The RecA family proteins mediate homologous recombination, a ubiquitous mechanism for repairing DNA double‐strand breaks (DSBs) and stalled replication forks. Members of this family include bacterial RecA, archaeal RadA and Rad51, and eukaryotic Rad51 and Dmc1. These proteins bind to single‐stranded DNA at a DSB site to form a presynaptic nucleoprotein filament, align this presynaptic filament with homologous sequences in another double‐stranded DNA segment, promote DNA strand exchange and then dissociate. It was generally accepted that RecA family proteins function throughout (...) their catalytic cycles as right‐handed helical filaments with six protomers per helical turn. However, we recently reported that archaeal RadA proteins can also form an extended right‐handed filament with three monomers per helical turn and a left‐handed protein filament with four monomers per helical turn. Subsequent structural and functional analyses suggest that RecA family protein filaments, similar to the F1‐ATPase rotary motor, perform ATP‐dependent clockwise axial rotation during their catalytic cycles. This new hypothesis has opened a new avenue for understanding the molecular mechanism of RecA family proteins in homologous recombination. BioEssays 30:48–56, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

This paper investigates relationships between procedural-memory, declarative-memory, and working-memory skills and adult native English speakers’ novel sound-category learning. Participants completed a sound-categorization task that required integrating two dimensions: one native (vowel quality), one non-native (pitch). Similar information-integration category structures in the visual and auditory domains have been shown to be best learned implicitly (e.g., Maddox, Ing, & Lauritzen, 2006). Thus, we predicted that individuals with greater procedural-memory capacity would better learn sound categories, because procedural memory appears to support implicit learning (...) of new information and integration of dimensions. Seventy undergraduates were tested across two experiments. Procedural memory was assessed using a linguistic adaptation of the serial-reaction-time task (Misyak, Christiansen, & Tomblin, 2010a, 2010b). Declarative memory was assessed using the logical-memory subtest of the Wechsler Memory Scale-4th edition (WMS-IV; Wechsler, 2009). Working memory was assessed using an auditory version of the reading-span task (Kane et al., 2004). Experiment 1 revealed contributions of only declarative memory to dimensional integration, which might indicate not enough time or motivation to shift over to a procedural/integrative strategy. Experiment 2 gave twice the speech-sound training, distributed over two days, and also attempted to train at the category boundary. As predicted, effects of declarative memory were removed and effects of procedural memory emerged, but, unexpectedly, new effects of working memory surfaced. The results may be compatible with a multiple-systems account in which declarative and working memory facilitate transfer of control to the procedural system. (shrink)

We investigate the causal manipulability hypothesis, according to which what partly explains (a) why people tend to prefer negative events to be in their further future rather than their nearer future and positive events to be in their nearer future rather than their further future and (b) why people tend to prefer that negative events be located in their past not their future and that positive events be located in their future not their past, is that people tend to discount (...) the value of events they are less able causally to manipulate. If people discount the value of events they are less able to causally manipulate, then since often temporally nearer future events are more causally manipulable than further ones, and since future events are manipulable whereas past ones aren’t, this could explain both (a) and (b). In turn, if the causal manipulability hypothesis is correct, this might suggest that insofar as people’s preferences are explained in this manner, those preferences are rationally permissible, since relative causal manipulability is normatively relevant. Thus, ascertaining whether the causal manipulability hypothesis is true may shed light on the normative status of such preferences. We investigate the cognitively mediated version of the causal manipulability hypothesis, according to which people’s consciously held beliefs about the relative causal manipulability of events explains (a) and (b). Contrary to expectations, we found no evidence in favour of this view. We suggest that either relative causal manipulability plays an explanatory role, but one that is not cognitively mediated, or that it does not play any role, even if it is sometimes associated with other factors, such as probability, that may play a role in explaining some time biased preferences. (shrink)

Accumulating research has identified the interactive effects of catechol-O-methyltransferase gene Val158Met polymorphism and environmental factors on aggression. However, available evidence was mainly based upon correlational design, which yields mixed findings concerning who are more affected by environmental conditions and has been challenged for the low power of analyses on gene–environment interaction. Drawing on a mixed design, we scrutinized how COMT Val158Met polymorphism impacts on aggression, assessed by hostility, aggressive motivation, and aggressive behavior, under different social conditions in a sample of (...) 70 Chinese male undergraduate students. We found that both Val/Val homozygote and Met alleles carriers showed differences in the feelings of hostility and aggressive motivation under conditions of exclusion versus inclusion, but these differences were more pronounced for Met allele carriers. These findings implied that COMT Val158Met polymorphism did not respond to environmental stimuli in an all-or-none way and shed light on the importance of examining the gene–environment interaction using a mixed design. (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

Diffusion MRI is widely used to investigate neuronal and structural development of brain. dMRI data is often contaminated with various types of artifacts. Hence, artifact type identification in dMRI volumes is an essential pre-processing step prior to carrying out any further analysis. Manual artifact identification amongst a large pool of dMRI data is a highly labor-intensive task. Previous attempts at automating this process are often limited to a binary classification of the dMRI volumes or focus on detecting a single type (...) of artifact. In this work, we propose a deep learning-based automated multiclass artifact classifier for dMRI volumes. Our proposed framework operates in 2 steps. In the first step, the model predicts labels associated with 3D mutually exclusive collectively exhaustive sub-volumes or “slabs” extracted from whole dMRI volumes. In the second step, through a voting process, the model outputs the artifact class present in the whole volume under investigation. We used two different datasets for training and evaluating our model. Specifically, we utilized 2,494 poor-quality dMRI volumes from the Adolescent Brain Cognitive Development and 4,226 from the Healthy Brain Network dataset. Our results demonstrate accurate multiclass volume-level main artifact type prediction with 96.61 and 97.52% average accuracies on the ABCD and HBN test sets, respectively. Finally, in order to demonstrate the effectiveness of the proposed framework in dMRI pre-processing pipelines, we conducted a proof-of-concept dMRI analysis exploring the relationship between whole-brain fractional anisotropy and participant age, to test whether the use of our model improves the brain-age association. (shrink)

When I was young, I read Major Barbara by George Bernard Shaw, and there was one scene that left a great impression on me. The industrial magnate Andrew Undershaft meets his son Stephen, whom he has not seen for many years, and asks him what he is interested in. The young man has no talent for science, the arts or law, but says there is one thing he is good at, and that is telling right from wrong. Undershaft pours (...) scorn on his son, and wants to know how, if he is unable to do anything else, he can possibly do something that has baffled all the scientists, politicians and philosophers, and distinguish right from wrong. I was only about twenty when I read this, and at once I made the major decision that it did not matter what I did in my life, but I must not become a person who is capable of nothing but telling right from wrong. For that reason, I became a member of the silent majority. The people I saw when I was young had grasped only a few superficial principles and thought they knew it all. They made wild judgments about the world, and the result was that the whole world was badly damaged. It was not until I was about forty that I realized Shaw's view was rather biased; but that came later—any-how, these comments of Shaw's acted as an antidote to all those shallow, arrogant people. (shrink)

This paper analyzes the determinants of corporate reputation within a sample of large UK companies drawn from a diverse range of industries. We pay particular attention to the role that philanthropic expenditures and policies may play in shaping the perceptions of companies among their stakeholders. Our findings highlight that companies which make higher levels of philanthropic expenditures have better reputations and that this effect varies significantly across industries. Given that reputational indices tend to reflect the financial performance of organizations above (...) other factors (Fryxell, G. E. and J. Wang: 1994, Journal of Management 20, 1–14) and that elements of the literature emphasise that discretionary aspects of social responsibility, including corporate donations, may not be in the financial interests of organizations (e.g. Friedman, M.: 1970, “The Social Responsibility of Business is to Increase its Profits”, New York Times Magazine, September 13), this is a significant finding. It suggests that philanthropic expenditures may play a significant role in stakeholder management and may, in particular, lead to stakeholders holding more positive impressions of philanthropic corporations. (shrink)

Why we get the world wrong -- Intuitive theories of the physical world -- Matter : what is the world made of? How do those components interact? -- Energy : what makes something hot? What makes something loud? -- Gravity : what makes something heavy? What makes something fall? -- Motion : what makes objects move? What paths do moving objects take? -- Cosmos : what is the shape of our world? What is its place in the cosmos? -- Earth (...) : why do continents drift? Why do climates change? -- Intuitive theories of the biological world -- Life : what makes us alive? What causes us to die? -- Growth : why do we grow bigger? Why do we grow older? -- Inheritance : why do we resemble our parents? Where did we get our traits? -- Illness : what makes us ill? How does illness spread? -- Adaptation : why are there so many lifeforms? How do they change over time? -- Ancestry : where do species come from? How are they related? -- How to get the world right. (shrink)

In this book about metaphysics the author defends a realistic view of universals, characterizing the notion of universal by considering language and logic, the idea of possibility, hierarchies of universals, and causation. He argues that neither language nor logic is a reliable guide to the nature of reality and that basic universals are the fundamental type of universal and are central to causation. All assertions and predications about the natural world are ultimately founded on these basic universals. A distinction is (...) drawn between unified particulars and arbitrary particulars ; unified particulars are the terms of causal relations and thus the real constituents of the world. The world is not made up of events but of unified particulars and basic universals. (shrink)

This article provides an overview of recent developments in solving the timing problem (discreteness vs. continuity) in cognitive neuroscience. Both theoretical and empirical studies have been considered, with an emphasis on the framework of Operational Architectonics (OA) of brain functioning (Fingelkurts and Fingelkurts, 2001, 2005). This framework explores the temporal structure of information flow and interarea interactions within the network of functional neuronal populations by examining topographic sharp transition processes in the scalp EEG, on the millisecond scale. We conclude, based (...) on the OA framework, that brain functioning is best conceptualized in terms of continuity-discreteness unity which is also the characteristic property of cognition. At the end we emphasize where one might productively proceed for the future research. (shrink)

This article provides a retrospective, current and prospective overview on developments in brain research and neuroscience. Both theoretical and empirical studies are considered, with emphasis in the concept of multivariability and metastability in the brain. In this new view on the human brain, the potential multivariability of the neuronal networks appears to be far from continuous in time, but confined by the dynamics of short-term local and global metastable brain states. The article closes by suggesting some of the implications of (...) this view in future multidisciplinary brain research. (shrink)

'Becoming Who We Are' clarifies the political and existential aspects of Stanley Cavell's understanding of ordinary language and of skepticism, and shows the close connection between his reception of Kant, Heidegger, and Austin and his exploration of what Emersonian Perfectionism offers to democracy and modern life.

Ralph Johnson argues that mathematical proofs lack a dialectical tier, and thereby do not qualify as arguments. This paper argues that, despite this disavowal, Johnson’s account provides a compelling model of mathematical proof. The illative core of mathematical arguments is held to strict standards of rigour. However, compliance with these standards is itself a matter of argument, and susceptible to challenge. Hence much actual mathematical practice takes place in the dialectical tier.

Key Philosophers in Conversation is a fascinating collection of interviews presenting the ideas of some of the worlds leading contemporary philosophers. Each interview features a discussion with a key philosopher looking at philosophical issues such as; the philosophy of mind, ethics, science, political philosophy and the history of philosophy. Those interviewed are; W.V.O Quine, Michael Dummet, Mary Warnock, Hilary Putnam, Alasdair MacIntyre, Daniel Dennett, Martha Nussbaum, Roger Scruton, Bernard Williams, Jean Hampton, Richard Dawkins, Derek Parfit, Peter Strawson, David Gauthier, Hugh (...) Mellor, John Cottingham, Adam Morton, Stefan Korner, Richard Sorabji and Nancy Cartwright. This book offers an excellent insight to contemporary philosophy and is ideal for anyone seeking an introduction to what is happening in Philosophy today. (shrink)

Radical democrats highlight dramatic moments of political action, which disrupt everyday habits of perception that sustain unequal social relations. In doing so, however, we sometimes neglect how social conditions—such as precarious employment, social dislocation, and everyday exposure to violence—undermine political agency or might be contested in uneventful ways. Despite their differences, two thinkers who have significantly influenced radical democratic theory (Hannah Arendt and Jacques Rancière) have been similarly criticized for contributing to such a socially weightless picture of politics. However, attending (...) to how they are each preoccupied by the social conditions of inequality and loneliness enables us to recognize two distinct aspects of democratic politics–emancipation and civility. Cultivating an interpretive flexibility to shift between these aspects of politics might enable radical democrats to more clearly picture how struggles for appearance are limited and shaped by the social conditions within which they are enacted. (shrink)

Mill's On Liberty has turned out to be, as he predicted, the most widely read and long-lasting of his writings. It has proved, however, extremely difficult to pin Mill down to any definite political doctrines. His contemporaries clearly had the same problems as have beset modern commentators. Some portray Mill as a dangerous revolutionary, a latter-day Jacobin; others see him as peddling mere platitudes. This volume traces the reception of On Liberty in the periodical literature, from the "rave" review of (...) Buckle in Fraser's Magazine, by way of the furious denunciations in such Tory journals as Blackwood's and the Quarterly, down to later liberals like John Morley and Leslie Stephen. (shrink)

The only collection of Mead's writings published during his lifetime, these essays have heretofore been virtually inaccessible. Reck has collected twenty-five essays representing the full range and depth of Mead's thought. This penetrating volume will be of interest to those in philosophy, sociology, and social psychology. "The editor's well-organized introduction supplies an excellent outline of this system in its development. In view of the scattered sources from which these writings are gathered, it is a great service that this volume renders (...) not only to students of Mead, but to historians."—H. W. Schneider, _Journal of the History of Philosophy_. (shrink)

Over the past twenty years, Private Military and Security Companies (PMSCs) have become significant elements of national security arrangements, assuming many of the functions that have traditionally been undertaken by state armies. Given the centrality of control over the use of coercive force to the functioning and identity of the modern state, and to international order, these developments clearly are of great practical and conceptual interest. This edited volume provides an interdisciplinary overview of PMSCs: what they are, why they have (...) emerged in their current form, how they operate, their current and likely future military, political, social and economic impact, and the moral and legal constraints that do and should apply to their operation. The book focuses firstly upon normative issues raised by the development of PMSCs, and then upon state regulation and policy towards PMSCs, examining finally the impact of PMSCs on civil-military relations. It takes an innovative approach, bringing theory and empirical research into mutually illuminating contact. Includes contributions from experts in IR, political theory, international and corporate law, and economics, and also breaks important new ground by including philosophical discussions of PMSCs. (shrink)

This dissertation is concerned with theories of mental content, and in particular with the relationships between a theory of content and truth and rationality. My strategy is to examine the metaphysics of various approaches to content and ask certain questions. What is it for a belief to be true on a particular theory? What is it for a thought process to be rational? Are truth and rationality useful explanatory properties on each theory? Are they useful normative or action-guiding properties? Does (...) a theory allow truth and rationality to be valuable? ;I argue that there is a useful categorization of theories of mental content in terms of the kinds of connection they make between content and truth and rationality. Some theories, most notably Donald Davidson's and other theories inspired by his work, make it a constitutive truth, and thus necessary, that any entity that has intentional states must believe mostly truths and be largely rational. This holistic theories can be contrasted with other atomistic approaches, including those championed by Jerry Fodor and others, that deny such necessary connections, and leave the question of just how much truth and falsehood can be believed, and how rational or irrational a believer can be, to be settled by empirical investigation. ;The various chapters of this dissertation examine these different types of theories, and also the teleological theory of Ruth Millikan. I argue that atomistic theories of content have certain undesirable consequences: truth and rationality will no longer be explanatorily or normatively useful properties. On the other hand, holistic theories of content that make truth and rationality necessary features of systems with intentional states face different problems, because the norms they claim are constitutive of content are unlikely to be true of evolved creatures. Teleological theories, which presume a weak, historical connection between content and truth and rationality, fare best against these tests--they make truth and rationality important parts of explanations, and provide some motivation for pursuing them. (shrink)

Socrates teaches in the Meno that in order for a belief to be justified, an appropriate relation must ‘tie down’ the belief to its truth. Alvin Goldman’s position of externalism holds that for a belief to be justified, an appropriately reliable process must have obtained. One need not be aware of this reliable process. Conversely, Laurence BonJour’s brand of internalism holds that this relation between a belief and its truth is just what the cognizer needs to be aware of in (...) order for that belief to be justified. This work examines their debate, with particular interest paid to BonJour’s case of Norman: a clairvoyant who forms a belief via this ability but has no evidence for or against the belief or his own clairvoyance. Using this case, I propose an ‘epistemological spectrum’ wherein the insight of externalism is appreciated – what Robert Brandom deems the Founding Insight of Reliabilism – that a reliably produced belief bears some epistemic legitimacy, while retaining the insight of internalism: that objective reliability cannot offset subjective irrationality. This is done by classifying cases wherein only the obtainment of a reliable process occurs as epistemically rational, though not justified. Ultimately I reconcile the virtues of both positions, and propose that Goldman’s brand of full blooded externalism was generated by following an intuitional illusion by way of affirming the consequent. (shrink)

First Published in 2004. Routledge is an imprint of Taylor & Francis, an informa company.