The transactivation response‐DNA binding protein of 43 kDa (TDP‐43) is an aggregation‐prone nucleic acid‐binding protein linked to the etiology of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). These conditions feature the accumulation of insoluble TDP‐43 aggregates in the neuronal cytoplasm that lead to cell death. The dynamics between cytoplasmic and nuclear TDP‐43 are altered in the disease state where TDP‐43 mislocalizes to the cytoplasm, disrupting Nuclear Pore Complexes (NPCs), and ultimately forming large fibrils stabilized by the C‐terminal prion‐like (...) domain. Here, we review three emerging and poorly understood aspects of TDP‐43 biology linked to its aggregation. First, how post‐translational modifications in the proximity of TDP‐43 N‐terminal domain (NTD) promote aggregation. Second, how TDP‐43 engages FG‐nucleoporins in the NPC, disrupting the pore permeability and function. Third, how the importin α/β heterodimer prevents TDP‐43 aggregation, serving both as a nuclear import transporter and a cytoplasmic chaperone. (shrink)

This research investigates 3- and 5-year-olds' relative fairness in distributing small collections of even or odd numbers of more or less desirable candies, either with an adult experimenter or between two dolls. The authors compare more than 200 children from around the world, growing up in seven highly contrasted cultural and economic contexts, from rich and poor urban areas, to small-scale traditional and rural communities. Across cultures, young children tend to optimize their own gain, not showing many signs of self-sacrifice (...) or generosity. Already by 3 years of age, self-optimizing in distributive justice is based on perspective taking and rudiments of mind reading. By 5 years, overall, children tend to show more fairness in sharing. What varies across cultures is the magnitude of young children's self-interest. More fairness (less self-interest) in distributive justice is evident by children growing up in small-scale urban and traditional societies thought to promote more collective values. (shrink)

To what extent do early intuitions about ownership depend on cultural and socio-economic circumstances? We investigated the question by testing reasoning about third party ownership conflicts in various groups of three- and five-year-old children (N = 176), growing up in seven highly contrasted social, economic, and cultural circumstances (urban rich, poor, very poor, rural poor, and traditional) spanning three continents. Each child was presented with a series of scripts involving two identical dolls fighting over an object of possession. The child (...) had to decide who of the two dolls should own the object. Each script enacted various potential reasons for attributing ownership: creation, familiarity, first contact, equity, plus a control/neutral condition with no suggested reasons. Results show that across cultures, children are significantly more consistent and decisive in attributing ownership when one of the protagonists created the object. Development between three and five years is more or less pronounced depending on culture. The propensity to split the object in equal halves whenever possible was generally higher at certain locations (i.e., China) and quasi-inexistent in others (i.e., Vanuatu and street children of Recife). Overall, creation reasons appear to be more primordial and stable across cultures than familiarity, relative wealth or first contact. This trend does not correlate with the passing of false belief theory of mind. (shrink)

Hursthouse :57–68, 1991) argues that arational actions—e.g. kicking a door out of anger—cannot be explained by belief–desire pairs. The Humean Response to Hursthouse :25–38, 2000b) defends the Humean model from Hursthouse’s challenge. We argue that the Humean Response fails because belief–desire pairs are neither necessary nor sufficient for causing emotional actions. The Emotionist Response is to embrace Hursthouse’s conclusion that emotions provide an independent source of explanation for intentional actions. We consider Döring’s :214–230, 2003) feeling-based Emotionist account and argue that (...) it fails to explain arational actions. Finally, we develop our own Emotionist account, grounded in the Motivational Theory of Emotions one of us has developed. On our account, arational actions form a non-homogeneous class, some members of which must be understood as instrumental actions and some members of which must be understood as displacement behaviors of the kind animals display when their motivations are thwarted or in conflict. (shrink)

Kant’s critique/doctrine distinction tracks the difference between a canon for the understanding’s proper use and an organon for its dialectical misuse. The latter reflects the dogmatic use of reason to attain a doctrine of knowledge with no antecedent critique. In the 1790s, Fichte collapses Kant’s distinction and redefines dogmatism. He argues that deriving a canon is essentially dialectical and thus yields an organon: critical idealism is properly a doctrine of science or Wissenschaftslehre. Criticism is furthermore said to refute dogmatism, by (...) which Fichte means Spinozism. Schelling repudiates Fichte’s position in his Philosophical Letters by reviving Kant’s distinction. First, ‘critique’ for Schelling names a canon that is valid for all systems—including Spinozism—and thus favours none—not even the Wissenschaftslehre. Second, Schelling coins ‘dogmaticism’ to refer to what Kant calls ‘dogmatism’: reason’s uncritical claim to doctrine. Hence, he says all systems—even Fichte’s—are susceptible to the ‘enthusiasm’ of mistaking themselves for doctrines or ‘objects of knowledge’, instead of subjectively valid ‘objects of freedom’. I reconstruct Schelling’s argument for reviving Kant’s distinction, while noting two consequences for German idealism. First, if criticism favours no system, a system’s origin cannot be an act of knowledge, e.g., intellectual intuition, but only an act of endorsement. Second, if dogmaticism entails enthusiasm, a system’s goal cannot be absolute knowledge, but only infinite striving. Hence, by retrieving Schelling’s notion of dogmaticism, we can both gain a better understanding of the Letters and register the impact of a core Kantian distinction on the German idealist project. (shrink)

This paper has two main foci: the history of curriculum design, and implications from the new sciences of chaos and complexity for the development of new forms of curriculum design and teaching implementation. Regarding the first focus, the paper posits that there exist—to use Wittgenstein's phrase—‘family resemblances’ between Peter Ramus’ 16th century curriculum design and that of Ralph Tyler in the 20th century. While this 400‐year linkage is by no means linear, there are overlapping strands from Ramus to Comenius to (...) the Puritans to colonial New England to Horace Mann to Ralph Tyler. What unites these strands, all belonging to the Protestant Methodization movement that swept across northern Europe into colonial America and the USA, is the concept of Method. Taylor's ‘time and motion’ studies set the stage for Tyler's Basic Principles of curriculum design—those starting with set goals and concluding with measured assessment. The second focus draws on the new sciences of chaos and complexity to develop a different sense of curriculum and instruction—open, dynamic, relational, creative, and systems oriented. The paper concludes with an integration of the rational/scientific with the aesthetic/spiritual into a view of education and curriculum informed by complexity. (shrink)

This paper has two main foci: (1) the history of curriculum design, and (2) implications from the new sciences of chaos and complexity for the development of new forms of curriculum design and teaching implementation. Regarding the first focus, the paper posits that there exist—to use Wittgenstein's phrase—‘family resemblances’ between Peter Ramus’ 16th century curriculum design and that of Ralph Tyler in the 20th century. While this 400‐year linkage is by no means linear, there are overlapping strands from Ramus to (...) Comenius to the Puritans to colonial New England to Horace Mann to Ralph Tyler. What unites these strands, all belonging to the Protestant Methodization movement that swept across northern Europe into colonial America and the USA, is the concept of Method. Taylor's ‘time and motion’ studies set the stage for Tyler's Basic Principles of curriculum design—those starting with set goals and concluding with measured assessment. The second focus draws on the new sciences of chaos and complexity to develop a different sense of curriculum and instruction—open, dynamic, relational, creative, and systems oriented. The paper concludes with an integration of the rational/scientific with the aesthetic/spiritual into a view of education and curriculum informed by complexity. (shrink)

Es gibt Gegenstände, von denen gilt, daß es dergleichen Gegenstände nicht gibt. Dieser Satz hat dem Österreicher Alexius Meinong nicht nur Berühmtheit, sondern auch vernichtende Urteile beschert. Hindern konnten sie ihn jedoch keinesfalls daran, die weltweit bekannte Schule der Grazer Gegenstandstheorie zu etablieren. Wertphilosophische, erkenntnistheoretische sowie psychologische Schriften und die Gründung des ersten experimentalpsychologischen Laboratoriums in Österreich komplettieren das Schaffen dieses Philosophen. Meinongs Lebensgeschichte ist die Verquickung der Geschichte seiner Publikationen und der akademischen Aktivitäten seiner kleinen Schule von Schülern. Platz (...) für private Belange schien in jenem Leben, das sich nahezu vier Jahrzehnte in der steiermärkischen Universitätsstadt Graz abspielte, kaum zu sein. Eine äußerst starke Sehschwäche, die Meinong vor Kollegen, Freunden und sogar seiner Frau auf ungewöhnliche Weise zu verbergen suchte, lastete schwer auf ihm. In der ersten vollständigen Biographie Meinongs zeichnet Evelyn Dölling das leidenschaftliche Ringen dieses Denkers um höchste wissenschaftliche Präzision nach. Aus der Recherche des umfangreichen Nachlaßmaterials sowie der zahlreichen Korrespondenzen (8 300 Briefe) entsteht ein Bild von Meinongs Familienleben und seinen Beziehungen zu Freunden, wie man es so bislang nicht kannte. (shrink)

Meillassoux seeks knowledge of transcendental reality, blaming Kant for the ‘correlationist’ proscription of independent access to either thought or being. For Meillassoux, correlationism blocks an account of the meaning of ‘ancestral statements’ regarding reality prior to humans. I examine three charges on which Meillassoux’s argument depends: (1) Kant distorts ancestral statements’ meaning; (2) Kant fallaciously infers causality’s necessity; (3) Kant’s transcendental idealism cannot grasp ‘the great outdoors’. I reject these charges: (1) imposes a Cartesian misreading, hence Meillassoux’s false assumption that, (...) for Kant, objects don’t exist without subjects; (2) misreads Kant, who infers causality’s necessity from the possibility of experience; (3) casts Kant’s idealism as subjective, ignoring his perspectival portrayal of it. (shrink)

Even though various investigations found a preponderance of negative emotions in dreams, the conclusion that human dream life is, in general, negatively toned is limited by several methodological issues. The present study made use of three different approaches to measure dream emotions: dream intensity rated by the dreamer, intensity rated by a judge, and scoring of explicitly mentioned emotions (Hall & Van de Castle, 1966). Results indicate that only in the case of external raters' estimates do negative emotions outweigh the (...) positive ones; but in the case of self-ratings (i.e., those made by the dreamer himself/herself), the ratio was balanced. Analyses showed that this is mainly due to the underestimation of positive emotions in the external ratings. Additionally, a positive correlation was found between the intensity of dream emotions and dream recall frequency, whereas gender differences were nonsignificant as regards the emotional tone of diary dreams. (shrink)

Like Letters in Running Water explores ways in which fiction (prose, drama, poetry, myth, fairytale) yields transformative insights for educational theory and practice. Through a series of intensely original, powerful essays drawing on curriculum theory, literary analysis, psychology, and feminist theory and practice, Doll seeks to confront a commonly held bias that reading literary fictions is "mere" entertainment (not a learning experience). She suggests that fiction has immense teaching power because it connects readers with their alliances within themselves and this (...) connection attends to social, outer issues addressed by traditional pedagogies with greater, deeper awareness. Her elaboration in this book of the concept of currere --the lived experience of curriculum--through literature, drama, and myth is a major contribution to the field of curriculum theory. (shrink)

Der mathematische Logiker Gottlob Frege und der philosophische Logiker Franz Brentano hatten im Ausgang des 19.Jahrhunderts ein gemeinsames Anliegen: Sie wollten die Aristotelische Logik, insbesondere die Aristotelische Urteilslehre, reformieren. Ihre Bemuhungen mundeten in die Behauptung, dass sich alle kategorischen Urteile auf die Form von Existentialurteilen zuruckfuhren liessen. Den Motiven von Brentano und Frege fur den Entwurf einer neuen Urteilslehre nachzuspuren sowie einen Vergleich zwischen den Auffassungen beider vorzunehmen, ist das Anliegen des Aufsatzes. Konfrontiert werden ihre Untersuchungen mit der Kritik von (...) John P. Land und anderen Logikern, die Logiken entwickelt haben, in denen das Existentialurteil keine exponierte Stellung einnimmt. (shrink)

The development of physical theory is one of our greatest intellectual achievements. Its products--the currently prevailing theories of physics, astronomy, and cosmology--have proved themselves to possess intrinsic beauty and to have enormous explanatory and predictive power. This anthology of primary readings chronicles the birth and maturation of five such theories (the heliocentric theory, the electromagnetic field theory, special and general relativity, quantum theory, and the big bang theory) in the words of the scientists who brought them to life. It is (...) the first historical account that captures the rich substance of these theories, each of which represents a fascinating story of the interplay of evidence and insight--and of dialogue among great minds. Readers sit in with Copernicus, Kepler, and Galileo as they overturn the geocentric universe; observe the genius of Faraday and Maxwell as they "discover" the electromagnetic field; look over Einstein's shoulder as he works out the details of relativity; listen in as Einstein and Bohr argue for the soul of quantum mechanics in the Completeness Debate; and watch as Hubble and others reveal the history of the universe. The editors' approach highlights the moments of discovery that rise from scientific creativity, and the presentation humanizes the scientific process, revealing the extent to which great scientists were the first to consider the philosophical implications of their work. But, most significantly, the editors offer this as their central thesis: although each was ushered in by a revolution, and each contains counterintuitive elements that delayed its acceptance, these five theories exhibit a continuous rational development that has led them to a permanent place in the worldview of science. Accessible to the general reader yet sufficiently substantive that working scientists will find value in it, The Tests of Time offers an intimate look into how physical theory has been developed, by the brilliant people who have developed it. (shrink)

Meinongs Leben vollzog sich in engen räumlichen Grenzen. Es scheint kaum von besonderen Höhepunkten gekennzeichnet zu sein. Als neunjähriger, im Jahre 1862, verließ er seine Geburtsstadt Lemberg und ging nach Wien, um dort die Schule zu besuchen und später deutsche Philologie und Geschichte zu studieren. Nach Abschluß einer Dissertation über Arnold von Brescia wandte er sich der Philosophie zu und habilitierte sich auf Empfehlung von Franz Brentano mit einer Arbeit über David Hume. Ein schweres Augenleiden, das sehr zeitig schon zu (...) einer fast vollständigen Blindheit führte und das er mit großem Erfindungsreichtum vor Familie, Freunden und administrativen Einrichtungen zu verbergen suchte, hat sein Leben maßgeblich bestimmt. Meinongs weitere akademische Karriere, die Beziehungen zu seiner Frau Doris, zu seinen Freunden und Studenten werden unter besonderer Berücksichtigung seiner Sehschwäche nachgezeichnet. (shrink)

SummaryIn 1968, a prospective study was started in collaboration with the Family Planning Association to try to provide a balanced view of the beneficial and harmful effects of different methods of contraception. This investigation is now in progress at seventeen clinics and over 17,000 women are under observation. At the time of recruitment, all these women were married white British subjects, aged 25–39 years, who voluntarily agreed to participate. Fifty-six per cent were using oral contraceptives, 25% were using a diaphragm (...) and 19% were using an intrauterine device. During follow-up each woman is questioned at return visits to the clinic and a record of pregnancies and their outcome, hospital referrals, changes in contraceptive methods and the results of cervical smears, is accumulated. Women who default are sent a postal questionnaire and, if this is not returned, are telephoned or visited in their homes to collect the necessary information.So far, data obtained during 56,000 woman-years of observation are available for analysis. Follow-up has been maintained with an annual lapse rate of about 0.3%due to withdrawal of co-operation or loss of contact; adherence to the method of contraception in use at recruitment has been reasonably good, and the reporting of pregnancies and hospital admissions appears to have been both reliable and unbiased.The present data include only 24 deaths, so the mortality associated with different contraceptive methods cannot yet be estimated. With regard to morbidity, however, our preliminary results closely resemble those obtained in the prospective study carried out by the Royal College of General Practitioners and in the principal retrospective studies carried out in Britain and the United States. Women who used oral contraceptives at the start of the study experienced adeficiencyof hospital referrals for cancer, benign lesions of the breast, menstrual disorders other than amenorrhoea, duodenal ulcer, and retention cysts of the ovary; they showed anexcessof referrals for cerebrovascular disease, cervical erosion, skin disorders, self-poisoning, migraine, venous thrombosis and embolism, hayfever, gallbladder disease, amenorrhoea, and sterility. Women who used a diaphragm showed adeficiencyof hospital referrals for carcinoma-in-situ and dysplastic lesions of the cervix uteri and accidental injury; and anexcessof referrals for haemorrhoids and cystitis. Women who used an IUD experienced anexcessof hospital referrals for anaemia, varicose veins and salpingitis. About half of these differences were predicted from other studies while some suggestive evidence already existed for a further five. Of the remaining six, some probably reflect the influence of selective factors or chance.Multiple pregnancies, stillbirths, malformations, the sex ratio and birthweight showed no consistent relationship to method of contraception. The outcome of unplanned pregnancies occurring in women using an IUD, however, was remarkably unfavourable both in terms of ectopic gestation and miscarriage.Clear evidence was found of impairment of fertility after discontinuation of oral contraceptives. Whether this is likely to lead to permanent sterility in some women is uncertain.The study has provided data on the efficacy of a wide variety of contraceptive methods. In general the failure rates are in keeping with those obtained in other large-scale studies, save that those for the diaphragm and the sheath are much lower than those usually quoted.The available evidence does not yet allow a final balance to be struck between the benefits and risks associated with the new methods of contraception that have become widely used during the last two decades. It seems clear, however, that there are no material risks associated with the use of the diaphragm apart from the risk of pregnancy and that there may be some unintended benefits. (shrink)