We highlight the various domains of the flavivirus virulence factor NS1 and speculate on potential implications of the NS1 3D structure in understanding its role in flavivirus pathogenesis. Flavivirus non‐structural protein 1 (NS1) is a virulence factor with dual functions in genome replication and immune evasion. Crystal structures of NS1, combined with reconstructions from electron microscopy (EM), provide insight into the architecture of dimeric NS1 on cell membranes and the assembly of a secreted hexameric NS1‐lipid complex found in patient sera. (...) Three structural domains of NS1 likely have distinct roles in membrane association, replication complex assembly, and immune system avoidance. A conserved hydrophobic inner face is sequestered either on the membrane or in the interior of the secreted hexamer and contains regions implicated in viral replication. The exposed variable outer face is presented to cellular and secreted components of the immune system in infected patients and contains candidate regions for immune system modulation. We anticipate that knowledge of the distinct NS1 domains and assembly will lead to advances in elucidating virus‐host interactions mediated through NS1 and in dissecting the role of NS1 in viral genome replication. (shrink)

This chapter describes the potential far‐reaching consequences of contemplative higher education for the fields of science and medicine.

Intuitively, vagueness involves some sort of indeterminacy: if Plato is a borderline case of baldness, then there is no fact of the matter about whether or not he’s bald—he’s neither bald nor not bald. The leading formal treatments of such indeterminacy—three valued logic, supervaluationism, etc.—either fail to validate the classical theorems, or require that various classically valid inference rules be restricted. Here we show how a fully classical, yet indeterminist account of vagueness can be given within natural semantics, an alternative (...) semantics for classical proof theory. The key features of the account are: there is a single notion of truth—definite truth—and a single notion of validity; sentences can be true, false, or undetermined; all classical theorems and all classical inference rule are valid; the sorites argument is unsound; ‘definitely’ is treated as a meta-language predicate; higher-order vagueness is handled via semantic ascent. (shrink)

Every step forward, in life and in thought, is a return to a beginning in that it empties that much more the plan by which the journey is directed. The journey that began this work was with the recondite lore of aphasia. This early work led to a psychology of language, perception, action, and feeling based on the principle of microgenesis. This psychology and its corre sponding brain process are detailed in my book, Life of the Mind, a vade mecum (...) for the ideas that are developed further in this work. Now this psychology, a single thought exposed at progressively deeper levels, is extended to the problems of time awareness, consciousness and the nature of the self. It is astonishing, is it not, that an aphasic error, a slip of the tongue, can be a peephole on some of the ultimate mysteries of life? Over the last few years I have had the occasion to present portions of this work at various conferences and to different audiences, and have found, to my dismay, that the theory is often difficult for many to grasp. (shrink)

It describes and explains the patient-centered model examining and evaluating qualitative and quantitative research. It comprehensively covers the evolution and the six interactive components of the patient-centered clinical method, taking the reader through the relationships between the patient and doctor and the patient and clinician. All the editors are professors in the Department of Family Medicine at the University of Western Ontario, London, Canada.

By utilizing new information from both clinical and experimental (lesion, electrophysiological, and gene-activation) studies with animals, the anatomy underlying anterograde amnesia has been reformulated. The distinction between temporal lobe and diencephalic amnesia is of limited value in that a common feature of anterograde amnesia is damage to part of an comprising the hippocampus, the fornix, the mamillary bodies, and the anterior thalamic nuclei. This view, which can be traced back to Delay and Brion (1969), differs from other recent models in (...) placing critical importance on the efferents from the hippocampus via the fornix to the diencephalon. These are necessary for the encoding and, hence, the effective subsequent recall of episodic memory. An additional feature of this hippocampalanterior thalamic and the perirhinal–medial dorsal thalamic systems are compromised, leading to severe deficits in both recall and recognition. (shrink)

The initial motivating question for this thesis is what the standard of rigour in modern mathematics amounts to: what makes a proof rigorous, or fail to be rigorous? How is this judged? A new account of rigour is put forward, aiming to go some way to answering these questions. Some benefits of the norm of rigour on this account are discussed. The account is contrasted with other remarks that have been made about mathematical proof and its workings, and is tested (...) and illustrated by considering a case study discussed in the literature. On the view put forward here one can obtain a manner of informal, rigorous mathematics founded on any of a variety of proof systems. The latter part of the thesis is concerned with the question of how we should decide which of these competing proof systems we should base our mathematics on: i.e., the question of which proof system we should take as a foundation for our mathematics. A novel answer to this question is proposed, in which the key property we should require of a proof system is that for as many different kinds of structures as possible, when the proof system allows a generalization about that kind of structure to be proved, the generalization actually holds of all real examples of that kind of structure which exist. This is the requirement of soundness of the proof system. It is argued that the best way to establish the soundness of a proof system may be by giving an interpretation of its axioms on which they are established as true. As preparation for this discussion, the thesis first investigates the logical and conceptual basis of various arithmetic concepts, with the results obtained used in the final discussion of soundness. (shrink)

This contribution explores the psychological basis of illusion and the feeling of what is real in relation to a process theory (microgenesis) of mind/brain states. The varieties of illusion and the alterations in the feeling of realness are illustrated in cases of clinical pathology, as well as in everyday life. The basis of illusion does not rest in a comparison of appearance to reality nor in the relation of image to object, since these are antecedent and consequent phases in the (...) same mental state. The study of pathological illusions and hallucinations shows that the feeling of realness in an object depends on its coherence within and across perceptual modalities. Illusion is shown to be not the taking of the phenomenal for the real, but the overlooking of the real in the phenomenal, since all things exist, i.e. are real, as categories of intrinsic relations in the unique mode of their conception. Finally, the implications of the account are discussed in relation to moral conduct, self-realization, acceptance, and the will to enjoy a world of 'brain-born' mental phenomena. (shrink)

The recent move to naturalize phenomenology through a mathematical protocol is a significant advance in consciousness research. It enables a new and fruitful level of dialogue between the cognitive sciences and phenomenology of such a nuanced kind that it also prompts advancement in our phenomenological analyses. But precisely what is going on at this point of ‘dialogue’ between phenomenological descriptions and mathematical algorithms, the latter of which are based on dynamical systems theory? It will be shown that what is happening (...) is something more than a mere ‘passing of the baton’ from phenomenology to mathematics. For this sophisticated naturalization to prove a worthy endeavour it must produce more than just correlation, it must prove some form of interrelation to the extent that phenomenology is deterministic. But such interrelational and deterministic requirements are the start of a slippery slope, and it will be argued that this slope only loses more friction once a further demand of formal and precise descriptions is made of phenomenology. Such deterministic and formally precise demands misconstrue phenomenology’s ideal goal of a unification of genuine/originary reason and truth. Not a deductive and definitive discipline, phenomenology is rather from the outset descriptive and critical. Phenomenology’s descriptive beginnings will thus be employed as an essential barrier to the naturalization of phenomenology. (shrink)

Given its brevity, Plato's Meno covers an astonishingly wide array of topics: politics, education, virtue, definition, philosophical method, mathematics, the nature and acquisition of knowledge and immortality. Its treatment of these, though profound, is tantalisingly short, leaving the reader with many unresolved questions. This book confronts the dialogue's many enigmas and attempts to solve them in a way that is both lucid and sympathetic to Plato's philosophy. Reading the dialogue as a whole, it explains how different arguments are related to (...) one another and how the interplay between characters is connected to the philosophical content of the work. In a new departure, this book's exploration focuses primarily on the content and coherence of the dialogue in its own right and not merely in the context of other dialogues, making it required reading for all students of Plato, be they from the world of classics or philosophy. (shrink)

This essay examines several recent philosophical attempts to define ‘disease’. Two prominent ones are considered in detail, an objective approach by Christopher Boorse and a normative approach by Caroline Whitbeck. Both are found to be inadequate for a variety of reasons, though Whitbeck's is superior because of her careful preliminary distinctions and because of its normative approach which is more nearly in accord with medical and lay usage. The paper concludes with a discussion of the nature of such efforts at (...) definition and suggests that their limitations are due both to the nature of our language and concepts in general, and to the nature of medicine in particular. It is the practical and changing character of medicine and its language that frustrates the efforts of philosophers to formulate such definitions. Keywords: disease, definition CiteULike Connotea Del.icio.us What's this? (shrink)

The medial prefrontal cortex (mPFC) has been the subject of intense interest as a locus of cognitive control. Several computational models have been proposed to account for a range of effects, including error detection, conflict monitoring, error likelihood prediction, and numerous other effects observed with single-unit neurophysiology, fMRI, and lesion studies. Here, we review the state of computational models of cognitive control and offer a new theoretical synthesis of the mPFC as signaling response–outcome predictions. This new synthesis has two interacting (...) components. The first component learns to predict the various possible outcomes of a planned action, and the second component detects discrepancies between the actual and intended responses; the detected discrepancies in turn update the outcome predictions. This single construct is consistent with a wide array of performance monitoring effects in mPFC and suggests a unifying account of the cognitive role of medial PFC in performance monitoring. (shrink)

Clarifying the essential experiential structures at work in our everyday moral engagements promises both (1) to provide a perspicacious self-understanding, and (2) to significantly contribute to theoretical and practical matters of moral philosophy. Since the phenomenological enterprise is concerned with revealing the a priori structures of experience in general, it is then well positioned to discern the essential structures of moral experience specifically. Phenomenology can therefore significantly contribute to matters pertaining to moral philosophy. In this paper I would like to (...) contribute to the relatively small yet burgeoning field of phenomenological ethics. I endea­vour to do so by first identifying and consolidating the basic level of sense-bestowal, and then outlining the a priori structures of volition in order to demonstrate how such phenomenologically discerned structures are required for moral experience. Specifically, in section one I locate moral experience as at the level of meaning that is phenomenologically identified as the life-world, and then vindicate the life-world by illustrating how it is immune to naturalistic rationalisation. By thus both securing the level of meaning that is of concern and importantly delimiting the scope of our analysis, I proceed in section two to relate the volitional analyses of Aristotle, Husserl, and Heidegger. This relation is achieved thanks to a conceptual point of con­tinuity: ‘prohairesis’. By examining the function of this concept (as an intentional structure) and its phenomenological continuity, the ground is then prepared for further phenomenological analyses of the virtues. (shrink)