Clamp loaders are pentameric AAA+ assemblies that use ATP to open and close circular DNA sliding clamps around DNA. Clamp loaders show homology in all organisms, from bacteria to human. The eukaryotic PCNA clamp is loaded onto 3′ primed DNA by the replication factor C (RFC) hetero‐pentameric clamp loader. Eukaryotes also have three alternative RFC‐like clamp loaders (RLCs) in which the Rfc1 subunit is substituted by another protein. One of these is the yeast Rad24‐RFC (Rad17‐RFC in human) that loads a (...) 9‐1‐1 heterotrimer clamp onto a recessed 5′ end of DNA. Recent structural studies of Rad24‐RFC have discovered an unexpected 5′ DNA binding site on the outside of the clamp loader and reveal how a 5′ end can be utilized for loading the 9‐1‐1 clamp onto DNA. In light of these results, new studies reveal that RFC also contains a 5′ DNA binding site, which functions in gap repair. These studies also reveal many new features of clamp loaders. As reviewed herein, these recent studies together have transformed our view of the clamp loader mechanism. (shrink)

Popper's paradox of ideal evidence has long been viewed as a telling criticism of Keynes's logical theory of probability and its associated concept of the weight of argument. This paper shows that a simple addition to Keynes's definitions of irrelevance enables his theory to elude the paradox with ease. The modified definition draws on ideas already present in Keynes's Treatise on Probability (1973). As a consequence, relevant evidence and the weight of argument may increase, even when new evidence leaves the (...) probability unaltered. (shrink)

DIVUses a discussion of contemporary films and literary works to present an understanding of paranoia as a defining element in postmodern late-capitalist structure./div.

In this article, Aislinn O'Donnell offers a set of reflections on the relation between therapy and education. In the first section, she examines criticisms of therapeutic education, mobilizing the example of prison education to highlight the difficulties that arise from imposing prescriptive modes of subjectification and socialization in pedagogy. In the second section, she addresses the relation between therapy and education by focusing on just one element of the experience of education: those moments at which a subject has the potential (...) of becoming significant in the life of a student. An important dimension of the educator's authority involves noticing such moments, fostering the conditions that make them more likely, and engaging in the creative process and practice of deciding how best pedagogically to respond to these moments. In the third section, O'Donnell develops this idea by detailing a philosophical approach and practice that understands “effectiveness” in education as bound to practice, creative responsiveness, and the judgment of the educator in concrete, singular pedagogical situations, rather than construed in terms of generic models of “best practice.”. (shrink)

Depue & Morrone-Strupinsky (D&M-S) present a thorough case for the role of “reward” brain circuits in affiliative bonding. Integration of information in the nucleus accumbens shell (NA), the role of dopamine in this processing, and opioid (primarily via mu receptors) control of these circuits are the primary elements of the model. Although the overall picture is quite compelling, the description leans excessively in the view of dopamine systems as “reward” circuits.

In 1886, Nietzsche wrote: ‘I am still waiting for a philosophical doctor in the extraordinary sense of the term’: a doctor who pursues not truth, but an exceptional kind of health. Nietzsche's will to health, his theory of drive organisation, and his insistence that the philosopher put himself at risk, all work together in his overall project, which consists of taking up the very role of the highly revalued physician for whom he is waiting. Deleuze and Guattari engage this same (...) task of a revalued doctoring in the Capitalisme et Schizophrénie books, attacking the disease of oedipality and providing instructions for the deorganisation of the organism as self-cure. Offering tips on this radical treatment, they employ the figure of the hypochondriac to show how it can fail. Both Nietzsche and Deleuze and Guattari perform a revaluation of health as a condition of chronic critique, a condition that wraps itself around illness to keep itself critical. (shrink)

Failure is seen as a problem in education. From failing schools, to failing students to rankings of universities, literacy or numeracy, the perception that one has failed to compete or to compare favourably with others has led to a series of policy initiatives internationally designed to ensure ‘success for all’. But when success is measured in comparison with others or against benchmarks or standards, then it is impossible to see how all could be successful given the parameters laid down. What (...) are the implications of a culture that values success and achievement? How difficult is it to become the kind of individual who is flourishing, autonomous and becomes ‘all she can be’, in particular under the precarious conditions of contemporary capitalism? Samuel Beckett was sceptical of the quest for progress, production and prestige. His philosophy invites another way of thinking about failure, not as something one is, but rather as something one does: the pain and fear of inadequacy that can mark educational relations and experiences is alleviated by a more renunciative, gentle philosophy of education. There are two interwoven strands in this article. One questions the emphasis on competition and achievement in contemporary education and explores its implications for our relationship to failure. The second, strongly influenced by Beckett, explores ways of reimagining our relationship to failure in such a way that allows us to reflect on what matters in life. (shrink)

pt. 1. Modernity, sociology and the structure/agency debate -- pt. 2. Critical theory; structuration theory; critical realism; and identity theory -- pt. 3. Structure/agency theories applied -- pt. 4. Network theory, globalisation theory, hegemony -- pt. 5. Conclusion/continuation.

L'article étudie la méthode de la théologie transcendantale et son application à la doctrine chrétienne de Dieu. Certains auteurs représentatifs de cette école théologique sont choisis, à savoir Lonergan, Donceel, Tracy et K. Rahner. Dans chaque cas trois questions sont posées: la relation entre expérience et notre compréhension de Dieu; la raison par rapport à la croyance en Dieu; le concept de Dieu qui ressort de l'emploi de la méthode transcendantale. Parmi les mérites de la méthode transcendantale il faut noter (...) sa rigueur intellectuelle et son ouverture au dialogue avec la non-croyance. Les auteurs dont il est question cherchent à montrer que la dimension religieuse est partie nécessaire de l'expérience humaine. Parmi les faiblesses on peut noter que les penseurs transcendantaux sont peut-être trop anthropologiques et ont une conception unilatérale de l'homme qui tend à négliger sa corporéité et son historicité. Leur affirmation sans compromis de la transcendance de Dieu fait aussi surgir la question comment l'apologétique chrétienne répond au problème de la souffrance humaine. La transcendance de Dieu ne doit-elle pas être compensée par son immanence afin que la relation de Dieu au monde ne soit pas unilatérale? (shrink)

There is an anomaly about the origins of Augustine’s great work of anti-pagan polemic and Christian apologetic that has not been accorded due weight in discussion of the development of the work’s idea in Augustine’s mind. The purpose of this brief note is to point out a hitherto unrecognized explanation for this anomaly, while leaving aside a full-scale development of the implications of this discovery.

O'Donnell, J. R. Anton Charles Pegis on the occasion of his retirement.--Conlan, W. J. The definition of faith according to a question of MS. Assisi 138: study and edition of text.--Spade, P. V. Five logical tracts by Richard Lavenham.--Maurer, A. Henry of Harclay's disputed question on the plurality of forms.--Brown, V. Giovanni Argiropulo on the agent intellect: an edition of Ms. Magliabecchi V 42.--Synan, E. A. The Exortacio against Peter Abelard's Dialogus inter philosophum, Iudaeum et Christianum.--Fitzgerald, W. Nugae Hyginianae.--Sheehan, M. (...) M. Marriage and family in English conciliar and synodal legislation.--Shook, L. K. Riddles relating to the Anglo-Saxon scriptorium.--Boyle, L. E. The De regno and the two powers.--Colledge, E. A Middle English Christological poem.--Gough, M. R. E. Three forgotten martyrs of Anazarbus in Cilicia.--Häring, N. Chartres and Paris revisited.--Hayes, W. Greek recentiores, (Ps.) Basil, Adversus eunomium, IV-V.--Owens, J. The physical world of Parmenides. (shrink)

The eukaryotic helicase is an 11-subunit machine containing an Mcm2-7 motor ring that encircles DNA, Cdc45 and the GINS tetramer, referred to as CMG. CMG is “built” on DNA at origins in two steps. First, two Mcm2-7 rings are assembled around duplex DNA at origins in G1 phase, forming the Mcm2-7 “double hexamer.” In a second step, in S phase Cdc45 and GINS are assembled onto each Mcm2-7 ring, hence producing two CMGs that ultimately form two replication forks that travel (...) in opposite directions. Here, we review recent findings about CMG structure and function. The CMG unwinds the parental duplex and is also the organizing center of the replisome: it binds DNA polymerases and other factors. EM studies reveal a 20-subunit core replisome with the leading Pol ϵ and lagging Pol α-primase on opposite faces of CMG, forming a fundamentally asymmetric architecture. Structural studies of CMG at a replication fork reveal unexpected details of how CMG engages the DNA fork. The structures of CMG and the Mcm2-7 double hexamer on DNA suggest a completely unanticipated process for formation of bidirectional replication forks at origins. Here, we review the structure and function of CMG, the 11 subunit helicase for eukaryotic DNA replication. Two CMGs are assembled at origins starting from two Mcm2-7 hexamers oriented N-to-N. The orientation of CMG at a forked DNA implies that the two CMGs at an origin pass one another. (shrink)

What is the future of Philosophy of education? Or as many of scholars and thinkers in this final ‘future-focused’ collective piece from the philosophy of education in a new key Series put it, what are the futures—plural and multiple—of the intersections of ‘philosophy’ and ‘education?’ What is ‘Philosophy’; and what is ‘Education’, and what role may ‘enquiry’ play? Is the future of education and philosophy embracing—or at least taking seriously—and thinking with Indigenous ethicoontoepistemologies? And, perhaps most importantly, what is that (...) ‘Future’? These debates have been located in the work of diverse scholars: from the West, from Global South, from indigenous thinkers. In this collective piece, we purposefully juxtapose diverse takes on the future of these intersections. We have given up the urge to organise, place together, separate with subheadings or connect the paragraphs that follow. Instead, we let these philosophers of education and thinkers who use philosophical texts and ideas to sit together in one long read as potentially ‘strange and unusual bedfellows’. This text urges us to understand how these scholars and thinkers perceive our educational philosophical futures, and how the work and thinking they have done on thinking about what the future of that new key in philosophy of education may look like is embedded in a much deeper and richer literature, and personal experience. (shrink)

The project of this paper is to deliver a semantics for a broad subset of bare plural generics about racial kinds, a class which I will dub 'Type C generics.' Examples include 'Blacks are criminal' and 'Muslims are terrorists.' Type C generics have two interesting features. First, they link racial kinds with ​ socially perspectival predicates ​ (SPPs). SPPs lead interpreters to treat the relationship between kinds and predicates in generic constructions as nomic or non-accidental. Moreover, in computing their content, (...) interpreters must make implicit reference to socially privileged​ ​ perspectives which are treated as authoritative about whether a given object fits into the extension of the predicate. Such deference grants these authorities influence over both the conventional meaning of these terms and over the nature of the ​ objects ​ in the social ontology that these terms purport to describe, much the way a baseball umpire is authoritative over the meaning and metaphysics of 'strike'/​ strike ​. Second, terms like 'criminal' and 'terrorist' receive default ​ racialized ​ interpretations in which these terms conventionally token racial or ethnic identities. I show that neither of these features can be explained by Sarah-Jane Leslie's influential 'weak semantics' for generics, and show how my own 'socially perspectival semantics' fares better on both counts. Finally, I give an analysis of 'Blacks are criminal' which explores the semantic mechanisms that underlie default racialized interpretations. (shrink)