Intracellular NLR (Nucleotide‐binding domain and Leucine‐rich Repeat‐containing) receptors are sensitive monitors that detect pathogen invasion of both plant and animal cells. NLRs confer recognition of diverse molecules associated with pathogen invasion. NLRs must exhibit strict intramolecular controls to avoid harmful ectopic activation in the absence of pathogens. Recent discoveries have elucidated the assembly and structure of oligomeric NLR signalling complexes in animals, and provided insights into how these complexes act as scaffolds for signal transduction. In plants, recent advances have provided (...) novel insights into signalling‐competent NLRs, and into the myriad strategies that diverse plant NLRs use to recognise pathogens. Here, we review recent insights into the NLR biology of both animals and plants. By assessing commonalities and differences between kingdoms, we are able to develop a more complete understanding of NLR function. (shrink)

In biomedical measurement, biomarkers are used to achieve reliable prediction of, and useful causal information about patient outcomes while minimizing complexity of measurement, resources, and invasiveness. A biomarker is an assayable metric that discloses the status of a biological process of interest, be it normative, pathophysiological, or in response to intervention. The greatest utility from biomarkers comes from their ability to help clinicians (and researchers) make and evaluate clinical decisions. In this paper we discuss a specific methodological use of clinical (...) biomarkers in pharmacological measurement: Some biomarkers, called ‘surrogate markers’, are used to substitute for a clinically meaningful endpoint corresponding to events and their penultimate risk factors. We confront the reliability of clinical biomarkers that are used to gather information about clinically meaningful endpoints. Our aim is to present a systematic methodology for assessing the reliability of multiple surrogate markers (and biomarkers in general). To do this we draw upon the robustness analysis literature in the philosophy of science and the empirical use of clinical biomarkers. After introducing robustness analysis we present two problems with biomarkers in relation to reliability. Next, we propose an intervention-based robustness methodology for organizing the reliability of biomarkers in general. We propose three relevant conditions for a robust methodology for biomarkers: (R1) Intervention-based demonstration of partial independence of modes: In biomarkers partial independence can be demonstrated through exogenous interventions that modify a process some number of “steps” removed from each of the markers. (R2) Comparison of diverging and converging results across biomarkers: By systematically comparing partially-independent biomarkers we can track under what conditions markers fail to converge in results, and under which conditions they successfully converge. (R3) Information within the context of theory: Through a systematic cross-comparison of the markers we can make causal conclusions as well as eliminate competing theories. We apply our robust methodology to currently developing Alzheimer’s research to show its usefulness for making causal conclusions. (shrink)

In this paper I want to do the following things. First I want to show that in the part of the Theaetetus where the relationship between knowledge and perception is examined, the concept of knowledge that is in question is very clearly characterized. We are left in no doubt as to what is to count as knowing. Secondly I want to unravel in some detail the case that Socrates puts on Protagoras’ behalf where he draws on what Protagoras actually wrote (...) (151 E-152C); as opposed to what he may have taught secretly to his pupils (152C-160D). Thirdly I wish to argue that if we let the dialogue speak for itself, it is manifest that this case put up on Protagoras’ behalf at 151 E-152C is not overthrown; it is not even shaken. (shrink)

In this paper I want to do the following things. First I want to show that in the part of the Theaetetus where the relationship between knowledge and perception is examined, the concept of knowledge that is in question is very clearly characterized. We are left in no doubt as to what is to count as knowing. Secondly I want to unravel in some detail the case that Socrates puts on Protagoras’ behalf where he draws on what Protagoras actually wrote (...) ; as opposed to what he may have taught secretly to his pupils. Thirdly I wish to argue that if we let the dialogue speak for itself, it is manifest that this case put up on Protagoras’ behalf at 151 E-152C is not overthrown; it is not even shaken.In that part of the dialogue where the question is under examination whether or not knowledge and perception are the same, Socrates uses an idealized concept of knowledge. That is, he restricts the use of the word by setting down what he will consider to be the essential characteristics of knowledge, the sufficient and necessary conditions of its being instantiated. An excellent piece of philosophical procedure. (shrink)

Because anticipated and retrospective regret play important roles in practical deliberation and motivation, better understanding them can illuminate the contours of human agency. However, the possibility of self-ignorance and the fact that we change over time can make regret—especially anticipatory regret—not only a poor predictor of where the agent will be in the future but also an unreliable indicator of where the agent stands. Granting these, this paper examines the way in which prospective and, particularly, retrospective regret can nevertheless yield (...) important insight into the sorts of creatures we are, both generally and individually. The experience of retrospective regret can show a person she values something in a way she did not know or that she is (or was) a different person than she had thought, insights which can factor into forward-looking, or prospective, deliberation. Such instances of revelatory regret reveal something to the agent about herself as agent. I examine two cases of agential self-ignorance. In the first, the experience of regret reveals what the agent values, not only to others but even to the agent himself. In the second, the agent anticipates experiencing regret for an action but does not experience the regret, suggesting that the agent did not value the rejected alternative in the way she thought. Anticipatory regret is forward-looking and can play an important role in practical deliberation. But insofar as anticipatory regret flows from one’s imperfect judgment and prospection about oneself, retrospective regret can be an important corrective in helping the agent understand her own standpoint. (shrink)

In his newly updated version of The Anatomy of a Constitutional Law Case, Alan F. Westin provides a documentary portrait of historically important constitutional law case, 'Youngstown Sheet & Tube Co. v. Sawyer, ' from its rise in a bargaining dispute in the steel industry during 1952 to the aftermath of its decision by the United States Supreme Court. Westin has added to his classic book additional materials and personal commentaries collected since the work was first published. The new information (...) covers what went on within the Truman administration, what went on within the Supreme Court when analyzing and resolving issues that come before it. Westin includes selections from transcripts, briefs and other official proceedings, adds notes describing each phase of the constitutional process, and a section of commentary and questions relating this case to others. (shrink)

In past and modern psychophysics there are several unresolved methodological and philosophical problems of human and animal perception, including the outstanding question of the relational basis of whole psychophysics. Here the main issue is discussed: if, and to what extent, there are viable bridges between the traditional “gestalt” oriented approaches and the modern perceptual-cognitive perspectives in psychophysics. Thereby the key concept of psychological “frame of reference” is presented by pointing to Hermann Ebbinghaus' geometric-optical illusions, on the one hand, and Max (...) Wertheimer's treatment of the traditional transposition phenomenon, on the other hand. A much-needed theoretical reorientation of future research may help to overcome the philosophical narrowness of present-day human and comparative psychophysics. (shrink)

It is not quite as easy to see that there is in fact no formula of this modal language having the same truth conditions (in terms of S5 Kripke semantics) as (1). This was rst conjectured by Allen Hazen2 and later proved by Harold Hodes3. We present a simple direct proof of this result and discuss some consequences for the logical analysis of ordinary modal discourse.

First published in 1984. Routledge is an imprint of Taylor & Francis, an informa company.

In recent years, there has been a heated debate about how to interpret findings that seem to show that humans rapidly and automatically calculate the visual perspectives of others. In the current study, we investigated the question of whether automatic interference effects found in the dot-perspective task (Samson, Apperly, Braithwaite, Andrews, & Bodley Scott, 2010) are the product of domain-specific perspective-taking processes or of domain-general “submentalizing” processes (Heyes, 2014). Previous attempts to address this question have done so by implementing inanimate (...) controls, such as arrows, as stimuli. The rationale for this is that submentalizing processes that respond to directionality should be engaged by such stimuli, whereas domain-specific perspective-taking mechanisms, if they exist, should not. These previous attempts have been limited, however, by the implied intentionality of the stimuli they have used (e.g. arrows), which may have invited participants to imbue them with perspectival agency. Drawing inspiration from “novel entity” paradigms from infant gaze-following research, we designed a version of the dot-perspective task that allowed us to precisely control whether a central stimulus was viewed as animate or inanimate. Across four experiments, we found no evidence that automatic “perspective-taking” effects in the dot-perspective task are modulated by beliefs about the animacy of the central stimulus. Our results also suggest that these effects may be due to the task-switching elements of the dot-perspective paradigm, rather than automatic directional orienting. Together, these results indicate that neither the perspective-taking nor the standard submentalizing interpretations of the dot-perspective task are fully correct. (shrink)

Are we witnessing progress or regress in the recent increasing popularity and electoral success of populist politicians and parties in consolidated democratic nations? ... Is the innovative use of popular referendum in Great Britain to settle fundamental constitutional questions a progressive or regressive innovation? ... Similarly, is the increasing use of constituent assemblies to change constitutions across the world evidence of progress in democratic constitutionalism, or, a worryingly regressive change back toward unmediated popular majoritarianism? ... This paper reflects on some (...) of the perils and promise of framing such questions with the conceptual couplet of progress and regress. It considers four compelling critiques of the use of ‘progress’ and its cognates in sociopolitical theory, as well as arguing that such concepts are nevertheless ineliminable for our normative theories. The paper concludes by suggesting that we can avoid the most serious problems by employing only conceptions of political progress and regress that are piecemeal, pragmatic, and processual. (shrink)

Theorists of public reason such as John Rawls often idealize constitutional courts as exemplars of public reason. This paper raises questions about the seduction and limits of analogies between theorists’ account of public reason and actual constitutional jurisprudence. Examining the work product of the United States Supreme Court, the paper argues that while it does engage in reason-giving to support its decisions—as the public reason strategy suggests— those reasons are (largely) legalistic and specifically juristic reasons—not the theorists’ idealized moral-political reasons (...) on matters of fundamental principle. But if constitutional courts do not engage on matters of fundamental principle, then a public reason strategy for assuaging democratic worries about judicial review would no longer be open: prominent liberal and deliberative democratic theorists could no longer point to the alleged superiority of constitutional courts to speak in the name of, and for, the people’s shared political principles. The paper extends beyond the U.S. case study by pointing to three institutional factors explaining the disanalogy between what some constitutional courts do and what public reason theories require them to do. It concludes with considerations about whether the public reason strategy might be more successfully applied to international courts. (shrink)

Autobiography and Teacher Development in China investigates the roles of autobiography in teacher education, as several scholars in China recontextualize Western conceptions of teacher development, combining them with uniquely Chinese cultural conceptions to articulate a reconceptualization of teacher development that holds worldwide significance. Framed by the work of Zhang Hua and William F. Pinar, these theoretical and practical essays point to an internationally inflected reconceptualization of teachers' professional development, pre-service and in-service. This volume addresses multiple movements of teacher education reform (...) worldwide, focused on crafting a nationally distinctive course not only internationally, but also culturally, historically, and locally. (shrink)

From climate change to fossil fuel dependency, from the uneven effects of natural disasters to the loss of biodiversity: complex socio-environmental problems indicate the urgency for cross-disciplinary research into the ways in which the social, the natural and the technological are ever more entangled. This ground breaking text moves between environmental sociology and environmental geography, political and social ecology and critical design studies to provide a definitive mapping of the state of environmental social theory in the age of the anthropocene. (...) Environments, Natures and Social Theory provokes dialogue and confrontation between critical political economists, actor network theorists, neo-Malthusians and environmental justice advocates. It maps out the new environmental politics of hybridity moving from hybrid neo-liberals to end times ecologists, from post environmentalists to cyborg eco-socialists. White, Rudy and Gareau insist on the necessity of a critical but optimistic hybrid politics, arguing that a more just, egalitarian, democratic and sustainable anthropocene is within our grasp. This will only be brought into being, however, by reclaiming, celebrating and channeling the reconstructive potential of entangled hybrid humans as inventive hominids, creative gardeners, critical publics and political agents. Written in an accessible style, Environments, Natures and Social Theory is an essential resource for undergraduate and postgraduate students across the social sciences. (shrink)

Since Mueller’s 1958 article calling Hegelian dialectics a “legend,” it has been fashionable to deny that Hegel used thesis-antithesis-synthesis dialectics. But in truth, Hegel’s Phenomenology of Spirit has 28 dialectics hidden on four outline levels, and The Philosophy of History has 10 more on three outline levels. In Phenomenology’s macrodialectic, Hegel’s nonsupernatural Spirit–all reality, everything in the universe, including man and artificial objects–advances from unconscious + union (thesis) to conscious + separation (antithesis) to a synthesis of conscious (from the antithesis) (...) + union (from the thesis). Previous interpretations of Phenomenology have missed this dialectic: they have assumed that Spirit’s journey begins with consciousness, whereas the journey actually begins in the primordial state of nature, before man arrives and provides Spirit with its Mind (the collective mind of man). Mind then misperceives itself as a multitude of separate alien “objects”–things other than itself. The macrodialectic and all other dialectics are based on Christianity’s Johannine separation-and-return mythology; all Hegelian dialectics separate from a concept in the thesis, going to that something’s opposite (antithesis), and then return to the thesis concept. Thus, in Hegel’s master-and-slave dialectic (God = master, man = slave), man advances from potential + freedom to actual + bondage (religiosity) to actual + freedom (atheism). Only Marx and Tillich understood Hegelian dialectics. Marx’s basic dialectic (one of four) saw history separating from and returning to Communism, going from communal ownership + poverty (primitive communism, or gens) to private ownership + wealth (slavery, feudalism, capitalism) to communal ownership + wealth (final communism). Tillich’s basic dialectic (one of many) separates from and returns to God, advancing from Yes to God + Yes to supernaturalism (theism) to No to God + No to supernaturalism (atheism) to Yes to God + No to supernaturalism (humanism: humanity is the nonsupernatural “God above the God of theism”). (shrink)

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Whiskey Lao -- Fair warning -- Randomness at large -- We the addicted -- The best possible world -- The importance of being doomed -- Moral responsibility -- The upper limit to the value of possible worlds.