LEIBNIZ\u2019S MIRROR THESIS. SOLIPSISM, PRIVATE PERSPECTIVES AND CONCEPTUAL HOLISM

One of the symbolic images to which Leibniz constantly entrusted the synthesis of his philosophy regards the idea of considering one and the same city from various visual perspectives. Such an image is diffused throughout all Leibniz\u2019s writings and clearly reflects the philosopher\u2019s interest for matters regarding perspective as well as optical phenomena. The point of view of its inhabitants can therefore be compared to a mirror that reflects some different portions of reality. But what do the city-viewers really see? Do they all see exactly the same thing? And assuming the plurality of points of view, how one can be sure that they share the same representative content? The paper presented here tries to offer a plausible interpretation of this topic also by linking different and somehow remote Leibnizian doctrines together

Infinite vs. Singularity. Between Leibniz and Hegel

The aim of this paper is to reconsider the controversial problem of the relationship between the philosophy of Hegel and Leibniz. Beyond the thick curtain of historical references (which have been widely developed by scholars), it is in fact possible to assume some guideline concepts (i.e. those of \u2018singularity\u2019 and \u2018infinity\u2019) to reconstruct the deep theoretical influence which Leibniz played in Hegel\u2019s thought since the Jenaer Systementwurf of 1804/05

The lingua franca of Nominalism. Sellars on Leibniz

The paper is not built upon a single central thesis. It has been composed as an attempt to investigate a virtually unexplored theme of inquiry. A kind of historiographical thesis may be put in the following terms: Leibniz can be counted among the remote, but still significant, sources of Sellars's philosophy. Such thesis, however, is meaningless unless its conceptual relevance is displayed. Therefore, it will be immediately added that Sellars's relation with Leibniz is focused on three main fundamental issues, which respectively concern (1) the concept of nature, (2) the concept of truth and (3) the concept itself of nominalism. Besides, there are other seemingly minor topics, which actually refers to the definition of abstract entities, of predicates, of proper names and to the datum/factum distinction. Another challenge the paper is faced with, regards the fact that Sellars does not consider Leibniz only in himself, given that he very often positions him in a close relation to Kant: it is as though there were multifaceted issues brought forward by Leibniz and Kant together forming a complex theoretical unity (over and above their differences). According to Sellars, in fact, they both undermine some of the most solid epistemological principles of the early modern times (mainly founded upon the subject- object lexicon and the idea of veritas as adaequatio rei et intellectus) and they both reshape the meaning of expressions such as \u201cbeing actual\u201d or \u201cbeing true\u201d

A New Stability Result for Viscosity Solutions of Nonlinear Parabolic Equations with Weak Convergence in Time

We present a new stability result for viscosity solutions of fully nonlinear parabolic equations which allows to pass to the limit when one has only weak convergence in time of the nonlinearities

Is it plausible to distinguish between "intraorganic" and "interorganic" relations within Leibniz's theory of organic matter?

The paper aims to establish whether the technical distinction introduced by scholars between “intra-monadic” and “inter-monadic” relations could also apply to the organic world. As is well known, the expression “intramonadic relations” denotates the relations which bind every individual with its internal representational states; whereas the expression “intermonadic relations” indicates the external relations, which every individual maintains with other monadic individuals. In my paper I will argue that this distinction, mutatis mutandis, might also be useful as well to differentiate the general level of “organic” qualities in bodies from the peculiar organic qualities, which are present just in living entities (like plants or animals). The ground for textual analysis will mainly be the text of the Animadversiones contra Stahl (also because in 2011 falls the anniversary of its last part, which was completed by Leibniz in 1711, when he wrote the last set of replicationes). The thesis will also be supported by other references, including the discussion of more advanced scholarly’ literature concerning these topics

The «Morbid Fear of the Subjective» : Privateness and Objectivity in Mid-twentieth Century American Naturalism

The “Morbid Fear of the Subjective” (copyright by Roy Wood Sellars) represents a key-element of the American naturalist debate of the Mid-twentieth century. On the one hand, we are witnessing to the unconditional trust in the objectivity of scientific discourse, while on the other (and as a consequence) there is the attempt to exorcise the myth of the “subjective” and of its metaphysical privateness. This theoretical roadmap quickly assumed the shape of an even sociological contrast between the “democraticity” of natural sciences and the fanaticism implicit in supernatural metaphysical systems. In between these two extremes stood phenomenology, in its early days on American soil. Its notion of “evidence”, which is less easily to naturalize than it might seem, was in fact hardly consistent with the widespread concept of “natural experience” of the world

Limit state analysis of RC structures

The inelastic static pushover analysis has become a popular tool for evaluating the seismic capacity of structures. It is able of predicting the seismic force and deformation demands by accounting in an approximate manner for the inelastic redistribution of internal forces. Though approximate in nature and based on static loading, if properly used the pushover analysis can provide many significant insights into the structural behaviour and also put forward the design weaknesses that may be hidden in the elastic analysis. The main features of the conventional pushover analysis are well described in [1], where are also emphasized limitations and possible causes that may produce loss of accuracy of the method. A basic prerequisite for successful applications of the method is an adequate knowledge of the inelastic behaviour of structural elements. This is particularly true for those structures containing shear walls that, if not properly described, may render the results of the analysis completely meaningless. In this work we show how, under appropriate hypotheses, one can introduce steel reinforcement into shear walls by appealing to a semi-analytical multi-scale approach. In particular, reinforcements are taken into account using an embedded beam approach, the usual conventional material behaviour, i.e. the the so-called parabolic-rectangular stress block for concrete and ideal elastic-plastic for steel as of Eurocode 2, and a fiber-free integration, that provides the exact solution for stress resultants over the cross section of the beam itself. Representative numerical simulations are shown that illustrate the capabilities of the proposed approach, that allows one to carry out accurate nonlinear analyses of full-scale reinforced concrete structures with relatively reduced computational effort

The subcellular trafficking of the prion protein: Characterisation of the function of the PrPc N-terminus

Transmissible spongiform encephalopathies (TSEs) are degenerative diseases of the central nervous system in humans and animals, and include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and bovine spongiform encephalopathy in cattle. These spongiform encephalopathies can manifest as sporadic, familial and acquired disorders and are caused by the conformational alteration of the non-pathogenic cellular prion protein (PrPc) into a infectious isoform denoted PrPSc. The latter therefore represents a pathogenic agent (prion) which does not contain nucleic acids. During biogenesis, PrPc undergoes posttranslational modifications with the addition of two N-linked carbohydrate chains and a glycosyl-phosphatidyl-inositol-(GPI)-anchor. Properly folded PrPc transits through the Golgi compartment and the secretory pathway and is attached to the outer leaflet of the plasma membrane by the GPI-anchor. The cellular function of the prion protein is still unknown, although binding of copper to the octapeptide repeat sequence located at its N-terminus suggests a role of PrPc related to this phenomenon. In the present work, the physiological function of the N-terminal part of PrPc in subcellular trafficking was analysed. Metabolic labelling and surface-biotinylation assays were performed in order to compare the intracellular trafficking and turnover of PrPc mutants showing specific deletions within their N-terminal sequence with those of wild type PrPc (wtPrPc). Upon transient expression of these constructs in murine neuroblastoma cells, these deletions, although not influencing the biochemical properties or the cell surface expression of these proteins, lead to a delay in their endocytosis. The prolongation of the internalisation kinetics was shown to be dependent on the length of the deletion: truncation of the complete N-terminus leads to the almost complete inhibition of internalisation. The analysis of the kinetics of degradation showed a similar correlation with the N-terminal part of PrPc, since the half-life of the PrP-mutants was significantly prolonged when compared to that of the wild type protein. Additionally performed detailed analysis of the secretory pathway with immunoprecipitation assays showed that N-terminally truncated PrP molecules reach the plasma membrane at a later time point, when compared with wtPrPc. A closer analysis of the processing of the sugar molecules linked to these proteins performing an Endo-H digestion revealed that this delay in the transport to the cell surface takes place in a cellular compartment following the mid-Golgi. The following studies were done with a chimeric protein consisting of the short N-terminal segment of Xenopus laevis, which does not contain the copper-binding octarepeat region, fused to the N-terminally truncated mouse PrPc. These studies showed that endocytosis of this protein and its transport through the secretory pathway were comparable to those of the mouse wtPrPc. It was therefore concluded that the N-terminus belonging to a phylogenetically remote species can rescue the wild type trafficking phenotype. These results indicate that the N-proximal domain of the prion protein functions as a targeting element and is essential for both transport to the plasma membrane and modulation of endocytosis. The data support a model in which the N-terminal part of PrPc represents an epitope for binding to a transmembrane receptor containing internalisation-promoting motifs or for inclusion of PrPc into the secretory raft-compartments. The present work also indicates for the first time that copper affinity of the octarepeats and subcellular trafficking represent separate aspects in the life-cycle of the prion protein.Die transmissiblen spongiformen Enzephalopathien (TSEs) bilden eine Gruppe fataler degenerativer Erkrankungen des zentralen Nervensystems von Mensch und Tier, deren bekannteste Erscheinungsformen die bovine spongiforme Enzephalopathie (BSE) beim Rind, die Traberkrankheit beim Schaf sowie die Creutzfeldt-Jakob-Erkrankung beim Menschen sind. Diese Erkrankungen können als Folge von Mutationen familiär-genetisch bedingt sein, infektiös erworben werden oder ohne erkennbare Ursache (sporadisch) auftreten. Das Auftreten und die Übertragung dieser Erkrankungen sind auf eine posttranslationale Umwandlung des apathogenen zellulären Prion-Proteins (PrPc) in eine infektiöse Isoform (Scrapie-Form, PrPSc) zurückzuführen, sodass dieses Protein ohne eine damit assoziierte Nukleinsäure als pathogenes Agens (Prion) fungiert. PrPc wird posttranslational glykosyliert und gelangt im Verlauf seiner Maturierung entlang des sekretorischen Transportwegs an die Zelloberfläche, an die es durch einen GPI-Anker verknüpft wird. Die Funktion des Prion-Proteins ist noch unbekannt, obwohl mehrere Untersuchungen eine Bindung von Kupfer an die N-terminal vorliegenden „Octarepeats“ von PrPc feststellen konnten und deshalb dem Prion-Protein eine mit dieser Eigenschaft in Zusammenhang stehende Funktion zugeschrieben wird. In der vorliegenden Arbeit wurde die physiologische Funktion des N-terminalen Anteils von PrPc im intrazellulären Transport untersucht. Mittels metabolischer Markierung und Oberflächen-Biotinylierung wurde das Verhalten und die Halbwertszeit von PrP-Mutanten, die spezifische Deletionen in der N-terminalen Sequenz aufweisen, mit denen des Wildtyp-Proteins (wtPrPc) verglichen. Nach transienter Expression dieser Mutanten in murinen Neuroblastomzellen konnte gezeigt werden, dass die Deletionen weder die biochemischen Eigenschaften noch die Zelloberfächenexpression dieser Proteine beeinflussen, aber dennoch zu einer signifikanten Verlangsamung ihrer Endozytose führen. Die Verlängerung der Internalisierungskinetik erwies sich als abhängig von der Länge der Deletion: die Abspaltung des kompletten N-Terminus erbrachte nahezu eine Inhibierung der Internalisierung des Proteins. Eine Analyse der Degradationskinetik zeigte weiterhin, dass dieser Prozess im gleichen Zusammenhang mit dem N-terminalen Bereich von PrPc steht, da die Halbwertszeit der untersuchten PrP-Mutanten deutlich länger ist als die des Wildtyp-Proteins. Wie durch detaillierte Analyse des sekretorischen Transportweges mittels Immunpräzipitation weiterhin gezeigt werden konnte, erreichen N-terminal verkürzte PrPs die äußere Plasmamembran zu einem späteren Zeitpunkt als das wtPrPc. Die Untersuchung der Glykosylierung dieser Proteine mittels Endo-H Verdau ergab, dass die Verzögerungen im Transport zur Zelloberfläche erst stattfinden, nachdem PrPc das mid-Golgi Kompartiment erreicht hat. Die Analyse eines chimären PrPs, bestehend aus dem N-Terminus von Xenopus laevis, der keine für die Kupferbindung wichtigen Octapeptide enthält, und aus einem N-terminal verkürztem Maus PrP, zeigte, dass sowohl die Endozytose als auch der sekretorische Transportweg dieses Proteins mit dem von murinem wtPrPc vergleichbar waren. Daraus konnte man schließen, dass der N-Terminus einer phylogenetisch entfernten Spezies den Wildtyp-Phenotyp wiederherstellen kann. Diese Ergebnisse deuten auf eine wichtige, konservierte Funktion des N-Terminus von PrPc im gesamten intrazellulären Transport, indem er als Signal für die korrekte Internalisierung und für die Beförderung an die Zelloberfläche dient. Die vorliegenden Daten unterstützen ein Modell, in dem der N-terminale Anteil des Prion-Proteins eine Bindungsstelle für einen transmembranen Rezeptor darstellt, der die Internalisierung bzw. die Eingliederung von PrPc in die sekretorischen Raft-Kompartimente begünstigt. Es konnte weiterhin erstmals gezeigt werden, dass Kupferbindung an die Octapeptide und intrazellulärer Transport voneinander unabhängige Entitäten im Lebenszyklus des Prion-Proteins darstellen

Lineare o non lineare? Osservazioni sullo sviluppo dei concetti di "sostanza vivente" e di "organismo" in Leibniz

The doctrine of natural machines, of organisms, of composite substances, assumes a marked consistency in Leibniz starting from his mature years (let us say, from the publishing of New System in 1965 onwards). There is no doubt, therefore, that for a full explanation of the conceptual content of the reflection of Leibniz on the nature of living substances we must turn to the classic places in which it took form: from the letters to De Volder and Lady Masham of the early 1700s, to the Nouveaux Essais, to Animadversiones contra Stahl and, naturally to Principes de la Nature et de la Grace and to the Monadologie. We can in any case ask what are the elements of specific difference are that emerge in this vast doctrinal corpus regarding those elements of the theory of the living being that had already appeared with a certain frequency in the texts of the early 1780s. Put in other words: what link of continuity subsists between the proto-theory of the living being of the 80s and that of the mature years (let us say from New System on)? Or, overturning the formulation of the problem: what elements of discontinuity suddenly break into Leibniz's reflections from the second half of the 90s compared to the immediately preceding phases of his thought? Certainly, the monads, the machines of nature. But is it possibile to focus even more clearly the lens of our observations? I mean: after a decade of intense theoretical debate on the nature of corporeal substances, on organisms, on machines of nature, is it possibile to sketch a historical picture that accounts in a coherent manner for the development of Leibniz's thought in relation to the questions raised here

Voglio misurare l'odio

The author proposes a reflection on the experience of psychological and clinical listening in different and complexes situations in which individual’s and couple’s difficulty, such as the symptom, tells about an intrapsychic conflictuality that can be shown in separated couples through an acted and dramatized conflict inside consultation setting, while in psychological infertility cases it seems to find in the body the scene of this expression. A conflict that, in any case, asks to be mentalized and decoded by clinical’s listening. L'autrice propone una riflessione sull'esperienza di ascolto psicologico e clinico in situazioni diverse e complesse, in cui il disagio individuale e di coppia, così come il sintomo, raccontano di una conflittualità intrapsichica che, nel caso di coppie separate, si esprime manifestamente nel conflitto agìto e drammatizzato nella cornice della consultazione, mentre nei casi di sterilità psicogena sembra trovare nel corpo il suo luogo di espressione. Un conflitto che, in ogni caso, chiede di essere mentalizzato e decodificato dall'ascolto del clinico