Loop regions in proteins have traditionally been described as ‘random coil’, although they are known to adopt well‐defined conformations in most globular proteins. In this contribution we summarize the results of detailed analysis of the structures and sequences of these loop regions in proteins of known three‐dimensional structure. We also describe how these results can be used as an aid to protein design, modification and modelling.

The World Health Organisation recently listed air pollution as the most significant threat to human health. Air pollution comprises particulate matter (PM), metals, black carbon and gases such as ozone (O3), nitrogen dioxide (NO2) and carbon monoxide (CO). In addition to respiratory and cardiovascular disease, PM exposure is linked with increased risk of neurodegeneration as well as neurodevelopmental impairments. Critically, studies suggest that PM crosses the placenta, making direct in utero exposure a reality. Rodent models reveal that neuroinflammation, neurotransmitter imbalance (...) and oxidative stress are triggered following gestational/early life exposure to PM, and may be exacerbated by concomitant mitochondrial dysfunction. Gestational PM exposure (potentiated by mitochondrial impairment in the metabolically active neonatal brain) not only impacts neurodevelopment but may sensitise the brain to subsequent cognitive impairment. Having reviewed this field, we conclude that strategies are urgently required to reduce exposure to PM during this sensitive developmental period. (shrink)

Judges face difficult choices when the birth and genetic mothers of a child are separate people who dispute maternal access; the views of the general population may help them. Fifty women were asked whether, if they were infertile and could have only one child, they would prefer to be birth mothers (to carry a baby which was not genetically theirs) or genetic mothers (to have another woman carry their genetic baby). Similarly, fifty men were asked about their preference for a (...) partner's child. In both groups the strength of preferences was measured using a lottery technique. The direction and strength of preferences was similar between men and women, and approximately equally divided between birth and genetic motherhood. These attitudes should be taken into account by those adjudicating custody disputes between such mothers. (shrink)

Il y a vingt-cinq ans, j’étais un étudiant de doctorat intéressé par la philosophie d’Aristote et à la recherche d’un sujet de thèse. Au cours de mes études supérieures, j’ai eu la chance d’étudier l’Éthique à Nicomaque avec Rémi Brague et Les Politiques avec Judith Swanson. Ces deux érudits m’ont, à leur façon, fait prendre conscience de l’importance d’enquêter sur le public cible des œuvres d’Aristote. Tous deux parlaient en bien du livre Le philosophe et la cité (Les Belles Lettres, (...) 1982) de Richard Bodéüs, qui venait d’être traduit en anglais sous le titre The Political Dimensions of Aristotle’s Ethics (State University of New York Press, 1993). Il se trouva qu’un jour de printemps, ayant été appelé à siéger comme juré, je pris avec moi mon tout nouvel exemplaire du volume de Bodéüs. Heureusement, le jury ne fut pas convoqué, mais on ne me laissa pas partir avant la fin de l’après-midi. Aussi passai-je toute la journée au palais de justice à lire l’ouvrage de Bodéüs et à réfléchir à la relation entre le concept de justice déployé dans l’Éthique à Nicomaque et les analyses des constitutions qu’on trouve dans Les Politiques. Je découvris alors une réflexion savante, riche et profondément historique, portant sur la façon de comprendre les divers traités d’Aristote sur «la philosophie des choses humaines» (EN 10.9.1181b15). C’est ainsi que je fus mis sur la voie du sujet de sur lequel porterait ma thèse : la nature de la justice politique chez Aristote. C’est aussi ainsi que j’en vins à penser en compagnie de l’un des plus éminents spécialistes et traducteurs d’Aristote du siècle dernier. En 2018, la Northeast Political Science Association annonça que sa réunion annuelle allait se tenir à Montréal et invita ses membres à soumettre des contributions dans les deux langues officielles canadiennes. Étant donné que Montréal abrite également l’université dans laquelle Bodéüs avait enseigné, l’Université de Montréal, il m’est immédiatement venu à l’esprit de proposer un panel bilingue pour explorer la philosophie d’Aristote à la lumière de son ouvrage novateur, Le philosophe et la cité, qui fut déterminant pour mon parcours intellectuel. Deux panels furent constitués. Le premier rassemblait les participants anglophones : Jordan Jochim (Cornell University), Kevin Cherry (Richmond University) et moi-même (Quinnipiac University), et fut présidé par Jill Frank (Cornell University). Le second panel rassemblait les participants francophones : Léa Derome (Université McGill), Timothée Gautier (Université Paris 1 — Panthéon-Sorbonne), Louise Rodrigue (Collège universitaire dominicain), et fut présidé par Elsa Bouchard (Université de Montréal). Bodéüs, qui est à présent professeur émérite, accepta généreusement de lire toutes les contributions à l’avance et, combattant un mal de gorge le jour de la conférence, accompagna chacune d’entre elles de commentaires à la fois perspicaces et magnanimes. N’ayant pas pu inclure toutes les présentations de la conférence de novembre 2018, ce numéro de Dialogue comprend les versions révisées de trois contributions : mon “ὁμόνοια: The Hinge of Aristotle’s Ethics and Politics?”, la contribution de Kevin Cherry, “Lawgivers, Virtue, and the Mixed Regime: Reflections on Richard Bodéüs’s The Political Dimensions of Aristotle’s Ethics,” et celle de Louise Rodrigue, «La conception aristotélicienne de la servilité dans l’Éthique et la Politique». Nous remercions tout particulièrement Léa Derome, qui a édité cette tribune du livre, coordonné la soumission de nos documents et des réponses de Bodéüs à Dialogue, et a aidé à la traduction en français. Les trois articles présentés composent avec des interrogations héritées du travail du professeur Bodéüs. Nous sommes donc particulièrement reconnaissants qu’il ait accepté de contribuer à ce projet de publication. Nous espérons que l’ensemble parvienne à capturer ne serait-ce qu’un simulacre de l’expérience intellectuelle passionnante que fut notre journée de conférences de novembre 2018. (shrink)

Pierre Pellegrin has devoted his scholarly life to the understanding of Aristotle the political philosopher, Aristotle the life-scientist, and—perhaps most importantly—Aristotle the analyst of life-science who is also a political philosopher. Like D. M. Balme, Allan Gotthelf, and James Lennox—Pellegrin is one of the foremost scholars who has sought to understand Aristotle’s biological writings in a philosophically and philologically sophisticated fashion. Pellegrin is also one of the foremost scholars who has sought to understand the intersection between Aristotle’s biological studies and (...) his other works, especially the ethical/political writings, like current scholars such as Sophia Connell, Mariska Leunissen, and Adriel M. Trott. The volume under-review, Anthony Preus’ translation of Pellegrin’s L'Excellence menacée: Sur la philosophie politique d'Aristote (Paris: Classiques Garnier, 2017, reviewed by J.J. Mulhern for BMCR) is especially welcome because it brings together in one volume—ably rendered into English by Preus—analytical threads that Pellegrin has pursued in a number of independent essays on topics such as natural teleology and the Politics, slavery, the composition of the Politics, the nature of political friendship, and the structure and diversity of Aristotelian constitutions. (shrink)

In this 1974 book a practising scientist and gifted expositor sets forth an exciting point of view on the nature of science and how it works.

Certain organoid subtypes are particularly sensitive. We explore whether moral intuitions about the heartbeat warrant unique moral consideration for newly advanced contracting cardiac organoids. Despite the heartbeat’s moral significance in organ procurement and abortion discussions, we argue that this significance should not translate into moral implications for cardiac organoids.

Open peer commentary on the article “Exploring the Depth of Dream Experience: The Enactive Framework and Methods for Neurophenomenological Research” by Elizaveta Solomonova & Xin Wei Sha. Upshot: This commentary aims to sharpen the conceptual distinction between the breadth and the depth of dream experience. I discuss several possible readings and argue that the best one construes breadth and depth as distinct but complimentary research strategies distinguished not just by the kinds of evidence they rely on, but also by the (...) degree to which different types of data are integrated and focused on the same experiential episode. I identify promising candidates for depth approaches and challenges for future research. (shrink)

Decentralized clinical trials (DCTs) have the potential to advance the conduct of clinical trials, but raise several ethical issues, including obtaining valid informed consent. The debate on the ethical issues resulting from digitalization is predominantly focused on direct risks relating to for example data protection, safety, and data quality. We submit however, that a broader view on ethical aspects of DCTs is needed to touch upon the new challenges that come with the DCT practice. Digitalization has impacts that go beyond (...) its direct purposes, by shaping behaviors, experiences, social relations, and values. We examine four elements of the informed consent procedure that are affected by DCTs, while taking these soft impacts of technologies into account: (i) informing participants and testing understanding, (ii) freedoms in relation to responsibilities and burdens, (iii) trust in participant-researcher relations, and (iv) impacts on the concept of privacy. Our analysis reveals that a broad view is key for optimal conduct of DCTs. In addition, it provides insight into the ethical impacts of DCTs on informed consent. Technologies such as DCTs potentially have profound impacts which are not immediately addressed by the existing regulatory frameworks, but nonetheless important to recognize. These findings can guide future practices of DCTs to foster the important values of clinical research in this novel approach for conducting clinical trials. (shrink)

Sustained attention, a key cognitive skill that improves during childhood and adolescence, tends to be worse in some emotional and behavioural disorders. Sustained attention is typically studied in non-affective task contexts; here, we used a novel task to index performance in affective versus neutral contexts across adolescence (N = 465; ages 11–18). We asked whether: (i) performance would be worse in negative versus neutral task contexts; (ii) performance would improve with age; (iii) affective interference would be greater in younger adolescents; (...) (iv) adolescents at risk for depression and higher in anxiety would show overall worse performance; and (v) would show differential performance in negative contexts. Results indicated that participants performed more poorly in negative contexts and showed age-related performance improvements. Those at risk of depression performed more poorly than those at lower risk. However, there was no difference between groups as a result of affective context. For anxiety there was no difference in performance as a function of severity. However, those with higher anxiety showed less variance in their reaction times to negative stimuli than those with lower anxiety. One interpretation is that moderate levels of emotional arousal associated with anxiety make individuals less susceptible to the distracting effects of negative stimuli. (shrink)

Following the lead of Annette Baier, this essay argues that trust relations provide the ethical substance of everyday living. When A trusts B, A unreflectively allows B to approach sufficiently close so as to be able to harm A. In order for this to be possible, A practically presupposes that B perceives A as a person and will hence act accordingly. Trust relations are relations of mutual recognition in which we acknowledge our mutual standing and vulnerability with respect to one (...) another. A robust account of trust assumes: first, trust relations are primary and practical, and while monitored by reason, they are not rationally constituted; second, trust can sustain its practical primacy over moral reason because it is developmentally prior to reason; and third, trust relations can be the bearers of our worth and vulnerability because they are the developmental products of first love. (shrink)

The sudden emergence of the COVID-19 pandemic brought global disruption to every aspect of society including healthcare, supply chain, the economy, and social interaction. Among the many emergent considerations were the safety and public health of the public, patients, essential workers, and healthcare professionals. In certain locations, clinical research was halted—or terminated—in deference to the immediate needs of patient care, and clinical trials focusing on the treatment and prevention of coronavirus infection were prioritized over studies focusing on other diseases. Difficult (...) decisions were made rapidly; flexibility and reconsideration were necessary not only because the intensity and severity of infection varied over time and by locale but also because knowledge of the disease and understanding of its treatment grew. Here we discuss the ethical challenges in decision-making and competing ethical tensions during the pandemic in an effort to advance future preparedness. (shrink)

The innovative field of Regenerative Medicine (RM) is expected to extend the possibilities of prevention or early treatment in healthcare. Increasingly, clinical trials will be developed for people at risk of disease to investigate these RM interventions. These individuals at risk are characterised by their susceptibility for developing clinically manifest disease in future due to the existence of degenerative abnormalities. So far, there has been little debate about the ethical appropriateness of including such individuals at risk in clinical trials. We (...) discuss three main challenges of selecting this participant model for testing RM interventions: the challenge of achieving a proportional risk–benefit balance; complexities in the trial design in terms of follow-up and sample size; and the difficulty of obtaining informed consent due to the many uncertainties. We conclude that selecting the model is not ethically justifiable for first-in-man trials with RM interventions due to the high risks and uncertainties. However, the model can be ethically appropriate for testing the efficacy of RM interventions under the following conditions: interventions should be low risk; the degenerative abnormalities (and other risk factors) should be strongly related with disease within a short time frame; robust preclinical evidence of efficacy needs to be present; and the informed consent procedure should contain extra safeguards with regard to communication on uncertainties. (shrink)

Heuristics of evolutionary biology dictate that phylogenetically older processes are inherently more stable and resilient to disruption than younger processes. On the grounds that non-declarative behaviour emerged long before declarative behaviour, Reber argues that implicit learning is supported by neural processes that are evolutionarily older than those supporting explicit learning. Reber suggested that implicit learning thus leads to performance that is more robust than explicit learning. Applying this evolutionary framework to motor performance, we examined whether implicit motor learning, relative to (...) explicit motor learning, conferred motor output that was resilient to physiological fatigue and durable over time. In Part One of the study a fatigued state was induced by a double Wingate Anaerobic test protocol. Fatigue had no affect on performance of participants in the implicit condition; whereas, performance of participants in the explicit condition deteriorated significantly. In Part Two of the study a convenience sample of participants was recalled following a one-year hiatus. In both the implicit and the explicit condition retention of performance was seen and, contrary to the findings in Part One, so was resilience to fatigue. The resilient performance in the explicit condition after one year may have resulted from forgetting or from consolidation of declarative knowledge as implicit memories. In either case, implicit processes were left to more effectively support motor performance. (shrink)

Task unrelated thought (TUT) refers to thought directed away from the current situation, for example a daydream. Three experiments were conducted on healthy participants, with two broad aims. First, to contrast distributed and encapsulated views of cognition by comparing the encoding of categorical and random lists of words (Experiments One and Two). Second, to examine the consequences of experiencing TUT during study on the subsequent retrieval of information (Experiments One, Two, and Three). Experiments One and Two demonstrated lower levels of (...) TUT and higher levels of word-fragment completion whilst encoding categorical relative to random stimuli, supporting the role of a distributed resource in the maintenance of TUT. In addition the results of all three experiments suggested that experiencing TUT during study had a measurable effect on subsequent retrieval. TUT was associated with increased frequency of false alarms at retrieval (Experiment One). In the subsequent experiments TUT was associated with no advantage to retrieval based on recollection, by manipulating instructions at encoding (Experiment Two), and/or at retrieval (Experiment Three). The implications of the results of all three experiments are discussed in terms of recent accounts of memory retrieval and conscious awareness. (shrink)

The nonmetaphysical interpretation of Hegel's philosophy asserts that the metaphysical reading is not credible and so his philosophy must be rationally reconstructed so as to elide its metaphysical aspects. This article shows that the thesis of the extended mind approaches the metaphysical reading, thereby undermining denials of its credibility and providing the resources to articulate and defend the metaphysical reading of Hegel's philosophy. This fully rehabilitates the metaphysical Hegel. The article does not argue for the truth of the metaphysical Hegel's (...) claims. Rather, it defends the correctness of reading his philosophy as metaphysical. (shrink)

The aim of the present paper is to present a logical analysis of the concept of the free society. The symbolism used will be that of the Principia Mathematica—a few extra-logical symbols being explained when introduced. Regarding logical symbolism, it must be stressed, that the use of artificial symbols is not to be understood as a formalization. For formalization is a procedure by which one abstracts from the meaning of terms and operates on the shapes of the symbols alone—which will (...) not be done here. The symbolism is rather used as a useful shorthand, without which it would be difficult to obtain statements of the desired precision. (shrink)

Forcing with [κ] κ over a model of set theory with a strong partition cardinal, M. Spector produced a generic ultrafilter G on κ such that κ κ /G is not well-founded. Theorem. Let G be Spector-generic over a model M of $ZF + DC + \kappa \rightarrow (\kappa)^\kappa_\alpha, \kappa > \omega$ , for all $\alpha . 1) Every cardinal (well-ordered or not) of M is a cardinal of M[ G]. 2) If A ∈ M[ G] is a well-ordered subset (...) of M, then A ∈ M. Let Φ = κ κ /G. 3) There is an ultrafilter U on Φ such that every member of U has a subset of type Φ, and the intersection of any well-ordered subset of U is in U. 4) Φ satisfies Φ → (Φ) α β for all $\alpha and all ordinals β. 5) There is a linear order Φ' with property 3) above which is not "weakly compact", i.e., $\Phi' \nrightarrow (\Phi')^2$. (shrink)

In an important recent article T. C. W. Stinton reaffirmed the case that in Aristotle's Poetics, ch. 13, has a wide range of application. I do not wish to dispute the general conclusion of what seems to me a masterly analysis of the question but simply to discuss two areas where Stinton's argument may be thought defective–the interpretation of the examples given by Aristotle in Poetics 13, 5 3all and 53a2O–1 and the problem of the contradiction between 13, 53a13–15 and (...) 14, 54a4–9. (shrink)