The insulin/insulin‐like growth factor‐1 (IGF‐1) signaling (IIS) pathway is a pivotal genetic program regulating cell growth, tissue development, metabolic physiology, and longevity of multicellular organisms. IIS integrates a fine‐tuned cascade of signaling events induced by insulin/IGF‐1, which is precisely controlled by post‐translational modifications. The ubiquitin/proteasome‐system (UPS) influences the functionality of IIS through inducible ubiquitylation pathways that regulate internalization of the insulin/IGF‐1 receptor, the stability of downstream insulin/IGF‐1 signaling targets, and activity of nuclear receptors for control of gene expression. An age‐related (...) decline in UPS activity is often associated with an impairment of IIS, contributing to pathologies such as cancer, diabetes, cardiovascular, and neurodegenerative disorders. Recent findings identified a key role of diverse ubiquitin modifications in insulin signaling decisions, which governs dynamic adaption upon environmental and physiological changes. In this review, we discuss the mutual crosstalk between ubiquitin and insulin signaling pathways in the context of cellular and organismal homeostasis. (shrink)

Comprehensive work on Hindu philosophy and spiritual life.

In their recent article, scholars Keisha Ray and Jane Fallis Cooper claim that “bioethicists should not be deterred from advocating for a healthy environment […] instead, […] underscore the importa...

Jennifer Blumenthal-Barby (2024) argues that “[i]t is time for bioethics to end talk about personhood” (11). The author calls on the field to ask different kinds of normative questions about the mo...

We often feel powerless in our lives. We have many desires but are limited in our ability to transform those wishes into tangible results. We are confused and unsure about what will really make us happy. In Eternal Dharma, Vishnu Swami guides you on a journey to align yourself with the natural flow of existence through the ancient Eastern knowledge of Veda. Eternal Dharma distills 5,000 years of spiritual wisdom so you can learn to live an enlightened, effective, and (...) fulfilled life. Vishnu Swami inspires you to take action and manifest your fullest spiritual potential in everything you do: Explore the subtle and physical domains to achieve a totally new relationship with reality. Learn the radical new system of effectiveness. Gain clarity on all spiritual and religious paths. Free yourself from pain and suffering to reach pure, transcendental love. (shrink)

Lorsque l’on réfléchit à la signification positive que Foucault a pu octroyer à l’ontologie, en plaidant pour que la philosophie s’impose comme une « ontologie historique », ou bien une « ontologie critique de nous-mêmes », il peut être utile au préalable de préciser ce que le recours foucaldien à une telle notion ne doit pas, et ne souhaite pas devoir à l’autre grand projet de pensée qui, au XXe siècle,...

Philosophy and Phenomenological Research, EarlyView.

In this paper, I present a puzzle about the connection between an agent’s knowledge and her rationality and a way to solve it. The puzzle is that, intuitively, many of us want to accept both that it is rational for an agent to act on what she knows and that it is irrational for an agent to take what she knows for granting in her practical reasoning. These two claims about rationality present us with a puzzle because, holding fixed our (...) interpretation of rationality, we cannot accept them both. According to my view, the most compelling way of solving this puzzle is to distinguish between our primary and dispositional evaluations of actions. By making this distinction, we not only gain a unique perspective on the relationship between knowledge and rationality, we also see how doing what we know is best might still manifest an undesirable habit. (shrink)

In both the Consequences of Compassion and his response to my article, Goodman outlines a consequentialist theory that is both coherent and, in many ways, compelling. One can imagine that out of a concern toward—as Goodman puts it—“the impersonal events which fill the world”, we will accept “momentary experiences as the morally significant units”, and our actions will aim to promote the existence of “good dharmas.” However, as this brief reply argues, Goodman’s equating of a consequentialism focused on good dharmas (...) to a consequentialism focused on individual well-being is unjustified, and, as a consequence, the textual evidence he presents does not support his consequentialist view... (shrink)

There is an emerging consensus that human behavior is governed by two types of processes: System 1 processes, which are quicker, automatic, and run in parallel, and System 2 processes, which are slower, more conscious, and run in serial. Among such “dual-process” theorists, however, there is disagreement about whether the premises we use in our conscious, S2 reasoning should be considered as beliefs. In this exchange, one facet that has been largely overlooked is how conscious beliefs are structurally and functionally (...) similar to episodic memories. This article will argue that the similarities between beliefs and episodic memories, specifically in light of Daniel Schacter’s widely influential constructive memory framework, highlight a heretofore unexamined empirical weakness of dispositional accounts of S2 beliefs. In addition, this perspective helps situate beliefs within our broader understanding of how information is encoded and retrieved in the brain. (shrink)

Provides a systematic introduction to the theory of logic programming and shows how this theory can be applied to reason about pure Prolog programs. The text includes an introduction to programming in Prolog and deals with such programming issues as determination, occur-check freedom and absence of errors. It covers both the natural interpretations of logic programming, as declarative specification and as procedure for computer execution.

A number of scholars have attempted to situate the Buddha’s teachings within the primary Western ethical theories, namely consequentialism, deontology, and virtue ethics. One challenge that each has confronted is Buddhism’s emphasis on the ultimate non-existence of the self. In his writings, Charles Goodman has put forward an account of how the realization of the ultimate non-existence of the self would lead a practitioner to consequentialism. The present comment challenges the account offered by Goodman, and argues that an ethical-particularist account (...) better squares Buddhist ethics with Buddhist metaphysics. This comment also shows how Goodman’s more recent work, while constituting a significant retreat from his.. (shrink)

The Joint International Conference on Logic Programming, sponsored by the Association for Logic Programming, is a major forum for presentations of research, applications, and implementations in this important area of computer science. Logic programming is one of the most promising steps toward declarative programming and forms the theoretical basis of the programming language Prolog and its various extensions. Logic programming is also fundamental to work in artificial intelligence, where it has been used for nonmonotonic and commonsense reasoning, expert systems implementation, (...) deductive databases, and applications such as computer-aided manufacturing. Krzysztof R. Apt is project leader at the Centre for Mathematics and Computer Science in Amsterdam and part-time Professor in Computer Science at the University of Amsterdam. Topics covered: Theory Foundations. Programming Languages. Implementation. Programming Methodologies and Tools. Applications. Deductive Databases. Artificial Intelligence. Parallelism. (shrink)

Social movements driven by a combination of religious nationalism and economic fundamentalism are globally grabbing the levers of political, economic, and intellectual control. The consequence is a policy climate premised on polarization in which inequality and destruction of the natural environment are condoned. This creates demands on key academic institutions like business schools, with stakeholders who are complicit in the sustenance of these social movements. Scholars in these schools have an opportunity to respond through curricula that facilitate reflection on the (...) ideological preferences of such groups under their influence. However, stakeholders influenced by religious nationalism tend to reject the premises of liberal secular vocabulary as elitist or alien and hence suspicious. This article considers a teaching strategy to instill values of equality and respect for nature among the stakeholders by grounding curriculums in the tenets of the same religion valorized by the social movements. The consequences of such a strategy is discussed through its application to the business curriculums taught in India, where a regressive social movement with totalitarian pretensions—Hindutva—combined with neoliberalism has secured unparalleled power. Elements of this strategy could inform educators in other democratic societies facing similar challenges. (shrink)

There’s more to meriting praise than doing what’s objectively right. After all, one might do what’s objectively right as the result of a fluke or with malicious intent. While doing what’s objectively right is not enough to merit praise, it’s natural to think that some list of sufficient conditions can be assembled. The most common approach to such lists entails that, when one does what is objectively right with the appropriate epistemic state and/or motivation, one merits praise for one’s action. (...) In other words, according to the most influential extant views, if one both does what’s right and meets certain additional criteria, one will not only succeed in doing what is morality required but will also succeed in deserving positive moral evaluation for what one has done. In this paper, I use the example of extended actions to show that drawing any sort of link between doing what’s objectively right and being worthy of praise is much more difficult than has been previously appreciated. (shrink)

Journal of Political Philosophy, EarlyView.

This collection of current research on logic programming languages presents results from a three-year, ESPRIT-funded effort to explore the integration of the foundational issues of functional, logic, and object-oriented programming. It offers valuable insights into the fast-developing extensions of logic programming with functions, constraints, concurrency, and objects. Chapters are grouped according to the unifying themes of functional programming, constraint, logic programming, and object-oriented programming.

Investigating meta-programming within the logic programming paradigm, Meta-Logics and Logic Programming presents original research on an important extension of logic programming that makes it more amenable for knowledge representation and programming in general. The 12 contributions, many written especially for this book, explore the foundations, language design issues, and applications of meta-programming in logic programming. Meta-programming—the process of writing computer programs that can manipulate representations of other programs—has been key both in the foundations of computer science and in its practical (...) developments. Examples of meta-programs include compilers, interpreters, program analyzers, and partial evaluators. The choice of logic programming as a basis for meta-programming offers several practical and theoretical advantages: among them, the possibility of tackling critical foundational problems of meta-programming within a strong theoretical framework, and the surprising ease of programming. The usual framework of logic programming (and more generally first-order logic), however, has to be modified and extended to formally deal with meta-programs, extensions the editors call "meta-logics." Along with an exploration of meta-programming in logic programming, the definitions, formal properties, and use of these extensions constitute one of the book's main themes. The first part of the book, Foundations, focuses on the representation problem—how object programs are represented within meta-programs. The second part, Language Support for Meta-Logics, is concerned with language extensions that make meta-programming easier and more elegant. The third part, Meta-Logics for Knowledge Management, deals with the use of meta-logic for advanced knowledge representation purposes. Logic Programming series. (shrink)

This volume is a collection of papers presented at the colloquium, and it testifies to the growing importance of game theory as a tool that can capture concepts ...

It’s widely accepted that whether or not an agent merits praise for performing a particular action importantly depends on her motivation in doing so. What has received less attention is the importance of an agent’s moral understanding to whether she merits praise for performing a particular action, or whether her action has ‘moral worth.’ The first task of this paper is relatively straightforward: to show that two prominent attempts to address the importance of moral understanding to moral worth, namely that (...) of Zoe Johnson King and Paulina Sliwa, are unsuccessful. The second task of this paper, which is more novel and ambitious, is to show that agents who lack moral understanding are a challenge to more accounts of moral worth than has been previously recognized. My goal in this paper is largely negative: to show that extant accounts of such conditions are unable to account for the relevance of an agent’s understanding to her praiseworthiness for performing a particular action. In making clear these shortcomings, however, I also hope to make clear just how complicated it is to pin down exactly when an agent merits praise for her actions. (shrink)

Bastin et al. present a framework that draws heavily on existing ideas of dual processes in memory in order to make predictions about memory deficits in clinical populations. It has been difficult to find behavioral evidence for multiple memory processes but we offer some evidence for dual processes in a related domain: memory for the time-of-occurrence of events.

Context is an important construct in many domains of cognition, including learning, memory, and emotion. We used dynamical systems methods to demonstrate the episodic nature of experience by showing a natural separation between the scales over which within-context and between-context relationships operate. To do this, we represented an individual's emails extending over about 5 years in a high-dimensional semantic space and computed the dimensionalities of the subspaces occupied by these emails. Personal discourse has a two-scaled geometry with smaller within-context dimensionalities (...) than between-context dimensionalities. Prior studies have shown that reading experience and visual experience have a similar two-scaled structure. Furthermore, the recurrence plot of the emails revealed that experience is predictable and hierarchical, supporting the constructs of some influential theories of memory. The results demonstrate that experience is not scale-free and provide an important target for accounts of how experience shapes cognition. (shrink)

In his book The Opacity of Mind, Peter Carruthers presents the Interpretive Sensory Awareness theory, which holds that while we have direct access to our own sensory states, our access to “self-knowledge” is almost always interpretive. In presenting his view, Carruthers also claims that his account is the first of its kind; after a cursory examination of major theories of mind, he concludes that “transparent access” accounts of self-knowledge—the alternative to ISA—have been endorsed throughout history. This paper challenges this latter (...) claim. Contrary to Carruthers’ view, the paper argues that Buddhist theories of mind are not “transparent access” accounts. Instead, they not only have an analysis of sensory processing and conscious experience similar to that of ISA, but also share what Carruthers sees as ISA’s central tenet: individuals lack transparent, conscious access to most of their propositional attitudes. Given this fundamental alignment, the Buddhist perspective can offer u.. (shrink)

In exploring the impact of cognitive science findings on compatibilist theories of moral responsibility such as Fischer and Ravizza’s, most attention has focused on whether agents are, in fact, responsive to reasons. In doing so, however, we have largely ignored our improved understanding of agents’ epistemic access to their reasons for acting. The “ownership” component of Fischer and Ravizza’s theory depends on agents being able to see the causal efficacy of their conscious deliberation. Cognitive science studies make clear that a (...) variety of situational factors, implicit attitudes, and unconscious mental states influence agents’ behavior, and that they are generally unaware of their impact. If an agent is skeptical of the extent to which her conscious deliberation has causal upshots in the world, then she – like a natural incompatibilist – may not take ownership over her action-generating mechanism. Instead, she may seek a more general account of moral responsibility or revise her moral intuitions altogether. (shrink)

Many accounts of moral responsibility have emerged recently that question the importance of conscious choice for moral responsibility. Instead of this ‘volitional’ requirement, these ‘attributionist’ accounts claim that agents are responsible for their actions when their actions reflect who they are and what they value. This paper argues that attributionist accounts are too quick to dismiss the connection between volition and moral responsibility. By excising conscious control from their accounts, attributionists leave open the undesirable possibility that an agent may fulfil (...) all necessary conditions for moral responsibility even when she is under the conscious control of another person. Through analyzing situations in which attributionist conditions for moral responsibility are met while an agent is controlled by someone else, the link between an agent's volition and her moral responsibility becomes more apparent. (shrink)

Weakly acyclic games form a natural generalization of the class of games that have the finite improvement property. In such games one stipulates that from any initial joint strategy some finite improvement path exists. We classify weakly acyclic games using the concept of a scheduler introduced in Simon and Apt. We also show that finite games that can be solved by the iterated elimination of never best response strategies are weakly acyclic. Finally, we explain how the schedulers allow us to (...) improve the bounds on finding a Nash equilibrium in a weakly acyclic game. (shrink)

Concern for corporate influence on democratic decisions has mostly focused on campaign funding and access to legislators. While these are certainly worrisome, corporations have another tool to influence decisions, which they are increasingly using. They can threaten to move their operations or cancel expansion plans in a municipality unless its public officials pass (or kill) certain policies. In one sense, this is business as usual. Companies have the right to decide where to operate, and it is important for officials to (...) consider how policy will impact local businesses that provide jobs and tax revenue. On the other hand, companies can use these threats to get their way on any policy, whether or not it impacts them. How do we tell when this kind of corporate action is illegitimate? We argue that such actions are illegitimate when they violate democratic norms of reason-giving, which occurs when companies offer the public “created” rather than “natural” reasons for their proposed policy. (shrink)

We show that various paradoxes can arise in a natural class of social networks. They demonstrate that more services or products may have adverse consequences for all members of the network and conversely that restricting the number of choices may be beneficial for every member of the network. These phenomena have been confirmed by a number of empirical studies. In our analysis we use a simple threshold model of social networks introduced in Apt and Markakis, and more fully in Apt (...) and Markakis. In this model the agents, influenced by their neighbours, can adopt one out of several alternatives. We identify and analyze here four types of paradoxes that can arise in these networks. These paradoxes shed light on possible inefficiencies arising when one modifies the sets of products available to the agents forming a social network or the network structure. One of the paradoxes corresponds to the well-known Braess paradox in congestion games and shows that by adding more choices to a node, the network may end up in a situation that is worse for everybody. We exhibit a dual version of this, according to which removing a product available to an agent can eventually make everybody better off. The other paradoxes that we identify show that by adding or removing a product from the choice set of an agent may lead to permanent instability. Finally, we also identify conditions under which some of these paradoxes cannot arise. (shrink)

Lipid droplets (LDs) are ubiquitous, neutral lipid storage organelles that act as hubs of metabolic processes. LDs are structurally unique with a hydrophobic core that mainly consists of neutral lipids, sterol esters, and triglycerides, enclosed within a phospholipid monolayer. Nascent LD formation begins with the accumulation of neutral lipids in the endoplasmic reticulum (ER) bilayer. The ER membrane proteins such as seipin, LDAF1, FIT, and MCTPs are reported to play an important role in the formation of nascent LDs. As the (...) LDs grow, they unmix from the highly charged ER membrane to form mature LDs. LD biogenesis is an exciting, emerging research area, and herein, we discuss the recent progress in our understanding of the formation of eukaryotic nascent LDs. We focus on the role of ER membrane shaping proteins such as reticulons and reticulon‐like proteins, membrane lipids, and cytoskeleton proteins such as septin in the formation of nascent LDs. (shrink)

In Het regeren van precairen analyseert Isabell Lorey hoe het mogelijk is dat een aanzienlijk deel van de bevolking van neoliberale samenlevingen met onzekerheid leeft zonder zich te verzetten. Zij concludeert dat de logica van het liberalisme precariteit tegenover veiligstelling plaatst, waardoor individuen zichzelf middels zelfregeringstechnieken proberen af te schermen en zich niet verzetten tegen precariteit.