The size and organization of the brain are determined by the activity of progenitor cells early in development. Key mechanisms regulating progenitor cell biology involve miRNAs. These small noncoding RNA molecules bind mRNAs with high specificity, controlling their abundance and expression. The role of miRNAs in brain development has been studied extensively, but their involvement at early stages remained unknown until recently. Here, recent findings showing the important role of miRNAs in the earliest phases of brain development are reviewed, and (...) it is discussed how loss of specific miRNAs leads to pathological conditions, particularly adult and pediatric brain tumors. Let‐7 miRNA downregulation and the initiation of embryonal tumors with multilayered rosettes (ETMR), a novel link recently discovered by the laboratory, are focused upon. Finally, it is discussed how miRNAs may be used for the diagnosis and therapeutic treatment of pediatric brain tumors, with the hope of improving the prognosis of these devastating diseases. (shrink)

This chapter critically examines various proposals for liability of a person to defensive harm. Drawing on the idea that there is an important relationship between a person’s liability to be harmed and the enforceable duties that she incurs as a result of posing a threat to others, it demonstrates that no simple account of liability will be successful. As there are many considerations that bear on the duties that a person has, there are many considerations which bear on a person’s (...) liability to be harmed. This general claim is supported through a demonstration both that culpability without causation can ground liability, and that causal contribution without culpability can ground liability. (shrink)

The book outlines the contribution of passivity to the constitution of phenomena as diverse as temporal syntheses, perceptual associations, memory fulfillment and cross-cultural communication.

This debate, I shall argue, has everything to do with Aristotle. Aristotle raises the charge of epiphenomenalism himself against a theory that seems to have close affinities to his own, and he offers what has the makings of an emergentist response. This leads to controversy within his own school. We find opponents ranged on both sides, starting with his own pupils, several of whom are stout defenders of epiphenomenalism, and culminating in the developed emergentism of later commentators. Aristotle’s theory and (...) the debate that ensued are thus quite relevant to contemporary discussions. But first we need to get clear on terms. (shrink)

Two hundred and twenty-six state employees completed a structured questionnaire that investigated their ethical values and training needs. Top management were more likely to have attitudes against cronyism and giving advantage to others. Individuals higher in the organizational hierarchy, and female employees were more likely to believe that discriminatory practices were an ethical concern. In addition, employees with a larger number of clients outside of the organization were more supportive of the need to maintain strict confidentiality in business dealings. Employees'' (...) awareness and use of the organization''s code of conduct generally proved to be poor predictors of ethical values. Other analyses revealed that a variety of sociodemographic factors, job characteristics and ethical values predicted specific areas of training needs in ethics. (shrink)

From 1929 through 1944, Wittgenstein endeavors to clarify mathematical meaningfulness by showing how (algorithmically decidable) mathematical propositions, which lack contingent "sense," have mathematical sense in contrast to all infinitistic "mathematical" expressions. In the middle period (1929-34), Wittgenstein adopts strong formalism and argues that mathematical calculi are formal inventions in which meaningfulness and "truth" are entirely intrasystemic and epistemological affairs. In his later period (1937-44), Wittgenstein resolves the conflict between his intermediate strong formalism and his criticism of set theory by requiring (...) that a mathematical calculus (vs. a "sign-game") must have an extrasystemic, real world application, thereby returning to the weak formalism of the Tractatus. (shrink)

ABSTRACT There has been much discussion regarding the acceptable use of sedation for palliation. A particularly contentious practice concerns deep, continuous sedation given to patients who are not imminently dying and given without provision of hydration or nutrition, with the end result that death is hastened. This has been called ‘early terminal sedation’. Early terminal sedation is a practice composed of two legally and ethically accepted treatment options. Under certain conditions, patients have the right to reject hydration and nutrition, even (...) if these are life‐sustaining. Patients are also entitled to sedation as palliation for intolerable, intractable suffering. Though early terminal sedation is thought to be rare at present, the changing nature of palliative medicine suggests its use will increase. Arguments regarding early terminal sedation have failed to recognize early terminal sedation as a distinct legal and ethical entity. It can be seen as both the simple sum of treatment refusal and sedation for palliation, analogous to terminal sedation. It can also be seen as an indivisible palliative treatment, more analogous to assisted suicide or euthanasia. But ultimately, it is wholly analogous neither to terminal sedation given when death is imminent, nor to assisted suicide or euthanasia. This paper contends that early terminal sedation should be considered as a distinct entity. Such a reconception promises to provide a way forward in the debate, practice and policy regarding this contentious area of palliative medicine. (shrink)

It seems uncontroversial that Dalton wrongly believed that atoms are indivisible. However, the correct analysis of Dalton’s belief and the way it relates to contemporary beliefs about atoms is, on closer inspection, far from straightforward. In this paper, I introduce four features that any candidate analysis is plausibly bound to respect. I argue that theories that individuate concepts at the level of understanding are doomed to fail in this endeavor. I formally sketch an alternative and suggest that cases such as (...) the one presented provide support for the claim that the genuine source for concept individuation is public sharable thought. (shrink)

A hemi-implicative lattice is an algebra \((A,\wedge,\vee,\rightarrow,1)\) of type (2, 2, 2, 0) such that \((A,\wedge,\vee,1)\) is a lattice with top and for every \(a,b\in A\), \(a\rightarrow a = 1\) and \(a\wedge (a\rightarrow b) \le b\). A new variety of hemi-implicative lattices, here named sub-Hilbert lattices, containing both the variety generated by the \(\{\wedge,\vee,\rightarrow,1\}\) -reducts of subresiduated lattices and that of Hilbert lattices as proper subvarieties is defined. It is shown that any sub-Hilbert lattice is determined (up to isomorphism) by (...) a triple (_L_, _D_, _S_) which satisfies the following conditions: _L_ is a bounded distributive lattice, _D_ is a sublattice of _L_ containing 0, 1 such that for each \(a, b \in L\) there is an element \(c \in D\) with the property that for all \(d \in D\), \(a \wedge d \le b\) if and only if \(d \le c\) (we write \(a \rightarrow _D b\) for the element _c_), and _S_ is a non void subset of _L_ such that _S_ is closed under \(\rightarrow _D\) and _S_, with its inherited order, is itself a lattice. Finally, the congruences of sub-Hilbert lattices are studied. (shrink)

Sometimes Strauss argues as if he thought it possible to understand man without raising questions about his relations to other things, and hence about his place in the whole. But when they are viewed in their broader context, such arguments are seen not to be his final word. Man's humanity cannot be understood in its own terms alone. The human soul differs from everything else in that it is "... open to the whole and therefore more akin to the whole (...) than anything else is." In ordinary usage, "whole" implies completeness and autonomy. But the openness of the soul--i.e., of a part--to the whole can only mean that the whole is open to itself. The whole is, then, not, in the ordinary sense of the term, whole. Nor is the soul which is "open" to it. Stripped of myths, "... the human soul is... more akin to the whole than anything else is" because neither of them is whole. The same conclusion follows when one tries to understand the definition of the philosopher as the man animated by quest for knowledge of the whole. Qua philosopher he knows neither that there is a whole, nor what it might be if there were one. To define the philosopher as the man who knows that he does not know only paraphrases the difficulty. It does not solve it. For "know" is here used equivocally. The same equivocation is at play in the comment "... one cannot know that one does not know without knowing what one does not know". Admittedly "knowledge of ignorance is not ignorance." The philosopher believes and perhaps divines more than he actually knows. All men do. The essential difference between the philosopher and other men may well consist in the fact that the philosopher distinguishes more conscientiously than do others between what he knows and what he believes, and that he strives more single-mindedly than do they to transform as large a share of his beliefs as possible into knowledge. He may conceivably at some point be said to have reached the stage where his aspirations have become reasoned expectations. But that is as far as he can possibly go as long as he remains a philosopher and has not become a wise man or a god. Until and unless the philosopher knows, in the strong sense of the term, he can no more decide whether his aspirations could be fulfilled than he can swim before getting wet. (shrink)

On the face of it, On Tyranny is a straightforward commentary on Xenophon's dialogue Hiero or Tyrannicus. As such it is a very model of thoroughness and learning. It amply repays careful study, and it goes a long way toward explaining Strauss's influence in training a generation of scholars. The dialogue proper takes up just under 20 pages. Its analysis runs to 90-odd pages, followed by another 30 pages of tightly packed notes that are largely devoted to parallels between the (...) Hiero, Xenophon's teaching as a whole, and the teachings of Plato, of Aristotle and, to a lesser extent, of Cicero. What at first appears as an exercise in textual analysis soon reveals itself as a much broader undertaking: the delineation of the main features of classical political philosophy. Strauss does not mean to deny that differences in perspective, procedure, and even conclusions separate the major representatives of classical political philosophy. He does want to maintain, however, that their agreements are more fundamental than are their differences. But even this is incidental to his main purpose: to understand classical political philosophy for the guidance it might provide in understanding the great moral and political problems that confront us here and now. He conceives of these problems in large measure as the consequence of modern philosophy, of what he calls "the modern project." But modern philosophy cannot be understood on its own terms alone any more than it can be understood by directly confronting it with the phenomena. For it does not owe its most characteristic features to such a confrontation. It owes them, rather, to the fact that, from its very outset, it defined itself in explicit contrast to classical philosophy. Modern philosophy is essentially derivative. It presupposes the tradition it opposes. Classical philosophy, and in particular classical political philosophy, on the other hand "... belongs to the fertile moment when all political traditions were shaken, and there was not yet in existence a tradition of political philosophy." Hence "only in the light of the quarrel between the ancients and the moderns can modernity be understood. By rediscovering the urgency of this quarrel we return to the origins of modernity." It further follows from this line of reasoning that the quarrel must be re-kindled if we are once again to gain access to the phenomena themselves. To this end historical studies become necessary which do not presuppose that the whole issue has, for all intents and purposes, been settled in favor of the moderns. The most basic and most constant assumption of Strauss's historical studies is, therefore, the assumption that classical philosophy is truer than are any of the teachings that criticize or reject it. The passion and the inventiveness with which he defends this assumption sufficiently prove that he does not put it forward merely for reasons of method or of rhetoric. Yet it seems to fall short of being his settled belief. By stressing his agreements with the ancients and his disagreements with the moderns, by holding the moderns responsible for the great problems that face us while calling for a restoration of classical political philosophy, he fosters the impression that his own views coincide fully with those of classical political philosophy. But even if classical political philosophy spoke with a single clear voice, the fact remains that "no competent man of our age would regard as simply true the complete teaching of any thinker of the past." Presumably only someone who thinks himself competent would issue such a warning. (shrink)

This is a response to the four essays on Wrongs and Crimes.

Understanding how neurons represent, process, and manipulate information is one of the main goals of neuroscience. These issues are fundamentally abstract, and information theory plays a key role in formalizing and addressing them. However, application of information theory to experimental data is fraught with many challenges. Meeting these challenges has led to a variety of innovative analytical techniques, with complementary domains of applicability, assumptions, and goals.

ABBREVIATIONS Note. If the bibliography contains only one work by a certain author, and if a certain work in the bibliography is marked with an asterisk, ...

Elizabeth Anscombe’s classic paper Causality and Determination claims that causation can be perceived. It also defends causal singularism, the idea that the causal relation is fundamentally between the particular cause and effect, and does not depend on regularities holding elsewhere in the universe. But does the former furnish an argument for the latter? The present paper analyses a special type of causal experience involving emotional reactions to present stimuli; for instance, being frightened by a spider. It argues that such experiences (...) are strongly local, in the sense that they justify belief in a local causal relation independently of our knowledge about events elsewhere in the universe. If this analysis is correct, Humean regularity theories of causation are false; and all other non-singularist theories of causation face a difficult explanatory challenge. This means that the case for causal singularism comes out considerably strengthened. (shrink)

We show that the first-order theory of a large class of plane geometries and the first-order theory of their groups of motions, understood both as groups with a unary predicate singling out line-reflections, and as groups acting on sets, are mutually inter-pretable.

Two theories of excuses are currently popular in criminal law theory: the character theory and the capacity theory. In the former the defendant claims that although he performed a wrongful action, it did not properly reflect his character. In the latter, the defendant claims that although he performed a wrongful action he lacked the capacity to do otherwise. In John Gardner's view neither claim is adequate to provide the defendant with an excuse. Excuses, Gardner thinks, are only appropriate where the (...) defendant can claim that he has lived up to the standards reasonably to be expected of a person performing the role that the defendant was performing. The view defended here is that whilst the Gardner style excuse is an excuse, both of the claims that he rejects properly ground excuses in the criminal law as well. Furthermore, they do not exhaust the field of excuses. Excuses are best seen as defences that mop up where an application of the other rules of the criminal law would not adequately serve its principles. No further ordering of excuses is possible. (shrink)

In Sparing Civilians, Seth Lazar claims that in war, with rare exceptions, killing noncombatants is worse than killing combatants. This paper raises some doubts about whether this is an important principle – at least, once we understand Lazar’s clarifications. It also suggests that however it is clarified, it seems false. And it suggests a related principle that more plausible. This related principle applies only to those with just aims, and it applies only to intentional killing rather than to all forms (...) of killing. (shrink)

The eighth-century Latin manuscript Milan, Veneranda Biblioteca Ambrosiana, L 99 Sup. contains fifteen palimpsest leaves previously used for three Greek scientific texts: a text of unknown authorship on mathematical mechanics and catoptrics, known as the Fragmentum Mathematicum Bobiense (three leaves), Ptolemy's Analemma (six leaves), and an astronomical text that has hitherto remained unidentified and almost entirely unread (six leaves). We report here on the current state of our research on this last text, based on multispectral images. The text, incompletely preserved, (...) is a treatise on the construction and uses of a nine-ringed armillary instrument, identifiable as the “meteoroscope” invented by Ptolemy and known to us from passages in Ptolemy's Geography and in writings of Pappus and Proclus. We further argue that the author of our text was Ptolemy himself. (shrink)