Cell signalling mediators derived from membrane phospholipids are frequent participants in biological processes. The family of phosphoinositide 3-kinases (PI3Ks) phosphorylate the membrane lipid phosphatidylinositol, generating second messengers that direct diverse responses. These PI3K products are fundamental for leukocyte migration or chemotaxis, a pivotal event during the immune response. This system is therefore of significant biomedical interest. This review focuses on the biochemistry and signalling pathways of PI3K, with particular emphasis on chemokine (chemotactic cytokine)-directed responses. The key objectives of chemotaxis are (...) motility and direction. The latter—direction—requires distinct events at the front and back of a cell. In light of this, the coordinated localisation of signalling factors, an event choreographed by a sharp intracellular gradient of PI3K-derived products, is a common theme. BioEssays 27:153–163, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

C. S. Lewis is one of the most beloved Christian apologists of the twentieth century; David Hume and Bertrand Russell are among Christianity’s most important critics. This book puts these three intellectual giants in conversation with one another on various important questions: the existence of God, suffering, morality, reason, joy, miracles, and faith. Alongside irreconcilable differences, surprising areas of agreement emerge. Curious readers will find penetrating insights in the reasoned dialogue of these three great thinkers.

There are several theses in political science that are usually explicitly called ‘laws’. Other theses are generally thought of as laws, but often without being explicitly labelled as such. Still other claims are well-supported and arguably interesting, while no one would be tempted to call them laws. This situation raises philosophical questions: which theses deserve to be called laws and which not? And how should we decide about this? In this paper we develop and motivate a strategy for thinking about (...) laws in political science which integrates two core concepts: spatio-temporal stability and social mechanisms. The proposed strategy is a set of guidelines that political scientists can use to reflect on and argue about specific cases within their discipline, not a clear-cut demarcation criterion. We defend and motivate this strategy and apply it to two cases (one with respect to state repression, one about parliamentary elections). After we have developed and motivated our strategy for political science, we show that our proposal is relevant for other disciplines in the social sciences. We explain how our views fit into critical realism and embed them in the debate on laws in general philosophy of science and in the philosophy of the social sciences. (shrink)

Develops a logical analysis of dialogue in which two or more parties attempt to advance their own interests. It includes a classification of the major types of dialogues and a discussion of several important informal fallacies.

In everyday life we often act adequately, yet without deliberation. For instance, we immediately obtain and maintain an appropriate distance from others in an elevator. The notion of normativity implied here is a very basic one, namely distinguishing adequate from inadequate, correct from incorrect, or better from worse in the context of a particular situation. In the first part of this paper I investigate such ‘situated normativity’ by focusing on unreflective expert action. More particularly, I use Wittgenstein’s examples of craftsmen (...) (tailors and architects) absorbed in action to introduce situated normativity. Situated normativity can be understood as the normative aspect of embodied cognition in unreflective skillful action. I develop Wittgenstein’s insight that a peculiar type of affective behaviour, ‘directed discontent’, is essential for getting things right without reflection. Directed discontent is a reaction of appreciation in action and is introduced as a paradigmatic expression of situated normativity. In the second part I discuss Wittgenstein’s ideas on the normativity of what he calls ‘blind’ rule-following and the ‘bedrock’ of immediate action. What matters for understanding the normativity of (even ‘blind’) rule-following, is not that one has the capacity for linguistic articulation or reflection but that one is reliably participating in a communal custom. In the third part I further investigate the complex relationships between unreflective skillful action, perception, emotion, and normativity. Part of this entails an account of the link between normativity at the level of the expert’s socio-cultural practice and the individual’s situated and lived normativity. (shrink)

The counterfactual comparative account of harm faces problems in cases that involve overdetermination and preemption. An influential strategy for dealing with these problems, drawing on a suggestion made by Derek Parfit, is to appeal to _plural harm_—several events _together_ harming someone. We argue that the most well-known version of this strategy, due to Neil Feit, as well as Magnus Jedenheim Edling’s more recent version, is fatally flawed. We also present some general reasons for doubting that the overdetermination and preemption problems (...) for the counterfactual comparative account can be satisfactorily solved by appealing to plural harm. (shrink)

Stimmung in music -- The philosophy of Stimmung -- Playing in between -- History -- Duration -- Aftersong.

The book revives the neutral monism of Mach, James, and Russell and applies the updated view to the problem of redefining physicalism, explaining the origins of sensation, and the problem of deriving extended physical objects and systems from an ontology of events.

A consideration of Mach's elements, his philosophy of neutral monism, and philosophy of physics, especially space and time, much of it based on unpublished writings from the Nachlass and other original sources. The historical connection between Mach and logical positivism is shown to be superficial at best, and Mach's elements are shown to be mind independent natural qualities (world-elements) with dynamic force, not limited to human sensations.

In Consequentialism Reconsidered, Carlson strives to find a plausible formulation of the structural part of consequentialism. Key notions are analyzed, such as outcomes, alternatives and performability. Carlson argues that consequentialism should be understood as a maximizing rather than a satisficing theory, and as temporally neutral rather than future oriented. He also shows that certain moral theories cannot be reformulated as consequentialist theories. The relevant alternatives for an agent in a situation are taken to comprise all actions that they can perform (...) in the situation. The defense of this idea necessitates certain modifications to the standard consequentialist criteria of obligatoriness, rightness and wrongness. The problem of whether agents should adapt their actions to their own future actions is also addressed. Further, a conditional analysis of performability is suggested, and it is argued that particular actions should in this connection be regarded as `abstract' rather than `concrete'. The final chapter sketches a consequentialist theory for collective agents. (shrink)

Forms, Matter and Mind. Three Strands in Plato’s Metaphysics -/- This book offers a new interpretation of Plato’s conception of man and of how it develops in the Corpus. Commonly, Plato’s anthropology is considered to be a version of naïve Orphism with the soul being a heavenly, but fallen, daemon. This is shown to be a misleading over-simplification. An examination of three basic and interrelated strands in Plato’s thought (Forms, Matter and Mind) demonstrates how Plato’s conception of man is an (...) integrated part of his metaphysics and develops with it. Thus, a change can be seen from a fairly unreflecting Socratic beginning via a transcendent soul to a rather sophisticated ‘Aristotelianism’. What is at issue is a non-materialistic, or more precisely, a dualistic view of man that has been discredited in modern times by two preconceptions: a widespread opinion that dualism must mean or involve Cartesianism, which seems untenable, and an equally widespread and, until recently, unshaken belief that man can be exhaustively described in materialistic terms. Both assumptions are questioned today. The present work shows that Plato’s view of man is fundamentally different from Cartesianism and furthermore that he rejects the materialist view as well. Hence, the book shows Plato’s increasing relevance for the current debate on the nature and possibilities of man. (shrink)

There are important structural similarities in the way that animals and humans engage in unreflective activities, including unreflective social interactions in the case of higher animals. Firstly, it is a form of unreflective embodied intelligence that is ‘motivated’ by the situation. Secondly, both humans and non-human animals are responsive to ‘affordances’ (Gibson 1979); to possibilities for action offered by an environment. Thirdly, both humans and animals are selectively responsive to one affordance rather than another. Social affordances are a subcategory of (...) affordances, namely possibilities for social interaction offered by an environment: a friend’s sad face invites comforting behavior, a person waiting for a coffee machine can afford a conversation, and an extended hand affords a handshake. I will review recent insights in the nature of the bodily intentionality characteristic of unreflective action. Such ‘motor intentionality’ can be characterized as “our direct bodily inclination to act in a situated, environmental context” (Kelly 2005, p. 106). Standard interpretations of bodily intentionality see grasping an object as the paradigmatic example of motor intentionality. I will discuss the implications of another, novel perspective that emphasizes the importance of unreflective switches from one activity to another (Rietveld 2004) and understands bodily intentionality in terms of adequate responsiveness to a field of relevant affordances. In the final section I will discuss some implications for cognitive neuroscientists who use empirical findings related to the ‘mirror neuron system’ as a starting point for a theory of motor intentionality and social cognition. (shrink)

In cognitive science, long-term anticipation, such as when planning to do something next year, is typically seen as a form of ‘higher’ cognition, requiring a different account than the more basic activities that can be understood in terms of responsiveness to ‘affordances,’ i.e. to possibilities for action. Starting from architects that anticipate the possibility to make an architectural installation over the course of many months, in this paper we develop a process-based account of affordances that includes long-term anticipation within its (...) scope. We present a framework in which situations and their affordances unfold, and can be thought of as continuing a history of practices into a current situational activity. In this activity affordances invite skilled participants to act further. Via these invitations one situation develops into the other; an unfolding process that sets up the conditions for its own continuation. Central to our process account of affordances is the idea that engaged individuals can be responsive to the direction of the process to which their actions contribute. Anticipation, at any temporal scale, is then part and parcel of keeping attuned to the movement of the unfolding situations to which an individual contributes. We concretize our account by returning to the example of anticipation observed in architectural practice. This account of anticipation opens the door to considering a wide array of human activities traditionally characterized as ‘higher’ cognition in terms of engaging with affordances. (shrink)

One of the lecture plates in the collection of the Museum of the University of Amsterdam, generally believed to be used by the Dutch botanist Hugo de Vries, has aroused much discussion in relation to the question of whether or not de Vries knew Mendel's laws before he published his rediscovery of them in 1900. The plate suggests that de Vries observed Mendelian segregation ratios in 1895 and 1896 in the progeny of a cross of two varieties of Papaver with (...) different flower colour. According to his own account, it was through this cross that he first deduced the laws of Mendel in 1896. Some researchers have accepted the lecture plate as proof for this claim. My conclusion is that the plate was not made before 1900 but in 1904 for a lecture course in the USA and, as a consequence, that it is not a contemporary piece of evidence. A closer look at the descriptions of the depicted experiment in de Vries' publications revealed that its original goal was not to investigate segregation but to transfer a monstrosity. The segregation of the flower colour was a accidental event. No research notes of the experiment have survived, but a note on an experiment with Veronica, performed in the same successive years as the Papaver experiment and definitely intended to investigate the segregation of flower colour, shows that this experiment was interpreted in a theoretically conceived, more or less Mendelian way. Because of a sloppy performance, no firm conclusions could be drawn from the experiment, but de Vries clearly had the idea of Mendelian segregation in 1896. That he never brought it up before 1900 suggests that he could not establish the general validity of segregation rules, as is shown in the case of Veronica. The reading of Mendel's paper in 1900 immediately put an end to de Vries' doubts. He scrapped the failures and kept the successes, proudly presenting these to the public as proof for the laws of segregation and, at the same time, of the independence of his discovery. (shrink)

One can (for the most part) formulate a model of a classical system in either the Lagrangian or the Hamiltonian framework. Though it is often thought that those two formulations are equivalent in all important ways, this is not true: the underlying geometrical structures one uses to formulate each theory are not isomorphic. This raises the question of whether one of the two is a more natural framework for the representation of classical systems. In the event, the answer is yes: (...) I state and sketch proofs of two technical results—inspired by simple physical arguments about the generic properties of classical systems—to the effect that, in a precise sense, classical systems evince exactly the geometric structure Lagrangian mechanics provides for the representation of systems, and none provided by Hamiltonian. The argument not only clarifies the conceptual structure of the two systems of mechanics, but also their relations to each other and their respective mechanisms for representing physical systems. It also shows why naïvely structural approaches to the representational content of physical theories cannot work. [Lagrange] grasped that he had gained a method of stating dynamical truths in a way, which is perfectly indifferent to the particular methods of measurement employed in fixing the positions of the various parts of the system. Accordingly, he went on to deduce equations of motion, which are equally applicable whatever quantitative measurements have been made, provided that they are adequate to fix positions. The beauty and almost divine simplicity of these equations is such that these formulae are worthy to rank with those mysterious symbols which in ancient times were held directly to indicate the Supreme Reason at the base of all things. (Whitehead [1948], p. 63)1. Introduction2.Classical Systems3. The Possible Interactions of a Classical System and the Structure of Its Space of States4. Classical Systems Are Lagrangian5. Classical Systems Are Not Hamiltonian6. How Lagrangian and Hamiltonian Mechanics Represent Classical Systems7. The Conceptual Structure of Classical Mechanics. (shrink)

An energy condition, in the context of a wide class of spacetime theories, is, crudely speaking, a relation one demands the stress-energy tensor of matter satisfy in order to try to capture the idea that "energy should be positive". The remarkable fact I will discuss in this paper is that such simple, general, almost trivial seeming propositions have profound and far-reaching import for our understanding of the structure of relativistic spacetimes. It is therefore especially surprising when one also learns that (...) we have no clear understanding of the nature of these conditions, what theoretical status they have with respect to fundamental physics, what epistemic status they may have, when we should and should not expect them to be satisfied, and even in many cases how they and their consequences should be interpreted physically. Or so I shall argue, by a detailed analysis of the technical and conceptual character of all the standard conditions used in physics today, including examination of their consequences and the circumstances in which they are believed to be violated. (shrink)

We propose to understand social affordances in the broader context of responsiveness to a field of relevant affordances in general. This perspective clarifies our everyday ability to unreflectively switch between social and other affordances. Moreover, based on our experience with Deep Brain Stimulation for treating obsessive-compulsive disorder (OCD) patients, we suggest that psychiatric disorders may affect skilled intentionality, including responsiveness to social affordances.

The increasing strategic importance of environmental, social and ethical issues as well as related performance measures has spurred interest in corporate sustainability performance measurement and management systems. This paper focuses on the balanced scorecard, a performance measurement and management system aiming at balancing financial and non-financial as well as short and long-term measures. Modifications to the original BSC which explicitly consider environmental, social or ethical issues are often referred to as sustainability balanced scorecards. There is much scholarly discussion about SBSC (...) architecture and how it can be designed to relate performance dimensions, strategic objectives and the logical links among these elements. To synthesise the widely scattered research findings and publications on the SBSC, we conducted a thematic analysis based on a systematic literature review containing 69 relevant articles spanning a period of two decades. We found that sustainability-oriented modifications of the BSC architecture are motivated by instrumental, social/political or normative theoretical perspectives. Moreover, these modifications can be mapped with a typology of generic SBSC architectures. The first dimension of the typology describes the hierarchy between performance perspectives and strategic objectives and how it is related to the organisational value system. The second dimension describes how sustainability-related strategic objectives are integrated into SBSC performance perspectives and how this is related to corporate sustainability strategy. This study contributes to the development of the emerging SBSC literature and practice and, more generally, to research on corporate sustainability performance measurement and management. We conclude with a research agenda and implications for management. (shrink)

Ruth Chang has defended a concept of "parity", implying that two items may be evaluatively comparable even though neither item is better than or equally good as the other. This article takes no stand on whether there actually are cases of parity. Its aim is only to make the hitherto somewhat obscure notion of parity more precise, by defining it in terms of the standard value relations. Given certain plausible assumptions, the suggested definiens is shown to state a necessary and (...) sufficient condition for parity, as this relation is envisaged by Chang. (shrink)

We have argued that the counterfactual comparative account of harm and benefit (CCA) violates the plausible adequacy condition that an act that would harm an agent cannot leave her much better off than an alternative act that would benefit her. In a recent paper in this journal, however, Neil Feit objects that our argument presupposes questionable counterfactual backtracking. He also argues that CCA proponents can justifiably reject the condition by invoking so-called plural harm and benefit. In this reply, we argue (...) that Feit’s lines of criticism are both unsuccessful. (shrink)

The E-Z Reader model (Reichle et al. 1998; 1999) provides a theoretical framework for understanding how word identification, visual processing, attention, and oculomotor control jointly determine when and where the eyes move during reading. In this article, we first review what is known about eye movements during reading. Then we provide an updated version of the model (E-Z Reader 7) and describe how it accounts for basic findings about eye movement control in reading. We then review several alternative models of (...) eye movement control in reading, discussing both their core assumptions and their theoretical scope. On the basis of this discussion, we conclude that E-Z Reader provides the most comprehensive account of eye movement control during reading. Finally, we provide a brief overview of what is known about the neural systems that support the various components of reading, and suggest how the cognitive constructs of our model might map onto this neural architecture. Key Words: attention; eye-movement control; E-Z Reader; fixations; lexical access; models; reading; regressions; saccades. (shrink)

For the purpose of contributing to a clarification of the term “process”, different kinds of musical processes are investigated: A rule-determined phase shifting process in Steve Reich's Piano Phase (1966), a model for an indeterminate composition process in John Cage's Variations II (1961), a number of evolution processes in György Ligeti's In zart fliessender Bewegung (1976), and a generative process of fractal nature in Per Nørgård's Second Symphony (1970). In conclusion I propose that six process categories should be included in (...) a typology of processes: Rule-determined, goal-directed and indeterminate transformation processes, and rule-determined, goal-directed and indeterminate generative processes. (shrink)

John Broome has argued that alleged cases of value incomparability are really examples of vagueness in the betterness relation. The main premiss of his argument is ‘the collapsing principle’. I argue that this principle is dubious, and that Broome's argument is therefore unconvincing. Correspondence:c1 Erik[email protected].

Logical pluralism is the view that there is more than one correct logic. This very general characterization gives rise to a whole family of positions. I argue that not all of them are stable. The main argument in the paper is inspired by considerations known as the “collapse problem”, and it aims at the most popular form of logical pluralism advocated by JC Beall and Greg Restall. I argue that there is a more general argument available that challenges all variants (...) of logical pluralism that meet the following three conditions: that there are at least two correct logical systems characterized in terms of different consequence relations, that there is some sort of rivalry among the correct logics, and that logical consequence is normative. The hypothesis I argue for amounts to conditional claim: If a position satisfies all these conditions, then that position is unstable in the sense that it collapses into competing positions. (shrink)

Every physical theory has two different forms of mathematical equations to represent its target systems: the dynamical and the kinematical. Kinematical constraints are differentiated from equations of motion by the fact that their particular form is fixed once and for all, irrespective of the interactions the system enters into. By contrast, the particular form of a system's equations of motion depends essentially on the particular interaction the system enters into. All contemporary accounts of the structure and semantics of physical theory (...) treat dynamics, i.e., the equations of motion, as the most important feature of a theory for the purposes of its philosophical analysis. I argue to the contrary that it is the kinematical constraints that determine the structure and empirical content of a physical theory in the most important ways: they function as necessary preconditions for the appropriate application of the theory; they differentiate types of physical systems; they are necessary for the equations of motion to be well posed or even just cogent; and they guide the experimentalist in the design of tools for measurement and observation. It is thus satisfaction of the kinematical constraints that renders meaning to those terms representing a system's physical quantities in the first place, even before one can ask whether or not the system satisfies the theory's equations of motion. (shrink)

In a discussion of Parfit's Drops of Water case, Zach Barnett has recently proposed a novel argument against “No Small Improvement”; that is, the claim that a single drop of water cannot affect the magnitude of a thirsty person's suffering. We first show that Barnett's argument can be significantly strengthened, and also that the fundamental idea behind it yields a straightforward argument for the transitivity of equal suffering. We then suggest that defenders of No Small Improvement could reject a Pareto (...) principle that is presupposed in Barnett's argument and our developments of it. However, this does not save No Small Improvement, since there is a convincing argument against this claim that does not presuppose the Pareto principle. (shrink)

In this article we move beyond the problematic distinction between ‘higher’ and ‘lower’ cognition by accounting for so-called ‘higher’ cognitive capacities in terms of skillful activities in practices, and in terms of the affordances exploited in those practices. Through ethnographic research we aim to further develop the new notion of skilled intentionality by turning to the phenomenon of the tendency towards an optimal grip on a situation in real-life situations in the field of architecture. Tending towards an optimal grip is (...) an inherently affective and dynamic phenomenon. It has been under explored in philosophy, despite its central place in Merleau-Ponty’s phenomenology. When the architects experience discontent, attention is typically solicited by the affordances through which possible ways of continuing the improvement of the design can be explored. In various ways this tension or disequilibrium - fueling a tendency towards an optimal grip - is encountered in the complex architectural design practices that we observed. Based on our field material we distinguish between: a) grip in visual perception, b) grip on the design, and c) grip on ‘how to design’. The move towards an optimal grip takes shape by joining forces with a landscape of affordances. This landscape includes, for instance, affordances for grasping a cup of coffee, affordances provided by a cardboard model to improve it, as well as for engaging with a person who is not physically present. Because they are skilled, the architects can be responsive to these different affordances in similar ways. Furthermore, in practice the architects are responsive to multiple affordances simultaneously. Through our analysis of the tendency towards an optimal grip we show that our surroundings contribute to skillful action and cognition in a far more complex way than is currently acknowledged in philosophy and cognitive science. (shrink)

In this paper, we put forward two novel arguments against the counterfactual comparative account (CCA) of harm and benefit. In both arguments, the central theme is that CCA conflicts with plausible judgements about benefit and prudence.

Although black holes are objects of central importance across many fields of physics, there is no agreed upon definition for them, a fact that does not seem to be widely recognized. Physicists in different fields conceive of and reason about them in radi- cally different, and often conflicting, ways. All those ways, however, seem sound in the relevant contexts. After examining and comparing many of the definitions used in practice, I consider the problems that the lack of a universally accepted (...) definition leads to, and discuss whether one is in fact needed for progress in the physics of black holes. I conclude that, within reasonable bounds, the profusion of different definitions is in fact a virtue, making the investigation of black holes possible and fruitful in all the many different kinds of problems about them that physicists consider, although one must take care in trying to translate results between fields. (shrink)

A growing literature documents the existence of individuals who make a living by participating in phase I clinical trials for money. Several scholars have noted that the concerns about risks, consent, and exploitation raised by this phenomenon apply to many (other) jobs, too, and therefore proposed improving subject protections by regulating phase I trial participation as work. This article contributes to the debate over this proposal by exploring a largely neglected worry. Unlike most (other) workers, subjects are not paid to (...) produce or achieve anything but to have things done to them. I argue that this passivity is problematic for reasons of distributive justice. Specifically, it fails to enable subjects to realize what Gheaus and Herzog call “the goods of work”—a failure not offset by adequate opportunities to realize these goods outside of the research context. I also consider whether granting subjects worker-type protections would accommodate this concern. (shrink)

The differences between critics and proponents of enhancement technologies are easily overblown. Both sides of this debate share the moral ideal of being “authentic” to oneself. They differ in how they prefer to understand authenticity, but even this difference is not as stark as it sometimes seems.

A popular view of harming is the causal account (CA), on which harming is causing harm. CA has several attractive features. In particular, it appears well equipped to deal with the most important problems for its main competitor, the counterfactual comparative account (CCA). However, we argue that, despite its advantages, CA is ultimately an unacceptable theory of harming. Indeed, while CA avoids several counterexamples to CCA, it is vulnerable to close variants of some of the problems that beset CCA.

Within philosophy there is not yet an integrative account of unreflective skillful action. As a starting point, contributions would be required from philosophers from both the analytic and continental traditions. Starting from the McDowell-Dreyfus debate, shared Aristotelian-Wittgensteinian common ground is identified. McDowell and Dreyfus agree about the importance of embodied skills, situation-specific discernment and responsiveness to relevant affordances. This sheds light on the embodied and situated nature of adequate unreflective action and provides a starting point for the development of an (...) account that does justice to insights from both philosophical traditions. (shrink)

I explain the difficulty of making various concepts of and relating to probability precise, rigorous and physically significant when attempting to apply them in reasoning about objects living in infinite-dimensional spaces, working through many examples from cosmology. I focus on the relation of topological to measure-theoretic notions of and relating to probability, how they diverge in unpleasant ways in the infinite-dimensional case, and are even difficult to work with on their own. Even in cases where an appropriate family of spacetimes (...) is finite-dimensional, and so admits a measure of the relevant sort, however, it is always the case that the family is not a compact topological space, and so does not admit a physically significant, well behaved probability measure. Problems of a different but still deeply troubling sort plague arguments about likelihood in that context, which I also discuss. I conclude that most standard forms of argument used in cosmology to estimate the likelihood of the occurrence of various properties or behaviors of spacetimes have serious mathematical, physical and conceptual problems. (shrink)

: The differences between critics and proponents of enhancement technologies are easily overblown. Both sides of this debate share the moral ideal of being "authentic" to oneself. They differ in how they prefer to understand authenticity, but even this difference is not as stark as it sometimes seems.

I examine the debate between substantivalists and relationalists about the ontological character of spacetime and conclude it is not well posed. I argue that the hole argument does not bear on the debate, because it provides no clear criterion to distinguish the positions. I propose two such precise criteria and construct separate arguments based on each to yield contrary conclusions, one supportive of something like relationalism and the other of something like substantivalism. The lesson is that one must fix an (...) investigative context in order to make such criteria precise, but different investigative contexts yield inconsistent results. I examine questions of existence about spacetime structures other than the spacetime manifold itself to argue that it is more fruitful to focus on pragmatic issues of physicality, a notion that lends itself to several different explications, all of philosophical interest, none privileged a priori over any of the others. I conclude by suggesting an extension of the lessons of my arguments to the broader debate between realists and instrumentalists. 1 Introduction2 The Hole Argument3 Limits of Spacetimes4 Pointless Constructions5 The Debate between Substantivalists and Relationalists6 Existence and Physicality: An Embarassment of Spacetime Structures7 Valedictory Remarks on Realism and Instrumentalism, and the Structure of Our Knowledge of Physics. (shrink)