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The molecular nanoscale organization of the surfaceome is a fundamental regulator of cellular signaling in health and disease. Technologies for mapping the spatial relationships of cell surface receptors and their extracellular signaling synapses would unlock theranostic opportunities to target protein communities and the possibility to engineer extracellular signaling. Here, we develop an optoproteomic technology termed LUX-MS that enables the targeted elucidation of acute protein interactions on and in between living cells using light-controlled singlet oxygen generators (SOG). By using SOG-coupled antibodies, small molecule drugs, biologics and intact viral particles, we demonstrate the ability of LUX-MS to decode ligand receptor interactions across organisms and to discover surfaceome receptor nanoscale organization with direct implications for drug action. Furthermore, by coupling SOG to antigens we achieved light-controlled molecular mapping of intercellular signaling within functional immune synapses between antigen-presenting cells and CD8+ T cells providing insights into T cell activation with spatiotemporal specificity. LUX-MS based decoding of surfaceome signaling architectures thereby provides a molecular framework for the rational development of theranostic strategies. The spatial organization of cell surface receptors is critical for cell signaling and drug action. Here, the authors develop an optoproteomic method for mapping surface protein interactions, revealing cellular responses to antibodies, drugs and viral particles as well as immunosynapse signaling events. [ABSTRACT FROM AUTHOR]

Philosophical anarchists claim that all states lack political authority and are illegitimate, but that some states are nevertheless morally justified and should not be abolished. I argue that philosophical anarchism is either incoherent or collapses into either statism or political anarchism. [ABSTRACT FROM AUTHOR]

It seems natural to think that compromises ought to be fair. But it is false. In this paper, I argue that it is never a moral desideratum to reach fair compromises and that we are sometimes even morally obligated to try to establish unfair compromises. The most plausible conception of the fairness of compromises is David Gauthier's principle of minimax relative concession. According to that principle, a compromise is fair when all parties make equal concessions relative to how much they can gain from an agreement and relative to how much they would lose without an agreement. To find out whether reaching a fair compromise sometimes is a moral desideratum, I discuss several paradigmatic cases in friendships, economics and politics, and I try to show that even when the parties have moral reasons to refrain from trying to maximize utility in the negotiations, they do not have moral reasons to aim at a fair compromise. My second claim is that we are sometimes morally obligated to try to establish unfair compromises, in particular when we are dealing with parties that try to establish morally very bad political arrangements. In such cases, we should try to concede as little as possible to achieve an outcome that is morally acceptable. Fair compromises, in other words, are morally much more dubious than is usually appreciated. [ABSTRACT FROM AUTHOR]

Sufficientarian libertarianism is a theory of justice that combines libertarianism's focus on property rights and non-interference with sufficientarianism's concern for the poor and needy. Persons are conceived as having stringent rights to direct their lives as they see fit, provided that everyone has enough to live a self-guided life. Yet there are different ways to combine libertarianism and sufficientarianism and hence different types of sufficientarian libertarianism. In the article I present and discuss three types, and I argue that the last one overcomes the problems of the other two. The first type combines libertarianism with a sufficiency principle in what is sometimes called the 'ethics of distribution'. The second incorporates modest welfare rights into a libertarian theory of justice. The third endorses a sufficientarian Lockean proviso for practices of private property within a libertarian theory of justice. I argue that it is superior to the others. [ABSTRACT FROM AUTHOR]

Philip Pettit's republican conception of freedom is presented as an alternative both to negative and positive conceptions of freedom. The basic idea is to conceptualize freedom as non-domination, not as non-interference or self-mastery. When compared to negative freedom, Pettit's republican conception comprises two controversial claims: the claim that we are unfree if we are dominated without actual interference, and the claim that we are free if we face interference without domination. Because the slave is a widely accepted paradigm of the unfree person, the case of a slave with a non-interfering master is often cited as providing a good argument for the first republican claim and against a negative conception of freedom. One aim of this article is to raise doubts about whether this is true. The other aim of the article is to show that the prisoner-also a paradigm of the unfree person-presents a good argument against the second republican claim and in favour of a negative conception of freedom. This is called the 'prisoner-argument'. It will be argued that neither Pettit's distinction between free persons and free choices nor his distinction between compromising and conditioning factors of freedom can help to rebut the charge of the prisoner-argument. [ABSTRACT FROM AUTHOR]