Co‐expression of two or more genes at the single‐cell level is usually associated with functional co‐regulation. While mRNA co‐expression—measured as the correlation in mRNA levels—can be influenced by both transcriptional and post‐transcriptional events, transcriptional regulation is typically considered dominant. We review and connect the literature describing transcriptional and post‐transcriptional regulation of co‐expression. To enhance our understanding, we integrate four datasets spanning single‐cell gene expression data, single‐cell promoter activity data and individual transcript half‐lives. Confirming expectations, we find that positive co‐expression necessitates (...) promoter coordination and similar mRNA half‐lives. Surprisingly, negative co‐expression is favored by differences in mRNA half‐lives, contrary to initial predictions from stochastic simulations. Notably, this association manifests specifically within clusters of genes. We further observe a striking compensation between promoter coordination and mRNA half‐lives, which additional stochastic simulations suggest might give rise to the observed co‐expression patterns. These findings raise intriguing questions about the functional advantages conferred by this compensation between distal kinetic steps. (shrink)

A long‐standing debate in the study of human communication centers on the degree to which communicators tune their communicative signals (e.g., speech, gestures) for specific addressees, as opposed to taking a neutral or egocentric perspective. This tuning, called recipient design, is known to occur under special conditions (e.g., when errors in communication need to be corrected), but several researchers have argued that it is not an intrinsic feature of human communication, because that would be computationally too demanding. In this study, (...) we contribute to this debate by studying a simple communicative behavior, communicative pointing, under conditions of successful (error‐free) communication. Using an information‐theoretic measure, called legibility, we present evidence of recipient design in communicative pointing. The legibility effect is present early in the movement, suggesting that it is an intrinsic part of the communicative plan. Moreover, it is reliable only from the viewpoint of the addressee, suggesting that the motor plan is tuned to the addressee. These findings suggest that recipient design is an intrinsic feature of human communication. (shrink)

Plants belonging to the genus Salsola (Family: Chenopodiaceae) are common in the arid and semiarid regions of our planet with no less than 69 different Salsola species found in Namibia and the Republic of South Africa. This genus is used as a traditional medicine and aqueous extracts of Salsola have been used by Bushmen women as an oral contraceptive. Ingestion of the Namibian shrub Salsola tuberculatiformis Botsch. by pregnant Karakul sheep leads to prolonged gestation and fetal post‐maturity and, as a (...) result, the pelts of the new‐born karakul lambs are worthless. This initiated an investigation into the active agents in the plant, using the terminal enzyme in adrenal corticosteroidogenesis, cytochrome P450‐dependent 11β‐hydroxylase (P450c11), as a bioassay. Although the active fraction, S2, was extremely labile, partial structure determination suggested the presence of synephrine and a highly reactive aziridine. Therefore a more stable analogue, 2‐(4‐acetoxyphenyl)2‐chloro‐N‐methylethylammonium‐chloride (compound A), was synthesised, which, like the active plant extracts, inhibited adrenal steroidogenesis and acted as a contraceptive. In addition, compound A was stabilised by interaction with steroid‐binding globulins in plasma thus enhancing biological activity in vivo. These findings provided explanations for the complex biological effects of the shrub as well as a new insight into the mode of action of chemically labile plant products in vivo. BioEssays 25:612–619, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

For decades, the discussion on children’s competence to consent to medical issues has concentrated around normative concerns, with little progress in clinical practices. Decision-making competence is an important condition in the informed consent model. In pediatrics, clinicians need to strike a proper balance in order to both protect children’s interests when they are not fully able to do so themselves and to respect their autonomy when they are. Children’s competence to consent, however, is currently not assessed in a standardized way. (...) Moreover, the correlation between competence to give informed consent and age in children has never been systematically investigated, nor do we know which factors exactly contribute to children’s competence. (shrink)

Although law is established on a strong presumption that persons younger than a certain age are not competent to consent, statutory age limits for asking children’s consent to clinical research differ widely internationally. From a clinical perspective, competence is assumed to involve many factors including the developmental stage, the influence of parents and peers, and life experience. We examined potential determining factors for children’s competence to consent to clinical research and to what extent they explain the variation in competence judgments.

One way to address such questions about artifact kinds is to look for clues in the available literature on parallel questions that have been posed with respect to kinds in the natural domain. Philosophers have long been concerned with the ...

BackgroundFor many decades, the debate on children’s competence to give informed consent in medical settings concentrated on ethical and legal aspects, with little empirical underpinnings. Recently, data from empirical research became available to advance the discussion. It was shown that children’s competence to consent to clinical research could be accurately assessed by the modified MacArthur Competence Assessment Tool for Clinical Research. Age limits for children to be deemed competent to decide on research participation have been studied: generally children of 11.2 (...) years and above were decision-making competent, while children of 9.6 years and younger were not. Age was pointed out to be the key determining factor in children’s competence. In this article we reflect on policy implications of these findings, considering legal, ethical, developmental and clinical perspectives.DiscussionAlthough assessment of children’s competence has a normative character, ethics, law and clinical practice can benefit from research data. The findings may help to do justice to the capacities children possess and challenges they may face when deciding about treatment and research options. We discuss advantages and drawbacks of standardized competence assessment in children on a case-by-case basis compared to application of a fixed age limit, and conclude that a selective implementation of case-by-case competence assessment in specific populations is preferable. We recommend the implementation of age limits based on empirical evidence. Furthermore, we elaborate on a suitable model for informed consent involving children and parents that would do justice to developmental aspects of children and the specific characteristics of the parent-child dyad.SummaryPrevious research outcomes showed that children’s medical decision-making capacities could be operationalized into a standardized assessment instrument. Recommendations for policies include a dual consent procedure, including both child as well as parents, for children from the age of 12 until they reach majority. For children between 10 and 12 years of age, and in case of children older than 12 years in special research populations of mentally compromised patients, we suggest a case-by-case assessment of children’s competence to consent. Since such a dual consent procedure is fundamentally different from a procedure of parental permission and child assent, and would imply a considerable shift regarding some current legislations, practical implications are elaborated. (shrink)

In this paper we disambiguate the design stance as proposed by Daniel C. Dennett, focusing on its application to technical artefacts. Analysing Dennett’s work and developing his approach towards interpreting entities, we show that there are two ways of spelling out the design stance, one that presuppose also adopting Dennett’s intentional stance for describing a designing agent, and a second that does not. We argue against taking one of these ways as giving the correct formulation of the design stance in (...) Dennett’s approach, but propose to replace Dennett’s original design stance by two design stances: an intentional designer stance that incorporates the intentional stance, and a teleological design stance that does not. Our arguments focus on descriptions of technical artefacts: drawing on research in engineering, cognitive psychology and archaeology we show that both design stances are used for describing technical artefacts. A first consequence of this disambiguation is that a design stance, in terms of interpretative assumptions and in terms of the pragmatic considerations for adopting it, stops to be a stance that comes hierarchically between the physical stance and the intentional stance. A second consequence is that a new distinction can be made between types of entities in Dennett’s approach. We call entities to which the intentional designer stance is applied tools and entities to which the teleological design stance is applied instruments, leading to a differentiated understanding of, in particular, technical artefacts. (shrink)

This publication deals with the practical philosophy in Barhebraeus's enclyclopaedia of Aristotelian wisdom "Butyrum sapientiae". The three Syriac books on Ethics, Politics and Economy are unique and the only specimens of its kind, surviving in the Syriac language and literature.

This publication deals with the practical philosophy in Barhebraeus's enclyclopaedia of Aristotelian wisdom "Butyrum sapientiae". The three Syriac books on Ethics, Politics and Economy are unique and the only specimens of its kind, surviving in the Syriac language and literature.

In this paper we present a functional analysis of biotechnology and identify the particular status that genetic engineering has relative to other biotechnological techniques such as domestication. The analysis builds on work by Dan Sperber and characterises biotechnology in primarily technical and biological functional terms as symbiotic interactions in which humans modify other organisms. We identify three main routes by which these interactions are established in biotechnology. We argue that two of these routes have in-built mechanisms for preventing an uncontrolled (...) dissemination of the modified organisms, and that one has an in-built mechanism for promoting such dissemination. The three routes are available to traditional forms of biotechnology as to state-of-the-art genetic engineering. Drawing now on work by Alfred Nordmann on the uncanniness of modern technologies, we show that genetic engineering is set apart by the epistemic consequences of the microscopic size of its progeny: genetically modified organisms, when disseminating, do so beyond our perceptual and conceptual control. Existing strategies against unwanted dissemination of organisms modified in traditional biotechnology are therefore typically not adequate against possible unwanted dissemination of genetically modified organisms, giving this dissemination a status similar to that of untraceable natural disasters. (shrink)

Selection on grandparental investment is more complex than Coall & Hertwig (C&H) propose. Patterns of investment are subject to an intergenerational conflict over how resources should be distributed to maximize fitness. Grandparents may be selected to distribute resources unevenly, while their descendants will be selected to manipulate investment in their own favor. Here we outline the evolutionary basis of this conflict.

Philosophe apatride, porte-voix des 'bons Européens' au XIXe siècle, Nietzsche se fit le représentant d'un européanisme assez contraire aux vues de son temps. Une posture intempestive et paradoxale car elle signifiait la dévalorisation des valeur suprêmes qui régissaient la vie des Européens, depuis deux millénaires. Dès lors, comment Nietzsche entendait-il 'penser l'Europe', au moment même où celle-ci menaçait, selon lui, de voir ses fondements culturels remis en question? Sans doute en prophétisant l'avènement du 'nihilisme européen', tout en remontant le cours (...) du temps et en pensant une généalogie de l'Europe pour, ensuite, dresser sa vision de 'deux siècles' à venir. C'est, en somme, une sorte de futurologie, adressée aux 'Européens d'après-demain'. Ce que nous sommes désormais. Ce livre rassemble des contributions majeures qui tentent de cerner ces 'pensées pour après-demain' et l'européanisme nietzschéen, mais aussi ce qu'ils disent de son actualité, toujours féconde pour éclairer les questions de notre temps. (shrink)

The contribution that Professor Pieter M. Venter has made to the study of the Old Testament during his academic and ecclesiastic career is reviewed. After a brief biographical introduction, the article surveys the development of his research interests, focusing specifically on his contributions to the study of wisdom literature, narratives and narratology, second temple literature, the formation of the canon, and Old Testament Theology. The review concludes with reference to his way of practising critical theology, taking full cognisance of (...) research into the linguistic, historical critical, narratological and ideological aspects of Old Testament texts, but always with a sensitivity for the needs of the church as interpretive community. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Journal of the History of Philosophy 41.2 (2003) 276-277 [Access article in PDF] Wiep Van Bunge. From Stevin to Spinoza: An Essay on Philosophy in the Seventeenth-Century Dutch Republic. Leiden: Brill, 2001. Pp. xii + 217. Cloth, $80.00 By 1660 there were probably more followers of Descartes in the Dutch Republic, population 1.4 million, than in France, population 20 million. Protestantism and prosperity encouraged high rates of literacy and (...) the universities of Leiden and Utrecht were among the liveliest in the world. This vibrancy infused the metaphors that Descartes put into his great Discours de la methode published first in Leiden in 1637. In it he spoke about the beauty of cities that looked as if they had been built by a single architect and of the freedom to be found among people so busy with their business as to leave thinkers to their pursuits. Indirectly he spoke about his adopted homeland where he found many followers—some more eager than loyal. By the 1640s disputes raged in the Republic and the anti-Cartesian forces were led by the Aristotelian and anti-Copernican Gisbertus Voetius. What has been missing in our scholarship up to now has been any convincing account as to why these disputes occurred, and how they resonated within the Dutch context. Wiep Van Bunge's book takes a big step toward closing that knowledge gap.Van Bunge convincingly argues that the vibrancy of the stadtholder-less period up to 1672 produced a willingness to entertain new ideas. It also did not hurt to have Descartes on the scene and active on behalf of his mechanical philosophy, even to the point of addressing the Utrecht magistrates publicly and asking that his critics be chastised. What is remarkable—especially given the resistance to Descartes seen at Oxford and Cambridge—was the speed with which Cartesian ideas entered the Dutch classrooms where as many as a third of the students came from abroad. Again Van Bunge provides context when he starts with the Dutch engineer Simon Stevin and demonstrates the vitality of mathematics for a commercial society but also for a militant one. (The Netherlands was at war with Spain up to 1609.) A recent exhibition at the J. Paul Getty Museum in Los Angeles, April to July 2002, also illustrates another aspect of mathematics in the Republic. Precisely in the 1630s when Descartes was putting the finishing touches on his Discours, Pieter Saenredam applied geometry to the interiors of the elegant Utrecht churches so as to give his paintings a regularity and precision worthy of the Cartesian dream of order and clarity. The Dutch commitment to discipline and order also made their army one of the most accomplished in the world. It was perhaps over-determined that Descartes, who had trained with it, would find such a sympathetic audience in the Republic.One of the more fascinating aspects of Van Bunge's detailed study, first of Cartesianism and then of Spinozism in the Republic, concerns the political and ideological meanings to be extracted from the new philosophy. Hobbes also finds a place in the narrative, surprisingly taken up by republicans eager to construct a state that could control the passions. Abraham van Berkel, who put Hobbes's Leviathan into Dutch in 1667, gave the allegiance of his text and himself to Jan de Witt and the cause of the regents and the estates. We can only wonder what Hobbes would have made of the association. The republican affiliations of the mechanical philosophy in the Republic provide a distinctively Dutch context to the [End Page 276] political writings of Spinoza, the most famous and outrageous Cartesian of the century. Van Bunge is especially deft in finding Spinozists and providing far more evidence than I could back in 1981 when I argued for a radical enlightenment within the late seventeenth-century Dutch context (see The Radical Enlightenment. Pantheists, Freemasons and Republicans [London: 1981]). None of these positions with their deeply heretical implications could be taken lightly or without danger. Men lost... (shrink)