Vacuolar ATPases (V‐ATPases, V1Vo‐ATPases) are rotary motor proton pumps that acidify intracellular compartments, and, when localized to the plasma membrane, the extracellular space. V‐ATPase is regulated by a unique process referred to as reversible disassembly, wherein V1‐ATPase disengages from Vo proton channel in response to diverse environmental signals. Whereas the disassembly step of this process is ATP dependent, the (re)assembly step is not, but requires the action of a heterotrimeric chaperone referred to as the RAVE complex. Recently, an alternative pathway (...) of holoenzyme disassembly was discovered that involves binding of Oxidation Resistance 1 (Oxr1p), a poorly characterized protein implicated in oxidative stress response. Unlike conventional reversible disassembly, which depends on enzyme activity, Oxr1p induced dissociation can occur in absence of ATP. Yeast Oxr1p belongs to the family of TLDc domain containing proteins that are conserved from yeast to mammals, and have been implicated in V‐ATPase function in a variety of tissues. This brief perspective summarizes what we know about the molecular mechanisms governing both reversible (ATP dependent) and Oxr1p driven (ATP independent) V‐ATPase dissociation into autoinhibited V1 and Vo subcomplexes. (shrink)

In order to maximize human performance, defence forces continue to explore, develop, and apply human performance enhancement (HPE) methods, ranging from pharmaceuticals to (bio)technological enhancement. This raises ethical, legal, and societal concerns and requires organizing a careful reflection and deliberation process, with relevant stakeholders. We discuss a range of ethical, legal, and societal aspects (ELSA), which people involved in the development and deployment of HPE can use for such reflection and deliberation. A realistic military scenario with proposed HPE application can (...) serve as a starting point for such an iterative and participatory process. Stakeholders can discuss this application, modify its features, and design appropriate processes around it – for instance, procedures for informed consent. We propose that organizing aspects into these three categories – ethical, legal, and societal – can help involve appropriate interlocutors at different moments: legal aspects with people in strategy or management roles, from the start of a project; ethical aspects with people in operations and medical roles, during development; and societal aspects with people in communication and personnel roles, during deployment. Notably, we developed and discussed this framework and the three aspects in close collaboration with personnel from the military. (shrink)

Abstract:Extrapolating from Carroll’s four domains of corporate social responsibility (1979) and Pyramid of CSR (1991), an alternative approach to conceptualizing corporate social responsibility (CSR) is proposed. A three-domain approach is presented in which the three core domains of economic, legal, and ethical responsibilities are depicted in a Venn model framework. The Venn framework yields seven CSR categories resulting from the overlap of the three core domains. Corporate examples are suggested and classified according to the new model, followed by a (...) discussion of limitations and teaching and research implications. (shrink)

Research on interdisciplinary science has for the most part concentrated on the institutional obstacles that discourage or hamper interdisciplinary work, with the expectation that interdisciplinary interaction can be improved through institutional reform strategies such as through reform of peer review systems. However institutional obstacles are not the only ones that confront interdisciplinary work. The design of policy strategies would benefit from more detailed investigation into the particular cognitive constraints, including the methodological and conceptual barriers, which also confront attempts to work (...) across disciplinary boundaries. Lessons from cognitive science and anthropological studies of labs in sociology of science suggest that scientific practices may be very domain specific, where domain specificity is an essential aspect of science that enables researchers to solve complex problems in a cognitively manageable way. The limit or extent of domain specificity in scientific practice, and how it constrains interdisciplinary research, is not yet fully understood, which attests to an important role for philosophers of science in the study of interdisciplinary science. This paper draws upon two cases of interdisciplinary collaboration; those between ecologists and economists, and those between molecular biologists and systems biologists, to illustrate some of the cognitive barriers which have contributed to failures and difficulties of interactions between these fields. Each exemplify some aspect of domain specificity in scientific practice and show how such specificity may constrain interdisciplinary work. (shrink)

The paper discusses Linda Zagzebski's account of epistemic authority. Building on Joseph Raz's account of political authority, Zagzebski argues that the basic contours of epistemic authority match those Raz ascribes to political authority. This, it is argued, is a mistake. Zagzebski is correct in identifying the pre-emptive nature of reasons provided by an authority as central to our understanding of epistemic authority. However, Zagzebski ignores important differences between practical and epistemic authority. As a result, her attempt to explain the rationality (...) of belief on authority by applying an analogue of Raz's Normal Justification Thesis to the domain of belief fails. A successful explanation of the rationality of belief on authority will need to be attuned to the differences between political and epistemic authorities. (shrink)

The paper interrogates the status, nature and significance of epistemological relativism as a key element of constructionism and critical realism. It finds that epistemological relativism is espoused by authorities in critical realism and marginalized or displaced in the field of management and organization studies, resulting in forms of analysis that are empirically, but not fully critically, realist. This evaluation prompts reflection on the question of whether, how and with what implications epistemological relativism might be recast at the heart of critical (...) realist studies of management and organization. (shrink)

People attribute purposes in both mundane and profound ways—such as when thinking about the purpose of a knife and the purpose of a life. In three studies (total N = 13,720 observations from N = 3,430 participants), we tested whether these seemingly very different forms of purpose attributions might actually involve the same cognitive processes. We examined the impacts of four factors on purpose attributions in six domains (artifacts, social institutions, animals, body parts, sacred objects, and human lives). Study 1 (...) manipulated what items in each domain were originally created for (original design) and how people currently use them (present practice). Study 2 manipulated whether items are good at achieving a goal (effectiveness) and whether the goal itself is good (morality). We found effects of each factor in every domain. However, whereas morality and effectiveness had remarkably similar effects across domains, the effects of original design and present practice differed substantially. Finally, Study 3 revealed that, within domains, the effects of original design and present practice depend on which entities design and use items. These results reveal striking similarities in purpose attributions across domains and suggest that certain entities are treated as authorities over the purposes of particular items. (shrink)

Carrie Figdor presents a critical assessment of how psychological terms are used to describe the non-human biological world. She argues against the anthropocentric attitude which takes human cognition as the standard against which non-human capacities are measured, and offers an alternative basis for naturalistic explanation of the mind.

Current approaches to formal representation in biomedicine are characterized by their focus on either the static or the dynamic aspects of biological reality. We here outline a theory that combines both perspectives and at the same time tackles the by no means trivial issue of their coherent integration. Our position is that a good ontology must be capable of accounting for reality both synchronically (as it exists at a time) and diachronically (as it unfolds through time), but that these are (...) two quite different tasks, whose simultaneous realization is by no means trivial. The paper is structured as follows. We begin by laying out the methodological and philosophical background of our approach. We then summarize the structure and elements of the Basic Formal Ontology on which it rests, in particular the SNAP ontology of objects and the SPAN ontology of processes. Finally, we apply the general framework to the specific domain of biomedicine. (shrink)

The paper addresses the referring problem in quantum mechanics, by spelling out the alternatives with complete or individual concepts, with directly referential labels, and with intuition. The connection between the way of referring and some metaphysical theses about objects will be explained. Then, the paper intends to make plausible that the Kantian way is the best way for the quantum domain, including quantum field theories.

Berger, U., Total sets and objects in domain theory, Annals of Pure and Applied Logic 60 91-117. Total sets and objects generalizing total functions are introduced into the theory of effective domains of Scott and Ersov. Using these notions Kreisel's Density Theorem and the Theorem of Kreisel-Lacombe-Shoenfield are generalized. As an immediate consequence we obtain the well-known continuity of computable functions on the constructive reals as well as a domain-theoretic characterization of the Heriditarily Effective Operations.

This paper elaborates distinctions between a core and a periphery in the ontological and the conceptual domain associated with natural language. The ontological core-periphery distinction is essential for natural language ontology and is the basis for the central thesis of my 2013 book Abstract Objects and the Semantics of Natural Language, namely that natural language permits reference to abstract objects in its periphery, but not its core.

Artificial intelligence (AI) has become nearly ubiquitous in modern society, from components of mobile applications to medical support systems, and everything in between. In societally impactful systems imbued with AI, there has been increasing concern related to opaque AI, that is, artificial intelligence where it is unclear how or why certain decisions are reached. This has led to a recent boom in research on “explainable AI” (XAI), or approaches to making AI more explainable and understandable to human users. In the (...) military domain, numerous bodies have argued that autonomous and AI-enabled weapon systems ought not incorporate unexplainable AI, with the International Committee of the Red Cross and the United States Department of Defense both explicitly including explainability as a relevant factor in the development and use of such systems. In this article, I present a cautiously critical assessment of this view, arguing that explainability will be irrelevant for many current and near-future autonomous systems in the military (which do not incorporate any AI), that it will be trivially incorporated into most military systems which do possess AI (as these generally possess simpler AI systems), and that for those systems with genuinely opaque AI, explainability will prove to be of more limited value than one might imagine. In particular, I argue that explainability, while indeed a virtue in design, is a virtue aimed primarily at designers and troubleshooters of AI-enabled systems, but is far less relevant for users and handlers actually deploying these systems. I further argue that human–machine teaming is a far more important element of responsibly using AI for military purposes, adding that explainability may undermine efforts to improve human–machine teamings by creating aprima faciesense that the AI, due to its explainability, may be utilized with little (or less) potential for mistakes. I conclude by clarifying that the arguments are not against XAI in the military, but are instead intended as a caution against over-inflating the value of XAI in this domain, or ignoring the limitations and potential pitfalls of this approach. (shrink)

In this article, I explain why stabilizing constructs is important to the success of the Research Domain Criteria Project and identify one measure for facilitating such stability.

In this issue of The Journal of Medical Ethics, xxx and colleagues report a randomized trial of the influence of default options on delivery room management of an extremely premature infant. They report that among respondents to the hypothetical vignette, those who received the resuscitation default were significantly more likely to choose resuscitation compared with those who were told that the default was comfort care. While the results warrant attention and further investigation, several methodological shortcomings limit the conclusions that can (...) be drawn from this study. (shrink)

What does it mean to call the so-called second Arab awakening a liberal revolution? In this article, the author tries to answer that question by first framing it in the larger historical context by reference to the origins of the liberal narrative. Second, he attempts to probe the question of why and how the recent events of the Middle East can be put in the context of that narrative. Finally, he turns to evolutionary theory to see what kind of paradigm (...) can be prescriptive for the second Arab awakening. (shrink)

ABSTRACTThe recent rise in popularity of nurture groups in British schools appears to be aligned with a broader shift towards therapeutic education. With initial origins in attachment theory, nurtu...

We propose a typology of representational artifacts for health care and life sciences domains and associate this typology with different kinds of formal ontology and logic, drawing conclusions as to the strengths and limitations for ontology in a description logics framework. The four types of domain representation we consider are: (i) lexico-semantic representation, (ii) representation of types of entities, (iii) representations of background knowledge, and (iv) representation of individuals. We advocate a clear distinction of the four kinds of representation (...) in order to provide a more rational basis for using ontologies and related artifacts to advance integration of data and enhance interoperability of associated reasoning systems. We highlight the fact that only a minor portion of scientifically relevant facts in a domain such as biomedicine can be adequately represented by formal ontologies as long as the latter are conceived as representations of entity types. In particular, the attempt to encode default or probabilistic knowledge using ontologies so conceived is prone to produce unintended, erroneous models. (shrink)

In this paper we report on an investigation into the principles underlying the choice of a particular referential expression to refer to an object located in a domain to which both participants in the dialogue have visual as well as physical access. Our approach is based on the assumption that participants try to use as little effort as possible when referring to objects. This assumption is operational-ized in two factors, namely the focus of attention and a particular choice of (...) features to be included in a referential expression. We claim that both factors help in reducing the effort needed to, on the one hand, refer to an object and, on the other hand, to identify it. As a result of the focus of attention the number of potential target objects is reduced. The choice of a specific type of feature determines the number of objects that have to be identified in order to be able to understand the referential expression. An empirical study was conducted in which pairs of participants cooperatively carried out a simple block-building task, and the results provided empirical evidence that supported the aforementioned claims. Especially the focus of attention turned out to play an important role in reducing the total effort. Additionally, focus acted as a strong coherence-establishing device in the studied domain. (shrink)

The main thrust of the present work is to show why truth and truth bearers lie essentially beyond the descriptive reach of semantics, and to outline a theory of ...

The thesis of multiple realisation that Borsboom et al. are relying on should not be taken for granted. In dissolving the apparent multiple realisation, the reductionist research strategies in psychopathology research (the Research Domain Criteria [RDoC] framework, in particular) are bound to lead to eliminativism rather than reductionism. Therefore, Borsboom et al. seem to be aiming at a wrong target.

In this article, we argue for the distinction of three different types of predicates: existence entailing, (existence) neutral, and nonexistence entailing predicates. We provide linguistic tests as well as examples to motivate this distinction. After motivating our views on predicates, we show how our theory is able to deal with a multitude of problematic data both known from the literature as well as new. Then, we develop a multi-domain predicate logic inspired by certain versions of free logics in order (...) to represent these entailments in a formal way. (shrink)

The contemporary Platonists in the philosophy of mathematics argue that mathematical objects exist. One of the arguments by which they support this standpoint is the so-called Enhanced Indispensability Argument (EIA). This paper aims at pointing out the difficulties inherent to the EIA. The first is contained in the vague formulation of the Argument, which is the reason why not even an approximate scope of the set objects whose existence is stated by the Argument can be established. The second problem is (...) reflected in the vagueness of the very term indispensability, which is essential to the Argument. The paper will remind of a recent definition of the concept of indispensability of a mathematical object, reveal its deficiency and propose an improvement of this definition. Following this, we will deal with one of the consequences of the arbitrary employment of the concept of indispensability of a mathematical theory. We will propose a definition of this concept as well, in accordance with the common intuition about it. Eventually, on the basis of these two definitions, the paper will describe the relation between these two concepts, in the attempt to clarify the conceptual apparatus of the EIA. (shrink)

This paper informally summarizes a two-day symposium held at the U.S. National Academy of Sciences in Washington, D.C., September 5–6, 2002. The issue was to what extent the progress of science and societal capacity for continued technological innovation are threatened by excessive protection of intellectual property. Excessive protection creates disadvantages not only for scientists and inventors but also for educators/students and for librarians/clientele. Speakers from a variety of disciplines and institutions agreed unanimously that scientific and technological progress is, indeed, under (...) serious threat. Various opinions were expressed about the degree of threat, currently and prospectively, as well as what counter-measures are best suited to resist undue restrictions on creative uses of scientific and technical data and information. This summary is based entirely on the author’s notes from the symposium, and the commentary offered is his alone. My apologies to the speakers if this paper does not accurately reflect the primary intent of their presentations. The “Suggested Readings” offered at the end are not specific to the speakers’ statements but rather are offered as a general resource to aid further research. The definitive record of the symposium is planned to be available from the National Academies Press as a Proceedings publication in the summer of 2003. (shrink)