Dissertations / Theses on the topic 'Spinta contributiva'

La crisi economico-finanziaria in atto e le dimensioni dell’economia sommersa pongono la fiscalità in primo piano sulla scena economica e politica. La Teoria della illusione finanziaria (1903) di Amilcare Puviani costituisce uno dei primi contributi sistematici per spiegare l’attività finanziaria dello Stato in cui i meccanismi psicologici rivestono un ruolo centrale. Con la presente ricerca ho ripreso alcune intuizioni offerte da Puviani, col fine di vagliarle sperimentalmente e contestualizzarle nel panorama più ampio della psicologia fiscale. Ciò ha comportato la costruzione di due scale, una per misurare il sacrificio fiscale percepito, l’altra per misurare la spinta contributiva, ovvero la forza morale ad adempiere i propri doveri fiscali. A parte alcune precisazioni, sono state confermate le ipotesi di riduzione della percezione del sacrificio fiscale in seguito alla rateizzazione del tributo, all’inclusione del tributo nel prezzo del bene, all’insensibilità generata dal pagamento di un tributo principale con il pagamento di un tributo di entità inferiore e associato al primo, all’avvicinamento del tributo a uno stato di benessere, o ancora nella condizione di ridotto guadagno, piuttosto che di perdita, in cui può avvenire un pagamento fiscale.

Le présent travail a pour objet d'étudier les formes grâce auxquelles, dans la philosophie de Spinoza, se résolvent ou, à tout le moins, se négocient des oppositions entre ce qui n'est pas de même ordre, entre ce qui se pose comme relativement ou absolument "autre" par rapport à telle chose donnée (un thème, un concept ou un "exemple" destine à figurer ceux-ci). A partir d'éléments recueillis dans le système et de leur commentaire, une première partie élabore des propositions susceptibles d'expliquer les raisons pour lesquelles le langage, bien qu'il soit un produit de l'"imagination", est à même d'exprimer adéquatement des pensées et des idées vraies. Dans une deuxième partie, en se réglant sur une analyse des lemmes de l'éthique II, sont examinées des questions de physique concernant l'individuation des corps composes et la possible différence entre leur "découpage" en et pour dieu (dans son entendement infini) et leur "découpage" pour nous. Une troisième partie enfin montre quels liens existent entre le thème de la suppression de l'extériorité comme condition pour un être quelconque d'une existence d'une durée illimitée et le thème de la complète altérite des natures respectives de celui qui vénère et de celui qui est l'objet de cette vénération comme condition d'un sentiment d'amour extatique voire sacré (éthique III, proposition IV, corollaire II)
The central topic of this work is to study through which ways Spinoza’s philosophy solves or, at least, negotiates oppositions between absolutely or relatively heterogeneous figures (themes, notions or examples) it yields. Starting with an analysis of theoretical material provided by Spinoza himself, the first part exhibits the reasons why, in spite of originating from "imagination", the language can express true thoughts or true ideas. The second part, pondering on the lemmas of ethics II, deals with questions of physics and, more precisely, with the problem of the individuality of any given thing; it shows that there is probably a discrepancy between the consistency of an individual thing in itself or for god and its consistency for us. The third part establishes some connections between the idea that, if its outdoor surrounding is suppressed, any being will get an everlasting duration of existence and the idea that, according to ethics III, proposition IV, corollary II, a complete dissimilarity between the nature of a worshipper and the nature of the object of his adoration is the very condition of pure or even sacred love

A propos de Dieu, la raison a besoin des deux théories de la connaissance, de la morale et de la religion : la pensée de Spinoza et celle de Kant, le dogmatisme et le criticisme. D'un côté, la raison philosophique a besoin d'une conception objective de l'absolu. Dieu est la substance. C'est la pensée de Spinoza. D'un autre côté, la raison philosophique a besoin d'une conception subjective de l'absolu, celle de Kant. Dieu n'est pas l'absolu, mais seulement une idée. L'absolu est la dignité humaine. Comme Schelling, nous pensons que Kant et Spinoza ont le même but, chercher la destination ultime du monde ; mais ils n'utilisent pas les mêmes moyens. Pour démontrer cela, notamment, nous avons du prouver que, même si Spinoza avait une conception absolue de Dieu, il n'en était pas pour autant un mystique ; et, même si l'homme exprimait la nécessité divine, il n'en était pas pour autant un automate privé de liberté. Nous avons du prouver également que, même si Kant avait une conception subjective de Dieu, il niait que la religion avait une conception originale du Christ (un être surnaturel, et pas seulement un idéal).

La religion est une donnée humaine universelle. De multiples et de diverses manières, dans leur histoire, et jusqu'à nos jours, les hommes manifestent leur désir inlassable d'une quête de dieu par leurs croyances et leurs comportements religieux. La religion tout comme la philosophie se présentent comme des besoins profonds de l'homme dans la quête de dieu, source du salut et du bonheur. Pourtant, Spinoza semble opposer philosophie et religion. C'est ce souci de séparer philosophie et religion (et les enjeux sous-jacents) qui retient notre attention chez ce philosophe souvent mal compris, condamné et vilipendé de tous côtés. Ce retour à Spinoza aujourd'hui se révèle lié à la crise ; de l'humanisme athée, négateur de la transcendance absolue, et du communisme d'une part, et a l'actuelle renaissance ; du sentiment religieux qui caractérise la fin du xx e siècle, d'autre part : crise ; devant désormais être envisagée non seulement comme une sorte de revanche de l'esprit humain contre les étroitesses du rationalisme philosophique. Scientifique et technique mais comme une interpellation au réalisme philosophique, scientifique et technique : la dimension éthique (et spirituelle) est plus que jamais essentielle à l'homme. L'homme sans Dieu est un homme perdu, vide et sans profondeur: par conséquent le but de la philosophie serait de rendre service à l'homme en l'élevant à Dieu
Religion is a universal fact of human existence. In many different ways throughout their history up to the present, men have manifested their tireless desire in their search for god through their religious beliefs and practices. Religion just as philosophy are presented as the profound needs of man in the search for god, the source of salvation and happiness. However, Spinoza seems to oppose philosophy and religion. It is this concern of separating philosophy and religion (and the underlying stakes) that has caught our interest in the works of this philosopher who is often misunderstood, condemned and vilified from all sides. The return to Spinoza today is linked to the "crisis" of atheistic humanism, contradictory to absolute transcendence, and to that of communism, on the one hand, and to the present rebirth of the religious feeling which is characteristic of the late twentieth century, on the other. This "crisis" should now be considered not only as a sort of revenge of the human spirit on the narrow-mindedness of philosophic, scientific and technical rationalism but also as call to philosophic, scientific and technical realism. The ethical (and spiritual) realm is more than ever essential to man. A man without god is a man who is lost, empty and shallow; consequently, the aim of philosophy would be to help man by elevating him towards god

xviii, 125p. : ill. (some col.) A print copy of this thesis is available through the UO Libraries. Search the library catalog for the location and call number.
Trunk control is critical for all functional movement, yet little is known about the development of trunk stability. Previous research considered the trunk to be one rigid segment ignoring the complexity of multiple spinal segments. In healthy adults spinal control is so well orchestrated that this assumption is reasonable; however during development and more specifically in pathological conditions in which spinal control is immature or compromised, this assumption may prevent accurate analysis and/or treatment of the condition. This dissertation investigates the mechanisms used by typical infants in gaining postural control of spinal segments for independent sitting. Infant data were compared to data from children with cerebral palsy (CP). The contribution of spinal segments was assessed by stabilizing the trunk in vertical alignment with four levels of support (axillae, mid-ribs, waist or hips). Documentation of postural sway of the head reflected the motor control available in the free segments of the spine. Kinematic data were collected bimonthly from 3 to 9 months of age in typically developing infants and 3-4 times over a 4 month time span in children with CP. The infants' response to external support changed in a non-linear, stage-like fashion as they transitioned from immature to mature spinal control. Head stability emerged first at higher levels of trunk support and gradually progressed in a cephalocaudal pattern to lower levels of support. Emergence of functional sitting was associated with mastery of postural control in the lower lumbar and pelvic regions of the spine. The severity of CP was related to the level of spinal control achieved. Children with severe CP had control in the cervical or upper thoracic spine while those with moderate CP had control into the mid to lower thoracic spine. In addition, behavioral patterns seen in children with CP were consistent with developmental stages seen in typical infants during acquisition of vertical alignment. These findings challenge the existing clinical practice of evaluating and treating the trunk as a single segment, offer intermediate measures of progression of spinal control and propose that a more specific approach may create the foundation for improved motor outcomes in pathological populations.
Committee in charge: Marjorie Woollacott, Chairperson, Human Physiology; Paul van Donkelaar, Member, Human Physiology; Andrew Karduna, Member, Human Physiology; Shawn Lockery, Outside Member, Biology

Spinal cord injury (SCI) is a catastrophic injury which can change the lives of an individual and their family in an instant. Much research in the field of SCI has focused upon the burden and distress brought about by SCI, however recent studies have considered individuals and families who have adjusted well to SCI, demonstrating strength and resilience. At the same time, within the wider areas of health and disability interest is growing regarding the role of spirituality in building resilience. Spirituality has been identified as a key process contributing toward family resilience, but few studies have investigated this relationship empirically. Studies of the role of spirituality after SCI are growing in number, but have tended to focus upon the injured individual, rather than the wider family context. Many questions remain unanswered regarding the role of spirituality within the family after SCI, and over time. Furthermore, very little research has considered staff perceptions or clinical implications regarding the role of spirituality after SCI.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Human Services and Social Work
Griffith Health
Full Text

Qu'est-ce qu'un signe pour Spinoza ? Quel rapport entre signification et causalité ? Une réponse peut être esquissée en parcourant la voie d'une définition génétique du signe (signum). Celle-ci nous renvoie a la nature de l'image, dont la genèse se trouve dans la théorie physique de la trace (vestigium). Si les signes ne peuvent être considérés comme l'origine de la connaissance, ils en sont les moyens nécessaires. Or la réalité moyenne qu'ils recouvrent tient au fait qu'ils sont le fruit d'un ordre de signification dont l'homme est partie en cause comme interprète imaginatif. Cependant signe, image, trace ne peuvent être limités à la connaissance humaine, ils expriment plutôt la sémiose de l'ordre commun de toute la nature. Il s'agit alors de penser la réalité du signe comme partie de la cause, et de comprendre une théorie complète de la signification comme la théorie de la causalité elle-même.

L'huile d'argane est traditionnellement utilisée au Maroc en usage externe pour le traitement des affections cutanées et en usage interne pour prévenir les troubles cardiovasculaires. Particulièrement riche en acides gras insaturés, l'huile d'argane est caractérisée également par ses composés mineurs : polyphénols, tocophérols, stérols, du squalène, et alcools triterpéniques.L'objectif de ce travail est de contribuer à la valorisation de l'huile d'argane et de ses co-produits. C'est un travail pluridisciplinaire car il est composé de deux parties : phytochimie et activité pharmacologique.Pour la partie phytochimique, onze polyphénols des co-produits d'argane ont été identifiés et quantifiés par LC-ESI-MS. Leur activité antioxydante a été évaluée par plusieurs techniques. La composition chimique des composés volatiles de l'huile d'argane a été étudiée en fonction du temps de torréfaction des amandons. Ces arômes, obtenus par microextraction en phase solide (SPME), ont été élucidés et quantifiés par CPG-MS. La deuxième partie de ce travail, a mis en exergue pour la première fois des propriétés photoprotoctrices et antioxydantes de l'huile d'argane. En effet, l'effet antioxydant de l'huile d'argane a été confirmé, lors d'une étude clinique, par la mesure sérique de la vitamine E chez des femmes ménopausées après 8 semaines de consommation de 25 ml d'huile d'argane vs huile d'olive. Les résultats sont significatifs chez le groupe consommant de l'huile d'argane. Le dosage de la vitamine E dans le sérum, a été réalisé par HPLC. Les propriétés photoprotectrices de l'huile d'argane ont été mises en évidence in-vitro par l'action des UVC sur un model moléculaire de l'ADN : la thymidylyl-(3',5')-thymidine. Les résultats préliminaires sont encourageants. L'huile d'argane, même diluée 9 fois par la paraffine, reste toujours active
Argan oil is traditionally used in Morocco as an ointment to cure some skin pathlogies or is ingested to prevent cardiovascular diseases. Its content in unsaturated fatty acids is high as is its content in polyphenols, tocopherols, sterols, squalene and triterpenic alcohols.The aim of this thesis was to increase the value of argan oil and derivatives. Our work focuses on phytochemistry and pharmacology.Concerning the phytochemical aspect, 11 polyphenols were identified and quantified by LC-ESI-SM. Their anti-oxidant activity has been evaluated as a function of kernel roasting time. Volatils obtained by microextraction were also quantified using CPG-SM.In a second section, photoprotective and anti-oxidant properties of argan oil were studied. Blood vitamine E level was determined in post menopausal women after 8 weeks of daily consumption of 25 ml of argan. Olive oil was given as a blank. Photoproptective properties of argan oil were evidenced in vitro using UV-C and Thymidylyl-(3',5') thymidine as DNA model. Preliminary results indicate a good photoproective activity even when argan oil is diluted (1/10) in parafin oil

Ce travail analyse la constitution du système spinozien à partir du concept de puissance et du rapport que ce même système entretient avec la pensée baroque espagnole. A travers la mise en oeuvre de ce rapport, le système spinozien révèle la logique de sa constitution, et cela dans trois domaines thématiques précis : ontologie, anthropologie, politique. Chacun de ces trois domaines exprime en effet une modalité constitutive de la puissance : dans l'ontologie, la puissance de l'infini, dans l'anthropologie, la puissance du désir et dans la politique, la puissance de la multitude. L'infini, le désir et la multitude permettent de définir les modalités de constitution du système spinozien par rapport au baroque espagnol ainsi que de déterminer le déploiement de son affirmation conceptuelle dans les trois domaines pris en compte : les concepts de fortune, de providence, d'appétit, d'imagination, d'affect, de vertu, de souveraineté représentent les formes privilégiées de ce déploiement. Rapportée au baroque, la philosophie spinozienne, comme système de la puissance, produit une dynamique qui correspond à la constitution de ces différentes structures de rationalité. Cette dynamique est productive et créatrice de formes de pensabilité justement parce que son affirmation se confronte au baroque. Par cette confrontation, le baroque éclate vis-à-vis du système spinozien et sa résolution devient l'une des intensités propagées par ce système
This work analyses the constituting of the Spinoza's system from the concept of power and its relation with the Spanish baroque thought. Through this relation, Spinoza's system shows its constituting in three different fields: ontology, anthropology, politics. Indeed, each field is expressing a power-constituting modality: in the field of ontology, the power of infinite; in that one of anthropology, the power of desire and in politics, the power of multitude. Infinite, desire and multitude can define the constituting modalities of Spinoza' s system in its relation with Spanish baroque. They can also determine the unfolding of its conceptual affirmation in the three fields seen above: the concepts of fortune, providence, desire, imagination, passion, virtue, sovereignty fully embody this unfolding. Spinoza's philosophy as a system of power, in its relation with baroque is creating a dynamic process in accordance with the constituting of these different structures of rationality. This dynamic process is producing some forms of thinking just because its affirmation is confronted with baroque. Through this confrontation, baroque breaks itself in front of Spinoza's system and this produces one of the intensities of the system

Recent evidence suggests an inability of those with a prior hamstring strain injury to fully voluntarily activate the previously injured muscle. This may limit gains in strength and muscle fibre length during rehabilitation, both of which are linked to increased risk of injury. Understanding the mechanisms contributing to voluntary activation deficits may assist in developing effective rehabilitation strategies and consequently limiting re-injury risk. The aim of this body of work was to determine the site(s) of failure within the nervous system underpinning lower levels of voluntary activation in participants with prior hamstring injury.

Philosophiae Doctor - PhD
HIV/AIDS has made a huge impact on human development and sexual reproductive habits in this century in the world and especially in sub-Saharan Africa. It has only recently been acknowledged that HIV/AIDS has an equal if not greater effect on or threat to people with disabilities. Survivors of traumatic spinal cord injury (TSCI) with resultant disability are incorrectly believed to be sexually inactive, unlikely to use drugs or alcohol and at less risk of violence or rape than their non-disabled peers. This group can thus be described as economically, educationally and socially disadvantaged, which in itself, suggest that they are a high-risk group for HIV infection. The overall aim of this study is to examine the factors that could contribute to the risk and vulnerability to HIV/AIDS among individuals with spinal cord injuries in South Africa. The specific objectives of the study are to assess the behavioral and protective factors that could contribute to risk and vulnerability to HIV infection among individuals and spinal cord injuries; and to explore the socio-cultural issues that might increase individuals with spinal cord injuries’ vulnerability to HIV/AIDS. The design of this study was a mixed methods design, particularly the sequential explanatory strategy was used will used in this study. The study was conducted in four (4) conveniently selected provinces (highest prevalence of SCI). The Quad-Para Association of South Africa’s (QASA) provincial databases was used to invite individuals with SCI to participate in the study. Data for quantitative part of the study was collected by means of self-administered questionnaires. The questionnaire consisted of various sections requesting for information on: Demographics; HIV-Knowledge (HIV- KQ-18); Sexual behaviours; Sexual communication and negotiation skills; Self-efficacy to refuse sex. Separate binary logistics analysis was done to assess which of the selected factors are associated with risky sexual behaviour. The forced entry method approach was used to determine which of these factors have the greatest productive power to predict sexual risk behaviour. No “a priori” sample size was developed for the qualitative part, but participants were recruited until saturation has been reached of all the categories. Consenting participants were visited by the researcher for data collection in the environment indicated by the participant. Permission to conduct the study was obtained from the Research Ethics Committee at the University of the Western Cape (UWC). The study was conducted according to ethical practices pertaining to the study of human subjects as specified by the UWC and Faculty of Community and Health Sciences Research Ethics Committee of the UWC.

L’augmentation des fréquences de commutation des alimentations induit de nouvelles problématiques pour les composants. Que ces composants soient actifs ou passifs, il est nécessaire de contrôler les pertes afin que les rendements restent acceptables. La thèse se propose d’étudier et de fabriquer une nouvelle structure de transformateur destiné à s’insérer dans une alimentation à découpage. Ces transformateurs sont produits à l’aide du procédé PECS/SPS, qui est une technologie de frittage. Cette technologie permet de fritter des ferrites tout autour des enroulements primaires et secondaires. Il en résulte que les composants sont monolithiques.Une première partie présente l’état de l’art, ainsi que le magnétisme dans la matière. Il s’ensuit un chapitre dédié à la fabrication des matériaux magnétiques utilisés durant la thèse : les ferrites.Une deuxième partie concerne les ferrites fabriqués par le procédé PECS/SPS. Il est question dans un premier temps d’étudier l’anisotropie magnétocristalline de ces matériaux, et il est possible de la diminuer en jouant sur la composition chimique. Dans un second temps, d’autres grandeurs telles que la perméabilité ou la polarisation sont mesurées, toujours en fonction de la composition chimique. Les principaux résultats montrent que le frittage par le procédé PECS/SPS est plus réducteur que le frittage classique, ce qui dégrade certaines propriétés comme la résistivité des ferrites. Un dernier chapitre est dédié à la réalisation des transformateurs monolithiques. Un protocole détaillé de la fabrication est alors présenté.Une troisième partie illustre le fonctionnement des transformateurs réalisés. Les mesures usuelles permettent d’identifier les inductances propres, mutuelles et de fuite. Les valeurs de ces inductances montrent qu’il est plus judicieux d’utiliser les composants fabriqués non pas en tant que transformateur, mais en tant que coupleur. Enfin un convertisseur basé sur une structure de type VRM est réalisé. La fréquence de découpage est de 2 MHz, le rendement est supérieur à 90 %, et la densité de puissance est de 15 kW/litre
The increase in switching frequency of power supply induces new problems for the components. These components are active or passive, it is necessary to control the losses so that efficiency remains acceptable. The thesis deals with the study and production of a new transformer structure intended to be part of a switching power supply. These transformers are produced using PECS/SPS method, which is a sintering technology. This technology can be sintered ferrite around the primary and secondary windings. It follows that the components are monolithic.A first part presents the state of the art, and magnetism in the matter. It follows a chapter dedicated to the manufacture of magnetic materials used in the thesis : the ferrites.A second part concerns the ferrites produced by the PECS / SPS process. Firstly, the magnetocrystalline anisotropy of these materials is studied, and it is possible to decrease it by varying the chemical composition. In a second stage, other variables such as the permeability or the polarization are measured, always depending on the chemical composition. The main results show that the sintering by PECS / SPS method is more reducing than conventional sintering, which degrades certain properties such as the resistivity of the ferrites. The last chapter is dedicated to the realization of monolithic processors. A detailed manufacturing protocol is presented.A third part shows the operation of the realized transformers. The usual measurements allow identifying self, mutual and leakage inductances. The values of these inductances show that it is better to use components made not as a transformer, but as a coupler. Finally a converter based on a VRM structure is realized. The switching frequency is 2 MHz, the efficiency is greater than 90%, and the power density is 15 kW / liter

Ces travaux de thèse se concentrent sur l’instrumentation de la ME à travers le développement d’un dispositif expérimental. Il met en œuvre une méthode de suivi par Imagerie Optique Diffuse (IOD), qui permet de quantifier en direct les variations locales de flux sanguin. Pour cela, différents prototypes ont été conçus et testés durant des expérimentations animales. Une caractérisation optique a été menée sur des échantillons de ME ex vivo et sur des modèles animaux in vivo. Ces courbes, inédites dans la littérature, sont utilisées pour dresser les premières lignes d’un cahier des charges satisfaisant de ce dispositif embarqué dans un environnement biologique fort contraignant. Ce faisant, la faisabilité du suivi de l’état fonctionnel par IOD sur le gros animal (modèle porcin FBM) a été prouvée. La méthodologie de conception est également abordée, afin de permettre l’établissement plus aisé des interdépendances entre la mesure et les caractéristiques du système. Les résultats obtenus dans cette thèse sont très prometteurs. Ils ouvrent une voie d’exploration, complémentaire aux outils présents dans le parcours de santé actuel, qui permettra de fournir des index quantitatifs importants pour l’évaluation et la prise en charge des pathologies médullaires. À l’origine destiné au personnel hospitalier, de nombreux usages pourraient en découler, à la fois dans le domaine de l’orthopédie que dans la pratique chirurgicale vasculaire chez l’humain, comme chez l’animal. Les chercheurs bénéficieraient également d’un tel dispositif qui leur permettrait d’approfondir leurs connaissances sur le fonctionnement de la ME et son indépendance vis-à-vis du cerveau
This thesis focuses on the instrumentation of the SC, through the development of an experimental device. It uses the Diffuse Optical Imaging (DOI) technique to quantify the local variations of blood flow. For this purpose, several prototypes were designed and used during animal experiments. An optical characterisation was performed on SC samples, ex vivo and in vivo. We built up on this information, representing a first for the state of art, to establish guidelines for the development of the embedded device in the hostile biological environment. The feasability of the functional monitoring with DOI in the big animal (FBM pig) is now proven. The design methodology is addressed in order to highlight the interdependances between the measurement and the system. The results are very promising. They open a new path of exploration, complementary to the ones in everyday medical routine. In fine, this approach will be able to give quantitative indicators for the evaluation and the care of medullar pathologies. Destined for hospital praticians first, several purposes may be drawn from this device ranging from orthopedic to vascular surgeries for pets and humans. Researchers may also benefit from such a tool that would help them understand better the SC and its independance regarding the brain

Pour comprendre la genese du spinozisme, nous avons mise sur la personnalite libertine cachee du maitre en latinite de spinoza, van den enden dont meinsma a fait l'eleve de son eleve, dissumulant ainsi l'importance historique du cercle de van den enden au profit de celui de spinoza| l'etude du compat politique de v. D. Enden, de son gendre kerckrinck (qui a laisse une correspondance) et des libertins francais contre louis xiv (1671-74) nous a revele les oeuvres politiques anonymes du maitre de spinoza (proces rohan,an): vrye politijke stellingen, t. 1,1665,65r (libres theses politiques); extrait mss. Du t. 2 (de l'economie politique) et du t. 3 (etat democratique fonde sur une federation de villes puissantes); puis korte verhael van nieuw nederlants, 62,63r, 65r (?) (courte histoire des nouveaux pays-bas) (amerique). Nous decouvrions par suite le philedonius (1657) a la bn sous son nom| nous avons etabli la filiation directe entre ces oeuvres et celles de spinoza dans leur tentative de donner une traduction profane de la secrete tradition hermetico-alchimique. La piece de theatre hermetique de 57 defend une ethique liberatrice centree sur le mystere ontologique de la corporeite: le court traite (cours remanie de v. D. Enden (?) et surtout l7ethique formalisent le systeme de la nature hermetique fonde sur l'analogie microcosme macrocosme. Le theologico-politique est le pendant des libres theses (1) (cf. Le scheme anonyme politico-religieux opposant moise christ & l'ineditum spinozanum (?). Le traite politique reflete ces plaidoyers (anti-regents) pour la liberte populaire* la korte, extrapolation du projet communautaire americain de plockhoy; les stellingen (3), son extension
In order to understand the genesis of spinozism, we have relied on the free-thinking and secret personality of spinoza's master in latinity, v. D. Enden whom meinsma made his disciple's disciple, thus concealing the historical importance of v. D. Enden's circle for the benefit of spinoza's| the study of the political struggle waged by v. D. Enden, by his son-in-law kerckrinck (cf. His letters) and by french free-thinkers against louis xiv (1671-74) showed us the anonymous political works of spinoza's master (rohan' s criminal trial,an): vrye politijke stellingen, p. 1,1665,65r; extract mss. Rom p. 2(on political economics) and p. 3 (a democratic state based on a federation of powerful towns); then korte verhael van nieuw nederlants, 62,63r,65r(?). Thus we discovered the philedonius (57) at the bn| we have shown a direct line between these works and those of spinoza in their attempt to give a lay translation of the secret alchemical and hermetic tradition. The hermetic play of 57 supports a liberating ethics centred on the ontological mystery of corporeity: the short treatise (adapted lessons v. D. Enden's (?) and above all ethics formalize the hermetic system of nature founded on the analogy microcosm macrocosm. The theologico-political is the equivalent to stellingen (1) (cf. The anonymous scheme opposing moses christ & ineditum spinozanum (?). The political treatise reflects these anti-regents speeches for the people's freedom: korte, an extrapolation of plockhoy's american communal plan; stellingen (3), its extension

L’objectif de cette thèse est de contribuer à améliorer la connaissance des phénomènes physiques d’interaction fluide/structure qui régissent les mouvements du cerveau à l’intérieur de la boîte crânienne. Pour cela, un protocole expérimental est développé isolant les phénomènes qui nous intéressent, à savoir, le couplage entre une structure déformable (cerveau) et un fluide (liquide céphalorachidien (LCR)). Ainsi, nous nous intéressons au comportement, en rotation, d’un modèle cylindrique rigide (aluminium) contenant un cylindre déformable (gel de silicone utilisé comme matériau de substitution de la matière cérébrale dans de nombreux modèles physiques de la tête humaine) avec ou non une couche de fluide (eau jouant le rôle du LCR) entre les deux cylindres. La cinématique complète du modèle, ainsi que la déformation du gel, sont obtenues au cours de la sollicitation grâce à des techniques optiques. La comparaison des modèles avec ou sans eau a permis de quantifier l’influence du fluide sur le comportement du gel. Pour le modèle avec eau, le gel a principalement un mouvement de corps rigide puisqu’il est libre de tourner à l’intérieur de la cuve, ce qui induit des déformations relativement faibles à l’intérieur du gel et des déplacements périphériques importants. Pour le modèle sans eau, le gel adhère parfaitement aux parois du modèle en aluminium. De ce fait, son mouvement est restreint, induisant de grandes déformations dans le gel. Parallèlement, les résultats de cette campagne expérimentale sont utilisés pour tester la capacité des codes actuels à représenter les phénomènes physiques observés et dégager des options de modélisation pour le couplage LCR/cerveau
The aim of this study is to enhance the knowledge of fluid/structure interaction phenomena that governs brain movement inside the head subjected to a transient loading. An experimental protocol has been developed to understand the coupling phenomenon between a deformable structure (brain) and a fluid (cerebrospinal fluid (CSF)). A simplified physical head model subjected to an angular acceleration has been developed. This model consists of an aluminium cylinder filled with a silicone gel simulating the brain, either detached from the vessel or not by a layer of water representing the CSF. Complete kinematics of the model, displacements and strains induced in the gel has been determined by optical measurements. Fluid influence on gel kinematics is evaluated by comparing gel responses for the models with and without water. When a fluid layer prevents the gel to stick to the vertical walls of the aluminium vessel, displacements and strains inside the gel are lower than those observed for the model without water, while external movements of the gel with respect to the aluminium vessel are more important for the model with water. This can be explained by the fact that the gel mainly exhibits a rigid body motion in the model with water because the gel is free to rotate relatively to the vertical walls of the rigid model. For the model without water, the gel sticks to the aluminium vessel walls and its movement is restrained. In parallel, results from experimental study are used to estimate the capacity of actual FE codes to simulate the physical phenomena observed, as well as proposed modelling options for CSF/brain coupling representation

Les avancées de la biologie contemporaine, posent de façon nouvelle des problèmes philosophiques anciens. Ceux des rapports entre le vivant et l'inanimé, entre le corps et l'esprit, l'erreur et la vérité, sont les plus évidents. La philosophie de Spinoza, bien que datant du 17e siècle, apporte à ces problèmes des solutions plus pertinentes que la plupart des philosophies plus récentes, développées dans les siècles qui l'ont suivie. En retour, les acquis actuels des sciences physiques et biologiques, notamment des neurosciences cognitives, permettent de porter un nouveau regard sur certaines notions propres à la philosophie de Spinoza, telles que sa «petite physique», la nature cause de soi, la notion de matière, l'essence des choses, les genres de connaissance, qui acquièrent de ce fait un surcroît d'actualité
Old philosophical problems are raised in renewed ways by advances in biology of today. Most obvious are the problems of relationship between living and non-living, mind and body, error en truth. Spinoza's philosophy, although from 17th century, offers solutions to these problems more relevant than most more recent philosophies. In return, present knowledge from physical and biological sciences, especially cognitive neurosciences, can provide a new look at some specifically Spinozist notions such as his "little physics", Nature as cause of itself, the notion of matter, the essence of a thing, kinds of knowledge, which gain all the more interest from a present day point of view

Les erreurs innées du métabolisme (EIM) constituent un large panel de désordres métaboliques héréditaires. Parmi les EIM, les anomalies de la neurotransmission peuvent affecter, entre autres, la synthèse ou le transport des neurotransmetteurs, notamment les amines biogènes (dopamine et sérotonine) et les folates. La reconnaissance de ces affections est d’une importance capitale pour le diagnostic et le traitement éventuel. L’analyse chimique du liquide céphalo-rachidien (LCR) est incontournable pour le diagnostic de ces pathologies. Or, les méthodes actuelles de dosage ne sont pas simples. Longues et fastidieuses, elles ont été, pendant longtemps, réservées aux laboratoires spécialisés. L’objectif de ce travail était de développer des méthodes simples et rapides de diagnostic des troubles de la neurotransmission et d’établir les valeurs normales fréquentes dans la population française. Le travail réalisé a permis, dans un premier temps, de développer une méthode de dosage directe, en une seule étape, de la tetrahydrobioptérine (BH4), cofacteur des hydroxylases intervenant dans la synthèse des amines biogènes, et des ptérines impliquées dans le cycle de synthèse et de dégradation de ce cofacteur, dans le LCR. Auparavant, le dosage de ces substances nécessitait au moins deux analyses chromatographiques précédées chacune d’une étape propre de préparation de l’échantillon. Par la suite, nous avons développé une méthode de diagnostic rapide, en moins de 10 minutes, par UHPLC (chromatographie liquide à ultra haute performance), couplée à une détection séquentielle par coulométrie et par fluorescence, des troubles dopaminergique et sérotoninergique. Cette méthode permet de doser simultanément, en une seule étape, tous les métabolites de la dopamine, de la sérotonine et de la noradrénaline, ainsi que les ptérines d’intérêt diagnostic, principalement la dihydroneoptérine (NH2) et la dihydrobioptérine (BH2). L’ensemble de ces explorations nécessitait, auparavant, la mise en œuvre d’au moins trois méthodes de dosage par HPLC (chromatographie liquide à haute performance), précédées chacune d’une étape propre de préparation de l’échantillon. Pour compléter l’exploration du métabolisme de la BH4 et du suivi thérapeutique des troubles de la neurotransmission, nous avons également proposé une méthode de dosage rapide, en une seule étape, par UHPLC, de tous les métabolites et de toutes les ptérines, incluant la BH4. Enfin, une méthode rapide de dosage (moins de 2 minutes), par UHPLC, du 5-méthyltetrahydrofolate dans le LCR a été développée, afin de compléter le diagnostic biologique de l’ensemble des troubles neurologiques visés. L’application des outils ainsi développés à plus de 1400 patients nous a permis d’établir des valeurs normales fréquentes dans la population française ainsi que de poser le diagnostic de quelques déficits enzymatiques
Inborn errors of metabolism (IEM) consist of a wide range of hereditary metabolic disorders. Among IEM, neurotransmission anomaly can affect the synthesis or the transport of neurotransmitters, notably biogenic amines (dopamine and serotonin) and folates. Early diagnosis of such affections is of utmost importance especially as some of them can be treated effectively. Chemical analysis of cerebrospinal fluid (CSF) is essential for the diagnosis of neurotransmitter disorders; however, current quantitative methods are tedious and time consuming. For a long time the chemical diagnosis of neurotransmitter disorders has been available only in specialized laboratories. The purpose of this work was to develop simple and fast diagnosis methods of neurotransmitter disorders as well as to establish the reference values in French population. For this purpose, in a first step, we developed a single step direct method of simultaneous quantification of tetrahydrobiopterin (BH4), which is the main cofactor of the hydroxylases involved in biogenic amines syntheses, and the relevant reduced and oxidized forms of pterins involved in the cycle of synthesis – regeneration of BH4. Formerly, the quantification of those compounds required at least two chromatographic methods with two specific sample preparation procedures. Thereafter we developed a method of fast diagnosis in less than 10 minutes of dopaminergic and serotoninergic disorders using UHPLC (ultra high performance liquid chromatography) hyphenated to a sequential coulometric and fluorimetric detection. With only a simple filtration step as sample preparation procedure, this method enables the simultaneous quantification of all dopamine, serotonin and noradrenaline metabolites as well as dihydroneopterin (NH2) and dihydrobiopterin (BH2), the relevant pterin forms for the complete diagnosis. Formerly, at least three HPLC (high performance liquid chromatography) quantification methods preceeded by three tedious specific sample preparation procedures were required for such a diagnosis. To complete the investigation of BH4 metabolism and the follow up of neurotransmission disorders, we also developed a fast UHPLC method of simultaneous quantification of all the cited metabolites and pterins including BH4. In order to complete the rapid diagnosis of all targeted neurological disorders, we finally developed an UHPLC method of 5-methyltetrahydrofolate quantification in CSF. The application of these analytical tools in more than 1400 CSF samples, collected from patients followed in some Neurology centers located in several French areas covering nearly the entirety of the territory, allowed us to establish the reference values in French population as well as to diagnose several cases of enzymatic deficits

L'Ethique prétend nous conduire comme par la main vers la béatitude et le salut, Elle nous montre le chemin qui nous permet, en associant le plus possible nos affects à des idées vraies, de parvenir à la connaissance vraie et à l'amour de Dieu. A qui s'adresse l' « Ethique » ? Notre hypothèse est qu'elle s'adresse aux mêmes lecteurs que ceux du « Traité théologico-politique » qui philosopheraient plus librement s'ils n'en étaient empêchés par l'idée que la raison doit être la servante de la théologie. Après avoir montré que l'Ecriture Sainte devait être interprétée avant d'être affirmée Parole de Dieu, que la certitude prophétique n'était qu'une certitude morale, Spinoza propose la certitude mathématique de l'entendement, comme véritable parole de Dieu qui parle directement à notre âme, Dieu qui se fait connaître, non comme un Dieu transcendant, mais comme un Dieu immanent, cause efficiente de toutes choses et donc de nos idées claires et distinctes, qui nous permettront de découvrir un Dieu qui agit librement par nécessité de nature, en totale opposition avec les doctrines scolastique et cartésienne. Cette révélation rationnelle n'annule néanmoins pas la révélation prophétique dont la vérité ne se trouve pas dans la spéculation, mais dans les enseignements moraux, et surtout par le message d'amour du Christ, modèle de vie vraie. Mais si le but ultime de chacune des révélations est de jouir de l'amour de Dieu, quelle est en chacune la nature de cet amour ?
Ethic purports to lead us, as if by the band, towards beatitude and salvation. It shows us the way which allows us, by associating as much as possible our affects to real ideas, to attain true knowledge and the love of God. Whom does “Ethics” address ? Our hypothesis is that it addresses the same readers as the “Theologico-Political Treatise” does, who would philosophize more f eely would they not be prevented from it by the thought that reason should serve theology. After having shown that scripture should be interpreted before being claimed God's word, that prophetic certainty was just moral certainty, Spinoza offers the mathematical certainty of understanding, as the true word of God which speaks directly to our soul ; God who becomes known not as a transcendental God but as an immanent God, efficient cause of all things and thus of our ideas, distinct and clear, which shall allow us to discover a God which acts feely out of necessity of nature, in outright opposition to the scholastic and Cartesian doctrines. This rational revelation nonetheless does not cancel the prophetic revelation, which truth isn't in speculation, but in moral teachings, and especially by in Christ's message of love, model of true life. But if the ultimate goal of each of the revelations is to enjoy the love of God, what is in each of them the nature of this love?

La diversite biologique du cercle d'anzi est apprehendee sous trois formes etroitement liees: specifique, pedologique et genetique. La premiere partie approfondit nos connaissances sur le climat et tente une estimation de l'evolution de l'arganeraie au cours des trente dernieres annees. Sont aussi developpees une analyse frequentielle et une etude chronologique de longues series de precipitations. La deuxieme partie presente la carte de la vegetation spontanee et montre l'impact de l'homme sur l'environnement. Quatre communautes vegetales correspondant a de nombreuses sous-associations et facies sont decrites et leurs exigences ecologiques precisees. La troisieme partie presente la zonation bioclimatique des sols, tous caracterises par un appauvrissement de leur horizon de surface et une importante argilisation. A l'inframediterraneen, les sols sont brun-rouge subarides et rouges fersiallitiques appauvris et satures; au thermomediterraneen le sol climacique est un sol fersiallitique generalement desature et tres appauvri. La quatrieme partie traduit la microevolution chez l'arganier en mesurant le niveau de polymorphisme des feuilles et en determinant son regime de reproduction. La variation est plus grande a l'interieur de chaque population qu'entre populations elles-memes et l'analyse des descendances conforme que l'arganier est bien allogame dans de grandes proportions

The formation of the central nervous system (CNS) requires the generation of a remarkable diversity of neurons, which must be produced in adequate amounts in the location and timing during development. Studies on the development of the spinal cord, the caudal and simpler anatomically vertebrate CNS, have shown that the neuronal diversity is progressively acquired through the processes of cell type specification. In amniotes, patterning of the neural tube along the dorsal-ventral axis generate 11 distinct domains of neural progenitors. Thus, the developing spinal cord, may be subdivided into 6 dorsal domains of progenitors (dP1-6, from dorsal to ventral) and a ventral part consisting of 5 domains (p3, pMN, p2-0, of ventral to dorsal). Dorsal and ventral domains of progenitors generate classes spinal neurons involved in sensory and motor circuits, respectively. Thus, accurate identification of each of the molecules that regulate this process is crucial. First, in this study, we focus on the function of LMO4 during neurogenesis in the development of the dorsal spinal cord. Using electroporation in ovo, in chicken embryos, as a method for modulating the activity of LMO4 in vivo, we demonstrated that LMO4 is dispensable for maintaining patterns progenitor cells, but is necessary for proper generation of discrete classes of interneurons ie , dI1/3/5. Further we provided evidence that LMO4 activity is essential for the promotion of these identities by the canonical BMP activity and suggest that LMO4 and SMAD1 / 5 contribute to the multi-protein complexes that regulate the genetic program for the specification of interneurons dI1 / 3/5. In the second part of this thesis, we study the peripheral nervous system, PNS, and one type of cancer that is derived from the PNS. Neuroblastoma (NB) is a neurological tumor that arises from neural crest cells (NC) and is the most common extracranial tumor in children. NB represents a very heterogeneous group of tumors in terms of biological, genetic and morphological characteristics. Clinically, these tumors can develop differently, since spontaneous remission differentiation or apoptosis (NC behavior resembling normal) to aggressive metastatic disease with low rates of overall survival. The neuroectodermal origin of NB suggests that these tumors can spread from its primary site using mechanisms similar to those involved in the delamination and dispersion of embryonic neural crest cells, and genes involved in cell migration of neural crest cells may also be involved in the acquisition of the phenotype of invasive NB. We developed marker for neural crest lineage and taking the hypothesis that the molecular mechanisms that mediate the neural crest delamination may also be involved in the spread of neuroblastoma, we were able to identify genes that are expressed in the neural crest development and formation of neuroblastoma. A subsequent search in the NBGS (neuroblastoma gene server) for the human orthologous of genes differentially expressed in neural crest chicken embryo, retrieved LMO4 which was expressed in both cell types tested. Functional experiments in these two systems, revealed that the activity LMO4 is required for delamination of the neural crest and for neuroblastoma cell invasion. Moreover, LMO4 identified as an essential cofactor in the cadherin repression mediated Snail2 and epithelial to mesenchymal transition from neural crest cells and neuroblastoma. Together, our results suggest that the association of high levels of LMO4 with aggressive neuroblastomas, depends on the regulation of cadherin expression by LMO4 and therefore tumor invasiveness.
La formación del sistema nervioso central requiere la generación de una gran diversidad de neuronas, y la identificación de las señales moleculares que regulan este proceso es por lo tanto crucial. En esta tesis, me he centrado primero en estudiar la función de LMO4 durante la neurogénesis en la médula espinal dorsal. Mediante las electroporación in ovo, en embriones de pollo, como una metodología para modular la actividad LMO4 in vivo, se demostró que LMO4 era prescindible para el mantenimiento de los patrones de progenitores, pero que se requiere para la correcta generación de subtipos concretos de interneuronas dorsales (dI1/3/5). Por otra parte, se demostró que la actividad LMO4 es esencial para la promoción de estas identidades mediante la actividad BMP canónica, y proponemos que LMO4 y Smad1 / 5 forman parte de los complejos de proteínas que impulsan el programa genético de especificación de dI1/3/5. En la segunda parte de la tesis, he estudiado el sistema nervioso periférico, así como tumores que surgen de él. El neuroblastoma es un tumor embrionario derivado de células de la cresta neural. Aprovechando un nuevo marcador desarrollo para el linaje de cresta neural y en base a la hipótesis de que los mecanismos moleculares que median la delaminación de la cresta neural también están involucrados en la propagación del neuroblastoma, identificamos varios genes comunes en el desarrollo de la cresta neural y el neuroblastoma. Una búsqueda posterior de los ortólogos humanos del NBGS (genes expresados en neuroblastoma) observamos que LMO4 se expresa en ambos tipos de células analizadas. Experimentos funcionales en estos dos sistemas modelo revelaron que se requiere la actividad LMO4 durante la invasión de células del neuroblastoma y durante la delaminación de la cresta neural. Además, identificamos LMO4 como un cofactor esencial de Snail2, en la represión de la expresión de cadherina, y por tanto en la transición epitelio mesenchyma de la cresta neural y de las células de neuroblastoma. En conjunto, nuestros resultados sugieren que la asociación de altos niveles de LMO4 con neuroblastomas agresivos depende de la regulación de cadherina y, por tanto, de la invasividad tumoral.

Previous research has demonstrated that the spinal cord is capable of a simple form of instrumental learning. In this instrumental learning paradigm, rats typically receive a complete spinal transection at the second thoracic vertebra, and are tested 24 hours after surgery. Subjects that receive shock to a hind leg quickly learn to maintain the leg in a flexed position, which reduces net shock exposure (Grau et al., 1998). Prior studies have examined the mechanisms that mediate this learning, but little is known about how or where the consequences of learning are stored (memory). The goal of this dissertation proposal is to examine the neural modification(s) that preserve learned behavioral effects over time. It is clear that the central nervous system plays an essential role in instrumental learning. During the acquisition of instrumental learning, the connections between the peripheral nervous system (PNS) and the central nervous system must remain intact (Crown et al., 2002a). Acquisition is also disrupted by intrathecal application of pharmacological agents (lidocaine) that inhibit spinal reflexes (Crown et al., 2002a). The experiments outlined in this dissertation are motivated by an unexpected observation: while application of lidocaine to the spinal cord prior to training blocks acquisition of the instrumental response, inactivating spinal neurons has no effect on the maintenance of the instrumental response. These data suggest that, after the instrumental response is acquired, a peripheral component is capable of maintaining the instrumental response. Aim 1 examined how inhibiting the spinal cord influenced the maintenance of instrumental learning. Intrathecal lidocaine inhibited a spinal withdrawal reflex and instrumental learning, but did not affect the maintenance of the learned response. Expanding on these results, Aim 2 examined how disconnecting the PNS from the spinal cord would influence the maintenance of instrumental learning. If a PNS to spinal cord connection is needed for the maintenance of instrumental learning, then removing that connection by a sciatic transection should disrupt performance of the instrumental response. Together, the results of Aims 1 & 2 confirm that a peripheral alteration contributions to the maintenance of instrumental behavior. In Aim 3, I developed a procedure that would allow for drug delivery directly to the tibialis anterior muscle. If the neuromuscular junction is capable of influencing a spinal reflex, then blocking the neuromuscular junction with an antagonist (curare) should disrupt the acquisition and maintenance of the instrumental response. Based on the results of Aim 3, Aim 4 investigated how other pharmacological manipulations at the neuromuscular junction can influence the acquisition and maintenance of the instrumental response. Using glutamate receptor antagonists (CNQX and MK-801), I showed that glutamatergic signaling plays an essential role.

碩士
國立臺灣科技大學
機械工程系
103
Pedicle screw can be used for fixation of hip trochanteric fractures. It should have higher bending strength and pullout strength to resist breakage and loosening. Both of the strengths are relative to thread designs. We could get the optimal design factors of pedicle screw from neuro-genetic method which involves artificial neural networks(ANN) and genetic algorithm(GA). But the “black box” problem of ANN was not disclosed. The purpose of this study is to establish a fair standard of comparison and illuminate the black box by calculating contribution of each factor with different methods. 　　In our study, the bending and pullout functions of the pedicle screws were first simulated by finite element models(FEM). With L25 orthogonal arrays, the result of Taguchi robust design method with analysis of variation(ANOVA) is considered as the standard. The partial derivative(PaD), modified PaD, Garson weight method, Olden weight method, profile method, minimum substitution, weight elimination, maximum substitution, random substitution, data permutation and full range substitution in ANN are compared to find which one’s contribution is the most accurate. The performance of these methods was evaluated in four aspects, including selecting the important factors, finding the action direction of the important factors, ranking and relative contribution proportion. 　　In addition, using full range substitution could calculate accurate contribution of the design factors in bending and pullout analyses.

Tese de Doutoramento em Ciências Veterinárias
A lesão da medula espinhal é uma condição extramente grave que acarreta elevados custos socioeconómicos devido às limitações físicas e stresse psicológico que lhe estão associados. Apesar de décadas de investigação e ensaios clínicos, a recuperação funcional em pessoas que sofrem de lesão aguda ou crónica da medula espinhal é ainda muito limitada. A lesão secundária que sucede ao dano inicial na medula espinhal origina localmente uma resposta regenerativa espontânea limitada, mas é também responsável por eventos moleculares e celulares que originam um ambiente inibitório para a regeneração axonal. Os fatores inibitórios associados à mielina que se acumulam no local da lesão, exercem várias ações que contribuem para a incapacidade regenerativa dos axónios maduros da medula espinhal. Estes componentes são responsáveis pelo desencadear de uma cascata de processos intracelulares que resulta na contração dos filamentos de actina e miosina no cone de crescimento levando ao seu colapso. Vários estudos demonstraram que o aumento dos níveis de adenosina monofostato cíclico (cAMP) pode reduzir este efeito inibitório e reforçar a capacidade dos neurónios da medula espinhal de regenerar para além da lesão. Nestes estudos, a elevação do cAMP produziu-se pela administração de seus análogos ou indiretamente pela inibição de enzimas responsáveis pela sua degradação, levando à sua acumulação intracelular. Nesta tese estudamos o efeito da administração contínua de rolipram, um inibidor da fosfodiesterase 4, na recuperação funcional e na preservação da substância branca da medula espinhal após a sua lesão experimental. Este agente foi administrado isoladamente durante duas semanas após lesão contusiva moderada da medula espinhal torácica em fêmeas adultas de ratos Wistar. A avaliação funcional realizou-se usando a escala de classificação locomotora BBB de 21 pontos, o teste de locomoção em barra estreita e a análise cinemática tridimensional do movimento dos membros pélvicos em tapete rolante. A análise estereológica das medulas espinhais lesionadas, realizada oito semanas após a lesão, permitiu-nos estimar o volume e comprimento da lesão e a área de substância branca preservada no epicentro da lesão. Os nossos resultados mostraram que administração de rolipram após contusão moderada da medula espinhal proporcionou um melhor desempenho motor nos ratos lesionados durante todo o período de teste. A avaliação dinâmica do movimento do pé durante a marcha realizada oito semanas após a lesão revelou uma diminuição significativa da rotação externa durante todo ciclo de passada nos animais tratados com rolipram. A análise estereológica não revelou diferenças significativas no volume e comprimento da lesão em animais tratados e não-tratados com rolipram. Em contrapartida, a quantidade de substância branca preservada foi significativamente maior no grupo tratado com rolipram. Estes resultados sugerem um potencial terapêutico para o rolipram em situações agudas de lesão da medula espinhal. Devido às limitações da escala locomotora BBB, desenvolvemos um protocolo de análise computadorizada da marcha do rato que nos permitiu obter medições contínuas e precisas de parâmetros cinemáticos. Nesta tese fornecemos uma descrição detalhada deste protocolo e expomos de que forma superáramos as várias limitações da avaliação cinemática, nomeadamente o artefacto de deslizamento da pele, o efeito da velocidade de locomoção nos parâmetros cinemáticos e as diferenças entre as abordagens cinemáticas bidimensionais e tridimensionais. Os resultados obtidos confirmam a fiabilidade da avaliação cinemática da locomoção em tapete rolante, sempre que se minimizem as possíveis influências da velocidade de marcha, do movimento da pele a nível do joelho e dos erros de paralaxe nos parâmetros angulares obtidos durante a locomoção. Velocidades elevadas de marcha no rato originam maior extensão das articulações do membro pélvico e diminuição de parâmetros temporais como o tempo de suporte e a duração da passada. Os investigadores devem estar cientes do potencial efeito da velocidade de marcha nos parâmetros cinemáticos obtidos em modelos animais de locomoção. Demonstrámos que a análise cinemática tridimensional proporciona a obtenção de valores exatos e precisos e permite determinar as rotações externas ou internas do pé. Os nossos resultados mostraram que há um movimento considerável da pele do membro pélvico que se propaga como artefacto na determinação da posição do joelho e na análise cinemática do membro, diminuindo a fiabilidade dos dados obtidos por marcação cutânea desta articulação. A estimativa computadorizada indireta da posição do joelho reduz os efeitos deste artefacto e, por conseguinte, melhora a análise biomecânica do membro pélvico durante a locomoção.
Spinal cord injury (SCI) is a devastating condition affecting millions of people all over the world with overwhelming socioeconomic costs associated with physical disability and psychological stress. Unfortunately, despite decades of research and clinical trials, functional recovery is still very limited in patients suffering from acute or chronic spinal cord lesion. The secondary progressive tissue damage that follows the initial injury leads to a limited spontaneous regenerative response at the lesion site, but is also responsible for a multitude of cellular and molecular events that originate an inhibitory environment to axonal regeneration. Myelin-associated inhibitory components that accumulate on the lesion site, due to its very slow clearance, exert multiple inhibitory actions contributing to the inability of mature spinal cord axons to regenerate after injury. These components are responsible for triggering an intracellular cascade that results on contraction of myosin actin filaments at the filopodia originating growth cone collapse. Several studies have demonstrated that the elevation of cyclic adenosine monophosphate (cAMP) can reduce this inhibitory effect and enhance the ability of spinal cord neurons to extend their damaged axons. In those studies, elevation of spinal cAMP was accomplished either by cAMP analogues administration or indirectly by inhibiting the enzymes responsible for its degradation leading to its intracellular accumulation. In this thesis we studied the effect of continuous administration of rolipram, a Phosphodiesterase 4 (PDE4) inhibitor, on locomotor recovery and spinal white matter sparing following experimental SCI. Rolipram was administered as a sole agent for two weeks following moderate thoracic spinal cord contusion injury in Wistar adult female rats. Functional assessment was performed using the 21-point Basso, Beattie, and Bresnahan (BBB) locomotor rating scale, beam walk test and three-dimensional kinematic evaluation of hindlimbs movement on treadmill locomotion. Stereological analysis of injured spinal cords, performed eight weeks postinjury, allowed us to estimate lesion volume, lesion length and area of spared white matter at lesion epicentre. Our results showed that administration of rolipram following acute spinal cord contusion resulted in improved motor performance during the entire testing period. Dynamic assessment of foot motion during treadmill walking revealed a significantly decreased external rotation during the entire step cycle after 8 weeks in rolipram-treated animals. Stereological analysis revealed no significant differences in lesion volume and length. By contrast, spared white matter was significantly higher in the group treated with rolipram. These results suggest a therapeutic role for rolipram delivered alone following acute SCI. Due to the limitations and subjectivity of the BBB locomotor rating scale we developed a computerized rat gait analysis protocol which allowed us to obtain and process highly accurate continuous kinematic measurements. In this thesis we provide a detailed description of this protocol and we expose how we did overcome several limitations of kinematic evaluation, namely the skin slippage artifact, the effects of speed on angular parameters and the differences between two-dimensional and threedimensional kinematic approaches. Concerning the kinematic evaluation of the rat´s hindlimbs, our results suggest that reliable kinematic measurements can be obtained from the treadmill gait analysis in rats, if the experimenter is able to minimize the potential influences of gait speed, skin movement and parallax errors on the angular parameters obtained during rat locomotion. Increased walking velocities in the rat are associated with increased hindlimb joints extension and decreased temporal parameters. Researchers should be aware of the potential role of walking velocity differences in gait research models. We demonstrated that maximal precision and accuracy of the kinematic values are expected when the experimental protocol includes a three-dimensional motion analysis methodology in order to determine the external or internal rotation of the foot. Our results revealed the presence of a considerable skin movement artifact which propagates to knee joint position and hindlimb kinematics decreasing data reliability in the research of rat gait analysis. The indirect computerized estimation of the knee position can largely reduce the effects of this artefact and therefore improve biomechanical analyses.

碩士
國立臺灣科技大學
機械工程系
102
Pedicle screws used for fixation of hip trochanteric fractures should have higher bending strength to resist breakage and bone holding power to resist migration. The present optimization study is to find screws with the highest bending or bone holding power. Besides, the “black box” problem of ANN was not disclosed. We could get the predictive value from the artificial neural networks conveniently, but the less information about the relative influence of the independent variables was provided. The purpose of the study is to find the optimal solution and illuminate the black box by calculating contribution of each factor with different methods. The bending and pullout functions of the pedicle screws were first simulated by finite element models (FEM). With L25 orthogonal arrays, optimal screw designs with highest bending or bone holding power were then investigated by Taguchi robust design methods and Neuro-Genetic method hybridizing artificial neural networks (ANN) and genetic algorithm (GA). The mechanical performances of the optimal designs, the predictability of the performances and the contribution of the design factors obtained in these methods were compared. On the aspect of contribution, the result of analysis of variance (ANOVA) is considered as standard. The weight method, weight elimination, partial derivative and sensitivity analysis are compared to find which one’s contribution is the most accurate. For optimization studies, Neuro-Genetic method could yield better results than Taguchi methods by -3.01% in bending and 10.14% in pullout analyses. For predicting the performances, the errors of NG algorithm were 0.65% and 1.42% for bending and pullout analyses respectively, much lower than -21.26% and 15.95% of Taguchi method. In addition, using weight elimination or factor division could calculate accurate contribution of the design factors.

博士
長庚大學
臨床醫學研究所
94
The management of septic patients posts a professional challenge because of the reduction in systemic vascular resistance and the progressively diminished response to sympathomimetic pressor agents. The refractory hypotension remains a significant cause of morbidity and mortality in septic patients. Under physiological conditions, neurogenic vasomotor tone plays an important role in the maintenance of normal blood pressure. A better understanding of the regulatory machinery on neurogenic vasomotor tone during sepsis is therefore of vital importance. The integrity of rostral ventrolateral medulla (RVLM), bulbospinal tract, and intermediolateral cell column (IML) plays an important role in maintaining resting vasomotor tone. The vasomotor components of the systemic arterial pressure (SAP) spectrum reflect the activities of the sympathetic premotor neurons in RVLM, and the vasomotor signals are transmitted through activation of glutamate receptors on sympathetic preganglionic neurons (SPN) in IML. However, the relative contribution of the two major subtypes of glutamate receptors, NMDA and non-NMDA receptors, to the generation of neurogenic vasomotor tone under physiological conditions or during experimental endotoxemia is basically unknown. We addressed this issue by using a combination of physiological, pharmacological and double immunofluorescence approaches to delineate the relative contribution of NMDA and non-NMDA receptors on SPN to the generation of neurogenic vasomotor tone under physiological conditions and during experimental endotoxemia. For more accurate distribution of drugs over the specific IML region, a pre-implanted catheter in the thoracic subarachnoid space is mandatory. The currently available methods for catheterization of the thoracic spinal subarachnoid space in rats have been associated with relatively high postoperative mortality and morbidity. In our study, we developed a better method of catheterization. An intrathecal catheter was fabricated with a small silicon bead at one end of a PE-10 catheter, which was cannulated with a 4/0 suture that served as a guide. Using the L-shape hook of the suture guide as an anchorage, the catheter was advanced into the subarachnoid space until the silicon bead was lodged on a drilled hole (2 x 2 mm) over the lamina proper on the T13 vertebrae. The applicability of the implanted catheter was demonstrated by myelogram and pharmacological studies. Adult male Sprague-Dawley rats maintained under propofol anesthesia were used. Intrathecal administration of equimolar concentrations (75, 150 or 300 nmol) of a NMDA antagonist, dizocilpine (MK801) or a non-NMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) into T10-T12 spinal cord elicited a reduction in resting vasomotor tone that was comparable in time-course and in magnitude. At the same time, both glutamate receptor antagonists exacerbated mortality and potentiated the elicited hypotension, bradycardia or reduction in vasomotor tone during experimental endotoxemia induced by intravenous administration of Escherichia coli lipopolysaccharide (30 mg/kg). Results comparable to CNQX at 150 nmol were obtained only when MK801 was given at 300 nmol. Confocal microscopy further showed that augmented immunoreactivity of NR1 subunit of the NMDA receptor on IML neurons coincided with the phase of endotoxemia when vasomotor tone was augmented; the immunoreactivity GluR1 subunit of the non-NMDA receptor remained stable throughout experimental endotoxemia. Correct localization and identification of SPN was crucial to the interpretation of our results. We thus have to be familiar with the location, morphology, and distribution of SPN in IML for accurate location of glutamate receptor expression on SPN. c-fos protein was induced in SPN through electrical stimulation to RVLM and visualized by immunohistochemical method. It was found that c-fos positive cells were not present in the spinal cord except within the IML region. We concluded that NMDA and non-NMDA receptors on IML neurons contribute equally to the generation of resting sympathetic vasomotor tone. However, upregulation of NMDA receptors on IML neurons plays a crucial role in the maintenance of vasomotor tone during endotoxemia.