While outcomes for children with T-cell acute lymphoblastic leukemia have improved dramatically, survival rates for patients with relapsed/refractory disease remain dismal. Prior studies indicate that glucocorticoid resistance is more common than resistance to other chemotherapies at relapse. In addition, failure to clear peripheral blasts during a prednisone prophase correlates with an elevated risk of relapse in newly diagnosed patients. Here we show that intrinsic GC resistance is present at diagnosis in early thymic precursor T-ALLs as well as in a subset (...) of non-ETP T-ALLs. GC-resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to interleukin-7 stimulation. Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs, and a subset of ETP T-ALLs, to GCs. The combination of the GC dexamethasone and the JAK1/2 inhibitor ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent GC resistance, but not in samples with IL7-independent GC resistance. Together, these data suggest that the addition of ruxolitinib or other inhibitors of IL7 receptor/JAK/STAT signaling may enhance the efficacy of GCs in a biologically defined subset of T-ALL.Leukemia advance online publication, 30 May 2017; doi:10.1038/leu.2017.136. (shrink)

This collection of papers by prominent feminist thinkers advances the positive feminist project of remapping the moral by developing theory that acknowledges the diversity of women.

_Origins of Chinese Political Philosophy_. explores the composition, language, thought, and early history of the _Shangshu_ (Classic of Documents), showing its texts as dynamic cultural products that expressed and shaped the political and intellectual discourses of different times and communities.

_Origins of Chinese Political Philosophy_. explores the composition, language, thought, and early history of the _Shangshu_ (Classic of Documents), showing its texts as dynamic cultural products that expressed and shaped the political and intellectual discourses of different times and communities.

In this consensus report by a diverse group of academics who conduct and/or are concerned about social and behavioral genomics (SBG) research, the authors recount the often‐ugly history of scientific attempts to understand the genetic contributions to human behaviors and social outcomes. They then describe what the current science—including genomewide association studies and polygenic indexes—can and cannot tell us, as well as its risks and potential benefits. They conclude with a discussion of responsible behavior in the context of SBG research. (...) SBG research that compares individuals within a group according to a “sensitive” phenotype requires extra attention to responsible conduct and to responsible communication about the research and its findings. SBG research (1) on sensitive phenotypes that (2) compares two or more groups defined by (a) race, (b) ethnicity, or (c) genetic ancestry (where genetic ancestry could easily be misunderstood as race or ethnicity) requires a compelling justification to be conducted, funded, or published. All authors agree that this justification at least requires a convincing argument that a study's design could yield scientifically valid results; some authors would additionally require the study to have a socially favorable risk‐benefit profile. (shrink)

In 1978, the authors began a paper, “S (for Syllogism),” henceforth [S4S], intended as a philosophical companion piece to the technical solution [SPW] of the Anderson-Belnap P–W problem. [S4S] has gone through a number of drafts, which have been circulated among close friends. Meanwhile other authors have failed to see the point of the semantics which we introduced in [SPW]. It will accordingly be our purpose here to revisit that semantics, while giving our present views on syllogistic matters past, present (...) and future, especially as they relate to not begging the question via such dubious theses as A →’ A. We shall investigate in particular a paraconsistent attitude toward such theses. (shrink)

Abstract.Mandatory risk assessment is intended to reassure concerned citizens and introduce reason into the heated European controversies on genetically modified crops and food. The authors, examining a case of risk assessment of genetically modified oilseed rape, claim that the new European legislation on risk assessment does nothing of the sort and is not likely to present an escape from the international deadlock on the use of genetic modification in agriculture and food production. The new legislation is likely to stimulate the (...) kind of emotive reactions it was intended to prevent. In risk assessment exercises, scientific uncertainty is turned into risk, expressed in facts and figures. Paradoxically, this conveys an impression of certainty, while value-disagreement and conflicts of interest remain hidden below the surface of factuality. Public dialogue and negotiation along these lines are rendered impossible. The only option left to critics is to resort to claims of fear and to call for new risk assessments to be performed, on and on again. Science is allowing itself to be abused by accepting the burden of proof in matters more suited to reflection and negotiation. The specific challenge to science would be to take care of itself – rethinking the role and the limitations of science in a social context, and, thereby gaining the strength to fulfill this role and to enter into dialogue with the rest of society. Scientific communities appear to be obvious candidates for prompting reflection and dialogue on this issue. (shrink)

Martin F. Meyer untersucht die Entwicklung des lebenswissenschaftlichen Denkens von den frühsten Anfängen bis zur Geburt der wissenschaftlichen Biologie bei Aristoteles. Der Autor zeigt im ersten Teil, wie sich zentrale biologische Begriffe (Leben, Lebewesen, Mensch, Tier, Pflanze) im frühgriechischen Denken, bei den Vorsokratikern und in der sogenannten Hippokratischen Medizin entwickelt haben. Im zweiten Teil beleuchtet er die Ziele, Methoden und die Systematik der von Aristoteles begründeten Biologie im Kontext seines naturwissenschaftlichen Programms.​.

The dominant consequentialist, Kantian, and contractualist theories by virtue ethicists such as G.E.M. Anscombe, Alisdair MacIntyre, Martha Nussbaum, and Michael Stocker have been criticized for their neglect of the emotions. There are three reasons why it might be a mistake for moral philosophy to neglect the emotions. Emotions have an important influence on motivation, and proper cultivation of the emotions is helpful, perhaps essential, to our ability to lead ethical lives. It is a plausible thesis that an ethical life involves (...) feeling certain ways in certain circumstances and acting from certain feelings in certain circumstances. Some emotions are forms of ethical perception, judgment, or even knowledge. This chapter examines the Ancient ethical tradition that inspires the virtue ethicists' critique, revealing versions of each of these three theses in one guise or another. It first considers the medieval transformations of the ancient doctrines, and then focuses on the third, more contentious thesis, distinguishing several versions of it in the moral philosophies of the seventeenth and eighteenth century and indicating some contemporary exemplars as well. (shrink)

Biology is the most extensive field in the Corpus Aristotelicum. In his fundamental work De anima, Aristotle tries to fix the borders of this life science. The term ψυχή has a twofold explanatory status. On the one hand, ψυχή is understood as a principle of all living beings. On the other hand, it is understood as a cause of the fact that all living beings are alive. The paper is divided into three sections. The first part shows why Aristotle discusses (...) these issues in a work entitled Περὶ ψυχῆς. Since Pythagoras and Heraclitus, ψυχή was understood as a life principle: Pythagoras believed that men, animals and plants share the same nature: they are all ἔμψυχα and they are homogenous qua ψυχή. The second part of this article deals with Aristotle’s definition of the soul in DA II: ψυχή is the principle of all living things. This establishes the external criteria to divide living and non-living beings and the internal criteria to divide living beings. The third part of this paper is concerned with the methodological consequences of this definition: the life functions are the central explanandum in Aristotle’s biology. De anima II defines such various life-functions as nourishment, sense-perception and locomotion. These capacities contour the main fields of the philosopher’s biological investigation. For Aristotle, the faculty of reproduction is a subtype of nourishment. Reproduction is the most important and most natural function of all living beings. Genetics is, therefore, the most important field in Aristotle’s biology. (shrink)

What made Socrates so special that he became the object of mockery, slander and hate? The answer in the Apology is expressed in the formula of the ‘Socratic pragma’. Plato claims that Socrates’ philosophical enterprise was a reaction to the Delphic oracle according to which no living Greek was wiser than Socrates. But does this really explain what it pretends to explain? The paper argues that this explanation tells us more about Plato’s philosophical approach than about this alleged turning point (...) in Socrates’ life. Our understanding of Socrates’ philosophical development should be based on other Platonic dialogues and the Old Comedy as well, for they inform us about the historical shift of philosophical interest from questions of physics to questions of ethics and political anthropology. (shrink)

In 1978, the authors began a paper, “S,” henceforth [S4S], intended as a philosophical companion piece to the technical solution [SPW] of the Anderson-Belnap P–W problem. [S4S] has gone through a number of drafts, which have been circulated among close friends. Meanwhile other authors have failed to see the point of the semantics which we introduced in [SPW]. It will accordingly be our purpose here to revisit that semantics, while giving our present views on syllogistic matters past, present and future, (...) especially as they relate to not begging the question via such dubious theses as A →’ A. We shall investigate in particular a paraconsistent attitude toward such theses. (shrink)

The core thesis of the paper is that the constitution of biological science begins with a conceptual innovation with far-reaching consequences with effect up to the present: by conceiving the parts of living beings as organs (that is, as tools), Aristotle laid the foundation stone for a functional explanation of animate nature. Comparative anatomy is thus transformed from a merely descriptive to an explanatory theory. The point of the discussion is above all that a functional explanation must not be confused (...) with the sort of teleology according to which the function of an organ is understood as the cause of its existence. The first section outlines the theoretical motives that Aristotle adduces in arguing for biology (against contemporary contempt for biological research). The second step addresses the significance of the parts of animals in Aristotle's larger collection of zoological material, the Historia animalium . The third section demonstrates how in the major explanatory work De partibus animalium the term organon takes on the status of a key methodological concept. Finally, the fourth section discusses the significance of the Aristotelian determination of the organic with respect to current discourses in natural science. (shrink)

The language comprehension system preferentially assumes that agents come first during incremental processing. While this might reflect a biologically fixed bias, shared with other domains and other species, the evidence is limited to languages that place agents first, and so the bias could also be learned from usage frequency. Here, we probe the bias with electroencephalography (EEG) in Äiwoo, a language that by default places patients first, but where sentence-initial nouns are still locally ambiguous between patient or agent roles. Comprehenders (...) transiently interpreted nonhuman nouns as patients, eliciting a negativity when disambiguation was toward the less common agent-initial order. By contrast and against frequencies, human nouns were transiently interpreted as agents, eliciting an N400-like negativity when the disambiguation was toward patient-initial order. Consistent with the notion of a fixed property, the agent bias is robust against usage frequency for human referents. However, this bias can be reversed by frequency experience for nonhuman referents. (shrink)