260 research outputs found

    Contracts for Interacting Two-Party Systems

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    This article deals with the interrelation of deontic operators in contracts -- an aspect often neglected when considering only one of the involved parties. On top of an automata-based semantics we formalise the onuses that obligations, permissions and prohibitions on one party impose on the other. Such formalisation allows for a clean notion of contract strictness and a derived notion of contract conflict that is enriched with issues arising from party interdependence.Comment: In Proceedings FLACOS 2012, arXiv:1209.169

    Cytosolic chaperones influence the fate of a toxin dislocated from the endoplasmic reticulum

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    The plant cytotoxin ricin enters target mammalian cells by receptor-mediated endocytosis and undergoes retrograde transport to the endoplasmic reticulum (ER). Here, its catalytic A chain (RTA) is reductively separated from the cell-binding B chain, and free RTA enters the cytosol where it inactivates ribosomes. Cytosolic entry requires unfolding of RTA and dislocation across the ER membrane such that it arrives in the cytosol in a vulnerable, nonnative conformation. Clearly, for such a dislocated toxin to become active, it must avoid degradation and fold to a catalytic conformation. Here, we show that, in vitro, Hsc70 prevents aggregation of heat-treated RTA, and that RTA catalytic activity is recovered after chaperone treatment. A combination of pharmacological inhibition and cochaperone expression reveals that, in vivo, cytosolic RTA is scrutinized sequentially by the Hsc70 and Hsp90 cytosolic chaperone machineries, and that its eventual fate is determined by the balance of activities of cochaperones that regulate Hsc70 and Hsp90 functions. Cytotoxic activity follows Hsc70-mediated escape of RTA from an otherwise destructive pathway facilitated by Hsp90. We demonstrate a role for cytosolic chaperones, proteins typically associated with folding nascent proteins, assembling multimolecular protein complexes and degrading cytosolic and stalled, cotranslocational clients, in a toxin triage, in which both toxin folding and degradation are initiated from chaperone-bound states

    Cytosolic chaperones influence the fate of a toxin dislocated from the endoplasmic reticulum

    Get PDF
    The plant cytotoxin ricin enters target mammalian cells by receptor-mediated endocytosis and undergoes retrograde transport to the endoplasmic reticulum (ER). Here, its catalytic A chain (RTA) is reductively separated from the cell-binding B chain, and free RTA enters the cytosol where it inactivates ribosomes. Cytosolic entry requires unfolding of RTA and dislocation across the ER membrane such that it arrives in the cytosol in a vulnerable, nonnative conformation. Clearly, for such a dislocated toxin to become active, it must avoid degradation and fold to a catalytic conformation. Here, we show that, in vitro, Hsc70 prevents aggregation of heat-treated RTA, and that RTA catalytic activity is recovered after chaperone treatment. A combination of pharmacological inhibition and cochaperone expression reveals that, in vivo, cytosolic RTA is scrutinized sequentially by the Hsc70 and Hsp90 cytosolic chaperone machineries, and that its eventual fate is determined by the balance of activities of cochaperones that regulate Hsc70 and Hsp90 functions. Cytotoxic activity follows Hsc70-mediated escape of RTA from an otherwise destructive pathway facilitated by Hsp90. We demonstrate a role for cytosolic chaperones, proteins typically associated with folding nascent proteins, assembling multimolecular protein complexes and degrading cytosolic and stalled, cotranslocational clients, in a toxin triage, in which both toxin folding and degradation are initiated from chaperone-bound states

    The Role of Deontic Logic in the Specification of Information Systems

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    In this paper we discuss the role that deontic logic plays in the specification of information systems, either because constraints on the systems directly concern norms or, and even more importantly, system constraints are considered ideal but violable (so-called `soft¿ constraints).\ud To overcome the traditional problems with deontic logic (the so-called paradoxes), we first state the importance of distinguishing between ought-to-be and ought-to-do constraints and next focus on the most severe paradox, the so-called Chisholm paradox, involving contrary-to-duty norms. We present a multi-modal extension of standard deontic logic (SDL) to represent the ought-to-be version of the Chisholm set properly. For the ought-to-do variant we employ a reduction to dynamic logic, and show how the Chisholm set can be treated adequately in this setting. Finally we discuss a way of integrating both ought-to-be and ought-to-do reasoning, enabling one to draw conclusions from ought-to-be constraints to ought-to-do ones, and show by an example the use(fulness) of this

    Nudges and other moral technologies in the context of power: Assigning and accepting responsibility

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    Strawson argues that we should understand moral responsibility in terms of our practices of holding responsible and taking responsibility. The former covers what is commonly referred to as backward-looking responsibility , while the latter covers what is commonly referred to as forward-looking responsibility . We consider new technologies and interventions that facilitate assignment of responsibility. Assigning responsibility is best understood as the second- or third-personal analogue of taking responsibility. It establishes forward-looking responsibility. But unlike taking responsibility, it establishes forward-looking responsibility in someone else. When such assignments are accepted, they function in such a way that those to whom responsibility has been assigned face the same obligations and are susceptible to the same reactive attitudes as someone who takes responsibility. One family of interventions interests us in particular: nudges. We contend that many instances of nudging tacitly assign responsibility to nudgees for actions, values, and relationships that they might not otherwise have taken responsibility for. To the extent that nudgees tacitly accept such assignments, they become responsible for upholding norms that would otherwise have fallen under the purview of other actors. While this may be empowering in some cases, it can also function in such a way that it burdens people with more responsibility that they can (reasonably be expected to) manage

    Current-Driven Magnetization Dynamics in Magnetic Multilayers

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    We develop a quantum analog of the classical spin-torque model for current-driven magnetic dynamics. The current-driven magnetic excitation at finite field becomes significantly incoherent. This excitation is described by an effective magnetic temperature rather than a coherent precession as in the spin-torque model. However, both the spin-torque and effective temperature approximations give qualitatively similar switching diagrams in the current-field coordinates, showing the need for detailed experiments to establish the proper physical model for current-driven dynamics.Comment: 5 pages, 2 figure

    Individual Rights, Economic Transactions, and Recognition: A Legal Approach to Social Economics

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    Modernity brought the idea of individual property rights as a com- plex phenomenon. However, economics adopted a simplistic view of property as a fundamental institution, understating the complex interaction of different rights and obligations that frame the legal environment of economic processes with an insufficiently elaborated tool. Here, a more elaborate view of legal elements will be propose

    Safety, fairness, and inclusion: transgender athletes and the essence of Rugby

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    In this paper, I link philosophical discussion of policies for trans inclusion or exclusion, to a method of policy making. I address the relationship between concerns about safety, fairness, and inclusion in policy making about the inclusion of transwomen athletes into women’s sport. I argue for an approach based on lexical priority rather than simple ‘balancing’, considering the different values in a specific order. I present justifying reasons for this approach and this lexical order, based on the special obligations of International Federations such as World Rugby. As a result, I provide a justificatory framework for the WR Guidelines that exclude transwomen from the women’s game in WR competitions. Finally, I give an account of a maximally safe, maximally fair and maximally inclusive form of sex categorisation in sport
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