G protein‐coupled receptors (GPCRs) constitute the largest family of transmembrane proteins and play a crucial role in regulating diverse cellular functions. They transmit their signaling via binding to intracellular signal transducers and effectors, such as G proteins, GPCR kinases, and β‐arrestins. To influence specific GPCR signaling behaviors, β‐arrestins recruit effectors to form larger signaling complexes. Intriguingly, they facilitate divergent functions for the binding to different receptors. Recent studies relying on advanced structural approaches, novel biosensors and interactome analyses bring us closer (...) to understanding how this specificity is achieved. In this article, we share our hypothesis of how active GPCRs induce specific conformational rearrangements within β‐arrestins to reveal distinct binding interfaces, enabling the recruitment of a subset of effectors to foster specialized signaling complexes. Furthermore, we discuss methods of how to comprehensively assess β‐arrestin conformational states and present the current state of research regarding the functionality of these multifaceted scaffolding proteins. (shrink)

An action-oriented perspective changes the role of an individual from a passive observer to an actively engaged agent interacting in a closed loop with the world as well as with others. Cognition exists to serve action within a landscape that contains both. This chapter surveys this landscape and addresses the status of the pragmatic turn. Its potential influence on science and the study of cognition are considered (including perception, social cognition, social interaction, sensorimotor entrainment, and language acquisition) and its impact (...) on how neuroscience is studied is also investigated (with the notion that brains do not passively build models, but instead support the guidance of action). A review of its implications in robotics and engineering includes a discussion of the application of enactive control principles to couple action and perception in robotics as well as the conceptualization of system design in a more holistic, less modular manner. Practical applications that can impact the human condition are reviewed (e.g., educational applications, treatment possibilities for developmental and psychopathological disorders, the development of neural prostheses). All of this foreshadows the potential societal implications of the pragmatic turn. The chapter concludes that an action-oriented approach emphasizes a continuum of interaction between technical aspects of cognitive systems and robotics, biology, psychology, the social sciences, and the humanities, where the individual is part of a grounded cultural system. (shrink)

This paper examines the importance of aspirations as reference points in a multi-period decision-making context. After stating their personal aspiration level, 172 individuals made six sequential decisions among risky prospects as part of a choice experiment. The results show that individuals make different risky-choices in a multi-period compared to a single-period setting. In particular, individuals’ aspiration level is their main reference point during the early stages of decision-making, while their starting status (wealth level at the start of the experiment) becomes (...) the central reference point during the later stages of their multi-period decision-making. (shrink)

Responding to a major pandemic and planning for allocation of scarce resources under crisis standards of care requires coordination and cooperation across federal, state and local governments in tandem with the larger societal infrastructure. Maryland remains one of the few states with no state-endorsed ASR plan, despite having a plan published in 2017 that was informed by public forums across the state. In this article, we review strengths and weaknesses of Maryland’s response to COVID-19 and the role of the Maryland (...) Healthcare Ethics Committee Network in bridging gaps in the state’s response to prepare health care facilities for potential implementation of ASR plans. Identified “lessons learned” include: Deliberative Democracy Provided a Strong Foundation for Maryland’s ASR Framework; Community Consensus is Informative, Not Normative; Hearing Community Voices Has Inherent Value; Lack of Transparency & Political Leadership Gaps Generate a Fragmented Response; Pandemic Politics Requires Diplomacy & Persistence; Strong Leadership is Needed to Avoid Implementing ASR … And to Plan for ASR; An Effective Pandemic Response Requires Coordination and Information-Sharing Beyond the Acute Care Hospital; and The Ability to Correct Course is Crucial: Reconsidering No-visitor Policies. (shrink)

Volume 20, Issue 7, July 2020, Page 150-152.

ABSTRACT Causes must be distinct from their effects. If the temperature in a room is 15°F, this can cause water pipes to freeze. However, the temperature’s being 15°F is not a cause of the temperature’s being below the freezing point. In general, conceptual, logical, mathematical, and other non-causal dependence relations should not be misclassified as causal. In this paper, I discuss how interventionist theories of causation can meet the challenge of distinguishing between (direct or indirect) causal relations and dependence relations (...) that are due to non-causal factors. I survey several approaches to solving this problem, and propose a novel criterion based on the notion of supervenience. According to this criterion, variables are sufficiently distinct to qualify as the relata of a causal relation iff they do not have overlapping minimal supervenience bases. (shrink)

Open peer commentary on the article “Second-Order Science of Interdisciplinary Research: A Polyocular Framework for Wicked Problems” by Hugo F. Alrøe & Egon Noe. Upshot: Alrøe and Noe are right in addressing Rittel and Webber’s notion of “wicked problems” as crucial for interdisciplinary research. However, I can see neither that they are providing a sufficiently clear understanding of “science” in their concept of a “second-order science of interdisciplinary research,” nor that their “polyocular framework” can contribute anything useful to addressing the (...) practical challenges posed by wicked problems. (shrink)

In his classic work The Mind and its Place in Nature published in 1925 at the height of the development of quantum mechanics but several years after the chemists Lewis and Langmuir had already laid the foundations of the modern theory of valence with the introduction of the covalent bond, the analytic philosopher C. D. Broad argued for the emancipation of chemistry from the crass physicalism that led physicists then and later—with support from a rabblement of philosophers who knew as (...) much about chemistry as etymologists—to believe that chemistry reduced to physics. Here Broad’s thesis is recast in terms more familiar to chemists. In the hard sell of particle physics, several prominent figures in chemistry—Hoffmann, Primas, and Pauling—have had their views interpreted to imply that they were sympathetic to greedy reductionism when in fact they were not. Indeed, being chemists without physicists as alter egos, they could not but side with Broad’s contention that chemistry, as a science that deals primarily in emergent phenomena which are beyond the purview of physicalism, owes no acquiescence to particle physics and its ethereal wares. Historically, among the most widely used expediencies in chemistry and materials science are additivity or mixture rules and their cohort transferability, all of which are devised and used under the mantle of naive reductionism. Here it is argued that while the transfer of functional groups between molecules works empirically to an extent, it is strictly outlawed by the no-cloning theorem of quantum mechanics. Several illustrative examples related to chemistry’s irreducibility to physics are presented and discussed. The failure of naive reductionism exhibited by the deep-inelastic scattering of leptons by A > 2 nuclei is traced to the same flawed reasoning that was the original basis of Moffitt’s ‘atoms in molecules’ hypothesis, the neglect of context, nuclei in the case of high-energy physics and molecules in the case of chemistry. A non-exhaustive list of other contexts from physics, chemistry, and molecular biology evidencing similar departures from the ideal of additivity or reductionism is provided for the perusal of philosophers. Had the call by the mathematician J. T. Schwartz for developments in mathematical linguistics possessed of a less single, less literal, and less simple-minded nature been met, perhaps it might have persuaded scientists to abandon their regressive fixation with unphysical reductionism and to adapt to new methodologies that engender a more nuanced handling of ubiquitous emergent phenomena as they arise in Nature than is the case today. (shrink)

The use of upper limb vibration during exercise and rehabilitation continues to gain popularity as a modality to improve function and performance. Currently, a lack of knowledge of the pathways being altered during ULV limits its effective implementation. Therefore, the aim of this study was to investigate whether indirect ULV modulates transmission along spinal and corticospinal pathways that control the human forearm. All measures were assessed under CONTROL and ULV conditions while participants maintained a small contraction of the right flexor (...) carpi radialis muscle. To assess spinal pathways, Hoffmann reflexes elicited by stimulation of the median nerve were recorded from FCR with motor response amplitudes matched between conditions. An H-reflex conditioning paradigm was also used to assess changes in presynaptic inhibition by stimulating the superficial radial nerve 37 ms prior to median nerve stimulation. Cutaneous reflexes in FCR elicited by stimulation of the SR nerve at the wrist were also recorded. To assess corticospinal pathways, motor evoked potentials elicited by transcranial magnetic stimulation of the contralateral motor cortex were recorded from the right FCR and biceps brachii. ULV significantly reduced H-reflex amplitude by 15.7% for both conditioned and unconditioned reflexes. Therefore, ULV inhibits cutaneous and H-reflex transmission without influencing corticospinal excitability of the forearm flexors suggesting increased presynaptic inhibition of afferent transmission as a likely mechanism. A general increase in inhibition of spinal pathways with ULV may have important implications for improving rehabilitation for individuals with spasticity. (shrink)

This landmark work provides a systematic introduction to systems of modal logic and stands as the first presentation of what have become central ideas in philosophy of language and metaphysics, from the "new theory of reference" and non-linguistic necessity and essentialism to "Kripke semantics.".

Chemical structures are among the trademarks of our profession, as surely chemical as flasks, beakers and distillation columns. When someone sees one of us busily scribbling formulas or structures, he or she has no trouble identifying a chemist. Yet these familiar objects, which accompany our work from start to end, from the initial doodlings (Fig. I) to the final polished artwork in a publication (Fig. II), are deceptively simple. They raise interesting and difficult questions about representation. It is the intent (...) of this article to reflect upon molecular graphics. (shrink)

Diese Studie analysiert die Konzepte «Wissenskulturen» und «Experimentalkulturen», um sich dem Problem der Repräsentation mittels einer Mehrfaktoren-Analyse zu nähern.

Theories of graded causation attract growing attention in the philosophical debate on causation. An important field of application is the controversial relationship between causation and moral responsibility. However, it is still unclear how exactly the notion of graded causation should be understood in the context of moral responsibility. One question is whether we should endorse a proportionality principle, according to which the degree of an agent’s moral responsibility is proportionate to their degree of causal contribution. A second question is whether (...) a theory of graded causation should measure closeness to necessity or closeness to sufficiency. In this paper, we argue that we should indeed endorse a proportionality principle and that this principle supports a notion of graded causation relying on closeness to sufficiency rather than closeness to necessity. Furthermore, we argue that this insight helps to provide a plausible analysis of the so-called ‘Moral Difference Puzzle’ recently described by Bernstein. (shrink)

Over the last two decades, the capabilities approach has become an increasingly influential theory of development. It conceptualises human wellbeing in terms of an individual's ability to achieve functionings we have reason to value. In contrast, the African ethic of ubuntu views human flourishing as the propensity to pursue relations of fellowship with others, such that relationships have fundamental value. These two theoretical perspectives seem to be in tension with each other; while the capabilities approach focuses on individuals as the (...) locus of ethical value, an ubuntu ethic concentrates on the relations between individuals. In this article, we ask: to what extent is the capabilities approach compatible with this African ethical theory? We argue that, on reflection, relations play a much stronger role in the capabilities approach than often assumed. There is good reason to believe that relationality is part of the concept of a capability itself, where such relationality has intrinsic ethical value. This understanding of the ethical centrality of relations grounds new normative perspectives on the capabilities approach, and offers a more comprehensive grasp of the relevance of relationships to empirical enquiry. (shrink)

100 years ago, the editors of the Journal of Educational Psychology conducted one of the most famous studies of experts’ conceptions of human intelligence. This was reason enough to prompt the question where we stand today with making sense of “intelligence”. In this paper, we argue that we should overcome our anthropocentrism and appreciate the wonders of intelligence in nonhuman and nonbiological animals instead. For that reason, we study two cases of octopus intelligence and intelligence in machine learning systems to (...) embrace the notion of intelligence as a non-unitary faculty with pluralistic forms. Furthermore, we derive lessons for advancing our human self-understanding. (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.

With precision and profundity born of 30 years of devoted study, John Boyle offers an essential introduction to St. Thomas Aquinas on Scripture, shedding helpful light on the goals, methods, and commitments that animate the Angelic Doctor's engagement with the sacred page. Because the genius of St. Thomas's approach to the Bible lies not so much in its novelty but rather in the fidelity and clarity with which he recapitulates the riches of the preceding interpretive Tradition, this initiation into St. (...) Thomas's vision of Scripture is itself an orientation to the Church's vision of Scripture, from the Fathers through and beyond the Middle Ages. St. Thomas's embeddedness within the Church's Tradition and his own historical context is integral to his approach to Scripture, yet it sets him at some distance from modern readers, for whom his interpretive vision may seem perplexing or even impenetrable. In this Primer, Boyle first provides an acclimation to this medieval context through a survey and explanation of pertinent technical terminology used by St. Thomas and characteristic of the scholastic theology of the time. With an eye to the medieval practice of considering Scripture according to the fourfold division of causes, Boyle builds on this initial foundation by exploring in turn St. Thomas's accounts of the end or use of Scripture (final cause), its divine and human authorship (efficient cause), its order and division (material cause), and its literary styles or genres (formal cause). Drawing on writings from across St. Thomas's corpus, but especially his work On the Commendation and Division of Sacred Scripture and the prologues to his biblical commentaries, Boyle masterfully elucidates both the hermeneutical principles and deep wisdom of the Angelic Doctor's approach to Scripture, imparting invaluable guidance not only for reading and understanding St. Thomas and other great masters of the Tradition, but also-and ultimately-for understanding Scripture in light of this Tradition and reading it with greater benefit and joy. (shrink)

Many consumers implicitly associate sustainability with lower product strength. This so-called ethical = less strong intuition (ELSI) poses a major threat for the success of sustainable products. This article explores this pervasive lay theory and examines whether it is a key barrier for sustainable consumption patterns. Even more importantly, little is known about the underlying mechanisms that might operate differently at the implicit and explicit levels of the consumer’s decision-making. To fill this gap, three studies examine how the implicit judgments (...) that consumers activate automatically shape their consumption behaviors, in concert with their more controlled explicit beliefs about sustainable products. The Main Study investigates the ELSI’s imprint on actual shopping patterns and disentangles the implicit and explicit mechanisms of the lay theory. This paper also asks how this negative influence can be attenuated by examining whether the consumer’s interest in sustainable consumption reduces reliance on the ELSI. Two follow-up studies confirm the robustness from different methodological and practical perspectives. Implications for companies and policy makers are derived. (shrink)

Over twenty years have passed since JLME published “The Girl Who Cried Pain: A Bias Against Women in the Treatment of Pain.” This article revisits the conclusions drawn in that piece and explores what we have learned in the last two decades regarding the experience of men and women who have chronic pain and whether women continue to be treated less aggressively for their pain than men.

This contribution analyzes the general relation between nature and laboratory with respect to the alternative of a ,,presented" and a ,,self-presenting nature". It is argued that as essentially presented by technological means, ,,nature in the laboratory" has to be considered as a dimensionally reduced nature already incorporated to the objective world of man. The basic precondition of the emergence of laboratory science on the threshold of modern times was the introduction of a concept of an ,,active physics" which itself presupposed (...) the abandonment of a given ,,metaphysical" order of phenomena, especially in the sense of the Aristotelian substance-accidence-scheme. The logic of a suchlike forced ,,presentation of nature", and also the logic of the modern technology-dependent ways of progress in knowledge can precisely be analyzed within the theoretical framework of the Paul-Lorenzen-School (,,Methodological constructivism"). The concept of a ,,self-presenting nature", on the other hand, requires a genuine reflection of a philosophy of nature which is able to focus on the aspects of self-reference and differentiality of the genuine instances of nature. Finally three starting-points of a non-laboratorial way of thinking nature are discussed. German Der Beitrag analysiert das Verhältnis von Natur und Labor unter dem Gesichtspunkt der Alternative von ,,sich zeigender und ,,gezeigter Natur, wobei die im Labor auf dem Wege einer wesentlich technisch-praktischen Erwirkung konkret ,,gezeigte Natur eine der Gegenstandswelt des Menschen immer schon integrierte (und insoweit dimensional verkürzte) Natur ist. Die entscheidende Voraussetzung für die Entstehung der Laborwissenschaft an der Schwelle zur Neuzeit war die Einführung eines Konzepts ,,handelnder Physik, das seinerseits die Preisgabe einer vorgängigen ,,metaphysischen Ordnung der Phänomene (insbesondere im Sinne des Substanz-Akzidens-Gefälles) voraussetzt. Die Logik dieses ,,Zeigens der Natur ebenso wie die des modernen, technologieabhängig gewordenen Erkenntnisfortschritts ist wissenschaftstheoretisch mit den Mitteln des Methodischen Konstruktivismus präzise beschreibbar. Für den alternativen Begriff einer ,,sich zeigenden Natur als wesentlich polydimensionaler, einheitsbegrifflich nicht einholbarer Totalität bedarf es jedoch einer genuin naturphilosophischen Reflexion, die insbesondere die mit dem Natürlichen verbundenen Komponenten der Selbstbezüglichkeit und der Differentialität zu thematisieren vermag. Abschließend werden drei Ansatzpunkte eines ,,nichtlaboratorischen Naturdenkens diskutiert. (shrink)

Résumé L’article développe la thèse suivante : le phénomène évaluatif, ses instruments et ses institutions nouvellement créées (agences de notation, agences d’évaluation, hautes autorités) sont à la fois les révélateurs et les opérateurs d’une transformation des rapports entre deux institutions en crise : L’État et les professions. S’inspirant de la trilogie des pouvoirs de Freidson (2001), l’auteur suggère d’analyser l’alliance actuelle entre marché et État tandis qu’une crise et une mutation des élites traditionnelles françaises (haute fonction publique, experts d’État, élites (...) politiques) fragilisent l’alliance entre professions et État caractéristique de la construction de l’État social à la fin du xix e siècle. (shrink)

Résumé L’article développe la thèse suivante : le phénomène évaluatif, ses instruments et ses institutions nouvellement créées (agences de notation, agences d’évaluation, hautes autorités) sont à la fois les révélateurs et les opérateurs d’une transformation des rapports entre deux institutions en crise : L’État et les professions. S’inspirant de la trilogie des pouvoirs de Freidson (2001), l’auteur suggère d’analyser l’alliance actuelle entre marché et État tandis qu’une crise et une mutation des élites traditionnelles françaises (haute fonction publique, experts d’État, élites (...) politiques) fragilisent l’alliance entre professions et État caractéristique de la construction de l’État social à la fin du xix e siècle. (shrink)