Selective protein degradation maintains cellular homeostasis, but this process is disrupted in many diseases. Targeted protein degradation (TPD) approaches, built upon existing cellular mechanisms, are promising methods for therapeutically regulating protein levels. Here, we review the diverse palette of tools that are now available for doing so throughout the gene expression pathway and in specific cellular compartments. These include methods for directly removing targeted proteins via the ubiquitin proteasome system with proteolysis targeting chimeras (PROTACs) or dephosphorylation targeting chimeras (DEPTACs). Similar (...) effects can also be achieved through the lysosomal system with autophagy‐targeting chimeras (AUTACs), autophagosome tethering compounds (ATTECs), and lysosome targeting chimeras (LYTACs). Other methods act upstream to degrade RNAs (ribonuclease targeting chimeras; RIBOTACs) or transcription factors (transcription factor targeting chimeras; TRAFTACs), offering control throughout the gene expression process. We highlight the evolution and function of these methods and discuss their clinical implications in diverse disease contexts. (shrink)

Should citizens have equal say regarding the running of society? Following the principles of democracy, and most of political philosophy: yes (at least at a fundamental level, thus allowing for representatives and the like). Indeed, comparing the main alternative seemingly supports this intuition. Epistocracy would instead give power just to the most epistemically competent. Yet testing citizens’ political and economic knowledge looks apt to disproportionately disempower marginalised groups, making the position seem like a nonstarter and democracy the clear winner. Nevertheless, (...) this paper argues against giving citizens equal say, or at least, it offers the strongest possible motivation for this position. In particular, I introduce the progressive case for epistocracy, and what I term standpoint epistocracy. This account refigures the relevant notion of political competence such that it is not the most privileged classes who would most likely constitute our epistocracy, but rather, the least. The resulting picture considerably improves on traditional versions of epistocracy and also democracy. (shrink)

What determines qualitative sameness and difference? This book explores four principal accounts of the ontological basis of properties, including universals, trope theory, resemblance nominalism, and class nominalism, considering the assumptions and ontolological commitments which are required to make each into a plausible account of properties. -/- The latter half of the book investigates the applications of property theory and the different conceptions of properties which might be adopted with these in mind: first, the possibility and desirability of individuating properties, and (...) the distinction between sparse and abundant conceptions of properties; second, the distinction between intrinsic and extrinsic properties; third, the relationship between properties and their causal powers, and whether this is necessary or contingent; fourth, the relationship between properties and causation, modality, and laws of nature; finally, whether properties exist objectively, and if they do, what our epistemic position is with respect to such entities. (shrink)

Le Poidevin has recently presented an argument that gives rise to a serious problem for relationist theories of space. It appeals to the simple geometrical fact that if A, B and C are three points lying in a straight line, then AB and BC together entail AC. He suggests that an ontological relationship of supervenience must be appealed to to explain this entailment. Given this thesis of supervenience, relationism is implausible. I argue that the problem that Le Poidevin raises for (...) relationism should be rejected, because the thesis of supervenience is false. The latter rests upon what Le Poidevin refers to as ‘The explanatory principle', a principle which he claims to be a natural extension of the truthmaker principle. Contrary to this, I argue that given any plausible theory of truthmaking, the explanatory principle is false. With the rejection of this principle, Le Poidevin's argument against relationism collapses. (shrink)

What is salience? This collection addresses this neglected question by considering the role of salience in a wide variety of areas. All 13 chapters are specially commissioned, and written by an international team of contributors.

Many views rely on the idea that it can never be rational to have high confidence in something like, “P, but my evidence doesn’t support P.” Call this idea the “Non-Akrasia Constraint”. Just as an akratic agent acts in a way she believes she ought not act, an epistemically akratic agent believes something that she believes is unsupported by her evidence. The Non-Akrasia Constraint says that ideally rational agents will never be epistemically akratic. In a number of recent papers, the (...) Non-Akrasia Constraint has been called into question. The goal of this paper is to defend it... for the most part. (shrink)

Our fourteenth year of publication begins with an exceptional expansion of our sense of philosophy’s powers and resources. In our special featured article, Brian Schroeder’s groundbreaking essay, “...

v. 1. Li ze xue -- v. 2. Yu zhou lun xin li xue -- v. 3 Xing shang xue.

The most widespread statement of political philosophy is presented here in the simplified and trivialised form of “man is X; he must become Y. ” Man must do so at the same time for himself, for his own survival, but also for the good of all, of the Community, of the City: the plurality must absolutely, in any way whatsoever, give way to unity, subject to [sous peine] and under threat of chaos. The essential question found confronting political doctrines, moreover (...) since the prominence of the idea of democracy is the following: how to bring about the existence of a united society across a heterogeneous social body? The response from philosophy articulates itself around three principle schemas: the theoretical construction of a unified community under the order of similar laws to those of nature (Platonic schema); the search for the best regime, which will have as its ultimate end the moderation and perpetual regulation of conflicts, by an optimal combination of freedom and stability (Aristotelian schema); and the theorisation of the “end of politics” by the locating of a “social wrong” inscribed in a structure doomed to collapse by the practical negation of its ideological foundations (Marxian schema and derivatives). The mode of thought which imposes itself here is decisional. Beyond the third schema which constitutes in some way a meta-political critique, and necessitates that it alone has a particular analysis, in the two preceding, man constitutes a kind of material – raw or primary, depending – that philosophy will work on, and sculpt to give it a form that harmonises fully with the Whole that it prescribes. In political philosophy, we always turn more or less around the “Let’s make man” of Hobbes, that is, around the technical transformation of a material given. Or to say it otherwise: the creation of an oeuvre from crude and imperfect elements, an oeuvre thought like a masterpiece – that is to say, one that contains within it an idea of perfection and permanence – but doomed here to serial reproduction. (shrink)

勞思光、牟宗三、葛瑞漢、華靄仁、安樂哲， 探究當代孟學家學術理解之差異， 透過思想省察及文獻分析等方式，重釋及廓清《孟子》研究的爭議性課題。 中國儒家經典《孟子》，向來被研究得最廣泛、透澈卻又似乎未能獲致研究者共同認定的一致性成果。由於研究者的學養背景相異，援引的哲學路數不同，使得《孟子》研究呈現出理解上的莫衷一是及多元歧見的情況。 本書針對當代學者有關《孟子》研究的爭議性課題，試圖透過思想史的省察及文獻分析等方式予以廓清與重釋。首先，作者立基於《孟子》的歷史發展脈絡，並掌握經典文獻語義及架構價值。其次，藉由學術研究成績斐然的勞思 光先生與當代新儒家的重要代表人物牟宗三先生，對於《孟子》詮釋的差異性作比較與省思，深刻觸及了儒家哲學的內在問題。接著，探究葛瑞漢、華靄仁以及安樂哲三位漢學家，何以因為迥異的思維而產生不同的學術理解。最 後，疏理傳統與當代及西方詮釋孟學所引發的爭議。全書既省察當代孟學詮釋，並對比其論述脈絡，是一本孟學及儒學研究者必備專書。.

本书探讨了元代儒学学派与诗文流派之间的互动关系。全书分为上下两编，上编为总论部分，对南宋金元时期学术变迁与派别分化、学术与诗文的联动、理学门派传承与诗文流派的生成加以宏观性论述；同时重点考察了许衡与元 代中州文派、刘因与元代北方文派、许谦与元代金华文派、李齐贤与元代高丽文派等的儒学承传和文学创作。下编为考证部分，汇辑了元代高丽士人李齐贤研究资料，并考撰了“元代中朝（韩）越日间文学活动编年”。.

Believing rationally is epistemically valuable, or so we tend to think. It’s something we strive for in our own beliefs, and we criticize others for falling short of it. We theorize about rationality, in part, because we want to be rational. But why? I argue that how we answer this question depends on how permissive our theory of rationality is. Impermissive and extremely permissive views can give good answers; moderately permissive views cannot.

On sait peu de choses d’Edme Mariotte, membre de l’Académie royale des sciences de 1668 à 1684. Une analyse de son Essai de logique montre cependant que, pour défendre ses pratiques expérimentales, il s’appropria des bribes venues de différentes traditions intellectuelles. Ainsi, ce livre examine ce qu’on entendait par « méthode » à la fin du XVIIe siècle, les épistémologies de la physique qui s’affrontaient alors, quelques débats ouverts par la gestion de l’héritage cartésien. Mais l’essentiel sera peut-être la question (...) suivante : comment reconstituer les idées d’un savant ordinaire, qui n’a ni bouleversé l’ordre des sciences, ni montré une perspicacité épistémologique exceptionnelle ? (shrink)

Epistemologists often assume that rationality bears an important connection to the truth. In this paper I examine the implications of this commitment for permissivism: if rationality is a guide to the truth, can it also allow some leeway in how we should respond to our evidence? I first discuss a particular strategy for connecting permissive rationality and the truth, developed in a recent paper by Miriam Schoenfield. I argue that this limited truth-connection is unsatisfying, and the version of permissivism that (...) supports it faces serious challenges; so, for mainstream permissivism, the truth problem is still unsolved. I then discuss a strategy available to impermissivists, according to which rationality bears a quite strong connection to truth. I argue that this second strategy is successful. (shrink)

The subject of this book is young children's emotional-social learning and development within early childhood care and education settings in Aotearoa-New Zealand. The focus on emotional complexity fills a gap in early childhood care and education research where young children are frequently framed narrowly as 'learners,' ignoring the importance of emotional functioning and the feelings with which children make sense of themselves and the world. This book draws on original data in the form of narrative-like framed events to creatively illustrate (...) the complexities in children's diverse ways of feeling, thinking, playing, being, and becoming. Events illuminate the feelings and meanings of observed experiences in holistic and contextualised gestalts. Awareness of unconscious processes, the feeling of feelings, and cultural dimensions of development and meaning-making are addressed. The book emphasises the emergent and psychodynamic nature of children's development and learning with strong links to the role of play and playfulness in the events, drawing on two ethnographically inspired research projects that present theory, experience and practice in real-life events. (shrink)

This paper provides an analysis of the complex global reproduction networks driving the rapidly expanding cross-border surrogacy industry in Asia’s reproductive bioeconomy. It sheds light on the unique features of informal surrogacy networks, notable for their flexible business ties and non-standardized surrogate mother recruitment. These factors contribute to heightened vulnerability for surrogate mothers operating within these networks. While previous literature has underscored the merits of labor law in regulating the surrogacy industry, its application in informal cross-border surrogacy remains under-examined. To (...) address this gap, this research delves into innovative labor law strategies with potential to better regulate the surrogacy sector. Drawing inspiration from progressive labor regulations and supply chain strategies in Bulgaria and Australia, the proposed model aims to redefine the traditional employment relationship. This shift is aimed at bolstering protection for surrogate mothers and enforcing accountability throughout the surrogacy business network. The model further advocates for a collective framework that fosters collaboration and mandates the documentation and registration of surrogacy contracts. Moreover, it underscores the critical significance of international collaboration in bridging regulatory gaps and distributing accountability across consumer and supply states. (shrink)

Ce texte a déjà paru dans la revue Sociologie, N° 4, vol. 4 | 2014. Nous remercions Sophie Dubuisson-Quellier et Marie Plessz de nous avoir autorisé à le reproduire ici. Résumé : La théorie des pratiques est un courant d'analyse qui s'est développé en Grande-Bretagne et dans les pays scandinaves dans les années 2000. L'analyse de pratiques de consommation est l'un de ses domaines de prédilection. Se réclamant de Bourdieu et de Giddens, elle s'oppose à la fois aux analyses (...) de la consommation reposant sur (...) - Sociologie – Nouvel article. (shrink)

The conventional view of Hobbes’s commonwealth is that it was inspired by contemporary theories of tyranny. This article explores the idea that a paradigm for Hobbes’s state could in fact be found in early modern readings of Aristotle on democracy, as found in Book Three of the Politics. It argues that by the late sixteenth century, these meditations on the democratic body politic had developed claims about unity, mythology, and personation that would become central to Hobbes’s own theory of the (...) commonwealth. Tracing the history of commentary on the relevant passages in Aristotle reveals new perspectives not only on the political theories of both Aristotle and Hobbes but also introduces modern readers to the richness of early modern commentaries on classical political texts. The article ends with some thoughts on why attention to traditions of commentary might be valuable for political theorists today. (shrink)

Credences, unlike full beliefs, can’t be true or false. So what makes credences more or less accurate? This chapter offers a new answer to this question: credences are accurate insofar as they license true educated guesses, and less accurate insofar as they license false educated guesses. This account is compatible with immodesty; : a rational agent will regard her own credences to be best for the purposes of making true educated guesses. The guessing account can also be used to justify (...) certain coherence constraints on rational credence, such as probabilism. The chapter concludes by discussing some advantages of the guessing account over rival accounts of accuracy. (shrink)

This text provides an introduction to and exploration of the practices of global governance in contemporary international politics. It consists of a series of case studies written by specialists on the most important areas within global governance.

UK higher education reform (BIS, 2011) has been presented as a common‐sense movement towards efficiency. This article will argue that, in reality, the marketisation of higher education is a movement towards negative freedom, defined after Berlin (2007) as unrestricted choice. Using Shakespeare's Antony and Cleopatra as a means to explore the relationship between rationality and sensibility, it considers how negative freedom may undermine human connectivity and debase our relationships. In so doing, this article challenges the idea that importing the market (...) system into education will enhance the ‘student experience’. (shrink)

William James famously tells us that there are two main goals for rational believers: believing truth and avoiding error. I argues that epistemic consequentialism—in particular its embodiment in epistemic utility theory—seems to be well positioned to explain how epistemic agents might permissibly weight these goals differently and adopt different credences as a result. After all, practical versions of consequentialism render it permissible for agents with different goals to act differently in the same situation. -/- Nevertheless, I argue that epistemic consequentialism (...) doesn’t allow for this kind of permissivism and goes on to argue that this reveals a deep disanalogy between decision theory and the formally similar epistemic utility theory. This raises the question whether epistemic utility theory is a genuinely consequentialist theory at all. (shrink)

The Routledge Handbook of Emergence is an outstanding reference source and exploration of the concept of emergence, and is the first collection of its kind.

Do conceivability arguments work against physicalism if properties are causal powers? By considering three different ways of understanding causal powers and the modality associated with them, I will argue that most, if not all, physicalist powers theorists should not be concerned about the conceivability argument because its conclusion that physicalism is false does not hold in their favoured ontology. I also defend specific powers theories against some recent objections to this strategy, arguing that the conception of properties as powerful blocks (...) conceivability arguments unless a rather implausible form of emergence is true. (shrink)

This paper explores Zha Changping’s humanistic criticism of pioneering Chinese art as a new paradigm in art criticism after the postmodern disintegration of traditional art history with its linear art history writing. It introduces the “seven forming factors” at the heart of Zha’s “world relational aesthetics,” which, on one hand, gauges the pulse of the time, while on the other hand seeking to uncover the underlying relational logic informing this generation of pioneering artists’ intellectual outlook and artistic output.