Maintenance of skeletal muscle mass and strength throughout life is crucial for heathy living and longevity. Several signaling pathways have been implicated in the regulation of skeletal muscle mass in adults. TGF‐β‐activated kinase 1 (TAK1) is a key protein, which coordinates the activation of multiple signaling pathways. Recently, it was discovered that TAK1 is essential for the maintenance of skeletal muscle mass and myofiber hypertrophy following mechanical overload. Forced activation of TAK1 in skeletal muscle causes hypertrophy and attenuates denervation‐induced muscle (...) atrophy. TAK1‐mediated signaling in skeletal muscle promotes protein synthesis, redox homeostasis, mitochondrial health, and integrity of neuromuscular junctions. In this article, we have reviewed the role and potential mechanisms through which TAK1 regulates skeletal muscle mass and growth. We have also proposed future areas of research that could be instrumental in exploring TAK1 as therapeutic target for improving muscle mass in various catabolic conditions and diseases. (shrink)

Though dividing one’s attention between two input streams typically impairs performance, detecting a behaviorally relevant stimulus can sometimes enhance the encoding of unrelated information presented at the same time. Previous research has shown that selection of this kind boosts visual cortical activity and memory for concurrent items. An important unanswered question is whether such effects are reflected in processing quality and functional connectivity in visual regions and in the hippocampus. In this fMRI study, participants were asked to memorize a stream (...) of naturalistic images and press a button only when they heard a predefined target tone. Images could be presented with a target tone, with a distractor tone, or without a tone. Auditory target detection increased activity throughout the ventral visual cortex but lowered it in the hippocampus. Enhancements in functional connectivity between the ventral visual cortex and the hippocampus were also observed following auditory targets. Multi-voxel pattern classification of image category was more accurate on target tone trials than on distractor and no tone trials in the fusiform gyrus and parahippocampal gyrus. This effect was stronger in visual cortical clusters whose activity was more correlated with the hippocampus on target tone than on distractor tone trials. In agreement with accounts suggesting that subcortical noradrenergic influences play a role in the attentional boost effect, auditory target detection also caused an increase in locus coeruleus activity and phasic pupil responses. These findings outline a network of cortical and subcortical regions that are involved in the selection and processing of information presented at behaviorally relevant moments. (shrink)

In “The Runabout Inference Ticket” AN Prior (1960) examines the idea that logical connectives can be given a meaning solely in virtue of the stipulation of a set of rules governing them, and thus that logical truth/consequence.

Dooyeweerd’s account of abstraction is examined and found to be faulty. He holds that abstract thinking isolates aspects which must then be synthesized, whereas I argue that we cannot isolate any aspect from the others however so hard we try. But our very inability to isolate aspects is then turned into an alternative version of a transcendental critique of theory making. Instead of asking for a basis for synthesizing aspects we have isolated, the new version asks: what is the nature (...) of the aspectual connectedness which is so strong that it cannot be interrupted even by abstraction? I argue that it is impossible for anyone to understand the meaning of a concept fully without taking a position on this issue, whether that is done implicitly or explicitly. Moreover, every answer to this question presupposes a divinity belief. Hence, this recasting of the critique yields a demonstration of the religious regulation of all concepts and every theory. In this way the goal of Dooyeweerd’s critique is achieved, even if not in the way he envisioned. (shrink)

The problem of determinism arises in all the major areas of philosophy. The first part of this book, first published in 1991, is a critical and historical exposition of the problem and the most important ideas and arguments which have arisen over the many years of debate. The second part considers the various forms of determinism and the implications that they engender.

Timothy Williamson’s Modal Logic as Metaphysics is a book-length defense of necessitism about objects—roughly put, the view that, necessarily, any object that exists, exists necessarily. In more formal terms, Williamson argues for the validity of necessitism for objects (NO: ◻︎∀x◻︎∃y(x=y)). NO entails both the (first-order) Barcan formula (BF: ◇∃xΦ → ∃x◇Φ, for any formula Φ) and the (first-order) converse Barcan formula (CBF: ∃x◇Φ → ◇∃xΦ, for any formula Φ). The purpose of this essay is not to assess Williamson’s arguments either (...) for necessitism (although discussion of these arguments will play a central role in the dialectic) or for necessitism’s two famous corollaries. Instead, the focus shall be a general principle governing abstract objects—the abstract of principle (or AOP) —instances of which seems to be at work in some of Williamson’s central arguments for necessitism. The AOP can be straightforwardly formulated and applied within the neo-logicist framework—in fact, arguably the principle is most naturally formulated in neo-logicist terms. -/- After closely examining, and carefully formalizing, the AOP, the remainder of the paper focuses on arguments for necessitism-like claims (the exact meaning of “necessitism-like” will become clearer as the essay progresses) based on the AOP. In particular, we shall focus on the instance of the AOP that applies to the abstract objects governed by the most well-known and most fully studied abstraction principle: Hume’s Principle (HP). It turns out that, although we cannot reconstruct a valid argument for necessitism based on this numerical instance of the AOP, we can obtain valid arguments for weaker, but equally interesting conclusions. In particular, we shall show that, although HP combined with the AOP (and some additional, related assumptions) allows the contents of the domains of possible worlds to vary, the size of those domains must remain constant. The paper concludes by developing and critiquing some related arguments for necessitism based on applying relevant instances of the AOP to abstraction principles governing sets (or extensions), and to a simple objectual abstraction principle. (shrink)

The eighteenth century saw the publication of many scientific and technical dictionaries, particularly in France, one of the most important being P. J. Macquer's Dictionnaire de chymie. Both the original text of 1766 and the revised and enlarged version of 1778 were translated into several languages, sometimes with authoritative notes and additions by the translators. No mere list of definitions, Macquer's work contained long articles that made it a comprehensive treatise on chemistry, and it set the pattern for many subsequent (...) chemical dictionaries. We have endeavoured to give an account of the circumstances in which the various editions, reprints and translations were published, and we add detailed bibliographical descriptions of them. Bibliographical purists consider that all the copies of a book printed from the same setting of type constitute an ‘edition’, and that there is a new edition when all or most of the type has been reset. However, Macquer described his revised and expanded text of 1778 as the ‘second edition’ and this designation has been adopted by subsequent writers, even though the original text was reprinted several times from different settings of type before 1778. In order to avoid confusion we therefore refer to all versions of the 1766 and 1778 editions as ‘issues’, ‘printings’ or ‘reprints’ of the first and second edition respectively. (shrink)

The current spread of coronavirus has caught our modern world by surprise, which leads to widespread panic, fear and confusion. However, if we view the unfolding of these events from a scientific historical perspective of past human evolution, we may discover the reoccurring patterns of the environmental conditions that give rise to such epidemics. Hence, we can figure out better methods to prepare and react to the infectious agents that spread diseases that have shaped the course of human history before. (...) Here, I propose a holistic view of human evolution, with an interdisciplinary approach that studies how cyclic variation in solar UV energy affects the evolution of viruses and shapes the symbiotic dynamics of human life on earth. (shrink)

History is the science which investigates the successive changes that have taken place in the material and intellectual conditions of man; it inquires into the causes of those changes, and the influence which they have exerted in modifying the life and mind of mankind.

We consider domains with a natural property called top-circularity. We show that if such a domain satisfies either the maximal conflict property or the weak conflict property, then it is dictatorial. We obtain the result in Sato :331–342, 2010) as a corollary. Furthermore, it follows from our results that the union of a single-peaked domain and a single-dipped domain is dictatorial.

In this paper, we present a formal recipe that Frege followed in his magnum opus “Grundgesetze der Arithmetik” when formulating his definitions. This recipe is not explicitly mentioned as such by Frege, but we will offer strong reasons to believe that Frege applied it in developing the formal material of Grundgesetze. We then show that a version of Basic Law V plays a fundamental role in Frege’s recipe and, in what follows, we will explicate what exactly this role is and (...) explain how it differs from the role played by extensions in his earlier book “Die Grundlagen der Arithmetik”. Lastly, we will demonstrate that this hitherto neglected yet foundational aspect of Frege’s use of Basic Law V helps to resolve a number of important interpretative challenges in recent Frege scholarship, while also shedding light on some important differences between Frege’s logicism and recent neo-logicist approaches to the foundations of mathematics. (shrink)

One familiar philosophical use of the term ‘evil’ just contrasts it with ‘good’, i.e., something is an evil if it is a bad thing, one of life’s “minuses.” This is the sense of ‘evil’ that is used in posing the traditional theological problem of evil, though it is customary there to distinguish between moral evils and natural evils. Moral evils are those bad things that are caused by moral agents; natural evils are those bad things that are not caused by (...) moral agents. Since the existence of evils of both sorts is usually taken to be indubitable, the problem of evil is then construed as the problem of how to square their existence with the existence of an all-powerful and benevolent God. (shrink)

This is an exploration of recent trends in metaphysics, including deflationary and experimental metaphysics.

This paper presents a new argument against philosophical theories based on arguments in favor of ontological reductions. The argument is an experiment in thought that has transcendental force, because it demonstrates the impossibility of forming a concept of anything with a reductionist nature. So although we consider as examples only theories that try to reduce everything in accordance with the currently popular materialisms or dualism, the argument applies as well to every sort of reduction theory whatever.

_Der Mythos der religiösen Neutralität_ bietet eine radikale Neuinterpretation der allgemeinen Beziehungen zwischen Religion, Wissenschaft und Philosophie.

The use of cost-benefit analysis (CBA) in environmental decision-making and the contingent valuation (CV) technique as input into traditional CBA to elicit environmental values in monetary terms has stimulated an extensive debate. Critics have questioned the appropriateness of both the method and the technique. Some alternative suggestions for the elicitation of environmental values are based on a social process of deliberation. However, just like traditional economic theory, these alternative approaches may be questioned on their implicit value judgements regarding the legitimacy (...) of the social-political organisation of the process of value elicitation. Instead of making assumptions a priori, research efforts should be focused on the processes by which actual public attitudes and preferences towards the environment can best be elicited and fed into environmental or other public policy decision-making. In the study presented in this paper, support was found for both the individual WTP based approach and a participatory social deliberation approach to inform the environmental decision-making process, suggesting that a combination of both approaches is most appropriate. (shrink)

If A then B: How the World Discovered Logic is a historically oriented introduction to the basic notions of logic. In particular, and in the words of the authors, it is focused on the idea that ‘lo...