Heterogeneous nuclear ribonucleoprotein U (HNRNPU) is a nuclear protein that plays a crucial role in various biological functions, such as RNA splicing and chromatin organization. HNRNPU/scaffold attachment factor A (SAF‐A) activities are essential for regulating gene expression, DNA replication, genome integrity, and mitotic fidelity. These functions are critical to ensure the robustness of developmental processes, particularly those involved in shaping the human brain. As a result, HNRNPU is associated with various neurodevelopmental disorders (HNRNPU‐related neurodevelopmental disorder, HNRNPU‐NDD) characterized by developmental delay (...) and intellectual disability. Our research demonstrates that the loss of HNRNPU function results in the death of both neural progenitor cells and post‐mitotic neurons, with a higher sensitivity observed in the former. We reported that HNRNPU truncation leads to the dysregulation of gene expression and alternative splicing of genes that converge on several signaling pathways, some of which are likely to be involved in the pathology of HNRNPU‐related NDD. (shrink)

Pathogenic variants occurring in protein‐coding regions underlie human genetic disease through various mechanisms. They can lead to a loss of function (LOF) such as in recessive conditions or in dominant conditions due to haploinsufficiency. Dominant‐negative (DN) effects, counteracting the activity of the normal gene‐product, and gain of function (GOF) are also mechanisms driving dominance. Here, I discuss a few papers on these specific mechanisms. In short, there is accumulating evidence pointing to differences between LOF versus non‐LOF variants (DN and GOF). (...) The latter are thought to have milder effects on protein structure and, as expected, DN variants are enriched at protein interfaces. This tendency to cluster in 3D space can help improve the ability of computational tools to predict the pathogenicity of DN variants, which is currently a challenging issue. More recent results support the hypothesis whereby cotranslational assembly of macromolecular complexes can buffer deleterious consequences of variants that would otherwise lead to DN effects (DNEs). Indeed, subunits the variants of which are responsible for DNEs tend to elude cotranslational assembly, thus poisoning complexes involving wild‐type subunits. The constraints explaining why the buffering of DNEs is not universal require further investigation. (shrink)

Testis determination in most mammals is regulated by a genetic hierarchy initiated by the SRY gene. Early ovarian development has long been thought of as a default pathway switched on passively by the absence of SRY. Recent studies challenge this view and show that the ovary constantly represses male‐specific genes, from embryonic stages to adulthood. Notably, the absence of the crucial ovarian transcription factor FOXL2 (alone or in combination with other factors) induces a derepression of male‐specific genes during development, postnatally (...) and, even more interestingly, during adulthood. Strikingly, in the adult, targeted ablation of Foxl2 leads to a molecular transdifferentiation of the supporting cells of the ovary, which acquire cytological and transcriptomic characteristics of the supporting cells of the testes. These studies bring many answers to the field of gonadal determination, differentiation and maintenance, but also open many questions. (shrink)

Cooperative discourse procedures produce consensual siting proposals for NIMBY-projects-but only if these proposals do not affect the final siting decision. Then, the members of the discourse commissions stay independent and face few incentives to pursue consequentialist interests. However, the more influential discourse procedures become, the stronger the interest groups’ incentives are to take advantage of them. Thus, cooperative discourses turn into competitive, interest-centred procedures whose outcome is rejected by the less influential groups. The evolution of discourse procedures into functionally specialized (...) parliaments or even into FOCJ (Functional, Overlapping, Competing Jurisdictions) seems worth pursuing. (shrink)

Sollen und Sein klaffen bei uns weiter auseinander als bei anderen, weil eben das Sollen sehr hoch gesetzt ist. Thomas Mann, Doctor Faustus.

The conceptual incompatibility between General Relativity and Quantum Mechanics is generally seen as a sufficient motivation for the development of a theory of Quantum Gravity. If - so a typical argumentation - Quantum Mechanics gives a universally valid basis for the description of the dynamical behavior of all natural systems, then the gravitational field should have quantum properties, like all other fundamental interaction fields. And, if General Relativity can be seen as an adequate description of the classical aspects of gravity (...) and spacetime - and their mutual relation -, this leads, together with the rather convincing arguments against semi-classical theories of gravity, to a strategy which takes a quantization of General Relativity as the natural avenue to a theory of Quantum Gravity. And, because in General Relativity the gravitational field is represented by the spacetime metric, a quantization of the gravitational field would in some sense correspond to a quantization of geometry. Spacetime would have quantum properties. But, this direct quantization strategy to Quantum Gravity will only be successful, if gravity is indeed a fundamental interaction. Only if it is a fundamental interaction, the given argumentation is valid, and the gravitational field, as well as spacetime, should have quantum properties. - What, if gravity is instead an intrinsically classical phenomenon? Then, if Quantum Mechanics is nevertheless fundamentally valid, gravity can not be a fundamental interaction; a classical and at the same time fundamental gravity is excluded by the arguments against semi-classical theories of gravity. An intrinsically classical gravity in a quantum world would have to be an emergent, induced or residual, macroscopic effect, caused by a quantum substrate dominated by other interactions, not by gravity. Then, the gravitational field (as well as spacetime) would not have any quantum properties. And then, a quantization of gravity (i.e. of General Relativity) would lead to artifacts without any relation to nature. The serious problems of all approaches to Quantum Gravity that start from a direct quantization of General Relativity (e.g. non-perturbative canonical quantization approaches like Loop Quantum Gravity) or try to capture the quantum properties of gravity in form of a 'graviton' dynamics (e.g. Covariant Quantization, String Theory) - together with the, meanwhile, rich spectrum of (more or less advanced) theoretical approaches to an emergent gravity and/or spacetime - make this latter option more and more interesting for the development of a theory of Quantum Gravity. The most advanced emergent gravity (and spacetime) scenarios are of an information-theoretical, quantum-computational type. A paradigmatic model for the emergence of gravity and spacetime comes from the Pregeometric Quantum Causal Histories approach. (shrink)

Sollen und Sein klaffen bei uns weiter auseinander als bei anderen, weil eben das Sollen sehr hoch gesetzt ist.Thomas Mann, Doctor Faustus.

Terminale Sedierung ist unter bestimmten Umständen ethisch rechtfertigbar: Mit dem Wissen um die Begrenztheit des eigenen Lebens ist auch der Sterbeprozess ein bewusst zu gestaltender, dem eigenen Willen unterworfener Bestandteil des Lebens. Das schließt auch die (paradoxe) Möglichkeit ein, bewusst auf das Bewusstsein beim eigenen Sterben zu verzichten. Anhand eigener Studien kann der Autor zeigen, dass sich der Wunsch nach Sterbehilfe bei terminal kranken Menschen als die Folge einer konsequenten Einordnung in das System der Medizin deuten lässt. Infolgedessen begreifen Patienten (...) auch das Sterben als eine Aufgabe des Medizinsystems, so dass sie ärztliche Sterbehilfe als Ausdruck für ein menschenwürdiges Sterben, paradoxerweise sogar als natürlichen Tod auffassen können. In dieser Situation ermöglicht die terminale Sedierung einen Fortschritt: Das Medizinsystem kann der von ihm erwarteten Zuständigkeit für den Prozess des Sterbens nachkommen, ohne direkt und intentional zu töten. Trotzdem bleiben bezüglich der Missbrauchsmöglichkeiten, der Rollenkonfusion der Ärzte und der Grenzen menschlicher Handlungsräume Zweifel. Vor der „Illusion der glatten Lösungen“ (H. Thielicke) wird gewarnt und für den Versuch geworben, das jeweils Beste für die einzelnen Betroffenen zu erreichen. (shrink)

Human dignity is a prominent maxim in the contemporary ethical discussion in bioethics. In this debate the concept of human dignity acts as a warrant for human imperfection and fragility, particulary in the case of incapacitated, demented, or terminal ill persons. In this perspective the common foundations of human dignity, based on autonomy, capacity for rational thought, or man as imago dei, are deficient. As the above paper sketches, human dignity is to explain as a relational category rather than an (...) intrinsic quality of men. In addition to this, such an understanding offers numerous links to the reformational doctrine of justification: The value of humans does not depend on their own faculties. (shrink)

Paper edition (unseen), $16.95. Annotation copyrighted by Book News, Inc., Portland, OR.

Kant's general term 'categorical imperative' conceals two substantially different ethical principles namely (1) "the" fundamental principle of moral argumentation, called by kant "the principle of pure practical reason", and (2) "a" (one or more than one) procedure for testing maxims and norms for acting. this thesis of the two different functions of the categorical imperative is proved by a detailed systematic analysis of both kant's different formulas of the categorical imperative and kant's examination of four maxims in the "grundlegung".

O ponto de partida do presente artigo consiste na afirmação de que as religiões originárias do Próximo Oriente - Judaísmo, Cristianismo, e Islamismo - contêm em si mesmas inconsistências práticas e teóricas. Mais ainda, o autor afirma que estas religiões estão em contradição umas com as outras no que diz respeito a aspectos teológicos essenciais, para além de que entre elas existe um passado de guerra e de conflito. Ora estas são precisamente as razões pelas quais o autor considera que (...) a credibilidade epistemológica e moral destas religiões foi dramaticamente afectada. Daí o principal objectivo do artigo: contribuir para o esclarecimento do modo como Filosofia e Teologia podem cooperar entre si em ordem a uma mitigação destas deficiências. Nesse sentido, segundo o autor, uma e outra devem abraçar a possibilidade de demonstrar epistemologicamente que os conteúdos da revelação do ponto de vista da razão não são nem demonstráveis nem refutáveis, pois esses conteúdos não são proposições científicas acerca de eventos e processos interiores ao mundo, mas apenas a expressão de uma atitude religiosa em relação ao mundo no seu todo (e em relação a Deus). Nessa medida, diz o autor, nada justifica que atitudes religiosas de fé e de amor sejam caracterizadas como 'irracionais', antes a elas se devendo aplicar a designação de 'a-racional' ou simplesmente de 'transracional. Mais ainda, a Filosofia e a Teologia estão em posição de mostrar de que modo atitudes religiosas fundamentais estão construídas umas sobre as outras. Com efeito, básica em todas as formas de religião é uma atitude em relação ao mundo considerado como um todo, tal como se pode encontrar, por exemplo, no Taoismo ou no Zen-Budismo, de modo que aqui não se encontra qualquer forma de crença numa divindade transcendente; ora é precisamente esta atitude que o autor do artigo designa por 'Religiosidade A'. Como 'Religiosidade B', por outro lado, designa o autor toda a atitude religiosa de fundo que transcende o mundo presente e nos remete para a existência de um Deus único e da sua Revelação, tal como é o caso com o Judaísmo, o Cristianismo, e o Islamismo. Aqui, a tarefa consiste sobretudo em clarificar de forma lógica e conceptual a possibilidade de uma auto-revelação divina bem como da sua aceitabilidade nos termos de uma crença humanamente constituída. Finalmente, o artigo refere também aquela que o autor considera ser a 'Religiosidade C', expressão esta que simplesmente denota aquela atitude em que, com base nas premissas presentes nas formas A e B de religiosidade, somos especificamente remetidos para á Revelação cristã, ou seja, para a experiência nos termos da qual se professa a encarnação de Deus em Jesus de Nazaré e se afirma a sua condição de ser expressão do amor incondicional de Deus para com todos os seres humanos. Na verdade, a natureza incondicional deste amor apresenta-se como um escândalo moral diante da auto-compreensão ética da humanidade. Consequentemente, a incompreensibiliâade deste amor não pode ser senão objecto da revelação divina e da pura fé, únicos modos possíveis de ele se transformar numa possível justificação 'moral' dos seres humanos. /// Starting-point of this article is the fact that the religions originated from the Near East - Judaism, Christianity, and Islam - do contain in themselves theoretical and practical inconsistencies. Moreover, they contradict each other in essential theological regards, and they made war upon each other in the past. For these reasons, their epistemological and moral credibility has been dramatically diminished. In this context, the article aims at showing how philosophy and theology might be able to work together in alleviating these deficits. First, they may demonstrate epistemologically that the contents of revelation are neither rationally demonstrable nor refutable because they are not scientific statements upon events and processes within the world but the expression of a religious attitude towards the world as a whole (and towards God). Therefore, such attitudes as religious faith and love shouldn't be designated 'irrational', but rather as arational' or, 'transrational'. Furthermore, philosophy and theology are able to show in what manner fundamental religious attitudes are built upon another: Basic for all higher forms of religion is an attitude towards the world as a whole – as one can find for instance in Daoism or Zen-Buddhism – where there is not yet any belief in a transcendent deity; that attitude is called 'Religiosity A'. So called 'Religiosity B' is a fundamental attitude which transcends this world and refers to a sole God and his revelation as can be found among Jews, Christians, and Muslims. Here, the possibility of divine self-revelation and of its acceptability by human faith has to be clarified logically and conceptually. Finally, 'Religiosity C denotes that attitude which, on the premises of those Religiosities A and B, refers to the specifically Christian revelation which confesses the incarnation of God in Jesus and presents him as the expression of God's unconditional love to all human beings. The unconditionality of this love seems to be a moral scandal to human moral understanding. Therefore, this unconceivable love has to be object of divine revelation and of pure faith so that it might be the basis of all possible 'moral' justification of humankind. (shrink)

Nancy Cartwright relies upon an inference pattern known as inference to the best causal explanation (IBCE) to support a limited form of entity realism, according to which we are warranted in believing in entities that purportively cause observable effects. IBCE, as usually understood, is valid, even though all other forms of inference to the best explanation (IBE) are usually understood to be invalid. We argue that IBCE and IBE are in the same boat with respect to their ability to support (...) realist conclusions. Either rule can be interpreted as valid, this is a matter of semantic convention. However, doing so deprives the rule of the empirical content the realist needs, requiring the realist to find independent warrant for a strong (theoretical or causal) premise. We then examine the proposed means of obtaining this warrant, and find them as inadequate in the case of IBCE as they are in the case of IBE. (shrink)

Advances in psychology and neuroscience have elucidated the social aspects of human agency, leading to a broad shift in our thinking about fundamental concepts such as autonomy and responsibility. Here, we address a critical aspect of this inquiry by investigating how people consider the socio-relational nature of their own agency, particularly the influence of others on their perceived control over their decisions and actions. Specifically, in a series of studies using contrastive vignettes, we examine public attitudes about when external influences (...) on everyday decisions are perceived as " undue " – that is, as undermining the control conditions for these decisions to be considered autonomous – vs. when they are perceived as appropriate and even supportive of autonomous decision-making. We found that the influence of preauthorized agents – individuals and institutions with whom we share a worldview – was judged to be less undue than non-preauthorized agents, even after controlling for the familiarity of the agent. These effects persisted irrespective of the extent to which respondents identified as communitarian or individualistic, and were consistent across two distinct scenarios. We also found that external influences that were rational were perceived as less undue than those that were arational. Our study opens new avenues of inquiry into the " folk conception " of autonomy, and we discuss the implications of our findings for the ethics of public policies designed to influence decisions and for information sharing in social networks. (shrink)

In most everyday instances of reasoning, reasoners can gain, lose, and reacquire entitlement to (or justification for) a possible commitment (or belief) as a result of their consecutively acquiring new commitments. For example, we might initially conclude that ‘Tweety can fly’ from ‘Tweety is a bird,’ but later have to reject this conclusion as a result of our coming to learn that Tweety is a penguin. We could, even later, reacquire entitlement to ‘Tweety can fly’ if we became committed (and (...) presumably entitled) to the claim ‘Tweety has a jetpack.’ I will call this very common feature of reasoning entitlement recovery. In this paper I will argue that the types of inferential relations that are central to Brandom’s entire account of language and reasoning make entitlement recovery impossible. I will then briefly attempt to diagnose why this problem arises for Brandom and suggest how his account should be modified so that it will successfully allow entitlement recovery. (shrink)

Requirements for a Fundamental Physical Theory. The search for a so-called ‘Theory of Everything’ which should lead to the unification of all fundamental forces is seen, at present, as a matter of priority within theoretical high-energy physics. Some physicist identify this Theory of Everything today with aspecific type of superstring theory or its intended conceptual continuation, called M-Theory. The objective of this article is the discussion of the requirements a fundamental physical theory has to comply with. This question can only (...) be clarified if one takes into account that the claim that a physical theory is all-encompassing takes forgranted some tacit prerequisites which concern the conceptual and epistemological foundations of science and, not least, the question for the realizability of its reductionistic unity. (shrink)

In 1903 Rabbi Philipp Bloch, of Posen, published a unique Ashkenazic sixteenth-century polemical pamphlet which attested, so it seemed, to a heated controversy in yeshivah circles in the larger cities of the Ashkenazi cultural sphere in the late 1550s. Revolving around the place of philosophy in Judaism, the dispute reached one of its peaks in Prague some time before April 1559, probably in a public debate before a yeshivah audience, basically similar to the Disputationes then popular in European universities. The (...) disputants were two young scholars, one of whom, the writer of the pamphlet, enthusiastically supported the teaching of classical philosophical texts in Ashkenazi yeshivot, while the other fiercely opposed what he called “philosophy.” He accused Maimonides of heresy and unbelief, as he did anything that he associated with either “philosophy” or Maimonides. The resolution adopted by the yeshivah audience — at least, so we read in the pamphlet, our only source for the event — was unequivocal: the opponent of Maimonides and philosophy was forbidden, from that time on, to broadcast his views. (shrink)

This book offers a collection of essays in contemporary political philosophy from a wide range of Continental viewpoints. The authors include some of the most prominent European and European-oriented philosophers and political thinkers of our day. Two sections out of four focus on the debate between prescriptive and descriptive types of political thinking. On the prescriptive or normative side, Karl-Otto Apel, Robert Paul Wolff, Robert Spaemann, Hans Jonas, and Jean-Francois Lyotard discuss current forms of legitimating political life via some ultimate (...) grounding. On the descriptive or phenomenological side, Bernhard Waldenfels, Michel Henry, William J. Richardson, Jürgen Link, and Vincent Descombes argue that an understanding of praxis is always implied as one reaches insights into the life-world; there is no need to either construe or set normative standards for action. The remaining two sections deal with transcendental and institutional types of political philosophy, respectively. Manfred Riedel, Stanley Rosen, Thomas Seebohm, and Ludwig Siep develop Kant’s search for “a priori” conditions in the public realm; explicitly or implicitly, they confront the ancient Greek with the modern Enlightenment conceptions of life in public. Lastly, Agnes Heller, Alain Touraine, Reinhart Koselleck, and Bertram Schefold put to work many ways of looking at the life of our institutions. (shrink)

SummaryMutations in human genes encoding transcription factors are often dominant because one active allele cannot ensure a normal phenotype (haploinsufficiency). In other instances, heterozygous mutations of two genes are required for a phenotype to appear (combined haploinsufficiency). Here, we explore with models (i) the basis of haploinsufficiency and combined haploinsufficiency owing to mutations in transcription activators, and (ii) how the effects of such mutations can be amplified or buffered by subsequent steps in a transcription cascade. We propose that the non‐linear (...) (sigmoidal) response of transcription to the concentration of activators can explain haploinsufficiency. We further show that the sigmoidal character of the output of a cascade increases with the number of steps involved, the settings of which will determine the buffering or enhancement of the effects of a decreased concentration of an upstream activator. This exploration provides insights into the bases of compensatory mutations and on interloci interactions underlying oligogenic inheritance patterns. (shrink)

La «Règle d' Or» , qui est bien connue de la Bible (Tob. 4, 15; Matt. 7, 12; Luc. 6, 31) et qui nous invite à prendre pour critère de notre propre conduite envers autrui les modes d'action que nous (ne) voulons (pas) qu' on envisage envers nous-mêmes, est répandue parmi la plupart des peuples civilisés dès le 5e siècle av. J.-Chr. Elle s'articule principalement de trois façons: 1) comme «règle de sympathie» qui nous engage à (ne pas) imposer à (...) autrui ce que nous (ne) voulons (pas) subir nous-mêmes; 2) comme «règle d'authenticité» qui nous demande de nous en tenir nous-mêmes dans nos actes aux exigences que nous imposons à la conduite d'autrui et que, ce faisant, nous reconnaissons comme universellement valables; 3) comme «règle de réciprocité» qui nous engage à agir nous-mêmes envers autrui comme nous désirons qu'on agisse envers nous. Tout homme revendiquant son corps comme n'appartenant qu' à lui seul, cette règle amène par voie de réciprocité à poser le droit naturel d'un chacun à l'intégrité de son corps, à sa liberté, et à ses biens. (shrink)

The basic thought of Schweitzer's ethic, the reverence for life, has manifold significance. First, it is an appeal to our moral feeling. But secondly, Schweitzer lent this thought also a general, fundamental and therewith philosophical meaning: proceeding from the “most immediate and encompassing fact of consciousness,” described by him with the proposition “I am life that will live in the midst of life that will live,” Schweitzer believed to have found in the idea of reverence for life the fundamental principle (...) of all morality; this consists in the fact “that I experience the need to extend to all wills to live the same reverence that I extend to my own.” In addition to its effect on moral feeling and on ethical theory, the future of the thought, “reverence for life,” also depends on its compliance in the activity of men.The future prospects of the appeal to moral feeling appear good insofar as testimonies from history permit one to assume that the awareness of the reverence for life can be awakened in all men. The ancient Greeks knew such sensibility in theaidos, Goethe in the “reverence for that which is in our midst.” This ever strengthening recognition among the peoples of the earth will, through historically succeeding generations, increasingly eliminate a full disregard for such reverence.Less promising are the prospects of acknowledging the reverence for life as a fundamental principle of morality. On its basis Schweitzer rests his aversion to harming anything living. He does not fail to see thereby that, in order to preserve life, we must destroy some life (at least that of plants). But, says Schweitzer, I become guilty in sacrificing life, and we must constantly remain conscious of this guilt; any attempts at justification, through considerations of differences in the value of various lives, must be rejected.However, an ambiguity in the word “guilt” underlies Schweitzer's position. On the one hand “guilt” is understood as a regrettable cause for the subsistence or eventuation of an evil, on the other as the moral reprehensibility of an attitude. Only the latter represents guilt in a moral sense. Whoever follows the necessity to destroy other, less valuable life in order to preserve his own or another life, assumes guilt only in the second sense. Therefore ethics must raise and pursue the question concerning the value priority of one life over another. This question leads to an encounter with the modern directions of ethics which proceed from the concept of value, and to the continuation of Schweitzer's ethics through this encounter. Schweitzer's explanation that life in the world is “to be brought to its highest value” likewise conduces to the same point, since it necessitates an investigation of the rank order of values.We can note a slow progress of the reverence for life in the private domain of human activity. On the other hand in the interrelationship of peoples there is danger of monstrous mass murder through the atomic bomb. (shrink)

In a prior article, “Symbolic Difference,” I followed the indications provided by certain data in order to focus on the ontological locus of the symbol. A difference then appeared in the origin, which revealed itself through gesture, sign, use, and trace. The symbol, distended by definition between man and his origin, is the privileged region of language where this difference is thematized for itself. The search for the concealment-manifestation at work in the symbol led to the difficult problems surrounding its (...) interpretation, and it culminated with a summons or provocation towards existence. I mentioned some historical examples in which the symbol’s efficacy with regard to a life was blatant: the symbol opens up a path whose course makes one experience the origin. The condition of this experience is to “live without why,” to let that which is, be. (shrink)

In a prior article, “Symbolic Difference,” I followed the indications provided by certain data in order to focus on the ontological locus of the symbol. A difference then appeared in the origin, which revealed itself through gesture, sign, use, and trace. The symbol, distended by definition between man and his origin, is the privileged region of language where this difference is thematized for itself. The search for the concealment-manifestation at work in the symbol led to the difficult problems surrounding its (...) interpretation, and it culminated with a summons or provocation towards existence. I mentioned some historical examples in which the symbol’s efficacy with regard to a life was blatant: the symbol opens up a path whose course makes one experience the origin. The condition of this experience is to “live without why,” to let that which is, be. (shrink)

In a prior article, “Symbolic Difference,” I followed the indications provided by certain data in order to focus on the ontological locus of the symbol. A difference then appeared in the origin, which revealed itself through gesture, sign, use, and trace. The symbol, distended by definition between man and his origin, is the privileged region of language where this difference is thematized for itself. The search for the concealment-manifestation at work in the symbol led to the difficult problems surrounding its (...) interpretation, and it culminated with a summons or provocation towards existence. I mentioned some historical examples in which the symbol’s efficacy with regard to a life was blatant: the symbol opens up a path whose course makes one experience the origin. The condition of this experience is to “live without why,” to let that which is, be. (shrink)

The ambiguity regarding whether a given intervention is perceived as enhancement or as therapy might contribute to the angst that the public expresses with respect to endorsement of enhancement. We set out to develop empirical data that explored this. We used Amazon Mechanical Turk to recruit participants from Canada and the United States. Each individual was randomly assigned to read one vignette describing the use of a pill to enhance one of 12 cognitive, affective or social domains. The vignettes described (...) a situation in which an individual was using a pill to enhance the relevant domain under one of two possible enhancement conditions, one perceived as enhancing above the norm, what most people recognize as a clear case of enhancement, whereas the other perceived as enhancing towards the norm, with the individual using the enhancement having a modest, but subclinical deficit. Participants were asked how comfortable they were with the individual using the enhancement and about the impact the enhancement might have had in the individuals’ success in life. We found that irrespective of the domain to be enhanced, participants felt significantly more comfortable with ETN than with EAN, and they regarded the enhancement intervention as contributing to greater success in life with ETN rather than EAN. These data demonstrate that the therapy enhancement distinction is morally salient to the public, and that this distinction contributes to the angst that people feel when considering the propriety of CAS enhancement. (shrink)

The debate over the propriety of cognitive enhancement evokes both enthusiasm and worry. To gain further insight into the reasons that people may have for endorsing or eschewing pharmacological enhancement, we used empirical tools to explore public attitudes towards PE of twelve cognitive, affective, and social domains. Participants from Canada and the United States were recruited using Mechanical Turk and were randomly assigned to read one vignette that described an individual who uses a pill to enhance a single domain. After (...) reading the vignette, participants were asked how comfortable they were with the individual using the enhancement. People were significantly more comfortable when they read about enhancement of certain CAS domains than others. We found a modest negative correlation between comfort level and the degree to which the PE was perceived as changing core features of the person. We also found a modest correlation between comfort level and the degree to which the PE was perceived as improving success in life. Finally, using a sequential mixed method technique, we found that participants who felt uncomfortable about PE use overwhelmingly focused on a lack of need and, to a lesser degree, expressed concerns about safety; those who felt comfortable about PE use most frequently mentioned the safety of the pill and its ability to provide a positive outcome. The data provide novel insights into public enthusiasms and concerns over the use of PE. (shrink)

To gain insight into the reasons that the public may have for endorsing or eschewing pharmacological moral enhancement for themselves or for others, we used empirical tools to explore public attitudes towards these issues. Participants from the United States were recruited via Amazon’s Mechanical Turk and were randomly assigned to read one of several contrastive vignettes in which a 13-year-old child is described as bullying another student in school and then is offered an empathy-enhancing program. The empathy-enhancing program is described (...) as either involving taking a pill or playing a video game on a daily basis for four weeks. In addition, participants were asked to imagine either their own child bullying another student at school, or their own child being bullied by another student. This resulted in a 2 × 2 between-subjects design. In an escalating series of morally challenging questions, we asked participants to rate their overall support for the program; whether they would support requiring participation; whether they would support requiring participation of children who are at higher risk to become bullies in the future; whether they would support requiring participation of all children or even the entire population; and whether they would be willing to participate in the program themselves. We found that people were significantly more troubled by pharmacological as opposed to non-pharmacological moral enhancement interventions. The results indicate that members of the public for the greater part oppose pharmacological moral bioenhancement, yet are open to non-biomedical means to attain moral enhancement. [248 words]. (shrink)

To English language readers, Kostas Axelos is known for a single book on Marx --a regrettably small sample when compared to the number of his additional books in French, Greek, or German, and shamefully small in light of the stature of his thinking.

Interleukin 1β‐converting enzyme (ICE)‐like proteases (caspases) play an important role in programmed cell death (apoptosis), and elucidating the consequences of their proteolytic activity is central to our understanding of the molecular mechanisms of cell death. Diverse structural and regulatory proteins and enzymes, including protein kinase Cδ, the retinoblastoma protein (a protein involved in cell survival), the DNA repair enzyme DNA‐dependent protein kinase and the nuclear lamins, undergo specific and limited endoproteolytic cleavage by various caspases during apoptosis. Since individual caspases can (...) cleave multiple substrates, the consequences of cleavage of only a single substrate are still poorly understood. Nevertheless, proteolytic activation of protein kinase Cδ may be an important early step in the cell death pathway, and cleavage of the retinoblastoma protein could suppress its cell survival function, whereas proteolytic inactivation of DNA repair enzymes might compromise the ability of the cell to reverse DNA fragmentation. On the other hand, cleavages of nuclear and cytoplasmic structural proteins (e.g. the lamins and Gas2) appear to be required for or contribute to the dramatic rearrangements in cellular architecture that are necessary for the completion of the cell death process. An emerging theme is that parallel and sequential proteolytic activation and inactivation of key protein substrates occurs during the multiple steps of apoptosis. (shrink)

With the ever‐increasing lifespan along with societal changes, women can marry and procreate later than in previous centuries. However, pathogenic genetic variants segregating in the population can lead to female subfertility or infertility well before the average age of normal menopause, leading to counter‐selection of such deleterious alleles. In reviewing this field, we speculate that a logical consequence would be the later occurrence of menopause and the extension of women's reproductive lifespan. We illustrate this point with a simple model that (...) applies to other variants that contribute to female infertility, including epigenetic variation. We also consider the effect of medical interventions and lifestyle. (shrink)

Every metaphysic, according to Reiner Schürmann, involves the positing of a first principle for thinking and doing whereby the world becomes intelligible and masterable. What happens when such rules or norms no longer have the power they previously had? According to Cornelius Castoriadis, the world makes sense through institutions of imaginary significations. What happens when we discover that these significations and institutions truly are imaginary, without ground? Both thinkers begin their ontologies by acknowledging a radical finitude that threatens to (...) destroy meaning or order. For Schürmann it is the ontological anarchy revealed between epochs when principles governing modes of thinking and doing are foundering but new principles to take their place have not yet emerged. For Castoriadis it is chaos that names the indeterminationdetermination that governs the unfolding of the socio-historical with contingency and unpredictability. And yet for both thinkers their respective ontologies have political or ethical implications. On the basis of the anarchy of being, Schürmann unfolds an anarchic praxis or ethos of “living without why.” And on the basis of his notion of being as chaos, Castoriadis develops his political praxis of autonomy. The challenge for both is this move from ontology to practical philosophy, how to bridge theory and practice. The key for both seems to be a certain ontologically derived sense of freedom. In this paper, I analyze and compare their respective thoughts, and pursue the question of how anarchy or chaos and the implied sense of an ontological freedom might be made viable and sensible for human praxis, how radical finitude in the face of ontological groundlessness might nevertheless serve to situate a viable political praxis. (shrink)

The work of Reiner Schürmann’s which has received the most intense reception has been his monumental book on Heidegger. Both Emmanuel Levinas and Hans-Georg Gadamer have praised it warmly, and it is regarded as an astonishing work, combining both a thorough knowledge of Heidegger’s thought and an original and intriguing philosophical claim. In the following, I shall concentrate primarily on this philosophical claim and not on the question whether Reiner Schürmann’s reconstruction of Heidegger is sufficiently philologically accurate. I (...) do not harbor any doubt in this latter respect, but this lack of doubt on my part does not prove anything, for my knowledge of Heidegger is infinitely less deep than his. My concern will go to the philosophical ideas which he tries to defend, not to determining whether they are genuinely Heideggerian or more representative of Schürmann’s own position. In section one, I shall expose what seems to be essential to me in these ideas. In section two, I shall criticize and try to confute them. If not cogent reasons, personal and social causes must have led, as I see it, Schürmann’s quest in a wrong direction. In section three, I shall analyze these causes, since I believe that they are symptomatic of the best minds of our time. Finally, in section four, it will become possible to evaluate those ideas in more positive terms. In fact, it is always more difficult to see the greatness of an enterprise rather than its errors, and even with regard to the latter one should recognize that certain errors are indispensable and much more important than plain truisms. It is with great grief that I criticize a dead friend with whom I would prefer incomparably more to have this discussion openly. But, besides being an exellent philosopher, Reiner was an extremely noble and fine human being and he would accept the two maxims I have decided to follow in this lecture: Amica veritas, ergo legendus Reinerius; and Omnium hominum amicorum magis amica veritas ipsa. (shrink)

The article presents the sociology of knowledge approach to discourse (SKAD). SKAD, which has been in the process of development since the middle of the 1990s, is now a widely used framework among social scientists in discourse research in the German-speaking area. It links arguments from the social constructionist tradition, following Berger and Luckmann, with assumptions based in symbolic interactionism, hermeneutic sociology of knowledge, and the concepts of Michel Foucault. It argues thereby for a consistent theoretical and methodological grounding of (...) a genuine social sciences perspective on discourse interested in the social production, circulation and transformation of knowledge, that is in social relations and politics of knowledge in the so-called ‘knowledge societies’. Distancing itself from Critical Discourse Analysis, Linguistics, Ethnomethodology inspired discourse analysis and the Analysis of Hegemonies, following Laclau and Mouffe, SKAD’s framework has been built up around research questions and concerns located in the social sciences, referring to public discourse and arenas as well as to more specific fields of (scientific, religious, etc.) discursive struggles and controversies around problematizations (Foucault). (shrink)

With great sympathy for Roman Ingarden and his work, Edith Stein edited his book project The Literary Work Of Art. In the letters she exchanges with him shereflects on relationship between reality and ideality: she writes that those who do not see the world as a reality must be fools. The political events in the 1930s had an impact on phenomenology. While Edmund Husserl dissociates himself from his protégé Martin Heidegger with regard to the content of his philosophy as well (...) as with regard to his ideology, Edith Stein distances herself more and more from the phenomenological method, seeing it as removed from reality, and she eventually become a Carmelite nun. Roman Ingarden, on the other hand, reconsiders interpreting phenomenology as aesthetic theory. Literature and film are being re-analysed in terms of phenomenological mediality and as factors of human communication. (shrink)

Keine ausführliche Beschreibung für "Reflexion und Gefühl" verfügbar.

This paper puts forward a theoretical framework for the analysis of expertise and experts in contemporary societies. It argues that while prevailing approaches have come to see expertise in various forms and functions, they tend to neglect the broader historical and societal context, and importantly the relational aspect of expertise. This will be discussed with regard to influential theoretical frameworks, such as laboratory studies, regulatory science, lay expertise, post-normal science, and honest brokers. An alternative framework of expertise is introduced, showing (...) the limitations of existing frameworks and emphasizing one crucial element of all expertise, which is their role in guiding action. (shrink)

Expression of most genes is regulated by the interaction of multiple transcription factors with cis‐regulatory sequences. Many studies have focused on how changes in promoters and enhancers alter gene expression and phenotype. Recently, Hare et al., using elegant wet and computational approaches uncovered a series of enhancers driving the expression of the even‐skipped gene in scavenger flies (Sepsidae).1 Despite the strong sequence divergence between the enhancers in sepsids and drosophilids, they lead to remarkably similar patterns of gene expression in transgenic (...) Drosophila embryos. This can be explained by the existence of intra‐enhancer compensatory mutations and the presence of overlapping/near binding sites for activators and repressors. BioEssays 30:1052–1057, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Der Autor: Reiner Ruffing ist promovierter Philosoph, gibt in der Erwachsenenbildung und an Universitäten Lehrveranstaltungen und ist seit mehr als 20 Jahren Lehrer.