Current theories of breast cancer progression have been greatly influenced by the development and refinement of mouse transgenic and gene targeting technologies. Early transgenic mouse models confirmed the involvement of oncogenes, previously implicated in human breast cancer, by establishing a causal relationship between overexpression or activation of these genes and mammary tumorigenesis. More recently, the importance of genes located at sites of loss of heterozygosity in human breast cancer have been examined in mice by their targeted disruption via homologous recombination. (...) The union of these two approaches allows the generation of complex animal models that more accurately reflect the multistep nature of human breast cancer. This review will examine how the study of transgenic mice has increased our understanding of the molecular events responsible for oncogenic transformation of the mammary gland. BioEssays 22:554–563, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

Adherens (AJ) and tight junctions (TJ) maintain cell‐cell adhesions and cellular polarity in normal tissues. Afadin, a multi‐domain scaffold protein, is commonly found in both adherens and tight junctions, where it plays both structural and signal‐modulating roles. Afadin is a complex modulator of cellular processes implicated in cancer progression, including signal transduction, migration, invasion, and apoptosis. In keeping with the complexities associated with the roles of adherens and tight junctions in cancer, afadin exhibits both tumor suppressive and pro‐metastatic functions. In (...) this review, we will explore the dichotomous roles that afadin plays during cancer progression. (shrink)

Although the relationship of part to whole is one of the most fundamental there is, this is the first full-length study of this key concept. Showing that mereology, or the formal theory of part and whole, is essential to ontology, Simons surveys and critiques previous theories--especially the standard extensional view--and proposes a new account that encompasses both temporal and modal considerations. Simons's revised theory not only allows him to offer fresh solutions to long-standing problems, but also has far-reaching consequences for (...) our understanding of a host of classical philosophical concepts. (shrink)

The relationship of part to whole is one of the most fundamental there is; this is the first and only full-length study of this concept. This book shows that mereology, the formal theory of part and whole, is essential to ontology. Peter Simons surveys and criticizes previous theories, especially the standard extensional view, and proposes a more adequate account which encompasses both temporal and modal considerations in detail. 'Parts could easily be the standard book on mereology for the next (...) twenty or thirty years.' Timothy Williamson, Grazer Philosophische Studien. (shrink)

A way of reading the Tractatus has been proposed which, according to its advocates, is importantly novel and essentially distinct from anything to be found in the work of such previously influential students of the book as Anscombe, Stenius, Hacker or Pears. The point of difference is differently described, but the currently most used description seems to be Goldfarb’s term ‘resolution’ – hence one speaks of ‘the resolute reading’. I’ll shortly ask what resolution is. For now, it is enough that (...) it aims to give full weight to the penultimate section of the Tractatus in which Wittgenstein declares his propositions to be nonsense, where giving full weight to that declaration involves not hearing it as allowing that those ‘nonsensical’ propositions might have another kind of ‘sense’. In that same section Wittgenstein explains that these nonsense propositions, while devoid of meaning, have a use: to make the kind of use of them that their author intends – and so to understand him – requires recognizing that they are nonsense; and through that recognition one ‘surmounts’ these propositions, and is led ‘to see the world aright’. So there is a point to all this nonsense. What point? (shrink)

The relationship of part to whole is one of the most fundamental there is, yet until now there has been no full-length study of this concept. This book shows that mereology, the formal theory of part and whole, is essential to ontology. Peter Simons surveys and criticizes previous theories, especially the standard extensional view, and proposes a more adequate account which encompasses both temporal and modal considerations in detail. This has far-reaching consequences for our understanding of such classical philosophical (...) concepts as identity, individual, class, substance and accident, matter, form, essence, dependence, and integral whole. It also enables the author to offer new solutions to long-standing problems surrounding these concepts, such as the Ship of Theseus Problem and the issue of mereological essentialism. The author shows by his use of formal techniques that classical philosophical problems are amenable to rigorous treatment, and the book represents a synthesis of issues and methods from the analytical tradition and from the older continental realist tradition of Brentano and the early Husserl. (shrink)

In clinical ethics, there remains a great deal of uncertainty regarding the appropriateness of attempting cardiopulmonary resuscitation (CPR) for certain patients. Although the issue continues to receive ample attention and various frameworks have been proposed for navigating such cases, most discussions draw heavily on the notion of harm as a central consideration. In the following, I use emerging philosophical literature on the notion of harm to argue that the ambiguities and disagreement about harm create important and oft-overlooked challenges for the (...) ethics of CPR. I begin by elucidating the standard account of harm, called the Counterfactual Comparative Account (CCA). I then show that three challenges to the CCA—preemptive harms, the harm of death, and non-experiential harms—are particularly salient when assessing potential harms for candidates of CPR and likely impact-related decision-making and communication. I extend this argument to explore how the ambiguities of harm might extend to other realms of clinical decision-making, such as the use and limitations of life-sustaining treatments. To address these challenges, I propose two strategies for identifying and minimizing the impact of such uncertainty: first, clinicians and ethicists ought to promote pluralistic conversations that account for different understandings of harm; second, they ought to invoke harm-independent considerations when discussing the ethics of CPR in order to reflect the nuances of such conversations. These strategies, coupled with a richer philosophical understanding of harm, promise to help clinicians and ethicists navigate the prevalent and difficult cases involving patient resuscitation and many other harm-based decisions in the clinical setting. (shrink)

Traditional views of rationality posit general-purpose decision mechanisms based on logic or optimization. The study of ecological rationality focuses on uncovering the “adaptive toolbox” of domain-specific simple heuristics that real, computationally bounded minds employ, and explaining how these heuristics produce accurate decisions by exploiting the structures of information in the environments in which they are applied. Knowing when and how people use particular heuristics can facilitate the shaping of environments to engender better decisions.

A vital step to successfully orienting Deleuze with biosemiotics (and theories of biological complexity overall) is to discover a coherent scientific throughline in his work that also accounts for the aesthetic/creative dimension of his philosophy. This requires the heterodox move (from a Deleuzean point of view) of giving priority to the organism. I argue that Deleuze’s treatment of the organism does more than signal a superficial relation to biological complexity theory that, as a result of his nuanced take on the (...) matter, undermines the value of the organic body to his system. Instead, we can recognize a working theory of autopoiesis in the early Deleuze that scaffolds as well as substantiates his later ethological and biosemiotic observations and reveals a definite, albeit minimal, notion of subjectivity in his work. Most importantly, reorienting his logic of sense as a logic of sense-making, or the context-dependent signification between system and environment (Thompson, 2007), allows us to begin the work of mining a scientific throughline in Deleuze’s work akin to biological complexity theory that is of value to both Deleuze studies and biosemiotics. (shrink)

For most of the history of metaphysics, the subject has been dominated by the concept of substance. There is an everyday commonsense notion of substance which is perfectly harmless and which I shall defend against attempts to remove it or revise it away. But I deny that substance has to be construed as a primitive even in everyday terms. Borrowing Strawson’s distinction between descriptive and revisionary metaphysics, I press the legitimate claims of revisionary metaphysics and argue that there is no (...) place for a fundamental concept of substance within it, although aspects of the concept are likely to find their place therein. (shrink)

This book with an introduction by Witold Marciszewski, views the history of philosophy and logic from 1837 to 1939 from the perspective of the cradle of modern exact philosophy - Central Europe. In a series of case studies, it illuminates the developments in this region, most notably in Austria and Poland, examining thinkers such as Bolzano, Brentano, Meinong, Husserl, Twardowski, Lesniewski, and Tarski, as well as the logicians like Frege and Russell with whom they bore a close resemblance. The book (...) challenges established views about the history of philosophy and logic in Europe, and shows the vitality of the Central European tradition. (shrink)

While theories of rationality and decision making typically adopt either a single-powertool perspective or a bag-of-tricks mentality, the research program of ecological rationality bridges these with a theoretically-driven account of when different heuristic decision mechanisms will work well. Here we described two ways to study how heuristics match their ecological setting: The bottom-up approach starts with psychologically plausible building blocks that are combined to create simple heuristics that fit specific environments. The top-down approach starts from the statistical problem facing the (...) organism and a set of principles, such as the bias– variance tradeoff, that can explain when and why heuristics work in uncertain environments, and then shows how effective heuristics can be built by biasing and simplifying more complex models. We conclude with challenges these approaches face in developing a psychologically realistic perspective on human rationality. (shrink)

This critical review of Soames's history of analytic philosophy evaluates Soames's enterprise by reference to the degree to which it achieves his goals of (i) providing an overview of analytic philosophy 1900-75, (ii) explaining what the most important analytic philosophers thought, (iii) selecting some of the most important works of each philosopher for discussion, and (iv) properly evaluating the developments of the period. On all counts Soames's history is found sorely wanting. The overview it offers is riddled with distortion, its (...) explanations are frequently mistaken and uncomprehending, its selection is demonstrably inadequate and its evaluations ill-informed and ill-judged. (shrink)

Moving beyond the traditional, and unproductive, rivalry between the fields of motivation and cognition, this book integrates the two domains to shed new light ...

In the fall of 1991, voters in Washington state were asked to consider a public initiative that sought to legalize physician-assisted death: Initiative 119. Drafted by Washington Citizens for Death with Dignity, the initiative was intended to amend the existing state natural death act in several ways:1) expand the definition of “terminal condition” to include patients in irrevers ible coma or persistent vegetative state;2) specifically name “artificial nutrition and hydration” as life-sustaining medical procedures that could be refused or withdrawn;3) legally (...) allow mentally competent patients with certifiably terminal conditions to request and receive “aid-in-dying” from their physician as a medical service.The first two proposed amendments were widely acknowledged as timely and appropriate; a coalition of medical, religious, and community organizations had been actively working on such additions for several years. It was the proposal to legalize “aid-in-dying,” however, that represented a radical shift in the conduct of physicians towards their patients and a dramatic shift in social policy. (shrink)

SummaryLeśniewski presented his logical systems in a way which conformed to his nominalism, so the question arises whether Leśniewski's logic can be given a natural formal semantics which, unlike current versions, avoids commitment to abstract entities. Building on hints in Wittgenstein's Tractatus, I develop the idea of a way of meaning which is the basis for what I call combinatorial semantics. I then consider whether this commits us to abstract objects or an intensional metalogic.

SummaryLeśniewski presented his logical systems in a way which conformed to his nominalism, so the question arises whether Leśniewski's logic can be given a natural formal semantics which, unlike current versions, avoids commitment to abstract entities. Building on hints in Wittgenstein's Tractatus, I develop the idea of a way of meaning which is the basis for what I call combinatorial semantics. I then consider whether this commits us to abstract objects or an intensional metalogic.

This paper is a review of work on Newman's objection to epistemic structural realism (ESR). In Section 2, a brief statement of ESR is provided. In Section 3, Newman's objection and its recent variants are outlined. In Section 4, two responses that argue that the objection can be evaded by abandoning the Ramsey-sentence approach to ESR are considered. In Section 5, three responses that have been put forward specifically to rescue the Ramsey-sentence approach to ESR from the modern versions of (...) the objection are discussed. Finally, in Section 6, three responses are considered that are neutral with respect to one's approach to ESR and all argue (in different ways) that the objection can be evaded by introducing the notion that some relations/structures are privileged over others. It is concluded that none of these suggestions is an adequate response to Newman's objection, which therefore remains a serious problem for ESRists. Introduction Epistemic Structural Realism 2.1 Ramsey-sentences and ESR 2.2 WESR and SESR The Objection 3.1 Newman's version 3.2 Demopoulos and Friedman's and Ketland's versions Replies that Abandon the Ramsey-Sentence Approach to ESR 4.1 Redhead's reply 4.2 French and Ladyman's reply Replies Designed to Rescue the Ramsey-Sentence Approach 5.1 Zahar's reply 5.2 Cruse's reply 5.3 Melia and Saatsi's reply Replies that Argue that Some Structures/Relations are Privileged 6.1 A Carnapian reply 6.2 Votsis' reply 6.3 The Merrill/Lewis/Psillos reply Summary CiteULike Connotea Del.icio.us What's this? (shrink)

To understand the possible forms of extraterrestrial intelligence, we need not only astrobiology theories about how life evolves given habitable planets, but also evolutionary psychology theories about how intelligence emerges given life. Wherever intelligent organisms evolve, they are likely to face similar behavioral challenges in their physical and social worlds. The cognitive mechanisms that arise to meet these challenges may then be copied, repurposed, and shaped by further evolutionary selection to deal with more abstract, higher-level cognitive tasks such as conceptual (...) reasoning, symbolic communication, and technological innovation, while retaining traces of the earlier adaptations for solving physical and social problems. These traces of evolutionary pathways may be leveraged to gain insight into the likely cognitive processes of ETIs. We demonstrate such analysis in the domain of search strategies and show its application in the domains of emotional aversions and social/sexual signaling. Knowing the likely evolutionary pathways to intelligence will help us to better search for and process any alien signals from the search for ETIs and to assess the likely benefits, costs, and risks of humans actively messaging ETIs. (shrink)

How can anyone be rational in a world where knowledge is limited, time is pressing, and deep thought is often an unattainable luxury? Traditional models of unbounded rationality and optimization in cognitive science, economics, and animal behavior have tended to view decision-makers as possessing supernatural powers of reason, limitless knowledge, and endless time. But understanding decisions in the real world requires a more psychologically plausible notion of bounded rationality. In Simple heuristics that make us smart (Gigerenzer et al. 1999), we (...) explore fast and frugal heuristics – simple rules in the mind's adaptive toolbox for making decisions with realistic mental resources. These heuristics can enable both living organisms and artificial systems to make smart choices quickly and with a minimum of information by exploiting the way that information is structured in particular environments. In this précis, we show how simple building blocks that control information search, stop search, and make decisions can be put together to form classes of heuristics, including: ignorance-based and one-reason decision making for choice, elimination models for categorization, and satisficing heuristics for sequential search. These simple heuristics perform comparably to more complex algorithms, particularly when generalizing to new data – that is, simplicity leads to robustness. We present evidence regarding when people use simple heuristics and describe the challenges to be addressed by this research program. Key Words: adaptive toolbox; bounded rationality; decision making; elimination models; environment structure; heuristics; ignorance-based reasoning; limited information search; robustness; satisficing; simplicity. (shrink)

In this paper we articulate and diagnose a previously unrecognized problem for theories of entitlement, what we call the Claims Conundrum. It applies to all entitlements that are originally generated by some claim-generating action, such as laboring, promising, or contract-signing. The Conundrum is spurred by the very plausible thought that a later claim to the object to which one is entitled is a function of whether that original claim-generating action is attributable to one. This is further assumed to depend on (...) one’s being identical to the person who performed the claim-generating action. But the right theory of personal identity for grounding these later claims proves quite elusive. In demonstrating both the Claims Conundrum and diagnosing its source, we begin with its instantiation in John Locke’s theories of personal identity and initial acquisition, and then we gradually expand its net to include both Lockean and non-Lockean theories of both, moving ultimately to show that this is a problem for most entitlements generally. We then diagnose the source of the trouble, showing that a basic assumption about the link between attributability and identity that most people take to be obvious is in fact false, clearing a path for future investigation into this overlooked but serious problem’s resolution. (shrink)

This paper assesses those features of Lesniewski's Ontology which make it difficult to understand for logicians accustomed to more orthodox systems of logic. It is seen that certain general features of presentation and content can, by selective acceptance or modification, be accommodated with a fairly orthodox viewpoint. The chief difficulty lies in the interpretation of Le?niewski's names, and the constant ???. Four interpretations are suggested in turn: Le?niewski's names as monadic predicates; as class terms; as common nouns; and as empty, (...) singular or plural terms. This last and least orthodox interpretation is argued to be the most suitable, but it is shown how it can be made to live in harmony with either the common noun or the class interpretation. (shrink)

These new studies of Wittgenstein's Tractatus represent a significant step beyond recent polemical debate.

Introduction Max Horkheimer was born on February in Stuttgart. By the time he died, on 7 July in Nuremberg, he had played a decisive role in launching and ...

Introduction By the late fifth century BCE Panini had composed the Astadhyayi, consisting of nearly 4000 rules giving a precise and fairly complete ...

Wittgenstein presents in the Tractatus a variable purporting to capture the general form of proposition. One understanding of what Wittgenstein is doing there, an understanding in line with the ‘new’ reading of his work championed by Diamond, Conant and others, sees it as a deflationary or even an implosive move—a move by which a concept sometimes put by philosophers to distinctively metaphysical use is replaced, in a perspicuous notation, by an innocent device of generalization, thereby dispersing the clouds of philosophy (...) that formerly surrounded the concept. By asking how Wittgenstein supposed his variable to work, and what work he imagined it was fit for, the paper questions the adequacy of that understanding. (shrink)

This paper explains the absence of the problem of other minds in ancient philosophy and links its rise in early modern philosophy with the distinction between primary and secondary qualities and the consequent veil of ideas. The futile struggles of early modern philosophers with the problems is delineated. So too are the incoherent theories of modern neuroscientists and psychologists. The sources of the manifold confusions are pinned down to use and misuse of the concept of mind, to misunderstandings about the (...) nature of the human ability to say how things are subjectively with oneself, to misconstruals of the nature of introspection and self-knowledge, and to the misguided picture of the “inner” and the “outer”. Philosophical misunderstandings about knowledge of other minds has masked the genuine limitations on our knowledge and understanding of our fellow human beings. Some of these rest on ignorance, others on the constitutional indeterminacy of the mental. (shrink)

It is sometimes argued that Wittgenstein's conception of grammar and the role he allocated to grammar (in his sense of the term) in philosophy changed between the Big Typescript and the Philosophical Investigations. It is also held that some of the grammatical propositions Wittgenstein asserted prior to his writing of the Philosophical Investigations are theses, doctrines, opinions or dogmatism, which he abandoned by 1936/37. The purpose of this paper is to show these claims to be misunderstandings and misinterpretations. On all (...) important matters, his conception of grammar and of grammatical investigations, of grammatical statements or propositions and of grammatical clarification did not change between the Big Typescript and the Investigations. Grammatical propositions (e.g. the meaning of a word is its use; a sample in an ostensive definition belongs to the means of representation; belief is not a mental state) are no more theses, doctrines or opinions than is “a bachelor is an unmarried man.” Nor are they in any way dogmatic. (shrink)

The 1989 collapse of trade relations with the former socialist bloc plunged Cuba into an economic and food crisis. Cuban farmers, scientists, and planners have responded with alternative agricultural technology to make up for imported food and Green Revolution inputs that are no longer available. A review of Cuban experience to date with biological pest control practices shows that, on the one hand, significant progress has been made that may serve as a model for other countries, while, on the other (...) hand, there still remains a long way to go if Cuba is to create a truly sustainable agriculture. It is essential that we understand the Cuban case if we are to be concerned about ethical issues in biological control. The apparent ability of Cuba to overcome a food crisis without significant use of pesticides stretches our concept of the possible. It thus helps refute the most common argument – that we couldn't “feed the hungry” without pesticides – against taking the “ethical” position in real-world pest management policy debates. (shrink)

Within the context of sports, the term 'miracle' is regularly associated with game-winning shots, holes-in-one, completed Hail Marys and other improbable outcomes. These conceptions of miracles largely focus on the success of specific sport actions at specific times when such success is deemed highly improbable. While prominent in the popular sports literature, most scholars agree that this perspective on miracles is very simple and highly unsophisticated. Events portrayed as simply 'beating the odds' would represent pale versions of miracles at best. (...) Some conceptions of miracles, however, include characteristics that reach beyond improbable outcomes. From more sophisticated perspectives, miracles are often viewed as divine action guiding the ordinary course of human experience. To be considered 'miraculous', improbable outcomes in sport would need to be perceived as interactions between the supernatural (God or other divine entity) and the natural (physical world). In addition, miraculous occurrences would have to be a part of a divine master-plan. Scholars argue that without such connections, miracles would yield no direction or meaning to the evolving world. The differences between these two perceptions raises several questions: Why do some view these extraordinary athletic performances from spiritually sophisticated perspectives while others have not the 'ears to hear' or the 'eyes to see' the divine possibilities in these experiences? Why are common uses and perceptions of miracles in sport simplistic and thin? What is a sophisticated view of miracles? What human abilities and processes are needed for one to achieve a sophisticated perspective? And, finally, what is the purpose of the true or sophisticated miracle in sport? In this paper, I will examine the notion of the miracle in sport. At its core, this paper describes how an athlete intellectually and spiritually moves from the unsophisticated to the sophisticated conception of a miracle. Through the writings of James, Lewis, Polanyi and others, I will show how human intellectual operations allow one to have 'ears to hear' and 'eyes to see' the spiritually miraculous in sport. I will begin by presenting an unsophisticated version of miracles in sport. After critically examining several types of miracles, I will present a more sophisticated definition. I will then explore the human processes necessary to view miraculous experiences in sport as interactions between the natural and the supernatural rather than interpreting these experiences simply as improbable outcomes. Finally, I will show how miracles present opportunities for spiritual conversion and have a use and place in the divine's master plan. (shrink)