We highlight the various domains of the flavivirus virulence factor NS1 and speculate on potential implications of the NS1 3D structure in understanding its role in flavivirus pathogenesis. Flavivirus non‐structural protein 1 (NS1) is a virulence factor with dual functions in genome replication and immune evasion. Crystal structures of NS1, combined with reconstructions from electron microscopy (EM), provide insight into the architecture of dimeric NS1 on cell membranes and the assembly of a secreted hexameric NS1‐lipid complex found in patient sera. (...) Three structural domains of NS1 likely have distinct roles in membrane association, replication complex assembly, and immune system avoidance. A conserved hydrophobic inner face is sequestered either on the membrane or in the interior of the secreted hexamer and contains regions implicated in viral replication. The exposed variable outer face is presented to cellular and secreted components of the immune system in infected patients and contains candidate regions for immune system modulation. We anticipate that knowledge of the distinct NS1 domains and assembly will lead to advances in elucidating virus‐host interactions mediated through NS1 and in dissecting the role of NS1 in viral genome replication. (shrink)

Glowacki offers many new directions for understanding and even eliminating the problem of war, especially creating positive interdependencies with out-group members. We develop Glowacki's intriguing proposition that in-group dynamics provide a route to peace by describing a prosocial motivational system, the caregiving system, that aligns individual interests and eliminates the need to use coercion to achieve mutually beneficial outcomes.

Is there a link between how a firm manages its internal and external stakeholders? More specifically, are firms that give employees stock ownership and more say in running the enterprise more likely to engage with external stakeholders? This study seeks to answer these questions by elaborating on mechanisms that link employees to external stakeholders, such as the community, suppliers, and the environment. It tests these relationships using a sample of 347 private, mostly small-to-medium size firms, which completed a stakeholder impact (...) assessment organized by the non-profit B Lab. The results support the hypotheses that both employee ownership and employee involvement are positively associated with external stakeholder engagement. Further, we found that certification plays a role, as employee ownership contributes to external stakeholder engagement only in certified B Corporations, and not in firms that merely completed the B Lab Impact assessment. Our findings have import for stakeholder engagement frameworks, as we show that there is interplay between internal employee stakeholders and external stakeholders that may be important to overall firm–stakeholder management. (shrink)

ust-jackets are frequently adorned by quotations from famous people praising the book. At first glance, Andrew Brown's The Darwin Wars is no exception. Pithy quotations from Steve Jones, Richard Dawkins, John Maynard Smith, Stephen Jay Gould and Daniel Dennett. Who could ask for more? However, on closer inspection these quotations turn out not to be about Brown's book at all, but quotations that Brown uses in his book. Only Dennett's blurb refers to one of Brown's own (...) publications: "What a sleazy bit of trash journalism.". (shrink)

The shortage of organs for transplantation by its nature prompts ethical dilemmas. For example, although there is an imperative to save human life and reduce suffering by maximising the supply of vital organs, there is an equally important obligation to ensure that the process by which we increase the supply respects the rights of all stakeholders. In a relatively unexamined practice in the USA, organs are procured from unrepresented decedents without their express consent. Unrepresented decedents have no known healthcare wishes (...) or advance care planning document; they also lack a surrogate. The Revised Uniform Anatomical Gift Act (RUAGA) of 2006 sends a mixed message about the procurement of organs from this patient population and there are hospitals that authorise donation. In addition, in adopting the RUAGA, some states included provisions that clearly allow organ procurement from unrepresented decedents. An important unanswered question is whether this practice meets the canons of ethical permissibility. The current Brief Report presents two principled approaches to the topic as a way of highlighting some of the complexities involved. Concluding remarks offer suggestions for future research and discussion. (shrink)

1 Evidence-based policy requires researchers to provide the answers to ecological questions that are of interest to policy makers. To find out what those questions are in the UK, representatives from 28 organizations involved in policy, together with scientists from 10 academic institutions, were asked to generate a list of questions from their organizations. 2 During a 2-day workshop the initial list of 1003 questions generated from consulting at least 654 policy makers and academics was used as a basis for (...) generating a short list of 100 questions of significant policy relevance. Short-listing was decided on the basis of the preferences of the representatives from the policy-led organizations. 3 The areas covered included most major issues of environmental concern in the UK, including agriculture, marine fisheries, climate change, ecosystem function and land management. 4 The most striking outcome was the preference for general questions rather than narrow ones. The reason is that policy is driven by broad issues rather than specific ones. In contrast, scientists are frequently best equipped to answer specific questions. This means that it may be necessary to extract the underpinning specific question before researchers can proceed. 5 Synthesis and applications. Greater communication between policy makers and scientists is required in order to ensure that applied ecologists are dealing with issues in a way that can feed into policy. It is particularly important that applied ecologists emphasize the generic value of their work wherever possible. (shrink)

Theories of consciousness have a long and controversial history. One well-known proposal — integrated information theory — has recently been labeled as ‘pseudoscience’, which has caused a heated open debate. Here we discuss the case and argue that the theory is indeed unscientific because its core claims are untestable even in principle.

BackgroundThe ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines are widely endorsed but compliance is limited. We sought to determine whether journal-requested completion of an ARRIVE checklist improves full compliance with the guidelines.MethodsIn a randomised controlled trial, manuscripts reporting in vivo animal research submitted to PLOS ONE (March–June 2015) were randomly allocated to either requested completion of an ARRIVE checklist or current standard practice. Authors, academic editors, and peer reviewers were blinded to group allocation. Trained reviewers performed outcome adjudication (...) in duplicate by assessing manuscripts against an operationalised version of the ARRIVE guidelines that consists 108 items. Our primary outcome was the between-group differences in the proportion of manuscripts meeting all ARRIVE guideline checklist subitems.ResultsWe randomised 1689 manuscripts (control: n = 844, intervention: n = 845), of which 1269 were sent for peer review and 762 (control: n = 340; intervention: n = 332) accepted for publication. No manuscript in either group achieved full compliance with the ARRIVE checklist. Details of animal husbandry (ARRIVE subitem 9b) was the only subitem to show improvements in reporting, with the proportion of compliant manuscripts rising from 52.1 to 74.1% (X2 = 34.0, df = 1, p = 2.1 × 10−7) in the control and intervention groups, respectively.ConclusionsThese results suggest that altering the editorial process to include requests for a completed ARRIVE checklist is not enough to improve compliance with the ARRIVE guidelines. Other approaches, such as more stringent editorial policies or a targeted approach on key quality items, may promote improvements in reporting. (shrink)

Each contributor to this book has used personal experience as the basis from which to frame his individual sociological perspectives. Because they have personalized their work, their accounts are real, and recognizable as having come from 'real' persons, about 'real' experiences. There are no objectively-distanced disembodied third person entities in these accounts. These writers are actual people whose stories will make you laugh, cry, think, and want to know more.

We report the identification of a recurrent, 520-kb 16p12.1 microdeletion associated with childhood developmental delay. The microdeletion was detected in 20 of 11,873 cases compared with 2 of 8,540 controls and replicated in a second series of 22 of 9,254 cases compared with 6 of 6,299 controls. Most deletions were inherited, with carrier parents likely to manifest neuropsychiatric phenotypes compared to non-carrier parents. Probands were more likely to carry an additional large copy-number variant when compared to matched controls. The clinical (...) features of individuals with two mutations were distinct from and/or more severe than those of individuals carrying only the co-occurring mutation. Our data support a two-hit model in which the 16p12.1 microdeletion both predisposes to neuropsychiatric phenotypes as a single event and exacerbates neurodevelopmental phenotypes in association with other large deletions or duplications. Analysis of other microdeletions with variable expressivity indicates that this two-hit model might be more generally applicable to neuropsychiatric disease. © 2010 Nature America, Inc. All rights reserved. (shrink)

The Monographs produced by the International Agency for Research on Cancer (IARC) apply rigorous procedures for the scientific review and evaluation of carcinogenic hazards by independent experts. The Preamble to the IARC Monographs, which outlines these procedures, was updated in 2019, following recommendations of a 2018 expert Advisory Group. This article presents the key features of the updated Preamble, a major milestone that will enable IARC to take advantage of recent scientific and procedural advances made during the 12 years since (...) the last Preamble amendments. The updated Preamble formalizes important developments already being pioneered in the Monographs Programme. These developments were taken forward in a clarified and strengthened process for identifying, reviewing, evaluating and integrating evidence to identify causes of human cancer. The advancements adopted include strengthening of systematic review methodologies; greater emphasis on mechanistic evidence, based on key characteristics of carcinogens; greater consideration of quality and informativeness in the critical evaluation of epidemiological studies, including their exposure assessment methods; improved harmonization of evaluation criteria for the different evidence streams; and a single-step process of integrating evidence on cancer in humans, cancer in experimental animals and mechanisms for reaching overall evaluations. In all, the updated Preamble underpins a stronger and more transparent method for the identification of carcinogenic hazards, the essential first step in cancer prevention. (shrink)

Theologian, ethicist, and political analyst, Reinhold Niebuhr was a towering figure of twentieth-century religious thought. Now newly repackaged, this important book gathers the best of Niebuhr’s essays together in a single volume. Selected, edited, and introduced by Robert McAfee Brown—a student and friend of Niebuhr’s and himself a distinguished theologian—the works included here testify to the brilliant polemics, incisive analysis, and deep faith that characterized the whole of Niebuhr’s life. “This fine anthology makes available to a new generation the (...) thought of one of the most penetrating and rewarding of twentieth-century minds. Reinhold Niebuhr remains the great illuminator of the dark conundrums of human nature, history and public policy.”—Arthur Schlesinger, Jr. “Sparkling gems... brought from the shadows of history into contemporary light. Beautifully selected and edited,_ _they show that Niebuhr’s fiery polemics and gracious assurances still speak with power to us today.”—Roger L. Shinn “An extremely useful volume.”—David Brion Davis, _New York Review of Books _“This collection, which brings together Niebuhr’s most penetrating and enduring essays on theology and politics, should demonstrate for a new generation that his best thought transcends the immediate historical setting in which he wrote.... [Brown’s] introduction succinctly presents the central features of Niebuhr’s life and thought.”—_Library Journal_. (shrink)

In the paper of Brown and Priest 2004, the authors developed the chunk and permeate method, which they described as a ?paraconsistent reasoning strategy?. There it is suggested that the method of chunk and permeate could apply to the historical infinitesimal calculus. However, no attempt was made to look at actual historical examples. In this paper, I show that the method of chunk and permeate can indeed apply, as a rational reconstruction, to certain of Isaac Newton's arguments that use (...) infinitesimals. This rational reconstruction maintains and uses, rather than sidesteps, the apparent contradictions in Newton's arguments. The applicability of chunk and permeate to other historical arguments, e.g. of Leibniz/L'Hospital and Fermat, has also been investigated and will be communicated in future publications. (shrink)

© 2017. The American Astronomical Society. All rights reserved.We present new observations of the low-mass companion to HD 984 taken with the Gemini Planet Imager as a part of the GPI Exoplanet Survey campaign. Images of HD 984 B were obtained in the J and H bands. Combined with archival epochs from 2012 and 2014, we fit the first orbit to the companion to find an 18 au orbit with a 68% confidence interval between 14 and 28 au, an eccentricity (...) of 0.18 with a 68% confidence interval between 0.05 and 0.47, and an inclination of 119°with a 68% confidence interval between 114°and 125°. To address the considerable spectral covariance in both spectra, we present a method of splitting the spectra into low and high frequencies to analyze the spectral structure at different spatial frequencies with the proper spectral noise correlation. Using the split spectra, we compare them to known spectral types using field brown dwarf and low-mass star spectra and find a best-fit match of a field gravity M6.5 ±1.5 spectral type with a corresponding temperature of K. Photometry of the companion yields a luminosity of log=2.88 ± 0.07 dex with DUSTY models. Mass estimates, again from DUSTY models, find an age-dependent mass of 34 ±1 to 95 ±4 M Jup. These results are consistent with previous measurements of the object. (shrink)

William Connolly, one of the best-known and most important political theorists writing today, is a principal architect of the “new pluralism.” In this volume, leading thinkers in contemporary political theory and international relations provide a comprehensive investigation of the new pluralism, Connolly’s contributions to it, and its influence on the fields of political theory and international relations. Together they trace the evolution of Connolly’s ideas, illuminating his challenges to the “old,” conventional pluralist theory that dominated American and British political science (...) and sociology in the second half of the twentieth century. The contributors show how Connolly has continually revised his ideas about pluralism to take into account radical changes in global politics, incorporate new theories of cognition, and reflect on the centrality of religion in political conflict. They engage his arguments for an agonistic democracy in which all fundamentalisms become the objects of politicization, so that differences are not just tolerated but are productive of debate and the creative source of a politics of becoming. They also explore the implications of his work, often challenging his views to widen the reach of even his most recently developed theories. Connolly’s new pluralism will provoke all citizens who refuse to subordinate their thinking to the regimes in which they reside, to religious authorities tied to the state, or to corporate interests tied to either. _The New Pluralism_ concludes with an interview with Connolly in which he reflects on the evolution of his ideas and expands on his current work. _Contributors_: Roland Bleiker, Wendy Brown, David Campbell, William Connolly, James Der Derian, Thomas L. Dumm, Kathy E. Ferguson, Bonnie Honig, George Kateb, Morton Schoolman Michael J. Shapiro, Stephen K. White. (shrink)

How does science work? _Making Truth: Metaphor in Science_ argues that most laypeople, and many scientists, do not have a clear understanding of how metaphor relates to scientific thinking. With stunning clarity, and bridging the worlds of scientists and nonscientists, Theodore L. Brown demonstrates the presence and the power of metaphorical thought. He presents a series of studies of scientific systems, ranging from the atom to current topics in chemistry and biology such as protein folding, chaperone proteins, and global (...) warming. These case studies provide the basis for far-reaching conclusions about science as an intellectual and social practice and about the nature of scientific truth. (shrink)

Taking a schizoanalytic approach to audio-visual images, this article explores some of the radical potentia for deterritorialisation found within David Fincher's Fight Club (1999). The film's potential for deterritorialisation is initially located in an exploration of the film's form and content, which appear designed to interrogate and transcend a series of false binaries between mind and body, inside and outside, male and female. Paying attention to the construction of photorealistic digital spaces and composited images, we examine the actual (and (...) possible) ways viewers relate to the film, both during and after screenings. Recognising the film as an affective force performing within our world, we also investigate some of the real-world effects the film catalysed. Finally, we propose that schizoanalysis, when applied to a Hollywood film, suggests that Deleuze underestimated the deterritorialising potential of contemporary, special effects-driven cinema. If schizoanalysis has thus been reterritorialised by mainstream products, we argue that new, ‘post-Deleuzian’ lines of flight are required to disrupt this ‘de-re-territorialisation’. (shrink)

Legal decision-support systems have the potential to improve access to justice, administrative efficiency, and judicial consistency, but broad adoption of such systems is contingent on development of technologies with low knowledge-engineering, validation, and maintenance costs. This paper describes two approaches to an important form of legal decision support—explainable outcome prediction—that obviate both annotation of an entire decision corpus and manual processing of new cases. The first approach, which uses an attention network for prediction and attention weights to highlight salient case (...) text, was shown to be capable of predicting decisions, but attention-weight-based text highlighting did not demonstrably improve human decision speed or accuracy in an evaluation with 61 human subjects. The second approach, termed semi-supervised case annotation for legal explanations, exploits structural and semantic regularities in case corpora to identify textual patterns that have both predictable relationships to case decisions and explanatory value. (shrink)

Science fiction is often held up as a particularly philosophical genre. For, beyond actualising mind-experiment-like fantasies, science fiction films also commonly toy with speculative ideas, or else engineer encounters with the strange and unknown. Denis Villeneuve's Arrival is a contemporary science fiction film that does exactly this, by introducing Lovecraft-esque tentacular aliens whose arrival on Earth heralds in a novel, but ultimately paralysing, inhuman perspective on the nature of time and reality. This article shows how this cerebral film invites viewers (...) to confront a counterintuitive model of time that at once recalls and reposes what Gilles Deleuze called a “third synthesis” of time, and that which J. M. E. McTaggart named the a-temporal “C series” of “unreal” time. We finally suggest that Arrival's a-temporal conception of the future as having already happened can function as a key to understanding the fate of humanity as a whole as we pass from the anthropocene, in which humans have... (shrink)

Expressivists about normative thought and discourse traditionally deny that there are nondeflationary normative propositions. However, it has recently been suggested that expressivists might avoid a number of problems by providing a theory of normative propositions compatible with expressivism. This paper explores the prospects for developing an expressivist theory of propositions within the framework of cognitive act theories of propositions. First, I argue that the only extant expressivist theory of cognitive propositions—Michael Ridge's ‘ecumenical expressivist’ theory—fails to explain identity conditions for normative (...) propositions. Second, I argue that this failure motivates a general constraint—the ‘unity requirement’—that any expressivist theory of propositions must provide a unified nonrepresentational explanation of that in virtue of which propositional attitudes have the content that they have. Third, I argue that conceptual role accounts of content provide a promising framework in which to develop an expressivist theory of cognitive propositions. (shrink)

This paper examines the general prospects for conceptual role expressivism, expressivist theories that embrace conceptual role semantics. It has two main aims. The first aim is to provide a general characterisation of the view. The second aim is to raise a challenge for the general view. The challenge is to explain why normative concepts are not a species of defective concepts, where defective concepts are those that cannot meaningfully embed and participate in genuine inference. After rejecting existing attempts to answer (...) the challenge, I propose an alternative solution. However, the solution leaves conceptual role expressivism a far less distinctive and interesting position than its proponents claim. I conclude that we should be sceptical about how much expressivists gain by appealing to conceptual role semantics. (shrink)

This book is a collection of philosophical papers that explores theoretical and practical aspects and implications of nonviolence as a means of establishing peace. The papers range from spiritual and political dimensions of nonviolence to issues of justice and values and proposals for action and change.

Critical notice of Guy Fletcher's 'Dear Prudence: The Nature and Normativity of Prudential Discourse' and Dale Dorsey's 'A Theory of Prudence'.

The shape of a life hypothesis holds that the temporal sequence of good or bad times in a life can itself be a valuable feature of that life. This is generally thought to be incompatible with additivism about lifetime well-being, which holds that lifetime well-being is fully determined by momentary well-being. This paper examines Dale Dorsey’s recent argument that these views are in fact compatible. I argue that accepting the conjunction of these views requires stronger commitments than Dorsey recognizes. After (...) arguing that these commitments are problematic, I conclude that we should reject the compatibility claim. (shrink)

The struggle over legal abortion access in the United States is a religious controversy, not a scientific debate. Religious activists who believe that meaningful individual life (i.e., “personhood”) begins at a specific “moment-of-conception” are attempting to pass laws that force this view upon all pregnant persons, irrespective of their medical circumstances, individual preferences, or personal religious beliefs. This paper argues that such actions promote a constitutionally prohibited “establishment of religion.” Abortion policy in a secular state must be based upon scientifically (...) accurate biology, not unprovable theological presuppositions. The scientific facts regarding human pregnancy do not support the position that personhood begins with fertilization—at which point a pregnancy does not yet even exist. Abortion policy should regard the embryo/fetus as part of the pregnant individual’s body until delivery. We argue that individual “personhood” only begins when the _latent_ potentialities of the fetal nervous system are _actualized_ in the newborn after delivery. The paper argues that instantiating non-scientific beliefs concerning embryonic/fetal “personhood” into the law as the basis for abortion policy establishes a state-sponsored religion. The protection of religious liberty requires that abortion be decriminalized. Abortion should be treated like any other medical procedure and regulated similarly. To protect both religious freedom and sound medical practice, individual legal personhood should be recognized as beginning only at birth. (shrink)

Current models of autobiographical memory suggest that self-identity guides autobiographical memory retrieval. Further, the capacity to recall the past and imagine one’s self in the future can influence social problem solving. We examined whether manipulating self-identity, through an induction task in which students were led to believe they possessed high or low self-efficacy, impacted episodic specificity and content of retrieved and imagined events, as well as social problem solving. Compared to individuals in the low self efficacy group, individuals in the (...) high self efficacy group generated past and future events with greater specificity, positive words, and self-efficacious statements, and also performed better on social problem solving indices. A lack of episodic detail for future events predicted poorer performance on social problem solving tasks. Strategies that increase perceived self-efficacy may help individuals to selectively construct a past and future that aids in negotiating social problems. (shrink)

The negative emotions generated following stressful life events can increase one’s risk of depressive symptoms and promote higher levels of perceived stress. The process model of emotion regulation can help distinguish between adaptive and maladaptive emotion regulation strategies to determine who may be at the greatest risk of worse psychological health across the lifespan. Heart rate variability may affect these relationships as it indexes aspects of self-regulation, including emotion and behavioral regulation, that enable an individual to dynamically adapt to the (...) changing demands of both internal and external environments. In this study, we expected individual differences in resting vagally mediated HRV to moderate the influence of emotion regulatory strategies among our sample of 267 adults. We found support for the hypothesis that higher vagally mediated HRV buffers against the typical adverse effects of expressive suppression when evaluating depressive symptoms and found weak support when considering perceived stress. There was no evidence for an interaction between cognitive reappraisal and vagally mediated HRV but there was a significant, negative association between cognitive reappraisal and depressive symptoms and perceived stress. Future work may determine if intervening on either emotion regulation strategies or HRV may change these within-persons over time. (shrink)

Ethics has been identified as an important factor that potentially affects auditors’ professional skepticism. For example, prior research finds that auditors who are more concerned with professional ethics exhibit greater professional skepticism. Further, the literature suggests that professional skepticism may lead the auditor to more vigilantly resist the client’s position in financial reporting disputes. These reporting disputes are generally resolved through negotiations between the auditor and client to arrive at the final reported amounts. To date, the role that professional skepticism (...) potentially plays in the negotiation process has been relatively unexplored. The literature prior to the enactment of Sarbanes–Oxley (SOX) suggests that auditors are more likely to approve a client position when the matter in dispute is relatively ambiguous and when changing the client’s position will result in the client failing to meet analysts’ expectations. However, changes resulting from SOX have led auditors to be more vigilant and therefore results found in the pre-SOX environment may not hold in the current environment where auditors are held more accountable for their actions. Results from an experiment with experienced audit managers and partners suggest that in the post-SOX climate, auditors’ negotiations do not appear to be substantively influenced by management being able to meet or beat forecasts. Moreover, we find that when auditors exhibit heightened professional skepticism, they are more ethical by being conservative and they stand more resolute than when auditors do not exhibit heightened professional skepticism. Finally, although we do not find a main effect for the influence of earnings forecast, we do find a significant interaction between earnings forecast and heightened professional skepticism. Implications for practice and research are then presented. (shrink)