Cancer cells seem to exploit mechanisms that evolve as part of physiological tolerance, which is a complementary and often beneficial form of defense. The study of physiological systems of tolerance can therefore provide insights into the development of a state of host tolerance of cancer, and how to break it. Analysis of these models has the potential to improve our understanding of existing immunological therapeutic targets, and help to identify future targets and rational therapeutic combinations. The treatment of cancer with (...) immune checkpoint inhibitors aims to reverse the progression to tolerance of cancer, and achieve an immunogenic, rather than tolerogenic, homeostasis. Broadening the efficacy and durability of checkpoint inhibitors focuses on reversing tolerance and stimulating immunogenicity in the cancer, host, and environment. Two examples of important physiological states of tolerance that may inform tolerance of cancer are microbial infection and placental reproduction. These states of tolerance result from bilateral shaping of host and non‐self, akin to immunoediting in cancer, and offer reliable models to study the immune tolerance paradigm. (shrink)

Boyer suggests that laws cannot account for ownership intuitions, but there may be situations when intuitions hew to laws almost perfectly. Laws granting governments taxation powers provide an interesting case study. We report data here suggesting that people's intuitions track law very closely, and are unaffected by manipulating a P() tag input. We propose two hypotheses to explain this finding.

This paper focuses on the inheritance of human handedness and cerebral lateralization within the more general context of structural biological asymmetries. The morphogenesis of asymmetrical structures, such as the heart in vertebrates, depends upon a complex interaction between information coded in the cytoplasm and in the genes, but the polarity of asymmetry seems to depend on the cytoplasmic rather than the genetic code. Indeed it is extremely difficult to find clear-cut examples in which thedirectionof an asymmetry is under genetic control. (...) As one possible case, there is some evidence that the direction, clockwise or counterclockwise, of rotation of the abdomen in certain mutant strains ofDrosophilais controlled by a particular gene locus, although there appears to be some degree of confusion on this point. By contrast, it is much easier to find examples in which thedegreebut not the direction of asymmetry is under genetic control. For instance, there is a mutant strain of mice in which half of the animals displaysitus inversusof the viscera. The proportion has remained at one half despite many years of inbreeding, suggesting that the mutant allele effectively cancels the normalsitusand allows the asymmetry to be specified in random fashion.Although this account does not deny that the right hemisphere of humans may be the more specialized for certain functions, it does attribute a leading or dominant role to the left hemisphere (at least in most individuals). We suggest that so-called “right-hemisphere” functions are essentially acquired by default, due to the left hemisphere's prior involvement with speech and skilled motor acts; we note, for instance, that these right-hemisphere functions include rather elementary perceptual processes. But perhaps the more critical prediction from our account is that the phenomenon of equipotentiality should be unidirectional: the right (lagging) hemisphere should be more disposed to take over left-hemisphere functions following early lesions than is the left (leading) hemisphere to take over right-hemisphere functions. We note preliminary evidence that this may be so. (shrink)

Normative realists tend to consider evolutionary debunking arguments as posing epistemological challenges to their view. By understanding Sharon Street’s ‘Darwinian dilemma’ argument in this way, they have overlooked and left unanswered her unique scientific challenge to normative realism. This paper counters Street’s scientific challenge and shows that normative realism is compatible with an evolutionary view of human evaluative judgment. After presenting several problems that her adaptive link account of evaluative judgments faces, I outline and defend an evolutionary byproduct perspective on (...) evaluative judgment. I then argue that a consideration of levels of analysis in biological–behavioral explanation suggests that the realist who adopts the byproduct perspective I outline is not at a prima facie disadvantage to the normative anti-realist on grounds of parsimony. This perspective, I suggest, can enable normative realists to answer evolutionary challenges to their view. (shrink)

Nach Freuds anfänglichen Überlegungen hat die Verdrängung die Dissoziation als die primäre Abwehrreaktion auf ein schweres Trauma eher ersetzt als ergänzt. Dabei ist es zu einem unnötigen Schisma zwischen Traumatheorien und dem Mainstream der Psychoanalyse gekommen. Um die Rolle der Dissoziation in primitiven psychischen Zuständen wieder in den Blick zu bekommen, ist ein Verständnis der triadischen Natur des Traumas nötig, die die Faktoren der Triebökonomie, des strukturellen Konflikts und Defizits sowie der Objektbeziehung umfasst. Die Behandlungstechnik erfordert eine Beschäftigung mit verdrängten (...) Phantasien, die mit dem Trauma in Verbindung stehen, mit Objektbeziehungsmustern, die in die Bindung eingreifen, sowie mit den psychoökonomischen Problemen, die die Ich-Funktionen durcheinandergebracht haben. Eine klinische Fallstudie illustriert dies. (shrink)

This review essay examines Stephen Wolfe’s The Case for Christian Nationalism, focusing on his presentation of his book as a work of Christian political theory. His claims regarding national will and agency are analyzed, and problems with them are traced to his political theology and his methodological assumptions about Christian political theory. In place of those assumptions, Kuyper’s idea of architectonic critique is recommended as a more fruitful approach to Christian political theory in the Reformed tradition.

This paper argues that Moore’s principle of organic unities is false. Advocates of the principle have failed to take note of the distinction between actual intrinsic value and virtual intrinsic value. Purported cases of organic unities, where the actual intrinsic value of a part of a whole is allegedly defeated by the actual intrinsic value of the whole itself, are more plausibly seen as cases where the part in question has no actual intrinsic value but instead a plurality of merely (...) virtual intrinsic values. (shrink)

An Essay on Human Action seeks to provide a comprehensive, detailed, enlightening, and (in its detail) original account of human action. This account presupposes a theory of events as abstract, proposition-like entities, a theory which is given in the first chapter of the book. The core-issues of action-theory are then treated: what acting in general is (a version of the traditional volitional theory is proposed and defended); how actions are to be individuated; how long actions last; what acting intentionally is; (...) what doing one thing by doing another is; what basic action is; and what omitting to do something is. Attention is also given to the concepts of causation, intention, volition, deciding, choosing, and trying. Finally, a libertarian account of free action is tentatively proposed and defended. (shrink)

First published in 2002. Routledge is an imprint of Taylor & Francis, an informa company.

ABSTRACT The calls for us to find solace in our “together-apart-ness” obfuscate the calamity of Black lives being lost in numbers exponentially higher than white bodies. In the midst of a virus that “does not discriminate,” but is aided in its deadly spread by those systems that do, the concept of “wake work” demands our time and attention.

This paper is a critical assessment of argumentum ad baculum, or appeal to force. Its principal contention is that, contrary to common opinion, there is no general fallacy of ad baculum. Most real-life ad baculums are, in fact, fairly strong. A basic logical form for reconstructed ad baculums is proposed, and a number of heterodoxical conclusions are also advanced and argued for. They include that ad baculum is not necessarily a prudential argument, that ad baculum need not involve force, violence, (...) or threats, and that one can argue ad baculum to oneself. The starting point of the paper, however, is a critical evaluation of three ad baculums from the exercise sets of Irving Copi's well-known Introduction to Logic. (shrink)

Harsh blame can be socially destructive. This article examines how harsh blame can be “civilized.” A core construct here is the historicist narrative, which is a story-like account of how a person came to be the sort of person she is. We argue that historicist narratives regarding immoral actors can temper blame and that this happens via a novel mechanism. To illuminate that mechanism, we offer a novel theoretical perspective on lay beliefs about free will. We distinguish 2 senses of (...) free will: (a) Freedom of action, which portrays the will as a dynamic choice-making mechanism and concerns whether the actor can exert volitional control via that mechanism at the time of action, and (b) Control of self-formation, which portrays the will as an enduring disposition (e.g., persistent desire to humiliate) and refers to whether the actor is truly the source of that disposition. Six experiments show that historicist narratives have no effect on perceived freedom of action, but rather temper blame by reducing perceived self-formative control. We also provide evidence against several additional theoretically derived alternative mediators (e.g., intentionality, perceived suffering). Further underlining the need to distinguish free will concepts, we show that biological narratives—unlike historicist narratives—temper blame via reductions in perceived freedom of action. Finally, to illuminate the meaning of “civilized” blame,” we show that historicist narratives specifically reduce the urge to inflict spiteful punishments on offenders, but leave intact the urge to nonviolently guide the offender toward moral improvement. (PsycINFO Database Record (c) 2017 APA, all rights reserved). (shrink)

Screening for prostate cancer with the prostate-specific antigen blood test is controversial, as evidence to date has not demonstrated such screening does more good than harm. While the potential benefit of PSA screening on reducing prostate cancer mortality has not been documented in randomized trials, many risks of PSA screening have been well documented. These risks include a substantially higher risk of a prostate cancer diagnosis over a screenee’s lifetime, false-positive and false-negative test results, possible complications from biopsies done in (...) response to suspicious test results, and substantial risks of side effects from subsequent prostate cancer treatments. Nevertheless, PSA screening is widespread in the United States, and many physicians in a national survey reported supporting routine PSA screening as well as getting PSA tests themselves, despite the lack of evidence. (shrink)

Some biochemical systems require multiple, well-matched parts in order to function, and the removal of any of the parts eliminates the function. I have previously labeled such systems "irreducibly complex," and argued that they are stumbling blocks for Darwinian theory. Instead I proposed that they are best explained as the result of deliberate intelligent design. In a recent article Shanks and Joplin analyze and find wanting the use of irreducible complexity as a marker for intelligent design. Their primary counterexample is (...) the Belousov-Zhabotinsky reaction, a self-organizing system in which competing reaction pathways result in a chemical oscillator. In place of irreducible complexity they offer the idea of "redundant complexity," meaning that biochemical pathways overlap so that a loss of one or even several components can be accommodated without complete loss of function. Here I note that complexity is a quantitative property, so that conclusions we draw will be affected by how well-matched the components of a system are. I also show that not all biochemical systems are redundant. The origin of non-redundant systems requires a different explanation than redundant ones. (shrink)

From antiquity to the present, humans have debated whether intelligent life exists elsewhere in the universe. This presentation will survey this debate, examining the roles played in it by science, religion, philosophy, and other areas of human learning. One thesis that will be developed is that whether or not extraterrestrials exist, ideas about them have strongly influenced Western thought.

Studies of economic decision-making have revealed the existence of consistent contributors, who always make contributions to the collective good. It is difficult to understand such behavior in terms of mutualistic motives. Furthermore, consistent contributors can elicit apparently altruistic behavior from others. Therefore, although mutualistic motives are likely an important contributor to moral action, there is more to morality than mutualism.

Some unpleasant emotions, like fear and disgust, appear straightforwardly susceptible to evolutionary explanation on account of the benefits they seem to provide to individuals. But guilt is more puzzling in this respect. Like other unpleasant emotions, guilt is often associated with a host of negative effects on the individual, such as psychological suffering and social withdrawal. Moreover, many guilt-induced behaviors, such as revealing one’s offenses and placing oneself before the mercy of others, could levy a cost to individuals that is (...) not outweighed by guilt’s benefits. Supposing there is an evolutionary story to tell about the origins of guilt, the question is how such negative effects were sufficiently outweighed by the potential fitness payoffs that guilt might have yielded to individuals. In this article, we consider which forms of evolution could have resulted in guilt, and whether current evidence can tell us which form of evolution most likely occurred. (shrink)

The question of the metaphysical status of the laws of physics has received increased attention in recent years. Perhaps most well-known among this work are David Lewis’s Humean supervenience and Nancy Cartwright’s dispositionalism, both of which reject the classical conception of the laws of physics as necessary and real independent of the objects they govern, arguing instead that what we call laws are shorthand for the regularities of local states of affairs or the dispositions of objects. The properties of necessity (...) and reality are generally taken to go hand-in-hand when physical laws are concerned; however, this leaves aside the possibility that the laws of physics are independently real yet contingent. This paper will explore this third option which is found in the work of Quentin Meillassoux. We will ask: if laws both exist independent of their objects and are contingent, what happens when laws change? Specifically, the possibility of metaphysical retro-causation becomes a live option. This raises both questions of the ontological status of the past as well as our epistemic access to the past after a change in physical laws. Meillassoux’s ontology of hyper-chaos weathers this challenge with its consistency intact; however, it is an open question of whether or not saving the reality of physical laws by sacrificing their necessity is worth the epistemic limits and metaphysical strangeness that it implies. (shrink)

What is Leucippus and Democritus’ theory of the beginning of life? How, if at all, did Leucippus and Democritus distinguish different kinds of living things? These questions are challenging in part because these Atomists claim that all living beings – including plants – have a share of reason and understanding. We answer these questions by examining the extant evidence concerning their views on embryology, the soul and respiration, and sense perception, thereby giving an overview of life and lifeforms in early (...) Greek atomism. We show, first, that the generation of all living beings happens through the combining of miniature copies of their parents’ atomic structures. Second, we argue that the Atomists take respiration to mark the beginning of life. Yet they do not consider respiration nor being ensouled to distinguish humans, animals, and plants from each other. Finally, because Leucippus and Democritus make little distinction between sense perception and thought, these too cannot sharply distinguish between different kinds of living beings. We conclude that Leucippus and Democritus advocated a less anthropocentric and more holistic view of the cosmos. (shrink)

Examining how, and to what effect, the phrase “truly international” became central to the rhetoric and organization of the American-hosted 1950 International Congress of Mathematicians, this essay traces the negotiation of a “truly international” discipline from mathematicians’ first international congresses around the turn of the century across two world wars and their divisive interlude. Two failed attempts to host international congresses of mathematicians in the United States, for 1924 and 1940, defined the stakes for those who became the principal organizers (...) for 1950. Combining American organizational records with contexts and sources that extend across and beyond traditional mathematical centers in Europe and North America, the essay shows how a small cohort of American mathematicians marshaled an emphatic but ambiguous “international” rhetoric to guide policies and command cooperation and support while responding to persistent challenges. Their adaptations and compromises left a lasting mark on the terms and achievements of international inclusion, cooperation, and hegemony in mathematics. (shrink)

In 1989 the Oregon Legislature voted not to wait any longer for national leaders to serve up a solution to the problem of the millions of Americans (450,000 in Oregon) who are uninsured for health care. Under the leadership of Senator John Kitzhaber, President of the Oregon Senate, the lawmakers put together a package of bills designed to bring every Oregonian the security of third party financing for needed health care. The Oregon Plan's key innovation is the idea that, from (...) a societal perspective, some health services can be declared more important than others. From that central idea came the thought that the whole range of health services could be arrayed to reflect social priorities relevant to Medicaid budgeting and the design of new health insurance programs for “the uninsured.”. (shrink)