During the process of E. coli nucleotide excision repair, DNA damage recognition and processing are achieved by the action of the uvrA, uvrB, and uvrC gene products. The availability of highly purified proteins has lead to a detailed molecular description of E. coli nucleotide excision repair that serves as a model for similar processes in eukaryotes. An interesting aspect of this repair system is the protein complex's ability to work on a vast array of DNA lesions that differ widely in (...) their chemical composition and molecular architecture. Here we propose a model for damage recognition in which the UvrB protein serves as the component that confers enhanced specificity to a preincision complex. We hypothesize that one major determinant for the formation of a stable preincision complex appears to be the disruption of base stacking interactions by DNA lesions. (shrink)

We highlight a recent study exploring the hand‐off of UV damage to several key nucleotide excision repair (NER) proteins in the cascade: UV‐DDB, XPC and TFIIH. The delicate dance of DNA repair proteins is choreographed by the dynamic hand‐off of DNA damage from one recognition complex to another damage verification protein or set of proteins. These DNA transactions on chromatin are strictly chaperoned by post‐translational modifications (PTM). This new study examines the role that ubiquitylation and subsequent DDB2 degradation has during (...) this process. In total, this study suggests an intricate cellular timer mechanism that under normal conditions DDB2 helps recruit and ubiquitylate XPC, stabilizing XPC at damaged sites. If DDB2 persists at damaged sites too long, it is turned over by auto‐ubiquitylation and removed from DNA by the action of VCP/p97 for degradation in the 26S proteosome. (shrink)

This paper challenges a pervasive, if not always explicit assumption of the present state of theorising in business ethics. This is the idea that a workable theory of organizational ethics must provide a unified perspective on its subject matter. In this paper we will sketch the broad outlines of an alternative understanding of business ethics, which focuses on constraints on corporate conduct that cannot reasonably be rejected. These constraints stem from at least three different levels or spheres of social reality, (...) i.e. the preconditions of a well-ordered society, the internal morality of economic activity and the preconditions of autonomous agency. (shrink)

In his essay “Faith and Knowledge,” Derrida provides us with his most direct and explicit discussion of the phenomenon of religion. One of the important ideas of “Faith and Knowledge” is that faith and knowledge cannot be understood in a simple opposition to each other as if knowledge would not require forms of faith and as if faith would be completely purified of knowledge. In order to get a precise impression of Derrida's interpretation of faith and the holy, this chapter (...) begins with a presentation of these notions in Heidegger. The chapter discusses the question whether it is the case that Heidegger finds in his question of being what phenomenology of religion and theology consider to be characteristic of religious thinking, feeling, and acting. It also discusses with an analysis of abstraction and deracination, which are juxtaposed to the process of indemnification. (shrink)

This paper challenges a pervasive, if not always explicit assumption of the present state of theorising in business ethics. This is the idea that a workable theory of organizational ethics must provide a unified perspective on its subject matter. In this paper we will sketch the broad outlines of an alternative understanding of business ethics, which focuses on constraints on corporate conduct that cannot reasonably be rejected. These constraints stem from at least three different levels or spheres of social reality, (...) i.e. the preconditions of a well-ordered society, the internal morality of economic activity and the preconditions of autonomous agency. (shrink)

Behavior oftentimes allows for many possible interpretations in terms of mental states, such as goals, beliefs, desires, and intentions. Reasoning about the relation between behavior and mental states is therefore considered to be an effortful process. We argue that people use simple strategies to deal with high cognitive demands of mental state inference. To test this hypothesis, we developed a computational cognitive model, which was able to simulate previous empirical findings: In two-player games, people apply simple strategies at first. They (...) only start revising their strategies when these do not pay off. The model could simulate these findings by recursively attributing its own problem solving skills to the other player, thus increasing the complexity of its own inferences. The model was validated by means of a comparison with findings from a developmental study in which the children demonstrated similar strategic developments. (shrink)

Behavior oftentimes allows for many possible interpretations in terms of mental states, such as goals, beliefs, desires, and intentions. Reasoning about the relation between behavior and mental states is therefore considered to be an effortful process. We argue that people use simple strategies to deal with high cognitive demands of mental state inference. To test this hypothesis, we developed a computational cognitive model, which was able to simulate previous empirical findings: In two-player games, people apply simple strategies at first. They (...) only start revising their strategies when these do not pay off. The model could simulate these findings by recursively attributing its own problem solving skills to the other player, thus increasing the complexity of its own inferences. The model was validated by means of a comparison with findings from a developmental study in which the children demonstrated similar strategic developments. (shrink)

Behavior oftentimes allows for many possible interpretations in terms of mental states, such as goals, beliefs, desires, and intentions. Reasoning about the relation between behavior and mental states is therefore considered to be an effortful process. We argue that people use simple strategies to deal with high cognitive demands of mental state inference. To test this hypothesis, we developed a computational cognitive model, which was able to simulate previous empirical findings: In two-player games, people apply simple strategies at first. They (...) only start revising their strategies when these do not pay off. The model could simulate these findings by recursively attributing its own problem solving skills to the other player, thus increasing the complexity of its own inferences. The model was validated by means of a comparison with findings from a developmental study in which the children demonstrated similar strategic developments. (shrink)

We focus on two issues: (1) an unusual, counterintuitive prediction that quantum probability (QP) theory appears to make regarding multiple sequential judgments, and (2) the extent to which QP is an appropriate and comprehensive benchmark for assessing judgment. These issues highlight how QP theory can fall prey to the same problems of arbitrariness that Pothos & Busemeyer (P&B) discuss as plaguing other models.

ABSTRACT:The ethics of high frequency trading are obscure, due in part to the complexity of the practice. This article contributes to the existing literature of ethics in financial markets by examining a recent trend in regulation in high frequency trading, the prohibition of deception. We argue that in the financial markets almost any regulation, other than the most basic, tends to create a moral hazard and increase information asymmetry. Since the market’s job is, at least in part, price discovery, we (...) argue that simplicity of regulation and restraint in regulation are virtues to a greater extent than in other areas of finance. This article proposes criteria for determining which high-frequency trading strategies should be regulated. (shrink)

The idea that the state ought to be neutral towards different conceptions of the good life has been an influential principle in liberal theory since the 1970s. It has, however, been subject to criticism by communitarians, multiculturalists and liberal perfectionists. Recently, Peter Balint has attempted to defend state neutrality against its liberal critics as the adequate interpretation of the liberal project by redefining it as a range concept. By arguing that neutrality always occurs within a specific range of permissible conceptions (...) of the good life, Balint provides a convincing rebuttal of neutrality’s critics. In this paper I argue that while neutrality as a range concept provides an adequate account of state neutrality, it also makes it vulnerable to a new line of critique. Since the range of neutrality cannot be deduced from the principle of neutrality itself, neutrality is subject to political developments beyond its own control. I will start by clarifying the notion of neutrality as a range concept. Secondly, I will demonstrate that Balint’s notion of the range concept finds ample support in the wider literature on neutrality. Thirdly, I will argue that, as a range concept, neutrality ultimately depends on politically constituted value judgments. (shrink)

This article offers an interpretation of theories of management and organisation from the perspective of Hannah Arendt’s theory of free action. This endeavour will contribute to criticism and eventually improvement of the conceptual framework of management and organisation theory. We discuss conceptual tensions in this field, for instance with respect to the relationship between human action and the constraints of an organisation. To the extent that management and organisation theory are practiceoriented, such an analysis can help to understand tensions and (...) ambiguities in practice. Some of the optimism and high hopes found in the literature may have to be tempered as a consequence of a more adequate analysis of free action. The analysis therefore provides a critical point of view on the problems of managing freely acting people. (shrink)

This article offers an interpretation of theories of management and organisation from the perspective of Hannah Arendt’s theory of free action. This endeavour will contribute to criticism and eventually improvement of the conceptual framework of management and organisation theory. We discuss conceptual tensions in this field, for instance with respect to the relationship between human action and the constraints of an organisation. To the extent that management and organisation theory are practiceoriented, such an analysis can help to understand tensions and (...) ambiguities in practice. Some of the optimism and high hopes found in the literature may have to be tempered as a consequence of a more adequate analysis of free action. The analysis therefore provides a critical point of view on the problems of managing freely acting people. (shrink)

Carl Schmitt described the political in existential terms. The political consists in the distinction between friend and enemy, a distinction between collectivities that are existentially different. This led Richard Wolin to label Schmitt a “political existentialist” whose work relies on a specific cultural and philosophical climate of “vitalism.” Consequently, Schmitt’s thought is treated as ideology by Wolin. Instead of focusing on Schmitt’s underlying ideological affinity with a particular cultural climate, this paper attempts to conceptualize the notion of “political existentiality” as (...) a crucial element in Schmitt’s understanding of the political and defend it as a notion that reveals something about the political condition itself. In order to understand the meaning of existentiality, we will conceptualize it against the background of Max Weber’s disenchantment thesis and conclude that through the notion of political existentiality Schmitt conceptualizes the political sphere as a locus of meaning and values and thus reenchants the political. (shrink)

We are currently in the middle of the transformation from Martin Heidegger’s modern society to a society based on digital technology. In the developing digital society, humans in their current state of ‘Being’ are increasingly surrounded by systems that are networked and run based on algorithms, software, and data. These interconnected systems function, communicate, and interact in networks and driven by these algorithms, software, and data, which give them the ability to connect, calculate, and reveal. Jointly, these systems thus create (...) a new and actual reality based on their mathematical and scientific background. In the present-day digital society, humans’ actual ‘state of Being’ is increasingly framed by what the digital technology reveals to us and enables. The transition to this new digital reality conjures up more and more questions as to whether we as humans sufficiently understand the essence of digital technology and whether we as humanity have sufficient knowledge and insight to be able to analyze and fathom the essence of the new digital ecology around us. In this article, I will use Heideggerian phenomenology as a philosophy to create a framework that will allow us to, based on phenomenological research into our current ‘Dasein’ or ‘being there’, gain deeper insight into the ‘Being’ of digital technology and the ensuing development of a digital reality for humanity as a whole. (shrink)

Background Clients are invited to play a role in decisions about their care. Collaborative deliberation comprises constructive engagement, recognition of alternative actions, comparative learning, construction and elicitation of preferences and preference integration. Collaborative deliberation between clients and professionals is a process that requires an interest in each other, sharing of views on alternatives and preferences and integrating into decisions. The aim is to gain insight into collaborative deliberation in consultations and the clients’ perception of arranging long-term care. Design A descriptive (...) qualitative study to explore collaborative deliberation in consultations between clients and professionals. Six organisations providing long-term care were included. Data collection of nine clients involved observations of consultation with field notes and audio-records, interviews with clients and professionals shortly and 3–6 months after the consultation and questionnaires to collect background information. The data were analysed by deductive content analysis. Findings Constructive engagement was visible in all consultations. Clients and professionals showed respect, empathy and curiosity towards each other. In most consultations, two or more alternative actions are recognised and discussed. Comparative learning appears to be two sided, the client and the professional learn from each other's knowledge and experiences. Construction and elicitation of preference, and preference integration, seems to be present, but difficult to recognise in all consultations. Discussion/conclusion Although all propositions could be identified, there seems room for improvement in preference elicitation and integration of these preferences in the discussions on courses of action. Assistance seems needed with preference elicitation, both for the clients and for the professional. (shrink)

A blockchain can be considered a technological phenomenon that is made up of different interconnected and autonomous systems. Such systems are referred to here as cyber-physical systems: complex interconnections of cyber and physical components. When cyber-physical systems are interconnected, a new whole consisting of a system of systems is created by the autonomous systems and their intercommunication and interaction. In a blockchain, individual systems can independently make decisions on joint information transactions. The decision-making procedures needed for this are executed based (...) on fault-tolerant communication and voting and consensus procedures, while the results of these decision-making procedures are stored in distributed ledgers. Due to the intercommunication, interaction, and independent decision making by autonomous systems, the new whole of a blockchain is a complex entity. Complexity science rather than the usual reductionist scientific approach can help us better understand the behaviour of the new and continuously developing whole of a blockchain as a technological phenomenon. (shrink)

Van Gelder presents the distinction between dynamical systems and digital computers as the core issue of current developments in cognitive science. We think this distinction is much less important than a reassessment of cognition as a neurally, bodily, and environmentally embedded process. Embedded cognition lines up naturally with dynamical models, but it would also stand if combined with classic computation.

Packed with ideas designed to help children learn to sing, this booklet offers criteria for selecting songs, strategies to bring out the best in children's voices, and suggestions for games, ideas, and resources.

The objective of Working Group 4 of the COST Action NET4Age-Friendly is to examine existing policies, advocacy, and funding opportunities and to build up relations with policy makers and funding organisations. Also, to synthesize and improve existing knowledge and models to develop from effective business and evaluation models, as well as to guarantee quality and education, proper dissemination and ensure the future of the Action. The Working Group further aims to enable capacity building to improve interdisciplinary participation, to promote knowledge (...) exchange and to foster a cross-European interdisciplinary research capacity, to improve cooperation and co-creation with cross-sectors stakeholders and to introduce and educate students SHAFE implementation and sustainability. To enable the achievement of the objectives of Working Group 4, the Leader of the Working Group, the Chair and Vice-Chair, in close cooperation with the Science Communication Coordinator, developed a template to map the current state of SHAFE policies, funding opportunities and networking in the COST member countries of the Action. On invitation, the Working Group lead received contributions from 37 countries, in a total of 85 Action members. The contributions provide an overview of the diversity of SHAFE policies and opportunities in Europe and beyond. These were not edited or revised and are a result of the main areas of expertise and knowledge of the contributors; thus, gaps in areas or content are possible and these shall be further explored in the following works and reports of this WG. But this preliminary mapping is of huge importance to proceed with the WG activities. In the following chapters, an introduction on the need of SHAFE policies is presented, followed by a summary of the main approaches to be pursued for the next period of work. The deliverable finishes with the opportunities of capacity building, networking and funding that will be relevant to undertake within the frame of Working Group 4 and the total COST Action. The total of country contributions is presented in the annex of this deliverable. (shrink)

In most decision-making situations, there is a plethora of information potentially available to people. Deciding what information to gather and what to ignore is no small feat. How do decision makers determine in what sequence to collect information and when to stop? In two experiments, we administered a version of the German cities task developed by Gigerenzer and Goldstein (1996), in which participants had to decide which of two cities had the larger population. Decision makers were not provided with the (...) names of the cities, but they were able to collect different kinds of cues for both response alternatives (e.g., “Does this city have a university?”) before making a decision. Our experiments differed in whether participants were free to determine the number of cues they examined. We demonstrate that a novel model, using hierarchical latent mixtures and Bayesian inference (Lee & Newell, 2011) provides a more complete description of the data from both experiments than simple conventional strategies, such as the take–the–best or the Weighted Additive heuristics. (shrink)

The Charmides is among Plato's most intriguing and perplexing dialogues. The range of subjects touched or treated is extremely wide: matters logical, epistemological, moral, ethical, political, and religious. In many cases, these are discussed in a highly inconclusive and aporetic way, especially when it comes to the subject of knowledge. Finally, the dialogue is also difficult on almost every level of its expression; mock-reasonings, misunderstandings, ironies, paradoxes, and perplexities abound. As a result, the run of its many arguments, both on (...) the short and the long range, and its overall structure are not easy to discern. If a text of such a character is to be made completely accessible, a full-scale commentary is required; it is much to be regretted, therefore, that there is no commentary in which the difficulties of the Greek, the argument, and the place of the philosophical problems in the development of Plato's thought are comprehensively and coherently explained. This monograph does not aspire to that status, but makes an essential contribution towards achieving that aim (in addition to the many other works in the field, Lamb's scrupulous translation of 1927 and Bloch's penetrating study of 1973 in particular) by presenting a detailed examination of forty-two passages of which the interpretation is disputed; many more minor problems are dealt with along the way. In all matters of interpretation, special attention has been paid to defining the exact place of the passage within the run of the, often intricate, argument. The result of this attention can also be observed in an analytical 'Summary of the contents of the Charmides'. (shrink)

Lysophosphatidic acid (LPA) is a lipid mediator with a wide variety of biological actions, particularly as an inducer of cell proliferation, migration and survival. LPA binds to specific G‐protein‐coupled receptors and thereby activates multiple signal transduction pathways, including those initiated by the small GTPases Ras, Rho, and Rac. LPA signaling has been implicated in such diverse processes as wound healing, brain development, vascular remodeling and tumor progression. Knowledge of precisely how and where LPA is produced has long proved elusive. Excitingly, (...) it has recently been discovered that LPA is generated from precursors by ‘autotaxin’, a once enigmatic exo‐phosphodiesterase implicated in tumor cell motility. Exogenous phospholipases D can also produce LPA, which may contribute to their toxicity. Here we review recent progress in our understanding of LPA bioactivity, signaling and synthesis. BioEssays 26:870–881, 2004. © 2004 Wiley Periodicals, Inc. (shrink)