The human and mouse genomes are complex from a genomic standpoint. Each cell has the same genomic sequence, yet a wide array of cell types exists due to the presence of a plethora of regulatory elements in the non‐coding genome. Recent advances in epigenomic profiling have uncovered non‐coding gene proximal promoters and distal enhancers of transcription genome‐wide. Extension of promoter‐associated H3K4me3 histone mark across the gene body, known as a broad H3K4me3 domain (H3K4me3‐BD), is a signature of constitutive expression of (...) cell‐type‐specific regulation and of tumour suppressor genes in healthy cells. Recently, it has been discovered that the presence of H3K4me3‐BDs over oncogenes is a cancer‐specific feature associated with their dysregulated gene expression and tumourigenesis. Moreover, it has been shown that the hijacking of clusters of enhancers, known as super‐enhancers (SE), by proto‐oncogenes results in the presence of H3K4me3‐BDs over the gene body. Therefore, H3K4me3‐BDs and SE crosstalk in healthy and cancer cells therefore represents an important mechanism to identify future treatments for patients with SE driven cancers. (shrink)

Recent debate over World Health Organization reform has included unprecedented attention to international lawmaking as a future priority function of the Organization. However, the debate is largely focused on the codification of new binding legal instruments. Drawing upon lessons from the success of the Global AIDS Reporting Mechanism, established pursuant to the United Nations' Declaration of Commitment on HIV/AIDS, we argue that effective global health governance requires consideration of a broad range of instruments, both binding and nonbinding. A detailed examination (...) of the Global AIDS Reporting Mechanism reveals that the choice of the nonbinding format makes an important contribution to its effectiveness. For instance, the flexibility and adaptability of the nonbinding format have allowed the global community to: (1) undertake commitments in a timely manner; (2) adapt and experiment in the face of a dynamic pandemic; and (3) grant civil society an unparalleled role in monitoring and reporting on state implementation of global commitments. UNAIDS' institutional support has also played a vital role in ensuring the continuing effectiveness of the Global AIDS Reporting Mechanism. Overall, the experience of the Global AIDS Reporting Mechanism evidences that, at times, nimbler nonbinding instruments can offer benefits over slower, more rigid binding legal approaches to governance, but depend critically, like all instruments, on the perceived legitimacy thereof. (shrink)

In recent debates surrounding World Health Organization reform, international lawmaking has received unprecedented attention as a future priority function of the Organization. Although WHO's constitutional lawmaking authority was historically neglected and even resisted by WHO and its Member States until the adoption of its first treaty a decade ago, the widespread consensus in favor of a central role for lawmaking in visions of a reformed WHO reflects the crystallization of contemporary approaches to global health governance. Today it is widely recognized (...) that the trends toward globalization that have restricted the capacity of sovereign states to protect health through unilateral action alone have made innovative mechanisms to promote global cooperation and coordination, including international lawmaking, an essential component of governance of public health. (shrink)

Some secrets are fine to keep to ourselves, and others are not. At first glance, Clark’s secret seems to be fine, but it may not be if we look further into it. We all know Clark’s big secret: he is Superman. Secrets always belong to someone. This is one of the things that distinguish secrets from information we simply don’t have. Secrecy is morally neutral and can be used for good or bad ends. One other closely linked concept we must (...) distinguish from secrecy is privacy. Clark Kent is a citizen (sort of), but Superman is purely a public persona. In Superman, vol. 2, #2 (February 1987), Lex Luthor figured out Superman’s secret. Superman has confided his true identity to the Kents and Lana. In Clark’s case, there are several reasons for his secret, but the most compelling one is to protect his loved ones. (shrink)

The Swiss Cantons had no greater admirer in the eighteenth-century than the French political thinker Gabriel Bonnot de Mably. The feeling was mutual, at least to some extent, since the Bernese Patriotic Society awarded its first prize in 1763 to Mably, for his dialogue Entretiens de Phocion. The prize then led to an exchange of letters, stretching across some two decades, with Daniel Fellenberg, founder of the Patriotic society—the most important block of Mably's correspondence to have survived. This essay (...) considers the 1763 prize and the correspondence with Fellenberg for the light they cast both on Mably and on Bernese participation in the wider currents of eighteenth-century thought. (shrink)

“Employees have rights by virtue of employment law and the contract of employment. They also have a third right, however: that of being treated with respect…” What this implies is explored here in detail by the Senior Partner of Phoenix Human Resources Consultants, 17 Den Road, Shortlands, Bromley, Kent BR2 ONH. Ms Douglas originally gave this presentation at a meeting of The Ethical Business Forum at London Business School.

There are many mean and nasty things to say about mean and nasty talk, but I don't plan on saying any of them. There's a specific problem about slurring words that I want to address. This is a semantic problem. It's not very important compared to the real-world problems presented by bigotry, racism, discrimination, and worse. It's important only to linguistics and the philosophy of language.

Once upon a time it was assumed that speaking literally and directly is the norm and that speaking nonliterally or indirectly is the exception. The assumption was that normally what a speaker means can be read off of the meaning of the sentence he utters, and that departures from this, if not uncommon, are at least easily distinguished from normal utterances and explainable along Gricean lines. The departures were thought to be limited to obvious cases like figurative speech and conversational (...) implicature. However, people have come to appreciate that the meaning of a typical sentence, at least one we are at all likely to use, is impoverished, at least relative to what we are likely to mean in uttering it. In other words, what a speaker normally means in uttering a sentence, even without speaking figuratively or obliquely, is an enriched version of what could be predicted from the meaning of the sentence alone. This can be because the sentence expresses a “minimal” (or “skeletal”) proposition or even because it fails to express a complete proposition at all.1 Indeed, it is now a platitude that linguistic meaning generally underdetermines speaker meaning. That is, generally what a speaker means in uttering a sentence, even if the sentence is devoid of ambiguity, vagueness, or indexicality, goes beyond what the sentence means. The question is what to make of this Contextualist Platitude, as I’ll call it. It may be a truism, but does it require a radical revision of the older conception of the relation between what sentences mean and what speakers mean in uttering them? Does it lead to a major modification, or perhaps even outright rejection, of the semantic-pragmatic distinction? I think.. (shrink)

a comprehensive, somewhat Gricean theory of speech acts, including an account of communicative intentions and inferences, a taxonomy of speech acts, and coverage of many topics in pragmatics -/- .

This article makes a number of points about reference, both speaker reference and linguistic reference. The bottom line is simple: reference ain't easy — at least not nearly as easy as commonly supposed. Much of what speakers do that passes for reference is really something else, and much of what passes for linguistic reference is really nothing more than speaker reference. Referring is one of the basic things we do with words, and it would be a good idea to understand (...) what that involves and requires before worrying about the linguistic means by which this is done. (shrink)

It is common to hear talk of the aim of belief and to find philosophers appealing to that aim for numerous explanatory purposes. What belief 's aim explains depends, of course, on what that aim is. Many hold that it is somehow related to truth, but there are various ways in which one might specify belief 's aim using the notion of truth. In this article, by considering whether they can account for belief 's standard of correctness and the epistemic (...) norms governing belief, I argue against certain prominent specifications of belief 's aim given in terms of truth, and advance a neglected alternative. (shrink)

Think of linguistification by analogy with personification: attributing linguistic properties to nonlinguistic phenomena. For my purposes, it also includes attributing nonlinguistic properties to linguistic items, i.e., treating nonlinguistic properties as linguistic. Linguistification is widespread. It has reached epidemic proportions. It needs to be eradicated. That’s important because the process of communication is not simply a matter of one person putting a thought into words and another decoding them back into the same thought. Much of what a speaker means cannot be (...) traced to what his words mean or to their possibly context-sensitive semantic contents. Words carry information all right, but that information hardly determines what speakers mean in uttering them. They leave plenty of pragmatic gaps and sometimes even semantic slack. I’ll mention various reasons for that, but the important thing is to recognize how much people exploit extralinguistic information in communicating and to avoid confusing this process with semantic context sensitivity. To appreciate the limitations of semantics, we shouldn’t fall for the fallacy of misplaced information or for the more specific fallacies enumerated below. (shrink)

Where does normal brain or psychological function end, and pathology begin? The line can be hard to discern, making disease sometimes a tricky word. In addiction, normal ‘wanting’ processes become distorted and excessive, according to the incentive-sensitization theory. Excessive ‘wanting’ results from drug-induced neural sensitization changes in underlying brain mesolimbic systems of incentive. ‘Brain disease’ was never used by the theory, but neural sensitization changes are arguably extreme enough and problematic enough to be called pathological. This implies that ‘brain disease’ (...) can be a legitimate description of addiction, though caveats are needed to acknowledge roles for choice and active agency by the addict. Finally, arguments over ‘brain disease’ should be put behind us. Our real challenge is to understand addiction and devise better ways to help. Arguments over descriptive words only distract from that challenge. (shrink)

The _Physics_ is a foundational work of western philosophy, and the crucial one for understanding Aristotle's views on matter, form, essence, causation, movement, space, and time. This richly annotated, scrupulously accurate, and consistent translation makes it available to a contemporary English reader as no other does—in part because it fits together seamlessly with other closely associated works in the New Hackett Aristotle series, such as the _Metaphysics_, _De Anima_, and forthcoming _De Caelo_ and _On Coming to Be and Passing Away_. (...) Eventually the series will include all of Aristotle's works. Sequentially numbered endnotes provide the information most needed at each juncture, while a detailed Index of Terms indicates places where focused discussion of key notions occurs. An illuminating general Introduction describes the book that lies ahead, explaining what sort of work it is and what sorts of evidence it relies on. (shrink)

Different brain mechanisms seem to mediate wanting and liking for the same reward. This may have implications for the modular nature of mental processes, and for understanding addictions, compulsions, free will and other aspects of desire. A few wanting and liking phenomena are presented here, together with discussion of some of these implications.

Confusion in terms inspires confusion in concepts. When a relevant distinction is not clearly marked or not marked at all, it is apt to be blurred or even missed altogether in our thinking. This is true in any area of inquiry, pragmatics in particular. No one disputes that there are various ways in which what is communicated in an utterance can go beyond sentence meaning. The problem is to catalog the ways. It is generally recognized that linguistic meaning underdetermines speaker (...) meaning because of the need for disambiguation and reference assignment and because people can speak figuratively or indirectly. But philosophers and linguists are coming to recognize that these are not the only ways. The situation may be described in Gricean terms: the distinction between what is said and what is implicated is not exhaustive. Charting the middle ground between the two will require attending to specific examples, noting their distinctive features, and articulating the relevant concepts. That is what I aim to do here. The basic idea will be to distinguish not only the implied from the explicit but the implicit from the implied. (shrink)

Psychopaths constitute less than 1% of the general population, but they commit a much larger proportion of crime and violence in society. This volume chronicles the latest science of psychopathy, various ways that psychopaths challenge the criminal justice system, and the major ethical issues arising from this fascinating condition.

China is the world’s second largest economy and the largest emitter of carbon dioxide, yet we know little about environmental proactivity in the most populated country in the world. We address this gap through a survey of 161 Chinese companies with two respondents per firm (N = 322), where we seek to identify the antecedents and consequences of environmental proactivity. We identify two categorizations of environmental proactivity: Environmental operational improvements and environmental reporting. We find that ecological motivations and regulatory stakeholder (...) pressure are positively related to both types of environmental proactivity, and external stakeholder pressure is negatively related to environmental reporting. Furthermore, we find that (1) if a firm is environmentally proactive (as it relates to either measure) and they are ecologically motivated, there is a positive and significant cost advantage, and (2) if a firm makes use of environmental operational improvement and they are competitively motivated, there is a positive and significant reputation advantage. Implications for researchers, managers, and policy-makers in China are discussed. (shrink)

Introduction: dimensions of inquiry -- Speaker intent and convention; linguistic meaning and pragmatics; Vagueness and indeterminacy: three topics in the philosophy of language -- Literary interpretation, performance art, and related subjects -- Religious interpretation -- General theories of interpretation -- Starting from the bottom: informal instructions -- The law of agency -- Wills -- Contracts -- Judicial alterations of textual provisions: Cy Pres and relatives -- Conclusion and a comparison.

Presenting a novel account of singular thought, a systematic application of recent work in the theory of speech acts, and a partial revival of Russell's analysis of singular terms, this book takes an original approach to the perennial problems of reference and singular terms by separating the underlying issues into different levels of analysis.

Grice’s distinction between what is said and what is implicated has greatly clarified our understanding of the boundary between semantics and pragmatics. Although border disputes still arise and there are certain difficulties with the distinction itself (see the end of §1), it is generally understood that what is said falls on the semantic side and what is implicated on the pragmatic side. But this applies only to what is..

This paper offers a smattering of applications of pragmatics to epistemology. In most cases they concern recent epistemological claims that depend for their plausibility on mistaking something pragmatic for something semantic. After giving my formulation of the semantic/pragmatic distinction and explaining how seemingly semantic intuitions can be responsive to pragmatic factors, I take up the following topics: 1. Classic Examples of Confusing Meaning and Use 2. Pragmatic Implications of Hedging or Intensifying an Assertion 3. Belief Attributions 4. Knowledge-wh 5. The (...) Knowledge Rule on Assertion 6. Testimony 7. Asserting and Thinking of Possibilities 8. Concessive Knowledge Attributions 9. “Pragmatic Encroachment” 10. Epistemic Contextualism.. (shrink)

We examine three assumptions commonly held in the corporate reputation literature: (1) reputation ratings of owners and investors are generally representative of all stakeholders; (2) stakeholders will generally provide a higher reputation rating to firms that emphasize corporate social responsibility versus firms that do not; and (3) profitability is the primary criterion of importance to all stakeholders when rating a firm's reputation. Using an exploratory in‐class exercise, our findings suggest that: (1) there are significant differences among stakeholder groups in their (...) reputation ratings; (2) firms that emphasize corporate social responsibility are not rated more highly across all stakeholder groups; and (3) for all stakeholder groups, the ethicality criterion explained more of the variance in firms' reputation ratings than the profitability criterion. (shrink)

Examines the lived experience of social encounters drawing on phenomenological insights.