Airway mucin secretion is important pathophysiologically and as a model of polarized epithelial regulated exocytosis. We find the trafficking protein, SNAP23, selectively expressed in secretory cells compared with ciliated and basal cells of airway epithelium by immunohistochemistry and FACS, suggesting that SNAP23 functions in regulated but not constitutive epithelial secretion. Heterozygous SNAP23 deletant mutant mice show spontaneous accumulation of intracellular mucin, indicating a defect in baseline secretion. However mucins are released from perfused tracheas of mutant and wild-type mice at the (...) same rate, suggesting that increased intracellular stores balance reduced release efficiency to yield a fully compensated baseline steady state. In contrast, acute stimulated release of intracellular mucin from mutant mice is impaired whether measured by a static imaging assay 5 min after exposure to the secretagogue ATP or by kinetic analysis of mucins released from perfused tracheas during the first 10 min of ATP exposure. Together, these data indicate that increased intracellular stores cannot fully compensate for the defect in release efficiency during intense stimulation. The lungs of mutant mice develop normally and clear bacteria and instilled polystyrene beads comparable to WT mice, consistent with these functions depending on baseline secretion that is fully compensated. (shrink)

Ovid completes his narrative of the origin of Croton with the following lines :talia constabat certa primordia famaesse loci positaeque Italis in finibus urbis.It was agreed by sure fame that such were the beginningsof the place and of the city established within Italian borders.

Journal Name: Philologus Issue: Ahead of print.

This article proposes and interprets a previously undiscussed connection between Horace'sCarmen2.15 and the description of the Corycian gardener at Virgil'sGeorgics4.125–48. It argues that this allusion to Virgil sharpens the moral pessimism of Horace's ode. It first considers the circumstantial, general and formal elements connecting these two poems; it then considers how the model of the Corycian gardener brings further point and nuance to the moralizing message ofCarmen2.15 and the way in which this allusion is meaningfully echoed atCarmen3.16.

Similar to parasites, cancer cells depend on their hosts for sustenance, proliferation and reproduction, exploiting the hosts for energy and resources, and thereby impairing their health and fitness. Because of this lifestyle similarity, it is predicted that cancer cells could, like numerous parasitic organisms, evolve the capacity to manipulate the phenotype of their hosts to increase their own fitness. We claim that the extent of this phenomenon and its therapeutic implications are, however, underappreciated. Here, we review and discuss what can (...) be regarded as cases of host manipulation in the context of cancer development and progression. We elaborate on how acknowledging the applicability of these principles can offer novel therapeutic and preventive strategies. The manipulation of host phenotype by cancer cells is one more reason to adopt a Darwinian approach in cancer research. -/- . (shrink)

Should a principle of charity be applied to the interpretation of the colour concepts exercised in visual experience? We think not. We shall argue, for one thing, that the grounds for applying a principle of charity are lacking in the case of colour concepts. More importantly, we shall argue that attempts at giving the experience of colour a charitable interpretation either fail to respect obvious features of that experience or fail to interpret it charitably, after all. Charity to visual experience (...) is therefore no motive for resisting the natural, Galilean response to a scientific understanding of light and vision. The best interpretation of colour experience ends up convicting it of widespread and systematic error. (shrink)

Samuelson's text was first published in 1948, and it immediately became the authority for the principles of economics courses. The book continues to be the standard-bearer for principles courses, and this revision continues to be a clear, accurate, and interesting introduction to modern economics principles. Bill Nordhaus is now the primary author of this text, and he has revised the book to be as current and relevant as ever.

This volume presents a series of influential essays by Paul Boghossian on the theory of content and on its relation to the phenomenon of a priori knowledge. The essays are organized under four headings: the nature of content; content and self-knowledge; knowledge, content, and the a priori; and colour concepts.

In the latest edition of their popular overview text, Erickson and Murphy continue to provide a comprehensive, affordable, and accessible introduction to anthropological theory from antiquity to the present.

This paper argues that, given a certain apparently inevitable thesis about content, we could not know our own minds. The thesis is that the content of a thought is determined by its relational properties.

The paper asks under what conditions deductive reasoning transmits justification from its premises to its conclusion. It argues that both standard externalist and standard internalist accounts of this phenomenon fail. The nature of this failure is taken to indicate the way forward: basic forms of deductive reasoning must justify by being instances of 'blind but blameless' reasoning. Finally, the paper explores the suggestion that an inferentialist account of the logical constants can help explain how such reasoning is possible.

In this chapter a new problem about rule-following is outlined, one that is distinct both from Kripke’s and Wright’s versions of the problem. This new problem cannot be correctly responsed to, as Kripke’s can, by invoking Wright’s Intentional Account of rule-following. The upshot might be called, following Kant, an antinomy of pure reason: we both must — and cannot — make sense of someone’s following a rule. The chapter explores various ways out of this antinomy without here endorsing any of (...) them. (shrink)

ABSTRACTThis essay offers a reconfiguration of the possibility‐space of positions regarding the metaphysics and epistemology associated with historical knowledge. A tradition within analytic philosophy from Danto to Dummett attempts to answer questions about the reality of the past on the basis of two shared assumptions. The first takes individual statements as the relevant unit of semantic and philosophical analysis. The second presumes that variants of realism and antirealism about the past exhaust the metaphysical options . This essay argues that both (...) of these assumptions should be rejected. It develops as an alternative an irrealist account of history, a view based in part on work by Leon Goldstein and Ian Hacking. On an irrealist view, historical claims ought to be treated as subject to the same conditions and caveats that apply to any theory of empirical or scientific knowledge. Irrealism argues for pasts as made and not found. The argument emphasizes the priority of classification over perception in the order of understanding and so verification. Because nothing a priori anchors practices of classification, no sense can be attached to claims that some single structure must or does determine what events take place in human history. Irrealism denies to realism the very intelligibility of any imagined view from nowhere, that is, a determinately configured past subsisting sub specie aeternitatis. A plurality of pasts exists because constituting a past always depends to some degree on socially mediated negotiations of a fit between descriptions and experience. (shrink)

It is very common these days to come across the claim that the notions of mental content and linguistic meaning are normative notions. In the work of many philosophers, it plays a pivotal role. Saul Kripke made it the centerpiece of his influential discussion of Wittgenstein’s treatment of rulefollowing and private language; he used it to argue that the notions of meaning and content cannot be understood in naturalistic terms. Kripke’s formulations tend to be in terms of the notion of (...) linguistic meaning, but his argumentative strategy makes it clear that he holds both versions of the claim.... (shrink)

According to a very natural picture of rational belief, we aim to believe only what is true. However, as Bernard Williams used to say, the world does not just inscribe itself onto our minds. Rather, we have to try to figure out what is true from the evidence available to us. To do this, we rely on a set of epistemic rules that tell us in some general way what it would be most rational to believe under various epistemic circumstances. (...) We reason about what to believe; and we do so by relying on a set of rules.... (shrink)

An irrealist conception of a given region of discourse is the view that no real properties answer to the central predicates of the region in question. Any such conception emerges, invariably, as the result of the interaction of two forces. An account of the meaning of the central predicates, along with a conception of the sorts of property the world may contain, conspire to show that, if the predicates of the region are taken to express properties, their extensions would have (...) to be deemed uniformly empty. The question then becomes whether the predicates are best understood as expressing properties, and hence as founded on error, or whether they ought to be understood along non-factualist lines.z Historically, irrealist models were developed primarily in connection with evaluative discourse, although as physicalism has flourished and as reductionist programs have failed, their application has been extended to many other domains. Indeed, it is one of the more influential suggestions in contemporary philosophy of mind that they apply even to ordinary belief/desire psychology. A correct understanding of the semantics and metaphysics of content-based psychology leaves us, so the proponents of the in-. (shrink)

These essays examine the ways in which the consideration of ethical questions is shaped by the structures of knowledge and communication at work in clinical ...

Compatibilism combines an externalist view of mental content with a doctrine of privileged self‐knowledge. The essay presents a reductio of compatibilism by arguing that if compatibilism were true, we would be in a position to know certain facts about the world a priori, facts that no one can reasonably believe are knowable a priori. Whether this should be taken to cast doubt on externalism or privileged self‐knowledge is not discussed. Consideration is given to the ’empty case’—the case in which a (...) thinker expresses what he takes to be a genuine thought concerning a natural kind but where there is in fact no relevant natural kind, so that the putative natural kind term fails to refer. It is argued that, in such a case, on an externalist conception of natural kind terms, the thinker is deluded in taking himself to be expressing a complete thought, and that such delusions are not compatible with privileged self‐knowledge. (shrink)

The core idea seems clear enough. To say of something that it is socially constructed is to emphasize its dependence on contingent aspects of our social selves. It is to say: This thing could not have existed had we not built it; and we need not have built it at all, at least not in its present form. Had we been a different kind of society, had we had different needs, values, or interests, we might well have built a different (...) kind of thing, or built this one differently. The inevitable contrast is with a naturally existing object, something that exists independently of us and which we did not have a hand in shaping. (shrink)

Two major reports in the UK and USA have recently sanctioned as ethically acceptable genome editing of future generations for the treatment of serious rare inherited conditions. This marks an important turning point in the application of recombinant DNA techniques to humans. The central question this paper addresses is how did it became possible for human genetic engineering (HGE) of future generations to move from an illegitimate idea associated with eugenics in the 1980s to a concrete proposal sanctioned by scientists (...) and bioethicists in 2020? The paper uses the concept of a regime of normativity to understand the co-evolution and mutual shaping of technology, imaginaries, norms and governance processes in debates about HGE in the USA and UK. It will be argued that interlinked discursive, institutional, political and technological changes have made proposals for the use of genome editing in the genetic engineering of future generations both “thinkable” and legitimate. (shrink)

This comprehensive anthology offers over 40 readings that are critical to the understanding of anthropological theory and the development of anthropology as an academic discipline. The fourth edition maintains a strong focus on the "four-field" roots of the discipline in North America but has been reorganized with a new section on twenty-first-century theory, including coverage of postcolonial and public anthropology. New key terms and introductions accompany each reading and a revamped glossary makes the book more student-friendly. Used on its own, (...) or together with the overview text A History of Anthropological Theory, Fourth Edition, this anthology offers a flexible and unrivaled introduction to anthropological theory that reflects not only the history but also the changing nature of the discipline today. For additional resources, visit the "Teaching Theory" page at www.utpteachingculture.com. (shrink)

Rhodopsin, upon activation by light, transduces the photon signal by activation of the G‐protein, transducin. The well‐studied rhodopsin/transducin system serves as a model for the understanding of signal transduction by the large class of G‐protein‐coupled receptors. The interactive form of rhodopsin, R*, is conformationally similar or identical to rhodopsin's photolysis intermediate Metarhodopsin II (MII). Formation of MII requires deprotonation of rhodopsin's protonated Schiff base which appears to facilitate some opening of the rhodopsin structure. This allows a change in conformation at (...) rhodopsin's cytoplasmic surface that provides binding sites for transducin. Rhodopsin's 2nd, 3rd and putative 4th cytoplasmic loops bind transducin at sites including transducin's 5 kDa carboxyl‐terminal region. Site‐specific mutagenesis of rhodopsin is being used to distinguish sites on rhodopsin's surface that are important in binding transducin from those that function in activating transducin. These observations are consistent with and extend studies on the action of other G‐protein‐coupled receptors and their interactions with their respective G proteins. (shrink)

The very idea of narrative explanation invites two objections: a methodological objection, stating that narrative structure is too far from the form of a scientific explanation to count as an explanation, and a metaphysical objection, stating that narrative structure situates historical practice too close to the writing of fiction. Both of these objections, however, are illfounded. The methodological objection and the dispute regarding the status of historical explanation can be disposed of by revealing their motivating presupposition: the plausibility of an (...) exclusivist explication of explanation which appeals either to the unity-of-method thesis or some implicit notion of analytic equivalence, both problematic philosophical doctrines. The metaphysical objection fails with the rejection of the idea, in Mink's phrase, of an "untold story." The argument against history as an "untold story" develops from Danto's image of an Ideal Chronicler recording ideal events. A consequence of rejecting this view is that it no longer makes sense to speak of historical narratives as true or false. However, this failure engenders no special problem for assessing the objectivity or explanatory utility of narratives qua explanations. (shrink)

The Archaeology of Prehistoric Arabia: Adaptation and Social Formation from the Neolithic to the Iron Age. By Peter Magee. Cambridge World Archaeology. New York: Cambridge University Press, 2014. Pp. xv + 309, illus. $99.

The Early Bronze Age Tombs of Jebel Hafit. By Bo Madsen. Aarhus: Jutland Archaeological Society and Moesgaard Museum, 2017. Pp. 245, illus. DKK 350. [Distributed by Aarhus University Press].

Südarabien im Altertum: Kommentierte Bibliographie der Jahre 1997 bis 2011. By Walter W. Müller. Epigraphische Forschungen auf der Arabischen Halbinsel, vol. 6. Tübingen: Wasmuth, 2014. Pp. vii + 187. €19.80.

Philosophers and ethicists debate this controversial moral principle illustrating its application to current moral dilemmas such as war, suicide, nuclear power, affirmative action, and morphine use for terminal cancer patients.

The dispute between realists about color and anti-realists is actually a dispute about the nature of color properties. The disputants do not disagree over what material objects are like. Rather, they disagree over whether any of the uncontroversial facts about material objects--their powers to cause visual experiences, their dispositions to reflect incident light, their atomic makeup, and so on--amount to their having colors. The disagreement is thus about which properties colors are and, in particular, whether colors are any of the (...) properties in a particular set that is acknowledged on both sides to exhaust the properties of material objects. In a previous paper we discussed at length one attempt to identify colors with particular properties of material objects--namely, with their dispositions to cause visual experiences. Here we shall discuss a different and perhaps more influential version of realism, which says that the colors of material objects are microphysical properties of their surfaces. We shall call this theory physicalism about color (physicalism, for short). In order to evaluate this theory, however, we shall first have to clarify some methodological issues. Our hope is that we can bring some further clarity to the question of color realism, whether or not we succeed in our critique of the physicalists' answer. (shrink)

In this article, I show how traditional Thomistic claims about the creation and fall of the first human beings—or “Adam”—are compatible with the claims of evolutionary science concerning human origins. Aquinas claims that God created Adam in a state or condition of original justice, wholly subject to God and so fully virtuous, as well as internally immune to bodily corruption, suffering, and natural death. In defense of “Aquinas's Adam,” I first argue that affirming that the prelapsarian Adam was internally immune (...) to suffering and death does not require denying that these things predated his emergence within evolutionary history, or that he would have faced real challenges posed to him by his natural environment. Next, I rebut the claim that Adam must have been spiritually and morally fragile, given the traits he inherited from his evolutionary ancestors. Finally, I dispute the claim that Adam only could have fallen if he existed in a spiritually and morally fragile state. (shrink)

I believe that the notion of epistemic transparency does play an important role in our ordinary conception of mental content and I want to say what that role is. Unfortunately, the task is a large one; here I am able only to begin on its outline. I shall proceed somewhat indirectly, beginning with a discussion of externalist conceptions of mental content. I shall show that such conceptions violate epistemic transparency to an extent that has not been fully appreciated. Subsequently, I (...) shall look at the implications of this violation and at the reconstructive project that a rejection of transparency entails. I am inclined to think it unlikely that we will get a conception of propositional content that underwrites epistemic transparency. But I am concerned that we have not fully appreciated the role that transparency currently plays and the work that would need to be done were we to discard it. (shrink)

In this article I offer an extended, critical review of the analytic theology project. In the first part of the article, I investigate the origins and rise of analytic theology. I also offer some initial insights into the nature of analytic theology, based on some of what its chief proponents understand analytic theology to be. In the second part of the article, I summarize and evaluate some of the major contributions that already have been made within analytic theology. In the (...) third and final section of the article, I evaluate the analytic theology project as a whole, testing its compatibility with certain methods and movements within the Christian theological tradition. Based on this discussion, I then begin to narrate the advantages of construing analytic theology more narrowly, as a dogmatic project committed to articulating and defending Christian doctrine in rational pursuit of genuine theological knowledge and truth. My final claim is that analytic theologians should continue to engage in bold, speculative inquiry into the nature of the divine as well as related divine matters, and thus remain committed to developing and defending theology as a dogmatic and speculative enterprise. By doing so, analytic theologians will help fortify and elevate the contemporary theological enterprise as a whole. (shrink)

This article reflects on the assumption underlying the argument of Little et al. that "contested understandings" in the clinic are susceptible to reconciliation within a liberal framework described as "pragmatic pluralism". It is argued that no such reconciliation is possible or desirable because it is of the nature of the clinic that it provides a forum for multiple voices, ethical and cultural perspectives, and conceptual frameworks, and this is the source of its fecundity and creativity. Medicine itself cannot be represented (...) by a single discourse, precisely because it is itself an unruly collection of practices that, despite their heterogeneity, are able to engage in productive dialogues with each other. The heteroglossia of the clinic, therefore, is not a problem to be overcome. Rather, it is a rich resource to be mobilized in accordance with its multiple inherent purposes. (shrink)

W. V. Quine was the most important naturalistic philosopher of the twentieth century and a major impetus for the recent resurgence of the view that empirical science is our best avenue to knowledge. His views, however, have not been well understood. Critics charge that Quine’s naturalized epistemology is circular and that it cannot be normative. Yet, such criticisms stem from a cluster of fundamental traditional assumptions regarding language, theory, and the knowing subject – the very presuppositions that Quine is at (...) pains to reject. Through investigation of Quine’s views regarding language, knowledge, and reality, the author offers a new interpretation of Quine’s naturalism. The naturalism/antinaturalism debate can be advanced only by acknowledging and critiquing the substantial theoretical commitments implicit in the traditional view. Gregory argues that the responses to the circularity and non-normativity objections do just that. His analysis further reveals that Quine’s departure from the tradition penetrates the conception of the knowing subject, and he thus offers a new and engaging defence of Quine’s naturalism. (shrink)

The paper is a defense of the project of explaining the a priori via the notion of meaning or concept possession. It responds to certain objections that have been made to this project—in particular, that there can be no epistemically analytic sentences that are not also metaphysically analytic, and that the notion of implicit definition cannot explain a priori entitlement. The paper goes on to distinguish between two different ways in which facts about meaning might generate facts about entitlement—inferential and (...) constitutive. It concludes by outlining a theory of the latter. (shrink)

Preface: The dog's bollocks-- at the media dinner party -- Introduction: "The Marx brothers", "The Elvis of cultural theory", and other media clichés -- The mediated imp of the perverse -- Žižek's tickling shtick -- Big (Br)other : psychoanalysing the media -- Understanding the media : the sublime objectification of ideology -- The media's violence -- The joker's little shop of ideological horrors -- Conclusion: Don't just do it : negative dialectics in the age of Nike.

We live and thrive in a global society and economy where education and training is essential to a nation’s competitiveness and to the standard of living of its people. Opening the doors of higher or further education beyond the enrollments in elite or select universities has become a greater necessity. This has spawned a movement to develop or expand institutions that are more affordable, accessible, flexible, and tied to business and industry. Take a look at the systems that have been (...) developed in 20 countries worldwide that were designed to meet these needs. Historical development of each system, as well as the strategies for addressing national mandates for preparing a workforce for the global economy, are described throughout each chapter. (shrink)

The article argues, "contra" berger, that quine's advocacy alleged of classical logic is not based on any alleged "fit" between classical logic and some empirical account of language learning. roth begins by examining berger's claim that quine has changed his position on the acceptability of alternative logics. in berger's account, quine now accepts alternative logics because he could not defend his commitment to classical logic alone based on empirical evidence (e.g., verdict tables). roth argues that berger is mistaken both in (...) thinking that quine has changed his position and in berger's belief that evidence regarding language learning is the basis of quine's view on logic. the actual basis, roth argues, is pragmatic. (shrink)

In this paper we discuss the epistemological positions of evolution theories. A sharp distinction is made between the theory that species evolved from common ancestors along specified lines of descent (here called the theory of common descent), and the theories intended as causal explanations of evolution (e.g. Lamarck's and Darwin's theory). The theory of common descent permits a large number of predictions of new results that would be improbable without evolution. For instance, (a) phylogenetic trees have been validated now; (b) (...) the observed order in fossils of new species discovered since Darwin's time could be predicted from the theory of common descent; (c) owing to the theory of common descent, the degrees of similarity and difference in newly discovered properties of more or less related species could be predicted. Such observations can be regarded as attempts to falsify the theory of common descent. We conclude that the theory of common descent is an easily-falsifiable & often-tested & still-not-falsified theory, which is the strongest predicate a theory in an empirical science can obtain. Theories intended as causal explanations of evolution can be falsified essentially, and Lamarck's theory has been falsified actually. Several elements of Darwin's theory have been modified or falsified: new versions of a theory of evolution by natural selection are now the leading scientific theories on evolution. We have argued that the theory of common descent and Darwinism are ordinary, falsifiable scientific theories. (shrink)