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)

Sensory substitution devices (SSDs) aim to compensate for the loss of a sensory modality, typically vision, by converting information from the lost modality into stimuli in a remaining modality. “The vOICe” is a visual-to-auditory SSD which encodes images taken by a camera worn by the user into “soundscapes” such that experienced users can extract information about their surroundings. Here we investigated how much detail was resolvable during the early induction stages by testing the acuity of blindfolded sighted, naïve vOICe users. (...) Initial performance was well above chance. Participants who took the test twice as a form of minimal training showed a marked improvement on the second test. Acuity was slightly but not significantly impaired when participants wore a camera and judged letter orientations “live”. A positive correlation was found between participants' musical training and their acuity. The relationship between auditory expertise via musical training and the lack of a relationship with visual imagery, suggests that early use of a SSD draws primarily on the mechanisms of the sensory modality being used rather than the one being substituted. If vision is lost, audition represents the sensory channel of highest bandwidth of those remaining. The level of acuity found here, and the fact it was achieved with very little experience in sensory substitution by naïve users is promising. (shrink)

John Stuart Mill's Utilitarianism continues to serve as a rich source of moral and theoretical insight. This collection of articles by top scholars offers fresh interpretations of Mill's ideas about happiness, moral obligation, justice, and rights. Applying contemporary philosophical insights, the articles challenge the conventional readings of Mill, and, in the process, contribute to a deeper understanding of utilitarian theory as well as the complexity of moral life.

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)

Debate about deregulation has focused considerable attention on the pricing policies of public utilities. Much work has been done by economists on this subject, and in this book the results of that research are presented and made accessible to students of economics. The main subject is the policy to be followed by a regulated monopoly, but the analysis is broadened to take account of a fringe of competitive suppliers, making it relevant to electric utilities and local telephone companies in the (...) US, to PTT's in Europe, to the possible privatisatibn of telecommunications in Australia, and to the telecommunications structure in the UK where the dominant supplier has recently been privatised. The book gives a unified and simplified exposition of the modern theory of efficient pricing which is not available elsewhere. The theoretical discussion is supplemented by numerical simulation comparing Fully Distributed Cost Pricing, Ramsey Pricing, and Optimal Non-uniform Pricing. (shrink)

This handbook presents a comprehensive introduction to the core areas of philosophy of education combined with an up-to-date selection of the central themes. It includes 95 newly commissioned articles that focus on and advance key arguments; each essay incorporates essential background material serving to clarify the history and logic of the relevant topic, examining the status quo of the discipline with respect to the topic, and discussing the possible futures of the field. The book provides a state-of-the-art overview of philosophy (...) of education, covering a range of topics: Voices from the present and the past deals with 36 major figures that philosophers of education rely on; Schools of thought addresses 14 stances including Eastern, Indigenous, and African philosophies of education as well as religiously inspired philosophies of education such as Jewish and Islamic; Revisiting enduring educational debates scrutinizes 25 issues heavily debated in the past and the present, for example care and justice, democracy, and the curriculum; New areas and developments addresses 17 emerging issues that have garnered considerable attention like neuroscience, videogames, and radicalization. The collection is relevant for lecturers teaching undergraduate and graduate courses in philosophy of education as well as for colleagues in teacher training. Moreover, it helps junior researchers in philosophy of education to situate the problems they are addressing within the wider field of philosophy of education and offers a valuable update for experienced scholars dealing with issues in the sub-discipline. Combined with different conceptions of the purpose of philosophy, it discusses various aspects, using diverse perspectives to do so. Contributing Editors: Section 1: Voices from the Present and the Past: Nuraan Davids Section 2: Schools of Thought: Christiane Thompson and Joris Vlieghe Section 3: Revisiting Enduring Debates: Ann Chinnery, Naomi Hodgson, and Viktor Johansson Section 4: New Areas and Developments: Kai Horsthemke, Dirk Willem Postma, and Claudia Ruitenberg. (shrink)

The boundaries of honesty are the focal point of this exploration of the individualistic origins of modernist ethics and the consequent need for a more pragmatic approach to business ethics. The tendency of modernist ethics to see honesty as an individual responsibility is described as a contextually naive approach, one that fails to account for the interactive effects between individual choices and corporate norms. By reviewing the empirical accounts of managerial struggles with ethical dilemmas, the article arrives at the contextual (...) preconditions for encouraging the development of reflective moral agents in modern corporations. (shrink)

We performed a critical review of the historiographical studies on biogeography. We began with the pioneering works of Augustin and Alphonse de Candolle. Then, we analyzed the historical accounts of biogeography developed by (1) Martin Fichman and his history on the extensionism-permanentism debate; (2) Gareth Nelson and his critique of the Neo-Darwinian historiography of biogeography; (3) Ernst Mayr, with his dispersalist viewpoint; (4) Alan Richardson, who wrote a microhistory on the biogeographic model constructed by Darwin; (5) Michael Paul Kinch and (...) the ideas discussed in the 19th century about the geographical distribution of living beings; (6) Janet Browne, who highlighted the importance of the pre-Darwinian naturalists; (7) Peter Bowler, who focused mainly on the influence of paleontology on biogeography; (8) James Larson, who looked into the practices of the naturalists of Northern Europe in the late 18th century; and (9) Malte Ebach, who like Larson, was more interested in analysing the practices rather than the ideas of naturalists who studied the geographical distribution of organisms. Finally, these works are compared with each other. There has not been a dominant paradigm in the construction of historical narratives of biogeography; however, they provide a useful context for understanding problems of biogeography that continue to be debated to this day. (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)

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)

Abstract.In Islam, the acquisition of knowledge is a form of worship. But human achievement must be exercised in conformity with God's will. Warnings against feelings of superiority often are coupled with the command to remain within the confines of God's laws and limits. Because of the fear of arrogance and disregard of the balance created by God, any new knowledge or discovery must be applied with careful consideration to maintaining balance in the creation. Knowledge must be applied to ascertain equity (...) and justice for all of humanity. Research in Islam must be linked to the broad ethical base set forth in the Qur'an and the Sunnah. Whether embryonic stem cell research or cloning is ethically acceptable in Islam depends on the benefits derived from such applications. What is most important for the scholars is to adhere to the concepts of compassion, mercy, and benefit to everyone. (shrink)

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 meta-problem of consciousness is the problem of explaining why we have problem intuitions about consciousness, why we intuitively think that conscious experience cannot be scientifically explained. In his discussion of this problem, David Chalmers briefly considers the possibility of giving a 'genealogical' solution, according to which problem intuitions are 'accidents of cultural history' (2018, p. 33). Chalmers' response to this solution is largely dismissive. In this paper, we defend the viability of a genealogical solution. Our strategy is to (...) focus on a particular problem intuition: the thought that the phenomenal character of colour experience is irreducibly subjective. We use the history of the inverted spectrum thought experiment as a window into how various philosophers have thought about colour experience. Our genealogy reveals that problem intuitions about colour are not timeless, but instead arise in a specific historical context, one that, in large part, explains why we have these intuitions. (shrink)

The framework of quantum frames can help unravel some of the interpretive difficulties i the foundation of quantum mechanics. In this paper, I begin by tracing the origins of this concept in Bohr's discussion of quantum theory and his theory of complementarity. Engaging with various interpreters and followers of Bohr, I argue that the correct account of quantum frames must be extended beyond literal space–time reference frames to frames defined by relations between a quantum system and the exosystem or external (...) physical frame, of which measurement contexts are a particularly important example. This approach provides superior solutions to key EPR-type measurement and locality paradoxes. (shrink)

This article suggests that studies of self-esteem using scales have reached a dead end, and suggest alternative directions. First we show how significance tests have obscured meager results. According to reviews, this huge body of research has yielded no substantial findings. Some sub-fields show consistent, but trivially small, effects; reviews of the entire field show none at all. Most important, the size of effects does not seem to be increasing. Three questions are raised: 1. Are new standards needed to determine (...) when to continue or stop a given line of research? 2. Are new approaches needed alternative to standardized scales and statistical tests? 3. Should future studies of self-esteem emphasize feeling and social components at least as much as cognitive components? Studies of self-esteem using interview techniques by George Brown and his colleagues suggest the need to move closer to actual data. An exploratory study that takes this direction a step further is described. We analyze social and cognitive/emotional elements second by second in discourse about topics relevant to self-appraisal and self-feeling. (shrink)

Both David Lewis and Roderick Chisholm have proposed that beliefs are best understood, not as relations between people and the propositions they believe, but as relations between people and the properties they "directly attribute" to themselves or "self-ascribe." If this account is correct for belief, it seems that it ought to be possible to extend it to other "propositional attitudes" such as considering and wishing. But the most straightforward way of extending the account to such other attitudes faces difficulties, (...) some of which are discussed in a paper by Peter J. Markie. In this paper I will show how to apply the account to considering and wishing in a way that avoids such difficulties. (shrink)

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)

The essays in this book discuss the originally proposed Baldwin effect, how it was modified over time, and its possible contribution to contemporary empirical...

© 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)

This interdisciplinary and systematic collection of essays explores pragmatism in relation to three key episodes in American culture: Progressivism, Positivism, and Postmodernism.

This paper argues for more randomised controlled trials in educational research. Educational researchers have largely abandoned the methodology they helped to pioneer. This gold-standard methodology should be more widely used as it is an appropriate and robust research technique. Without subjecting curriculum innovations to a RCT then potentially harmful educational initiatives could be visited upon the nation's children.

In this seminal work, acclaimed philosopher Bernhard Waldenfels deals with the problem of the nature of order after the “shattering of the world,” and the loss of the idea of a universal or fundamental order._ _ Order in the Twilight__ unites phenomenological methodology with recent work on the theory of order, normativity, and dialogue, as well as structuralism and Gestalt theory. Philosophically stringent, it expresses a more optimistic attitude than much modern philosophy, especially deconstruction._ Waldenfels passes the question of order (...) through numerous defining aspects, and concludes that there is not one global order, but rather various conflicting domains of order. Whenever the boundary of a vital or experiential domain is crossed, a discourse speaks at the boundary, not about it, and across a threshold without abolishing it. The rest is rationalization, i.e., an attempt to find a place in the respective order for what is to-be-ordered. But why, the author concludes, should a theory be more unambiguous than reality? _ Order in the Twilight__ is an important book at this time, because it may help lift the humanities out of the skeptical, relativistic disarray in which they have been embroiled in recent decades. Waldenfels does not attempt to dictate what reality should be; rather, he is open to any valid evidences. His book offers a solid footing to the human and social sciences as they seek to escape from deconstructive irrationalism. (shrink)

This study explored calibrating a large item bank for use in multidimensional health measurement with computerized adaptive testing, using both item responses and response time (RT) information. The Activity Measure for Post-Acute Care is a patient-reported outcomes measure comprised of three correlated scales (Applied Cognition, Daily Activities, and Mobility). All items from each scale are Likert type, so that a respondent chooses a response from an ordered set of four response options. The most appropriate item response theory model for analyzing (...) and scoring these items is the multidimensional graded response model (MGRM). During the field testing of the items, an interviewer read each item to a patient and recorded, on a tablet computer, the patient’s responses and the software recorded RTs. Due to the large item bank with over 300 items, data collection was conducted in four batches with a common set of anchor items to link the scale. Van der Linden’s (2007) hierarchical modeling framework was adopted. Several models, with or without interviewer as a covariate and with or without interaction between interviewer and items, were compared for each batch of data. It was found that the model with the interaction between interviewer and item, when the interaction effect was constrained to be proportional, fit the data best. Therefore, the final hierarchical model with lognormal model for RT and the MGRM for response data was fitted to all batches of data via a concurrent calibration. Evaluation of parameter estimates revealed that (1) adding response time information did not affect the item parameter estimates and their standard errors significantly; (2) adding response time information helped reduce the standard error of patients’ multidimensional latent trait estimates, but adding interviewer as a covariate did not result in further improvement. Implications of the findings for follow up adaptive test delivery design are discussed. (shrink)