To see the other types of publications on this topic, follow the link: Active bonnet.

Dissertations / Theses on the topic 'Active bonnet'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the top 50 dissertations / theses for your research on the topic 'Active bonnet.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.

1

Galda, Michal. "Aktivní závěs kapoty." Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2013. http://www.nusl.cz/ntk/nusl-230500.

Full text
Abstract:
This thesis deals with designing the construction of an active bonnet hinge, tuning the kinematics and appropriate proportioning of individual parts of the hinge. The thesis consists of two main parts – the first part is an analysis of the current state of knowledge and the second part presents a designing the construction. The active hinge should serve as a safety element in automobiles to minimize consequences of head injury suffered during the collision of a pedestrian with an automobile.
APA, Harvard, Vancouver, ISO, and other styles
2

Mrázek, Jan. "Vliv prvku pasivní bezpečnosti vozidel při kolizích s chodci." Master's thesis, Vysoké učení technické v Brně. Ústav soudního inženýrství, 2011. http://www.nusl.cz/ntk/nusl-232560.

Full text
Abstract:
This thesis deals with the influence of passive safety features during vehicle collisions with pedestrians. The first part focuses on introducing the basic components of active and passive vehicle safety. The second part deals with construction and usage of modern components of passive safety during vehicle collisions with pedestrians. A comparing situation model of vehicle collisions with pedestrian is introduced in the third part for which a simulation programme has been used. At the close of this part there is a result synthesis of these model situations. The last part deals with the possibility of increasing pedestrian safety.
APA, Harvard, Vancouver, ISO, and other styles
3

Gawith, Corin B. E. "Novel active waveguide devices in direct-bonded structures." Thesis, University of Southampton, 2002. https://eprints.soton.ac.uk/15488/.

Full text
Abstract:
This thesis describes a series of experimental studies on the use of direct bonding for optical waveguide fabrication. The direct bonding technique involves contacting two ultra-clean polished surfaces to form an adhesive-free vacuum-tight bond. Optical materials bonded in this way can be formed into waveguide devices, and this work extends direct bonding to include periodically poled materials and a new solid-state ion-exchange process. The first result of this work describes the fabrication of a 5.5-mm-long, 12-µm-thick periodically poled LiNbO3 planar waveguide buried in LiTaO3. Frequency doubling experiments performed with this device demonstrate a conversion efficiency of 4.3 %W-1, a value 40% greater than that calculated for an optimised bulk device of similar length. Also demonstrated is a photorefractive iron-doped LiNbO3 waveguide buried in non-photorefractive magnesium-doped LiNbO3. In optical limiting experiments this device demonstrates a change in optical density of 2 and photorefractive response time of 5 milliseconds, representing 20 times greater optical limiting and 60 times faster operational speed than the bulk material. K+-Na+ ion-exchange between direct-bonded glass layers is studied and used as a novel solid-state technique for waveguide fabrication. This process is also developed to incorporate direct-UV-written channel waveguides in an ion-exchanged buried photosensitive glass layer. Finally, operation of a single-mode channel waveguide laser in neodymium-doped photosensitive SGBN glass (based on a composition of silica, germania, boron, and sodium) is demonstrated, with propagation losses of < 0.3 dB cm-1 and milliwatt-order lasing thresholds.
APA, Harvard, Vancouver, ISO, and other styles
4

Utas, Josefin. "Hydrogen Bonded Phenols as Models for Redox-Active Tyrosines in Enzymes." Doctoral thesis, Stockholm : Department of Organic Chemistry, Stockholm University, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1024.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

Jolly, Prateek. "Lamb wave based active damage identification in adhesively bonded composite lap joints." Thesis, Mississippi State University, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10100288.

Full text
Abstract:

Bonding composite structures using adhesives offers several advantages over mechanical fastening such as better flow stress, weight saving, improved fatigue resistance and the ability to join dissimilar structures. The hesitation to adopt adhesively bonded composite joints stems from the lack of knowledge regarding damage initiation and propagation mechanisms within the joint. A means of overcoming this hesitation is to continuously monitor damage in the joint. This study proposes a methodology to conduct structural health monitoring (SHM) of an adhesively bonded composite lap joint using acoustic, guided Lamb waves by detecting, locating and predicting the size of damage. Finite element modeling of a joint in both 2D and 3D is used to test the feasibility of the proposed damage triangulation technique. Experimental validation of the methodology is conducted by detecting the presence, location and size of inflicted damage with the use of tuned guided Lamb waves.

APA, Harvard, Vancouver, ISO, and other styles
6

Emmel, Marcus. "Development of active and reactive carbon bonded filter materials for steel melt filtration." Doctoral thesis, Technische Universitaet Bergakademie Freiberg Universitaetsbibliothek "Georgius Agricola", 2014. http://nbn-resolving.de/urn:nbn:de:bsz:105-qucosa-154256.

Full text
Abstract:
Kohlenstoffgebundene Filterwerkstoffe erfreuen sich stetig wachsender Beliebtheit seitens der Industrie. Deren Potenzial hinsichtlich stofflicher und verfahrenstechnischer Eigenschaften erscheint dennoch nicht in vollem Umfang genutzt. Daher wurden im Rahmen der vorliegenden Arbeit, welche innerhalb des Sonderforschungsbereiches 920 entstand, erstmals aktive (Al2O3-C) und reaktive (MgO C) Filter, sowie eine Kombination daraus entwickelt. Die aktiven Filtersysteme, deren Funktionalisierung einerseits über die Erhöhung des amorphen Kohlenstoffanteils, andererseits über die Beschichtung mit rein oxidischen Materialien stattfand, sowie die reaktiven Filter, bei denen sich der carbothermischen Reduktion des MgO bedient wurde, konnten, in Kollaboration mit der Industrie, erfolgreich getestet werden. Durch gezielte Kontamination des Stahls mit exogenen Einschlüssen auf Basis von Al2O3 und MgAl2O4, ist es gelungen dem Chemismus der jeweiligen Filter einen entscheidenden Beitrag zum Filtrationsprozess zuweisen zu können. So weist Aluminiumoxid, unabhängig vom Chemismus des Einschlusses, das vergleichsweise größte Filtrationspotenzial auf.
APA, Harvard, Vancouver, ISO, and other styles
7

Mondino, Lindsay Jean. "Isolation and characterization of cold-active heterotrophic bacteria from lakes Bonney and Vida, McMurdo Dry Valleys, Antarctica /." Available to subscribers only, 2008. http://proquest.umi.com/pqdweb?did=1650504141&sid=2&Fmt=2&clientId=1509&RQT=309&VName=PQD.

Full text
Abstract:
Thesis (M.S.)--Southern Illinois University Carbondale, 2008.
"Department of Molecular Biology, Microbiology and Biochemisty." Includes bibliographical references (p. 48-51). Also available online.
APA, Harvard, Vancouver, ISO, and other styles
8

Baxter, Frances R. "Electrically active ceramics for bone graft substitution." Thesis, University of Bath, 2008. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.512281.

Full text
Abstract:
Hydroxyapatite (HA) bioceramics are commercially available as bone graft substitute materials. The aim of the current research was to characterise the electrical properties of hydroxyapatite-barium titanate (HABT) composites and to assess in vitro biological responses to the composites in order to investigate their potential use as bone graft substitutes. A range of HABT ceramics of different compositions was manufactured and their electrical properties were measured. The microstructure and piezoelectric properties of the ceramics were both dependent on the proportion of barium titanate (BT) present. Composites containing more than 70% BT displayed piezoelectric charge coefficients (d33) of up to 86.3±7.9pCN-1 (95% BT). The ferroelectric nature of the 90 and 95% BT materials was confirmed by assessment of their ferroelectric hysteresis loops. The highest piezoelectric voltage coefficient (g33) recorded was 14x10-3Vm-1Pa-1 (90% BT). Following the assessment of the electrical properties, the HABT ceramic containing 90% BT was selected for the assessment of biological responses to the composites. The proliferation, viability, activity and morphology of human osteoblast-like cells cultured on HABT were comparable to those cultured on hydroxyapatite (HA) up to 7 days after seeding. The remnant polarisation of poled HABT induced an increase in cell attachment. This influence was independent of the nature (positive or negative) of the polarisation. Poling was not found to influence cell morphology, activity or differentiation in the first 7 days of incubation. At 14 days after seeding, results were inconsistent, indicating some variations in cell population and differentiation depending on the composition and poling of the ceramics respectively. This study has substantially defined the electrical properties of a range of HABT ceramics. It indicates their in vitro biocompatibility and thus their potential for use as bone graft substitutes. These results provide a benchmark against which future work investigating the influence of mechanical loading and longer term studies may be measured.
APA, Harvard, Vancouver, ISO, and other styles
9

Huang, Boyang. "Electro-active scaffolds for bone tissue engineering." Thesis, University of Manchester, 2018. https://www.research.manchester.ac.uk/portal/en/theses/electroactive-scaffolds-for-bone-tissue-engineering(e4374a7f-47fe-418f-a515-fe5a37668aa8).html.

Full text
Abstract:
Bone is a highly hierarchical tissue which is able to heal and remodel in case of small defects and damage. For critical-size defects, the most commonly used approach requires the use of synthetic grafts. These grafts, also known as scaffolds, are physical substrates designed for cell attachment, proliferation and differentiation. Scaffolds for bone applications must be biocompatible, biodegradable, and highly porous, presenting mechanical properties similar to bone and surface characteristics that promote cell-scaffold interactions. The final properties of a scaffold strongly depend on both material compositions and process conditions. This research project investigates different aspects related to the design fabrication and characterization of bioactive electro-active scaffolds. Scaffolds were produced using an extrusion-based additive manufacturing system and different material compositions based on Poly (ε-caprolactone) (PCL) mixed with hydroxyapatite (HA), β-tri-calcium phosphate (TCP) and multi-wall carbon nanotubes (MWCNTs) were investigated. HA and TCP are biocompatible and degradable ceramics related to improve the bioactivity of the scaffolds and MWCNTs were selected to improve mechanical properties and due to their excellent electrical conductivity characteristics, to promote both cell-cell and cell-substrate communication. Experimental work was conducted to characterize both pre-processed materials and produced scaffolds evaluating the rheological, mechanical, thermal, chemical and biological properties. Rheological tests show that printability strongly depends on the concentration of the inorganic fillers (MWCNTs, HA and TCP) and processing parameters such as temperature, screw rotational velocity and deposition velocity. The addition of MWCNTs, HA and TCP can enhance the compressive modulus of PCL scaffolds from 48 MPa to 75 MPa in the case of PCL/HA, or 88 MPa in the case of PCL/TCP and PCL/MWCNTs. Biological results show that all scaffolds containing MWCNTs, HA and TCP are biocompatible (more than 80% cell viability), bioactive (40% increase for TCP, 60% increase for HA and 86% increase for MWCNTs) and osteoconductive (significant increase of ALP activity). Results also show that the addition of MWCNTs improves the osteoinductive properties and the presence of nano-sized HA improves the mineralization process. This research shows that PCL/HA/MWCNTs can be viable scaffolds for bone tissue engineering, providing a promising way for bone tissue regeneration.
APA, Harvard, Vancouver, ISO, and other styles
10

Hafri, Mohamed. "Segmentation de l'os cortical pour la prédiction des fractures ostéoporotiques. Application à l'imagerie in vivo (HRpQCT)." Thesis, Orléans, 2017. http://www.theses.fr/2017ORLE2052/document.

Full text
Abstract:
Cette thèse concerne la segmentation d’images HRpQCT et l’évaluation d’indices morphologiques de l’os cortical pour le diagnostic de l’ostéoporose et la prédiction des fractures osseuses. Dans un premier temps,deux méthodes sont proposées pour la segmentation de l’os cortical. La première utilise une nouvelle approche des contours actifs basée sur la logique floue suivie d’une nouvelle technique de remplissage développée pour imiter le comportement des opérateurs pour séparer l’os cortical de l’os trabéculaire. La deuxième approche est une technique 3D à double contours actifs combinant à la fois les informations locales le long et entre les deux contours. Les deux approches de segmentation sont comparées à celles de l’état de l’art afin de valider leurs performances. Dans un second temps, différents indices extraits de l’os cortical sont utilisés pour déterminer leur potentiel de prédiction des fractures ostéoporotiques. Les résultats obtenus montent que l’analyse globale de l’os cortical masque des variations potentiellement importantes.Par conséquent, une décomposition régionale de l’enveloppe corticale est proposée afin d’améliorer la prédiction du risque fracturaire
This thesis concerns the segmentation of HRpQCT images and the evaluation of the cortical bone parameters for the osteoporosis characterization and the fracture prediction. Firstly, two approaches were proposed to segment the cortical bone. The first uses a new fuzzy energy active contours approach followed by a new filling technique designed to mimic the behaviour of clinicians while extracting the cortical bone from the trabecularone. The second approach is a local based 3D dual active contours approach proposed to separate between three regions constituting the image. To move, this approach combines the local information along each point in the two contours conjointly with the information between them. The segmentation results of these approaches were confronted to the state of the art methods to validate their performance. Secondly,different parameters were extracted from the segmented cortical bone to monitor the association of these parameters with the osteoporotic fracture prediction. Global analysis of the cortical bone obscures potentially important regional variations. Therefore, regional cortical decomposition was proposed to illustrate that cortical sub-regions could improve the evaluation of fracture risk than the global analysis of the cortical bone
APA, Harvard, Vancouver, ISO, and other styles
11

Xiong, Hui, and 熊暉. "Condylar adaptation to active mandibular forward positioning in non-growing rats." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B31374220.

Full text
APA, Harvard, Vancouver, ISO, and other styles
12

Hudson, Athol Peter Gilfillan. "Comparative bond strengths of stainless steel orthodontic brackets bonded with different bonding agents." Thesis, University of the Western Cape, 2007. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_4825_1256889166.

Full text
APA, Harvard, Vancouver, ISO, and other styles
13

Manent, Noémi. "Etablissement des spécifications d'un produit entrant dans la synthèse d'une substance active : contexte réglementaire et exemple." Paris 5, 1996. http://www.theses.fr/1996PA05P188.

Full text
APA, Harvard, Vancouver, ISO, and other styles
14

Frith, Julie C. "Studies into the mechanism of action of clodronate." Thesis, University of Sheffield, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299577.

Full text
APA, Harvard, Vancouver, ISO, and other styles
15

Santos, Marco Paulo Soares dos. "A new concept model for instrumented active orthopaedic implants." Doctoral thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/16315.

Full text
Abstract:
Doutoramento em Engenharia Mecânica
Total hip replacement (THR) is one of the most performed surgical procedures around the world. Millions of THR are carried out worldwide each year. Currently, THR revision rates can be higher than 10%. A significant increase of the number of primary and revision THRs, mainly among patients less than 65 years old (including those under 45 years old) has been predicted for the forthcoming years. A worldwide increase in the use of uncemented fixation has also been reported, incidence caused mainly by the significant increase of more active and/or younger patients. Besides the significant breakthroughs for uncemented fixations, they have not been able to ensure long-term implant survival. Up to date, current implant models have shown evidences of their inability to avoid revision procedures. The performance of implants will be optimized if they are designed to perform an effective control over the osseointegration process. To pursue this goal, improved surgical techniques and rehabilitation protocols, innovative bioactive coatings (including those for controlled delivery of drugs and/or other bio-agents in the bone-implant interface), the concepts of Passive Instrumented Implant and Active Instrumented Implant have been proposed. However, there are no conclusive demonstrations of the effectiveness of such methodologies. The main goal of this thesis is to propose a new concept model for instrumented implants to optimize the bone-implant integration: the self-powered instrumented active implant with ability to deliver controlled and personalized biophysical stimuli to target tissue areas. The need of such a new model is demonstrated by optimality analyses conducted to study the performance of instrumented and non-instrumented orthopaedic implants. Promising results on the potential of a therapeutic actuation driven by cosurface-based capacitive stimulation were achieved, as well as for self-powering instrumented active implants by magnetic levitation-based electromagnetic energy harvesting.
A artroplastia total da anca (THR) é um dos procedimentos cirúrgicos mais realizados à escala global. Milhões de THRs são realizadas todos os anos em todo o mundo. Atualmente, as taxas de revisão destas artroplastias podem ser superiores a 10%. O número de THRs primárias e de revisão têm aumentado e estima-se que cresçam acentuadamente nos próximos anos, principalmente em pacientes com idades inferiores a 65 anos (incluindo aqueles com menos de 45 anos). Também se tem verificado uma tendência generalizada para o uso de fixações não cimentadas, incidência principalmente causada pelo aumento significativo de pacientes mais jovens e/ou activos. Embora se tenham realizado avanços científicos no projeto de implantes não cimentados, têm-se verificado o seu insucesso a longo-prazo. Encontram-se evidências da ineficácia dos modelos de implantes que têm sido desenvolvidos para evitar procedimentos de revisão. O desempenho dos implantes será otimizado se estes foram projetados para controlarem eficazmente o processo de osseointegração. Para se alcançar este objetivo, têm sido propostas a melhoria das técnicas cirúrgicas e dos protocolos de reabilitação, a inovação dos revestimentos (onde se incluem os revestimentos ativos projetados para a libertação controlada de fármacos e/ou outros bio-agentes) e os conceitos de Implante Instrumentado Passivo e Implante Instrumentado Ativo. Contudo, não existem demonstrações conclusivas da eficácia de tais metodologias. O principal objetivo desta tese é propor um novo modelo de conceito para implantes instrumentados para se otimizar a integração osso-implante: o implante instrumentado ativo, energeticamente auto-suficiente, com capacidade de aplicar estímulos biofísicos em tecidos-alvo de forma controlada e personalizada. A necessidade de um novo modelo é demonstrada através da realização de análises de otimalidade ao desempenho dos implantes instrumentados e não-instrumentados. Foram encontrados resultados promissores para o controlo otimizado da osseointegração usando este novo modelo, através da atuação terapêutica baseada na estimulação capacitiva com arquitetura em co-superfície, assim como para fornecer energia elétrica de forma autónoma por mecanismos de transdução baseados em indução eletromagnética usando configurações baseadas na levitação magnética.
APA, Harvard, Vancouver, ISO, and other styles
16

Emmel, Marcus [Verfasser], Christos G. [Akademischer Betreuer] Aneziris, Christos G. [Gutachter] Aneziris, and Horst [Gutachter] Biermann. "Development of active and reactive carbon bonded filter materials for steel melt filtration / Marcus Emmel ; Gutachter: Christos G. Aneziris, Horst Biermann ; Betreuer: Christos G. Aneziris." Freiberg : Technische Universitaet Bergakademie Freiberg Universitaetsbibliothek "Georgius Agricola", 2014. http://d-nb.info/1220837660/34.

Full text
APA, Harvard, Vancouver, ISO, and other styles
17

Derbré, Séverine. "Quelques "bonnes réactions" de chimie organique pour élucider les mécanismes d'action de produits naturels actifs : application à la squamocine, une acétogenine des annonaceae." Paris 11, 2006. http://www.theses.fr/2006PA114817.

Full text
Abstract:
Afin de mieux comprendre les mécanismes d'action des acétogénines des Annonaceae cytotoxiques, la synthèse d'analogues structuraux et de sondes dérivées de la squamocine a été envisagée. La réaction de DRAQ a conduit à l'hémisynthèse d'une chimiothèque d'analogues quinoniques de squamocine dont les activités pro-apoptotiques et inhibitrices du complexe I de la chaîne respiratoire mitochondriale ont été évaluées. Aucun lien clair entre l'inhibition de cette enzyme supposée responsable de l'activité des acétogénines et l'induction de l'apoptose n'a pu être établi. La squamoquinone s'est avéré un meilleur inducteur de l'apoptose que la squamocine. Cette apoptose est mitochondriale et caspases-dépendante. La réaction de cycloaddition 1. 3-dipolaire de Huisgen catalysée par le cuivre (I) a permis la synthèse des premières sondes fluorescentes. Par microscopie , les mitochondries ont été identifiées comme les principales cibles. Le couplage de cette réaction au concept ABPP et aux techniques de protéomique, nous ont permis d'identifier six protéines cibles. Pour étudier le comportement supramoléculaire des acétogénines, la squamocine a été greffée sur des châssis p-tert-butylcalixarène et phloroglucinol par cette réaction de chimie "clic". La comparaison de la structure de deux diastéréoisomères de chamuvarinine, obtenus par hémisynthèse à partir de la squamocine, à celle de la chamuvarinine naturelle a conduit à réfuter l'hypothèse d'un lien biosynthétique entre les deux acétogénines
Radical decarboxylation and quinone addition reaction allowed us to obtain a library of squamocin quinonic analogues. We evaluated both pro-apoptotic potential and mitochondrial complex I inihibition, supposed to be responsible for acetogenins activity. No clear link between the enzyme inhibition and apoptosis induction appeared, suggesting the possible existence of other biological targets. Squamoquinone, ten times more potent than squamocin as an apoptotic inducer, emerged as a promising compound, as it induces apoptosis through a mitochondrial caspase-dependent pathway. Huisgen type 1,3-dipolar cycloaddition, catalysed by copper (I) led to the first fluorescent acetogenins. Mitochondria were identified as their major targets by confocal microscopy. We also studied the kinetics of cell penetration. The association of this "click chemistry" reaction both with the activity-based protein profiling (ABPP) concept and classical proteomic methods, allowed us to poiny out five proteins as targets of our fluorescent probes. Those proteins are currently under identification by mass spectrometry. This observation confirmed the hypothesis of a more comlex mechanism of action for acetogenins than the one initially describes. Aiming at understanding the particular supramolecular behaviour of acetogenins of Annonaceae, squamocin was branched onto p-tert-butylcalixarene and phloroglucinol scaffolds, using the same "click chemistry" reaction. We also obtained two diastereoismers of chamuvarinin from squamocin, using biomimetic synthesis. The comparison of their spectral data with natural chamuvarinin led to rule out a biosynthetic link between both acetogenins
APA, Harvard, Vancouver, ISO, and other styles
18

Duan, Xuchen. "Physiological and biological mechanisms of bisphosphonate action." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:36b0439d-2f89-4c1e-8bb3-941b4e6ee847.

Full text
Abstract:
Bisphosphonates (BPs) are stable analogues of pyrophosphate widely used for the treatment of bone diseases characterised by increased bone resorption. Studies over the years have shown that the pharmacological potencies of BPs are dependent both on their binding affinities for bone mineral and on their inhibitory actions on osteoclasts. In addition, potential effects on other cell types present locally in the environment of skeletal tissues have been reported. The present study systematically evaluated the relative mineral-binding affinities of individual BPs of clinically relevance in mixtures of these compounds and the changes with elution pH by using column chromatography with ceramic hydroxyapatite and fluoroapatite combined with mass spectrometric identification and quantitation of the individual BPs. The results indicate that pH has a profound effect on the ionisation of the phosphonate and R2 functional groups, with BPs having greater affinities at lower pH as shown by increased retention times. Moreover, two other approaches, namely using Langmuir adsorption isotherms and competition assays based on fluorescent BP, have been developed to assess the mineral-binding capacities and dissociation constants of BPs. These results suggest that there are substantial differences among BPs in their binding to hydroxyapatite. From the cellular aspect of my study, I present evidence for the anti-apoptotic effects of BPs in osteocytes and osteoblasts. However, the study of prosurvival signalling pathways involved in these cells needs to be optimised. The work described in this thesis provides novel insights into the physiological and biological mechanisms of BP action. My project has provided a better knowledge of the physicochemical properties of BPs, which are highly relevant to their differential distributions within bone, their biological potencies, and their durations of action. Additionally, the cell culture studies may provide new information on the cellular effects of BPs on osteocytes and osteoblasts.
APA, Harvard, Vancouver, ISO, and other styles
19

Gillespie, Indria. "Increasing Blacks' Representation and Utilization on the Bone Marrow Registry: An action-oriented needs assessment." Scholarly Commons, 2018. https://scholarlycommons.pacific.edu/uop_etds/3546.

Full text
Abstract:
The purpose of this action-oriented needs assessment was to ascertain the knowledge, motivation, and culture (KMC) needs of Blacks regarding joining the Be The Match bone marrow registry and participating in the bone marrow donation process. This needs assessment will be utilized to lay the foundation for an educational and research based nonprofit organization, Angels In Disguise, that I developed. This study will also be used to inform the bone marrow registry of the KMC needs of the Blacks who participated in this study. The data collection came from nine observations, four post-observation surveys, five donor interviews, two prototype development groups, and a prototype field test. The formative results from the data collection partially aligned with the literature, which showed that a lack of knowledge resulted in Blacks not joining the Registry. An outlier materialized from the formative data, indicating that all five donor interviewees had joined the bone marrow registry without having knowledge of it, its processes, or the critical need for Blacks to join. On the other hand, the formative data supported the literature when the donor interviewees became a bone marrow match and were faced with the decision to move forward with the bone marrow donation process. All five donor interviewees sought and obtained knowledge about the bone marrow registry prior to being able to move forward with the donation process. In contrast, the formative data around motivation fully aligned with the literature. Blacks who lacked motivation do not join the bone marrow registry or participate in the bone marrow donation process, whereas the literature stated that many Blacks do not join the bone marrow registry due to cultural attitudes and beliefs. Research indicates that the Black community distrusts the medical community due to their being used as medical guinea pigs in the past. Also, Blacks fear pain and their health being compromised due to bone marrow donation. Interestingly, the formative data results did not support or show a lack of support of the literature. Cultural attributes and beliefs did not manifest themselves in the formative data results. The two prototype development groups participated in design thinking utilizing iterative brainstorming exercises, rapid prototyping, and assumption testing. The prototype development groups analyzed the data by categorizing and coding the data into themes through participatory research and collaborative analysis. The results of the two prototype development groups culminated into a final prototype. The final prototype was aimed at addressing the KMC needs of the Black participants, which were two-fold. First, the Registry needs to build a relationship with the Black community. Second, participants required knowledge about the Registry, the matching and donation processes, and the critical need for Blacks to join the Registry and participate in the donation process be provided to them in an educational setting, a symposium. The final prototype culminated into a bone marrow symposium that was tested in the field. The final prototype consisted of three videos about the bone marrow registry, a panel discussion with three Black bone marrow donors who had donated to non-relatives, and a pre- and post-prototype field test survey. The summative findings of this study were the results of the pre- and post-prototype field test surveys and post prototype field test. The findings of the pre-prototype field test survey, regarding knowledge, indicate the participants knew nothing or very little about the bone marrow registry. After being exposed to the prototype, the participants indicated in the post-prototype field test survey they had learned by joining the bone marrow registry they could possibly save a life. They also indicated they did not need any additional information about the bone marrow registry in order to make a decision to join and participate in the bone marrow donation process. Regarding motivation, there was not much change between the pre- and post-prototype field test survey results. The participants had indicated in both the pre- and post-prototype field test surveys that they would be motivated to join the bone marrow registry and participate in the bone marrow donation process if it could save a life. With regard to culture, the participants indicated in both the pre- and post-prototype field test surveys that no beliefs would affect their decision to join the registry and participate in the bone marrow donation process.
APA, Harvard, Vancouver, ISO, and other styles
20

Dobie, Ross. "Mechanisms of GH action on the skeleton : role of SOCS2." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/21045.

Full text
Abstract:
Determining the mechanisms by which growth hormone (GH) enhances bone growth and development has proven difficult. GH can act either systemically via the stimulation of liver insulin like growth factor (IGF)-1, or locally via activation of the GH receptor (GHR). Furthermore, the local actions of GH may be IGF-1 dependent (indirect) or independent (direct). Suppressor of cytokine signalling 2 (SOCS2) has been identified as an important regulator of GH signalling via the JAK/STAT pathway. The SOCS2 knockout (Socs2-/-) mouse is characterised by its overgrowth phenotype despite no elevation in systemic GH and IGF-1 levels. It therefore offers a valid and novel model to investigate the local effects of enhanced GH signalling on the skeleton. The work presented in this thesis investigates the Socs2-/- mouse model to better understand the actions of local GH on longitudinal bone growth and bone accrual. Ex vivo metatarsal organ cultures, osteoblast cultures, and in vivo approaches are used to unravel the mechanisms of GH action on the skeleton. This thesis also explores the potential of SOCS2 as primary mediator of inflammatory induced bone loss through the utilisation of the dextran sulphate sodium (DSS) model of colitis. Embryonic and postnatal ex vivo metatarsal organ cultures are used to study the mechanism of GH action on longitudinal bone growth. Specifically, the present work highlights that enhanced linear growth in the absence of SOCS2 is associated with an increase in the GH regulated proteins, IGF-2 and IGF binding protein 3 (IGFBP3), but not IGF-1. This indicates that IGF-1 may not be essential for mediating GH action on bone growth. Completion of an in depth analysis of the bone phenotype of juvenile and adult, male and female Socs2-/- mice reveals an anabolic phenotype consistent with increased GH signalling. Male Socs2-/- mice are shown to have a greater enhancement of cortical parameters compared to females, resulting in increased bone strength. Investigation of the mechanisms behind the enhanced bone accrual in Socs2-/- mice identifies SOCS2 as the primary SOCS protein regulating GH signalling in primary osteoblasts. The JAK/STAT pathway is confirmed as the key signalling pathway targeted by SOCS2. Despite this enhanced signalling there is little evidence presented in this thesis to suggest that GH actions on osteoblasts and ultimately bone mass are mediated through increased Igf1 expression. GH treatment is shown to be anabolic to bone of young juvenile Socs2-/- mice, but not WT mice. This increase in bone mass is associated with increase bone p-STAT5 signalling, but no increase in Igf1 levels indicating that GH may have IGF-1 independent effects in the Socs2-/- mouse model. GH treatment of young mice also reveals an age and sex specific effect of GH action where GH does not stimulate growth until approximately 3 weeks of age. From 3 weeks of age, WT female mice show increased growth in response to GH, but males do not. The increased growth is associated with increased p-STAT5 signalling and increased bone area. This thesis also confirms SOCS2 a critical mediator of bone loss associated with inflammation. The present results show that deteriorated trabecular bone health in colitic mice is associated with elevated Socs2 expression in bone. Furthermore, despite similar levels of gut inflammation observed in Socs2-/- mice with DSS induced colitis these mice are partly protected from poor bone health. The work described herein has used the Socs2-/- mouse model to strengthen our understanding of the actions of local GH on skeletal growth and development. It also provides compelling evidence for the importance of SOCS2 as a mediator of bone loss in cases of inflammatory bowel disease.
APA, Harvard, Vancouver, ISO, and other styles
21

Komi, Abdoul Karim. "Impacts socio-économiques des bonnes pratiques du développement durable sur une entreprise et ses parties prenantes : de l’opérationnalisation de la performance sociale à une action collective dans la promotion immobilière." Thesis, Lille 1, 2016. http://www.theses.fr/2016LIL12002.

Full text
Abstract:
La Performance Sociale de l’Entreprise (PSE) s’inscrit dans une approche principes-processus-résultats fondée sur la Théorie des Parties Prenantes. Son opérationnalisation renvoie à des difficultés notamment imputables au concept de Développement Durable : complexité des enjeux socio-techniques, préoccupations (sociales, environnementales, économiques) incompatibles, ... A ces difficultés, s’ajoutent celles d’une approche par les Parties Prenantes (PP) : identification, conflits intra/inter-catégorie, dynamique des relations, … Partant, il s’agit de coordonner les PP pour éviter les conflits. Entre alors en jeu la question de l’action collective relative à l’opérationnalisation de la PSE. Cette "thèse CIFRE" s’intéresse particulièrement aux conditions de l’émergence et de la pérennisation d’une telle action ; ces conditions émanant de la concertation des PP et fondamentalement du dépassement (compromis) de leurs conflits. L’outillage proposé par les théories de l’action collective est mobilisé pour dépasser les difficultés de l’opérationnalisation de la PSE ; la théorie de l’ordre négocié pour mieux identifier les PP évoluant entre conflits et coalitions, s’inscrivant alors dans une dynamique ; les approches en termes d’Economies de la Grandeur pour saisir leurs conflits et compromis. Dans le secteur de la Promotion Immobilière, il y a une crise de confiance et - pour une action collective - il faut des règles. Notamment, le conflit fondé sur la valeur et sa création est profond ; et le compromis écolo-marchand en découlant est controversé. Si l’action collective y est donc voulue commune, elle ne peut être une "action à plusieurs" et reste une "action ensemble"
Corporate Social Performance (CSP) is part of an approach principles-process-results based on Stakeholder Theory. Its operationalization refers to difficulties particularly due to the concept of Sustainable Development: complex socio-technical issues, incompatible concerns (social, environmental and economic) ... To these difficulties, are added those of an stakeholder approach: identification, intra/inter-category conflicts, relationship dynamics, ... Accordingly, it is to coordinate the stakeholders to avoid conflicts. This engages the question of collective action on CSP operationalization. This "CIFRE-thesis" is particularly interested in the conditions for the emergence and sustainability of such action; these conditions emanating from the consultation of stakeholders and fundamentally the exceeding (compromise) of their conflicts. The tools offered by the theories of collective action is mobilized to overcome the difficulties in the CSP operationalization ; approaches in terms of "Economies de la Grandeur" to capture the conflicts and compromises; the theory of negotiated order to better identify the stakeholders moving between conflicts and coalitions, then enrolling in a dynamic. In the sector of real estate development, there is a deep crisis of confidence and - for collective action – rules are needed. Especially, the conflict based on value and its creation is deep; and the "écolo-marchand" compromise resulting is controversial. If collective action is therefore required "common", it cannot be an "action à plusieurs" and remains an "action ensemble"
APA, Harvard, Vancouver, ISO, and other styles
22

Cedras, Riaan Brinley. "The diet and feeding of the pelagic goby, sufflogobius bibarbatus, off Namibia." Thesis, University of the Western Cape, 2009. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_4393_1297410840.

Full text
Abstract:

The general diet of Sufflogobius bibarbatus in the northern Benguela upwelling ecosystem was investigated from gut content analysis in two separate studies. The first study was conducted over two 48 h diel sampling stations onboard the RV Dr. Fridtjof Nansen during a dedicated cruise conducted in January 2006, whilst the second was conducted on cruises of opportunity aboard the RV Welwitschia during 2001 and 2002. The results of both studies indicate that S. bibarbatus has a fairly generalised diet, feeding on benthic and pelagic animals for the most part: phytoplankton was uncommonly reported from the 3739 fish examined. Larger fish ate primarily benthic organisms, whereas smaller individuals include substantial number of pelagic organisms in their diet. There would appear to be a clear relationship between the environment occupied by individuals and their diet: large fish are predominantly demersal and display limited vertical migration, whilst small fish are thought to be more pelagic. Results strongly indicate that this species is opportunistic. The present study sheds new light on the ecology of the species, which is becoming increasingly important in the region.

APA, Harvard, Vancouver, ISO, and other styles
23

Bailly, Laurent. "Le secteur minéralisé du Cerro Bonete (sud ouest Bolivie) : étude du magmatisme, des minéralisations et altérations associées : essai de localisation de la source des métaux." Nancy 1, 1994. http://www.theses.fr/1994NAN10289.

Full text
Abstract:
Le massif du Cerro Bonete, district du sud Lipez, est situe à l'extrémité sud de l'altiplano bolivien, à proximité de la frontière avec l'Argentine. Il est recouvert par les formations volcaniques cénozoïques de rondal (andesi-basaltes, andésites, 23,5 ma) et de quehua, représentée par des nappes ignimbritiques, des brèches, des dômes et stocks de composition dacitique à rhyodacitique. Ces formations servent d'encaissant à de nombreuses mines et indices miniers a bi, ag, pb, zn, cu, as et sb. En s'éloignant des veines dans les encaissants dacitiques à rhyodacitiques, l'association à illite dominante-chlorite subordonnée passe latéralement à une association à chlorite dominante-illite et kaolinite subordonnées. Dans les laves basiques à intermédiaires de la formation rondal, une altération à smectites-interstratifiés se développé. Les températures de mise en place des dépôts, estimées par l'intermédiaire de géothermomètres minéraux et des inclusions fluides sont comprises entre 200 et 350c. Les métaux rencontrés dans les différentes veines ont pu être localisés dans les minéraux accessoires opaques des différentes formations et dans les phases silicatées d'origine magmatique et secondaire. Cependant, les bilans réalisés montrent que la source des métaux n'est pas l'encaissant proche des minéralisations, la géométrie des circulations hydrothermales dépassant largement celle des appareils volcaniques. Verticalement, les différents dépôts étudiés s'étageraient depuis des gisements de subsurface (200 à 300 m) proches des dépôts de type source chaude jusqu'à des gisements formes à une profondeur inferieure à 1 km proche des dépôts épithermaux de type adulaire-sericite. Dans un contexte plus général, il semble que le niveau actuel d'érosion joue un rôle non négligeable sur l'observation des paragenèses métalliques des différentes veines, ce qui permet d'expliquer la zonalité metallogenique observée au niveau régional et qui en terme de prospection pourrait conduire à la découverte d'autres gisements
APA, Harvard, Vancouver, ISO, and other styles
24

Chen, Cheng. "Mechanical and micro-structural modeling of trabecular bone by in vivo imaging." Diss., University of Iowa, 2016. https://ir.uiowa.edu/etd/2193.

Full text
Abstract:
Osteoporosis is a bone disease associated with fracture risk. Accurate assessments of fracture risk, guidelines to initiate preventive intervention, and monitoring treatment response are of paramount importance in public health. Clinically, osteoporosis is defined by low bone mineral density, which explains 65-75% of the variance in bone stiffness. The remaining variability is due to the cumulative and synergistic effects of various factors, including trabecular bone micro-architecture. Osteoporostic imaging is critically important in identifying fracture risks for planning of therapeutic intervention and monitoring response to treatments. In this work, quantitative analysis of trabecular bone micro-architecture using volumetric imaging techniques and computational biomechanical simulation through finite element modeling (FEM) are applied on in vivo imaging for various human studies. The ability of imaging methods in characterizing trabecular bone micro-architecture was experimentally examined using MRI and multi-row detector CT. They were found suitable for cross-sectional and longitudinal studies in monitoring changes of trabecular micro-architectural quality in clinical research. A framework which consists of robust segmentation of in vivo images and quality mesh generator, was constructed for FEM analysis. The framework was experimentally demonstrated effcient and effective to predict bone strength under limited spatial resolution. The ability of distinguishing bone strengths of different groups were evaluated on various human studies. And the relation between FEM and image-based micro-architectural measures was explored. Quantitative analysis supports the hypothesis that trabecular bone have distinct structural properties in different anatomic sites and the osteoporosis related change of the micro-architecture also varies. It highlight the importance of standardizing the definition of bone scan locations and the segmentation of such well-defined regions. A shape modeling method was proposed to solve the problem and its application in human proximal femur using MRI were presented. The method was compared with manual segmentation and found highly accurate. Together with tools developed for quantitative analysis, this work facilitates future researches of trabecular bone micro-architecture in different anatomic sites.
APA, Harvard, Vancouver, ISO, and other styles
25

Zhou, Lixiong, and 周立雄. "Differential action of bone morphogenetic protein BMP-2 and BMP-7 on nucleus pulposus cells of intervertebral disc." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/209509.

Full text
Abstract:
Low back pain (LBP) is associated with intervertebral disc (IVD) degeneration and exerts enormous socioeconomic burdens on the society. The nucleus pulposus (NP) is the structural and functional core of the IVD, and plays vital roles in its homeostasis. Although the etiology of IVD degeneration is not fully understood, the cellular changes of the NP have been proposed to be associated with degeneration. Conventional management for IVD degeneration primarily targets to relieve LBP and other symptoms without restoring or preserving disc function. Novel therapeutic strategies have emerged with an aim to retard or even reverse disc degeneration. In particular, the use of growth factors, such as the bone morphogenetic proteins (BMP), has received considerable attention due to their anabolic effects on extracellular matrix (ECM) synthesis by NP cells. BMP-2 and BMP-7 are of great interest for their involvement in osteogenesis, chondrogenesis, and development and maintenance of the IVD. To date, the benefits of BMP-2 on disc degeneration are controversial, given the inconsistent findings from animal model studies. The effectiveness of BMP-7 in disc repair, however, has been well demonstrated both in vitro and in vivo. A better understanding of the differences between BMP-2 and BMP-7 regulatory action on NP cells may facilitate future applications of BMP in disc repair/regeneration. This study hypothesized that BMP-2 and BMP-7 act differentially on human NP cells via different signal transduction processes. The differential effect of BMP-2 and BMP-7 was first tested in bovine NP cells using a three-dimensional culture system (alginate beads). Both BMP-2 and BMP-7 enhanced ECM production and phenotypic characteristics of bovine NP cells. Notably, BMP-7 was significantly more potent than BMP-2 in this regard. The effects of BMPs were further tested on non-degenerated (ND-NP) and degenerated (D-NP) human NP cells. The DMMB assay revealed that BMP-7 exerted a superior up-regulatory action on GAG production of D-NP cells compared to BMP-2. Furthermore, the overall response of D-NP cells to BMP-2 and BMP-7 was significantly lower than ND-NP cells. Immunohistochemical staining and quantitative RT-PCR assays demonstrated that D-NP cells possess a more fibroblastic and less chondrocyte-like phenotype than ND-NP cells. At the mRNA level, the BMP receptor BMPR1A was not expressed in D-NP cells. BMP-7, but not BMP-2, induced expression of BMPR1A in D-NP cells. On the other hand, gene expression of selected TGF-β pathway components and hypoxia pathway components were significantly up-regulated by BMP-2 but down-regulated by BMP-7. These findings suggest that D-NP cells can activate differential molecular cascades in response to BMP-2 and BMP-7. In conclusion, this study showed a superior effect of BMP7 in up-regulation of classical BMP signaling components including BMP receptor BMPR1A. The reduced responsiveness of D-NP cells to BMP-2 and BMP-7 stimulation may be related to a different expression pattern of BMP receptors. This study provides insights into the differential regulatory actions of BMP-2 and BMP-7 on human NP cells and facilitates the future application of BMPs in managing disc degeneration.
published_or_final_version
Orthopaedics and Traumatology
Doctoral
Doctor of Philosophy
APA, Harvard, Vancouver, ISO, and other styles
26

Bassi, Anita Kaur. "The use of phosphorous containing polymers to mimic the action of bisphosphonate drugs in bone repair." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/the-use-of-phosphorous-containing-polymers-to-mimic-the-action-of-bisphosphonate-drugs-in-bone-repair(a94df78f-96f1-4279-a99c-72b8636b57bc).html.

Full text
Abstract:
Bone has the capacity to regenerate itself, however for challenging defects such as non-uniform factures, repair can be problematic. A similar challenge is presented in the repair of osteoporotic bone. Osteoporotic bone becomes increasingly porous and brittle and the risk of fracture is greatly increased. A drug mimic, poly(vinyl phosphonic acid – co – acrylic acid)(PVPA), has been incorporated into FDA approved poly(ε-caprolactone)(PCL), and aims to mimic the action of bisphosphonates to reduce the activity of osteoclasts. The PVPA polymer contains pendant phosphonic acid groups which are hypothesised to mimic the P-C-P backbone found in bisphosphonates. The PCL/PVPA scaffold has been found to have sufficient mechanical strength in order to be used as a bone void filler as well as providing a hydrophilic surface for superior cell attachment. The substrate has been found to significantly enhance the deposition of collagen, alkaline phosphatase activity and the expression of osteocalcin. Alizarin red staining revealed an increase in the rate of mineralisation in the presence of the drug mimic. The PCL/PVPA substrates have been suggested to induce osteoblast cells from a proliferative phase to a mineralisation stage. This is believed to be due to the presence of phosphorous within the scaffold which could lead to the critical concentration required for the initiation of mineralisation being reached more rapidly and effectively. The PVPA polymer has been found to mimic the action of bisphosphonates by inducing osteoclast apoptosis in vitro, and its actions of osteoclast apoptosis are comparable to that of Alendronate, a commonly administered bisphosphonate. A critical size defect model has demonstrated that the PVPA polymer has the ability to heal critical size defects; the healing potential was two fold greater than the control PCL substrate. Initial in vivo studies using a subcutaneous model demonstrated an improvement in mineralisation in the presence of PVPA. Untreated PCL/PVPA substrates displayed a high level of branched blood vessel formation, essential for healthy bone formation. However PVPA samples pre-treated with VEGF, hindered blood vessel formation and the infiltration of cells. This suggests that the PVPA alone is capable of inducing neovascularisation without the addition of VEGF. The findings suggest that the PCL/PVPA system could be used to treat challenging bone defects such as non-unions and osteoporotic fractures.
APA, Harvard, Vancouver, ISO, and other styles
27

Cody, James Joseph. "A dual-action, armed replicating adenovirus for the treatment of bone metastases of breast cancer." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2008p/cody.pdf.

Full text
APA, Harvard, Vancouver, ISO, and other styles
28

Altunsoz, Omur Serdal. "Determine The Effects Of Long Term Playing Soccer On The Degeneration Of Lumbar Spine." Master's thesis, METU, 2006. http://etd.lib.metu.edu.tr/upload/12607487/index.pdf.

Full text
Abstract:
The main purpose of this study was to determine whether playing soccer at high intensity training for a long period causes degeneration of the lumbar spine or not. This degeneration may occur without any symptoms or low back pain. Results of the present study were discussed in the framework of lumbar disc degeneration, trunk strength, lumbar and hip bone mineral density, trunk flexibility, activity MET scores for active and veteran soccer groups. There have been four subject groups in this study (15 active soccer players, 15 sedentary participants, 14 veteran soccer players, 13 sedentary participants). The BMD was measured in anterior-posterior view with a second-generation dual energy X-ray absorptiometry (DEXA) device. Isokinetic trunk strength data were recorded with the Biodex System Dynamometer (Biobex Medical Inc, Shirly, NY) at the 60º
/sec and 120º
/sec. Plain lateral radiographs were taken. The presence of degenerative changes of each lumbar vertebra was determined by using the Kellgren and Lowrence Score. A modified Schober test was used to measure lumbar flexion. Findings of the study demonstrated that veteran soccer players displayed greater lumbar disc degeneration than other groups. Moreover, v active soccer group had more BMD than other groups, but the veteran group&
#8217
s BMD results were not different while comparing the control participants. Isokinetic test findings of the current study, trunk extension strength at 60/sec was significantly higher in active 1st group players than 2nd group participants, but there were no significant differences between the 1st group and 2nd group in terms of trunk flexion strength and agonist/antagonist ratio at 60/sec. In conclusion, Findings of the study support the main hypothesis that playing soccer at high intensity training at a long period of time may cause lumbar spine degeneration. Degeneration may occur without low back symptoms. Moreover, results supported the idea that Soccer can be accepted an impact loading sport that are to keep or accelerate bone mineral density. At last, having abnormal trunk extension strength while playing actively may cause lumbar disc degeneration on the spine at later years. A similar study should be carried out with a larger number of subjects, and longitudinal studies should be designed to examine the factors that effect the degeneration on the lumbar spine.
APA, Harvard, Vancouver, ISO, and other styles
29

Brusamarelo, Emanuele. "Utilização do metabólito 1,25-dihidroxicolecalciferol proveniente da Solanum glaucophyllum na alimentação de frangos de corte." Universidade Federal de Mato Grosso, 2014. http://ri.ufmt.br/handle/1/442.

Full text
Abstract:
Submitted by Simone Souza (simonecgsouza@hotmail.com) on 2017-08-23T14:00:22Z No. of bitstreams: 1 DISS_2014_Emanuele Brusamarelo.pdf: 1193853 bytes, checksum: ed950682d57e5c216154b030d0087cae (MD5)
Approved for entry into archive by Jordan (jordanbiblio@gmail.com) on 2017-08-24T15:13:12Z (GMT) No. of bitstreams: 1 DISS_2014_Emanuele Brusamarelo.pdf: 1193853 bytes, checksum: ed950682d57e5c216154b030d0087cae (MD5)
Made available in DSpace on 2017-08-24T15:13:12Z (GMT). No. of bitstreams: 1 DISS_2014_Emanuele Brusamarelo.pdf: 1193853 bytes, checksum: ed950682d57e5c216154b030d0087cae (MD5) Previous issue date: 2014-03-11
A nutrição vitamínica e mineral interfere no desempenho e nas características ósseas das aves. O suplemento de vitamina D utilizado sem restrição nas rações para frangos de corte é o colecalciferol inativo e o 25-hidroxicolecalciferol. O objetivo foi avaliar o desempenho, o rendimento de cortes comerciais e de carcaça e os parâmetros ósseos de frangos de corte machos suplementados com 1,25-dihidroxicolecalciferol e redução de cálcio e fósforo disponível nas rações. Um total de 648 machos foi distribuído, em delineamento em blocos ao acaso, com seis tratamentos: dieta controle - atendendo a exigência nutricional; dieta controle negativo - com redução em 15% dos níveis de cálcio e de fósforo disponível; dieta controle negativo suplementada com: 0,5; 1,0; 1,5 e 2,0 μg de vitamina D3 ativa/kg ração respectivamente, com seis repetições (boxes). O desempenho foi avaliado pelo ganho de peso (kg), consumo de ração (kg/ave) e conversão alimentar. As aves foram pesadas com um dia e aos 42 dias de idade, para obtenção do ganho de peso. O consumo de ração foi obtido pela diferença entre a quantidade de ração fornecida, descontando-se as sobras em cada fase da criação. A razão entre o consumo de ração corrigido e o ganho de peso originou a conversão alimentar. Quatro aves/unidade experimental foram amostradas, pesadas e sacrificadas por deslocamento cervical para avaliação dos rendimentos de carcaça e de cortes comerciais no 42º dia de idade. Uma ave/unidade experimental foi amostrada, pesada e sacrificada para a remoção dos tibiotarsos utilizados na avaliação dos parâmetros ósseos no 21º e 33º dias de idade. As características ósseas avaliadas foram: o peso (mg) e comprimento (mg) do osso, índice de Seedor (mg/mm), cinzas ósseas (%) e resistência à quebra (kgf). O suplemento de vitamina D3 ativa com redução de cálcio e de fósforo disponível nas rações não influenciou o desempenho e os rendimentos de carcaça e cortes comerciais (peito, coxa + sobrecoxa e asa) das aves. A redução em 15% dos níveis de cálcio e de fósforo disponível e o suplemento de vitamina D3 ativa nas rações não afetou o peso e o comprimento do osso, o índice de Seedor e a resistência à quebra. O percentual de deposição de cinzas em ossos de frangos de corte aos 21 e 33 dias de idade foi diferente entre tratamentos. Os menores valores para cinzas, sem interferência na resistência à quebra dos tibiotarsos, demonstra a possibilidade de reduzir em 15% os níveis de cálcio e de fósforo disponível nas dietas sem compromoter a estrutura óssea das aves.
The vitamin and mineral nutrition interferes with the production performance and bone characteristics of birds. The vitamin D supplement used without restriction in the feed for broilers is inactive cholecalciferol and 25-hydroxycholecalciferol. The objective of this study was to evaluate the performance, and yields of carcass and commercial cuts and bone parameters of male broilers supplemented with 1,25-dihydroxycholecalciferol and reduction of calcium and available phosphorus in feed. A total of six hundred and forty-eight males, was used in a randomized-block design, with six treatments: control diet - meeting nutritional requirement; negative control diet - with 15% reduction in the levels of calcium and available phosphorus; negative control diet supplemented with: 0.5; 1.0; 1.5 and 2.0 μg of vitamin D3 active/kg diet respectively, with six replicates (boxes). The performance was evaluated by weight gain (kg), feed intake (kg/bird) and feed conversion. The broilers were weighed one day and at 42 days of age, for obtaining the weight gain. Feed intake was calculated as the difference between the amount of feed, discounting the leftovers at each stage of creation. The ratio between feed intake and weight gain corrected feed conversion originated. Later, four broilers of each experimental unit were sampled, weighed and slaughtered by cervical dislocation to evaluate carcass yield and commercial cuts yield at 42 days of age. Later, a one bird of each experimental unit was sampled, weighed and sacrificed for removal of tibiotarsos for the assessment of bone parameters at 21 and 33 days of age. The bones were identified and cleaned of all adhering tissue and frozen (-20°C) until analysis begins. The bone parameters were evaluated weight (mg) and length (mg) of the bone Seedor index (mg/mm) bone ash (%) and breaking strength (kgf). The active vitamin D3 supplement with reduced calcium and available phosphorus in the diets did not influence performance and carcass and commercial cuts (breast, thigh + drumsticks and wing) of poultry. A 15% reduction in the levels of calcium and available phosphorus and vitamin D3 supplement active in the diets did not affect the weight and length of the bone, the index Seedor and resistance to breakage. The percentage of bone ash deposition in bones of broilers at 21 and 33 days of age was different between treatments. The lowest values for ash, without interference in breaking resistance force of tibiotarsos, demonstrates the possibility of reducing in the 15% levels of calcium and available phosphorus in diets without compromising the bone structure of birds.
APA, Harvard, Vancouver, ISO, and other styles
30

Eap, Sandy. "Développement d'implants nanofibreux actifs pour la régénération osseuse." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ053/document.

Full text
Abstract:
Notre équipe a développé une stratégie innovante de fonctionnalisation d’implants nanofibreux synthétiques à base de nanoréservoirs actifs pour la médecine régénérative osseuse. Notre objectif essentiel est de proposer un implant synthétique, biodégradable, et nanostructuré permettant d’accélérer la réparation du tissu osseux. Ces nouveaux implants synthétiques représentent un choix alternatif aux membranes de collagène d’origine animale. Notre stratégie consiste à construire des nanoréservoirs de chitosane, contenant des facteurs ostéoinducteurs tels que la BMP-2 afin d’enrober les nanofibres de nos implants. L’implant synthétique et biomimétique a été conçu à partir du le poly(ε-caprolactone) (PCL),polymère biocompatible et biodégradable approuvé par la FDA, et élaboré grâce à la technique de l’electrospinning afin de mimer la matrice extracellulaire. L’optimisation de ce procédé a permis la mise en oeuvre d’implants d’épaisseurs différentes (jusqu’à 10mm). La double fonctionnalisation de l’implant a permis de le rendre bioactif et vivant en utilisant la combinaison de facteur de croissance et de cellules souches mésenchymateuses. L’efficacité de la double fonctionnalisation des implants de PCL a ainsi été mise en évidence par l’accélération de la régénération osseuse in vivo.L’activité de ces implants fonctionnalisés de nanoréservoirs bioactifs est en cours d’analyse dans le cadre de tests précliniques pour une application maxillo-faciale, parodontale et orthopédique en vu d’obtenir un marquage CE. De plus, une start-up (ARTiOS NanoMed) basée sur cette nanotechnologie a été crée. En conclusion, nous pensons que la technologie développée par notre laboratoire a permis une avancée dans le domaine de la régénération osseuse et que cette technologie présente un fort potentiel d’application en clinique
Our team has developped a novel and unique strategy to functionnalize nanofibrous and synthetic implants based on active nanoreservoirs for bone regeneration. We propose a new synthetic biodegradable and nanostructured implant to accelarate restoration of bone tissue. These new implants could replace collagen membranes from animal origin. The nanoreservoirs are based on chitosan containing osteoinductive growth factors such as BMP-2. Poly(ε-caprolactone) (PCL) is a biodegradable and biocompatible polymer approved by FDA and has been used to produce the synthetic and biomimetic implants by electrospinning in order to mimic the bone extracellular matrix. Optimization of this process has allowed the elaboration of nanofibrous implants with different thicknesses reaching 10 mm. Using the combination of growth factors and mesenchymal stem cells in a double functionalization created a bioactive and living implant. This strategy has been validated in vitro and in vivo thanks to bone site implantation in murin model. Acceleration of bone regeneration in vivo has brought to light the efficiency of the double functionalization onto the PCL implants.The functionalized implants bioactivity is still currently in study for pre-clinical trials in order to obtain authorization for applications in maxillo-facial, parodontal, and orthopaedic fields. Moerover, astat-up (ARTiOS NanoMed) based on this nanotechnology has been founded.To conclude, we believe that our nanotechnology could lead to a new generation of engineered bone implants which has a great potential to be used in the clinic
APA, Harvard, Vancouver, ISO, and other styles
31

Willemin, Anne-Sophie. "Stratégies cellulaires et environnementales pour le développement d’un substitut osseux prévascularisé." Thesis, Université de Lorraine, 2018. http://www.theses.fr/2018LORR0191.

Full text
Abstract:
En cas de pertes de substances osseuses de grande étendue, la capacité naturelle de réparation du tissu osseux n’est pas suffisante et nécessite d’être assistée. La greffe d’os autologue constitue actuellement la référence. Cependant, cette thérapeutique présente tout de même des inconvénients qui ont entrainé le développement de substituts osseux. Mais, aucun matériau à ce jour ne peut remplacer totalement l’os autologue, en raison notamment de la difficulté à recréer un système vasculaire fonctionnel au niveau du site lésé. Depuis quelques années, les espoirs se tournent vers la création d’un substitut osseux prévascularisé afin de pallier la principale limite des alternatives actuelles : l’établissement d’un réseau vasculaire au sein de ce biomatériau. Notre projet vise à évaluer l’effet stimulateur d’un composé naturel, les principes actifs de la nacre solubles dans l’éthanol (appelé Ethanol Soluble Matrix, ESM), à la fois sur les capacités angiogéniques de cellules de la lignée endothéliale et sur la différenciation ostéogénique de cellules souches mésenchymateuses (CSM) avec comme objectif le développement d’un substitut osseux prévascularisé. Dans un premier temps, nous avons montré que l’ESM stimulait les capacités angiogéniques des cellules de la lignée endothéliale : cellules endothéliales matures (HUVECs, cellules endothéliales issues de la veine ombilicale humaine) et cellules progénitrices endothéliales (CPEs) issues de sang de cordon. L'ESM, utilisé à la concentration de 200µg/mL, a permis de dépasser les résultats obtenus (expression génique et test fonctionnel) avec le milieu de culture de référence des CPEs : l’EGM-2 (Endothelial Growth Medium). Nous avons ensuite mis en évidence que l’ESM exerçait un effet stimulateur également sur les CSMs en augmentant l’expression de marqueurs spécifiques des chondrocytes et des chondrocytes hypertrophiques, suggérant une orientation de ces cellules vers une ossification endochondrale. En parallèle de ces travaux, nous avons étudié l’effet paracrine des CSMs sur les cellules de la lignée endothéliale, HUVECs et CPEs. Les vésicules extracellulaires de taille nanométrique (nEVs) ont montré leur capacité à induire une stimulation in vitro de la formation de réseaux vasculaires et de l’expression de gènes endothéliaux. Ces résultats encourageants soulignent la faisabilité de l’utilisation de l’ESM en tant que stimulus à la fois de l’angiogenèse des CPEs et de l’ostéogenèse des CSMs. Ce stimulus pourrait être associé aux nEVs issues de CSMs et aux CPEs au sein d’une matrice tridimensionnelle pour développer un substitut osseux prévascularisé
In case of critical-sized defects, the bone tissue ability of natural healing is not sufficient and needs to be assisted. The autologous bone graft is currently the gold standard. However, this solution has drawbacks that have led to the development of bone substitutes. Nowadays, no substitute is able to supply autogenous bone, due to the difficulties to mimic the vascular system. In recent years, the hopes are focusing on the creation of a prevascularized bone substitute to overcome the main limitation of current alternatives: the creation of a functional vascular network inside the substitute. Our project aims to evaluate the stimulating effect of a natural compound, the nacre extracts called Ethanol Soluble Matrix (ESM), both on the angiogenic abilities of endothelial cell lineage and on the osteogenic differentiation of mesenchymal stem cells (MSCs) to develop a pre-vascularized bone substitute. First, we showed that ESM stimulates the angiogenic potential of two types of endothelial cells: mature endothelial cells (HUVECs, human umbilical vein endothelial cells) and endothelial progenitor cells (EPCs) from cord blood. The ESM, used at the concentration of 200µg/mL, exceeded results obtained with the reference culture medium of EPCs: the EGM-2 (Endothelial Growth Medium). Then, we demonstrated that ESM also exerted a stimulating effect on MSC by increasing the expression of chondrocyte and hypertrophic chondrocyte specific markers, suggesting an orientation of these cells towards endochondral ossification. In line with this work, we studied the paracrine effect of MSCs on endothelial cell lineage, HUVECs and EPCs. Nanoscale extracellular vesicles (nEVs) have been shown to induce an in vitro stimulation of the vascular network formation and of the endothelial gene expression. These encouraging results highlight the feasibility of using ESM as a stimulus for both angiogenesis of EPCs and osteogenesis of MSCs. This stimulus could be associated with MSC-derived nEVs and EPCs within a three-dimensional matrix to develop a pre-vascularized bone substitute
APA, Harvard, Vancouver, ISO, and other styles
32

Olivier, Florian. "Elaboration, caractérisation, dopages et évaluations in vitro et in vivo de matériaux hybrides : Tissus de fibres de carbone / Phosphates de calcium." Thesis, Orléans, 2018. http://www.theses.fr/2018ORLE2052/document.

Full text
Abstract:
Ce travail a consisté à optimiser la synthèse de phosphates de calcium (CaP) déposés sur tissus de fibres de carbone (TFC) par procédé de sono-électrodéposition afin d’obtenir des revêtements uniformes. Les paramètres électrochimiques clés optimisés sont le type et la durée de polarisation cathodique ainsi que la température de l’électrolyte. Pour un potentiel constant de -1 V à 70 °C, un régime d’électrolyse contrôlé de l’eau conduit à la formation d’un revêtement plaquettaire d’hydroxyapatite déficitaire en calcium (CDA) carbonatée. Les plaquettes sont composées de particules lamellaires (de quelques dizaines à centaines de nm) constituées de CDA carbonatée de structure ordonnée au coeur et de structure désordonnée car hydratée en surface des particules, organisation typique des apatites biomimétiques. Le matériau hybride a été dopé en strontium, engendrant la formation de revêtements où les ions Ca²+ sont substitués par des ions Sr²+ de manière contrôlée, conférant au biomatériau de nouvelles propriétés en vue d’une application en régénération osseuse. Ce travail a aussi démontré la possibilité d’adsorber de façon sélective des principes actifs ciblés (tétracycline, naproxène, aspirine) dans chaque constituant du matériau hybride. Les courbes de désorption ont mis en évidence deux modes de libération selon le principe actif.Une évaluation biologique des différentes matériaux hybrides a été réalisée. L’étude in vitro a porté sur la viabilité et la prolifération d’ostéoblastes humains en surface des biomatériaux hybrides, démontrant leur biocompatibilité. L’intérêt d’un dopage (Sr²+, aspirine et naproxène) sur l’activité des ostéoblastes a été démontré. Une expérience pilote in vivo a été menée, consistant à créer un défaut osseux dans des fémurs de rats et à étudier l’influence du type de biomatériaux TFC/CaP sur les évolutions quantitative et qualitative de la régénération osseuse
Optimization of the synthesis of calcium phosphates (CaP) on carbon fiber cloths (TFC) was performed in using sono-electrodeposition process in order to obtain uniform coatings. The electrochemical potential applied and the electrolyte temperature during the synthesis were determined as being key parameters. For a constant potential of -1 V at 70 ° C, a controlled water electrolysis regime results in the deposit of plate-like calcium-deficient apatite (CDA). This plate-like particles (from a few tens to hundreds of nm in length) consist in an ordered structure of carbonated CDA in their core and in a disordered structure in the hydrated surface, a typical organization of biomimetic apatites. The hybrid material was doped with strontium, resulting in a carbonated CDA coating where the Ca²+ ions are controllably substituted by Sr²+ ions, leading to new properties for a bone regeneration application. This work has also shown the possibility of selectively adsorb targeted active molecules (tetracycline, naproxen, aspirin) in each component of the hybrid material. The desorption curves revealed two modes of release depending on the active molecule.A biological evaluation of the different hybrid materials was carried out. The in vitro study investigated the viability and proliferation of human osteoblasts at the surface of hybrid materials, demonstrating their biocompatibility. The interest of a doping (Sr²+, aspirin and naproxen) on osteoblast activity was demonstrated. An in vivo pilot experiment was conducted, through the creation of a bone defect in rat thighbones to study the influence of TFC/CaP biomaterials on the quantitative and qualitative evolutions of bone regeneration
APA, Harvard, Vancouver, ISO, and other styles
33

Ferrand, Alice. "Développement de biomatériaux nanofibreux/microporeux actifs pour la régénération osseuse." Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAE030.

Full text
Abstract:
Les nanotechnologies sont en train de révolutionner le domaine biomédical et plus particulièrement l’ingénierie tissulaire. Elles permettent aujourd’hui, non seulement de réparer mais aussi de régénérer les tissus. Cette nanomédecine régénérative est particulièrement adaptée pour répondre aux besoins importants liés aux maladies dégénératives, au vieillissement et aux traumatismes.Mon travail de thèse s’inscrit dans ce contexte et concerne l’élaboration de biomatériaux nanofibreux et microporeux actifs pour la régénération osseuse. Notre objectif essentiel est de réaliser un implant biodégradable nanostructuré permettant d’accélérer la réparation du tissu osseux. Notre stratégie innovante repose non seulement sur la mise en oeuvre de membranes par électrospinning mais aussi sur leur fonctionnalisation par des facteurs de croissance. Cette fonctionnalisation originale a consisté à enrober ces principes actifs dans des nanoréservoirs en utilisant la technique multicouche de polyélectrolytes. Des membranes de polycaprolactone (PCL) nanofibreuses et microporeuses ont été obtenues par électrospinning puis les fibres ont été enrobées de réservoirs contenant le facteur ostéoinducteur, la protéine morphogénique osseuse 2 (BMP-2). L’induction osseuse engendrée par ces réservoirs actifs a été mise en évidence in vitro après culture d’ostéoblastes humains primaires. Des expérimentations in vivo chez la souris ont permis de confirmer l’accélération de la régénération osseuse grâce à ces nanoréservoirs.Cette même stratégie a été validée in vivo, chez la souris, en utilisant des membranes de collagène d’origine animal commerciales utilisées en clinique. L’activité de ces membranes fonctionnalisées par des nanoréservoirs de BMP-2 est en cours d’analyse dans le cadre de tests précliniques pour une application maxillofaciale et parodontale
Nanobiotechnology enables the emergence of entirely new classes of bioactive devices intended for targeted intracellular delivery for more efficiency and less toxicities. Tissue engineering is an interdisciplinary field that has attempted to implement a variety of processing methods for synthetic and natural polymers to fabricate tissue and organ regeneration scaffolds.We report here the first demonstration of bone regeneration by using a strategy based on a synthetic nanostructured membrane. This electrospun membrane is manufactured by using a FDA approved polymer, PCL, (polycaprolactone), and functionalized with nanoreservoirs of a growth factor (BMP-2). Our expected outcomes are the development of clinical applications in the field of tissue engineering and nanomedecine and particularly in bone regeneration.We propose the development of smart nanostructured active implants for regenerative medicine. Our strategycombines a synthetic biodegradable electrospun nanofibrous membrane based on PCL and a bioactive growth factor (BMP-2) entrapped into polymer nanoreservoirs built atop the nanofibers according to the layer-by-layer technology. In this study, by using primary osteoblasts, we have shown the capacity of these sophisticated implants to promote and accelerate not only in vitro bone induction; but also, in vivo, bone formation (mouse model).We have also validated our strategy, in vivo (mouse model), by using an already used in the clinic collagen membrane (animal origin) to accelerate bone regeneration. This unique strategy is used to entrap, protect and stabilize the therapeutic agent into polymer coating acting as nanoreservoirs enrobing fibers of membranes
APA, Harvard, Vancouver, ISO, and other styles
34

Shor, Audrey Cathryn. "Src kinase inhibitors for the treatment of sarcomas : cellular and molecular mechanisms of action." [Tampa, Fla] : University of South Florida, 2007. http://purl.fcla.edu/usf/dc/et/SFE0001906.

Full text
APA, Harvard, Vancouver, ISO, and other styles
35

Koulocheri, Stavroula. "La représentation et l'assistance du plaideur en justice." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS124.

Full text
Abstract:
« La représentation et l’assistance du plaideur en justice » constitue un sujet classique, mais plus que jamais contemporain. Face à la crise de la justice civile, mais aussi devant son évolution rapide, les choix de politique législative actuels font preuve d’une volonté de renforcer la représentation obligatoire par avocat. Bien que la représentation et l’assistance du plaideur en justice soient utilisées quotidiennement, leur définition et leur finalité en procédure civile restent obscures. Qu’est-ce que « la représentation et l’assistance du plaideur en justice » ? À quoi sert « la représentation et l’assistance du plaideur en justice » ? Notre étude tend à la résolution de ce double problème. À cette fin, nous examinons la nature et la fonction de la représentation et de l’assistance du plaideur en justice. Quant à leur nature, il convient d’analyser leurs composantes conventionnelle et institutionnelle comportant leurs réalités intérieures et extérieures qui les définissent en droit. Quant à leur fonction, il faut approfondir leurs finalités d’intérêt privé et d’intérêt général visant respectivement la protection des droits fondamentaux du plaideur et la bonne administration de la justice. Cette étude permet d’apporter une définition de la représentation et de l’assistance du plaideur en justice, de leur restituer toute leur valeur en procédure civile au regard de leur finalité, de fournir des réponses aux problématiques rencontrées dans la pratique juridictionnelle et d’enrichir la réflexion sur l’avenir de la procédure civile. Elle aboutit à des propositions sur une réforme de la procédure civile fondée sur la représentation à l’instance par avocat
"Legal representation and legal assistance of litigant" is a classic topic, more than ever contemporary, though. In front of civil justice crisis and its rapid evolution, current legislative choices show a willingness to strenghten legal representation by lawyer. Despite the use of legal representation and legal assistance of litigant on a daily basis, their definition and finality remain obscure. What is "legal representation and legal assistance of litigant" ? Which is the purpose of "legal representation and legal assistance of litigant" ? This study tends to solve this double question by examining the nature and the function of legal representation and legal assistance of litigant. As for their nature, it is their conventional and institutional components including their internal and external realities that contibute to their legal definition, that must be analysed. As for their function, it is necessary to delve into their private and general interest aims that respectively tend to protect the fundamental rights of the litigant and the proper administration of justice. This study permits a definition of legal representation and legal assistance of litigant, restores their value in civil procedure with regard to their purpose, provides answers to the judicial practice problems and permits to enrich the reflection on civil procedure’s futur. It leads to proposals for a reform of the civil procedure based on legal representation by lawyer
APA, Harvard, Vancouver, ISO, and other styles
36

Zhao, Guisheng. "PARACRINE/AUTOCRINE ACTIONS OF INSULIN-LIKE GROWTH FACTOR I (IGF-I) IN TRANSGENIC MICE: EFFECTS OF IGF-I IN BONE AND SMOOTH MUSCLE CELLS IN VIVO." Cincinnati, Ohio : University of Cincinnati, 2001. http://www.ohiolink.edu/etd/view.cgi?ucin983477992.

Full text
APA, Harvard, Vancouver, ISO, and other styles
37

Panizzon, Marion. "Good faith in the jurisprudence of the WTO : the protection of legitimate expectations, good faith interpretation and fair dispute settlement /." Oxford ; Portland, Or. : [Zürich] : Hart ; Schultsess, 2006. http://www.netlibrary.com/urlapi.asp?action=summary&v=1&bookid=216427.

Full text
APA, Harvard, Vancouver, ISO, and other styles
38

Geffroy, Alexandre. "La territorialisation de l'action publique en situation de crise : le cas des farines animales dans le contexte de l'Encéphalopathie Spongiforme Bovine (ESB) en France." Thesis, Normandie, 2018. http://www.theses.fr/2018NORMR112/document.

Full text
Abstract:
L’Encéphalopathie Spongiforme Bovine (ESB), maladie animale découverte en 1986, est reconnue comme un problème de santé publique depuis 1996, date à laquelle son lien avec la variante de la maladie de Creutzfeldt-Jakob fut avéré. Dans ce contexte, les autorités françaises et européennes développèrent différentes mesures afin d’endiguer l’épizootie et réduire les risques d’exposition des consommateurs. Les instances gouvernementales se concentrèrent, notamment, sur les farines animales. Ces produits, fabriqués à partir des déchets animaux non consommés par les êtres humains et distribués dans l’alimentation des animaux d’élevage, furent, en effet, reconnus comme le vecteur de propagation de l’agent pathogène dans les troupeaux. En France, ces farines furent complètement interdites d’usage dans les rations alimentaires des animaux d’élevage le 14 novembre 2000. Cette décision plaça alors les pouvoirs publics dans une situation de crise puisque, malgré leur interdiction, leur production demeura et demeure toujours obligatoire car ces dernières permettent de réduire en masse et en volume les quantités de déchets animaux. Les autorités durent ainsi trouver de nouveaux exutoires pour ces produits dont la production atteignait, en 2000, un volume hebdomadaire de 8 000 tonnes. C’est dans ce contexte de gestion d’un produit reconnu nationalement à risque sanitaire que s’inscrit ce travail. La thèse repose sur l’exploitation d’archives de différentes natures (gouvernementales, industrielles, médiatiques et associatives) et poursuit un double objectif. Elle cherche, d’une part, à reconstruire la temporalité de l’action publique dans la gestion des farines animales au regard des différents acteurs locaux impliqués et, d’autre part, à identifier les niveaux d’action et stratégies territoriales en jeu dans le maintien ou la résorption de cette crise. Pour mieux comprendre les processus de territorialisation de l’action publique, la thèse s’inscrit dans une approche mixte qui intègre dans le questionnement géographique les réflexions associées aux « instruments de l’action publique » [Halpern C., Lascoumes P., Le Galès P., 2014] et croise les apports des analyses quantitatives et qualitatives
Bovine Spongiform Encephalopathy (BSE), disease discovered in 1986, is known as public health problem since 1996. Indeed, it has been linked to the variant of Creutzfeldt-Jakob disease has shown. In this context, European and French authorities took several measures to control the epidemic and to decrease the chance of exposure of consumers. Governments especially focused on feed-bone meals, produced from animal waste and used in cattle feed, which were recognised as the vector of the spread of the disease. Feed-bone meal were totally banned the 14th November 2000 in France and this decision entailed a huge crisis. Indeed, feed-bone meal were declared unfit for cattle consumption but their production remained, and still remains, necessary. They allow to reduce in weight and volume the quantities of animal waste which are produced by agro-food industry. French government had to find new outlet for feed-bone meal which are massively produced (8 000 tons per week in 2000). This thesis analyses the way this crisis has been handled in France. She draws on archives from several sources (governmental, industrial, media, associative) and has two aims. Firstly, thesis points out the temporality of public action in the light of local actors who were in charge. Secondly, this work identifies levels of action and territorial strategies which have been mobilised to manage the French feed-bone meal crisis. To better understand territorialisation of public action, thesis sets in mix-methods methodology which integrate in geographical issue the considerations around “tools of public action” [Halpern C., Lascoumes P., Le Galès P., 2014] and crosses the contributions of qualitative and quantitative analysis
APA, Harvard, Vancouver, ISO, and other styles
39

Lévêque, Hubert. "Synthèse d'oxazolines fonctionnelles chirales : accès aux phases stationnaires polymériques et greffage sur silice pour l'application à la chromatographie énantiosélective." Rouen, 1994. http://www.theses.fr/1994ROUES058.

Full text
Abstract:
La synthèse de dérivés de l'oxazoline de Meyers à partir du (1S, 2S)-2-amino-1-phénylpropan-1,3-diol, a permis de préparer des phases stationnaires chirales pour évaluer le potentiel de ces hétérocycles en chromatographie énantiosélective. L'accès à des systèmes séparatifs, dont les performances ont été jugées satisfaisantes (séparation de dérivés d'aminoacides et d'amines aromatiques), a été effectué par introduction du motif chiral dans une chaîne polysiloxane ou par greffage sur silice. La mise au point de voies d'accès-sélectives à des oxazolines fonctionnelles chiales, isomères des précédentes, et à des fonctions amides dérivées d'amino ou cyano-oxazolines, a permis de disposer de plusieurs structures chirales dans cette série. Une étude, réalisée sur le greffage d'oxazolines fonctionnelles par des méthodes classiques (silanisation), nous a fourni des silices greffées à différents taux (de 0,36 a 1,06 mmol/g). D'autre part, le greffage d'une oxazoline chirale par un lien silicium-carbone a conduit à une phase stationnaire énantiosélective
APA, Harvard, Vancouver, ISO, and other styles
40

Meynaud-Zeroual, Ariane. "L’office des parties dans le procès administratif." Thesis, Paris 2, 2017. http://www.theses.fr/2017PA020067.

Full text
Abstract:
La procédure suivie devant le juge administratif est traversée par une double évolution qui justifie qu’une étude soit consacrée à l’office des parties. A mesure que le droit du contentieux administratif se transforme en un droit du procès administratif, on observe que ce procès n’est plus pensé comme un procès fait à un acte, mais comme un procès entre parties. Le renversement des perspectives auquel invite le point de vue des parties est possible grâce à un instrument d’analyse finaliste du droit : l’office. Ce concept permet de s’interroger sur l’adéquation entre les facultés dont disposent et les charges que supportent les parties – i.e. l’office stricto sensu – et les finalités que l’ordre juridique leur assigne – i.e. l’office lato sensu. Comprises comme les personnes physiques ou morales qui participent au lien juridique d’instance en raison d’un litige né de prétentions propres et contraires sur un droit, les parties au procès poursuivent deux finalités complémentaires : la détermination intéressée de la matière litigieuse et la participation loyale à l’instance. Dès lors, le point de vue des parties permet de mettre en lumière non seulement les facultés et les charges que la doctrine néglige lorsqu’elle envisage le procès administratif sous l’angle exclusif du juge, mais aussi que leur office stricto sensu peut être perfectionné en vue de mieux répondre aux finalités de leur office lato sensu. En permettant de renoncer à une opposition dogmatique entre les procès civil et administratif, l’étude de l’office des parties encourage à inscrire la recherche et l’enseignement du droit du procès administratif dans une perspective résolument processualiste
The procedure before administrative courts is characterised by a double evolution, which justifies a study to be devoted to the office of the parties in an administrative hearing. As the law of administrative litigation increasingly transforms itself into the law of administrative hearings, one can observe that this process is no longer considered as a trial made to an act, but as a trial between parties. The perspective switch, to which the point of view of the parties to the trial invites, is made possible thanks to an instrument of finalist analysis of the law : the office. This concept makes it possible to question the adequacy between the powers and the charges of the parties - that is, the office stricto sensu - with the goals assigned to them by the legal order - namely, the office lato sensu. Understood as the physical or legal persons who participate in the legal relationship because of a dispute arising from own and contrary claims to a right, the parties to the lawsuit pursue two complementary goals : the interested determination of the dispute and the fair participation in the instance. This study allows to draw two conclusions. On the one hand, the office stricto sensu can be improved in order to better converge toward the office lato sensu. On the other hand, it shows that an opposition between the civil lawsuit and the administrative lawsuit is no longer possible. This study about the parties office in administrative lawsuit reveals the importance of research and teaching in procedural law
APA, Harvard, Vancouver, ISO, and other styles
41

Götz, Anne, and Rolf Jessberger. "Dendritic Cell Podosome Dynamics Does Not Depend on the F-actin Regulator SWAP-70." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-127216.

Full text
Abstract:
In addition to classical adhesion structures like filopodia or focal adhesions, dendritic cells similar to macrophages and osteoclasts assemble highly dynamic F-actin structures called podosomes. They are involved in cellular processes such as extracellular matrix degradation, bone resorption by osteoclasts, and trans-cellular diapedesis of lymphocytes. Besides adhesion and migration, podosomes enable dendritic cells to degrade connective tissue by matrix metalloproteinases. SWAP-70 interacts with RhoGTPases and F-actin and regulates migration of dendritic cells. SWAP-70 deficient osteoclasts are impaired in F-actin-ring formation and bone resorption. In the present study, we demonstrate that SWAP-70 is not required for podosome formation and F-actin turnover in dendritic cells. Furthermore, we found that toll-like receptor 4 ligand induced podosome disassembly and podosome-mediated matrix degradation is not affected by SWAP-70 in dendritic cells. Thus, podosome formation and function in dendritic cells is independent of SWAP-70.
APA, Harvard, Vancouver, ISO, and other styles
42

Neves, Dalvaci da Cunha Lira. "Quantificação das células estreladas ativadas / miofibroblastos e análise da apoptose das células do fígado durante a terapia celular na fibrose hepática em ratos." Universidade do Estado do Rio de Janeiro, 2011. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=3730.

Full text
Abstract:
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
A fibrose hepática é o resultado de uma resposta cicatrizante frente a repetidas lesões no fígado, e é caracterizada pelo acúmulo excessivo de proteínas da matriz extracelular (MEC) no parênquima hepático, incluindo colágeno, fibronectina, elastina, laminina e proteoglicanos, com a participação de diferentes populações celulares do fígado. As principais células responsáveis pela síntese de proteínas da MEC na fibrose hepática são as células estreladas hepáticas ativadas e os miofibroblastos, que surgem após estímulo inflamatório e são caracterizadas pela expressão de alfa-actina de músculo liso (α-SMA). Sabe-se que durante a progressão da fibrose hepática, ocorre a morte de hepatócitos e sua substituição por células fibrogênicas α-SMA+. A apoptose dessas células fibrogênicas é de grande relevância para a regressão da fibrose e regeneração hepática. Nos últimos anos, a terapia com células tronco de medula óssea tem sido utilizada para estimular a regeneração hepática em diferentes modelos experimentais e protocolos clínicos. A fração mononuclear da medula óssea adulta possui duas populações de células-tronco importantes no tratamento de diversas doenças hepáticas: células-tronco hematopoiéticas e células-tronco mesenquimais. O objetivo deste estudo foi analisar a expressão de α-SMA e o processo de apoptose de células hepáticas durante a fibrose hepática induzida por ligadura do ducto biliar (LDB) e após o transplante de células mononucleares de medula óssea (CMMO). Os fígados foram coletados de ratos dos seguintes grupos: normal, 14 dias de LDB, 21 dias de LDB e animais que receberam CMMO após 14 dias de LDB, e foram analisados após 7 dias (totalizando 21 dias de LDB). Para quantificar a expressão de α-SMA por células fibrogênicas nos grupos experimentais, foi realizada imunoperoxidase para α-SMA, seguida de morfometria no programa Image Pro Plus. Para analisar a apoptose nas células hepáticas, foi realizada imunoperoxidase e Western Blotting (WB) para caspase-3 (proteína apoptótica) e imunofluorescência com dupla-marcação para caspase-3 e α-SMA, seguida de observação em microscópio confocal. Os resultados da quantificação de α-SMA por morfometria mostraram que a expressão de α-SMA aumentou significativamente 14 e 21 dias após a LDB. Entretanto, essa expressão diminuiu significativamente no grupo tratado com CMMO, que apresentou parênquima hepático mais preservado em relação ao grupo com 21 dias de LDB. Os resultados de imunoperoxidase, WB e microscopia confocal para expressão de caspase-3 demonstraram que essa proteína diminuiu nos animais fibróticos com 14 e 21 dias de LDB com relação ao grupo normal, e estava significativamente elevada no grupo tratado com CMMO. A análise por microscopia confocal demonstrou que algumas células coexpressaram α-SMA e caspase-3 nos animais tratados com CMMO, sugerindo a morte de células fibrogênicas e remodelamento do parênquima hepático.
Hepatic fibrosis is the result of a scarring response due to continued injury to the liver, and is featured by excessive accumulation of extracellular matrix (MEC) proteins in hepatic parenchyma. These proteins include collagen, fibronectin, elastin, laminin and proteoglicans, along with the participation of different cell populations within the liver. The main cells responsible for the synthesis of MEC proteins are activated hepatic stellate cells and myofibroblasts, which appear after inflammatory stimuli and are characterized by the expression of alpha-smooth muscle actin (α-SMA). It is known that hepatic fibrosis progression is accompanied by hepatocyte death and its substitution by α-SMA+ fibrogenic cells. Therefore, apoptosis of these fibrogenic cells is of main relevance to fibrosis regression and hepatic regeneration. In the later years, bone marrow stem cell therapy has been used to stimulate hepatic regeneration in different experimental models and clinical protocols. The adult bone marrow mononuclear fraction contains two stem cell populations particularly important in the treatment of diverse hepatic diseases: hematopoietic stem cells and mesenchymal stem cells. The aim of this study was to analyze α-SMA expression and the apoptotic process in hepatic cells during hepatic fibrosis induced by bile duct ligation (BDL) and after bone marrow mononuclear cell (BMMC) transplantation. Livers were collect from rats of the following groups: normal, 14 days of BDL, 21 days of BDL and rats that received BMMC 14 days after BDL and were analyzed after 7 days (total of 21 days of BDL). To quantify α-SMA expression by fibrogenic cells in the experimental groups, immunoperoxidase to α-SMA followed by morphometry in the Image Pro Plus software was performed. To analyze apoptosis in hepatic cells, immunoperoxidase and western blotting (WB) against caspase-3 (apoptotic protein) were used, along with double immunofluorescence against caspase-3 and α-SMA to confocal microscopy analysis. Results of α-SMA quantification by morphometry showed that α-SMA expression increased significantly 14 and 21 days after BDL. However, this expression was significantly decreased in the BMMC treated group, which presented a more preserved hepatic parenchyma in relation to the group with 21 days of BDL. Immunoperoxidase, WB and confocal microscopy results showed that caspase-3 is decreased in fibrotic livers with 14 and 21 days of BDL in comparison to normal group, and was significantly augmented in the BMMC treated group. Confocal microscopy analysis showed that were cells coexpressing α-SMA and caspase-3 in rats treated with BMMC, suggesting fibrogenic cells death and hepatic remodeling.
APA, Harvard, Vancouver, ISO, and other styles
43

Lardaud-Clerc, Caroline. "Le changement de comportement du créancier en cours d'exécution du contrat. Étude de droit français et anglais." Thesis, Lyon 3, 2015. http://www.theses.fr/2015LYO30060.

Full text
Abstract:
Le changement de comportement correspond à une situation dans laquelle, pendant l’exécution du contrat, le créancier adopte une attitude contraire au contenu de l’accord originel, pour ensuite exiger l’application de ce dernier. Confronté aux règles classiques du droit des contrats (intangibilité, consideration), cette volte-face ne devrait avoir aucune force juridique. Malgré cela, en interdisant au créancier de réclamer l’exécution de l’accord initial, les juges français et anglais introduisent cette situation dans la sphère juridique.Comme l’imprévision, le changement de comportement bouleverse l’exécution du contrat ; comme la bonne foi, il est fondé sur la morale ; comme l’abus de droit, il sanctionne l’inconstance ; comme l’apparence, il est à la frontière entre le fait et le droit. Il se singularise pourtant, car il ne se confond avec aucune autre insitution juridique. Par ailleurs distinct de la confiance légitime et de l’interdiction de se contredire auxquelles il est rattaché, il est en quête d’un régime juridique propre. Une construction s’impose alors. Elle est facilitée par le miroir de la comparaison des droits français et anglais.Le changement de comportement révèle une renonciation du créancier à la créance, rendue possible par les prérogatives contractuelles qu’il tient, elles-mêmes autorisées par sa propriété sur la créance ou le renforcement de sa titularité. L’efficacité de cette appréhension flexible du contenu contractuel requiert cependant l’anéantissement d’éventuels remparts procéduraux : l’interdiction du changement ne doit alors plus seulement être un moyen de défense contre la contradiction, mais exprimer un comportement juridiquement contraignant
The change of behaviour refers to a situation in which, during the performance stage of the contract, the promisor behaves in a manner which is contrary to the existing contractual rights, but later neverthless insists on their application. Faced with the classic rules of contract law (sanctity of contracts, consideration), this volte-face should have no legal force. Yet, by prohibiting the promisor’s demand to perform the original agreement, French and English judges nevertheless introduce this situation in the law of contracts.Like frustration, the change of behaviour disrupts the performance of the contract ; like good faith and Equity, it is based on morality ; like an abuse of right, it punishes inconsistency ; like the theory of « apparence », it is in between facts and law. In spite of this, the change of behaviour stands out ; as it does not share the exact same scope as the expectations theory or the inconsistent behaviour theory, no other legal theory can wholly translate it into the law of the contracts. The change of behaviour therefore needs its proper legal framework which must consequently be found. The search is helped by the prism of comparative law, between French and Englis laws.The change of behaviour reveals a waiver of the promisor’s debt. The waiver is made possible by the contractual prerogatives he holds, prerogatives which are justified by the ownership of the debt. The efficiency of this flexible understanding of contractual content requires the obliteration of any litigation shield. As a consequence, forbidding the change should not only be seen as a defense against inconsistency, but should highlight a legally binding behaviour
APA, Harvard, Vancouver, ISO, and other styles
44

Götz, Anne, and Rolf Jessberger. "Dendritic Cell Podosome Dynamics Does Not Depend on the F-actin Regulator SWAP-70." Public Library of Science, 2013. https://tud.qucosa.de/id/qucosa%3A27287.

Full text
Abstract:
In addition to classical adhesion structures like filopodia or focal adhesions, dendritic cells similar to macrophages and osteoclasts assemble highly dynamic F-actin structures called podosomes. They are involved in cellular processes such as extracellular matrix degradation, bone resorption by osteoclasts, and trans-cellular diapedesis of lymphocytes. Besides adhesion and migration, podosomes enable dendritic cells to degrade connective tissue by matrix metalloproteinases. SWAP-70 interacts with RhoGTPases and F-actin and regulates migration of dendritic cells. SWAP-70 deficient osteoclasts are impaired in F-actin-ring formation and bone resorption. In the present study, we demonstrate that SWAP-70 is not required for podosome formation and F-actin turnover in dendritic cells. Furthermore, we found that toll-like receptor 4 ligand induced podosome disassembly and podosome-mediated matrix degradation is not affected by SWAP-70 in dendritic cells. Thus, podosome formation and function in dendritic cells is independent of SWAP-70.
APA, Harvard, Vancouver, ISO, and other styles
45

Parinet, Pauline. "La carence de l'administration." Thesis, Tours, 2017. http://www.theses.fr/2017TOUR1012/document.

Full text
Abstract:
La carence de l’administration est à la fois évocatrice et ambigüe. Évocatrice pour l’administré, car elle ravive les mauvais souvenirs administratifs de chacun. Ambigüe pourtant, pour le juriste, car la carence évoque spontanément de multiples termes qui en sont proches, comme l’inertie ou l’abstention. Elle doit néanmoins en être distinguée et peut être définie comme le résultat de certaines inactions : celles qui n’auraient pas dû avoir lieu. Ainsi, la reconnaissance d’une carence administrative a une fonction : elle signale un comportement passif inadmissible. Elle dénonce à la fois une utilisation insuffisante de ses moyens pour remplir sa mission et une inaction administrative abusive. Le caractère anormal de l’inaction dénoncée par cette reconnaissance implique, alors, une réaction du système juridique, afin que le manque constaté ne puisse échapper à toute sanction, que celle-ci soit juridictionnelle ou non
The deficiency of the administration is meaningful and also ambiguous. Meaningful as it brings back administrative bad memories for every citizen. But ambiguous, for jurists, as the deficiency naturally reminds them of many terms which are very close, such as lethargy or abstention. Nevertheless, the deficiency has to be distinguished from these terms and can be defined as the result of some inactions : the ones which should not have happened. The recognition of the administrative deficiency has thus a function : highlighting an unacceptable passive behaviour. What it means an insufficient use of its means to fulfil its mission and an abusive abstention. So, the abnormal nature of this inaction highlighted by this recognition needs a reaction of the legal system, in order to condemn this noted lack, jurisdictionally or not
APA, Harvard, Vancouver, ISO, and other styles
46

Rao, Banna Trinadha. "The retentive strength of bonded amalgam restorations." Thesis, 2005. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_4904_1194341801.

Full text
Abstract:

Amalgam bonding agents have been shown to enhance retention of amalgam restorations by mechanical means. However, recent studies showed that the use o glass ionomer cements and resin cements as lining and bonding materials to amalgam restorations will increase the retentive strength of the amalgam restorations, hence reducing the micro leakage and secondary caries. The purpose of this study was to compare the relative retentive strength of conventional amalgam restorations and bonded amalgam restorations using resin adhesive, glass ionomer cements and resin cements.

APA, Harvard, Vancouver, ISO, and other styles
47

Delisle, Karine. "Les organisations non gouvernementales (ONG) locales comme réseaux d'acteurs hétérogènes : l'action quotidienne de l'Accueil Bonneau." Thèse, 2005. http://hdl.handle.net/1866/17404.

Full text
APA, Harvard, Vancouver, ISO, and other styles
48

Ohira, Taisuke. "Bio-action of piezoelectric bone surgery in rats." Thesis, 2017. https://hdl.handle.net/2144/26381.

Full text
Abstract:
Piezocision is a new periodontal method for cutting bone more precisely than conventional methods, such as bur drilling, with 3D ultrasonic vibration power. We have conducted a study on piezocision effect on periodontal tissue in rodents. Our previous animal studies demonstrated that piezocision hastens tooth movement in rodents compared to conventional methods. The histological results showed that piezocision induces bone resorption and regeneration quickly. In addition, we observed the same effect of piezocision surgery on clinical tooth movement in collaboration with the orthodontists at BUSDM. We believe that piezocision can contribute significantly to dental therapies. However, more studies of piezocision effects are necessary for a thorough understanding. Periodontal tissue healing requires the participation of regulatory molecules, cells, and scaffold or matrix. We hypothesized that piezosurgery induces alveolar bone regeneration by uncovered procedures. In this study, we focused on the cells contributing to synthesis or repair of periodontal tissue, such as osteocytes, osteoclasts, osteoblasts, white blood cells, and periodontal ligament cells in order to close the gap between clinical knowledge and cellular mechanisms Histological analysis and MRI data indicates that piezocision surgery enhanced alveolar bone degradation in the post-operative early phase (from day1 to day7), and induced bone regeneration in the post-operative mid phase (from day14 to day28). The structure of alveolar bone was similar to controls in the late phase (day70). Serum ALP activity, a bone formation marker, was significantly increased by Piezocision surgery (p<0.05). Piezocision increasd serum CTX, a bone degradation biomarker, at post-operative 7day in the 30Hz Piezocision surgery (p<0.05). In addition, Serum PINP, a bone formation biomarker, was significantly decreased in the post-operative early phase. TUNEL assays revealed that osteocyte apoptosis was induced in alveolar bone by piezocision at post-operative 1day. Apoptosis in osteocytes induces osteoclast activity that leads to bone degradation. In previous studies piezocision induced TRAP activity in the post-operative early phase. Runx2 positive osteoblast progenitor cells were observed in the post-operative day7 and 14 as assessed by Immunofluorescence microscopy analysis. The Runx2 positive cells accumulated near the new bone formation area. The structure of collagen was observed by histological staining with Pico Sirius Red. Piezocision resulted in deteriorated collagen structure in the post-operative early phase that recovered in the post-operative mid phase. Since the collagen fibers filled in the gap between alveolar bone and roots, we stained the sections with Periostin, a specific PDL biomarker. Periostin was observed on the collagen fibers that filled in the gap between bone and root. previous studies revealed that the expression of Periostin induced TGF beta, a pivotal molecule for osteoblast differentiation. Taken together, these studies indicate that periodontal tissue responds to Piezosurgery by alveolar bone decalcification and regeneration. Further elucidation of the role of the each conducting cells (eg. osteocytes, osteoclast, osteoblast, periodontal ligament cells) after piezosurgery in the periodontal tissue may provide a new target for the treatment of periodontal disease by stimulating the return to tissue homeostasis.
APA, Harvard, Vancouver, ISO, and other styles
49

Aguirre-Flores, Jessica Dafhne. "Structure Property Relationships for Dirhodium Antitumor Active Compounds: Reactions with Biomolecules and In Cellulo Studies." 2009. http://hdl.handle.net/1969.1/ETD-TAMU-2009-12-7614.

Full text
Abstract:
The molecular characteristics that affect the activity of various dirhodium complexes are reported. The importance of the axial position in the action of dirhodium compounds was studied. Three dirhodium complexes with increasing number of accessible axial coordination sites were synthesized and characterized. In cis-[Rh2(u-OAc)2(np)2]2+ (np = 1,8- naphthyridine) both axial sites are available for coordination, whereas for cis-[Rh2(u-OAc)2(np)(pynp)]+2 (pynp = 2-(2-pyridyl)1,8-naphthyridine) and cis-[Rh2(u-OAc)2(pynp)2]+2 the pyridyl arm on the ligand pynp blocks one and two axial sites, respectively. The availability of the axial positions affects the in vitro and in cellulo activity of these complexes demonstrating that open axial coordination sites are necessary for biological activity. The inhibitory activity of derivatives of dirhodium-dppz complexes (dppz = dipyrido[3,2-a:2',3'-c]phenazine) has also been investigated. The dppz derivatives included compounds with electron-withdrawing (Cl, CN, and NO2) as well as electro-donating (MeO and Me) substituents. These compounds inhibit transcription of T7-RNA polymerase by reducing accessible cysteine residues. The activity correlates with the electron withdrawing character of the substituent on the dppz ligand. Density functional theory (DFT) calculations reveal that the lowest unoccupied molecular orbitals (LUMOs) in the series are ligand-based pi* orbitals localized on the phenazine ring. These complexes represent the first family of dirhodium complexes whose inhibitory ability can be tuned by controlling their redox properties. The effect of the presence of diimine ligands in the dirhodium core in both in vitro and in cellulo activity is discussed. The presence of one diimine ligand allows for dual binding, intercalation and covalent, as observed by melting temperature and relative viscosity measurements, as well as electrophoretic mobility shift assay (EMSA). The mono-substituted dirhodium complexes are effective against HeLa and COLO-316 cell lines, with [Rh2(u-O2CCH3)2(n1-O2CCH3)(dppz)]+ being the most effective compound of the series. Results of the comet assay indicate that all of the monosubstituted complexes studied damage nuclear DNA, although in different degrees. The cytotoxic effect of these complexes is not affected by the presence of glutathione. The addition of the second diimine ligand hinders the ability of the complexes to damage DNA. The bis-substituted complexes are also slightly less cytotoxic than their mono-substituted congeners. Thus, the number of equatorial positions occupied by diimine ligands play a critical role in the mechanism of cytotoxicity of dirhodium(II,II) complexes. Finally, the results also demonstrate that improving the internalization of the dirhodium complexes can be achieved by co-incubation with cell penetrating peptides. This work provides a foundation for the preparation of new and more effective dirhodium complexes.
APA, Harvard, Vancouver, ISO, and other styles
50

Newnum, America Bethanne. "Bone Metabolism: The Role of STAT3 and Reactive Oxygen Species." 2013. http://hdl.handle.net/1805/3429.

Full text
Abstract:
Indiana University-Purdue University Indianapolis (IUPUI)
Signal Transducers and Activators of Transcription 3 (STAT3), a transcription factor expressed in many cell types, including osteoblasts and osteoclasts, is emerging as a key regulator of bone mass and strength. STAT3 mutations cause a rare human immunodeficiency disease characterized by extremely elevated levels of IgE in serum that have associated craniofacial and skeletal features, such as reduced bone mineral density and recurrent pathological fractures. Our microarray data and immunohistochemical staining using a normal rat model have shown that STAT3 mRNA and protein levels markedly increase in response to mechanical loading. In addition, as indicated by STAT3 phosphorylation in MC3T3-E1 osteoblastic cells, STAT3 activity significantly increases in response to 30 to 90 minutes fluid shear stress. In order to further study the role that STAT3 plays in bone responsiveness to loading, tissue-selective STAT3 knockout (KO) mice, in which inactivation of STAT3 occurs in osteoblasts, were generated by breeding the transgenic mice in which Cre recombinase cDNA was cloned downstream of a 3.6 or 2.3 kb fragment of the rat Col1a1 promoter (Col3.6-Cre and Col2.3-Cre, respectively) with a strain of floxed mice in which the two loxP sites flank exons 18-20 of the STAT3 gene were used. Mice engineered with bone selective inactivation of STAT3 in osteoblasts exhibited significantly lower bone mineral density (7-12%, p<0.05) and reduced ultimate force (21-34%, p<0.01) compared to their age-matched littermate controls. The right ulnae of 16-week-old bone specific STAT3 KO mice and the age-matched control mice were loaded with peak forces of 2.5 N and 2.75 N for female and male mice, respectively, at 2 Hz, 120 cycles/day for 3 consecutive days. Mice with inactivation of STAT3 specific in bone were significantly less responsive to mechanical loading than the control mice as indicated by decreased relative mineralizing surface (rMS/BS, 47-59%, p<0.05) and relative bone formation rate (rBFR/BS, 64-75%, p<0.001). Bone responsiveness was equally decreased in mice in which STAT3 is inactivated either in early osteoblasts (Col3.6-Cre) or in mature osteoblasts (Col2.3-Cre). Accumulating evidence indicates that bone metabolism is significantly affected by activities in mitochondria. For instance, although STAT3 is reported to be involved in bone formation and resorption through regulation of nuclear genes, inactivation of STAT3 is shown to disrupt mitochondrial activities and result in an increased level of reactive oxygen species (ROS). Inactivation of STAT3 suppressed load-driven mitochondrial activity, which led to an elevated level of ROS in cultured primary osteoblasts. Oxidative stress induced by administration of buthionine sulfoximine (BSO) significantly inhibits load-induced bone formation in wild type mice. Taken together, the results support the notion that the loss-of-function mutation of STAT3 in osteoblasts and osteocytes diminishes load-driven bone formation and impairs the regulation of oxidative stress in mitochondria.
APA, Harvard, Vancouver, ISO, and other styles
We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!

To the bibliography