Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

Trope theory is the view that the world is a world of abstract particular qualities. But if all there is are tropes, how do we account for the truth of propositions ostensibly made true by some concrete particular? A common answer is that concrete particulars are nothing but tropes in compresence. This answer seems vulnerable to an argument (first presented by F. H. Bradley) according to which any attempt to account for the nature of relations will end up either in (...) contradiction, nonsense, or will lead to a vicious infinite regress. I investigate Bradley’s argument and claim that it fails to prove what it sets out to. It fails, I argue, because it does not take all the different ways in which relation and relata may depend on one another into account. If relations are entities that are distinct from yet essentially dependent upon their relata, the Bradleyan problem is solved. We are then free to say that tropes in compresence are what make true propositions ostensibly made true by concrete particulars. (shrink)

Ever since F. H. Bradley first formulated his famous regress argument philosophers have been hard at work trying to refute it. The argument fails, it has been suggested, either because its conclusion just does not follow from its premises, or it fails because one or more of its premises should be given up. In this paper, the Bradleyan argument, as well as some of the many and varied reactions it has received, is scrutinized.

Trope theory is the view that the world consists (wholly or partly) of particular qualities, or tropes. This admittedly thin core assumption leaves plenty of room for variation. Still, most trope theorists agree that their theory is best developed as a one-category theory according to which there is nothing but tropes. Most hold that ‘sameness of property’ should be explained in terms of resembling tropes. And most hold that concrete particulars are made up from tropes in compresence (for an overview, (...) including an introduction to some alternative versions of the view, cf. Maurin, 2014). D. M. Armstrong disagrees. He thinks the world is a world of immanent universals, the thin particulars in which those universals are instantiated, and the states of affairs that—thereby—exist. He holds that ‘sameness of property’ should be explained in terms of numerically identical universals or—if the resembling things are the universals themselves—in terms of partially identical universals. And he believes that concrete particulars are made up from ‘thin particulars’ in which a (sufficient) number of universals are instantiated. In spite of their disagreements, proponents of tropes owe Armstrong a debt of gratitude. First, for being one of the theory’s earliest, most serious, and—not least—most prominent, critics (Armstrong for the first time considers, and rejects, what he then labels ‘particularism’, in his 1978a). But also for being one of the theory’s most ardent champions. Already in his 1989a, Armstrong regrets his 1978-rejection of the view. Equivalence classes of exactly resembling tropes, he now admits, for most purposes “serve as an excellent substitute for universals” (Armstrong 1989a, 122). But then why isn’t Armstrong a trope theorist? In this paper, Armstrong’s main reasons for rejecting the trope view are critically scrutinized. All of them, it is maintained, fail to convince. If this argument is accepted, Armstrong seems to have no—or, at least, no good—reason for not accepting the existence of tropes. But, then, ought Armstrong to have been a trope theorist? If the ‘best’ version of the trope view turns out to be ontologically more parsimonious than Armstrong’s own theory of universals, then, yes. That there is a version of the trope view, a version that is not (or, at least not seriously) considered by Armstrong, that is ontologically more parsimonious than the universals view, is argued in the next section. Why none of Armstrong’s reasons for preferring universals to tropes manage to convince, is explained in the section after that. First, however, and in order to avoid a common misunderstanding of the trope view and, as a consequence, of why one ought to reject it, a few more words about the core-difference between tropes and universals, and about how this difference matters (as well as does not matter) to what—and how well—these theories explain. (shrink)

Appearing in English for the first time, Schelling’s 1842 lectures develop the idea that many philosophical concepts are born of religious-mythological notions.

According to Johansson (2009: 22) an infinite regress is vicious just in case “what comes first [in the regress-order] is for its definition dependent on what comes afterwards.” Given a few qualifications (to be spelled out below (section 3)), I agree. Again according to Johansson (ibid.), one of the consequences of accepting this way of distinguishing vicious from benign regresses is that the so-called Russellian Resemblance Regress (RRR), if generated in a one-category trope-theoretical framework, is vicious and that, therefore, the (...) existence of tropes only makes sense if trope-theory is understood (minimally) as a two-category theory which accepts, besides the existence of tropes, also the existence of at least one universal: resemblance.1 I disagree. But how can that be? How can Johansson and I agree about what distinguishes a vicious from a benign regress, yet disagree about which regresses are vicious and which are benign? In this paper I attempt to answer that question by first setting out and defending the sense of viciousness which both Johansson and I accept, only to then argue that to be able to determine if a particular regress is vicious in this sense, more than features intrinsic to the regress itself must be taken into account. This is why, although the RRR as originally set out by Russell is vicious, the seemingly identical resemblance regress which ensues in a one-category (standard) trope-theoretical context is not (provided, that is, that we accept certain views about how the nature of tropes relates to the resemblance between tropes, and given that we set our theory in a truthmaker theoretical framework – all of which are standard assumptions for proponents of (the standard-version of) the trope-theory).2. (shrink)

The notorious ‘measurement problem’ has been roving around quantum mechanics for nearly a century since its inception, and has given rise to a variety of ‘interpretations’ of quantum mechanics, which are meant to evade it. We argue that no less than six problems need to be distinguished, and that several of them classify as different types of problems. One of them is what traditionally is called ‘the measurement problem’. Another of them has nothing to do with measurements but is a (...) profound metaphysical problem. We also analyse critically Maudlin’s (Topoi 14:7–15, 1995) well-known statement of ‘three measurements problems’, and the clash of the views of Brown (Found Phys 16:857–870, 1986) and Stein (Maximal of an impossibility theorem concerning quantum measurement. In: R. S. Cohen et al. (Eds.), Potentiality, entanglement and passion-at-a-distance, 1997) on one of the six measurement problems. Finally, we summarise a solution to one measurement problem which has been largely ignored but tacitly if not explicitly acknowledged. (shrink)

We use genomic information to tell us stories of evolutionary origins. But what does it mean when different genomes report wildly different accounts of lineage history? This genomic “discordance” can be a consequence of a fascinating suite of natural history and evolutionary phenomena, from the different inheritance mechanisms of nuclear versus cytoplasmic (mitochondrial and plastid) genomes to hybridization and introgression to horizontal transfer. Here, we explore how we can use these distinct genomic stories to provide new insights into the maintenance (...) of sexual reproduction, one of the most important unanswered questions in biology. We focus on the strikingly distinct nuclear versus mitochondrial versions of the story surrounding the origin and maintenance of asexual lineages in Potamopyrgus antipodarum, a New Zealand freshwater snail. While key questions remain unresolved, these data inspire multiple testable hypotheses that can be powerfully applied across a broad range of taxa toward a deeper understanding of the causes and consequences of mitonuclear discordance, the maintenance of sex, and the origin of new asexual lineages. (shrink)

Grounding theorists insist that grounding and explanation are intimately related. This claim could be understood as saying either that grounding ‘inherits’ its properties from explanation or it could be interpreted as saying that grounding plays an important—possibly an indispensable—role in metaphysical explanation. Or both. I argue that saying that grounding ‘inherits’ its properties from explanation can only be justified if grounding is explanatory by nature, but that this view is untenable. We ought therefore to be ‘separatists’ and view grounding and (...) explanation as distinct. As it turns out, though, once grounding has been in this sense distinguished from the explanation it backs, the view that the role grounding plays in explanation justifies its introduction ends up in serious trouble. I conclude that the role grounding plays in explanation does not justify attributing to grounding whatever nature we think it has, and it most likely does not give us any special reason to think grounding exists. (shrink)

Good work in nursing is work that is scientifically effective as well as morally and socially responsible. The purpose of this study was to examine variables that sustain good work among entering nurses (with one to five years of experience) and experienced professional nurses despite the obstacles they encounter. In addition to role models and mentors, entering and experienced nurses identified team work, cohesiveness and shared values as levers for good work. These nurses used prioritization, team building and contemplative practices (...) to overcome obstacles. Entering professional nurses tended to avoid conflict in the work setting. Experienced nurses reported forming teams of decision makers who share similar values to resolve conflict. These findings have implications for nurse education and nursing practice. Reflection on the importance of values and virtue in sustaining good work is important. Entering professional nurses should be encouraged to seek positive role models and reflect on the lessons that can be learned from experienced exemplary nurses. (shrink)

The treatise attempts to approach and deal with some of the most fundamental problems facing anyone who wishes to uphold some version of the so-called theory of tropes. Three assumptions serve as a basis for the investigation: tropes exist, only tropes exist, and a one-category trope-theory along these lines should be developed so that the tropes it postulates are able to serve as truth-makers for all kinds of atomic propositions. Provided that these assumptions are accepted, it is found that the (...) trope-theorist will have to deal with two important problems. First, some atomic propositions seem to require universal truth-makers. Second, some atomic propositions seem to require concrete truth-makers. As tropes are abstract particulars, it follows that the trope-theorist, in order to fulfil assumption, must provide an account of exactly how he or she could construct universality and concreteness from his or her basic stock of tropes. In the treatise such constructions are attempted and some basic problems with such constructions are revealed. Although these problems are serious enough it is argued that it is nevertheless possible to deal with these basic issues while staying squarely within the boundaries of a one-category trope-ontology. (shrink)

This paper starts with one of Chalmers’ basic points: first-hand experience is an irreducible field of phenomena. I claim there is no ‘theoretical fix’ or ‘extra ingredient’ in nature that can possibly bridge this gap. Instead, the field of conscious phenomena requires a rigorous method and an explicit pragmatics for its exploration and analysis. My proposed approach, inspired by the style of inquiry of phenomenology, I have called neurophenomenology. It seeks articulations by mutual constraints between phenomena present in experience and (...) the correlative field of phenomena established by the cognitive sciences. It needs to expand into a widening research community in which the method is cultivated further. (shrink)

In this chapter, we introduce the perennial and sometimes sprawling topic of properties, with a brief historical sketch from Ancient to Modern philosophy throughout various cultures and traditions. We argue that the importance of properties can be shown by explaining what explanatory work they can do in philosophical theorising across many areas of philosophy. The chapters in this volume do just that in their specific ways. We also outline the structure of the volume and summarise each Part, first describing the (...) larger context of each Part and then the upshot of each chapter. (shrink)

That there could be ontologically complex concrete particulars is self-evidently true. A reductio may however be formulated which contradicts this truth. In this paper I argue that all of the reasonable ways in which we might refute this reductio will require the existence of at least some tropes.

With fascinating historical anecdotes and incisive scientific analysis, this important work combines ancient thought with modern theory to reveal a new way of viewing our universe that can expand our awareness, our lives, and may well point the way to a new science for the twenty-first century.

Paper responding to critique of Maurin (2002) presented by Herbert Hochberg in his “Relations, Properties and Particulars” (2004).

Abstract:This article asks readers to consider expanding on ideas of Afro-Dominicanidad, and hegemonic narratives of blackness and anti-blackness. The goal is two-fold: first, to consider how ultra-nationalist movements in the Dominican Republic render dark-skinned Dominicans untenable to the viability of the Dominican nation-state and second: to identify how emic discourses of Afro-descent expand the epistemic grounds in the on-going fight against ultra-nationalism in the Dominican Republic.

In this paper I argue that the infinite regress of resemblance is vicious in the guise it is given by Russell but that it is virtuous if generated in a (contemporary) trope theoretical framework. To explain why this is so I investigate the infinite regress argument. I find that there is but one interesting and substantial way in which the distinction between vicious and virtuous regresses can be understood: The Dependence Understanding. I argue, furthermore, that to be able to decide (...) whether an infinite regress exhibits a dependence pattern of a vicious or a virtuous kind, facts about the theoretical context in which it is generated become essential. It is precisely because of differences in context that he Russellian resemblance regress is vicious whereas its trope theoretical counterpart is not. (shrink)

This is an English translation of Schelling's Ideas for a Philosophy of Nature (first published in 1797 and revised in 1803), one of the most significant works in the German tradition of philosophy of nature and early nineteenth-century philosophy of science. It stands in opposition to the Newtonian picture of matter as constituted by inert, impenetrable particles, and argues instead for matter as an equilibrium of active forces that engage in dynamic polar opposition to one another. In the revisions of (...) 1803 Schelling incorporated this dialectical view into a neo-Platonic conception of an original unity divided upon itself. The text is of more than simply historical interest: its daring and original vision of nature, philosophy, and empirical science will prove absorbing reading for all philosophers concerned with post-Kantian German idealism, for scholars of German Romanticism, and for historians of science. (shrink)

In this paper I critically investigate an unorthodox attempt to metaphysically explain in virtue of what there are states of affairs. This is a suggestion according to which states of affairs exist thanks to, rather than, as is the common view, in spite of, the infinite regress their metaphysical explanation seems to engender. I argue that, no matter in which form it is defended, or in which theoretical framework it is set, this suggestion cannot provide us with the explanation we (...) crave. (shrink)

Even though morally competent artificial agents have yet to emerge in society, we need insights from empirical science into how people will respond to such agents and how these responses should inform agent design. Three survey studies presented participants with an artificial intelligence agent, an autonomous drone, or a human drone pilot facing a moral dilemma in a military context: to either launch a missile strike on a terrorist compound but risk the life of a child, or to cancel the (...) strike to protect the child but risk a terrorist attack. Seventy-two percent of respondents were comfortable making moral judgments about the AI in this scenario and fifty-one percent were comfortable making moral judgments about the autonomous drone. These participants applied the same norms to the two artificial agents and the human drone pilot. However, people ascribed different patterns of blame to humans and machines as a function of the agent’s decision of how to solve the dilemma. These differences in blame seem to stem from different assumptions about the agents’ embeddedness in social structures and the moral justifications those structures afford. Specifically, people less readily see artificial agents as embedded in social structures and, as a result, they explained and justified their actions differently. As artificial agents will perform many actions with moral significance, we must heed such differences in justifications and blame and probe how they affect our interactions with those agents. (shrink)

I begin by criticizing an elaboration of an argument in this journal due to Hawley , who argued that, where Leibniz’s Principle of the Identity of Indiscernibles faces counterexamples, invoking relations to save PII fails. I argue that insufficient attention has been paid to a particular distinction. I proceed by demonstrating that in most putative counterexamples to PII , the so-called Discerning Defence trumps the Summing Defence of PII. The general kind of objects that do the discerning in all cases (...) form a category that has received little if any attention in metaphysics. This category of objects lies between indiscernibles and individuals and is called relationals: objects that can be discerned by means of relations only and not by properties. Remarkably, relationals turn out to populate the universe. (shrink)

Ethics for Enemies comprises three original philosophical essays on torture, terrorism, and war. F. M. Kamm deploys ethical theory in her challenging new treatments of these most controversial practical issues. First she considers the nature of torture and the various occasions on which it could occur, in order to determine why it might be wrong to torture a wrongdoer held captive, even if this were necessary to save his victims. In the second essay she considers what makes terrorism wrong--whether it (...) is the intention to harm civilians, rather than harm to them being 'collateral damage,' or something else--and whether terrorism is always wrong. The third essay discusses whether having a right reason, in the sense of a right intention, is necessary in order for a war to be just. Kamm then examines ways in which the harms of war can be proportional to the achievement of the just cause and other goods that war can bring about, so as to make the declaration of war permissible. (shrink)

Eklund vs. Bradley : Regress, Relation, Explanation.

This article is the text of an interview with D. H. Mellor conducted in Cambridge on 30 May 2001 by Anna-Sofia Maurin and Johannes Persson for the philosophical journal Theoria.

Cet article présente les premiers résultats d’un des volets d’une vaste recherche-action portée par une équipe pluridisciplinaire entre 2018 et 2021 et centrée sur les rapports familles/institutions. L’accueil et l’éducation des enfants dans le monde contemporain est en effet au cœur des problématiques institutionnelles et la famille, tout comme les institutions relevant de l’éducation, de la santé et du social, connaît d’importantes mutations tant structurelles qu’organisationnelles qui ont des conséquences au niveau des sujets, des groupes et des sociétés. Le présent (...) article apportera quelques éléments de compréhension de ce qui organise singulièrement les liens entre les familles et les collèges. L’auteure s’intéresse ici à la nature des liens qui unissent professionnels et parents autour des collégiens et autour des valeurs propres aux établissements ayant participé à la recherche. Elle propose quelques hypothèses pour appréhender ces rapports à nouveaux frais, entre défiance, résistance et créativité, du côté tant des familles que des professionnels et plus globalement des institutions. (shrink)

THERE WAS A TIME when many philosophers agreed that metaphysics was dead. Anyone aquatinted with the works of D.H. Mellor knows that the subject is alive and well. Two young philosophers who are familiar with his work, Anna-Sofia Maurin and Johannes Persson, met him in Cambrige for an interview.

The revisionary metaphysician seemingly faces a seriously unfortunate dilemma where she is forced to choose between the Scylla of too little regimentation and the Charbydes of too much. Many take this to be an impossible dilemma, and regard it as a reductio against the revisionary framework itself. In this paper, I argue that the dilemma is not necessarily impossible. To be justified, ontological theorising must be regimented just enough. To escape the dilemma, therefore, the revisionary metaphysician must, to be able (...) to answer the question: -/- Why should one hold that the world is a world of tropes? -/- first answer another question: -/- Can revisionary theorising be regimented just enough? -/- I will address both these questions in the order here indicated. I will suggest that the now popular truthmaker theory might, if added to a revisionary framework, offer the resources necessary to obtain just the right amount of regimentation for its revisionary ontological conclusions to be justified. The world is a world of tropes if (minimally) tropes can fulfil their truthmaking function. That tropes can fulfil their truthmaking function only tells us that the world could be a world of tropes, it does not tell us why we should prefer a theory of tropes as truthmakers to a theory of, say, states of affairs, however. I therefore end the paper with a discussion of the limits of theory comparison in revisionary ontology. (shrink)

Donald Davidson claims that, by studying the most general aspects of natural language, we will also be studying the most general aspects of reality.In particular, this means that, through the application of a systematic truththeory to natural language, we will be able to reveal its basic structure, its true logical form. Once this logical form has been spelled out, we will be able to determine the finite stock of important constituents of which sentences are built, and also the specific roles (...) these “atoms” play in the relevant structure. Since the structure of language can be said to “mirror” the structure of reality, this also means that we can now say something about the basic constituents of the world. We will be able to tell which kinds of entities exist and which do not. If, by spelling out the logical form, we find that there is a sentence (or several sentences) committing us to the existence of a certain (kind of) object (i.e. a sentence where an object (of this kind)serves as the value of a quantified variable) and, if we know the sentence to be true, then we have good reason to suppose that there is an object (of that kind) rather than not. This will hold given that there is no other way of spelling out the logical form of the sentence in question that is compatible with the nonexistence of that (kind of) object. So what exists is what, according to the (complete) theory, functions as values of the quantified variables, once thelogical form, the basic structure, of all the sentences of the language has been spelled out. Davidson has claimed that what all this quantificational structure will demand from ontology is the existence of objects and particular events. This should be taken somewhat at faith. In order to reach valid conclusions concerning the logical form of natural language, Davidson would have to examine allof its true sentences, and state allof their truth conditions, which he has not done. For practical reasons he has only been able to look at small segments of language, to consider how they normally function, to attempt to exhibit their logical structure by looking at entailment-relations, etc., and it is from this that he has drawn his ontological conclusions. In this paper, I concentrate on some of the likely consequences of the adoption of this method of reaching ontological conclusions. In particular, I will try to show that Davidson’s own way of arguing for the existence of events can be applied to cases where he seemingly would have to commit himself to the existence of properties too. To demonstrate this, I begin by considering whether the fact that Davidson spells out the logical form of natural language in first-order logic raises a serious objection to my claim or not. I then proceed by making a case for properties using an argument based on what Davidson has to say about the existence of events. What I will try to show is that, if Davidson is to be true to his general method of reaching conclusions regarding existence, which he claims to be, then he must go where this method leads him. This means that he has to keep his mind open as to the kinds of entities he should or should not allow. Finally, assuming that I have shown properties to be one of the different kinds of entities that a Davidsonian would have to allow, I conclude the paper by indicating what the consequence(s) of this may be. (shrink)

Although the subject matter of this Element is properties, do not expect in-depth introductions to the various views on properties 'on the market'. Instead, here that subject matter is treated meta-philosophically. Rather than ask and try to answer a question like do properties exist? this Element asks what reasons one might have for thinking that properties exist, what counts as solving that problems, as well as how we ought to proceed when trying to find out if properties exist. As it (...) turns out, these questions and their answers are all intricately intertwined. Theory comparison and theory evaluation is in other words tricky. Do properties exist? After reading this Element all we can say is therefore this: that depends. (shrink)

This paper investigates the One over Many, first as it was first introduced by Plato. Here, it is argued, the One over Many can be understood in at least two senses, both different from, but in a sense included in, the sense in which the One-over-Many is regarded as an argument for the existence of universals. In both of these senses, it is argued, it is possible to accept the One-over-Many while denying the existence of universals.This established, I examine the (...) argument from the One-over-Many as given within the framework of Armstrong’s theory of universals. Within this framework there is another thesis of great import, that of scientific realism. I will try to show that there exists a problematic tension, if not an outright contradiction, between this thesis and that of the argument from the One-over-Many. It seems that, as soon as you accept a scientific realism, the support provided by the argument from the One-over-Many dissolves, or, vice versa, if you claim support from the argument the results of your scientific realism seem to be contradicted. I will argue that the way to resolve this tension is to give up the argument from the One-over-Many. In particular, this will results in a weakening of Armstrong’s case for the existence of universals. In general, discussing the argument from the One-over-Many brings to the fore a feature common to all senses given to the One-over-Many, and thereby a feature affecting all theories of properties (since all theories of properties in one sense or another refer on the One-over-Many). (shrink)