We report evidence further supporting homology between proteins in the F1FO‐ATP synthetase and the bacterial flagellar motor (BFM). BFM proteins FliH, FliI, and FliJ have been hypothesized to be homologous to FO‐b + F1‐δ, F1‐α/β, and F1‐γ, with similar structure and interactions. We conduct a further test by constructing a gene order dataset, examining the order offliH,fliI, andfliJgenes across the phylogenetic breadth of flagellar and nonflagellar type 3 secretion systems, and comparing this to published surveys of gene order in the (...) F1FO‐ATP synthetase, its N‐ATPase relatives, and the bacterial/archaeal V‐ and A‐type ATPases. Strikingly, thefliHIJgene order was deeply conserved, with the few exceptions appearing derived, and exactly matching the widely conserved F‐ATPase gene orderatpFHAG, coding for subunits b‐δ‐α‐γ. The V/A‐type ATPases have a similar conserved gene order. Our results confirm homology between these systems, and suggest a rare case of synteny conserved over billions of years, predating the Last Universal Common Ancestor (LUCA). (shrink)

The Wnt family of developmental regulators were named after the Drosophila segmentation gene wingless and the murine proto‐oncogene int‐1. Homology between these two genes connected oncogenesis to cell‐cell signals in development. I review how wingless was initially characterized, and cloned, as part of the quest to identify developmental cell‐to‐cell signals, based on predictions of the Positional Information Model, and on the properties of homeotic and segmentation gene mutants. The requirements and cell‐nonautonomy of wingless in patterning multiple embryonic and adult structures (...) solidified its status as a candidate signaling molecule. The physical location of wingless mutations and transcription unit defined the gene and its developmental transcription pattern. When the Drosophila homolog of int‐1 was then isolated, and predicted to encode a secreted proto‐oncogene homolog, it's identity to the wingless gene confirmed that a developmental cell‐cell signal had been identified and connected cancer to development. (shrink)

In 1995, the eyeless (ey) gene was dubbed the “master‐regulator” of eye development in Drosophila. Not only is ey required for eye development, but its misexpression can convert many other tissues into eye, including legs, wings and antennae.(1) ey is remarkable for its ability to drive coordinate differentiation of the multiple cell types that have to differentiate in a very precise pattern to construct the fly eye, and for its power to override the previous differentiation programs of many other diverse (...) tissues. Even more remarkable, the ey homolog Pax6 and homologs of other eye determination genes from Drosophila are also required for eye development in vertebrates,(2,3) prompting reassessment of the evolution of vision throughout the animal kingdom.(4,5) Now Kumar and Moses have published a study that throws a new light on ey function in Drosophila.(6) According to their work, ey becomes a master regulator of eye development much later than previously thought, and is regulated by signalling through the Notch and EGFR signaling pathways. BioEssays 23:763–766, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

This paper seeks to think creatively about the body of research which claims there is a link between heavy metal music and adolescent alienation, self-destructive behaviours, self-harm and suicide. Such research has been criticised, often by people who belong to heavy metal subcultures, as systematically neglecting to explore, in a meaningful manner, the psychosocial benefits for individuals who both listen to contemporary heavy metal music and socialize in associated groups. We argue that notions of survival, strength, community, and rebellion are (...) key themes in contemporary heavy metal music. Through literary-lyrical analysis of a selection of heavy metal tracks, this paper aims to redress the balance of risk and benefit. We argue that listening to this type of music, the accompanying social relationships, sense of solidarity and even the type of dancing can ameliorate tumultuous and difficult emotions. Songs which could be read as negative can induce feelings of relief through the sense that someone else has felt a particular way and recovered enough to transform these emotions into a creative outlet. This genre of music may therefore not increase the risk of untoward outcomes in any simple sense but rather represent a valuable resource for young people in difficulty. (shrink)

Much progress has been made recently towards uncovering the mechanisms that control the size to which organisms and their organs grow, and identifying some of the genes responsible. Size control, however, is only half of the equation. In growing to the right size, tissues must also grow to the right shape. A recent paper1 suggests that a hitherto overlooked cellular behaviour governs the size and shape of a growing tissue, and issues a challenge to developmental biologists to identify the molecular (...) mechanisms involved. BioEssays 25:5–8, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

Deep convolutional networks exceed humans in sensitivity to local image properties, but unlike biological vision systems, do not discover and encode abstract relations that capture important properties of objects and events in the world. Coupling network architectures with additional machinery for encoding abstract relations will make deep networks better models of human abilities and more versatile and capable artificial devices.

DNA replication requires the unwinding of the parental duplex, which generates (+) supercoiling ahead of the replication fork. It has been thought that removal of these (+) supercoils was the only method of unlinking the parental strands. Recent evidence implies that supercoils can diffuse across the replication fork, resulting in interwound replicated strands called precatenanes. Topoisomerases can then act both in front of and behind the replication fork. A new study by Sogo et al. [J Mol Biol 1999;286:637–643 (Ref. 1)], (...) using a topological analysis, provides the best evidence that precatenanes exist in negatively supercoiled, partially replicated molecules in vivo. BioEssays 21:805–808, 1999. © 1999 John Wiley & Sons, Inc. (shrink)

The book aims at equipping you with 21st Century Skills key life skills that will drive your future employability, promotion and career success. These are required for effective reasoning, writing and decision-making in changing, evolving environments. You give reasons for what you do and think every day. You argue. You often argue about things that matter to you. For example you might argue that you are the best candidate for promotion, about whether your company should invest in China, about the (...) best way to help a friend or about what the right thing to do is in an ethical dilemma. The list is up to you. If you work your way carefully through this book you will become better at reasoning both in terms of understanding and clarifying other peoples’ arguments and also at producing increasingly sophisticated and compelling arguments of your own. You will learn how to recognize common but often seductive mistakes in reasoning and so be empowered to avoid making these mistakes yourself. Your writing and oral presentations will improve and you will hone your ability to define crucial terms in argument, debate and discussion. As this book is specifically written with everyday language considerations in mind, it is a valuable tool for anyone to understand, evaluate and construct arguments in ordinary language. (shrink)

There is a paucity of treatment options for cognitively normal individuals with drug resistant genetic generalized epilepsy. Centromedian nucleus of the thalamus deep brain stimulation may be a viable treatment for GGE. Here, we present the case of a 27-year-old cognitively normal woman with drug resistant GGE, with childhood onset. Seizure semiology are absence seizures and generalized onset tonic clonic seizures. At baseline she had 4–8 GTC seizures per month and weekly absence seizures despite three antiseizure medications and vagus nerve (...) stimulation. A multidisciplinary committee recommended off-label use of CM DBS in this patient. Over 12-months of CM DBS she had two GTC seizure days, which were in the setting of medication withdrawal and illness, and no GTC seizures in the last 6 months. There was no significant change in the burden of absence seizures. Presently, just two studies clearly document CM DBS in cognitively normal individuals with GGE or idiopathic generalized epilepsy [in contrast to studies of cognitively impaired individuals with developmental and epileptic encephalopathies ]. Our results suggest that CM DBS can be an effective treatment for cognitively normal individuals with GGE and underscore the need for prospective studies of CM DBS. (shrink)

Late in 1990, the Center for the Study of Ethics in the Professions at Illinois Institute of Technology (lIT) received a grant of more than $200,000 from the National Science Foundation to try a campus-wide approach to integrating professional ethics into its technical curriculum.! Enough has now been accomplished to draw some tentative conclusions. I am the grant's principal investigator. In this paper, I shall describe what we at lIT did, what we learned, and what others, especially philosophers, can learn (...) from us. We set out to develop an approach that others could profitably adopt. I believe that we succeeded. (shrink)

The contemporary operating environment for deployed United States military operations largely focuses on deployments to predominantly Islamic countries. The differences in cultural values between d...

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)

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)

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)

As teams of people increasingly incorporate robot members, it is essential to consider how a robot's actions may influence the team's social dynamics and interactions. In this work, we investigated the effects of verbal support from a robot on human team members' interactions related to psychological safety and inclusion. We conducted a between-subjects experiment where the robot team member either gave verbal support or did not give verbal support to the human team members of a human-robot team comprised of 2 (...) human ingroup members, 1 human outgroup member, and 1 robot. We found that targeted support from the robot had a positive effect on outgroup members, who increased their verbal participation after receiving targeted support from the robot. When comparing groups that did and did not have verbal support from the robot, we found that outgroup members received fewer verbal backchannels from ingroup members if their group had robot verbal support. These results suggest that verbal support from a robot may have some direct benefits to outgroup members but may also reduce the obligation ingroup members feel to support the verbal contributions of outgroup members. (shrink)

In the _Nichomachean Ethics_, Aristotle defines three kinds of friendship: utility, pleasure, and virtue. The characters in the films of Sean Baker fit into none of these categories. Friendship is central to all of Baker’s films, but it takes the non-Aristotelian form of “friends, no matter what,” which I interpret as a description of the aporia of friendship, of an impossible friend, or a friend in the realm of fantasy. In other words, friends are only friends when they (...) resist everything friends are supposed to do. Betrayal, lies, and complications sit at the heart of this new definition. One mechanism for this kind of friendship is _mourning_. Friends are only friends when friendship is mourned, or when it is part of a crypt, or a vault for losses that are too traumatic to confront fully, as set out in the work of Sigmund Freud, Jacques Derrida, Nicolas Abraham and Mária Török, and developed by Laurence Rickels. This reading of mourning puts a particular spin on fantasy, for if fantasy is generally assumed to be about wish-fulfillment, then when fantasy reaches into the crypt for inspiration, it is retooled into a vehicle for confronting what is too hard to face. This is the function of friendship in Baker’s films: his friends are Judas figures going against their friends in order to keep their friendship alive. In _Tangerine_ (2015), two transgender sex workers in West Hollywood develop their friendship around a fight over a man. In _Starlet_ (2012), a young woman hides a secret from her elderly female friend, and this friendship is only saved when another actress betrays this secret. In these films, friendship is paradoxically formed by attempting to ruin friendship. Thought on fantasy and mourning will help in defining this type of non-Aristotelian friendship, as well as Freud’s work on the “ambivalence of feeling” from his writing on the First World War. (shrink)

Do moral properties figure in the best explanatory account of the world? According to a popular realist argument, if they do, then they earn their ontological rights, for only properties that figure in the best explanation of experience are real properties. Although this realist strategy has been widely influential—not just in metaethics, but also in philosophy of mind and philosophy of science—no one has actually made the case that moral realism requires: namely, that moral facts really will figure in the (...) best explanatory picture of the world. This issue may have been neglected in part because the influential dialectic on moral explanations between philosophers Gilbert Harman and Nicholas Sturgeon has focused debate on whether moral facts figure in relevant explanations. Yet as others have noted, explanatory relevance is irrelevant when it comes to realism: after all, according to the popular realist argument, it is inference to the best explanation of experience that is supposed to confer ontological rights. I propose to ask, then, the relevant question about moral explanations: should we think that moral properties will figure in the best explanatory account of the world? (shrink)

Recent work combining cognitive neuroscience with computational modelling suggests that distributed patterns of neural firing may represent probability distributions. This paper asks: what makes it the case that distributed patterns of firing, as well as carrying information about (correlating with) probability distributions over worldly parameters, represent such distributions? In examples of probabilistic population coding, it is the way information is used in downstream processing so as to lead to successful behaviour. In these cases content depends on factors beyond bare information, (...) contra Brian Skyrms’ (2010) view that representational content can be fully characterised in information-theoretic terms. (shrink)

Tudor historians of Henry VIII's reign strove both to define the great political theological controversies of the day and to shape the future understanding of past events. This essay considers how Roman Catholic accounts of the life and martyrdom of Sir Thomas More, including those by Nicholas Harpsfield and Thomas Stapleton, shaped subsequent Protestant works of fiction, written during the 1590s. The essay explores, in particular, the collaborative play, Sir Thomas More, by Anthony Munday and revised by Shakespeare and (...) others; and Sir John Harington's references to More and Bishop John Fisher in the preface to his translation of Orlando Furioso and his extensive anecdotal remarks about More's scatological witticisms in his satirical tract, The Metamorphosis of Ajax. Such fictional works presage both the hesitant trend towards ecumenism and the imagined reunion of Christendom of the subsequent Jacobean reign, and the later emergence of the transnational secular public sphere, which transpired during the late seventeenth and eighteenth centuries. (shrink)

When Ecce Homo was finally published in 1908, a New York Times reviewer declared that its “the most interesting portions... are those in which Nietzsche..., without delving into the depths of philosophy, shows himself primarily as a master of charming satirical prose”. The review largely consists of quotations in which Nietzsche satirizes, which is to say, mocks, Germans. The author apparently missed Nietzsche’s sarcastic report of another reviewer who characterized Thus Spoke Zarathustra “as an advanced exercise in style, and expressed (...) the wish that later on I might provide some content as well”. Over a century later, Nicholas D. More argues that Ecce... (shrink)

The volume consists of twenty-one essays, many of which were part of a conference organized by the editors. Although the authors were apparently given the opportunity to revise their presentations, the collection retains the vibrancy of oral presentations. This seems entirely fitting given that the collection focuses on a short, cheerful book, one in which scholars are distinguished from professors. The collection’s organization somewhat follows the structure of EH. Like Nietzsche’s book, Martin and Large’s collection begins with their introduction, which (...) is followed by Daniel Conway’s discussion of the intercalated passage. “Why I am So Wise,” arguably the closest EH... (shrink)

Many traditional theists have said that God is propositionally omniscient, i.e. knows all truths. Many traditional theists also hold that God is timeless. That is, these theists hold that though God exists, there is no time at which He exists, and He does not exist earlier or later than anything. Some recent philosophers, among them Arthor Prior, Robert Coburn, Norman Kretz mann, Nicholas Wolterstorfl Richard Gale and Patrick Grim, have argued that There are truths to whose expression ‘now’ is (...) essential, and that – compose an inconsistent set of propositions. These writers argue that due to the semantics of ‘now’, a timeless God cannot know truths to whose expression ‘now’ is essential. To know a truth, it is claimed, one must be able to mentally token a proposition expressing what one knows. To token a truth to whose expression ‘now’ is essential, one must token ‘now’. ‘Now’ and relevantly similar terms inter alia locate those who use them in time: if one says truly that it is now 3 p.m., it follows that one exists at 3 p.m. So a timeless being cannot use ‘now’ and relevantly similar terms, and so cannot know truths for whose expression ‘now’ and its ilk are required. (shrink)