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)

Knowledge and its Limits presents a systematic new conception of knowledge as a kind of mental stage sensitive to the knower's environment. It makes a major contribution to the debate between externalist and internalist philosophies of mind, and breaks radically with the epistemological tradition of analyzing knowledge in terms of true belief. The theory casts new light on such philosophical problems as scepticism, evidence, probability and assertion, realism and anti-realism, and the limits of what can be known. The arguments are (...) illustrated by rigorous models based on epistemic logic and probability theory. The result is a new way of doing epistemology and a notable contribution to the philosophy of mind. (shrink)

This is not your psychoanalyst's unconscious.

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)

Without directly addressing the Demarcation Problem for logic—the problem of distinguishing logical vocabulary from others—we focus on distinctive aspects of logical vocabulary in pursuit of a second goal in the philosophy of logic, namely, proposing criteria for the justification of logical rules. Our preferred approach has three components. Two of these are effectively Belnap’s, but with a twist. We agree with Belnap’s response to Prior’s challenge to inferentialist characterisations of the meanings of logical constants. Belnap argued that for a logical (...) constant to exist, its rules must be conservative over a previously given consequence relation and guarantee the uniqueness of the constant. The twist is that we require logical vocabulary to be provably conservative, not over a previously given formal consequence relation, but over a previously given meaningful vocabulary of a language. Uniqueness is also a feature defined in terms of provability: if two syntactically distinguished expressions are governed by the same rules, then formulas with them as main operators are interderivable. Belnap’s criteria are not only those for the existence of a logical constant, but more: they are what distinguishes logical vocabulary from all other expressions. It is the defining mark of a logical constant that it is provably conservative over the fragment of the language which excludes it and that its rules guarantee its uniqueness. The third component is the topic neutrality of logic. The provable conservativeness of logic over a previously given vocabulary of a language is motivated, in part, by appeal to molecularism in the theory of meaning. Molecularity is a feature endorsed by the theory of meaning as a whole, so it does not distinguish logical constants from other expressions. The same is true for conservativeness. We argue that molecularity, and hence conservativeness, are implicit presuppositions of speakers’ use of language: the addition of new vocabulary to a language is presupposed to be conservative. But this presupposition is one that we should be able reflectively to endorse (such as when attempting a rational reconstruction of the use of the vocabulary). Thus, where conservativeness is found to fail, this defect should be remedied and the use of the vocabulary corrected (as in classical negation) or excised altogether (as in pejoratives). We go on to characterise a notion of topic neutrality, which we argue applies to logical vocabulary. We then note that reflective endorsement of the conservativeness of a topic neutral vocabulary requires a proof that the vocabulary is conservative relative to any base vocabulary. Thus we require that logical vocabulary be demonstrably conservative. Allying this requirement, distinctive of logic, to a general consideration about the commitments of assertion yields a mode of justification for logical constants akin to some conceptions of Harmony, i.e., to the idea that the consequences of assertion of a logical complex need to be warranted by the grounds and ought to be the strongest consequences warranted by the grounds. Intuitionistic logic acquires a somewhat familiar justification but emanating from a new motivation. (shrink)

This volume is an introduction to both newer and more established ideas in the growing field of critical phenomenology from a number of disciplinary perspectives.

Combining the philosophy and musicology of T.W. Adorno, Walter Benjamin, and Gilles Deleuze, Joseph Weiss makes an original contribution to the field of aesthetics and critical theory. Highlighting previously hidden connections between these philosophers' work brings into focus a new perspective on the dynamic relationship between music, nature, history, and technology. Musical expression in this study is presented as one of the core ways in which human beings are able to escape their more base natures and instincts. The complex (...) ways in which song is taken up across time and place is viewed through the prism of different technologies and histories. This historical process, which Weiss refers to as the 'instrumentalization of the voice', following Deleuze, is illuminated though a wide-ranging analysis encompassing lullaby, jazz, classical music, and the electroacoustic avant-garde. Deepening the aesthetic analysis of music in relation to the conceptual problems of continental philosophy, Weiss reveals enlightening theoretical consequences. By engaging with an eclectic range of 20th century theorists, including Primo Levi, James Baldwin, Édouard Glissant, Fred Moten, and Angela Davis, Weiss makes the argument that advanced music remains a refuge for political hopes that are as yet blocked from realization. Speaking to contemporary debates on post-humanism, memory, and the threat of neo-fascist social relations, the author outlines a bold new aesthetics of music. (shrink)

The paper explores the main competing interpretations of Aristotle's view of the relation between happiness and external goods in the Nicomachean Ethics. On the basis of a careful analysis of what Aristotle says in the Nicomachean Ethics (and other works such as the Eudemian Ethics, Politics, Rhetoric, etc.) it is argued that it is likely that Aristotle takes at least some external goods to be actual constituents of happiness provided that (1) they are accompanied by virtuous activity and (2) the (...) agent enjoying and using those external goods does so in ways compatible with the continuous aim of acting virtuously. (shrink)

Skeptical theism is a family of responses to the evidential problem of evil. What unifies this family is two general claims. First, that even if God were to exist, we shouldn’t expect to see God’s reasons for permitting the suffering we observe. Second, the previous claim entails the failure of a variety of arguments from evil against the existence of God. In this essay, we identify three particular articulations of skeptical theism—three different ways of “filling in” those two claims—and describes (...) their role in responding to evidential arguments of evil due to William Rowe and Paul Draper. But skeptical theism has been subject to a variety of criticisms, several of which raise interesting issues and puzzles not just in philosophy of religion but other areas of philosophy as well. Consequently, we discuss some of these criticisms, partly with an eye to bringing out the connections between skeptical theism and current topics in mainstream philosophy. Finally, we conclude by situating skeptical theism within our own distinctive methodology for evaluating world views, what we call “worldview theory versioning.”. (shrink)

Second-order logic and modal logic are both, separately, major topics of philosophical discussion. Although both have been criticized by Quine and others, increasingly many philosophers find their strictures uncompelling, and regard both branches of logic as valuable resources for the articulation and investigation of significant issues in logical metaphysics and elsewhere. One might therefore expect some combination of the two sorts of logic to constitute a natural and more comprehensive background logic for metaphysics. So it is somewhat surprising to find (...) that philosophical discussion of secondorder modal logic is almost totally absent, despite the pioneering contribution of Barcan. (shrink)

Things in common: an introduction -- Life -- Specters -- Subscendence -- Species -- Kindness.

Lewisian reference magnetism about linguistic content determination [Lewis 1983 has been defended in recent work by Weatherson [2003] and Sider [2009], among others. Two advantages claimed for the view are its capacity to make sense of systematic error in speakers' use of their words, and its capacity to distinguish between verbal and substantive disagreements. Our understanding of both error and disagreement is linked to the role of usage and first order intuitions in semantics and in linguistic theory more generally. I (...) argue, partially on the basis of these more general considerations, that reference magnetism delivers implausible results. Specifically, I argue that the proponent of reference magnetism maintains her analysis of genuinely systematic error at the cost of an empirically unjustifiable error theory regarding ordinary usage. In response, I describe an alternative view of content determination—MUMPS, or Meaning is Use Minus Pragmatics—which is not committed to such error theories. Despite this advantage, MUMPS has high prima facie costs. On such a view, there is a great deal of variation in linguistic meaning across speakers and times. As a result, a large number of seemingly mistaken claims are analysed as expressing true propositions. Correspondingly, a large number of seemingly substantive disagreements are analysed as terminological. However, I argue that these consequences are not as costly as they seem. Despite appearances, MUMPS is consistent with objective, metaphysically realist adjudication of disagreements, even in cases where meanings are not shared and where both parties to a dispute speak truly. MUMPS thus allows for a more nuanced understanding of linguistic usage, change, and variation, without imposing a commitment to any form of metaphysical anti-realism. (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)

Insofar as disagreement may in principle regard most of (maybe all) facets of information system ontologies’ [ISOs] debate, it may also produce a plurality of views – sometimes inconsistent with each other – on ISOs’ development and design. This paper analyzes a view that makes the recognition of – and provides a theoretical foundation for – such a plurality of views a trademark: perspectivism (on ISOs). The aim is to show what exactly endorsing perspectivism consists of, and how perspectivism differs (...) from different, competing views. Section 2 introduces the main claims of perspectivism, and remarks that perspectivism mainly deals with ISOs’ development and design. As for ISOs’ development, Sect. 3 considers domain’s partition and systematization, by distinguishing perspectivism from realism and relativism. Section 3 also shows that perspectivism implies some sort of variantism on ISOs’ representational primitives, about which perspectivism may not differ from its rivals. As for the ISOs’ design, Sect. 4 points out that despite perspectivism grants the possibility to use any procedural approach, principle, and ontological language, it is not committed to uphold that all those approaches, principles, and languages are legitimate. Finally, Sect. 5 focuses on both perspectivism’s weaknesses and (theoretical) contribution to ISOs’ debate. (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.

On method, discursive logics, and epistemology -- Questions of medieval discursive practice -- From the middle ages to the (w)hole of Utopia -- Kepler, his Dream, and the analysis and pattern of thought -- Campanella and Bacon: concerning structures of mind -- The masculine birth of time -- Cyrano and the experimental discourse -- The myth of sun and moon -- The difficulty of writing -- Crusoe rights his story -- Gulliver's critique of Euclid -- Emergence, consolidation, and dominance of (...) a discourse. (shrink)

Among Dunn’s many important contributions to relevance logic was his work on the system RM (R-mingle). Although RM is an interesting system in its own right, it is widely considered to be too strong. In this chapter, I revisit a closely related system, RM0 (sometimes known as ‘constructive mingle’), which includes the mingle axiom while not degenerating in the way that RM itself does. My main interest will be in examining this logic from two related semantical perspectives. First, I give (...) a purely operational bisemilattice semantics for it by adapting previous work of Humberstone. Second, I examine a more conventional algebraic semantics for it and discuss how this relates to the operational semantics. A novel operational semantics for J (intuitionistic logic) as well as its conventional Heyting algebraic semantics emerge as special cases of the corresponding semantics for RM0. The results of this chapter suggest that RM0 is a more interesting logic than has been appreciated and that Humberstone’s operational semantic framework similarly deserves more attention than it has received. (shrink)

Social science, history, and philosophy have often been neglect in thinking through their fundamentally intertwined relationship. The result is often an inattention to philosophy where social science and history is concerned, or a neglect of historicity and social analysis where philosophy is concerned. Meanwhile, the place of values in research is often uneasily passed over in silence. The inattention to, and loss of, the intersection between these different disciplines and their subject matters, leaves our investigations all the more impoverished as (...) a result. In resolving these problems, it is not enough to strive for cooperation or integration, but to rethink of the nature of the disciplines themselves; their interests, purposes, and presuppositions. In this volume, contributors explore different facets of these relationships, and move beyond the problematics erected by positivism often cast in terms of value-free or value-neutral science, that is, a science obsessed with empirical data, schematic classifications, and the pursuit of law-like forms. While positivism has been subject to critique, the influence and legacy of positivism remains. It remains in the way in which we often think about science; the line drawn between the sciences and the humanities; the norms researchers should follow; what a successful explanation looks like; and the ethical, normative, and political implications of scientific research. Aimed at students and researchers of philosophy, history and the social sciences, this book is driven by a desire to revindicate questions concerning ontology and social ontology, to rethink the nature of explanation, and to resituate normativity and values within scientific, social scientific, and historical pursuits. (shrink)

I. An argument is presented for the conclusion that the hypothesis that no one will ever decide a given proposition is intuitionistically inconsistent. II. A distinction between sentences and statements blocks a similar argument for the stronger conclusion that the hypothesis that I have not yet decided a given proposition is intuitionistically inconsistent, but does not block the original argument. III. A distinction between empirical and mathematical negation might block the original argument, and empirical negation might be modelled on Nelson''s (...) strong negation, but only on intuitionistically unacceptable assumptions. IV. Intuitionists may have to accept the original argument, and therefore be committed to a dubious view of time on which there cannot be merely inductive evidence for statements about the infinite future. (shrink)

In On the Trinity 15.12.21, Augustine appears to endorse the KK principle (that if one knows that φ, then one knows that one knows that φ) in the course of giving an argument – the Multiplicity Argument – against the Academic skeptics. Gareth Matthews has disputed Augustine’s endorsement of the KK principle and presented a different reading of the Multiplicity Argument. In this note, I show that Matthews’s construal of the Multiplicity Argument is both interpretively and technically defective and defend (...) the attribution of some form of the KK principle to Augustine. (shrink)

The chapter argues that a model‐building methodology like that widespread in contemporary natural and social science already plays a significant role in philosophy. One neglected form of progress in philosophy over the past fifty years has been the development of better and better formal models of significant phenomena. Examples are given from both philosophy of language and epistemology. Philosophy can do still better in the future by applying model‐building methods more systematically and self‐consciously, with consequent readjustments to its methodology. Although (...) it is neither likely nor desirable for model‐building to become the sole or even main philosophical method, its use enhances the power and reliability of philosophical thinking. (shrink)

The book covers a broad range of key topics, including theories of properties and particulars, the notion of truth-makers, powers and possibilities, material composition, and a variety of issues related to time and causation.

The Reader's Guide to Lesbian and Gay Literature identifies key resources for topics important to the theory and practice of lesbian and gay politics, literature, religion, and more. The book contains hundreds of entries that summarize key issues at stake and then identify (mostly) book-length analysis of this topics. The topics range from activism, to age of consent, to legal history as well as individual entries on key authors and regional areas.

I argue that a practice can only be taken to be one of apparent rule following if it contains a practice of policing moves within the practice. So the existence of an apparently rule-governed practice entails the existence of, what I call, a policing practice. I then argue that this entailment cannot be reconciled with a non-factualist construal of the policing practice. Thus non-factualism about the policing practice is false. Factualism about the policing practice entails realism about rules. So I (...) conclude that we ought to be realists about rules. Finally I distinguish a position which I call ultra-realism about rules and note that this too is a casualty of the view developed here. (shrink)

The philosophical relevance of experimental psychology is hard to dispute. Much more controversial is the so‐called negative program's critique of armchair philosophical methodology, in particular the reliance on ‘intuitions’ about thought experiments. This chapter responds to that critique. It argues that, since the negative program has been forced to extend the category of intuition to ordinary judgments about real‐life cases, the critique is in immediate danger of generating into global scepticism, because all human judgments turn out to depend on intuitions. (...) Recently, some proponents of the negative program have tried to demarcate the target of their critique more narrowly. However, their attempts are still far too indiscriminate, and over‐generate scepticism. Nevertheless, once experimental philosophy has refined its own methodology, it may contribute to the refinement of the methodology of mainstream philosophy, by filtering out the effects of cognitive bias, although it offers no prospect of doing without judgments on real or imaginary cases. (shrink)