A new type of steel plate shear wall has been devised which resists out-of-plane buckling without requiring stiffeners. The ring-shaped steel plate shear wall (RS-SPSW) includes a web plate that is cut with a pattern of holes leaving ring-shaped portions of steel connected by diagonal links. The ring shape resists out-of-plane buckling through the mechanics of how a circular ring deforms into an ellipse. It has been shown that the ring's compression diagonal will shorten a similar amount as the tension diagonal elongates, essentially eliminating the slack in the direction perpendicular to the tension field. Because of the unique features of the ring's mode of distortion, the load-deformation response of the resulting RS-SPSW system can exhibit full hysteretic behavior and possess greatly improved stiffness relative to thin unstiffened SPSW. The concept has been validated through testing on seven 34 in x 34 in panels. General conclusions about influence of different geometric parameters on plate behavior have been made. / Master of Science

Recent advances in technology have enabled the development of truly autonomous ground vehicles capable of performing complex navigation tasks. As a result, the demand for practical unmanned ground vehicle (UGV) systems has increased dramatically in recent years. Central to these developments is maturation of emerging mobile robotic intelligent and autonomous capability. While the progress UGV technology has been substantial, there are many challenges that still face unmanned vehicle system developers. Foremost is the improvement of perception hardware and intelligent software that supports the evolution of UGV capability. The development of a Next-generation Experimentation Robotic Vehicle (NERV) serves to provide a small UGV baseline platform supporting experimentation focused on progression of the state-of-the-art in unmanned systems. Supporting research and user feedback highlight the needs that provide justification for an advanced small UGV research platform. Primarily, such a vehicle must be based upon open and technology independent system architecture while exhibiting improved mobility over relatively structured terrain. To this end, a theoretical kinematic model is presented for a novel two-body multi degree-of-freedom, four-wheel drive, small UGV platform. The efficacy of the theoretical kinematic model was validated through computer simulation and experimentation on a full-scale proof-of-concept mobile robotic platform. The kinematic model provides the foundation for autonomous multi-body control. Further, a modular system level design based upon the concepts of the Joint Architecture for Unmanned Systems (JAUS) is offered as an open architecture model providing a scalable system integration solution. Together these elements provide a blueprint for the development of a small UGV capable of supporting the needs of a wide range of leading-edge intelligent system research initiatives. / Master of Science

Many grand societal challenges are rooted in the need for new materials, such as those related to energy, health, and the environment. However, the traditional way of discovering new materials is basically trial and error. This time-consuming and expensive method can't meet the quickly growing requirements for material discovery. To meet this challenge, the government of the United States started the Materials Genome Initiative (MGI) in 2011. MGI aims at accelerating the pace and reducing the cost of discovering new materials. The success of MGI needs materials innovation infrastructure including data tools, computation tools, and experiment tools. The last decade has witnessed significant progress for MGI, especially with respect to hard materials. However, relatively less attention has been paid to soft materials. One important reason is the lack of experimental tools, especially characterization tools for high-throughput experimentation. This dissertation aims to enrich the toolbox by trying new sensor tools for high-throughput characterization of hydrogels. Piezoelectric-excited millimeter-sized cantilever (PEMC) sensors were used in this dissertation to characterize hydrogels. Their capability to investigate hydrogels was first demonstrated by monitoring the synthesis and stimuli-response of composite hydrogels. The PEMC sensors enabled in-situ study of how the manufacturing process, i.e. bulk vs. layer-by-layer, affects the structure and properties of hydrogels. Afterwards, the PEMC sensors were integrated with robots to develop a method of high-throughput experimentation. Various hydrogels were formulated in a well-plate format and characterized by the sensor tools in an automated manner. High-throughput characterization, especially multi-property characterization enabled optimizing the formulation to achieve tradeoff between different properties. Finally, the sensor-based high-throughput experimentation was combined with active learning for accelerated material discovery. A collaborative learning was used to guide the high-throughput formulation and characterization of hydrogels, which demonstrated rapid discovery of mechanically optimized composite glycogels. Through this dissertation, we hope to provide a new tool for high-throughput characterization of soft materials to accelerate the discovery and optimization of materials. / Doctor of Philosophy / Many grand societal challenges, including those associated with energy and healthcare, are driven by the need for new materials. However, the traditional way of discovering new materials is based on trial and error using low throughput computational and experimental methods. For example, it often takes several years, even decades, to discover and commercialize new materials. The lithium-ion battery is a good example. Traditional time-consuming and expensive methods cannot meet the fast-growing requirements of modern material discovery. With the development of computer science and automation, the idea of using data, artificial intelligence, and robots for accelerated materials discovery has attracted more and more attention. Significant progress has been made in metals and inorganic non-metal materials (e.g., semiconductors) in the past decade under the guidance of machine learning and the assistance of automated robots. However, relatively less progress has been made in materials having complex structures and dynamic properties, such as hydrogels. Hydrogels have wide applications in our daily lives, such as drugs and biomedical devices. One significant barrier to accelerated discovery and engineering of hydrogels is the lack of tools that can rapidly characterize the material's properties. In this dissertation, a sensor-based approach was created to characterize the mechanical properties and stimuli-response of soft materials using low sample volumes. The sensor was integrated with a robot to test materials in high-throughput formats in a rapid and automated measurement format. In combination with machine learning, the high-throughput characterization method was demonstrated to accelerate the engineering and optimization of several hydrogels. Through this dissertation, we hope to provide new tools and methods for rapid engineering of soft materials.

京都大学 / 新制・課程博士 / 博士(人間・環境学) / 甲第25380号 / 人博第1122号 / 新制||人||261(附属図書館) / 京都大学大学院人間・環境学研究科共生人間学専攻 / (主査)准教授 金丸 敏幸, 教授 谷口 一美, 教授 守田 貴弘, 准教授 大谷 直輝 / 学位規則第4条第1項該当 / Doctor of Human and Environmental Studies / Kyoto University / DGAM

Made available in DSpace on 2015-04-11T14:02:49Z (GMT). No. of bitstreams: 1 marckson.pdf: 3476468 bytes, checksum: 74ae505f96e118da0f10a996c7f9fec2 (MD5) Previous issue date: 2013-06-10 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Laboratório de experimentação Hands-On é limitado temporalmente e geograficamente. O usuário tem que se deslocar até ao ambiente físico em seu horário de funcionamento para utilizá-lo, em seguida esperar que seja montado o experimento por um técnico e somente depois disso realizar os procedimentos experimentais. Na busca por amenizar essas limitações surgiram os Laboratórios de Experimento Remoto, também chamado de Laboratório de Acesso Remoto (ou LAR). Uma característica em Laboratórios de Acesso Remoto é a configuração de cenários experimentais encontra-se pronto para ser utilizado, tirando a oportunidade do usuário de escolher um domínio experimental a ser executado. Em geral, são limitados a executarem sempre os mesmos experimentos, se tornando um problema. Esta característica, primeiramente, foi identificado no trabalho de Mestrado de um integrante do Laboratório de Robótica Educativa do Amazonas (ou LaboREAM) com o projeto Laboratório de Acesso Remoto de Robótica (ou LARRE). Então, neste projeto de Mestrado realizou-se inicialmente o levantamento bibliográfico sobre o estado da arte dos Laboratórios de Acesso Remoto e foi identificada a mesma característica. O problema abordado nesse trabalho é como realizar a configuração e montagem autônoma de ambientes experimentais de ciências? A estratégia adotada a fim de solucionar o problema foi a combinação de um Sistema Multiagente (ou SMA) com o XML para assim definir os cenários experimentais a serem montados. Para montar o cenário experimental de forma autônoma, o Sistema Multiagente é usado em conjunto com um Sistema Robótico Móvel. E na modelagem do sistema foi usada a metodologia O-MaSE. Foi desenvolvida uma Rede de Petri (ou RdP) que representa as interações entre os agentes robóticos móveis montando o cenário e simulando a correta ordem de sincronismo ou paralelismo das tarefas. A partir dessa concepção, foi implementado o Sistema Multiagente usando framework JADE e firmware LeJOS. Os resultados obtidos com os testes qualitativos e quantitativos aplicados no sistema comprovam a validade e a viabilidade da solução. Em testes foram verificados a qualidade em montar os cenários, ou seja, a precisão em posicionar os objetos e também quantos cenários seguidos conseguem ser montados.

Ce travail de thèse a pour objet l’étude numérique et expérimentale de la déstabilisation de milieux granulaires immergés par fluidisation. Cette instabilité hydromécanique est un mécanisme précurseur de l’érosion régressive, processus de dégradation au coeur de la problématique de l’érosion interne des ouvrages hydrauliques en terre. La compréhension de ces mécanismes d’érosion nécessite une description rigoureuse du couplage et de l’interaction entre le fluide et les particules de sol. A cette fin, un modèle 2D a été utilisé en couplant deux méthodes particulaires, la méthode des éléments discrets (DEM) pour modéliser le comportement mécanique de la phase solide et la méthode Lattice Boltzmann (LBM) pour la phase fluide. Des expériences servant de validation à cette simulation numérique 2D ont également été réalisées en s’appuyant sur une technique de visualisation interne d’un empilement granulaire combinant l’ajustement d’indice de réfraction des deux phases et la fluorescence induite par plan laser. / The subject of this thesis is the numerical analysis and experimental investigation of the destabilization of submerged granular media caused by fluidization. This hydromechanical instability is one of the mechanisms that may trigger the regressive erosion, which is one of the main degradation phenomena driving the internal erosion of earthen hydraulic constructions. Such erosion mechanisms can only be understood through a rigorous description of the coupling and interaction between the eroding fluid and the soil particles. For this purpose, a 2D model has been used coupling two different numerical techniques, namely the discrete element method (DEM) for modelling the mechanical behaviour of the solid phase and the Lattice Boltzmann method (LBM) for the fluid phase. The experimental validation of this numerical 2D simulation has been carried out using two optical techniques for the internal visualization of a granular sample, namely the adjustment of the refraction index of the two phases and the laser-induced fluorescence.

This study examined the effect of preweanling methyphenidate exposure on later drug reward. We examined the induction, extinction, and reinstatement of morphine induced conditioned place preference (CPP) in rats that received methylphenidate pretreatment during the preweanling period.

In preschools it is common that mathematics mainly focuses on how children learn mathematics through everyday activities, or on children´s understanding of mathematical concepts. However, views on mathematics-learning are today deepened and extended, and embrace children’s own mathematical signs, visual representations and bodily experiences. The overall aim of this thesis is to experiment with how this extended view in which children´s engagement and creativity is affirmed, simultaneously as they are developing knowledge about the world of mathematics with its procedures and rules. With inspiration from the French philosophers Gilles Deleuze´s and Félix Guattari´s immanent ontology and transcendental empiricism, and from the pedagogical philosophy of the preschools in Reggio Emilia, I have experimented both with mathematics, and with toddlers’ explorations and potentiality. The research-material primarily consists of video observations and documentations, and it is taken from a project with a mathematical topic through a cooperative work by me, preschool teachers and children aged 1–3 years. Methodologically the work is based on one example from the project where some children explores and experiment on geometric objects. In relation to the example some concepts from Reggio Emilia’s pedagogical thinking and Deleuze´s and Guattari´s immanent ontology are put to work, by focusing on the connections that emerge. The study make visible that children explore and experiment with mathematics in what in the study has called “a relational field of potentiality”. In relation to preschool didactics the study stresses the importance of teachers paying attention to and “listening” to children’s experimentations and sign-making, in order not to interrupt what is emerging/becoming. This requires an environment that embraces “the hundred languages” and enables collective experimentation for thoughts and ideas to be shared in “togetherness”. / I förskolan är det vanligt att matematiken främst handlar om det som sker i barnens vardag eller fokuserar på barnens förståelse av matematiska begrepp. Synen på matematik i förskolan håller dock på att vidgas och inbegripa barns egna teckenskapande och kroppsliga erfarenheter. Licentiatuppsatsens övergripande syfte är att experimentera och utforska hur barns engagemang och kreativitet kan tas tillvara, samtidigt med att barnen kan utveckla sina kunskaper kring matematikens värld med dess procedurer och regler. Utifrån de franska filosoferna Gilles Deleuze’s och Félix Guattaris immanenta perspektiv och transcendentala empirism och Reggio Emilias pedagogiska filosofi, har jag experimenterat kring matematik och de yngsta förskolebarnens experimenterande och potentialitet. Forskningsmaterialet består främst av videoobservationer och pedagogisk dokumentation från ett projekt med ett matematiskt ämnesinnehåll genom ett kollektivt arbete med mig, pedagoger och barn i åldern 1–3 år. Metodologiskt utgår arbetet från ett exempel från projektarbetet där några barn utforskar och experimenterar kring geometriska objekt. I relation till exemplet sätts några begrepp från Reggio Emilias pedagogiska tänkande och Deleuze´s och Guattaris immanenta ontologi i arbete med särskilt fokus på vilka förbindelser som frambringas. Det som studien synliggör är att barn utforskar och experimenterar kring matematik i det som i studien kallats ”det relationella potentialitetsfältet”. Förskoledidaktiskt synliggör studien vikten av att pedagoger uppmärksammar och ”lyssnar” till barns experimenterande och teckenskapande, för att inte stoppa barns potentialitet och det som är i tillblivelse. Detta förutsätter en miljö som inbegriper de hundra språken och som gör ett kollektivt experimenterande möjligt där tankar och idéer kan delas i en ”tillsammansskap”.

This thesis examines the development of vivisection as a method of physiological research between 1875 and 1901 in Great Britain, by examining some of the arguments, discussions, and ideas put forth by physiologists for the utilisation of vivisection in their research. Because this study operates within the context of medical history, questions of legitimacy, scientific development, and professional image are lifted. The development of vivisection during this period took place with a larger shift in scientific practice playing out in the background, where experimentalism began overtaking the previously more analytical approach to medicine and the sciences. The First Royal Commission on Vivisection in 1875 marks the beginning of this study, and the discussions within allow for a more nuanced picture of the professional debates on the practice, where both proponents and sceptics at times found common ground. Technological and societal aspects were central to much of the argumentation for the further development of vivisection, with technology easing the practical aspects of the method, and the concept of the "gentleman" allowing British "vivisectors" to argue against charges of cruelty, pointing rather to continental schools of physiology as the culprits, whilst lifting the "humanity" behind animal experimentation in Great Britain. In conjunction with pointing out the importance of the method for the development of medical science, the Cruelty to Animals Act and the lobbying on behalf of the professional journals British Medical Journal and The Lancet helped legitimise the practice in Great Britain. The Act allowed vivisection under set circumstances, and the two journals served as megaphones for scientific development on behalf of vivisection, at times even openly criticising sceptical opinions. At the same time, some saw experimental research through vivisection as merely one aspect of medical practice. One which needed to gain foothold in order to help advance medical science for the larger benefit of all humanity.

Thesis (PhD)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: The Mechanism of -adrenergic preconditioning ( -PC) Ischaemic preconditioning (IPC), a potent endogenous protective intervention against myocardial ischaemia, is induced by exposure of the heart to repetitive short episodes of ischaemia and reperfusion. The protective effects of this phenomenon have been demonstrated to be mediated by release of autocoids such as adenosine, opioids and bradykinin. Release of endogenous catecholamines and activation of the beta-adrenergic receptors (b-AR) have also been shown to be involved in ischaemic preconditioning. However, the exact mechanism whereby activation of the - adrenergic signal transduction pathway leads to cardioprotection, is still unknown. In view of the above, the aims of the present study were to evaluate: (i) the respective roles of the 1-, 2- and 3-AR receptors as well as the contribution of Gi protein and PKA to -adrenergic preconditioning, (ii) the role of the prosurvival kinases, PKB/Akt and ERK 44/p42 MAPKinase in -drenergic preconditioning, (iii) whether b-AR stimulation protect via ischaemia and the formation of adenosine; the respective roles of the A1-, A2-, A3-adenosine receptors as well as the involvement of the PI3-K/PKB/Akt and ERKp44/p42 signal transduction pathways, in the cardioprotective phenomemon of -adrenergic preconditioning and (iv) the contribution of the mitochondrial KATP channels (mKATP), reactive oxygen species and NO to the mechanism of -AR-induced cardioprotection. Methods: Isolated perfused rat hearts were subjected to 35 min regional ischaemia (RI) and reperfusion. Infarct size (IS) was determined using tetrazolium staining (TTC) and data were analyzed with ANOVA. Hearts were preconditioned with 5 min isoproterenol 0.1 μM ( 1/ 2-AR agonist), or formoterol 1 nM ( 2-AR agonist) or BRL 37344 1 μM ( 3-AR agonist) followed by 5 min reperfusion. The roles of the 1-, 2- and 3-ARs as well as NO were explored by using the selective antagonists CGP-20712A (300 nM), ICI -18551 (50 nM), SR59230A (100 nM) and NOS inhibitors L-NAME (50 μM) or LNNA (50 μM) respectively. Involvement of ROS and the mK+ ATP channels was studied by administration of N-acetyl cysteine (NAC, 300 μM) and the mitK+ ATP iv channel blocker 5-HD (100 μM) during the triggering phase. The role of PKA and PI3-K/Akt was investigated by the administration of the blockers Rp-8-CPT-cAMPs (16 μM) and wortmannin (100 nM) respectively, prior to RI or at the onset of reperfusion. Pertussis toxin (PTX), 30 μg kg-1 was administered i.p., 48 h prior to experimentation. The role of adenosine and the adenosine A1, A3, A2A and A2B receptors was studied by using adenosine deaminase and the selective antagonists DPCPX (1 μM), MRS 1191(1 μM), ZM241385 (1 μM) and MRS1754 (1 μM). Activation of PKB/Akt and ERKp44/p42 was determined by Western blot. Results: Infarct sizes of hearts preconditioned with isoproterenol of formoterol were significantly smaller compared to those of non-preconditioned hearts. This was associated with an improvement in postischaemic mechanical performance. However the 3-AR agonist BRL37344 could not reduce infarct size. The 1- and 2-AR blockers CGP-20712A and ICI-118551 completely abolished the isoproterenol-induced reduction in infarct size and improvement in mechanical recovery, while the 3-AR blocker was without effect. Both Rp-8-CPT-cAMPs and wortmannin significantly increased infarct size when administered before 1/ 2-AR preconditioning or at the onset of reperfusion while it reduced mechanical recovery during reperfusion. PTX pretreatment had no significant effect on the reduction in infarct size induced by 1/ 2-AR or 2-AR preconditioning, however it reduced mechanical recovery in the latter. The NOS inhibitors had no effect on the reduction in infarct size induced by 1/ 2-AR preconditioning, but depressed mechanical function during reperfusion. The significant reduction in infarct size by 1/ 2-PC, was associated with activation of ERKp44/p42 and PKB/Akt during the triggering phase, as well as during reperfusion. DPCPX (A1-AdoR antagonist) had no effect on the 1/ 2-PC-induced reduced infarct size or ERK p44/p42 and PKB activation. A2A-AdoR, but not A2b-AdoR, blockade during the trigger phase abolished the reduction in infarct size of 1/ 2-PC. Both antagonists significantly reduced ERK and PKB activation in the trigger phase. In addition, when applied at the onset of reperfusion they significantly reduced ERK p44 / v p42 MAPK and PKB/Akt activation to an even greater extent. MRS-1191 (A3-AdoR antagonist) blocked 1/ 2-PC when applied prior to index ischaemia or when added during early reperfusion, significantly inhibiting both ERK p44 and PKB activation. Cardioprotection of 1/ 2-PC was abolished by inhibition of ROS generation with NAC in the triggering phase as well as at the start of reperfusion. However, the mitoK+ ATP channel blocker 5- HD was without effect. Conclusions: Protection afforded by an acute transient stimulation of the -ARs, depends on the activation of both 1-AR and 2-ARs but not the 3-AR. PKA as well as PI3-K activation prior to sustained ischemia and at the onset of reperfusion were essential for cardioprotection. With functional recovery as endpoint, it appears that NO is involved in 1/ 2-AR preconditioning, while the Gi protein may play a role in 2-AR preconditioning. The production of endogenous adenosine induced by transient b1/b2 stimulation of the isolated rat heart is involved in b−AR preconditioning. Cardioprotection was shown not to be dependent on the A1AdoR while activation of the A3-AdoR occurs during both the triggering and mediation phases. Both the adenosine A2A and, to a lesser extent, the adenosine A2B receptors participate in the triggering phase of b1/b2-PC. Generation of ROS during the triggering and reperfusion phases is involved in eliciting protection, but no role for the mKATP channels could be demonstrated. Finally, activation of the RISK pathway (PKB/Akt and ERKp44/p42) during the triggering phase is a prerequisite for protection. In addition, cardioprotection by b-AR is characterized by activation of the RISK pathway during reperfusion. / AFRIKAANSE OPSOMMING: Iskemiese prekondisionering (IPC) is ‘n kragtige endogene beskerming teen miokardiale iskemie, wat deur blootstelling van die hart aan kort opeenvolgende episodes van iskemie en herperfusie, ontlok word. Hierdie beskerming word medieer deur vrystelling van outakoïede soos adenosine, opioïede en bradikinien. Vrystelling van endogene katekolamiene en aktivering van die betaadrenerge reseptore (b-AR) is bewys om ook by hierdie proses betrokke te wees. Die presiese meganismes waardeur aktivering van die -adrenerge seintransduksiepad tot miokardiale beskerming lei, is nog onbekend. In die lig van bogenoemde, was die doel van die huidige studie om die volgende te evalueer: (i) die onderskeie rolle van die b1-, b2- en b3-AR sowel as die bydrae van die Gi proteïen en PKA in b- adrenerge prekondisionering, (ii) of b-AR stimulasie beskerming ontlok via iskemie en vorming van adenosien, die onderskeie rolle van die A1-, A2-, A3-adenosien reseptore (AdoRs) sowel as die PI3- K/PKB/Akt en ERKp44/p42 seintransduksie paaie, (iv) die mitochondriale KATP (mKATP) kanale, vry suurstof radikale en NO in b−AR prekondisionering. Metodes: Geïsoleerde, geperfuseerde rotharte is aan 35 minute streeksiskemie en herperfusie onderwerp. Infarktgrootte (IS) is deur die tetrazolium (TTC)-kleuringsmetode bepaal. Data is met behulp van ANOVA analiseer. Harte is geprekondisioneer vir 5 min met isoproterenol 0.1 μM ( 1/ 2-AR agonist), of formoterol 1 nM ( 2-AR agonist) of BRL 37344 1 μM ( 3-AR agonist), gevolg deur 5 min herperfusie, voor streeksiskemie. Die belang van die 1-, 2- en 3-ARs sowel as NO is ondersoek, deur onderskeidelik gebruik te maak van selektiewe antagoniste nl CGP- 20712A (300 nM), ICI -18551 (50 nM), SR59230A (100 nM) en NOS inhibitore L-NAME (50μM) of LNNA (50μM). Die rol van die mK+ ATP kanale en ROS is bepaal deur die toediening van die mK+ ATP kanaal blokker 5-HD (100 μM) en die vrye-radikaal opruimer, N-asetiel cysteine (NAC, 300 μM). Die belang van PKA en PI3-K/Akt is bepaal deur toediening van die PKA blokker Rp-8- CPT-cAMPs (16μM) en wortmannin (100nM) respektiewelik. Pertussis toxin (PTX), 30 μg kg-1 is i.p toegedien, 48 uur voor eksperimentasie. vii Die rol van adenosien en die adenosien A1, A2A, A2B en A3 reseptore is bestudeer, deur gebruik te maak van adenosien deaminase en die selektiewe antagoniste DPCPX (1 μM), MRS 1191(1 μM), ZM241385 (1 μM) and MRS1754 (1 μM),repektiewelik. Die middels is deurgaans toegedien tydens die prekondisioneringsprotokol (“snellerfase”) of tydens vroeë herperfusie. Aktivering van PKB/Akt en ERK p44/p42 is deur Western blot analise bepaal. Resultate: Infarktgrootte van harte wat geprekondisioneer is met of isoproterenol ( 1/ 2-PC) of formoterol ( 2-PC), was beduidend kleiner as díe van ongeprekondisioneerde harte. Dit is geassosieer met ‘n toename in postiskemiese meganiese herstel. Die 3-AR agonis BRL37344 ( 3- PC) het egter geen effek op infarktgrootte gehad nie. Die selektiewe 1- en 2-AR blokkers CGP- 20712A en ICI-118551 het die afname in infarktgrootte heeltemal opgehef, asook die verbetering in meganiese herstel tydens herperfusie terwyl die 3-AR blokker geen effek getoon het nie. Beide Rp- 8-CPT-cAMPs en wortmannin het infarktgrootte beduidend vergroot en meganiese herstel beduidend verlaag, wanneer dit net voor 1/ 2-prekondisionering of tydens die begin van herperfusie toegedien is. PTX voorafbehandeling het geen beduidende effek op die vermindering van infarktgrootte (geïnduseer deur 1/ 2-PC of 2-PC) gehad nie. Meganiese herstel is egter verminder in die geval van 2-PC. Die NOS inhibitore het geen effek op die vermindering in infarktgrootte geïnduseer deur b1/b2 gehad nie, maar het ook meganiese herstel onderdruk. Die beduidende afname in infarktgrootte deur b1/b2 prekondisionering is gekenmerk deur aktivering van ERKp42/p44 en PKB/Akt tydens die snellerfase. Soortgelyke aktivering van hierdie kinases is ook tydens herperfusie van b-AR geprekondisioneerde harte waargeneem. DPCPX (A1-AdoR antagonis) het geen effek op die infarkt-verminderde effek van 1/ 2- prekondisionering of op ERK p44/p42 en PKB aktivering gehad nie. A2A-AdoR, maar nie A2b – AdoR, blokkade tydens die snellerfase, het die effek van b-AR prekondisionering op infarktgroottee opgehef. Beide antagoniste het die aktivering van ERKp42/p44 en PKB/Akt tydens die snellerfase onderdruk. Wanneer toegedien tydens herperfusie, het dit die aktivering van hierdie kinases tot ‘n groter mate onderdruk. MRS-1191 (A3-AdoR antagonis) het infarktgrootte beduidend verhoog en 1/ 2-prekondisionering geblokkeer, beide wanneer dit voor indeks-iskemie toegedien is of tydens vroeë herperfusie, tesame met inhibisie van PKB en ERK p44/p44 aktivering. viii Die kardiobeskerming van 1/ 2-prekondisionering is opgehef deur middel van opruiming van vry suurstof radikale deur NAC in die snellerfase sowel as aan die begin van herperfusie. Die mK+ ATP kanaal blokker 5-HD het geen effek op b-AR prekondisionering gehad nie. Gevolgtrekking: Kardiobeskerming teweeggebring deur ‘n kort periode van stimulasie van die - ARs, is afhanklik van die aktivering van beide 1-AR en 2-ARs, maar nie 3-AR nie. PKA sowel as PI3-K aktivering, net voor volgehoue iskemie en tydens vroeë herperfusie, is aangedui om noodsaaklik vir 1/ 2-AR prekondisionering te wees. Waar funksionele herstel as eindpunt gebruik is, blyk dit dat NO wel betrokke is by 1/ 2-AR prekondisionering, terwyl die Gi protein ‘n rol mag speel in 2-AR prekondisionering. Vorming van endogene adenosien tydens b-adrenerge stimulasie is betrokke by b-AR prekondisionering. Hierdie beskerming is nie van die A1-AdoR afhanklik nie, maar aktivering van die A3-AdoR is nodig tydens beide die sneller en herperfusie fases. Beide die A2A-AdoR, en tot ‘n mindere mate die A2B–AdoR, is ook betrokke by die snellerfase. Vorming van vry suurstof radikale is nodig vir b-AR prekondisionering, nterwyl die mKATP kanale nie betrokke is nie. Ten slotte, aktivering van die RISK seintransduksiepad (ERKp42/p44 en PKB/Akt) tydens die snellerfase is ‘n voorvereiste vir die ontlokking van beskerming. Daarbenewens word b-AR prekondisionering gekarakteriseer deur aktivering van hierdie pad tydens herperfusie. / South African Medical Research Council / University of Stellenbosch