In the mid to late 1980s a debate arose over the moral and legal authority of advance medical directives. At the center of this debate were two point-counterpoint law journal articles by Rebecca Dresser and Nancy Rhoden. What appeared to have the makings of an ongoing critical dialogue ended with the untimely death of Nancy Rhoden. Rebecca Dresser, however, has continued her challenge of advance directives in numerous publications, most recently in a critique of Ronald Dworkin's Life's Dominion. Like Rhoden, (...) Dworkin has been a staunch advocate of advance directives as an exercise of what has come to be referred to as prospective or precedent autonomy. In this paper I will consider a number of the issues that Dresser has repeatedly raised about the infirmities of advance directives, and suggest that it is from an understanding of and appreciation for the narrative dimension of the life of a person that advanced directives draw one of their most powerful justifications. (shrink)

In the mid to late 1980s a debate arose over the moral and legal authority of advance medical directives. At the center of this debate were two point-counterpoint law journal articles by Rebecca Dresser and Nancy Rhoden. What appeared to have the makings of an ongoing critical dialogue ended with the untimely death of Nancy Rhoden. Rebecca Dresser, however, has continued her challenge of advance directives in numerous publications, most recently in a critique of Ronald Dworkin's Life's Dominion. Like Rhoden, (...) Dworkin has been a staunch advocate of advance directives as an exercise of what has come to be referred to as prospective or precedent autonomy. In this paper I will consider a number of the issues that Dresser has repeatedly raised about the infirmities of advance directives, and suggest that it is from an understanding of and appreciation for the narrative dimension of the life of a person that advanced directives draw one of their most powerful justifications. (shrink)

The disciplinary boundaries of social studies on the body, health and illness are widely dispersed and no less so when inquiring into the subject of media representations. So much research from a range of disciplines seeps into this area that it can be difficult to draw meaningful boundaries around it. Such issues as disability, eating disorders, sexually transmitted diseases, mental disorder, cosmetic surgery, drug cultures and much more, all fall within this area of concern. Moreover, debates in other areas of (...) media inquiry are often explained through a health-related lens. For instance, discussions about computer games are repeatedly subjected to health-related discourses over whether their use leads to an increasingly sedentary, young population – a claim that is not borne out in the literature. The breadth of this subject prompts us to consider how to limit the study of media representations of health, illness and the body, when each and every action we undertake can be interpreted through this conceptual lens. (shrink)

An alternative antigen receptor, named the variable lymphocyte receptor (VLR), was first identified in lampreys in 2004. Since then, the mechanism of VLR diversification via somatic gene assembly and the function of VLR‐expressing lymphocytes have been the subject of much research. VLRs comprise leucine‐rich repeat (LRR) motifs and are found only in the most phylogenetically distant vertebrates from mammals, lampreys, and hagfish. Previous reports showed that VLRA and VLRB are reciprocally expressed by lymphocytes that resemble T‐ and B cells; (...) however, more recent reports show that another VLR, VLRC, is expressed on a third lymphocyte lineage, which may be equivalent to γδ T cells. The existence of three major lymphocyte lineages – one B‐cell‐like and two T‐cell‐like – and their development in lampreys, parallels the mammalian adaptive immune system. This suggests that these three cell lineages were present in the common vertebrate ancestor approximately 500 million years ago. (shrink)

The acidic (leucine‐rich) nuclear phosphoprotein 32 kDa (ANP32) family is composed of small, evolutionarily conserved proteins characterized by an N‐terminal leucine‐rich repeat domain and a C‐terminal low‐complexity acidic region. The mammalian family members (ANP32A, ANP32B, and ANP32E) are ascribed physiologically diverse functions including chromatin modification and remodelling, apoptotic caspase modulation, protein phosphatase inhibition, as well as regulation of intracellular transport. In addition to reviewing the widespread literature on the topic, we present a concept of the ANP32s as having (...) a whip‐like structure. We also present hypotheses that ANP32C and other intronless sequences should not currently be considered bona fide family members, that their disparate necessity in development may be due to compensatory mechanisms, that their contrasting roles in cancer are likely context‐dependent, along with an underlying hypothesis that ANP32s represent an important node of physiological regulation by virtue of their diverse biochemical activities. (shrink)

Current models of insulin binding to the insulin receptor (IR) propose (i) that there are two binding sites on the surface of insulin which engage with two binding sites on the receptor and (ii) that ligand binding involves structural changes in both the ligand and the receptor. Many of the features of insulin binding to its receptor, namely B‐chain helix interactions with the leucine‐rich repeat domain and A‐chain residue interactions with peptide loops from another part of the receptor, are (...) also seen in models of relaxin and insulin‐like peptide 3 binding to their receptors. We show that these principles can likely be extended to the group of mimetic peptides described by Schäffer and coworkers, which are reported to have no sequence identity with insulin. This review summarizes our current understanding of ligand‐induced activation of the IR and highlights the key issues that remain to be addressed. (shrink)

Steroid hormones are signaling molecules important for normal growth, development and differentiation of multicellular organisms. Brassinosteroids (BRs) are a class of polyhydroxylated steroids that are necessary for plant development. Molecular genetic studies in Arabidopsis thaliana have led to the cloning and characterization of the BR receptor, BRI1, which is a transmembrane receptor serine/threonine kinase. The extracellular domain of BRI1, which is composed mainly of leucine‐rich repeats, can confer BR responsivity to heterologous cells and is required for BR binding. (...) Although downstream components of BR action are mostly unknown, multiple genes whose expression are regulated by BRs have been identified and suggest mechanisms by which BRs affect cell elongation and division. BioEssays 23:1028–1036, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

All surviving jawed vertebrate representatives achieve diversity in immunoglobulin‐based B and T cell receptors for antigen recognition through recombinatorial rearrangement of V(D)J segments. However, the extant jawless vertebrates, lampreys and hagfish, instead generate three types of variable lymphocyte receptors (VLRs) through a template‐mediated combinatorial assembly of different leucine‐rich repeat (LRR) sequences. The clonally diverse VLRB receptors are expressed by B‐like lymphocytes, while the VLRA and VLRC receptors are expressed by lymphocyte lineages that resemble αβ and γδ T lymphocytes, respectively. (...) These findings suggest that three basic types of lymphocytes, one B‐like and two T‐like, are an essential feature of vertebrate adaptive immunity. Around 500 million years ago, a common ancestor of jawed and jawless vertebrates evolved a genetic program for the development of prototypic lymphoid cells as a foundation for an adaptive immune system. This acquisition preceded the convergent evolution of alternative types of clonally diverse receptors for antigens in all vertebrates, as reviewed in this article. (shrink)

Parkinson's disease (PD) is generally sporadic but a number of genetic diseases have parkinsonism as a clinical feature. Two dominant genes, α‐synuclein (SNCA) and leucine‐rich repeat kinase 2 (LRRK2), are important for understanding inherited and sporadic PD. SNCA is a major component of pathologic inclusions termed Lewy bodies found in PD. LRRK2 is found in a significant proportion of PD cases. These two proteins may be linked as most LRRK2 PD cases have SNCA‐positive Lewy bodies. Mutations in both proteins (...) are associated with toxic effects in model systems although mechanisms are unclear. LRRK2 is an intracellular signaling protein possessing both GTPase and kinase activities that may contribute to pathogenicity. A third protein, tau, is implicated as a risk factor for PD. We discuss the potential relationship between these genes and suggest a model for PD pathogenesis where LRRK2 is upstream of pathogenic effects through SNCA, tau, or both proteins. (shrink)

Intracellular NLR (Nucleotide‐binding domain and Leucine‐rich Repeat‐containing) receptors are sensitive monitors that detect pathogen invasion of both plant and animal cells. NLRs confer recognition of diverse molecules associated with pathogen invasion. NLRs must exhibit strict intramolecular controls to avoid harmful ectopic activation in the absence of pathogens. Recent discoveries have elucidated the assembly and structure of oligomeric NLR signalling complexes in animals, and provided insights into how these complexes act as scaffolds for signal transduction. In plants, recent advances have (...) provided novel insights into signalling‐competent NLRs, and into the myriad strategies that diverse plant NLRs use to recognise pathogens. Here, we review recent insights into the NLR biology of both animals and plants. By assessing commonalities and differences between kingdoms, we are able to develop a more complete understanding of NLR function. (shrink)

The gelsolin gene family encodes a number of higher eukaryotic actin-binding proteins that are thought to function in the cytoplasm by severing, capping, nucleating or bundling actin filaments. Recent evidence, however, suggests that several members of the gelsolin family may have adopted unexpected nuclear functions including a role in regulating transcription. In particular, flightless I, supervillin and gelsolin itself have roles as coactivators for nuclear receptors, despite the fact that their divergence appears to predate the evolutionary appearance of nuclear receptors. (...) Flightless I has been shown to bind both actin and the actin-related BAF53a protein, which are subunits of SWI/SNF-like chromatin remodelling complexes. The primary sequences of some actin-related proteins such as BAF53a exhibit conservation of residues that, in actin itself, are known to interact with gelsolin-related proteins. In summary, there is a growing body of evidence supporting a biological role in the nucleus for actin, Arps and actin-binding proteins and, in particular, the gelsolin family of actin-binding proteins. (c) 2005 Wiley Periodicals, Inc. (shrink)

Trinucleotide repeat expansions are now a well‐established mutational mechanism in human genetic disease. An unstable CAG repeat is known to be responsible for three neurodegenerative disorders: Huntington's disease, spinal and bulbar musclar atrophy and spinocerebellar ataxia type 1. Similarities in the genetics of these diseases, the size of the repeat expansions and the position of the unstable repeat within the gene (when known) suggest a common basis to the observed phenotypes. The cloning of two regions at which chromosome breakage can (...) be induced (FRAXA and FRAXE) has in each case uncovered an unstable CG‐rich triplet repeat which becomes methylated when fully expanded. In addition to these two classes of mutation, the presence of an expanded CTG repeat in the 3′ untranslated region of a protein kinase causes myotonic dystrophy. The size of the respective expansions, repeat stability, mutational origins and possible mechanisms of action are discussed. (shrink)

The proportion of the genome encoding intrinsically unstructured proteins increases with the complexity of organisms, which demands specific mechanism(s) for generating novel genetic material of this sort. Here it is suggested that one such mechanism is the expansion of internal repeat regions, i.e., coding micro‐ and minisatellites. An analysis of 126 known unstructured sequences shows the preponderance of repeats: the percentage of proteins with tandemly repeated short segments is much higher in this class (39%) than earlier reported for all (...) Swiss‐Prot (14%), yeast (18%) or human (28%) proteins. Furthermore, prime examples, such as salivary proline‐rich proteins, titin, eukaryotic RNA polymerase II, the prion protein and several others, demonstrate that the repetitive segments carry fundamental function in these proteins. In addition, their repeat numbers show functionally significant interspecies variation and polymorphism, which underlines that these regions have been shaped by intense evolutionary activity. In all, the major point of this paper is that the genetic instability of repetitive regions combined with the structurally and functionally permissive nature of unstructured proteins has powered the extension and possible functional expansion of this newly recognized protein class. BioEssays 25:847–855, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Genomes of higher eukaryotes contain abundant non‐coding repeated sequences whose overall biological impact is unclear. They comprise two categories. The first consists of retrotransposon‐derived elements. These are three major families of retroelements (LINEs, SINEs and LTRs). SINEs are clustered in gene‐rich regions and are found in promoters of genes while LINEs are concentrated in gene‐poor regions and are depleted from promoters. The second class consists of non‐coding tandem repeats (satellite DNAs and TTAGGG arrays), which are associated with mammalian centromeres, (...) heterochromatin and telomeres. Terminal TTAGGG arrays are involved in telomere capping and satellite DNAs are located in heterochromatin, which is implicated in transcription silencing by gene repositioning (relocalization). It is unknown whether interstitial TTAGGG sequences, which are present in many vertebrates, have a function. Here, evidence will be presented that retroelements and TTAGGG arrays are involved in regulation of gene expression. Retroelements can provide binding sites for transcription factors and protect promoter CpG islands from repressive chromatin modifications, and may be also involved in nuclear compartmentalization of transcriptionally active and inactive domains. Interstitial telomere‐like sequences can form dynamically maintained three‐dimensional nuclear networks of transcriptionally inactive domains, which may be involved in transcription silencing like classic heterochromatin. BioEssays 30:338–348, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

The extent to which game play is experienced as engaging is an important criterion for the playability of video games. This study investigates how video games can be designed towards increased levels of experienced engagement over time. For this purpose, two experiments were conducted in which a total of 35 participants repeatedly played a video game. Results indicate that experienced engagement is based on the extent to which the game provides rich experiences as well as by the extent to which (...) the game provides a sense of control. In view of the influence of both game features and players’ expertise on the levels of experienced richness and control, it is concluded that game features should be modified over time to maintain optimal levels of engagement. (shrink)

Most people in the United States agree they want some income inequality but debate exactly how much is fair. High‐status people generally prefer more inequality than low‐status individuals. Here we examine how much preferences for inequality are (or are not) driven by self‐interest. Past work has generally investigated this idea in two ways: The first is by stratifying preferences by income, and the second is by randomly assigning financial status within lab‐constructed scenarios. In this paper, we develop a method that (...) combines both experimental control and the social experience of inequality—a simulated society experiment. Across two experiments (N = 138, observations = 690), participants voted on the distribution of rewards—first behind a veil of ignorance, and then when they were randomly assigned a status within a game of chance. Status varied repeatedly across five rounds, allowing us to measure dynamic preferences. Under the veil of ignorance, people preferred inequality favoring the top status. When the veil of ignorance disappeared, self‐interest immediately influenced inequality preferences. Those who randomly landed in top positions were satisfied with the status quo established under the veil of ignorance, whereas those who randomly landed in bottom positions wanted more equality. Yet these preferences were not stable; decisions about the optimal level of inequality changed according to changes in social status. Our results also showed that, when inequality grows in a society, preferences regarding inequality become polarized by social status. Individuals in low‐status positions, particularly, tend to demand more equality. (shrink)

Among the most significant findings of SUPPORT was that 50% of ICU patients suffered from moderate to severe pain during the last days of life. At the time of its publication late in 1995, SUPPORT was merely the latest in a long series of articles in the medical literature documenting the widespread and significant undertreatment of pain, beginning with a 1973 study of hospital inpatients. Much has been written about the phenomenon of undertreated pain and inadequate care of patients at (...) the end of life, and many positive suggestions for reform of clinical education and clinical practice have been iterated and reiterated in the two decades separating the studies. Proposals for modifying clinician behaviors in this aspect of patient care have tended to focus on particular barriers to effective pain management and palliative care. (shrink)

Modern philosophy is, for what appear to be good reasons, uniformly hostile to sui generis final causes. And motivated to develop philosophically and scientifically plausible interpretations, scholars have increasingly offered reductivist and eliminitivist accounts of Aristotle's teleological commitment. This trend in contemporary scholarship is misguided. We have strong grounds to believe Aristotle accepted unreduced sui generis teleology, and reductivist and eliminitivist accounts face insurmountable textual and philosophical difficulties. We offer Aristotelians cold comfort by replacing his apparent view with failed accounts. (...) And so we ought to admit Aristotle’s prima facie commitments and deal with — if not accept — the consequences. (shrink)

You meet someone new; you like them; you send them to your Facebook page. But how accurate is this representation of you? We all want to look our best, which is why we are drawn to the ability to fudge things a bit online. How does this projection of who we are distort us into who we want to be? Facebook allows us to hide our flaws that are all too visible in real life. We can embellish or correct what (...) we said earlier, edit out what we don’t like about ourselves, and only show photos where our chin is down and the lighting is blown out just enough to hide the bump on our nose. Our prospective employers can even turn to Facebook to assess our desirability. So might the constructed aesthetic of Facebook affect our approach to ethics – to interacting with other people? Does the way we design ourselves on Facebook directly impact the other people in our lives? Is each of us really just a rough draft that needs immediate editing? What about Facebook makes it possible to achieve genuine beauty? (shrink)

Charles Dickens began one of his many great works of literature with this seemingly paradoxical, self-contradictory statement. Reflecting on a jury verdict in Northern California in June of 2001, in the context of what has transpired during the decade of the 1990s with regard to the care of dying patients, observations in the genre of Dickens come readily to mind. In 1991, two of the most compelling books on the subject of pain, medicine, and society were published: Eric Cassell's The (...) Nature of Suffering and the Goals of Medicine and David Morris's The Culture of Pain. Both works unflinchingly recognized and explored the implications of the vast clinical literature documenting the failure of modern medicine to respond compassionately and effectively to what had by then become an epidemic of undertreated pain. (shrink)

When one considers the protracted and continuing struggle of the citizens of Oregon to include physician-assisted suicide among the panoply of measures available to dying patients and the physicians who care for them, the depth and breadth of the issue becomes inescapable. The potential intractability of the dispute is illustrated by the very fact, noted in the preceding parenthetical phrase, that consensus eludes us on even the most basic of semantic points—how we are to most aptly characterize the conduct in (...) question? The case featured in this issue's The Caduceus in Court must be examined as the latest battle in a long war of attrition waged by opponents of physician-assisted suicide against the Oregon Death with Dignity Act. After briefly reviewing that history, I will then consider the details of Oregon v. Ashcroft and the implications of the litigation not only for the care of dying patients but also for the regulation of medical practice in the United States and, more broadly still, the search for resolution of serious medical disputes in a democratic society. (shrink)

In the regime of Anglo-American tort law, every person has a responsibility to comport him- or herself with “due care” in going about day-to-day activities so as not to imperil the health, safety, or general welfare of others. The gold standard for determining what constitutes due care in any particular situation is what a reasonable person, similarly situated, would do. Determinations of due care are necessarily fact specific. Nevertheless, the general objective is to strike an appropriate balance between an unrealistically (...) high standard of caution and one that fails to take into account the known or foreseeable risks of any human endeavor. The same standard applies to individuals regardless of their age, gender, race, and level of education or economic status. The standard also applies to fictional “persons” such as corporations. The usual or prevailing custom and practice in an industry or occupation may provide relevant evidence of what constitutes “due care” in the activities common to it, but that evidence can be effectively overcome or rebutted by competent, credible evidence that the custom and practice either diverges from what it has been asserted to be or that the custom and practice is itself unsafe or otherwise poses an unreasonable risk of harm to others. Until quite recently, a singular exception to this general principle of tort law was made for the medical profession. We will consider this exception in the next section. (shrink)

A decision by the Supreme Court of California in the case Conservatorship of Wendland, issued in August 2001, forces us once again to confront the all-too-common situation in which an individual has, on multiple occasions, expressed strongly held personal convictions about life-sustaining interventions but failed to incorporate those convictions into a formal advance directive. Many courts have recognized that lay citizens do not consistently resort to written legal formalities in their day-to-day lives, and reasonable accommodation must be made to this (...) fundamental fact about human nature. However, a small but apparently growing minority of courts adamantly insist on either formal written directives or prescience and prophetic precision on the part of the patient before a surrogate can direct the withdrawal of life-sustaining treatment. The chronology of cases that comprise this minority position in American medical jurisprudence raise important ethical issues. (shrink)

This paper focuses on the cognitive/computational and evolutionary levels. It describes three proposals to make cognition computationally tractable, namely: Resource Rationality, the Adaptive Toolbox and Massive Modularity. While each of these proposals appeals to evolutionary considerations to dissolve the intractability of cognition, Rich, Blokpoel, de Haan, and van Rooij argue that, in each case, the intractability challenge is not resolved, but just relocated to the level of evolution.

This paper focuses on the cognitive/computational and evolutionary levels. It describes three proposals to make cognition computationally tractable, namely: Resource Rationality, the Adaptive Toolbox and Massive Modularity. While each of these proposals appeals to evolutionary considerations to dissolve the intractability of cognition, Rich, Blokpoel, de Haan, and van Rooij argue that, in each case, the intractability challenge is not resolved, but just relocated to the level of evolution.

Teleology is the study of ends and goals, things whose existence or occurrence is purposive. Aristotle’s views on teleology are of seminal importance, particularly his views regarding biological functions or purposes. This article surveys core examples of Aristotle’s invocations of teleology; explores philosophically puzzling aspects of teleology (including their normativity and the fact that ends can, apparently, act as causes despite never coming to exist); articulates two of Aristotle’s arguments defending commitment to teleology against critics who attempt to explain nature (...) solely through appeal to nonteleological efficient and material causes; and argues that Aristotle was an ontological realist when it came to teleology: he conceived of ends as an irreducible and ineliminable aspect of the causal structure of reality. Other interpretive controversies are addressed more briefly. (shrink)

In the current American iconoclash, certain monuments are subject to vandalism and municipal removal from their pedestals. Phrases such as “the erasure of history” and “damnatio memoriae” point to concerns that iconoclasm is an attempt to censor history or even remove certain individuals from public memory altogether. Because these phrases beckon the past, this wave of iconoclasm calls for a close examination of previous image-breaking to establish motives. Drawing first from art history, we analyze Byzantine iconoclasm and anxieties over the (...) nature of icons’ power, before contextualizing these findings within image destruction from the Paleolithic to the present day. Each comparison is suggestive of an enduring aesthetic principle: that what appears inanimate is not always inert. Next, drawing from cultural anthropology, we argue that principles of sympathetic magic are at the heart of contemporary iconoclasms, but not in the way media outlets often suggest. Instead, the fear of history’s erasure betrays a deeply rooted equivalence between the representation and the represented. In perceiving their fates as shared, sympathetic magic is seen to persist in the way humans create, interpret, and desecrate images. We conclude with the speculative realist proposition that iconoclasm can produce new, original artworks, which carries implications for the autonomy of art and its distribution between artist and artwork. (shrink)

Of the many opportunities and affordances that mobile technologies bring to our day-to-day lives, the ability to cheat physical separation and remain accessible to each other—in an instant—also brings pressure to bear on well-established social conventions as to how we should act when we are engaged with others in shared spaces. In this paper we explore some ethical dimensions of mobile communication by considering the manner in which individuals in everyday contexts balance interpretations of emergent social conventions with personal desires (...) to connect in the moment. As we later discuss, the decisions made in response to a ringing mobile phone or flashing text message emerge from consequential versus deontological ethical frames used to determine what to do versus what we ought to do. This is particularly true in western and North American cultural contexts from which our data are collected. Using Goffman's dramaturgy, we suggest that these conflicts occurring on an individual level provide evidence of social structure, and are simultaneously entwined with our less obvious ruminations on the maintenance of social order. (shrink)

Many interpretations of Hume's Dialogues Concerning Natural Religion have labored under the assumption that one of the characters represents Hume's view on the Design Argument, and Philo is often selected for this role. I reject this opinion by showing that Philo is inconsistent. He offers a decisive refutation of the Design Argument, yet later endorses this very argument. I then dismiss two prominent ways of handling Philo's reversal: first, I show that Philo is not ironic either in his skepticism or (...) in his theistic reversal. Second, I reject the suggestion that the Design Argument is a natural belief, since it differs significantly from causal and external world beliefs. Finally, I argue that the control the Design Argument exerts is the product of a youthful indoctrination that prevents Philo from consistently maintaining his skeptical position. (shrink)

Many interpretations of Hume's Dialogues Concerning Natural Religion have labored under the assumption that one of the characters represents Hume's view on the Design Argument, and Philo is often selected for this role. I reject this opinion by showing that Philo is inconsistent. He offers a decisive refutation of the Design Argument, yet later endorses this very argument. I then dismiss two prominent ways of handling Philo's reversal: first, I show that Philo is not ironic either in his skepticism or (...) in his theistic reversal. Second, I reject the suggestion that the Design Argument is a natural belief, since it differs significantly from causal and external world beliefs. Finally, I argue that the control the Design Argument exerts is the product of a youthful indoctrination that prevents Philo from consistently maintaining his skeptical position. (shrink)

There are two prominent viewpoints regarding the nature of rationality and how it should be evaluated in situations of interest: the traditional axiomatic approach and the newer ecological rationality. An obstacle to comparing and evaluating these seemingly opposite approaches is that they employ different language and formalisms, ask different questions, and are at different stages of development. I adapt a formal framework known as SCOP to address this problem by providing a comprehensive common framework in which both approaches may be (...) defined and compared. The main result is that the axiomatic and ecological approaches are in far greater agreement on fundamental issues than has been appreciated; this is supported by a pair of theorems to the effect that they will make accordant rationality judgements when forced to evaluate the same situation. I conclude that ecological rationality has some subtle advantages, but that we should move past the issues currently dominating the discussion of rationality. (shrink)

Sarah Moss’ thesis that we have probabilistic knowledge is from some perspectives unsurprising and from other perspectives hard to make sense of. The thesis is potentially transformative, but not yet elaborated in sufficient detail for epistemologists. This paper interprets Mossean probabilistic knowledge in a suitably-modified Kripke framework, thus filling in key details. It argues that probabilistic knowledge looks natural and plausible when so interpreted, and shows how the most pressing challenges to the thesis can be overcome. Most importantly, probabilistic knowledge (...) can satisfy factivity in the framework, though we are not forced to accept a specific account of probabilistic “facts”. The framework also reflects Moss’ claim that old-fashioned propositional knowledge is just a limiting case of probabilistic knowledge, and all knowledge is fundamentally probabilistic. Finally, Moss endorses a failure of contraposition: for example, p implies probably p, but not probably p does not imply not p. The framework makes clear the sense in which the valid inferences regarding probably p are as Moss claims. (shrink)

This paper addresses the problems that must be considered if computers are going to treat their users as individuals with distinct personalities, goals, and so forth. It first outlines the issues, and then proposes stereotypes as a useful mechanism for building models of individual users on the basis of a small amount of information about them. In order to build user models quickly, a large amount of uncertain knowledge must be incorporated into the models. The issue of how to resolve (...) the conflicts; hot will arise along such inferences is discussed. A system, Grundy, is described that builds models of its users, with the aid of stereotypes, and then exploits those models to guide it in its task, suggesting novels that people may find interesting. If stereotypes are to be useful to Grundy, they must accurately characterize the users of the system. Some techniques to modify stereotypes on the basis of experience are discussed. An analysis of Grundy's performance shows that its user models are effective in guiding its performance. (shrink)

Knowledge-first epistemology includes a knowledge norm of action: roughly, act only on what you know. This norm has been criticized, especially from the perspective of so-called standard decision theory. Mueller and Ross provide example decision problems which seem to show that acting properly cannot require knowledge. I argue that this conclusion depends on applying a particular decision theory which is ill-motivated in this context. Agents’ knowledge is often most plausibly formalized as an ambiguous epistemic state, and the theory of decision (...) under ambiguity is then the appropriate modeling tool. I show how to model agents as acting rationally on the basis of their knowledge according to such a theory. I conclude that the tension between the knowledge norm of action and formal decision theory is illusory; the knowledge-first paradigm should be used to actively select the decision-theoretical tools that can best capture the knowledge-based decisions in any given situation. (shrink)