DNA helicases are a class of molecular motors that catalyze processive unwinding of double stranded DNA. In spite of much study, we know relatively little about the mechanisms by which these enzymes carry out the function for which they are named. Most current views are based on inferences from crystal structures. A prominent view is that the canonical ATPase motor exerts a force on the ssDNA resulting in “pulling” the duplex across a “pin” or “wedge” in the enzyme leading to (...) a mechanical separation of the two DNA strands. In such models, DNA base pair separation is tightly coupled to ssDNA translocation of the motors. However, recent studies of the Escherichia coli RecBCD helicase suggest an alternative model in which DNA base pair melting and ssDNA translocation occur separately. In this view, the enzyme‐DNA binding free energy is used to melt multiple DNA base pairs in an ATP‐independent manner, followed by ATP‐dependent translocation of the canonical motors along the newly formed ssDNA tracks. Repetition of these two steps results in processive DNA unwinding. We summarize recent evidence suggesting this mechanism for RecBCD helicase action. (shrink)

Unregulated patient treatments and approved clinical trials have been conducted with haematopoietic stem cells and mesenchymal stem cells for children with autism spectrum disorder. While the former direct-to-consumer practice is usually considered rogue and should be legally constrained, regulated clinical trials could also be ethically questionable. Here, we outline principal objections against these trials as they are currently conducted. Notably, these often lack a clear rationale for how transplanted cells may confer a therapeutic benefit in ASD, and thus, have ill-defined (...) therapeutic outcomes. We posit that ambiguous and unsubstantiated descriptions of outcome from such clinical trials may nonetheless appeal to the lay public as being based on authentic scientific findings. These may further fuel caregivers of patients with ASD to pursue unregulated direct-to-consumer treatments, thus exposing them to unnecessary risks. There is, therefore, a moral obligation on the part of those regulating and conducting clinical trials of stem cell-based therapeutic for ASD minors to incorporate clear therapeutic targets, scientific rigour and reporting accuracy in their work. Any further stem cell-based trials for ASD unsupported by significant preclinical advances and particularly sound scientific hypothesis and aims would be ethically indefensible. (shrink)

Rule is commonly conceptualized with reference to the compliance it invokes. In this article, we propose a conception of rule via the practice of resistance instead. In contrast to liberal approaches, we stress the possibility of illegitimate rule, and, as opposed to critical approaches, the possibility of legitimate authority. In the international realm, forms of rule and the changes they undergo can thus be reconstructed in terms of the resistance they provoke. To this end, we distinguish between two types of (...) resistance—opposition and dissidence—in order to demonstrate how resistance and rule imply each other. We draw on two case studies of resistance in and to international institutions to illustrate the relationship between rule and resistance and close with a discussion of the normative implications of such a conceptualization. (shrink)

Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need (...) to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent. (shrink)

In July, the Department of Health and Human Services and the Office of Science and Technology Policy published an advance notice of proposed rulemaking proposing sweeping changes to the rules governing oversight of research on human subjects—changes aimed at “better protect[ing] human subjects who are involved in research, while facilitating valuable research and reducing burden, delay, and ambiguity for investigators.”1 The process is likely to amend not only the core regulation on human-subjects research , but also regulations governing vulnerable subjects, (...) IRB registration requirements, research regulations of the Food and Drug Administration, and the “privacy rule” of the .. (shrink)

Learning and Teaching in Early Childhood: Pedagogies of Inquiry and Relationships is an introduction for early childhood educators beginning their studies. Reflecting the fact that there is no single correct approach to the challenges of teaching, this book explores teaching through two lenses: teaching as inquiry and teaching as relating. The first part of the book focuses on inquiry, covering early childhood learning environments, learning theories, play pedagogies, approaches to teaching and learning, documentation and assessment, and the policy, curriculum and (...) regulatory requirements in Australia. The second part explores relationships in early childhood contexts and covers topics such as fostering meaningful and respectful relationships with children, and working with families, staff and the wider community. Written by well-respected academics in the field, Learning and Teaching in Early Childhood is a vital resource for those entering the early childhood education and care profession. (shrink)

Little consensus exists about the effectiveness of transnational private governance in domains such as labor, the environment, or human rights. The paper builds on recent scholarship on labor standards to emphasize the role of labor agency in transnational private governance. It argues that the relationship between transnational private regulatory initiatives and labor agency depends on three competences: first, the ability of workers’ organizations to gain access to processes of employment regulation, implementation, and monitoring; second, their ability to insist on the (...) inclusion of employers and state agencies within such processes; and third, the ability of workers to effectively exercise leverage in pursuit of particular goals. The paper develops a framework, called hybrid production regime, for examining how workers’ capacity to act at the local level depends on how these three collective competences are addressed in the institutionalization of capital–labor relations between the transnational and national levels. (shrink)

Previous research on scalar implicature has primarily relied on meta-linguistic judgment tasks and found varying rates of such inferences depending on the nature of the task and contextual manipulations. This paper introduces a novel interactive paradigm involving both a production and a comprehension side and a precise conversational goal. The main research question is what is reliably communicated by some in this communicative setting, both when the quantifier occurs in unembedded and embedded positions. Our new paradigm involves an action-based task (...) from which participants’ interpretation of utterances can be inferred. It incorporates a game-theoretic design, thereby including a precise model to predict participants’ behaviour in the experimental context. Our study shows that embedded and unembedded implicatures are reliably communicated by some. We propose two cognitive principles that describe what can be left unsaid. In our experimental context, a production strategy based on these principles is more efficient than a strategy based on literal descriptions. (shrink)

Depuis le début du XXI e siècle, la globalisation est devenue un thème central dans les sciences humaines, même si la mondialisation croissante des discours dans les sciences humaines apparaît en réalité dès le XX e siècle. Dans le domaine de la philosophie, la mondialisation du cadre thématique a été encouragée en particulier par les Congrès mondiaux de philosophie depuis 1900. Sous l’impulsion de ces évolutions, les histoires de différentes philosophies ont émergé à travers le monde et dans de nombreuses (...) langues différentes. En outre, des ouvrages d’histoires globales de la philosophie se multiplient depuis une vingtaine d’années. Pour faire face à cette diversité thématique dans la philosophie d’aujourd’hui, l’approche d’une phénoménologie transformative est abordée à la fin de l’article. (shrink)

This article is about the Indian Evidence Act. It also explains how evidence is the script that carries law’s unconscious. One one hand, evidence is the site of reason, on the other hand it is also the performative site of the unconscious. The operation of the Evidence Act requires a court, arguments, ways of producing evidence, counter-arguments, scrutiny of the nature of the evidence submitted, and finally the disputation around what constitutes an evidence, and then the judgement. The article argues (...) through a brief presentation of the history of the Act, how law in this way combines the normative and the performative – science of inquiry and the unpredictable script of outcome, procedure and the spectacle built around elements such as - live deposition and the hermeneutic power of the image, rational considerations and emotion, virtuality and the event, serious business in the court and the element of drama. The article suggests with a bit of irony the injunction that to see what law is and how it functions we can go to the cinema; to see what cinema is we can go to the court. (shrink)

The consequences of foreign direct investment (FDI) for human rights protection are poorly understood. We propose that the impact of FDI varies across industries. In particular, extractive firms in the oil and mining industries go where the resources are located and are bound to such investment, which creates a status quo bias among them when it comes to supporting repressive rulers (“location-bound effect”). The same is not true for nonextractive multinational corporations (MNCs) in manufacturing or services, which can, in comparison, (...) exit problematic countries more easily. We also propose that strong democratic institutions can alleviate negative impacts of extractive FDI on human rights (“democratic safeguard effect”). Using U.S. FDI broken up into extractive and nonextractive industries in 157 host countries (1999–2015), we find support for these propositions.1 Extractive FDI is associated with more human rights abuse, but nonextractive FDI is associated with less abuse, after controlling for other factors, including concerns about endogeneity. We find also that the negative human rights impact of extractive FDI vanishes in countries where democratic institutions are stronger. Our results are robust to a range of alternative estimation techniques. (shrink)

Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need (...) to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent. (shrink)

This paper explores the possibility that Zhuangzi can be fruitfully interpreted as a fictionalist. It proceeds in four parts. Part one discusses two distinct and very general types of fictionalism—force and content—that might prove useful for an interpreter of the Zhuangzi. The former type of view would have it that the expressions in question—that is, the expressions that Zhuangzi is held to advocate using and interpreting non-literally—are not best seen as used in a way that aims at, e.g., truth, whereas (...) the latter type of view would have it that the expressions in question are best seen as used in a way that aims at truth, if in a non-literal fashion. Part two surveys evidence in favor of the claim that Zhuangzi can be interpreted in terms of one or the other of these two types of fictionalism and argues that he is better characterized as endorsing a version of the former. Part three explains how interpreting Zhuangzi as a fictionalist can help to resolve notable tensions in the text and briefly explores a few additional merits of this reading of the Zhuangzi: namely, that it can give us a clearer idea of what Zhuangzi’s positive project is, unify seemingly disparate scholarly interpretations of it, and reconcile objectivist and non-objectivist strands in his work. Finally, part four concludes by gesturing toward how the interpretation proposed here might bring the Zhuangzi into productive dialogue with two longstanding philosophical questions: specifically, the question of how we should respond to skeptical arguments, and the question of how aesthetic features of works of art—and in particular, literature—might be related to their cognitive or epistemic value. (shrink)

The shortages of baby formula in the US resulting from the voluntary recall of contaminated products and shutdown of manufacturing facility in February led to increases in the national out-of-stock rate of the baby formula from 18 to 70% over the summer of 2022. This study utilizes social media listening and data analysis to examine how online media reactions to the physical shortage changed over time and how the reaction to the shortage differed from to the initial recall announcements. Improved (...) understanding of reactions to emergent issues in foods through this lens may improve communication efficiency to mitigate potential consequences. (shrink)

L’utopie est nominalement un nulle part qui est aussi, comme nous le dit Thomas More, un “bon” endroit. Bien qu’il existe des notions concurrentes, la description grecque occupe une place importante dans la plupart des récits d’utopie. Les détails de cet idéal sont si précis que la littérature utopique consiste en un catalogue (et une critique) de ces caractéristiques. Cet essai attire l’attention sur le parfum attribué aux « Îles des bienheureux » de Lucien, ainsi que sur la description qu’en (...) fait Nietzsche, sur sa sensibilité à l’odorat et sur l’attention portée par Illich à l’« atmosphère » et au nez. On aborde également le scepticisme envers l’utopie et des parallèles sont établis, d’une part, avec les critiques pragmatiques de l’utopie comme étant intrinsèquement totalitaires, d’autre part, avec la « bonne vie » dans la théorie politique et le défaut programmatique de la fantaisie techno-utopique. L’article se termine par une discussion d’Illich sur la pax – c’est-à-dire la respiration. (shrink)

Editors' introduction to Puncta's February 2022 Special Issue, "Pandemic Politics and Phenomenology.".

Publication pressure has been touted to promote questionable research practices (QRP) and scientific or research misconduct (RM). However, logically attractively as it is, there is no unequivocal evidence for this notion, and empirical studies have produced conflicting results. Other than difficulties in obtaining unbiased empirical data, a direct causal relationship between perceived publication pressure (PPP) and QRP/RM is inherently difficult to establish, because the former is a complex biopsychosocial construct that is variedly influenced by multiple personal and environmental factors. To (...) effectively address QRP/RM by tackling the sources of PPP would also be difficult because of the competitive nature of the reward and merit system of contemporary science. We might do better with efforts in enhancing knowledge in research ethics and integrity among the practitioners, as well as institutional infrastructures and mechanisms to fairly and efficiently adjudicate cases of QRP/RM. (shrink)

In this paper, we discuss how phenomenology might cogently express the way painful experiences are layered with complex intersubjective meaning. In particular, we propose a critical conception of pain as an intricate multi-levelled phenomenon, deeply ingrained in the constitution of one’s sense of bodily self and emerging from a web of intercorporeal, social, cultural, and political relations. In the first section, we review and critique some conceptual accounts of pain. Then, we explore how pain is involved in complex ways with (...) modalities of pleasure and displeasure, enacted personal meaning, and contexts of empathy or shame. We aim to show why a phenomenology of pain must acknowledge the richness and diversity of peculiar painful experiences. The second section then weaves these critical insights into Husserlian phenomenology of embodiment, sensation, and localisation. We introduce the distinction between Body-Object and Lived-Body to show how pain presents intersubjectively. Furthermore, we stress that, while pain seems to take a marginal position in Husserl’s whole corpus, its role is central in the transcendental constitution of the Lived-Body, interacting with the personal, interpersonal, and intersubjective levels of experiential constitution. Taking a critical-phenomenological perspective, we then concretely explore how some people may experience structural conditions which may make their experiences more or less painful. (shrink)

This exploratory study investigates the divergent ways that people make sense of their own charisma. Through in-depth, semi-structured qualitative interviews with people who self-identified as charismatic (_n_ = 11), findings reveal that self-identified charismatic people hold divergent views regarding (1) who they believe benefits from their charisma (self or others), (2) how they believe they came to be charismatic (developed or innate), (3) how they experience self-confidence (self-conscious or self-assured), and (4) how they manage rejection (preparation or resilience). Taken together, (...) these divergent views reflect at least two charisma profiles—what we term _opportunistic charisma_ (i.e., charisma employed for personal gain) and _humanistic charisma_ (i.e., charisma employed to empower others)—with implications for humanistic management theory and practice. (shrink)

Der Band setzt sich mit den Bedingungen und Möglichkeiten internationalen oder globalen Regierens in einer sozialen Umwelt (Weltgesellschaft) unter drei Perspektiven auseinander: der Perspektive von Theorien globaler Ordnung, der Perspektive spezifischer Formen globaler Ordnungsbildung und der Perspektive die Normativität globaler Ordnung. Die Beiträge des Bandes besetzen Schnittstellen in einer Reihe von Diskussionen, die in den Internationalen Beziehungen zu Ordnung und Ordnungsbildung in der internationalen Politik, zum Regieren jenseits des Nationalstaates, sowie zur Stellung internationaler Politik in der Weltgesellschaft geführt werden.

For certain classes of Dedekind domains S we want to characterize S-modules U such that Ext=0 for some module SMQ. We shall call these modules M-Whitehead modules. On the one hand we will show that assuming all M-Whitehead modules U are S0-free, i.e. US0 is a free S0-module where S0 is the nucleus of M. On the other hand if there is a ladder system on a stationary subset of ω1 that satisfies 2-uniformization, then there exists a non-S0-free M-Whitehead module. (...) Conversely, we will show that in the special case of Abelian groups the existence of a non-S0-free R-Whitehead group–here R is a rational group–implies that there is a ladder system on a stationary subset of ω1 that satisfies 2-uniformization. (shrink)

Mathematics word problems provide students with an opportunity to apply what they are learning in their mathematics classes to the world around them. However, students often neglect their knowledge of the world and provide nonsensical responses (e.g., they may answer that a school needs 12.5 buses for a field trip). This study examined if the question design of word problems affects students' mindset in ways that affect subsequent sense‐making. The hypothesis was that rewriting standard word problems to introduce inherent uncertainty (...) about the result would be beneficial to student performance and sense‐making because it requires students to reason explicitly about the context described in the problem. Middle school students (N = 229) were randomly assigned to one of three conditions. In the standard textbook condition, students solved a set of six word problems taken from current textbooks. In the modified yes/no condition, students solved the same six problems rewritten so the solution helped answer a “yes” or “no” question. In the disfluency control condition, students solved the standard problems each rewritten in a variety of fonts to make them look unusual. After solving the six problems in their assigned condition, all students solved the same three “problematic” problems designed to assess sense‐making. Contrary to predictions, results showed that students in the modified yes/no condition solved the fewest problems correctly in their assigned condition problem set. However, consistent with predictions, they subsequently demonstrated more sense‐making on the three problematic problems. Results suggest that standard textbook word problems may be able to be rewritten in ways that mitigate a “senseless” mindset. (shrink)

Medicine and its allied health sciences have for too long been peripherally involved in work on human rights. Fifty years ago, the door to greater involvement was opened by Article 25 of the Universal Declaration of Human Rights, which underlined social and economic rights: “Everyone has the right to a standard of living adequate for the health and well-being of himself and his family, including food, clothing, housing, and medical care and necessary social services, and the right to security in (...) the event of unemployment, sickness, disability, widowhood, old age or other lack of livelihood in circumstances beyond his control.”. (shrink)

Graphic and gut-wrenching images of death, violence, and pain fill our news media, despite debate about their effect on audiences and their potential to harm their subjects. This research uses in-d...

Prospective Memory, the ability to remember to realize intended actions in the future, is crucial for maintaining autonomy. Decades of research has focused on a so-called age PM paradox, where older adults outperformed younger adults on some PM tasks, but not others. Contributing to this paradox is heterogeneity in and a lack of valid assessment methods. Previous research showed a lack of convergent validity between performance-based PM and both self-report and informant-report measures. We argue that questionnaires may be relevant to (...) obtain information regarding patients’ awareness of their PM difficulties but need to be used in conjunction with performance-based tools. Within performance-based PM tools there are also difficulties in measurement: 15–60 min experimental tasks and batteries have a good reliability but cannot usually fit in a standard clinical evaluation, while shorter PM measures have lower reliability and sensitivity. In this perspective paper, we encourage researchers to develop more ecologically valid tools. Innovative PM paradigms that allow participants to generate their own intentions and that take task costs into consideration should be developed. Future research will also need to focus on cognitive factors, personality and online evaluation, to improve PM assessment and develop ad-hoc rehabilitation programs. (shrink)

Birks and Buyx (2018) argue that punishment of criminal offenders using mandatory neurointerventions constitutes a morally objectionable intervention in the mental state of an offender. Birks and B...

ZUSAMMENFASSUNGIn diesem Aufsatz wird versucht, exegetische Einsichten über die johanneische Konzeption von δóξα and δoξάζειν mit dogmatischen und ästhetischen Bezügen zu »Herrlichkeit« und »Verherrlichung« in Verbindung zu setzen. Zwei Aspekte des Gebrauchs von δóξα and δoξάζειν im vierten Evangelium werden vorgestellt: erstens die Unterscheidung zwischen δóξα πατϱóς und δóξα πατϱί , die eine Veränderung in Jesu Beziehung zu der einen Herrlichkeit Gottes bezeichnet; zweitens der Aufbau eines christologischen Deutungszusammenhangs im Evangelium, in welchem die δóξα-Begrifflichkeit dazu dient, den Tod Jesu in (...) den theologischen Rahmen des Evangeliums zu integrieren.Vor diesem Hintergrund werden die »Herrlichkeits-bezogenen« Werke von Reinhard Hoeps, Das Gefühl des Erhabenen und die Herrlichkeit Gottes. Studien zur Beziehung von philosophischer und theologischer Ästhetik, 1989, und von Wolf Krötke, Gottes Klarheiten. Eine Neuinterpretation der Lehre von Gottes ›Eigenschaften‹, 2001, analysiert. Insbesondere Krötkes Werk scheint bemerkenswerte Übereinstimmungen mit der johanneischen δóξα-Theologie aufzuweisen.In einem abschließenden Ausblick werden weitere Möglichkeiten der Rezeption der johanneischen δóξα-Konzeption in der Dogmatik angedeutet, nämlich die Impulse für eine konkretere Bestimmung des Verhältnisses zwischen Gott und seinem Sohn und Gesandten, für die Spezifizierung des Selbstverständnisses der glaubenden Gemeinde und ihrer Verantwortung für die Welt und für eine Deutung des Todes Jesu, die die sühnetheologische Deutung ergänzt, überragt und überschreitet.SUMMARYThis paper seeks to relate exegetical insights concerning the Johannine concept of δóξα and δoξάζειν to dogmatic and aesthetic references to “glory” and “glorification”. Two features of the Fourth Gospel's use of δóξα and δoξάζειν are introduced: First, the distinction of a δóξα πατϱóς and a δóξα πατϱί , signifying a change in Jesus' relation to the one glory of God; second, the establishment of a Christological network throughout the Gospel, in which δóξα terminology serves to integrate Jesus' death into the theological framework of the Gospel. With this in mind, the “glory-centered” works of Reinhard Hoeps, Das Gefühl des Erhabenen und die Herrlichkeit Gottes. Studien zur Beziehung von philosophischer und theologischer Ästhetik, 1989, and, most extensively, Wolf Krötke, Gottes Klarheiten. Eine Neuinterpretation der Lehre von Gottes ‘Eigenschaften’, 2001, are analyzed; especially Krötke's work seems to yield remarkable consonances with Johannine δóξα theology. In a concluding outlook, some further ways for a dogmatic evaluation of the Johannine δóξα concept are suggested, namely its potential for a specification of the relationship between God and his Son and Sent One; for a specification of the self-understanding of the believing community and their responsibility for the world; and for an understanding of Jesus' death that supplements, surmounts and transcends the traditional soteriology of atonement. (shrink)

The “prescription” of humans' social learning bifocals is fine-tuned by cultural norms and, as a result, the readiness with which the instrumental or conventional lenses are used to view behavior differs across cultures. We present evidence for this possibility from cross-cultural work examining children's imitation and innovation.

E.O. Wright, using the labourtransfer and game theory approach of J. Roemer, provides a general framework for a comparative analysis of the different class systems, the historical variations of which are founded on the peculiar nature of the "asset" the dominant class appropriates.