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)

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)

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)

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.

Humean arguments from evil are some of the most powerful arguments against Theism. They take as their data what we know about good and evil. And they argue that some rival to Theism better explains, or otherwise predicts, that data than Theism. However, this paper argues that there are many problems with various methods for defending Humean arguments. I consider Philo’s original strategy; modern strategies in terms of epistemic probability; phenomenological strategies; and strategies that appeal to scientific and metaphysical explanations. (...) None of these methods have been sufficiently developed to provide a clear and distinctive defense of Humean arguments. Defenders of Humean arguments need to spend more time on the underlying methodology of their arguments. (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.

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)

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)

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 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)

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

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.

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)

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

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)

Early practitioners of the social studies of science turned their attention away from questions of institutionalisation, which had tended to emphasize macrolevel explanations, and attended instead to microstudies of laboratory practice. The author is interested in re-investigating certain aspects of institution formation, notably the formation of scientific, medical, and engineering disciplines. He emphasises the manner in which science as cultural practice is imbricated with other forms of social, political, and even aesthetic practices. The author considers the following topics: the organic (...) physics of 1847; the innovative research program of Carl Ludwig as a model for institutionalising science-based medicine, optics, painting, and ideology in Germany, 1845-95; the Haber-Bosch synthesis of ammonia; and the introduction of nuclear magnetic resonance instrumentation into the practice of organic chemistry. (shrink)

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)

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)

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)

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)

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.

This essay defends an epistemicist response to the phenomenon of vagueness concerning moral terms. I outline a traditional model of - and then two novel approaches to - epistemicism about moral predicates, and I demonstrate how the foregoing are able to provide robust explanations of the source of moral, as epistemic, indeterminacy. The first approach to moral epistemicism concerns the extensions of moral predicates, as witnessed by the non-transitivity of a value-theoretic sorites paradox. The second approach to moral epistemicism is (...) induced by the status of moral dilemmas in the epistemic interpretation of two-dimensional semantics. I examine the philosophical significance of the foregoing, and compare the proposal to those of ethical expressivism, constructivism, and scalar act-consequentialism. Finally, I examine the status of moral relativism in light of the epistemicist models of moral vagueness developed in the paper. (shrink)

Disorders of volition are often accompanied by, and may even be caused by, disruptions in the phenomenology of agency. Yet the phenomenology of agency is at present little explored. In this paper we attempt to describe the experience of normal agency, in order to uncover its representational content.

This paper argues that the types of intention can be modeled both as modal operators and via a multi-hyperintensional semantics. I delineate the semantic profiles of the types of intention, and provide a precise account of how the types of intention are unified in virtue of both their operations in a single, encompassing, epistemic space, and their role in practical reasoning. I endeavor to provide reasons adducing against the proposal that the types of intention are reducible to the mental states (...) of belief and desire, where the former state is codified by subjective probability measures and the latter is codified by a utility function. I argue, instead, that each of the types of intention -- i.e., intention-in-action, intention-as-explanation, and intention-for-the-future -- has as its aim the value of an outcome of the agent's action, as derived by her partial beliefs and assignments of utility, and as codified by the value of expected utility in evidential decision theory. (shrink)

Imagine a philosophy conference in Presocratic Greece. The hot question is: what are things made of? Followers of Thales say that everything is made of water, followers of Anaximenes that everything is made of air, and followers of Heraclitus that everything is made of fire. Nobody is quite clear what these claims mean, and some question whether the founders of the respective schools ever made them. But amongst the groupies there is a buzz about all the recent exciting progress. The (...) mockers and doubters make plenty of noise too. They point out that no resolution of the dispute between the schools is in sight. They diagnose Thales, Anaximenes and Heraclitus as suffering from a tendency to overgeneralize. We can intelligibly ask what bread is made of, or what houses are made of, but to ask what things in general are made of is senseless, some suggest, because the question is posed without any conception of how to verify an answer; language has gone on holiday. Paleo-pragmatists invite everyone to relax, forget their futile pseudo-inquiries and do something useful instead. (shrink)

There’s a growing sense among philosophers of religion that Humean arguments from evil are some of the most formidable arguments against theism, and skeptical theism fails to undermine those arguments because they fail to make the inferences skeptical theists criticize. In line with this trend, Wes Morriston has recently formulated a Humean argument from evil, and his chief defense of it is that skeptical theism is irrelevant to it. Here I argue that skeptical theism is relevant to Humean arguments. To (...) do this, I reveal the common structure of skeptical theism’s critiques. Seeing the common structure reveals why some versions of skeptical theism are irrelevant to Humean arguments from evil. It also points the way forward to formulating a relevant version. By combining skeptical theism with a plausible principle concerning reasonable belief, I formulate a version of skeptical theism that undermines Morriston’s argument that is also immune from his objections. (shrink)

This paper targets a series of potential issues for the discussion of, and modal resolution to, the alethic paradoxes advanced by Scharp (2013). I proffer four novel extensions of the theory, and detail five issues that the theory faces.

Over the years, Skolem’s Paradox has generated a fairly steady stream of philosophical discussion; nonetheless, the overwhelming consensus among philosophers and logicians is that the paradox doesn’t constitute a mathematical problem (i.e., it doesn’t constitute a real contradiction). Further, there’s general agreement as to why the paradox doesn’t constitute a mathematical problem. By looking at the way firstorder structures interpret quantifiers—and, in particular, by looking at how this interpretation changes as we move from structure to structure—we can give a technically (...) adequate “solution” to Skolem’s Paradox. So, whatever the philosophical upshot of Skolem’s Paradox may be, the mathematical side of Skolem’s Paradox seems to be relatively straightforward. (shrink)

To desire something is a condition familiar to everyone. It is uncontroversial that desiring has something to do with motivation, something to do with pleasure, and something to do with reward. Call these "the three faces of desire." The standard philosophical theory at present holds that the motivational face of desire presents its unique essence--to desire a state of affairs is to be disposed to act so as to bring it about. A familiar but less standard account holds the hedonic (...) face of desire to reveal to true nature of desire. In this view, to desire something is to tend to pleasure if it seems that the desired state of affairs has been achieved, or displeasure if it seems otherwise, thus tying desire to feelings instead of actions. In Three Faces of Desire, Schroeder goes beyond actions and feelings to advance a novel and controversial theory of desire that puts the focus on desire's neglected face, reward. Informed by contemporary science as much as by the philosophical tradition, Three Faces of Desire discusses recent scientific discoveries that tell us much about the way that actions and feelings are produced in the brain. In particular, recent experiments reveal that a distinctive system is responsible for promoting action, on the one hand, and causing feelings of pleasure and displeasure, on the other. This system, the brain's reward system, is the causal origin of both action and feeling, and is the key to understanding the nature of desire. (shrink)

The influence of Heidegger's on current thought has been pervasive. In reaction to Enlightenment ideas, he presents a view of the modern world as destructive of nature, community, tradition, individuality, and more. His writings have influenced such central social and literary thinkers as Derrida and Foucault. This volume is the first thorough introduction to his work on language and literature. Heidegger's reputation for being difficult has scared off many who would have otherwise profited from a knowledge of his work. This (...) guide is written with these people in mind. It is "student-friendly" and presents Heidegger's ideas in a clear and comprehensible manner. Understanding Heidegger is essential for anyone who wants to understand current literary theory, and this guide is essential for anyone seeking to understand Heidegger. (shrink)

Medical practice is ideally based on robust, relevant research. However, the lack of disease-modifying treatments for Alzheimer’s disease has motivated “innovative practice” to improve patients’ well-being despite insufficient evidence for the regular use of such interventions in health systems treating millions of patients. Innovative or new non-validated practice poses at least three distinct ethical questions: first, about the responsible application of new non-validated practice to individual patients ; second, about the way in which data from new non-validated practice are communicated (...) via the scientific and lay press ; and third, about the prospect of making new non-validated interventions widely available before more definitive testing. We argue that the authors of metabolic enhancement protocols for Alzheimer’s disease have overstated the evidence in favor of these interventions within the scientific and lay press, failing to communicate weaknesses in their data and uncertainty about their conclusions. Such unmeasured language may create false hope, cause financial harm, undermine informed consent, and frustrate the production of generalizable knowledge necessary to face the societal problems posed by this devastating disease. We therefore offer more stringent guidelines for responsible innovation in the treatment of Alzheimer’s disease. (shrink)