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)

This is a welcome reprint of a book that continues to grow in importance.

The author presents and defends three theses: (1) "the first is that it is not profitable for us at present to do moral philosophy; that should be laid aside at any rate until we have an adequate philosophy of psychology." (2) "the second is that the concepts of obligation, And duty... And of what is morally right and wrong, And of the moral sense of 'ought', Ought to be jettisoned if this is psychologically possible...." (3) "the third thesis is that (...) the differences between the well-Known english writers on moral philosophy from sidgwick to the present day are of little importance." (staff). (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)

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)

This book offers an introduction to the Sophists of fifth-century Athens and a new overall interpretation of their thought. Since Plato first animadverted on their activities, the Sophists have commonly been presented as little better than intellectual mountebanks - a picture which Professor Kerferd forcefully challenges here. Interpreting the evidence with care, he shows them to have been part of an exciting and historically crucial intellectual movement. At the centre of their teaching was a form of relativism, most famously expressed (...) by Protagoras as 'Man is the measure of all things', and which they developed in a wide range of views - on knowledge and argument, virtue, government, society, and the gods. On all these subjects the Sophists did far more than simply provoke Plato to thought. Their contributions were substantial and serious; they inaugurated the debate on many central philosophical questions and decisively shifted the focus of philosophical attention from the cosmos to man. (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)

Normal propositional modal systems This first chapter has two main aims. One is to give a general account of the propositional modal systems that we shall ...

An examination of verbal hallucinations and thought insertion as examples of "alienated self-consciousness.".

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)

This book traces the intellectual revolution initiated by Thales in the sixth century BC to its culmination in the metaphysics of Parmenides.

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)

This entirely new work guides the reader through the most basic systems of modal propositional logic up to systems of modal predicate with identity, dealing with both technical developments and discussing philosophical applications.

Biological evolution is a complex blend of ever changing structural stability, variability and emergence of new phe- notypes, niches, ecosystems. We wish to argue that the evo- lution of life marks the end of a physics world view of law entailed dynamics. Our considerations depend upon dis- cussing the variability of the very ”contexts of life”: the in- teractions between organisms, biological niches and ecosys- tems. These are ever changing, intrinsically indeterminate and even unprestatable: we do not know ahead of (...) time the ”niches” which constitute the boundary conditions on selec- tion. More generally, by the mathematical unprestatability of the ”phase space”, no laws of mo- tion can be formulated for evolution. We call this radical emergence, from life to life. The purpose of this paper is the integration of variation and diversity in a sound concep- tual frame and situate unpredictability at a novel theoretical level, that of the very phase space. Our argument will be carried on in close comparisons with physics and the mathematical constructions of phase spaces in that discipline. The role of symmetries as invariant preserving transformations will allow us to under- stand the nature of physical phase spaces and to stress the differences required for a sound biological theoretizing. In this frame, we discuss the novel notion of ”enablement”. Life lives in a web of enablement and radical emergence. This will restrict causal analyses to differential cases. Mutations or other causal differ- ences will allow us to stress that ”non conservation princi- ples” are at the core of evolution, in contrast to physical dynamics, largely based on conservation principles as sym- metries. Critical transitions, the main locus of symmetry changes in physics, will be discussed, and lead to ”extended criticality” as a conceptual frame for a better understanding of the living state of matter. (shrink)

Editor James Fetzer presents an analytical and historical introduction and a comprehensive bibliography together with selections of many of Carl G. Hempel's most important studies to give students and scholars an ideal opportunity to appreciate the enduring contributions of one of the most influential philosophers of science of the 20th century.

Hume's Reception in Early America: Expanded Edition brings together the original American responses to one of Britain's greatest men of letters, David Hume. Now available as a single volume paperback, this new edition includes updated further readings suggestions and dozens of additional primary sources gathered together in a completely new concluding section. From complete pamphlets and booklets, to poems, reviews, and letters, to extracts from newspapers, religious magazines and literary and political journals, this book's contents come from a wide variety (...) of sources published in colonial America and the early United States between 1758 and 1850. As well as classics by Thomas Jefferson, John Adams and Alexander Hamilton, it contains scores of unknown and hard-to-locate items, many of which have not been reprinted since their original publication. These responses are divided into four parts covering Hume's Essays; his Philosophical Writings; his History of England; and his Character and Death. Each of those parts has a separate introductory essay, and every selection is introduced by a short headnote that sets the piece in its historical context and provides bibliographical references. Packed with new insights into Hume and American thought and culture, Hume's Reception in Early America reveals the relevance and impact of Hume on American political, philosophical, historical, religious, and aesthetic debates. (shrink)

One of Hume's most well-known works and a masterpiece of philosophy, A Treatise of Human Nature is indubitably worth taking the time to read.

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)

Today's digital revolution is a worldwide phenomenon, with profound and often differential implications for communities around the world and their relationships to one another. This book presents a new, explicitly international theory of media ethics, incorporating non-Western perspectives and drawing deeply on both moral philosophy and the philosophy of technology. Clifford Christians develops an ethics grounded in three principles - truth, human dignity, and non-violence - and shows how these principles can be applied across a wide range of cases and (...) domains. The book is a guide for media professionals, scholars, and educators who are concerned with the global ramifications of new technologies and with creating a more just world. (shrink)