We present evidence of a potentially serious source of error intrinsic to all spotted cDNA microarrays that use IMAGE clones of expressed sequence tags (ESTs). We found that a high proportion of these EST sequences contain 5V-end poly(dT) sequences that are remnants from the oligo(dT)-primed reverse transcription of polyadenylated mRNA templates used to generate EST cDNA for sequence clone libraries. Analysis of expression data from two single-dye cDNA microarray experiments showed that ESTs whose sequences contain repeats of consecutive 5V- end (...) dT residues appeared to be strongly coexpressed, while expression data of all other sequences exhibited no such pattern. Our analysis suggests that expression data from sequences containing 5V poly(dT) tracts are more likely to be due to systematic cross-hybridization of these poly(dT) tracts than to true mRNA coexpression. This indicates that existing data generated by cDNA microarrays containing IMAGE clone ESTs should be filtered to remove expression data containing significant 5V poly(dT) tracts. D 2003 Elsevier Inc. All rights reserved. (shrink)

Conditioning can make imprecise probabilities uniformly more imprecise. We call this effect "dilation". In a previous paper (1993), Seidenfeld and Wasserman established some basic results about dilation. In this paper we further investigate dilation on several models. In particular, we consider conditions under which dilation persists under marginalization and we quantify the degree of dilation. We also show that dilation manifests itself asymptotically in certain robust Bayesian models and we characterize the rate at which dilation occurs.

We report two issues concerning diverging sets of Bayesian (conditional) probabilities-divergence of "posteriors"-that can result with increasing evidence. Consider a set P of probabilities typically, but not always, based on a set of Bayesian "priors." Fix E, an event of interest, and X, a random variable to be observed. With respect to P, when the set of conditional probabilities for E, given X, strictly contains the set of unconditional probabilities for E, for each possible outcome X = x, call this (...) phenomenon dilation of the set of probabilities (Seidenfeld and Wasserman 1993). Thus, dilation contrasts with the asymptotic merging of posterior probabilities reported by Savage (1954) and by Blackwell and Dubins (1962). (1) In a wide variety of models for Robust Bayesian inference the extent to which X dilates E is related to a model specific index of how far key elements of P are from a distribution that makes X and E independent. (2) At a fixed confidence level, (1-α), Classical interval estimates A n for, e.g., a Normal mean θ have length O(n -1/2 ) (for sample size n). Of course, the confidence level correctly reports the (prior) probability that θ ∈ A n ,P(A n )=1-α , independent of the prior for θ . However, as shown by Pericchi and Walley (1991), if an ε -contamination class is used for the prior on the parameter θ , there is asymptotic (posterior) dilation for the A n , given the data. If, however, the intervals A ′ n are chosen with length $O(\sqrt{\log (\text{n})/\text{n})}$ , then there is no asymptotic dilation. We discuss the asymptotic rates of dilation for ClassClassical and Bayesian interval estimates and relate these to Bayesian hypothesis testing. (shrink)

DNA microarrays are perfectly suited for comparing gene expression in different populations of cells. An important application of microarray techniques is identifying genes which are activated by a particular drug of interest. This process will allow biologists to identify therapies targeted to particular diseases, and, eventually, to gain more knowledge about the biological processes in organisms. Such an application is described in this paper. It is focused on diabetes and obesity, which is a genetically heterogeneous disease, meaning that multiple defective (...) genes are responsible for the diseases. The paper is divided in three parts, each dealing with a different problem addressed to our study. First we validate the data from our microarray experiment. We identified significant systematic sources of variability which are potentially issues for other microarray datasets. Second, we applied multiple hypothesis testing to identify differentially expressed genes. We found a set of genes which appear to change in expression level over time in response to a drug treatment. Third, we tried to address the problem of identification of co-expressed genes using cluster analysis. This last problem is still under discussion. (shrink)

James M. Robins, Richard Scheines, Peter Spirtes, and Larry Wasserman. The Limits of Causal Knowledge.

This volume concerns the status and ambitions of metaphysics as a discipline.

(This insularity was further promoted by the guileless duplicity of scholars in other fields, who were all too prepared to bequeath "the problem of ...

What is the relation between a clay statue andthe lump of clay from which it is made? According to the defender of the standardaccount, the statue and the lump are distinct,enduring objects that share the same spatiallocation whenever they both exist. Suchobjects also seem to share the samemicrophysical structure whenever they bothexist. This leads to the standard objection tothe standard account: if the statue and thelump of clay have the same microphysicalstructure whenever they both exist, how canthey differ in their (...) de re temporalproperties, de re modal properties and soon? In this paper I develop amereological answer to this question – thestatue and the lump differ with respect totheir parts and this explains theirdifference with respect to de re temporalproperties, de re modal properties andthe like. (shrink)

Rabbi Simcha Wasserman was a rosh yeshivah; kiruv pioneer; advisor; foster father; storyteller; transmitter of tradition; founder of yeshivos; hatzalah activist. This book captures him speaking with patience, simplicity, and intellect, about burning topics such as Holocaust, Kabbalah, Providence, and child-rearing. Includes a biographical sketch.

What is the best question to ask an omniscient being? The question is intriguing; is it also paradoxical? We discuss several versions of what Ned Markosian calls the paradox of the question and suggest solutions to each of those puzzles. We then offer some practical advice about what do if you ever have the opportunity to query an omniscient being.

This paper critically engages ethical issues in the allocation of novel, and potentially costly, health care resources to patients with disorders of consciousness. First, we review potential benefits of novel health care resources for patients and their families and outline preliminary considerations to address concerns about cost. We then address two problems regarding the allocation of health care resources to patients with disorders of consciousness: (1) the problem of uncertain moral status; and (2) the problem of accurately measuring the welfare (...) burdens these resources would relieve. We conclude by suggesting that opportunity-based frameworks might complement standard approaches for justifying resources allocation to patients with disorders of consciousness. (shrink)

By targeting and critiquing these assumptions, he lays the groundwork for a post-positivist philosophy of science that does not provide aid and comfort to the enemies of reason. This book consists of thirteen essays.

Our purpose in this article is to identify and suggest resolution for two core problematics of grounded theory. First, while grounded theory provides transparency to one part of the conceptualization process, where codes emerge directly from the data, it provides no such systematic or transparent way for gaining insight into the conceptual relationships between discovered codes. Producing a grounded theory depends not only on the definition of conceptual pieces, but the delineation of a relationship between at least two of those (...) pieces. Second, the conceptualization process of grounded theory is done in hierarchical fashion, where individual codes emerge from the data but then are used to generate insight into more general concepts and thematic statements. But various works on grounded theory have failed to provide any systematic way of using data specific levels of scale (the codes) to gain insight into more macro levels of scale (concepts and themes). We offer fractal concept analysis as a means of resolving both of these issues. By using a logic structure generator, fractal concept analysis delineates self-similar conceptual frameworks at various levels of abstraction, yielding a method for linking concepts together within and between levels of scale encountered in the grounded theory coding and categorization process. We conclude that this fractal analytic technique can bolster the aims of grounded theory as a formalized and systematic process for generating theory from empirical data. (shrink)

This text addresses various topics in applied ethics from Western and non-Western perspectives. Multicultural perspectives are fully integrated throughout the text.

Appraisal theories of emotion generally presuppose that emotions are “directed at” various items. They also hold that emotions have motivational properties. However, although it coheres well with their views, they have yet to seriously develop the idea that the function of emotional direction is to guide those properties. I argue that this “guidance hypothesis” can open up a promising new field of research in emotion theory. But I also argue that before appraisal theorists can take full advantage of it, they (...) must drop their further assumption that to determine an emotion's direction, one need only retrace the process that caused it. Contrary to this “retracing view,” I argue for an “independence thesis”: directed emotions are produced by two functionally independent sub-processes. The first, “affect-causation,” functions in part to produce a state with certain motivational properties given certain representations. The second, “affect-direction,” has the function of optimally guiding those motivational properties by associating them with representations that may properly be quite dissimilar from the causal ones. By provisionally adopting the independence thesis and empirically testing the guidance hypothesis, I argue that appraisal theorists stand a good chance of significantly increasing the explanatory power of their theories. (shrink)

Jesse Prinz (2004) argues that emotional feelings (“state emotions”) can by themselves perceptually represent significant organism-environment relations. I object to this view mainly on the grounds that (1) it does not rule out the at least equally plausible view that emotional feelings are non-representational sensory registrations rather than perceptions, as Tyler Burge (2010) draws the distinction, and (2) perception of a relation requires perception of at least one of the relation’s relata, but an emotional feeling by itself perceives neither the (...) subject’s environment, nor in many cases the relevant subject itself. I then explore two ways in which emotional feelings as non-perceptual sensory registrations might still contribute to significant relation representation when associated with representations of the subject and/or its environment. After briefly discussing some difficulties presented by a multimodal, sensory-perceptual view of such representation, I argue in favor of a “cognitive recognition theory” that holds that significant relation instances are represented during emotion occurrences via applications of emotion-type concepts to "incoming" emotional feelings and their associated mental states. (shrink)

Precision medicine is emerging as a scientific bandwagon within the contemporary biomedical sciences in the United States. PM brings together concepts and tools from genomics and bioinformatics to develop better diagnostics and therapies based on individualized information. Developing countries like China and Brazil have also begun pursuing PM projects, motivated by a desire to claim genomic sovereignty over its population. In spite of commonalities, institutional arrangements produced by the history of genomics research in China and Brazil are ushering PM along (...) different trajectories. In the Chinese case, we identify a strong state-backed push for PM combined with a dynamic network of international academic and private actors along the lines of networked technonationalism that has made large-scale, speculative PM projects possible. The Brazilian case is characterized by an institutional void at the federal level in which PM is driven by domestic academic actors in universities in the regional level, resulting in smaller scale, needs-driven PM projects. Through these cases, this paper shows how a scientific bandwagon adapts to national histories and institutions. Through this peripheral translation of the scientific bandwagon, the global infrastructure of biomedical knowledge has the potential to be transformed. (shrink)

African American distrust of medicine has consequences for treatment seeking and healthcare behaviour. Much work has been done to examine acute events that have contributed to this phenomenon and a sophisticated bioethics discipline keeps watch on current practices by medicine. But physicians and clinicians are not the only actors in the medical arena, particularly when it comes to health beliefs and distrust of medicine. The purpose of this paper is to call attention not just to ethical shortcomings of the past, (...) but to the structural contexts of those events and the contributions and responsibilities of popular media and academic disciplines in the production of knowledge. We argue that ignoring context and producing inaccurate work has real impacts on health and healthcare, particularly for African Americans, and thus engenders ethical obligations incumbent on disciplines traditionally recognised as purely academic. (shrink)

This is the second volume in a sub-series of specially commissioned collaborative volumes on key topics at the heart of contemporary philosophy of law that will be appearing regularly within Cambridge Studies in Philosophy and Law. A distinguished international team of legal theorists examine the issue of constitutionalism and pose such foundational questions as: why have a constitution? How do we know what the constitution of a country really is? How should a constitution be interpreted? Why should one generation feel (...) bound by the constitution of an earlier one? The volume will be of particular importance to those in philosophy, law, political science and international relations interested in what kinds of constitutions should be adopted in countries without them, and involved in debates about constitutional interpretation. (shrink)

Temkin's book is a very original and deeply unsettling work of skeptical philosophy that mounts an important new challenge to contemporary ethics.

This article asks whether personal ventilators should be redistributed to maximize lives saved in emergency condition, like the COVID-19 pandemic. It begins by examining extant claims that items like ventilators are literally parts of their user’s bodies. Arguments in favor of incorporation for ventilators fail to show that they meet valid sufficient conditions to be body parts, but arguments against incorporation also fail to show that they fail to meet clearly valid necessary conditions. Further progress on this issue awaits clarification (...) of difficult normative, conceptual, and metaphysical questions about the possible boundaries of a person’s body. Rather than relying solely on incorporation arguments, we propose an argument against reallocation from widely accepted anti-discrimination principles. Possession of a personal ventilator is an obvious marker of disability identity; thus, reallocating ventilators from those that already possess them discriminates on the basis of a stigmatized trait – a paradigm case of presumptively wrongful discrimination. This discrimination claim, taken together with uncertainty about the bodily status of ventilators, yields a strong presumption against personal ventilator reallocation. (shrink)

In coming decades, fetal medicine may become a routine part of reproductive care. The measures pregnant women now take to protect fetal health are largely generic, like restricting their diets and using supplements. Relatively few interventions are based on specific conditions revealed by ultrasound or genetic testing. A recent finding, though, may herald a dramatic rise in “personalized” fetal medicine: certain drugs already approved by the Food and Drug Administration can apparently boost neural growth in fetuses with Down syndrome, improving (...) cognitive functioning in the future child. Many more condition‐specific findings are likely in the near future. But as commentators have frequently observed about prenatal testing, technologies that appear to increase reproductive options also complicate and constrain them. (shrink)

The present volume encapsulates the contemporary scholarship on John Dewey and shows the place of Dewey’s thought on the philosophical arena. The authors are among the leading specialists in the philosophy of John Dewey from universities across the US and in Europe.

Working memory resources are needed for processing and maintenance of information during cognitive tasks. Many models have been developed to capture the effects of limited working memory resources on performance. However, most of these models do not account for the finding that different individuals show different sensitivities to working memory demands, and none of the models predicts individual subjects' patterns of performance. We propose a computational model that accounts for differences in working memory capacity in terms of a quantity called (...) source activation, which is used to maintain goal‐relevant information in an available state. We apply this model to capture the working memory effects of individual subjects at a fine level of detail across two experiments. This, we argue, strengthens the interpretation of source activation as working memory capacity. (shrink)

This book presents a comprehensive overview of what the criminal law would look like if organised around the principle that those who deserve punishment should receive punishment commensurate with, but no greater than, that which they deserve. Larry Alexander and Kimberly Kessler Ferzan argue that desert is a function of the actor's culpability, and that culpability is a function of the risks of harm to protected interests that the actor believes he is imposing and his reasons for acting in (...) the face of those risks. The authors deny that resultant harms, as well as unperceived risks, affect the actor's desert. They thus reject punishment for inadvertent negligence as well as for intentions or preparatory acts that are not risky. Alexander and Ferzan discuss the reasons for imposing risks that negate or mitigate culpability, the individuation of crimes, and omissions. (shrink)

While procreation is ubiquitous, attention to the ethical issues involved in creating children is relatively rare. In Debating Procreation, David Benatar and David Wasserman take opposing views on this important question. David Benatar argues for the anti-natalist view that it is always wrong to bring new people into existence. He argues that coming into existence is always a serious harm and that even if it were not always so, the risk of serious harm is sufficiently great to make procreation (...) wrong. In addition to these "philanthropic" arguments, he advances the "misanthropic" one that because humans are so defective and cause vast amounts of harm, it is wrong to create more of them.David Wasserman defends procreation against the anti-natalist challenge. He outlines a variety of moderate pro-natalist positions, which all see procreation as often permissible but never required. After criticizing the main anti-natalist arguments, he reviews those pronatalist positions. He argues that constraints on procreation are best understood in terms of the role morality of prospective parents, considers different views of that role morality, and argues for one that imposes only limited constraints based on the well-being of the future child. He then argues that the expected good of a future child and of the parent-child relationship can provide a strong justification for procreation in the face of expected adversities without giving individuals any moral reason to procreate. (shrink)

We are gratified by Nelson's response to our commentary. It shows, for the first time, an appreciation of the distinctive character of our criticism of individual decisions to test and terminate for fetal impairment. Although we still find much to disagree with in Nelson's characterization and critique of our views, he has given us a welcome opportunity to clarify and develop them.

Constitutivists about one's cognitive access to one's mental states often hold that for any rational subject S and mental state M falling into some specified range of types, necessarily, if S believes that she has M, then S has M. Some argue that such a principle applies to beliefs about all types of mental state. Others are more cautious, but offer no criterion by which the principle's range could be determined. In this paper I begin to develop such a criterion, (...) arguing that although the principle applies when M is a belief, it does not apply when M is an emotion. I account for this asymmetry by focusing on differences in the commitments that belief and emotion conceptually involve, and briefly sketch out a psychological explanation of those differences. I conclude that one can reasonably split one's epistemological loyalties between constitutivism regarding meta-beliefs and non- constitutivism regarding beliefs about one's emotions. (shrink)

Assume that, even with a time machine, Tim does not have the ability to travel to the past and kill Grandfather. Why would that be? And what are the implications for traditional debates about freedom? We argue that there are at least two satisfactory explanations for why Tim cannot kill Grandfather. First, if an agent’s behavior at time _t_ is causally dependent on fact _F_, then the agent cannot perform an action (at _t_) that would require _F_ to have not (...) obtained. Second, if an agent’s behavior at time _t_ is causally dependent on fact _F_, then the agent cannot perform an action (at _t_) that would prevent _F_ from obtaining. These two explanations have distinct upshots for more traditional debates over freedom. The first implies that causal determinism is incompatible with the ability to do otherwise and also raises questions about the traditional arguments for the incompatibility of divine foreknowledge and the ability to do otherwise; the second does neither. However, both explanations imply that the Molinist account of divine providence renders agents unable to do otherwise, at least in certain circumstances. (shrink)

INTRODUCTION The appeal to teleological principles of explanation within the body of natural science has had an unfortunate history. ...

Analyses of dispositional ascriptions in terms of conditional statements famously confront the problems of finks and masks. We argue that conditional analyses of dispositions, even those tailored to avoid finks and masks, face five further problems. These are the problems of: (i) Achilles' heels, (ii) accidental closeness, (iii) comparatives, (iv) explaining context sensitivity, and (v) absent stimulus conditions. We conclude by offering a proposal that avoids all seven of these problems.