The gain of a selective advantage in cancer as well as the establishment of complex traits during evolution require multiple genetic alterations, but how these mutations accumulate over time is currently unclear. There is increasing evidence that a mutator phenotype perpetuates the development of many human cancers. While in some cases the increased mutation rate is the result of a genetic disruption of DNA repair and replication or environmental exposures, other evidence suggests that endogenous DNA damage induced by AID/APOBEC cytidine (...) deaminases can result in transient localized hypermutation generating simultaneous, closely spaced (i.e. “clustered”) multiple mutations. Here, we discuss mechanisms that lead to mutation cluster formation, the biological consequences of their formation in cancer and evidence suggesting that APOBEC mutagenesis can also occur genome‐wide. This raises the possibility that dysregulation of these enzymes may enable rapid malignant transformation by increasing mutation rates without the loss of fitness associated with permanent mutators. (shrink)

Somatic mutations arising in human skin cancers are heterogeneously distributed across the genome, meaning that certain genomic regions (e.g., heterochromatin or transcription factor binding sites) have much higher mutation densities than others. Regional variations in mutation rates are typically not a consequence of selection, as the vast majority of somatic mutations in skin cancers are passenger mutations that do not promote cell growth or transformation. Instead, variations in DNA repair activity, due to chromatin organization and transcription factor binding, have been (...) proposed to be a primary driver of mutational heterogeneity in melanoma. However, as discussed in this review here, recent studies indicate that chromatin organization and transcription factor binding also significantly modulate the rate at which UV lesions form in DNA. The authors propose that local variations in lesion susceptibility may be an important driver of mutational hotspots in melanoma and other skin cancers, particularly at binding sites for ETS transcription factors. (shrink)

When do descriptive regularities become prescriptive norms? We examined children's and adults' use of group regularities to make prescriptive judgments, employing novel groups that engaged in morally neutral behaviors. Participants were introduced to conforming or non-conforming individuals. Children negatively evaluated non-conformity, with negative evaluations declining with age. These effects were replicable across competitive and cooperative intergroup contexts and stemmed from reasoning about group regularities rather than reasoning about individual regularities. These data provide new insights into children's group concepts and have (...) important implications for understanding the development of stereotyping and norm enforcement. (shrink)

Psychological essentialism is a folk theory characterized by the belief that a causal internal essence or force gives rise to the common outward behaviors or attributes of a category's members. In two studies, we investigated whether 4- to 7-year-old children evidenced essentialist reasoning about heart transplants by asking them to predict whether trading hearts with an individual would cause them to take on the donor's attributes. Control conditions asked children to consider the effects of trading money with an individual. Results (...) indicated that children reasoned according to essentialism, predicting more transfer of attributes in the transplant condition versus the non-bodily money control. Children also endorsed essentialist transfer of attributes even when they did not believe that a transplant would change the recipient's category membership. This finding runs counter to predictions from a strong interpretation of the “minimalist” position, an alternative to essentialism. (shrink)

Aristotle contends that in perception the sense organ is “made like” its object, but only “in a certain way.” Much controversy has surrounded these remarks, primarily about how to understand being “made like.” One camp has understood this to require literal exemplification, such that the sense organs manifest the sensible qualities of their objects. Others have understood likeness to require no physical alteration at all in the sense organs.I accept as a starting point in this paper that understanding perceptual likeness (...) in terms of exemplification is a non-starter. By doing so, however, I also reject the easiest and most direct understanding of what it means for the sense organs to be “made like” their objects. Others who have shared this assumption have suggested that likeness consists in “isomorphism.” Unfortunately, they have not adequately explicated how this notion is to be understood, with the result that Aristotle’s theory of perception remains crucially underdeveloped. I argue that the key is to understand the form of isomorphism at work in Aristotle’s account of thinking. (shrink)

This paper argues that a well known passage from Plato’s Meno exemplifies how to employ scaffolded learning in the philosophy classroom. It explores scaffolded learning by fully defining it, explaining it, and gesturing at some ways in which scaffolding has been implemented. We then offer our own model of scaffolded learning in terms of four phases and eight stages, and explicate our model using a well known example from Plato’s Meno as an exemplar. We believe that any practical concerns one (...) might have against the employment of scaffolded learning in the philosophy classroom ought not serve as an impediment to adopting our model. (shrink)

While Euthyphro and Apology are widely taught, they do not offer a complete picture of the variety of ways in which Socrates interacts with his interlocutors in Plato’s dialogues. Perhaps the most important point we wish to bring home is that most, if not all, of Socrates’ discussions are carefully calibrated according to a certain social awareness. Through careful analysis of sections of the dialogues, we argue that aspects of discussions between Socrates and his interlocutors should serve as lessons for (...) students and instructors. Students should see that learning to philosophize is a matter of skill development, Instructors should see that one ought to be cognizant of students’ abilities, as well as other relevant information. The upshot of paying attention to Socrates’ interactions is to augment instructors’ and students’ understanding, facilitating the cultivation and development of philosophical skills. (shrink)

We regularly teach for the Wyoming High School Institute (“HSI”), a three-week college experience for rising high school juniors. The purpose of HSI is to introduce pre-college students to subjects not regularly taught in the secondary school curriculum. In our course, we introduce moral philosophy through the use of feature films. More narrowly, we challenge the students to examine moral reasoning through analysis of the moral reasoning of characters in these films. Our pedagogical approach is based in the methods of (...) Socrates and in the technique of “scaffolding.” We attempt to show how our approach can be incorporated into any pre-college philosophy classroom. (shrink)

It's often been said that Chomsky is to linguistics what Einstein is to physics. His 1957 treatise, Syntactic Structures, initiated the so-called Chomskyan Revolution; in that book, Chomsky proposed a new linguistic theory which defined language as an innate human faculty hard-wired into our brains. Consequently, in Chomsky's view, there is a kind of "universal grammar" underlying all languages. Imagine that an alien came to Earth and observed the way we humans communicate with each other. According to Chomsky, this alien (...) would perceive all languages on Earth as pretty much the same, with only superficial variations distinguishing, for example, English from Chinese. (shrink)

Empirical research pertaining to cardiopulmonary resuscitation (CPR), clinician behaviors related to do-not-resuscitate (DNR) orders and substituted judgment suggests potential contributions to medical ethics. Research quantifying the likelihood of surviving CPR points to the need for further philosophical analysis of the limitations of the patient autonomy in decision making, the nature and definition of medical futility, and the relationship between futility and professional standards. Research on DNR orders has identified barriers to the goal of patient involvement in these life and death (...) discussions. The initial data on surrogate decision making also points to the need for a reexamination of the moral basis for substituted judgment, the moral authority of proxy decision making and the second-order status of the best interests standard. These examples of empirical research suggest that an interplay between empirical research, ethical analysis and policy development may represent a new form of interdisciplinary scholarship to improve clinical medicine. (shrink)

‘Scaffolded learning’ describes a cluster of instructional techniques designed to move students from a novice position toward greater understanding, such that they become independent learners. Our Socratic Model of Scaffolded Learning includes two phases not normally included in discussions of scaffolded learning, the preparatory and problematizing phases. Our article will illuminate this blind spot by arguing that these crucial preliminary elements ought to be considered an integral part of a scaffolding model. If instructors are cognizant of the starting position of (...) students, then students are more likely to develop a proper sense of autonomy. We turn, then, to examples from Socrates, the archetypal teacher, that cast light on the importance of preparation and problematizing for the student. Finally, we address the concern that integrating these preliminary elements into scaffolded learning would unnecessarily complicate a useful and effective pedagogical method. Ultimately, if it is effective and autonomous learners we wish to cultivate in the classroom, then something like SMSL must include preliminary elements that calibrate the instructor’s approach to the members of the class. After all, the unexamined student is not worth teaching. (shrink)

Important features of the self-concept can be located outside of the individual and inside close or related others. The authors use this insight to reinterpret data previously said to support the empathy-altruism model of helping, which asserts that empathic concern for another results in selflessness and true altruism. That is, they argue that the conditions that lead to empathic concern also lead to a greater sense of self-other overlap, raising the possibility that helping under these conditions is not selfless but (...) is also directed toward the self. In 3 studies, the impact of empathic concern on willingness to help was eliminated when oneness--a measure of perceived self-other overlap--was considered. Path analyses revealed further that empathic concern increased helping only through its relation to perceived oneness, thereby throwing the empathy-altruism model into question. The authors suggest that empathic concern affects helping primarily as an emotional signal of oneness. (shrink)

The current investigation examines the incidence of clients telling their psychotherapists of committing violent crimes for which they have not been prosecuted. Thirteen percent of the psychologists surveyed indicated that on at least one occasion a client self-disclosed to them during a psychotherapy session that he/she had murdered someone, not including the killing of another person in the line of duty in the military or as a public peace officer. One third of the psychologists had clients self-disclose an unprosecuted incident (...) of a sexual assault, and more than two thirds had clients self-disclose an unprosecuted incident of a physical assault during a psychotherapy session. Data are reported on psychotherapists' views of the impact of such disclosures on the psychotherapy relationship, adequacy of being informed regarding legal obligations after hearing such reports of violence, and adequacy of graduate preparation to deal with these clinical situations. (shrink)

The acceptability of sentences in natural language is constrained not only grammaticality, but also by the relationship between what is being conveyed and such factors as context and the beliefs of interlocutors. In many languages the critical element in a sentence (its focus) must be given grammatical prominence. There are different accounts of the nature of focus marking. Some researchers treat it as the grammatical realization of a potentially arbitrary feature of universal grammar and do not provide an explicit account (...) of its origins; others have argued, however, that focus marking is a (grammaticalized) functional solution to the problem of efficiently transmitting information via a noisy channel. By adding redundancy to highlight critical elements in particular, focus protects key parts of the message from noise. If this information‐theoretic account is true, then we should expect focus‐like behavior to emerge even in non‐linguistic communication systems given sufficient noise and pressures for efficiency. We tested this in an experiment in which participants played a simple communication game in which they had to click cells on a grid to communicate one of two line figures drawn across the grid. We manipulated the noise, available time, and required effort, and measured patterns of redundancy. Because the lines in many cases overlapped, meaning that only some parts of each line could be used to distinguish it from the other, we were able to compare the extent to which effort was expended on adding redundancy to critical (non‐overlapping) and non‐critical (overlapping) parts of the message. The results supported the information‐theoretic account of focus and shed light on the emergence of information structure in language. (shrink)

The law of torts is concerned with the secondary obligations generated by the infringement of primary rights. This work seeks to show that this apparently simple proposition enables us to understand the law of torts as found in the common law. Using primarily English materials, but drawing heavily upon the law of other common law jurisdictions, Stevens seeks to give an account of the law of torts which relies upon the core material familiar to most students and practitioners with a (...) grasp of the law of torts. This material is drawn together in support of a single argument in a provocative and accessible style, and puts forward a new theoretical model for analysing the law of torts, providing an overarching framework for radically reconceiving the subject. (shrink)