The correct positioning of organs during embryonic development requires multiple cues. The Xenopus cement gland is a mucus‐secreting epithelium that is a simple model for organogenesis, allowing detailed analysis of this complex process. The cement gland forms at a conserved anterior position, where embryonic ectoderm and endoderm touch. In all deuterostomes, this region will form the stomodeum (primitive mouth) and, in some aquatic larva, will also form a cement gland. In recent years, a model has been put forward suggesting that (...) an intermediate level of BMP signaling in the ectoderm leads to cement gland formation. We propose an alternative model whereby, during gastrulation, the cement gland (CG) is positioned by the overlap of three domains, corresponding to anterodorsal identity (AD), ventrolateral identity (VL), and ectodermal outer layer identity (EO), defining the equation (AD + VL + EO = CG). Anterodorsal identity requires a contribution by the transcription factor Otx2 while ventrolateral identity requires the BMP4 signaling pathway. These postional cues are integrated to activate cement gland differentiation. This integration appears to require intermediate steps, including expression of pitx genes, and members of the ATF/CREB and Ets transcription factor families. BioEssays 25:717–726, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Background Scientific and technological advancements in mapping and understanding the interrelated pathways through which biological and environmental exposures affect disease development create new possibilities for detecting disease risk factors. Early detection of such risk factors may help prevent disease onset or moderate the disease course, thereby decreasing associated disease burden, morbidity, and mortality. However, the ethical implications of screening for disease risk factors are unclear and the current literature provides a fragmented and case-by-case picture. Methods To identify key ethical considerations (...) arising from the early detection of disease risk factors, we performed a systematic scoping review. The Scopus, Embase, and Philosopher’s Index databases were searched for peer-reviewed, academic records, which were included if they were written in English or Dutch and concerned the ethics of (1) early detection of (2) disease risk factors for (3) disease caused by environmental factors or gene-environment interactions. All records were reviewed independently by at least two researchers. Results After screening 2034 titles and abstracts, and 112 full papers, 55 articles were included in the thematic synthesis of the results. We identified eight common ethical themes: (1) Reliability and uncertainty in early detection, (2) autonomy, (3) privacy, (4) beneficence and non-maleficence, (5) downstream burdens on others, (6) responsibility, (7) justice, and (8) medicalization and conceptual disruption. We identified several gaps in the literature, including a relative scarcity of research on ethical considerations associated with environmental preventive health interventions, a dearth of practical suggestions on how to address expressed concerns about overestimating health capacities, and a lack of insights into preventing undue attribution of health responsibility to individuals. Conclusions The ethical concerns arising with the early detection of risk factors are often interrelated and complex. Comprehensive ethical analyses are needed that are better embedded in normative frameworks and also assess and weigh the expected benefits of early risk factor detection. Such research is necessary for developing and implementing responsible and fair preventive health policies. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Philosophy and Literature 27.1 (2003) 211-222 [Access article in PDF] Criticism and the Terror of Nothingness C. Jason Lee DESTINY IS OFTEN ANOTHER NAME for narrative, it being the order we retrospectively find in scattered events. It is traditionally the role of the storyteller to create a believable narrative, with the reader investing attention into believing the story while the critic dissects the results to ascertain whether the magic (...) works. As Wallace Stevens put it, "we orchestrate a whole history and then imprison ourselves in the score, as if someone else had written it." 1 In the author's note to the second edition (1962) of Wise Blood (1949) Flannery O'Connor makes the point that her novel is a comic novel, yet its comedy does not lessen the depth of understanding it offers concerning the complexity of freedom. 2 The obsession with fate and destiny that swamps her characters, leads the reader into a gothic nightmare where humans in their attempt to re-create themselves dig themselves further into the graves of their dead relatives. For O'Connor free will does not mean one will but many wills conflicting in one man, and she explains the integrity of the central character of Wise Blood, Hazel Motes, as stemming from his vigorous attempts to rid himself of the "ragged figure who moves from tree to tree in the back of his mind."This figure is the Jesus of his grandfather, and it is also the religious preoccupation of the Deep South. Destiny has shaped his features and his character in the mold of his grandfather, and whomever he meets believes he too is a preacher. After establishing the Church Without Christ, like many sons attempting to shake off their origin, Hazel Motes realizes that his new way of behaving is in some sense being controlled [End Page 211] by his past and that he must shake off all vestiges to possess freedom. One might argue that, by eventually blinding himself, Hazel Motes is behaving as a soul who has given into the temptation of purgation, as if this is destiny. But it can be argued that this act is going against destiny, as it is an act that is perhaps trying to persuade God of something, despite the Oedipal connotations.Questioned by his landlady why he blinded himself he says to pay, and when asked to pay for what, he replies it does not matter what. Mrs. Flood is frightened of death, particularly death being one long blind existence, and Hazel Motes is a reminder to her of her destiny. This can be read as a judgment on life also. Yet she eventually decides to take care of him, for both altruistic and materialistic reasons, believing that his widow would inherit his war pension. Mrs. Flood, her name evocative of apocalyptic occurrences and Old Testament punishment, is a critic of the text; the text in this instance is nothing written but rather Motes himself. It seems that Hazel Motes, his name a reference to taking the mote out of one's own eye before you try and take the splinter out of another's, is punishing himself for his previous denial of Christ and for his sins, such as fornication, as with Mrs. Watts the prostitute and Sabbath Hawks, and murder, but also something more primal.After trying desperately to break the curse of his biological inheritance, his wise blood, just like the character Enoch Emery, it forces him to once again take on roles that deny him freedom. Hazel Motes may seem to a contemporary reader as a caricature, the mad preacher/antipreacher of the American South, but as V. S. Pritchett puts it, Hazel Motes is "entirely real" (p. viii). His self-blinding is part of his further alienation from the world, the world he has come back to after the "Great War." O'Connor shows how this watershed in human history was so devastating, Motes's new theology entirely rational. After having an insight into the world in reality through war, Hazel Motes is now "going to do some things... (shrink)

This article surveys most of the recent reviews of Sarah Richmond’s excellent new translation of L’Être et le néant. It offers some close textual comparisons between Richmond’s translation, Hazel Barnes’ translation, and the Checklist of Errors of Hazel Barnes’ Translation of L’Être et le néant. This article concludes that Richmond delivers a higher semantic resolution translation that overcomes nearly all the liabilities found in Barnes and does so without sacrificing much by way of readability.

Existentialism, 2/e, offers an exceptional and accessible introduction to the richness and diversity of existentialist thought. Retaining the focus of the highly successful first edition, the second edition provides extensive material on the "big four" existentialists--Kierkegaard, Nietzsche, Heidegger, and Sartre--while also including selections from twenty-four other authors. Giving readers a sense of the variety of existentialist thought around the world, this edition also adds new readings by such figures as Luis Borges, Viktor Frankl, Gabriel Garcia M'arquez, Keiji Nishitani, and Rainer (...) Maria Rilke. Existentialism, 2/e, also features: * New translations of Kierkegaard, Heidegger, and Buber * More extensive selections from Kierkegaard, Nietzsche, Heidegger, and Sartre * New selections by Hazel E. Barnes, Miguel de Unamuno, Joseph Heller, Philip Roth, and Colin Wilson * The Grand Inquisitor (from Dostoevsky's The Brothers Karamazov) Ideal for undergraduate courses in existentialism and Continental philosophy, Existentialism, 2/e, is fascinating reading for anyone interested in the subject. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:IntroductionAnna Mastroianni (bio) and Jeffrey Kahn (bio)In this issue of the Kennedy Institute of Ethics Journal, we subject the work of the Advisory Committee on Human Radiation Experiments to examination from many angles. Nearly one year has passed since the release of the Committee’s final report and recommendations, and it seems an appropriate time to invite discourse and reflection on the influence and impact of the Committee and its (...) efforts. Our intent is to advance understanding of the Committee and its work, its place in the evolution of bioethics and public policy, as well as the broader legacy of restoring trust in the conduct of human subjects research.In 1993, President Clinton and Secretary of Energy Hazel O’Leary initiated an investigation of America’s involvement in radiation experiments on its citizens during the Cold War. The investigation resulted in the appointment of the Committee in January 1994. Some issues raised by these radiation experiments were brought to the attention of the nation by revelations contained in a Pulitzer Prize-winning series of newspaper stories about plutonium injections carried out by the government on allegedly unsuspecting subjects during the Cold War. The Committee faced a broad mandate, which included piecing together the history of Cold War radiation experiments and human subjects research, as well as recommending remedies for past wrongs and mechanisms to ensure that such wrongs could not be repeated in the future.This issue of the Journal consists of articles and accompanying commentaries on historical, philosophical, policy, and political aspects of the Committee’s work that are important to bioethics. This collection of articles, authored by Committee members, staff, and leading scholars, is designed to paint a picture of the breadth and complexity of the Committee’s efforts and to provide context and to stimulate discussion of significant issues.In the first article, Ruth Faden provides her unique perspective as chair of the Committee. She goes beyond the necessary overview and background of the Committee to reflect on the impact and meaning of the Committee’s work to bioethics and public policy.Much of the Committee’s effort was directed at gathering and uncovering information about the history of Cold War radiation experiments, an endeavor fairly foreign to bioethics but critically important to understanding the context in which to make moral judgments about the past. Jonathan Moreno and Susan Lederer discuss how the Committee’s work changed some of the traditional views of the history of research ethics. The commentary by Allan Brandt and Lara Freidenfelds further illuminates the value of understanding this recovered history. [End Page ix]In making moral judgments about the past, the Committee confronted complex questions about how to assess wrongdoing and the culpability of the government and its agents. Allen Buchanan explains why this was such a difficult but crucial task and how the Committee worked through some of the answers to these questions. His discussion illustrates the challenges to consensus in the committee decision-making process described in Ruth Macklin’s article in this issue on committees and consensus. Tom Beauchamp analyzes the frameworks for making retrospective moral judgments developed by two committees, the Advisory Committee and the University of California at San Francisco Ad Hoc Fact Finding Committee on World War II Human Radiation Experiments, and critiques their applications of the frameworks in the case of the plutonium injection experiments.The Committee recognized that in order to prevent wrongs seen in the past from occurring in the future, it would be necessary to understand the human subjects protections now in place. Nancy Kass and Jeremy Sugarman discuss the results of the Committee’s attempts to measure the operation and effectiveness of the current system for protection of human subjects. Paul Appelbaum comments on the relevance and value of the Committee’s empirical projects to contemporary human subjects research.The Committee’s work, and the products of any commission’s work, must be viewed partly in light of the place of commissions in bioethics scholarship and policymaking. Appointed commissions can have significant impacts on scholarly and public thinking, policymaking, and future direction, and bring high visibility to issues. It is important to realize that the conclusions of the Committee... (shrink)

Are there universal values of right and wrong, good and bad, shared by virtually every human? The tradition of natural law argues that there is. Drawing on the work of psychoanalyst Melanie Klein, whose analyses have touched upon issues related to original sin, trespass, guilt, and salvation through reparation, in this 2006 book C. Fred Alford adds an extra dimension to this argument: we know natural law to be true because we have hated before we have loved and have wished (...) to destroy before we have wanted to create. Natural law is built upon the desire to make reparation for the goodness we have destroyed, or have longed to destroy. Through reparation, we earn salvation from the most hateful part of ourselves, that which would destroy what we know to be good. (shrink)

La réception tardive de l'oeuvre de Ernst Troeltsch en France nous a privés d'une analyse du christianisme originale et féconde. Elle nuance et enrichit ce que nous savons, au travers de la réflexion wébérienne notamment, des relations de la religion chrétienne à la modernité. Contre les interprétations usuelles qui datent l'émergence de cette dernière de la Renaissance et de la Réforme, Troeltsch insiste sur la centralité des Lumières comme marquant la fin de la civilisation ecclésiastique ; c'es l'évanouissement de la (...) référence structurante à l'ordre divin qui inau­gure selon lui l'entrée dans le monde moderne. Sur la base de ce constat, il s'agit pour Troeltsch de trouver une définition du christianisme qui soit en adéquation avec les conditions de l'existence moderne. Dans son ouvrage datant de 1912, « Les doctrines sociales des Églises et groupes chrétiens », il examine les types « Église », « secte » et « mystique » pré­sents depuis les origines évangéliques, circonscrivant trois modes socio­logiques et éthiques qu'il confronte à la modernité. Aucun n'est seul adéquat. Pour durer, le christianisme devra, selon Troeltsch, renoncer à la réalisation d'un programme éthique d'essence religieuse au sein du monde et accepter le cantonnement de la foi dans l'intimité des cons­ciences, tout en s'articulant à des réalités socio-culturelles à l'échelle de tous dont les formes et les transformations internes sont toujours à repenser.The delayed reception of the work of Ernst Troeltsch in France deprived us of an analysis of an original and fertile Christianity. It nuances and enriches what we know, especially through a Weberian reflection, about the relations of the Christian religion and modernity. Against the customary interpretations that date the emergence of the latter from the Renaissance and the Reformation, Troeltsch insists on the centrality of the Enlightenment as marking the end of an ecclesiastical civilization. It is the disappearance of the structuring reference to the divine order that inaugurated, according to him, the entrance to the modern world. On the basis of this observation, Troeltsch is interested in finding a definition of Christianity that would be in harmony with the conditions of modern existence. In his work dating from 1912, "The social doctrines of the Churches and Christian groups ", he examines the categories "Church", "sect", and "mystic" that were present evangelical times, circumscribing three sociological and ethical modes, which he confronts with modernity. No single one is adequate. In order to endure, Christian­ity should, according to Troeltsch, renounce the attempt to set up an ethical program of a religious essence in the heart of the world and accept the establishment of a faith in the intimacy of consciences, all the while adapting its« to socia-cultural realities applicable to everyone, of which the forms and internal transformations are always to be re-thought. (shrink)

Stiff Person Syndrome is a rare autoimmune disorder associated with antibodies against glutamic acid decarboxylase, the key enzyme in γ -aminobutyric acid synthesis. In order to investigate the role of cerebral benzodiazepinereceptor binding in SPS, we performed [ 11 C]flumazenil positron emission tomography in a female patient with SPS compared to nine healthy controls. FMZ is a radioligand to the postsynaptic central benzodiazepine receptor which is co-localized with the GABA-A receptor. In the SPS patient, we found a global reduction of (...) cortical FMZ binding. In addition, distinct local clusters of reduced radiotracer binding were observed. These data provide first in vivo evidence for a reduced postsynaptic GABA-A receptor availability which may reflect the loss of GABAergic neuronal inhibition in SPS. (shrink)

least this was his later view. He had begun with the more obvious but more naive view that need was the key to the process and that removal of the need ...

The author examines "the prelude" by wordsworth in order to illuminate precisely how wordsworth believed the spirit, Particularly as it manifested itself in the works of nature, Could influence and shape the mind of man. (staff).

We describe the development, testing, and formative evaluation of nine role-play scenarios for teaching central topics in the responsible conduct of research to graduate students in science and engineering. In response to formative evaluation surveys, students reported that the role-plays were more engaging and promoted deeper understanding than a lecture or case study covering the same topic. In the future, summative evaluations will test whether students display this deeper understanding and retain the lessons of the role-play experience.

In a general account of this Livian MS. given in the Classical Review of 1904 I dealt more especially with the text of the first decade; now that my study of its text of the third decade is completed, it is possible to give a brief estimate of its importance and interest in this portion also.

The model of DNA-histones has the following elements: The hydrogen bonds between the complementary nucleotide bases function as informational gates. When the electrons π of one nucleotide base are excited, an exchange of protons is produced between the two complementary bases. The result is the displacement of the conjugated double bonds which facilitates the inter-molecular transmission of the electronic wave of excitation by electro-magnetic coupling. Each triplet of nucleotide bases of DNA fixes one definite amino acid . Between the nucleotide (...) bases and the amino acids there are constituted informational gates, which ensure the circulation of the electronic wave of excitation. An input signal molecule arrives at the receiver gene and unleashes the activity of the enzymes which introduce in the DNA-histones system the electronic wave of excitation. The electronic wave of excitation arises as a result of the break of the high-energy bonds of ATP. Then, the electronic excitation is transmitted to the productor gene where it represents the signal for starting the synthesis of the mRNA.Le modèle de système ADN-Histone a les éléments suivants: Les liaisons d'hydrogène entre les bases nucléotidiques complémentaires fonctionnent comme des portes informationnelles. Quand les électrons π d'une base nucléotidique sont excités, il se produit un échange de protons entre les bases complémentaires. Le résultat est un déplacement des doubles liaisons conjugées qui facilite la transmission de l'onde d'excitation électronique par un couplage électromagnétique. Chaque triplet de bases nucléotidiques de l'ADN fixe un certain amino-acide . Entre les bases nucléodiques et les amino-acides se constituent des portes informationnelles qui assurent la circulation de l'onde d'excitation dlectronique. Une molécule signal d'entrée arrive au gène récepteur et déclenche l'activité des enzymes qui introduisent dans le système ADN-histone l'excitation électronique. L'excitation électronique apparait comme résultat de la rupture des liaisons de haute énergie del' ATP. l'Onde d'excitation électronique est transmise au gène producteur, où elle rdprésente le signal pour faire commencer la synthèse de l'ARNm.Das Modell des DNS-Histonen Systems weist folgende Elemente auf: Die Wasserstoffbindungen zwischen den komplementäaren Nukleotidbasen funktionieren wie informationale Pforten. Wenn die π Elektronen einer Nukleotidbase erregt werden, ensteht ein Protonenwechsel zwischen den Komplementären Basen. Das Ergebnis ist eine Verschiebung der konjugierten Doppelbindungen, die die Weiterleitung der elektronischen Erregungswelle durch eine elektromagnetische Kupplung erleichtert. Jedes Nukleotidbasentriplett der DNS fixiert eine bestimmte Aminosäure . Zwischen den Nukelotidbasen und den Aminosäuren entstehen Informationspforten, welche den Umlauf der elektronischen Erregungswelle sichern. Ein Eintrittsignal Moleküul gelangt zur Rezeptorgen und löst die Aktivität von Enzymen aus, welche die elektronische Erregungswelle in das DNS-Histonen System einführen werden. Die elektronische Erregungswelle erscheint als Ergebnis der Spaltung der hochenergetischen Bindungen des ATP-s. Die elektronische Erregungswelle wird alsdann zur Produktorgen weitergeleitet, wo sie das Signal zum Beginn der Synthese der mRNS darstellt. (shrink)

This a special issue of the Journal of Logic Language and Information that I edited.