Interferons (IFNs) are a diverse group of cytokines whose potent antitumor effects have piqued the interest of scientists for decades. Some of the most sustained clinical accomplishments have been in the field of myeloproliferative neoplasms (MPNs). Here, we discuss how both historical and novel breakthroughs in our understanding of IFN function may lead to more effective therapies for MPNs. The particular relevance and importance of modulating the novel IFN‐regulated ULK1 pathway to optimize IFN responses is highlighted.

Perry argues that certain sorts of indexicals are 'essential', in the sense that they cannot be eliminated in favor of descriptions. This paper also introduces the influential idea that certain sorts of indexicals play a special role in thought, and have a special connection to action.

Several philosophical issues in connection with computer simulations rely on the assumption that results of simulations are trustworthy. Examples of these include the debate on the experimental role of computer simulations :483–496, 2009; Morrison in Philos Stud 143:33–57, 2009), the nature of computer data Computer simulations and the changing face of scientific experimentation, Cambridge Scholars Publishing, Barcelona, 2013; Humphreys, in: Durán, Arnold Computer simulations and the changing face of scientific experimentation, Cambridge Scholars Publishing, Barcelona, 2013), and the explanatory power of (...) computer simulations :277–292, 2008; Durán in Int Stud Philos Sci 31:27–45, 2017). The aim of this article is to show that these authors are right in assuming that results of computer simulations are to be trusted when computer simulations are reliable processes. After a short reconstruction of the problem of epistemic opacity, the article elaborates extensively on computational reliabilism, a specified form of process reliabilism with computer simulations located at the center. The article ends with a discussion of four sources for computational reliabilism, namely, verification and validation, robustness analysis for computer simulations, a history of successful implementations, and the role of expert knowledge in simulations. (shrink)

Proceedings of the Aristotelian Society, Volume 115, Issue 3pt3, Page 211-233, December 2015.

This collection gathers a set of central papers from the emerging area of ethics and climate change.

Husserl seldom refers to feelings, and when he does, he mainly focuses on their axiological character, which corresponds to a specific kind of value apprehension. This paper aims to discuss the role of feelings in Husserl from a different angle. For this purpose it makes a detour through Husserl’s early account of attention. In a text from 1898 on attention the aspect of interest, which is said to have a basis in feeling, plays an essential role. Although Husserl argues (...) here that every specific interest is dependent on an objectifying act of perception, he at the same time states that every act of perception necessarily has to be accompanied by an interest of some sort. In the latter sense, the genuine motivational force and necessity of this feeling aspect, namely interest, is emphasized. This ambiguity – or even contradiction – shall be the point of departure for the following considerations. The paper argues that it is possible to interpret the role of feelings in intentionality in a different way, namely not as an effect of current perception but as a cause of further perceptions. This tendency is first indicated in the text from 1898 and elaborated further in Husserl’s genetic approach in Experience and Judgment. In Experience and Judgment Husserl develops a broader notion of interest, defining it as a general perceptual drive. This general drive – so the paper will argue – expresses itself in concrete perception as a specific preference: it discloses or makes manifest what is relevant for an individual subject at a given time. (shrink)

Ideal for students and scholars alike, this edition of _Zhuangzi _ includes the complete Inner Chapters, extensive selections from the Outer and Miscellaneous Chapters, and judicious selections from two thousand years of traditional Chinese commentaries, which provide the reader access to the text as well as to its reception and interpretation. A glossary, brief biographies of the commentators, a bibliography, and an index are also included.

The environment impacts human health in profound ways, yet few theories define the form of the relationship between human physiology and the environment. It is conjectured that such complex systems cannot interact directly, but rather their interaction requires the formation of an intermediary “interface.” This position contrasts with current epidemiological constructs of causation, which implicitly assume that two complex systems transfer information directly while remaining separate entities. Further, it is contended that dynamic, process‐based interfaces incorporate components from all the interacting (...) systems but exhibit operational independence. This property has many consequences, the foremost being that characteristics of the interface cannot be fully resolved by only studying the systems involved in the interaction. The interface itself must be the subject of inquiry. Without refocusing the attention on biodynamic interfaces, how the environment impacts health cannot be discerned. Also see the video abstract here https://youtu.be/XeyjeZeyo4o. (shrink)

"Ludwig Wittgenstein's brief Tractatus Logico-Philosophicus is one of the most important philosophical works of the Twentieth Century, yet it offers little orientation for the reader. The first-time reader is left wondering what it could be about, and the scholar is left with little guidance for interpretation. In Tractatus in Context, James C. Klagge presents the vital background necessary for appreciating Wittgenstein's gnomic masterpiece. Tractatus in Context contains the early reactions to the Tractatus, including the initial reviews written in 1922-1924. And (...) while we can't talk with Wittgenstein, we can do the next best thing-hear what he had to say about the Tractatus. Klagge thus presents what Wittgenstein thought about germane issues leading up to his writing the book, in discussions and correspondence with others about his ideas, and what he had to say about the Tractatus after it was written-in letters, lectures and conversations. It offers, you might say, Wittgenstein's own commentary on the book. Key Features: Illuminates what is at stake in the Tractatus, by providing the views of others that engaged Wittgenstein as he was writing it. Includes Wittgenstein's earlier thoughts on ideas in the book as recorded in his notebooks, letters, and conversations as well as his later, retrospective comments on those ideas. Draws on new or little-known sources, such as Wittgenstein's coded notebooks, Hermine's notes, Frege's letters, Hänsel's diary, Ramsey's notes, and Skinner's dictations. Draws connections between the background context and specific passages in the Tractatus, using a proposition-by-proposition commentary"--. (shrink)

Tens of millions of adults and children die each year from illnesses that are treatable or preventable with existing medicines. Each year over 500 million people are infected with malaria, and the disease kills two million people annually. Hundreds of thousands more die annually from a myriad of lesser known diseases including diphtheria, measles, tetanus, and syphilis. Approximately 30 percent of the world’s population, over 1.7 billion people, has inadequate access or no access at all to essential medicines.Not surprisingly, (...) the vast majority of these illnesses are contracted in poor countries. Four million lives could be saved annually through prompt diagnosis and treatment of illnesses in Africa and Southeast Asia alone, and access to pharmaceutical drugs could likely save millions more. Many of the health problems facing the developing world do not arise from lack of understanding of complex diseases. Rather, the problem arises from a striking lack of availability of life-saving medicines for the consumers that need these medicines the most. (shrink)

Michael Ravvin, Department of Political Science, Columbia University, 420 W. 118th Street, New York, NY 10027 Email: mer2133{at}columbia.edu ' + u + '@' + d + ' '//--> Abstract The existing intellectual property regime discourages the innovation of, and access to, essential medicines for the poor in developing countries. A successful proposal to reform the existing system must address these challenges of access and innovation. This essay will survey the problems in the existing pharmaceutical patent system and offer critical (...) analysis of some reform proposals. I will argue that existing mechanisms that are intended to mitigate the harms of the current pharmaceutical patent system, such as bulk buying, differential pricing and compulsory licenses, are inadequate and perhaps even counter-productive over the long-term. Other incentive mechanisms based on push funding, such as government research grants, are inefficient and limited in scope. Pull mechanisms, which offer some reward for successful pharmaceutical innovations, offer a more promising incentive mechanism. I will evaluate three pull mechanisms -- Priority Review Vouchers, Advance Market Commitment (AMC) and the Health Impact Fund -- on the basis of their capacity to incentivize access and innovation, as well as their efficiency and political feasibility. Though the Health Impact Fund appears to be the most promising proposal, more work must be done to overcome challenges of its implementation. CiteULike Connotea Del.icio.us What's this? (shrink)

Since the publication of Roy Bhaskar's A Realist Theory of Science in 1975, critical realism has emerged as one of the most powerful new directions in the philosophy of science and social science, offering a real alternative to both positivism and postmodernism. This reader makes accessible in one volume key readings to stimulate debate about and within critical realism, including: the transcendental realist philosophy of science elaborated in A Realist Theory of Science ; Bhaskar's critical naturalist philosophy of social science; (...) the theory of explanatory critique, which is central to critical realism; and the theme of dialectic, which is central to Bhaskar's most recent writings. The volume includes extracts from Bhaskar's most important books, as well as selections from all of the other most important contributors to the critical realist program. It also includes both a general introduction and original introductions to each section. (shrink)

Deployment Realism resists Laudan’s and Lyons’ objections to the “No Miracle Argument” by arguing that a hypothesis is most probably true when it is deployed essentially in a novel prediction. However, Lyons criticized Psillos’ criterion of essentiality, maintaining that Deployment Realism should be committed to all the actually deployed assumptions. But since many actually deployed assumptions proved false, he concludes that the No Miracle Argument and Deployment Realism fail. I reply that the essentiality condition is required by Occam’s razor. In (...) fact, there is a simpler formulation of essentiality which escapes Lyons’ criticisms and rescues the No Miracle Argument and Deployment Realism from their purported historical counterexamples: a hypothesis is essential when it has no proper parts (in Yablo’s sense) sufficient to derive the same prediction. Although essentiality so conceived cannot be detected prospectively, this is just natural, and it is not a problem but an advantage for Deployment Realism. (shrink)

Frege appears to hold both that thoughts are internally articulated, in a way that mirrors the semantic articulation of the sentences that express them, and that the same thought can be analyzed in different ways, none of which has to be more fundamental than the others. Commentators have often taken these theses to be mutually incompatible and have tended to polarize into two camps, each of which attributes to Frege one of the theses, but maintains that he is only apparently (...) committed to the other. This paper argues that there are good exegetical and philosophical reasons for reconciling the two theses; that this reconciliation can be achieved by rejecting an assumption shared by the two opposite camps of the exegetical debate, i.e., the assumption that essential articulatedness implies unique articulation; and finally, that this crucial assumption can be resisted by appreciating Frege’s anti-atomistic and ‘organic’ conception of the internal complexity of thoughts. (shrink)

The idea of artificial intelligence for social good is gaining traction within information societies in general and the AI community in particular. It has the potential to tackle social problems through the development of AI-based solutions. Yet, to date, there is only limited understanding of what makes AI socially good in theory, what counts as AI4SG in practice, and how to reproduce its initial successes in terms of policies. This article addresses this gap by identifying seven ethical factors that are (...) essential for future AI4SG initiatives. The analysis is supported by 27 case examples of AI4SG projects. Some of these factors are almost entirely novel to AI, while the significance of other factors is heightened by the use of AI. From each of these factors, corresponding best practices are formulated which, subject to context and balance, may serve as preliminary guidelines to ensure that well-designed AI is more likely to serve the social good. (shrink)

On September 30–October 2, 2005, a group of individuals drawn from civil society organizations, governments, international agencies, and academic institutions came together in Montréal, Québec, Canada, for an international workshop entitled “Human Rights and Access to Essential Medicines: The Way Forward.” At the conclusion of the workshop, we drafted the “Montréal Statement on the Human Right to Essential Medicines.” This “Statement” is reprinted at the end of this comment, which offers some background on the problem addressed at the (...) workshop. (shrink)

Perscrutar os processos semânticos do conceito de justiça, no espaço bíblico, conduz-nos à descoberta de percursos de sinonímia, em que os múltiplos campos semânticos se cruzam com outros instrumentos conceptuais, no intuito de recolher numa fórmula aquilo que é essencial. Por este caminho podemos contemplar as modalidades com que as culturas do mesmo contexto organizam as suas evidências mais profundas, em sistemas harmónicos de referência e numa hierarquia orgânica de valores.

This volume will be of great interest to scholars and students in epistemology.

A novel treatment of an issue central to much current work in metaphysics: the distinction between the essential and accidental properties of individuals. Mackie challenges widely held views, and arrives at what she calls "minimalist essentialism," an unorthodox theory according to which ordinary individuals have relatively few interesting essential properties. Mackie's clear and accessible discussions of issues surrounding necessity and essentialism mean that the book will appeal as much to graduate students as it will to seasoned metaphysicians.

In two recent essays, Thomas Pogge addresses the question of how research and development of essential drugs should be incentivized. Essential drugs are drugs for diseases that ruin human lives. The current incentivizing scheme for such drugs is, according to Pogge, a significant causal factor in bringing about a state of affairs in which millions of people die or suffer from lack of access to essential drugs. Pogge, therefore, suggests a reform plan for how to incentivize research (...) and development of these drugs, and he is of the opinion that implementation of this plan will have a significant positive impact on the global disease burden. This paper is a critical examination of Pogge's reform plan. In the first part of the paper, Pogge's reasons for being dissatisfied with the current incentivizing scheme are spelled out. The reform plan is then presented, and in the final part of the paper, it is argued that the reform plan is flawed at a number of levels. (shrink)

The 2017 Commission on Public Relations Education report found new professionals are not meeting employers’ expectations regarding ethics knowledge, skills and abilities. This mixed-method s...

This article argues that to advance the struggle for access to essential medicines, it is necessary to identify the global and local regimes that shape the rules that give impetus to particular policy options, while undermining others. In exploring the role of law and politics in this process, the author first outlines the globalization of a standardized, corporate-inspired, intellectual property regime. Second, the author uses the example of the HIV/aids pandemic to demonstrate how the stability of this new regime (...) came under pressure, both locally and globally. Finally, it is argued that while the global HIV/aids pandemic and the social movements that emerged in response to government inaction have effectively challenged the TRIPS regime, this complex contestation has reached an unsustainable stalemate in which development aid, corporate, and non-governmental philanthropy is simultaneously providing increased availability to drugs while precluding a more lasting solution to the crisis of access to essential medicines in developing countries. (shrink)

BackgroundEngagement of people with lived experience and members of the public is an ethically and scientifically essential component of health research. Authentic engagement means they are involved as full partners in research projects. Yet engagement as partnership is uncommon in practice, especially during priority-setting for research projects. What is needed for agenda-setting to be shared by researchers and people with lived experience and/or members of the public (or organisations representing them)? At present, little ethical guidance exists on this matter, (...) particularly that which has been informed by the perspectives of people with lived experience and members of the public. This article provides initial evidence about what they think are essential foundations and barriers to shared decision-making in health research priority-setting and health research more broadly.MethodsAn exploratory, qualitative study was conducted in 2019. 22 semi-structured interviews were performed with key informants from the UK and Australia.ResultsThree main types of foundations were thought to be essential to have in place before shared decision-making can occur in health research priority-setting: relational, environmental, and personal. Collectively, the three types of foundations addressed many (but not all) of the barriers to power sharing identified by interviewees.ConclusionsBased on study findings, suggestions are made for what researchers, engagement practitioners, research institutions, and funders should do in their policy and practice to support meaningful engagement. Finally, key international research ethics guidelines on community engagement are considered in light of study findings. (shrink)

Fibroblast growth factors (FGFs) comprise a large family of developmental and physiological signaling molecules. All FGFs have a high affinity for the glycosaminoglycan heparin and for cell surface heparan sulfate proteoglycans. A large body of biochemical and cellular evidence points to a direct role for heparin/heparan sulfate in the formation of an active FGF/FGF receptor signaling complex. However, until recently there has been no direct demonstration that heparan is required for the biological activity of FGF in a developmental system in (...) vivo. A recent paper by Lin et al.(1) has broken through this barrier to demonstrate that heparan sulfate is essential for FGF function during Drosophila development. The establishment of a role for heparan sulfate in FGFR activation in vivo suggests that tissue-specific differences in the structure of heparan may modulate the activity of FGF. BioEssays 22:108–112, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

Although Auguste Comte is conventionally acknowledged as one of the founders of sociology and as a key representative of positivism, few new editions of his writings have been published in the English language in this century. He has become virtually dissociated from the history of modern positivism and the most recent debates about it. Gertrud Lenzer maintains that the work of Comte is, for better or for worse, essential to an understanding of the modern period of positivism. This collection (...) provides new access to the work of Comte and gives practitioners of various disciplines the possibility of reassessing concepts that were first introduced in Comte's writings. Today much of the ordinary business of academic disciplines is conducted under the assumption that the realm of science is essentially separate from the realms of politics and science. A close reading of Comte will reveal how deeply such current ideas and theories were originally embedded in a particular political context. One of his central methodological principles was that the theory of society had to be removed from the arena of political practice precisely in order to control that practice by means of these same sciences. It is in Comte's work that the reader will be able to observe how the forces of social and political reaction began to be powerfully organized to combat the critical forces in its own and later eras. Auguste Comte and Positivism will be of importance to the work of philosophers, sociologists, political theorists, and historians. (shrink)

The two opinions concerning real essences that Locke mentions in III.iii.17 represent competing theories about the way in which naturally occurring objects are divided into species. In this paper I explain what these competing theories amount to, why he denies the theory of kinds that is embodied in the first of these opinions, and how this denial is related to his general critique of essentialism. I argue first, that we cannot meaningfully ask whether Locke accepts the existence of natural kinds, (...) per se, since he affirms the theory of kinds that is embodied in the second opinion, while he denies the theory that is embodied in the first opinion. Second, I show that his denial of this theory is not solely or even primarily directed against the scholastic/Aristotelian theory of substantial forms, since he is most interested in refuting a corpuscularian version of this theory. And third, I argue that Locke’s anti-essentialism does not follow solely from his denial of (deeply objective) natural kinds, since one could consistently make this denial and affirm the existence of de re essential properties. (shrink)

This is a collection of papers that helped shape the field of formal semantics in linguistics.

This collection provides a selection of the most essential contributions to the contemporary free will debate. Among the issues discussed and debated are skepticism and naturalism, alternate possibilities, the consequence argument, libertarian metaphysics, illusionism and revisionism, optimism and pessimism, neuroscience and free will, and experimental philosophy.

Dominant paradigms in science foster integration of research findings, but at what cost? Forcing convergence requires centralizing decision-making authority, and risks reducing the diversity of methods and contributors, both of which are essential for the breakthrough ideas that advance science.

This collection of readings with extensive editorial commentary brings together key texts of the most influential philosophers of the medieval era to provide a comprehensive introduction for students of philosophy. Features the writings of Augustine, Thomas Aquinas, Boethius, John Duns Scotus and other leading medieval thinkers Features several new translations of key thinkers of the medieval era, including John Buridan and Averroes Readings are accompanied by expert commentary from the editors, who are leading scholars in the field.

In 1931 eminent chemist Fritz Paneth maintained that the modern notion of “element” is closely related to (and as “metaphysical” as) the concept of element used by the ancients (e.g., Aristotle). On that basis, the element chlorine (properly so-called) is not the elementary substance dichlorine, but rather chlorine as it is in carbon tetrachloride. The fact that pure chemicals are called “substances” in English (and closely related words are so used in other European languages) derives from philosophical compromises made by (...) grammarians in the late Roman Empire (particularly Priscian [fl. ~520 CE]). When the main features of the constitution of isotopes became clear in the first half of the twentieth century, the formal (IUPAC) definition of a “chemical element” was changed. The features that are “essential” to being an element had previously been “transcendental” (“beyond the sphere of consciousness”) but, by the mid-twentieth century the defining characteristics of elements, as such, had come to be understood in detail. This amounts to a shift in a “horizon of invisibility” brought about by progress in chemistry and related sciences. Similarly, chemical insight is relevant to currently-open philosophical problems, such as the status of “the bundle theory” of the coherence of properties in concrete individuals. (shrink)

Animal Philosophy is the first text to look at the place and treatment of animals in Continental thought.

The fine‐structure analyses of the nopaline synthase (nos) promoter which is active constitutively in a wide range of plant tissues reveal that a portion of the upstream essential region for maximal transcription is a potential Z‐DNA‐forming element. Z‐DNA sequences are found in almost all plant‐promoter regions, suggesting that these structural elements may play important roles in plant gene expression.

A central debate in philosophy and neuroscience pertains to whether PFC activity plays an essential role in the neural basis of consciousness. Neuroimaging and electrophysiology studies have revealed that the contents of conscious perceptual experience can be successfully decoded from PFC activity, but these findings might be confounded by post- perceptual cognitive processes, such as thinking, reasoning, and decision-making, that are not necessary for con- sciousness. To clarify the involvement of the PFC in consciousness, we present a synthesis of (...) research that has used intracranial electrical stimulation (iES) for the causal modulation of neural activity in the human PFC. This research provides compelling evidence that iES of only certain prefrontal regions (i.e., orbitofrontal cortex and anterior cingu- late cortex) reliably perturbs conscious experience. Conversely, stimulation of anterolateral prefrontal sites, often con- sidered crucial in higher-order and global workspace theories of consciousness, seldom elicits any reportable alterations in consciousness. Furthermore, the wide variety of iES-elicited effects in the PFC (e.g., emotions, thoughts, and olfactory and visual hallucinations) exhibits no clear relation to the immediate environment. Therefore, there is no evidence for the kinds of alterations in ongoing perceptual experience that would be predicted by higher-order or global workspace theories. Nevertheless, effects in the orbitofrontal and anterior cingulate cortices suggest a specific role for these PFC subregions in supporting emotional aspects of conscious experience. Overall, this evidence presents a challenge for higher-order and global workspace theories, which commonly point to the PFC as the basis for con- scious perception based on correlative and possibly confounded information. (shrink)