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)

Appearing in English for the first time, Schelling’s 1842 lectures develop the idea that many philosophical concepts are born of religious-mythological notions.

The notorious ‘measurement problem’ has been roving around quantum mechanics for nearly a century since its inception, and has given rise to a variety of ‘interpretations’ of quantum mechanics, which are meant to evade it. We argue that no less than six problems need to be distinguished, and that several of them classify as different types of problems. One of them is what traditionally is called ‘the measurement problem’. Another of them has nothing to do with measurements but is a (...) profound metaphysical problem. We also analyse critically Maudlin’s (Topoi 14:7–15, 1995) well-known statement of ‘three measurements problems’, and the clash of the views of Brown (Found Phys 16:857–870, 1986) and Stein (Maximal of an impossibility theorem concerning quantum measurement. In: R. S. Cohen et al. (Eds.), Potentiality, entanglement and passion-at-a-distance, 1997) on one of the six measurement problems. Finally, we summarise a solution to one measurement problem which has been largely ignored but tacitly if not explicitly acknowledged. (shrink)

This paper starts with one of Chalmers’ basic points: first-hand experience is an irreducible field of phenomena. I claim there is no ‘theoretical fix’ or ‘extra ingredient’ in nature that can possibly bridge this gap. Instead, the field of conscious phenomena requires a rigorous method and an explicit pragmatics for its exploration and analysis. My proposed approach, inspired by the style of inquiry of phenomenology, I have called neurophenomenology. It seeks articulations by mutual constraints between phenomena present in experience and (...) the correlative field of phenomena established by the cognitive sciences. It needs to expand into a widening research community in which the method is cultivated further. (shrink)

Good work in nursing is work that is scientifically effective as well as morally and socially responsible. The purpose of this study was to examine variables that sustain good work among entering nurses (with one to five years of experience) and experienced professional nurses despite the obstacles they encounter. In addition to role models and mentors, entering and experienced nurses identified team work, cohesiveness and shared values as levers for good work. These nurses used prioritization, team building and contemplative practices (...) to overcome obstacles. Entering professional nurses tended to avoid conflict in the work setting. Experienced nurses reported forming teams of decision makers who share similar values to resolve conflict. These findings have implications for nurse education and nursing practice. Reflection on the importance of values and virtue in sustaining good work is important. Entering professional nurses should be encouraged to seek positive role models and reflect on the lessons that can be learned from experienced exemplary nurses. (shrink)

With fascinating historical anecdotes and incisive scientific analysis, this important work combines ancient thought with modern theory to reveal a new way of viewing our universe that can expand our awareness, our lives, and may well point the way to a new science for the twenty-first century.

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)

This is an English translation of Schelling's Ideas for a Philosophy of Nature (first published in 1797 and revised in 1803), one of the most significant works in the German tradition of philosophy of nature and early nineteenth-century philosophy of science. It stands in opposition to the Newtonian picture of matter as constituted by inert, impenetrable particles, and argues instead for matter as an equilibrium of active forces that engage in dynamic polar opposition to one another. In the revisions of (...) 1803 Schelling incorporated this dialectical view into a neo-Platonic conception of an original unity divided upon itself. The text is of more than simply historical interest: its daring and original vision of nature, philosophy, and empirical science will prove absorbing reading for all philosophers concerned with post-Kantian German idealism, for scholars of German Romanticism, and for historians of science. (shrink)

I begin by criticizing an elaboration of an argument in this journal due to Hawley , who argued that, where Leibniz’s Principle of the Identity of Indiscernibles faces counterexamples, invoking relations to save PII fails. I argue that insufficient attention has been paid to a particular distinction. I proceed by demonstrating that in most putative counterexamples to PII , the so-called Discerning Defence trumps the Summing Defence of PII. The general kind of objects that do the discerning in all cases (...) form a category that has received little if any attention in metaphysics. This category of objects lies between indiscernibles and individuals and is called relationals: objects that can be discerned by means of relations only and not by properties. Remarkably, relationals turn out to populate the universe. (shrink)

Even though morally competent artificial agents have yet to emerge in society, we need insights from empirical science into how people will respond to such agents and how these responses should inform agent design. Three survey studies presented participants with an artificial intelligence agent, an autonomous drone, or a human drone pilot facing a moral dilemma in a military context: to either launch a missile strike on a terrorist compound but risk the life of a child, or to cancel the (...) strike to protect the child but risk a terrorist attack. Seventy-two percent of respondents were comfortable making moral judgments about the AI in this scenario and fifty-one percent were comfortable making moral judgments about the autonomous drone. These participants applied the same norms to the two artificial agents and the human drone pilot. However, people ascribed different patterns of blame to humans and machines as a function of the agent’s decision of how to solve the dilemma. These differences in blame seem to stem from different assumptions about the agents’ embeddedness in social structures and the moral justifications those structures afford. Specifically, people less readily see artificial agents as embedded in social structures and, as a result, they explained and justified their actions differently. As artificial agents will perform many actions with moral significance, we must heed such differences in justifications and blame and probe how they affect our interactions with those agents. (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)

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

The present book is intended to help students overcome difficulties by presenting Jaspers' thoughts in comparatively clear and straightforward fashion. While it denies that philosophy is "practical" in any cheap and obvious sense, it follows Jaspers in attempting to avoid the otiose and emphasize the relevance of philosophy to matters of ultimate concern. Those who wish a more theoretical and systematic presentation may well call to mind that, as Heidegger's followers express it, Jaspers, like Kierkegaard- and to some extent Sartre- (...) quite deliberately spurned the "ontological" in favor of the "ontic.". (shrink)

Disjunctivism about perceptual appearances, as I conceive of it, is a theory which seeks to preserve a naïve realist conception of veridical perception in the light of the challenge from the argument from hallucination. The naïve realist claims that some sensory experiences are relations to mind-independent objects. That is to say, taking experiences to be episodes or events, the naïve realist supposes that some such episodes have as constituents mind-independent objects. In turn, the disjunctivist claims that in a case of (...) veridical perception like this very kind of experience that you now have, the experiential episode you enjoy is of a kind which could not be occurring were you having an hallucination. The common strategy of arguments from hallucination set out to show that certain things are true of hallucinations, and hence must be true of perceptions. For example, it is argued that hallucinations must have non-physical objects of awareness, or that such states are not relations to anything at all, but are at best seeming relations to objects. In insisting that veridical perceptual experience is of a distinct kind from hallucination, the disjunctivist denies that any of these conceptions of hallucination challenges our conception of veridical perceptions as relations to mind-independent objects. More specifically, I assume that the disjunctivist advocates naïve realism because they think that this position best articulates how sensory experience seems to us to be just through reflection. If the disjunctivist is correct in this contention, then anyone who accepts the conclusion of the argument from hallucination must also accept that the nature of sensory experience is other than it seems to us to be. In turn, one may complain that any such error theory is liable to lead to sceptical consequences. A Humean scepticism about the senses launches a challenge about our knowledge of the world through questioning the conception we have of what sense experience is, and how it can provide knowledge of the world. (shrink)

John F. Post argues that physicalistic materialism is compatible with a number of views often deemed incompatible with it, such as the objectivity of values, the irreducibility of subjective experience, the power of the metaphor, the normativity of meaning, and even theism.