The Cas9 endonuclease is the central component of the Type II CRISPR/Cas system, a prokaryotic adaptive restriction system against invading nucleic acids, such as those originating from bacteriophages and plasmids. Recently, this RNA‐directed DNA endonuclease has been harnessed to target DNA sequences of interest. Here, we review the development of Cas9 as an important tool to not only edit the genomes of a number of different prokaryotic and eukaryotic species, but also as an efficient system for site‐specific transcriptional repression or (...) activation. Additionally, a specific Cas9 protein has been observed to target an RNA substrate, suggesting that Cas9 may have the ability to be programmed to target RNA as well. Cas proteins from other CRISPR/Cas subtypes may also be exploited in this regard. Thus, CRISPR/Cas systems represent an effective and versatile biotechnological tool, which will have significant impact on future advancements in genome engineering. (shrink)

Little is known about how researchers view ethically salient aspects of human studies. As part of a National Institutes of Mental Health-funded study, the authors performed a confidential written survey to assess the attitudes, views, and experiences of researchers with institutional review board approved protocols at the University of New Mexico. A total of 363 researchers (57% response rate) participated. Investigators overall held favorable views of general ethical aspects of research and ethics-based safeguards, and they identified a positive role of (...) ethics training. Investigators with more experience encountering ethical problems (p < .001), more ethics training (p = .001), and a PhD or MD/PhD (p = .003) held more favorable general ethical perspectives. Women investigators (p < .03), nonphysician investigators (p < .001), those whose training had been helpful in resolving ethical dilemmas (p = .006), and those for whom spirituality is important (p = .008) more strongly endorsed ethical safeguards. Investigators perceive the scientific and ethical aspects of their work as valuable and linked, and they affirm the role of safeguards in human studies. Formal ethics preparation and training initiatives were also viewed positively by investigators. (shrink)

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 and X-linked CLDN2 through a two-stage genome-wide study. The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is (...) associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men. © 2012 Nature America, Inc. All rights reserved. (shrink)

Timothy Williamson gives an original and provocative treatment of deep metaphysical questions about existence, contingency, and change, using the latest resources of quantified modal logic. Contrary to the widespread assumption that logic and metaphysics are disjoint, he argues that modal logic provides a structural core for metaphysics.

Vagueness provides the first comprehensive examination of a topic of increasing importance in metaphysics and the philosophy of logic and language. Timothy Williamson traces the history of this philosophical problem from discussions of the heap paradox in classical Greece to modern formal approaches such as fuzzy logic. He illustrates the problems with views which have taken the position that standard logic and formal semantics do not apply to vague language, and defends the controversial realistic view that vagueness is a (...) kind of ignorance--that there really is a grain of sand whose removal turns a heap into a non-heap, but we cannot know which one it is. (shrink)

Certain anti-realisms about mathematics are distinguished by their taking proof rather than truth as the central concept in the account of the meaning of mathematical statements. This notion of proof which is meaning determining or canonical must be distinguished from a notion of demonstration as more generally conceived. This paper raises a set of objections to Dummett's characterisation of the notion via the notion of a normalised natural deduction proof. The main complaint is that Dummett's use of normalised natural deduction (...) proofs relies on formalisation playing a role for which it is unfit. Instead I offer an alternative account which does not rely on formalisation and go on to examine the relation of proof to canonical proof, arguing that rather than requiring an explicit characterisation of canonical proofs we need to be more aware of the complexities of that relation. (shrink)

Roslyn Weiss offers a new interpretation of Platonic moral philosophy based on an unconventional reading of the Republic. Her basic argument begins with the point that Plato means for us to react badly to the philosopher-rulers of Book 7. She then makes the case that there are two distinct kinds of philosopher in the Republic--one that is ideal and one that is farcical--and that each represents a separate type of justice. Finally, she argues that Plato recognizes this dualism and (...) points the way toward a resolution"--Publisher's Web site. (shrink)

The seventh edition of this pragmatic guide to determining right and wrong in the workplace is updated with new case studies and ancillary materials to combine stakeholder perspectives with a deep dive on workplace ethics issues. Using a unique stakeholder-based approach, this book takes business ethics out of the theory realm and provides practical ways to analyze any business decision. Including dozens of cases, Joseph Weiss looks beyond the impacts of ethical lapses on share price and profit to focus (...) on relationships between stakeholders, including individuals, groups, corporations, and governments. The new seventh edition includes seven new cases and ten new Point/Counterpoint exercises, which challenge students to argue both sides of a contemporary issue. It incorporates the latest research as well as updated cases dealing with recent scandals at organizations such as Boeing, Facebook, and Uber. Professors will have access to online support, including teaching notes, PowerPoint slides, and sample tests. The book is equipped with a step-by-step guide to implementing stakeholder analysis, tips to help students apply ethical principles in their personal and professional lives, and comprehensive coverage of employee workplace issues. Addressing relevant topics such as risk management, preferential hiring, and sexual harassment in conjunction with the digital divide, bribery, the environment, and more, Business Ethics, seventh edition explores ethical implications in today's increasingly interconnected global business environment. (shrink)

The second volume in the _Blackwell Brown Lectures in Philosophy_, this volume offers an original and provocative take on the nature and methodology of philosophy. Based on public lectures at Brown University, given by the pre-eminent philosopher, Timothy Williamson Rejects the ideology of the 'linguistic turn', the most distinctive trend of 20th century philosophy Explains the method of philosophy as a development from non-philosophical ways of thinking Suggests new ways of understanding what contemporary and past philosophers are doing.

Epistemic Value Monism is the view that there is only one kind of thing of basic, final epistemic value. Perhaps the most plausible version of Epistemic Value Monism is Truth Value Monism, the view that only true beliefs are of basic, final epistemic value. Several authors—notably Jonathan Kvanvig and Michael DePaul—have criticized Truth Value Monism by appealing to the epistemic value of things other than knowledge. Such arguments, if successful, would establish Epistemic Value Pluralism is true and Epistemic Value Monism (...) is false. This paper critically examines those arguments, finding them wanting. However, I develop an argument for Epistemic Value Pluralism that succeeds which turns on general reflection on the nature of value. (shrink)

In this paper we discuss how Causal Decision Theory should be modified to handle a class of problematic cases involving deterministic laws. Causal Decision Theory, as it stands, is problematically biased against your endorsing deterministic propositions (for example it tells you to deny Newtonian physics, regardless of how confident you are of its truth). Our response is that this is not a problem for Causal Decision Theory per se, but arises because of the standard method for assessing the truth of (...) certain counterfactuals. The truth of deterministic laws is `modally fragile' on the standard semantics for counterfactuals: if determinism is true and you were to do otherwise, the laws would be different. We provide two ways of avoiding this problem: 1) supplement the standard semantics for counterfactuals with impossible worlds, or 2) introduce rigid designators into the description of problematic decision situations. We argue that both of these approaches are well-motivated and can be readily incorporated into Lewisian Causal Decision Theory. (shrink)

The paper clarifies and defends the orthodox view that counterfactual conditionals with impossible antecedents are vacuously true against recent criticisms. It argues that apparent counterexamples to orthodoxy result from uncritical reliance on a fallible heuristic used in the processing of conditionals. A comparison is developed between such counterpossibles and vacuously true universal generalizations.

Truthmaker theorists hold that there is a metaphysically explanatory relation that holds between true claims and what exists. While some critics try to provide counterexamples to truthmaker theory, that response quickly leads to a dialectical standoff. The aim of this paper is to move beyond that standoff by attempting to undermine some standard arguments for truthmaker theory. Using realism about truth and a more pragmatic account of explanation, I show how some of those arguments can be undermined.

When I take off my glasses, the world looks blurred. When I put them back on, it looks sharpedged. I do not think that the world really was blurred; I know that what changed was my relation to the distant physical objects ahead, not those objects themselves. I am more inclined to believe that the world really is and was sharp-edged. Is that belief any more reasonable than the belief that the world really is and was blurred? I see more (...) accurately with my glasses on than off, so visual appearances when they are on have some cognitive priority over visual appearances when they are off. If I must choose which kind of visual appearance to take at face value, I will choose the sharp-edged look. But what should I think when I see a mist, which looks very blurred however well I am seeing? Indeed, why choose to take any of the looks at face value? Why not regard all the choices as illegitimate projections of ways of seeing the world onto the world itself? (shrink)

Author note: Penny A. Weiss, Associate Professor of Political Science at Purdue University, is the author of Gendered Community: Rousseau, Sex, and Politics. Marilyn Friedman, Associate Professor of Philosophy at Washington University, is the author of What Are Friends For? Feminist Perspectives on Personal Relationships and Moral Theory.

In recent years scholars have begun to question the usefulness of the category of ''religion'' to describe a distinctive form of human experience and behavior. In his last book, The Ideology of Religious Studies (OUP 2000), Timothy Fitzgerald argued that ''religion'' was not a private area of human existence that could be separated from the public realm and that the study of religion as such was thus impossibility. In this new book he examines a wide range of English-language texts (...) to show how religion became transformed from a very specific category indigenous to Christian culture into a universalist claim about human nature and society. These claims, he shows, are implied by and frequently explicit in theories and methods of comparative religion. But they are also tacitly reproduced throughout the humanities in the relatively indiscriminate use of ''religion'' as an a priori valid cross-cultural analytical concept, for example in historiography, sociology, and social anthropology. Fitzgerald seeks to link the argument about religion to the parallel formation of the ''non-religious'' and such dichotomies as church-state, sacred-profane, ecclesiastical-civil, spiritual-temporal, supernatural-natural, and irrational-rational. Part of his argument is that the category ''religion'' has a different logic compared to the category ''sacred,'' but the two have been consistently confused by major writers, including Durkheim and Eliade. Fitzgerald contends that ''religion'' imagined as a private belief in the supernatural was a necessary conceptual space for the simultaneous imagining of ''secular'' practices and institutions such as politics, economics, and the Nation State. The invention of ''religion'' as a universal type of experience, practice, and institution was partly the result of sacralizing new concepts of exchange, ownership, and labor practices, applying ''scientific'' rationality to human behavior, administering the colonies and classifying native institutions. In contrast, shows Fitzgerald, the sacred-profane dichotomy has a different logic of use. (shrink)

Previous research has suggested that bodily signals from internal organs are associated with diverse cortical and subcortical processes involved in sensory-motor functions, beyond homeostatic reflexes. For instance, a recent study demonstrated that the preparation and execution of voluntary actions, as well as its underlying neural activity, are coupled with the breathing cycle. In the current study, we investigated whether such breathing-action coupling is limited to voluntary motor action or whether it is also present for mental actions not involving any overt (...) bodily movement. To answer this question, we recorded electroencephalography (EEG), electromyography (EMG), and respiratory signals while participants were conducting a voluntary action paradigm including self-initiated motor execution (ME), motor imagery (MI), and visual imagery (VI) tasks. We observed that the voluntary initiation of ME, MI, and VI are similarly coupled with the respiration phase. In addition, EEG analysis revealed the existence of readiness potential (RP) waveforms in all three tasks (i.e., ME, MI, VI), as well as a coupling between the RP amplitude and the respiratory phase. Our findings show that the voluntary initiation of both imagined and overt action is coupled with respiration, and further suggest that the breathing system is involved in preparatory processes of voluntary action by contributing to the temporal decision of when to initiate the action plan, regardless of whether this culminates in overt movements. -/- . (shrink)

This paper challenges the soundness of the two-dimensional conceivability argument against the derivation of phenomenal truths from physical truths in light of a hyperintensional, ground-theoretic regimentation of the ontology of consciousness. The regimentation demonstrates how ontological dependencies between truths about consciousness and about physics cannot be witnessed by epistemic constraints, when the latter are recorded by the conceivability—i.e., the epistemic possibility—thereof. Generalizations and other aspects of the philosophical significance of the hyperintensional regimentation are further examined.

Yet recent thinkers have expressed deep reservations about the concept and the term has become marginalized in the humanities and social sciences.Eschewing this ...

In this original work of cultural criticism, Allen S. Weiss explores the meaning of radio to the modern imagination.

Subjectivity theories of consciousness take self-reference, somehow construed, as essential to having conscious experience. These theories differ with respect to how many levels they posit and to whether self-reference is conscious or not. But all treat self-referencing as a process that transpires at the personal level, rather than at the subpersonal level, the level of mechanism. -/- Working with conceptual resources afforded by pre-existing theories of consciousness that take self-reference to be essential, several attempts have been made to explain seemingly (...) anomalous cases, especially instances of alien experience. These experiences are distinctive precisely because self-referencing is explicitly denied by the only person able to report them: those who experience them deny that certain actions, mental states, or body parts belong to self. The relevant actions, mental states, or body parts are sometimes attributed to someone or something other than self, and sometimes they are just described as not belonging to self. But all are referred away from self. -/- The cases under discussion here include somatoparaphrenia, schizophrenia, depersonalization, anarchic hand syndrome, and utilization behavior; the theories employed, Higher-Order Thought, Wide Intrinsicality, and Self-Representational. Below I argue that each of these attempts at explaining or explaining away the anomalies fails. Along the way, since each of these theories seeks at least compatibility with science, I sketch experimental approaches that could be used to adduce support for my position, or indeed for the positions of theorists with whom I disagree. -/- In a concluding section I first identify two presuppositions shared by all of the theorists considered here, and argue that both are either erroneous or misleading. Second, I call attention to divergent paths adopted when attempting to explain alienation experiences: some theorists choose to add a mental ingredient, while others prefer to subtract one. I argue that alienation from experience, action, or body parts could result from either addition or subtraction, and that the two can be incorporated within a comprehensive explanatory framework. Finally, I suggest that this comprehensive framework would require self-referencing of a sort, but self-referencing that occurs solely on the level of mechanism, or the subpersonal level. In adumbrating some features of this “subpersonal self,” I suggest that there might be one respect in which it is prior to conscious experience. (shrink)

The author argues that all forms of life are interconnected and that no being, construct, or object can exist independently from the ecological entanglement, nor does "nature" exist as an entity separate from the uglier or more synthetic elements of life. Realizing this interconnectedness is what the author calls the ecological thought. He investigates the philosophical, political, and aesthetic implications of this interconnectedness.

An investigation of the nature of truth, ethics, and deception.

Possession Trance and Dramatic Perversity Dionysus arrives as a stranger, enigmatic, disquieting, contagious, spreading an epidemic of mania leading to ...

At any given time, a subject has a multiplicity of conscious experiences. A subject might simultaneously have visual experiences of a red book and a green tree, auditory experiences of birds singing, bodily sensations of a faint hunger and a sharp pain in the shoulder, the emotional experience of a certain melancholy, while having a stream of conscious thoughts about the nature of reality. These experiences are distinct from each other: a subject could experience the red book without the singing (...) birds, and could experience the singing birds without the red book. But at the same time, the experiences seem to be tied together in a deep way. They seem to be unified, by being aspects of a single encompassing state of consciousness. (shrink)

Two opposing tendencies in the philosophy of language go by the names of ‘referentialism’ and ‘inferentialism’ respectively. In the crudest version of the contrast, the referentialist account of meaning gives centre stage to the referential semantics for a language, which is then used to explain the inference rules for the language, perhaps as those which preserve truth on that semantics (since a referential semantics for a language determines the truth-conditions of its sentences). By contrast, the inferentialist account of meaning gives (...) centre stage to the inference rules for the language, which are then used to explain its referential semantics, perhaps as the semantics on which the rules preserve truth. On pain of circularity, we cannot combine both directions of explanation. (shrink)

This book presents in translation writings by six medieval philosophers which bear on the subject of conscience. Conscience, which can be considered both as a topic in the philosophy of mind and a topic in ethics, has been unduly neglected in modern philosophy, where a prevailing belief in the autonomy of ethics leaves it no natural place. It was, however, a standard subject for a treatise in medieval philosophy. Three introductory translations here, from Jerome, Augustine and Peter Lombard, present the (...) loci classici on which subsequent discussions drew; there follows the first complete treatise on conscience, by Philip the Chancellor, while the two remaining translations, from Bonaventure and Aquinas, have been chosen as outstanding examples of the two main approaches which crystallised during the thirteenth century. (shrink)

The fundamental freedoms of speech, conscience, privacy, and religion are now an essential part of the fabric of contemporary society, set down in our most basic laws and regularly invoked in our political and cultural debates. These freedoms play a vital role in securing the spaces and opportunities within which people are able to pursue their own lives in their own ways. Independence of Mind takes this accepted thought a step further, by exploring the ways in which the fundamental freedoms (...) help us to achieve something even more profound, by enabling us to arrive at beliefs, convictions and voices of our own, so that we truly come to think, believe and speak for ourselves in the rich and various ways that the freedoms then protect. Privacy grants us the distance and refuge from others necessary to develop views of our own; freedom of speech calls on us to imagine ways of expressing ourselves that are both true to the views we have developed and innovative in their own right; freedom of conscience enables each of us to create a distinctive rational personality in which to embed the convictions that we wish to treat as non-negotiable; freedom of religion allows groups of us to endorse certain beliefs as articles of faith, free from the full demands of rational scrutiny. Much has been written about the political and legal implications of the fundamental freedoms and their entrenchment in bills of rights. This is the first book to undertake a comprehensive philosophical examination of their moral bases. It offers a penetrating analysis of what makes these particular freedoms matter to us in the ways that they do, and of the true significance of their entrenchment in law. (shrink)

This paper discusses the nature and the status of inference to the best explanation. We outline the foundational role given IBE by its defenders and the arguments of critics who deny it any place at all ; argue that, on the two main conceptions of explanation, IBE cannot be a foundational inference rule ; sketch an account of IBE that makes it contextual and dependent on substantive empirical assumptions, much as simplicity seems to be ; show how that account avoids (...) the critics ' complaints and leaves IBE an important role ; and sketch how our account can clarify debates over IBE in arguments for scientific realism. (shrink)

Skeptical theism is a family of responses to arguments from evil. One important member of that family is Stephen Wykstra’s CORNEA-based criticism of William Rowe’s arguments from evil. A cornerstone of Wykstra’s approach is his CORNEA principle. However, a number of authors have criticized CORNEA on various grounds, including that it has odd results, it cannot do the work it was meant to, and it problematically conflicts with the so-called common sense epistemology. In this paper, I explicate and defend a (...) CORNEA principle. After sketching a brief argument for it, I show how it can be acquitted of these recent charges. (shrink)

Can moral judgements be true or false? Can rational methods be applied to ethics? In this landmark study, Sprigge gives an account of how philosophers have tackled these questions and puts forward his own theory on the matter.

This article endeavors to identify the strongest versions of the two primary arguments against epistemic scientific realism: the historical argument—generally dubbed “the pessimistic meta-induction”—and the argument from underdetermination. It is shown that, contrary to the literature, both can be understood as historically informed but logically validmodus tollensarguments. After specifying the question relevant to underdetermination and showing why empirical equivalence is unnecessary, two types of competitors to contemporary scientific theories are identified, both of which are informed by science itself. With the (...) content and structure of the two nonrealist arguments clarified, novel relations between them are uncovered, revealing the severity of their collective threat against epistemic realism and its “no-miracles” argument. The final section proposes, however, that the realist’s axiological tenet “science seeks truth” is not blocked. An attempt is made to indicate the promise for a nonepistemic, purely axiological scientific realism—here dubbed “Socratic scientific realism.”. (shrink)

In his book, _Interpretation without Truth_, Pierluigi Chiassoni articulates the sceptical view that the province of legal interpretation is ‘a province without truth’. A misinterpretation is a false interpretation, and I argue that the widespread phenomenon of legal misinterpretation gives us reason to resist the sceptical conclusion. The potential for a legal interpretation to be a false interpretation –a misinterpretation– implies that a legal interpretation can be true. And legal misinterpretations can be understood as interpretations (and not as the product (...) of some activity other than interpretation) because of the grain of truth in the arguments for them. (shrink)

Few would contest the fact that analytical philosophy has dominated philosophical practice in the English speaking world for about the last century. But dispute continues about both its origins and nature; whilst others question its value. Michael Dummett wholly embraced the analytical approach to philosophy, as he conceived of it. For him analytical philosophy marked itself off from its precursors and its alternatives, embodied in the Continental tradition, by taking the linguistic turn. And Frege was unequivocally the first philosopher to (...) take that auspicious turn, which ushered in a new method in philosophy. Henceforth philosophers were to approach the business of analyzing thought via the enterprise of analyzing language. So Dummett is presenting us with both a history lesson and a recommendation about how we ought to do philosophy. But is his reading of the history accurate? And is his conception of the nature of analytical philosophy viable? In order to reflect on these questions this collection brings together eight scholars who have made a serious business of reading Dummett. (shrink)