The role of the microenvironment in cancer development is being increasingly appreciated. This paper will review data that highlight an emerging distinction between two different entities: the microenvironment that altered/preneoplastic/neoplastic cells find in the tissue where they reside, and the peculiar microenvironment inside the focal lesion (tumor) that these cells contribute to create. While alteration in the tissue environment can contribute to the selective clonal expansion of altered cells to form focal proliferative lesions, the atypical, non‐integrated growth pattern that defines (...) such focal lesions leads to the appearance of what is correctly referred to as the tumor microenvironment. The latter represents a new and unique biological milieu, characterized by hypoxia, acidosis and other biochemical and metabolic alterations, including genetic instability, that can set the stage for tumor progression to occur. Thus, the two microenvironments act in sequence and play complementary roles in the development of overt neoplasia. This distinction has important implications for the understanding of disease pathogenesis and for the management of preneoplastic/neoplastic lesions at various stages of cancer development. BioEssays 29:738–744, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Cancers rely on multiple, heterogeneous processes at different scales, pertaining to many biomedical fields. Therefore, understanding cancer is necessarily an interdisciplinary task that requires placing specialised experimental and clinical research into a broader conceptual, theoretical, and methodological framework. Without such a framework, oncology will collect piecemeal results, with scant dialogue between the different scientific communities studying cancer. We argue that one important way forward in service of a more successful dialogue is through greater integration of applied sciences (experimental and clinical) (...) with conceptual and theoretical approaches, informed by philosophical methods. By way of illustration, we explore six central themes: (i) the role of mutations in cancer; (ii) the clonal evolution of cancer cells; (iii) the relationship between cancer and multicellularity; (iv) the tumour microenvironment; (v) the immune system; and (vi) stem cells. In each case, we examine open questions in the scientific literature through a philosophical methodology and show the benefit of such a synergy for the scientific and medical understanding of cancer. (shrink)

According to the Simple View of intentional action famously refuted by Bratman , φ-ing is intentional only if the agent intended to φ. In this paper I show that none of five different objections to Bratman's counter-example – McCann's , Garcia's , Sverdlik's , Stout's , and Adams's – works. Therefore Bratman's contention that SV is false still stands.

In higher eukaryotes, circadian behaviour patterns have been dissected at the molecular level in Drosophila and, more recently, in the mouse. Considerable progress has been made in identifying some of the molecular components of the clock in the fly, where two genes, period (per) and timeless (tim), are essential for behavioural rhythmicity. The PER and TIM proteins show circadian cycles in abundance, and are part of a negative feedback loop with their own mRNAs. Within the pacemaker neurons, the PER and (...) TIM products are believed to form a complex which allows them to translocate to the nucleus, but how they repress their own transcription is unclear. TIM is rapidly degraded by light, a feature which permits a compelling molecular description of both behavioural light entrainment and phase responses to light pulses. The regulation of per and tim is altered in different Drosophila tissues, however, and comparative analyses of the two genes outside the Diptera reveals further unusual patterns of tissue‐specific regulation. Evolution appears to have modified the way in which the two genes are utilised to generate circadian phenotypes. More recently, the cloning of mouse clock genes, including putative per homologues, opens up exciting possibilities for mammalian molecular chronobiology. (shrink)

According to the Simple View of intentional action famously refuted by Bratman, φ-ing is intentional only if the agent intended to φ. In this paper I show that none of five different objections to Bratman's counter-example – McCann's, Garcia's, Sverdlik's, Stout's, and Adams's – works. Therefore Bratman's contention that SV is false still stands.

In higher eukaryotes, circadian behaviour patterns have been dissected at the molecular level in Drosophila and, more recently, in the mouse. Considerable progress has been made in identifying some of the molecular components of the clock in the fly, where two genes, period (per) and timeless (tim), are essential for behavioural rhythmicity. The PER and TIM proteins show circadian cycles in abundance, and are part of a negative feedback loop with their own mRNAs. Within the pacemaker neurons, the PER and (...) TIM products are believed to form a complex which allows them to translocate to the nucleus, but how they repress their own transcription is unclear. TIM is rapidly degraded by light, a feature which permits a compelling molecular description of both behavioural light entrainment and phase responses to light pulses. The regulation of per and tim is altered in different Drosophila tissues, however, and comparative analyses of the two genes outside the Diptera reveals further unusual patterns of tissue‐specific regulation. Evolution appears to have modified the way in which the two genes are utilised to generate circadian phenotypes. More recently, the cloning of mouse clock genes, including putative per homologues, opens up exciting possibilities for mammalian molecular chronobiology. (shrink)

Frankfurt sets out to refute the principle according to which ‘a person is morally responsible for what he has done only if he could have done otherwise’. Frankfurt devises a counterexample in which an agent is intuitively responsible even though she could not have done otherwise: Suppose someone – Black, let us say – wants Jones to perform a certain action. Black is prepared to go to considerable lengths to get his way, but he prefers to avoid showing his hand (...) unnecessarily. So he waits until Jones is about to make up his mind what to do, and he does nothing unless it is clear to him that Jones is going to decide to do something other than what he wants him to do. If it does become clear that Jones is going to decide to do something else, Black takes effective steps to ensure that Jones decides to do, and that he does do, what he wants him to do. Whatever Jones's initial preferences and inclinations, then, Black will have his way … Now suppose that Black never has to show his hand because Jones, for reasons of his own, decides to perform and does perform the very action Black wants him to perform. In that case, it seems clear, Jones will bear precisely …. (shrink)

The correspondence between Leibniz and Samuel Clarke was probably the most famous and influential philosophical exchange of the eighteenth century. It focused on the clash between the Newtonian and Leibnizian world systems, involving disputes in physics, theology, and metaphysics. Vailati's book provides a comprehensive overview and commentary on this important body of letters. He not only identifies and evaluates the various arguments, but situates the views advanced by the correspondence in the context of their principal writings.

Les designers et théoriciens Ezio Manzini et Virginia Tassinari répondent à la question posée par le titre du dossier, Design is the answer, but what was the question? Si, d’une part, se pose la question de l’impact social et politique du design et de sa responsabilité dans les changements sociaux, de l’autre s’impose une réflexion sur les modes d’action du design et sur les fondements de cette action. Dans cette perspective, Manzini met en avant les pratiques d’ engendrement et (...) d’ engagement comme stratégies d’action communes et communautaires, alors que Tassinari explique comment la définition du designing (plus que du design) comme une action politique nécessite une remise en question du cadre épistémologique qui la fonde. (shrink)

Der Aufsatz sucht die Berechtigung der Leibnizschen Unterscheidung zwischen notwendigen und kontingenten Aussagen nachzuweisen. Das entscheidende Problem ist für den Autor die Frage nach der Verbindung zwischen dem Subjektbegriff und seinen Teilbegriffen, Teilbegriffe, ohne die der Subjektbegriff nicht gedacht werden kann, kommen ihm wesentlich und notwendig zu. Teilbegriffe, deren Zukommen jedoch nur bei Hinzunahme externer Bedingungen -letzlich des göttlichen Willens und seiner Wahl der besten Welt -begründet werden kann, kommen in kontingenter Weise zu. Notwendige Sätze können durch eine Analyse der (...) Begriffe in endlich vielen Schritten bewiesen werden, kontingente Sätze erfordern eine unendliche Analyse und sind deshalb nicht beweisbar. Leibniz' Annahme kontingenter Aussagen beruht daher nach der Überzeugung des Autors nicht auf der Unterscheidung zwischen Möglichkeit und Existenz, wie z. B. Russell geglaubt hat, sondern auf der Unterscheidung von Wesensbegriffen und Individualbegriffen. Mit Hilfe dieser Unterscheidung ist die Annahme kontingenter Aussagen nach der Meinung des Autors zu rechtfertigen. (shrink)

The digital revolution has generated huge changes in the world of work, with relevant implications for the Human Resources Management function. New challenges arise in facing digital work, digital employees, and digital management, such that the connection between new technologies and HRM is now described as electronic HRM. Challenges and connection entail the possibility to review the notion of HRM itself, examining new research perspectives and lines of interpretation following a Critical Management Studies approach, thus developing a more contextualized view (...) in conceiving HRM, a more expansive consideration of stakeholders, and a longer-term perspective in approaching the results of digital transformation and HRM outcomes. The article analyzes a specific organizational case, involving a multinational enterprise, and explores how the case study enhances the understanding of HRM as a social practice embedded in specific situated contexts. Such a conception enables the engagement of multiple rationalities, related to both internal and external stakeholders, overcoming a “mere antiperformance stance” and achieving forms of reconstructive reflexivity concerning the interconnection between the digital age, HRM, and the innovative generation of social value through an authentic corporate responsibility. (shrink)

Interaction between geology and mining was a decisive element for the development of stratigraphy during the eighteenth century in Germany, Sweden, England, and also Italy. This paper analyses the importance of mining background and experience, and interest in mining, among some eighteenth-century Italian scholars who studied mountains and other terrestrial reliefs paying particular attention to their rocks, strata and formations. Several primary sources are examined, from the early case of Antonio Vallisneri-who, being a physician, used the mines and the quarries (...) as necessary tools of his 'anatomy' of the mountains-up to the geological travels in the Alps and the Apennines promoted in the late eighteenth century with mining perspectives. Rigorous empirical approaches to the study of the Earth's surface-shown by scientists such as Luigi Ferdinando Marsili, Giovanni Targioni Tozzetti and Giovanni Arduino-are here investigated in the light of their mining expertise. This practical knowledge was an essential element of their theoretical work on the 'classification' of mountains. (shrink)

Este livro poderia de facto definir-se também "Razão e Lógicas da Totalidade do Real na filosofia africana contemporânea". Quatro objectivos, por assim dizer, se vislumbram logo duma leitura atenta deste texto: antes de mais a preocupação dos autores de propor nos nossos dias, uma leitura transversal da filosofia africana moderna e contemporânea a partir, diríamos, do conceito da "razão". Trata-se, neste caso, de introduzir os leitores não na história da filosofia africana como tal, mas somente, como especifica Ezio Bono, (...) de delinear "algumas questões principais que consideram ser mais significativas e recorrentes no actual debate" da filosofia africana moderna e contemporânea e a sua "traversée" (Bidima), por assim dizer, no âmbito moçambicano (José Castiano). Este texto, cuja vocação principal é transformar-se, "grosso modo", numa espécie de "Humanidades Clássicas Africanas" (Cheikh Anta Diop), se quer sintético e ao mesmo tempo panorâmico. Ele é sintético, pois os autores partem duma leitura temática (a razão). Ele é também panorâmico, já que partindo deste focus temático, eles oferecem uma visão global desta matéria, do ponto de vista histórico, teorético, epistemológico, cultural, panafricano (Procesi) e particular moçambicano (Bono e Castiano). (shrink)

La dimension immatérielle de notre réalité, grâce aux prothèses informatiques et médiatiques, est devenue de plus en plus étendue et puissante. Cet article suggère que la prétendue « dématérialisation » comporte le recel des conditions matérielles nécessaires à son propre essor. Il examine le rôle joué par la logistique dans ce processus de refoulement systématique de la jointure entre matériel et immatériel. Permettant que la marchandise puisse « apparaître » presque magiquement sur les rayons des magasins ou directement chez nous, (...) et que les déchets puissent « disparaître » tout aussi magiquement, l’organisation logistique actuelle repose sur un mix unique de transparence et d’opacisation. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Leibniz and Clarke on Miracles EZIO VAILATI IN ONE OF THE MOST tense moments of the exchange with Clarke, answering the accusation of removing God from the world, Leibniz curtly told his interlocutor he had explained the continual dependence of creation on God better than any other: But, says the author, this is all that I contended for. To this I answer: your humble servant for that, sir. (...) Our dispute consists in many other things. The question is, whether God does not act in the most regular and most perfect manner? Whether his machine is liable to disorders, which he is obliged to mend by extraordinary means? Whether the will of God can act without reason? Whether space is an absolute being? Also concerning the nature of miracles; and many such things, which make a wide difference between us.' ' Leibniz to Clarke, third letter, section 16, in A. Robinet, ed., Correspondance Leibniz-Clarke (Paris, 1957), 56-57. In the rest of the essay, the following abbreviations are used. S. Clarke, The Works (New York, 1978) = W, followed by volume and page. C. I. Gerhard, ed., Die Philosophische Schriften yon G. W. Leibniz (Hildesheim, 1961) = GP, followed by volume and page. C. I. Gerhard, ed., Die Mathematische Schriften yon G. W. Leibniz (Hildesheim, 1963) = GM, followed by volume and page. L. Loemker, ed., G. W. Leibniz. Philosophical Papers and Letters (Dordrecht, 1976) = L, followed by page. P. Remnant and J. Bennett, trans. & eds., G. W. Leibniz. New Essays on Human Understanding = NE, followed by book, chapter, and section. A. Robinet, ed., CorrtsporldangtLeibniz-Clarke (Paris, 1957) = CI, followed by letter number and section for Clarke's letters to Leibniz; Lz, followed by letter number and section for Leibniz's letters to Clarke; R, followed by page number, for other material. Since I refer to Clarke's and Leibniz's letters by letter number and paragraph, the reader can consult any edition of the Leibniz-Clarke correspondence. The most common edition of the correspondence in English is H. G. Alexander, ed., The Leibniz-Clarke Corresporu~gnge(Manchester, 1956). In addition to the correspondence it contains a helpful introduction, Clarke's appendix to the correspondence, relevant extracts from Newton's works and from Leibniz's letters relating to the correspondence, all translated into English. Robinet's edition is in effect a critical edition, containing the correspondence, various drafts by Leibniz, and relevant letters by Leibniz and his correspondents. However, it does not contain Clarke's appendix to his edition of the correspondence. Alexander's and Robinet's editions complement each other. However, neither contains Clarke's own marginal additions to the Boyle Lectures, in which he explicitly refers to Leibniz or to the correspondence. [563] 564 JOURNAL OF THE HISTORY OF PHILOSOPHY 33:4 OCTOBER i99 5 At first sight, the reference to miracles as one of the main issues of the correspondence may seem odd. When thinking about miracles and the seventeenth century, one is likely to think about Spinoza's impassioned attempt to prove that they are impossible.' Indeed, one may even think of miracles as belonging to an odd and antiquated frame of thought in fundamental antithesis with the new world-view brought about by modern science and soon to be swept away. However, this view would be wrong. Many of the philosopherscientists who directly brought about the scientific revolution, or like Clarke were closely associated with it, did believe in miracles and engaged in debates concerning their possibility and their evidential role in support of Christianity.3 Furthermore, in both Leibniz and Clarke the topic of miracles was connected with significant metaphysical issues of the power of creatures and the nature of natural laws. On these Clarke and Leibniz disagreed deeply, and consequently to a large extent the issue of miracles became a rallying cry for a deeper confrontation. In this essay, we shall look first at Clarke's and Leibniz's views on miracles in works preceding their exchange, and then at the correspondence itself. 1. CLARKE Since Clarke was a divine, it is not surprising that the motivations behind his interest in miracles were mainly apologetic. However, it would be a mistake to attribute that interest merely to his... (shrink)

Franz Rosenzweig devoted particular attention to the problem of individuality in Hermann Cohen’s philosophy. He writes that, in comparison with the individuality of the man of religion, “the human being about which aesthetics knew [...] fades now in all its aesthetic individuality to a ‘mere type’”. This statement is actually based on Cohen’s writings: in Ästhetik des reinen Gefühls, Cohen explicitly maintains that the human being that is the object of artistic representation is not a type, but rather an individual. (...) Just three years later, however, in his first book about philosophy of religion, Der Begriff der Religion im System der Philosophie, Cohen states that the human being that is represented by art is not really an individual; only the man of religion is really individual; the human being represented by art is merely a type. In this paper my aim is to argue for the thesis that these opposite statements belong to different points of view. From an aesthetic point of view the human being represented by art has to be considered as truly individual, but the systematic overview adopted in Der Begriff der Religion can teach us that the individuality of the human being represented by art can’t be maintained from a different point of view than the aesthetic one. (shrink)

In this paper I refute an apparently obvious objection to Frankfurt-type counterexamples to the Principle of Alternate Possibilities according to which if in the counterfactual scenario the agent does not act, then the agent could have avoided acting in the actual scenario. And because what happens in the counterfactual scenario cannot count as the relevant agent's actions given the sort of external control that agent is under, then we can ground responsibility on that agent having been able to avoid acting. (...) I illustrate how this objection to Frankfurt's famous counterexample is motivated by Frankfurt's own 'guidance' view of agency. My argument consists in showing that even if we concede that the agent does not act in the counterfactual scenario, that does not show that the agent could have avoided acting in the actual scenario. This depends on the crucial distinction between 'not φ-ing' and 'avoiding φ-ing'. (shrink)

1. Il pensiero -- 2. Fondi manoscritti e opere a stampa.

1. Elementi metodologici e storici.--2. Struttura logico-dialettica dell'esperienza morale.

The central focus of my dissertation is the study of the naturality in Leibniz's philosophy. Leibniz makes a number of statements concerning natural predication, including: the soul is naturally immortal; personal identity naturally presupposes the identity of the soul; reflective apperception cannot naturally deceive; matter cannot naturally think or act at a distance. These claims are not only central to Leibniz's philosophy of mind, but to his system as a whole; moreover, some of them constitute the basis of his criticism (...) of Locke in the New Essays. Nevertheless, these claims have never received the attention they deserve, nor have they been studied as a whole. ;In the course of my thesis, I argue that Leibniz's statements concerning naturality are best understood as involving a type of necessity which is weaker than logical, or metaphysical, necessity. I develop the position that a subject S is naturally P if and only if: It is logically or metaphysically possible for S not to be P , and It is logically or metaphysically impossible for S to be not-P except through miraculous divine intervention. Simply put, I argue that these two conditions follow from Leibniz's views on inherence in combination with the logical version of the Principle of Sufficient Reason, which he thinks entails that every event has a cause. ;The thesis is divided into two main parts. The first studies the general concepts, such as inherence and contingent predication, which are necessary to understand the notion of natural necessity and to show that it plays a legitimate role in Leibniz's system. The second part examines in detail some particular cases of natural necessity, such as the natural veridicality of reflection and the natural immortality of the soul, as well as the natural inability of matter to think. (shrink)