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)

The article reviews the book Jak to jest być świadomym? Analityczne teorie umysłu a problem świadomości [What Is It Like to be Conscious? Analytical Theories of Mind and the Problem of Consciousness], by Józef Bremer.

Political violence in the form of wars, insurgencies, terrorism and violent rebellion constitutes a major human challenge. C. A. J. Coady brings a philosophical and ethical perspective as he places the problems of war and political violence in the frame of reflective ethics. In this book, Coady re-examines a range of urgent problems pertinent to political violence against the background of a contemporary approach to just war thinking. The problems examined include: the right to make war and conduct war, terrorism, (...) revolution, humanitarianism, mercenary warriors, the ideal of peace and the right way to end war. Coady attempts to vindicate the contemporary relevance of the just war tradition to current problems without applying the tradition in a merely mechanical or uncritical fashion. (shrink)

Platónovy pokusy o určení dobra lze nalézt v celém jeho díle. Zahrnují jak relativně „univoční“ koncepci dobra ve smyslu sókratovského intelektualismu, tak pluralističtější koncepci obsaženou v politickém projektu Zákonů. Podle vývojové interpretace Platónových dialogů to naznačuje posun v autorově myšlení způsobený poznáním obtížnosti problému. Byl to přitom údajně teprve Aristotelés, kdo vyřešil Platónův problém dobra pomocí pojmu analogie. Proti této interpretaci článek zdůrazňuje, že aristotelské pojetí analogie je hluboce zakořeněno v Platónově vlastním potýkání se s rozdílem mezi morálním a politickým (...) dobrem. Byla to především Platónovo pochopení specifické hodnoty politické plurality, které stojí v základě akademického rozlišení mezi analogia a pros hen. (shrink)

It stands to reason that ekphrasis cannot be limited to the detailed but plain description of the artifact, for it often concerns what is not there in the painting as well. Authors of the ekphrases sometimes “animate” or “revive” a work of art, which manifests itself in narrativization of painted scenes. The process is also frequently supplemented by its continuation or backstory and fictitious utterances of figures depicted in the painting. The paper discusses a specific literary form of that kind (...) of “animation”, that is texts in which characters that can be seen in a painting receive the voice through the prosopopoeia and expose their selfawareness of “artificiality”. The precise subject of this study is P. Assouline’s novel Le Portrait which is narrated by baroness Betty de Rothschild, the figure from the J.A.D. Ingres’ painting. In this article, I am focusing on the mode and meaning of prosopopoeia in Assouline’s novel. I am also trying to examine whether every text that is based on the concept of a “speaking” work of art can be described as ekphrasis. (shrink)

This is the first full discussion of Philoponus' account of matter.

C. A. J. Coady; VIII*—Descartes' Other Myth, Proceedings of the Aristotelian Society, Volume 83, Issue 1, 1 June 1983, Pages 121–142, https://doi.org/10.1093/ar.

Newborn screening involves a complex logistical process, which depends on the close cooperation of many professionals, such as midwives, laboratory technicians, general practitioners and pediatricians. These professionals may encounter moral problems in the process, which have not been systematically studied before. This study fills this gap. We conducted interviews with 36 professionals involved in NBS in the Netherlands and made an inventory of the moral problems they encounter, as well as of the ways in which they tend to respond to (...) them. The moral problems professionals encounter stem from interpersonal conflicts and intrapersonal conflicts. Given the complexity of the work of NBS professionals, the study suggests that the moral problems that occur on the work floor cannot easily be solved by means of offering better or more stringent policy guidelines. Rather, it should be appreciated that professionals contribute significantly to shaping the morality of NBS with the help of their daily choices, and they should be supported in carrying out this task—for example with the help of a moral training or regular multidisciplinary moral deliberation, facilitated by an ethicist. (shrink)

Článek analyzuje funkci, kterou v díle raného M. Heideggera plní myšlenka destrukce, a zkoumá na tomto základě, jak je obecně možné charakterizovat vztah mezi hermeneutikou a destrukcí, resp. vzhledem k pozdějšímu vývoji filozofie mezi hermeneutikou a dekonstrukcí. Při analýze pojmu destrukce je položen důraz na to, jak je postup destrukce použit na tradici aristotelské substancialistické ontologie a na Kantovu teorii poznání, což jsou dvě klíčová témata raného Heideggera. Při zkoumání vztahu mezi hermeneutickou a dekonstruktivní intencí filozofování se naproti tomu článek (...) soustředí na to, jak jsou oba tyto přístupy rozvinuty u pozdějších autorů, na něž měla Heideggerova filozofie silný vliv: u J. Derridy a u H.-G. Gadamera. V závěru článku je upozorněno na to, že určité pojítko mezi hermeneutikou a dekonstrukcí lze navzdory všem rozdílům spatřovat v pojmu kritiky. (shrink)

Ten new essays critique the practice of armed humanitarian intervention, whereby one state sends its armed forces into another to protect citizens against major human rights abuses. The contributors examine a range of concerns, for instance about potential adverse effects and about ulterior motives.

Localised configurations of the free electromagnetic field are constructed, possessing properties of massive, spinning, relativistic particles. In an inertial frame, each configuration travels in a straight line at constant speed, less than the speed of lightc, while slowly spreading. It eventually decays into pulses of radiation travelling at speedc. Each configuration has a definite rest mass and internal angular momentum, or spin. Each can be of “electric” or “magnetic” type, according as the radial component of the magnetic or electric field (...) vanishes in the rest frame, and each has an “antiparticle.” Any such configuration, of electric or magnetic type, is characterized in part by a set of labels (κ, ω0, σ,l, m), where ω0 is the mean of the angular frequencies of the plane waves making up the configuration, σ is the variance of those frequencies, κ is a positive constant with dimensions of action, andl, m are angular momentum “quantum numbers” withl a positive integer andm an integer such that ‖m‖≤l. The rest energy of the “particle” is κω0, its spin is κ ‖m‖, and its lifetime is of the order of 1/σ. Its antiparticle has ω0 replaced by −ω0. (shrink)

To what extent should scientists, doctors and the community be constrained in their decision-making by a duty to posterity? How should we as a community balance our desire to benefit the present generation against the need not to irretrievably harm our successors? These questions are discussed with particular reference to genetic research and treatment that may have great potential for people suffering from genetic disease but may cause inherited changes in future generations, either deliberately or inadvertently. We conclude that the (...) community should take account of the interests of its successors but this should not immobilise us in the decisions we make for the present. (shrink)

With the dawn of the day of the Battle of Salamis in ch. 83 of Book 8, Herodotus heightens the tone of his language. An unfortunate result of his more elaborately worked writing has been failure to understand his words, and hence much misplaced editorial intervention. In particular, the words at 8.83.1, προηγρενε εῢ Χοντα μν κ πντων Θεμιστοκλης, have regularly been mistranslated. Powell even wanted to rewrite the Greek here to read: γρευε μν πρó πντων Θεμιστοκλης . Few would (...) wish to follow such a drastic and arbitrary alteration of the transmitted text, but the conjectural emendation highlights the difficulty of understanding Herodotus' words at this point. (shrink)