, especially its Menippean elements. The result is perhaps the first satisfying reading of the _Consolation_ to be produced, a satisfaction felt also in the ways Relihan mirrors Boethius himself in the thoroughness of his scholarship and the elegance of his exposition. No one who studies Boethius will be able to ignore this book.“ — Joseph Pucci, Brown University _ "Anyone who has been fascinated, intrigued, or perhaps puzzled by the meaning, structure, or argument of Boethius's _Consolation of Philosophy_ will find Joel Relihan's new book a welcome addition to the study of this core text of the early medieval world whose influence extends to the present time. Relihan's study is a tour de force that belongs in the library of all those who appreciate Boethius's depth and subtlety. Fortune's wheel has indeed turned in the favor of those who wish to explore with Relihan the intricacies and brilliance of the _Consolation_." —_Fr. John Fortin, O.S.B., Saint Anselm College _. (shrink)

So the modern editions print the opening words of the work more popularly known as the Caesares. The Symposium begins with what I consider to be a playful encounter between the narrator and his interlocutor, in which the latter's expectations of seriousness in the myth which is to follow are frustrated. This playfulness has not been appreciated by Julian's commentators. I suggest that we have here a concealed trimeter which figures largely in the dynamics of this dialogue : γελοον οδν (...) σδ τερπνν οδ' γ. (shrink)

So the modern editions print the opening words of the work more popularly known as the Caesares. The Symposium begins with what I consider to be a playful encounter between the narrator and his interlocutor, in which the latter's expectations of seriousness in the myth which is to follow are frustrated. This playfulness has not been appreciated by Julian's commentators. I suggest that we have here a concealed trimeter which figures largely in the dynamics of this dialogue :γελο⋯ον οὐδ⋯ν σὐδ⋯ (...) τερπν⋯ν οἶδ' ⋯γώ. (shrink)

Compassion is a prosocial motivation that is critical to the development and survival of the human species. Cultivating compassion involves developing deep wisdom, insight, and understanding into the nature and causes of human suffering; and wisdom and commitment to take positive action to alleviate suffering. This perspective piece discusses how compassion relates to the context of modern technology, which has developed at a rapid pace in recent decades. While advances in digital technology build on humankind’s vast capacity to develop practical (...) tools that promise to enrich our lives and improve our social connections, in reality the effects are often far from benign. The motives underlying the development of many contemporary digital platforms seem rooted in competitiveness and capitalism; while modern social media and online platforms are having a profound and pervasive impact on the mental health and wellbeing of humans around the globe. Nonetheless, digital technology holds considerable potential to promote compassionate insight, wisdom, and prosocial behavior. We reflect on the current state of technology within human society and examine the notion of compassionate technologies; discuss how contemporary paradigm shifts such as the inclusive design movement may be harnessed to build tools and platforms that promote collective good and increase prosocial behavior; and highlight examples of initiatives that are harnessing modern technology to advance democracy, collective knowledge, and personal freedoms and agency. (shrink)

Volume 20, Issue 4, May 2020, Page 76-78.

Civility is an essential feature of health care, as it is in so many other areas of human interaction. The article examines the meaning of civility, reviews its origins, and provides reasons for its moral significance in health care. It describes common types of uncivil behavior by health care professionals, patients, and visitors in hospitals and other health care settings, and it suggests strategies to prevent and respond to uncivil behavior, including institutional codes of conduct and disciplinary procedures. The article (...) concludes that uncivil behavior toward health care professionals, patients, and others subverts the moral goals of health care and is therefore unacceptable. Civility is a basic professional duty that health care professionals should embrace, model, and teach. (shrink)

Although Broad published many books in his lifetime, this volume is unique in presenting some of his most interesting unpublished writings. Divided into five clear sections, the following figures and topics are covered: Autobiography, Hegel and the nature of philosophy, Francis Bacon, Hume's philosophy of the self and belief, F. H. Bradley, The historical development of scientific thought from Pythagoras to Newton, Causation, Change and continuity, Quantitative methods, Poltergeists, Paranormal phenomena. -/- Each section is introduced and placed in context by (...) the editor, Joel Walmsley. The volume also includes an engaging and informative foreword by Simon Blackburn. It will be of great value to those studying and researching the history of twentieth-century philosophy, metaphysics, and the recent history and philosophy of science, as well as anyone interested in Broad's philosophical thought and his place in the history of philosophy. (shrink)

Biological evolution provides a creative fount of complex and subtle adaptations, often surprising the scientists who discover them. However, because evolution is an algorithmic process that transcends the substrate in which it occurs, evolution’s creativity is not limited to nature. Indeed, many researchers in the field of digital evolution have observed their evolving algorithms and organisms subverting their intentions, exposing unrecognized bugs in their code, producing unexpected adaptations, or exhibiting outcomes uncannily convergent with ones in nature. Such stories routinely reveal (...) creativity by evolution in these digital worlds, but they rarely fit into the standard scientific narrative. Instead they are often treated as mere obstacles to be overcome, rather than results that warrant study in their own right. The stories themselves are traded among researchers through oral tradition, but that mode of information transmission is inefficient and prone to error and outright loss. Moreover, the fact that these stories tend to be shared only among practitioners means that many natural scientists do not realize how interesting and lifelike digital organisms are and how natural their evolution can be. To our knowledge, no collection of such anecdotes has been published before. This paper is the crowd-sourced product of researchers in the fields of artificial life and evolutionary computation who have provided first-hand accounts of such cases. It thus serves as a written, fact-checked collection of scientifically important and even entertaining stories. In doing so we also present here substantial evidence that the existence and importance of evolutionary surprises extends beyond the natural world, and may indeed be a universal property of all complex evolving systems. (shrink)

This is the first book to offer the best essays, articles, and speeches on ethics and intelligence that demonstrate the complex moral dilemmas in intelligence collection, analysis, and operations. Some are recently declassified and never before published, and all are written by authors whose backgrounds are as varied as their insights, including Robert M. Gates, former Director of the Central Intelligence Agency; John P. Langan, the Joseph Cardinal Bernardin Professor of Catholic Social Thought at the Kennedy Institute of Ethics, Georgetown (...) University; and Loch K. Johnson, Regents Professor of Political Science at the University of Georgia and recipient of the Owens Award for contributions to the understanding of U.S. intelligence activities. Creating the foundation for the study of ethics and intelligence by filling in the gap between warfare and philosophy, this is a valuable collection of literature for building an ethical code that is not dependent on any specific agency, department, or country. (shrink)

The earlier volume in this series dealt with two religions of Indian origin, namely, Buddhism and Jainism. The Indian religious scene, however, is characterized by not only religions which originated in India but also by religions which entered India from outside India and made their home here. Thus religious life in India has been enlivened throughout its history by the presence of religions of foreign origin on its soil almost from the very time they came into existence. This volume covers (...) three such religions—Zoraoastrianism, Judaism, and Islam. In the case of Zoraostianism, even its very beginnings are intertwined with India, as Zoroastrianism reformed a preexisting religion which had strong links to the Vedic heritage of India. This relationship took on a new dimension when a Zoroastrian community, fearing persecution in Persia after its Arab conquest, sought shelter in western India and ultimately went on to produce India’s pioneering nationalist in the figure of Dadabhai Naoroji ( 1825-1917), also known as the Grand Old Man of India. Jews found refuge in south India after the destruction of the Temple by the Romans in 70 C.E. and have remained a part of the Indian religious scene since then, some even returning to Israel after it was founded in 1948. Islam arrived in Kerala as soon as it was founded and one of the earliest mosques in the history of Islam is found in India. Islam differs from the previously mentioned religions inasmuch as it went on to gain political hegemony over parts of the country for considerable periods of time, which meant that its impact on the religious life of the subcontinent has been greater compared to the other religions. It has also meant that Islam has existed in a religiously plural environment in India for a longer period than elsewhere in the world so that not only has Islam left a mark on India, India has also left its mark on it. Indeed all the three religions covered in this volume share this dual feature, that they have profoundly influenced Indian religious life and have also in turn been profoundly influenced by their presence in India. (shrink)

The earlier volume in this series dealt with two religions of Indian origin, namely, Buddhism and Jainism. The Indian religious scene, however, is characterized by not only religions which originated in India but also by religions which entered India from outside India and made their home here. Thus religious life in India has been enlivened throughout its history by the presence of religions of foreign origin on its soil almost from the very time they came into existence. This volume covers (...) three such religions—Zoraoastrianism, Judaism, and Islam. In the case of Zoraostianism, even its very beginnings are intertwined with India, as Zoroastrianism reformed a preexisting religion which had strong links to the Vedic heritage of India. This relationship took on a new dimension when a Zoroastrian community, fearing persecution in Persia after its Arab conquest, sought shelter in western India and ultimately went on to produce India’s pioneering nationalist in the figure of Dadabhai Naoroji ( 1825-1917), also known as the Grand Old Man of India. Jews found refuge in south India after the destruction of the Temple by the Romans in 70 C.E. and have remained a part of the Indian religious scene since then, some even returning to Israel after it was founded in 1948. Islam arrived in Kerala as soon as it was founded and one of the earliest mosques in the history of Islam is found in India. Islam differs from the previously mentioned religions inasmuch as it went on to gain political hegemony over parts of the country for considerable periods of time, which meant that its impact on the religious life of the subcontinent has been greater compared to the other religions. It has also meant that Islam has existed in a religiously plural environment in India for a longer period than elsewhere in the world so that not only has Islam left a mark on India, India has also left its mark on it. Indeed all the three religions covered in this volume share this dual feature, that they have profoundly influenced Indian religious life and have also in turn been profoundly influenced by their presence in India. (shrink)

Volume 20, Issue 6, June 2020, Page 17-19.

Because no single person or group holds knowledge about all aspects of research, mechanisms are needed to support knowledge exchange and engagement. Expertise in the research setting necessarily includes scientific and methodological expertise, but also expertise gained through the experience of participating in research and/or being a recipient of research outcomes. Engagement is, by its nature, reciprocal and relational: the process of engaging research participants, patients, citizens and others brings them closer to the research but also brings the research closer (...) to them. When translating research into practice, engaging the public and other stakeholders is explicitly intended to make the outcomes of translation relevant to its constituency of users. In practice, engagement faces numerous challenges and is often time-consuming, expensive and ‘thorny’ work. We explore the epistemic and ontological considerations and implications of four common critiques of engagement methodologies that contest: representativeness, communication and articulation, impacts and outcome, and democracy. The ECOUTER methodology addresses problems of representation and epistemic foundationalism using a methodology that asks, “How could it be otherwise?” ECOUTER affords the possibility of engagement where spatial and temporal constraints are present, relying on saturation as a method of ‘keeping open’ the possible considerations that might emerge and including reflexive use of qualitative analytic methods. This paper describes the ECOUTER process, focusing on one worked example and detailing lessons learned from four other pilots. ECOUTER uses mind-mapping techniques to ‘open up’ engagement, iteratively and organically. ECOUTER aims to balance the breadth, accessibility and user-determination of the scope of engagement. An ECOUTER exercise comprises four stages: engagement and knowledge exchange; analysis of mindmap contributions; development of a conceptual schema ; and feedback, refinement and development of recommendations. ECOUTER refuses fixed truths but also refuses a fixed nature. Its promise lies in its flexibility, adaptability and openness. ECOUTER will be formed and re-formed by the needs and creativity of those who use it. (shrink)

This book broadens the inquiry into emotion to comprehend a comparative cultural outlook. It begins with an overview of recent work in the West, and then proceeds to the main business of scrutinizing various relevant issues from both Asian and comparative perspectives. Original essays by experts in the field. Finally, Robert Solomon comments and summarizes.

The relationship between democracy and constitutions is a long and fractious one. Those who lean towards the constitutionalist side have tended to perceive democracy as a threat to political order and the preservation of important values, whereas those who take a more democratist stance tend to treat constitutions as elite hindrances to popular rule as much as anything else. In this paper, we will give the constitutionalist thesis a broader theoretical and political scrutiny. By way of explanation, we will address (...) and recommend the possibilities and problems for putting into practical operation such an anti-constitutionalist stance; the recent experience of the U.S. State of California offers itself as a good forcing-ground for these ideas. In short, from a democratic standpoint, the challenge for the citizenry is not so much about defining the values of constitutions, but constitutions whose change is outside the scope of popular decision making, supposed to exclusively take place through judicial interpretation or through an amendment formula designed precisely to make change difficult and unlikely. Too often, constitutions place checks and limits on democratic participation in the name of some other set of vaunted truths or elite-favouring values. For the strong democrat, it is formal constitutions and their institutional paraphernalia that do more to inhibit and dull democracy's emancipatory potential than to nurture and fulfil it. (shrink)

Is the societal-level of analysis sufficient today to understand the values of those in the global workforce? Or are individual-level analyses more appropriate for assessing the influence of values on ethical behaviors across country workforces? Using multi-level analyses for a 48-society sample, we test the utility of both the societal-level and individual-level dimensions of collectivism and individualism values for predicting ethical behaviors of business professionals. Our values-based behavioral analysis indicates that values at the individual-level make a more significant contribution to (...) explaining variance in ethical behaviors than do values at the societal-level. Implicitly, our findings question the soundness of using societal-level values measures. Implications for international business research are discussed. (shrink)

This chapter introduces the articles by Marie C. Swabey, Thelma Z. Lavine, Grace A. de Laguna and Dorothy Walsh on the objectivity of scientific knowledge. We will see Swabey placing herself outside the historicist traditions of (later) authors (e.g., Thomas Kuhn), and arguing that the rationality and objectivity of science are grounded in synthetic a priori justified logical principles. Lavine and de Laguna, by contrast, embrace socio-historical approaches to the study of science, thus anticipating later developments in philosophy of science. (...) Still, whereas Lavine embraces a relativist notion of objectivity, de Laguna argues that science, at least in some respects, actually is universally valid. Walsh, finally, like Swabey, believes in context-independent objectivity that is grounded in metaphysics, but like de Laguna and Lavine, contends that such objectivity is discipline-specific. (shrink)

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping is the gold standard for the identification of “eloquent” areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects. Broadband gamma activity recorded with extraoperative electrocorticography during cognitive tasks may be an alternative to ESM but until now has not proven of definitive clinical value. Considering their role in cognition, the alpha and beta bands could further (...) improve the identification of eloquent cortex. We compared gamma, alpha and beta activity, and their combinations for the identification of eloquent cortical areas defined by ESM. Ten patients with intractable focal epilepsy participated in a delayed-match-to-sample task, where syllable sounds were compared to visually presented letters. We used a generalized linear model approach to find the optimal weighting of each band for predicting ESM-defined categories and estimated the diagnostic ability by calculating the area under the receiver operating characteristic curve. Gamma activity increased more in eloquent than in non-eloquent areas, whereas alpha and beta power decreased more in eloquent areas. Diagnostic ability of each band was close to 0.7 for all bands but depended on multiple factors including the time period of the cognitive task, the location of the electrodes and the patient’s degree of attention to the stimulus. We show that diagnostic ability can be increased by 3–5% by combining gamma and alpha and by 7.5–11% when gamma and beta were combined. We then show how ECoG power modulation from cognitive testing can be used to map the probability of eloquence in individual patients and how this probability map can be used in clinical settings to optimize ESM planning. We conclude that the combination of gamma and beta power modulation during cognitive testing can contribute to the identification of eloquent areas prior to ESM in patients with refractory focal epilepsy. (shrink)

BackgroundInvolvement of adolescent girls in biomedical HIV research is essential to better understand efficacy and safety of new prevention interventions in this key population at high risk of HIV infection. However, there are many ethical issues to consider prior to engaging them in pivotal biomedical research. In Uganda, 16–17-year-old adolescents can access sexual and reproductive health services including for HIV or other sexually transmitted infections, contraception, and antenatal care without parental consent. In contrast, participation in HIV prevention research involving investigational (...) new drugs requires adolescents to have parental or guardian consent. Thus, privacy and confidentiality concerns may deter adolescent participation. We describe community perspectives on ethical considerations for involving adolescent girls in the MTN 034 study in Uganda.MethodsFrom August 2017 to March 2018, we held five stakeholder engagement meetings in preparation for the MTN 034 study in Kampala, Uganda (NCT03593655): two with 140 community representatives, two with 125 adolescents, and one with 50 adolescents and parents. Discussions were moderated by the study team. Proceedings were documented by notetakers. Summary notes described community perspectives of adolescent participation in HIV research including convergent, divergent or minority views, challenges, and proposed solutions.ResultsMost community members perceived parental or guardian consent as a principal barrier to study participation due to concerns about adolescent disclosure of pre-marital sex, which is a cultural taboo. Of 125 adolescent participants, 119 (95%) feared inadvertent disclosure of sexual activity to their parents. Community stakeholders identified the following critical considerations for ethical involvement of adolescents in HIV biomedical research: (1) involving key stakeholders in recruitment, (2) ensuring confidentiality of sensitive information about adolescent sexual activity, (3) informing adolescents about information to be disclosed to parents or guardians, (4) offering youth friendly services by appropriately trained staff, and (5) partnering with community youth organizations to maximize recruitment and retention.ConclusionsStakeholder engagement with diverse community representatives prior to conducting adolescent HIV prevention research is critical to collectively shaping the research agenda, successfully recruiting and retaining adolescents in HIV clinical trials and identifying practical strategies to ensure high ethical standards during trial implementation. (shrink)

In the conclusion to this multi-part article I first review the discussions carried out around the six essential questions in psychiatric diagnosis – the position taken by Allen Frances on each question, the commentaries on the respective question along with Frances’ responses to the commentaries, and my own view of the multiple discussions. In this review I emphasize that the core question is the first – what is the nature of psychiatric illness – and that in some manner all further (...) questions follow from the first. Following this review I attempt to move the discussion forward, addressing the first question from the perspectives of natural kind analysis and complexity analysis. This reflection leads toward a view of psychiatric disorders – and future nosologies – as far more complex and uncertain than we have imagined. (shrink)