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)

Drawing on a landscape analysis of existing data-sharing initiatives, in-depth interviews with expert stakeholders, and public deliberations with community advisory panels across the U.S., we describe features of the evolving medical information commons. We identify participant-centricity and trustworthiness as the most important features of an MIC and discuss the implications for those seeking to create a sustainable, useful, and widely available collection of linked resources for research and other purposes.

DNA polymerases which duplicate cellular chromosomes are multiprotein complexes. The individual functions of the many proteins required to duplicate a chromosome are not fully understood. The multiprotein complex which duplicates the Escherichia coli chromosome, DNA polymerase III holoenzyme (holoenzyme), contains a DNA polymerase subunit and nine accessory proteins. This report summarizes our current understanding of the individual functions of the accessory proteins within the holoenzyme, lending insight into why a chromosomal replicase needs such a complex structure.

Although the E-Z Reader model accounts well for eye-tracking data, it will be judged by new predictions and consistency with evidence from brain imaging methodologies. The stage architecture proposed for lexical access seems somewhat arbitrary and calculated timings are conservatively slow. There are certain effects in the literature that seem incompatible with the model.

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)

This volume explores how Catholicism began and continues to open its doors to the wider world and to other confessions in embracing ecumenism, thanks to the vision and legacy of the Second Vatican Council. It explores such themes as the twentieth century context preceding the council; parallels between Vatican II and previous councils; its distinctively pastoral character; the legacy of the council in relation to issues such as church-world dynamics, as well as to ethics, social justice, economic activity. Several chapters (...) discuss the role of women in the church before, during, and since the council. Others discern inculturation in relation to Vatican II. The book also contains a wide and original range of ecumenical considerations of the council, including by and in relation to Free Church, Reformed, Orthodox, and Anglican perspectives. Finally, it considers the Council’s ongoing promise and remaining challenges with regard to ecumenical issues, including a groundbreaking essay on the future of ecumenical dialogue by Cardinal Walter Kasper. (shrink)

An unconventional formalization of the canonical square of opposition in the notation of classical symbolic logic secures all but one of the canonical square’s grid of logical interrelations between four A-E-I-O categorical sentence types. The canonical square is first formalized in the functional calculus in Frege’s Begriffsschrift, from which it can be directly transcribed into the syntax of contemporary symbolic logic. Difficulties in received formalizations of the canonical square motivate translating I categoricals, ‘Some S is P’, into symbolic logical notation, (...) not conjunctively as \, but unconventionally instead in an ontically neutral conditional logical symbolization, as \. The virtues and drawbacks of the proposal are compared at length on twelve grounds with the explicit existence expansion of A and E categoricals as the default strategy for symbolizing the canonical square preserving all original logical interrelations. (shrink)

L'A. pubblica una quaestio di Gilberto di Stratton, contenuta nel ms. Assisi, Bibl. Comunale, 158 dal titolo Utrum aliquod eviternum potuit fuisse Deo coeternum che, a suo avviso, rappresenta forse il primo esempio di difesa della posizione assunta da Tommaso all'interno del dibattito de aeterniate mundi, posizione che, come è noto, fu oggetto di condanna nel 1277 . Nella breve introd. che precede il testo, l'A. sottolinea il fatto che Gilberto oltre a riprendere e ad assumere la posizione di Tommaso, (...) ed in particolare quella della non contradditorietà tra l'esse factum e l'esse aeternum, mostra di conoscere le critiche che aveva mosso Bonaventura al Doctor angelicus e gli argomenti ex infinito formulati dal maestro francescano per dimostrare l'inizio temporale del mondo. Di Gilberto esiste un'altra quaestio contenuta nello stesso ms. e che sembra una versione alterata del De aeternitate di Tommaso e che l'A. ha pubblicato con O. Argerami in Leiden 1993. (shrink)

Is it ethical to perform a surgery whose purpose is to make a male look like a female or a female to appear male? Is it medically appropriate? Sexual reassignment surgery (SRS) violates basic medical and ethical principles and is therefore not ethically or medically appropriate. (1) SRS mutilates a healthy, non-diseased body. To perform surgery on a healthy body involves unnecessary risks; therefore, SRS violates the principle primum non nocere, “first, do no harm.” (2) Candidates for SRS may believe (...) that they are trapped in the bodies of the wrong sex and therefore desire or, more accurately, demand SRS; however, this belief is generated by a disordered perception of self. Such a fixed, irrational belief is appropriately described as a delusion. SRS, therefore, is a “category mistake”—it offers a surgical solution for psychological problems such as a failure to accept the goodness of one’s masculinity or femininity, lack of secure attachment relationships in childhood with same-sex peers or a parent, self-rejection, untreated gender identity disorder, addiction to masturbation and fantasy, poor body image, excessive anger, and severe psychopathology in a parent. (3) SRS does not accomplish what it claims to accomplish. It does not change a person’s sex; therefore, it provides no true benefit. (4) SRS is a “permanent,” effectively unchangeable, and often unsatisfying surgical attempt to change what may be only a temporary (i.e., psychotherapeutically changeable) psychological/psychiatric condition. National Catholic Bioethics Quarterly 9.1 (Spring2009): 97–125. (shrink)

According to the “standard framing” of racial appeals in political speech, politicians generally rely on coded language to communicate racial messages. Yet recent years have demonstrated that politicians often express quite explicit forms of racism in mainstream political discourse. The standard framing can explain neither why these appeals work politically nor how they work semantically. This paper moves beyond the standard framing, focusing on the politics and semantics of one type of explicit appeal, candid racial communication. The linguistic vehicles of (...) CRC are neither true code words, nor slurs, but a conventionally defined class of “racialized terms.”. (shrink)

In this essay, I examine the concept of thinking in Hannah Arendt's writings. Arendt's interest in the experience of thinking allowed her to develop a concept of thinking that is distinct from other forms of mental activity such as cognition and problem solving. For her, thinking is an unending, unpredictable and destructive activity without fixed outcomes. Her understanding of thinking is distinguished from other approaches to thinking that equate it with, for example, problem solving or knowledge. Examples of a ‘problem-solving’, (...) skills-based approach to thinking that place a premium on behavioural change are drawn from the context of the prison. I offer an alternative example of thinking with others from my philosophy classes in the prison. I draw upon Arendt's insights to develop a concept of ‘thinking-in-concert’. Whilst Arendt believes that thinking must be a solitary activity, I argue that the concept of ‘thinking-in-concert’ helps to capture experiences of thinking with others in a manner that is more hesitant and provisional than some descriptions of communities of enquiry or democratic education. The embodied presence of others matters when ‘thinking-in-concert’. I describe this approach as educational as well as conversational. This helps to communicate the way in which we turn towards others and may be pulled up short by them as we strive to think together or experience moments of conversion or insight whilst enjoying the ordinary activity of talking with others. This concept may help us to understand the difference between the experience of thinking, teaching and learning when we are physically present to one another and the experience of virtual learning or teaching. (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)

This is a long critical discussion of Frank Wilderson's Afropessimism, focusing primarily on Wilderson's claim that Blackness is equivalent to Slaveness. The article draws out some strengths of the book, but argues that the book's central arguments often rest on shaky methodological, metaphysical, epistemic, and political grounds. Along the way, we consider some complications endemic to the project of evaluating a text so clearly geared towards Black audiences from the perspective of a non-Black reader.

Key to Rahner's understanding of Easter is his linking faith in the resurrection with anthropology. The human person is transcendence, always moving beyond self to the ever-greater God. The subject therefore seeks a definitive realization of freedom, and this realization must be bodily, since the human person is spirit-in-matter. Rahner makes an original point about the credibility of the resurrection, in that our human hope, under the influence of grace, enables us to open ourselves to the truth of Christ's resurrection. (...) Another original point of Rahner's theology is that he can accept either the theory of an intermediate state between death and final resurrection, or a resurrection which is simultaneous with death. According to Rahner, the virtue of hope functions as the link between faith and love, enabling the subject to project himself into God's future. (shrink)

The existential, experiential, ethical, pathic and pre-pathic dimensions of education are essential for the creative composition of subjectivities in institutional spaces, yet educational research and policy tend increasingly to privilege technical discourses and prescriptive approaches both when evaluating ‘what is effective in education’ and when determining educational policy. This essay explores those aspects of the educational experience and educational institutions that are often felt and sensed pre-cognitively by students, parents and teachers, but are seldom given further elaboration or articulation in (...) educational research. We will reflect on what is meant by the experience of education and experience in education, including the struggles to make sense of or understand something, the surprises that strike pre-reflectively, and the ways in which such moments are noticed, pursued, and explored rather than reflexively ‘evaluated’. We then explore the idea of experimentation in institutions, in particular in relation to the range of concepts that Jean Oury introduces in order to move our attention and awareness to questions of experience, existence, atmosphere, and the pathic—the way in which we undergo, sense and participate in the world prior to cognition and the desire for mastery and control of our encounters. Finally, we address the question of the ethics of institutions. (shrink)

In this introduction I closely read Marquand’s arguments in “On Scientific Method in the Study of Art” both in relation to their sources and in relation to Marquand’s own subsequent scholarship. My thesis is that Charles Sanders Peirce’s writing is the most conspicuous and important inspiration for the essay; however I also contend that Marquand’s handwritten corrections to the surviving manuscript of the text reveal a struggle with Peirce’s ideas that can – especially in light of Marquand’s later writing – (...) be read to expose an ambivalent or potentially even critical attitude toward central aspects of Peirce’s thought. I conclude by noting that Marquand’s intellectual relationship with Peirce speaks to both the past, present, and future of art historical scholarship. (shrink)

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)

Since the turn of the millennium, theologians and secular scholars of religion have increasingly begun exploring the relationship between transhumanism and religion. However, analyses of anti-transhumanist apocalypticisms are still rare, and those that exist are situated mainly among broader explorations of religious and secular bioconservatism. This article addresses this lack of specificity by drawing analyses of transhumanism and religion into dialogue with explorations of contemporary demonology through a close study of the beliefs of the evangelical conspiracist Thomas Horn and the (...) anti-transhumanist milieu around him. Exploring the milieu's multifaceted demonology of the secular world in light of genealogies of religion and secularity, the article situates Horn's demonology as one attempt to negotiate these genealogies, using what Sean McCloud terms a “‘supernatural’ hermeneutics of suspicion” that sees spiritual forces as the structural base of reality. It argues that, while fringe, milieus like Horn's illuminate broader cultural tensions and genealogical relations surrounding the place of religion in a secular world. (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.

ABSTRACT In this article the Irish harp tradition is re-configured as a space consisting of visual and sonic dimensions. The visual dimension of the Irish harp space incorporates the employment of the instrument in contemporary iconography; the sonic dimension includes the employment of the instrument as a metaphor in contemporary literature and songs. By employing Bloch’s concept of surplus and tracing the path of the Irish harp from its earliest employment in Christian iconography, its prominence as an icon of colonial (...) and Ascendancy rule, and finally its utilisation as an utopian tool to inspire members of the Volunteer and United Irish movements in the late eighteenth century, I identify how the accumulation of centuries of utopian surplus resulted in the creation of an utopian icon that had the capacity to inspire a generation of Irish men and women to critique the prevailing social and political order in the eighteenth century. (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.

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)