The presence and role of microbes in human cancers has come full circle in the last century. Tumors are no longer considered aseptic, but implications for cancer biology and oncology remain underappreciated. Opportunities to identify and build translational diagnostics, prognostics, and therapeutics that exploit cancer's second genome—the metagenome—are manifold, but require careful consideration of microbial experimental idiosyncrasies that are distinct from host‐centric methods. Furthermore, the discoveries of intracellular and intra‐metastatic cancer bacteria necessitate fundamental changes in describing clonal evolution and selection, (...) reflecting bidirectional interactions with non‐human residents. Reconsidering cancer clonality as a multispecies process similarly holds key implications for understanding metastasis and prognosing therapeutic resistance while providing rational guidance for the next generation of bacterial cancer therapies. Guided by these new findings and challenges, this Review describes opportunities to exploit cancer's metagenome in oncology and proposes an evolutionary framework as a first step towards modeling multispecies cancer clonality. Also see the video abstract here: https://youtu.be/-WDtIRJYZSs. (shrink)

This volume gathers together for the first time are all the key texts in a crucial debate in modern philosophy, centered on Leibniz's famous 1695 essay, the "New System of the Nature of Substances and their Communication," in which he introduced his strikingly original theory of metaphysics. His "system" became increasingly famous and drew him into discussion and development of these ideas, both in public and in private, with a variety of thinkers, most notably the great French philosopher Pierre Bayle. (...) Woolhouse's and Francks's new English edition gives the only full representation of this debate, and will therefore be essential reading for anyone who wishes to gain a proper understanding of Leibniz's philosophy and its intelletual context. All the texts are newly translated and extensively annotated; many appear in English for the first time. (shrink)

Social embeddedness, defined as the interaction of economic activities and social behavior, is used in this study as a conceptual tool to describe the growing phenomenon of food community networks (FCNs). The aim in this paper was to map the system of relations which the FCNs develop both inside and outside the network and, from the number of relations, it was inferred the influence of each FCN upon the formation of new socially embedded economic realities. A particular form of FCN (...) was taken under consideration: solidarity purchase groups (SPGs). Performed with the aid of social network analysis on a sample of SPGs in Sicily (a region in southern Italy), the study allowed us to identify a relational (internal) social embeddedness, in which groups of consumers and farmers are directly influenced by reciprocal interactions, giving rise to more or less numerous links of reciprocity and trust depending on the number of interactions. It was also identified a structural (external) social embeddedness, generated by the nature of relations that the SPGs undertake with the various social actors. From the results of our analysis it emerges that SPGs lie at the intersection of many social realities, influencing them and in turn being influenced by such realities. We highlight the major role played by consumer and environmental associations in affecting the phenomenon of social embeddedness. (shrink)

This chapter offers a proceduralist argument against capital punishment. More specifically, it contends that the possibility of irrevocable mistakes precludes the just administration of the death penalty. At stake is a principle of political morality: legal institutions must strive to remedy their mistakes and to compensate those who suffer from wrongful sanctions. The incompatibility of remedy and execution is the crux of the irrevocability argument: because the wrongly executed cannot enjoy the morally required compensation, execution is impermissible. Along with defending (...) his key premises, Yost explains the complicated role that sentencing uncertainty plays in the argument. He concludes by noting some of the flaws in substantive consequentialist and retributivist justifications of capital punishment. (shrink)

Plato's dialogues frequently criticize traditional Greek myth, yet Plato also integrates myth with his writing. Daniel S. Werner confronts this paradox through an in-depth analysis of the Phaedrus, Plato's most mythical dialogue. Werner argues that the myths of the Phaedrus serve several complex functions: they bring nonphilosophers into the philosophical life; they offer a starting point for philosophical inquiry; they unify the dialogue as a literary and dramatic whole; they draw attention to the limits of language and the limits of (...) knowledge; and they allow Plato to co-opt cultural authority as a way of defining and legitimating the practice of philosophy. Platonic myth, as a species of traditional tale, is thus both distinct from philosophical dialectic and similar to it. Ultimately, the most powerful effect of Platonic myth is the way in which it leads readers to participate in Plato's dialogues and to engage in a process of self-examination. (shrink)

Many books explain what is known about the universe. This book investigates what cannot be known. Rather than exploring the amazing facts that science, mathematics, and reason have revealed to us, this work studies what science, mathematics, and reason tell us cannot be revealed. In The Outer Limits of Reason, Noson Yanofsky considers what cannot be predicted, described, or known, and what will never be understood. He discusses the limitations of computers, physics, logic, and our own thought processes. Yanofsky describes (...) simple tasks that would take computers trillions of centuries to complete and other problems that computers can never solve; perfectly formed English sentences that make no sense; different levels of infinity; the bizarre world of the quantum; the relevance of relativity theory; the causes of chaos theory; math problems that cannot be solved by normal means; and statements that are true but cannot be proven. He explains the limitations of our intuitions about the world -- our ideas about space, time, and motion, and the complex relationship between the knower and the known. Moving from the concrete to the abstract, from problems of everyday language to straightforward philosophical questions to the formalities of physics and mathematics, Yanofsky demonstrates a myriad of unsolvable problems and paradoxes. Exploring the various limitations of our knowledge, he shows that many of these limitations have a similar pattern and that by investigating these patterns, we can better understand the structure and limitations of reason itself. Yanofsky even attempts to look beyond the borders of reason to see what, if anything, is out there. (shrink)

We propose a formal framework for interpretable machine learning. Combining elements from statistical learning, causal interventionism, and decision theory, we design an idealised explanation game in which players collaborate to find the best explanation for a given algorithmic prediction. Through an iterative procedure of questions and answers, the players establish a three-dimensional Pareto frontier that describes the optimal trade-offs between explanatory accuracy, simplicity, and relevance. Multiple rounds are played at different levels of abstraction, allowing the players to explore overlapping causal (...) patterns of variable granularity and scope. We characterise the conditions under which such a game is almost surely guaranteed to converge on a optimal explanation surface in polynomial time, and highlight obstacles that will tend to prevent the players from advancing beyond certain explanatory thresholds. The game serves a descriptive and a normative function, establishing a conceptual space in which to analyse and compare existing proposals, as well as design new and improved solutions. (shrink)

MYC is a transcription factor, which not only directly modulates multiple aspects of transcription and co‐transcriptional processing (e.g. RNA‐Polymerase II initiation, elongation, and mRNA capping), but also indirectly influences several steps of RNA metabolism, including both constitutive and alternative splicing, mRNA stability, and translation efficiency. As MYC is an oncoprotein whose expression is deregulated in multiple human cancers, identifying its critical downstream activities in tumors is of key importance for designing effective therapeutic strategies. With this knowledge and recent technological advances, (...) we now have multiple angles to reach the goal of targeting MYC in tumors, ranging from the direct reduction of MYC levels, to the dampening of selected house‐keeping functions in MYC‐overexpressing cells, to more targeted approaches based on MYC‐induced secondary effects. (shrink)

From the concrete experience of war, Michael S. Yandell constructs a phenomenology of “negative revelation” in which false or distorted claims of goodness and justice disintegrate and become meaningless, adding depth to the term moral injury.

t. 1. Apo ton prōto skeptomeno anthrōpo mechri ton 6. aiōna M.Ch. -- t. 2. Apo ton 7. aiōna M.Ch. mechri to sēmera.

Kant famously insists that free will is a condition of morality. The difficulty of providing a demonstration of freedom has left him vulnerable to devastating criticism: critics charge that Kant's post-Groundwork justification of morality amounts to a dogmatic assertion of morality's authority. My paper rebuts this objection, showing that Kant offers a cogent demonstration of freedom. My central claim is that the demonstration must be understood in practical rather than theoretical terms. A practical demonstration of x works by bringing x (...) into existence, and what the demonstration of freedom brings into existence is a moral will, a will regulated by the moral law and capable of acting in accordance with it. Since to act morally is to act freely, bringing a moral will into existence actualizes our capacity for freedom and demonstrates that we possess it. To confirm the viability of such a demonstration, Kant must establish that agents can regulate their wills by practical principles, and that practical judgments are efficacious of themselves (i.e., that non-Humean motivational internalism is true). Kant, I argue, is successful on both counts. (shrink)

Purpose. To examine the existential anthropology of G. Marcel and E. Minkowski, in order to demonstrate the necessity of distinguishing the universal-spiritual, as human in human being, apart from the individual-existential in him, and to reveal the hierarchical correlation of biosocial, existential and spiritual spheres in personality. Theoretical basis. Within existential philosophy the author differentiates two separate traditions and proceeds from the insufficiency of the distinction of existential sphere, proposed by phenomenological tradition, showing the necessity of its correlation with the (...) spiritual sphere as a sphere of humanity, proposed by non-phenomenological tradition of G. Marcel and E. Minkowski. Originality. The author presents the anthropological conception of G. Marcel and E. Minkowski, in which human personality is understood as unity of individual-existential and universal-spiritual, which requires a special trans-empirical field of culture, which contains senses, images and symbols of humanity. Also, the author presents the recent developments of existential thinkers in distinguishing existential and spiritual dimensions, both not reducible to the physical and social dimensions. Conclusions. In both existential traditions, the specifically human was founded as a trans-biological and trans-social phenomenon, which appears as indefinable and non-predetermined. But in first tradition, humanity is understood as an existence, as a unique individuality, "project", variant of humanity, equivalent to other variants, and universal is understood as a community of human condition in the world. While in the second tradition, the universal is understood as spiritual. Thus, horizontal level of our private existence, as the process of movement from birth to death, is supplemented by vertical of human, universal ideals and images. Humanity appears as a task, on the way to which human being transcends beyond the limits of his individual "self" to the "super-individual", through inclusion into spiritual community, into universal culture. (shrink)

Dmitri Nikulin is one of the few contemporary philosophers to have devoted books to the topic of dialogue and the dialogical self, especially in the last fifteen years. Yet his work on dialogue and the dialogical has received scant attention by philosophers, and this neglect has hurt the ongoing development of contemporary philosophical work on dialogicality. I want to address this lacuna in contemporary philosophical scholarship on dialogicality and suggest that, although Nikulin’s account is no doubt insightful and thought-provoking, it (...) is problematic for two main reasons: first, his account fails to recognize the proper relationship between dialogue and agency; and second, his enumeration of the necessary and sufficient conditions for dialogue contains conceptual inconsistencies. (shrink)

In this original work of cultural criticism, Allen S. Weiss explores the meaning of radio to the modern imagination.