Thesis (MSc)--Stellenbosch University, 2003. / ENGLISH ABSTRACT: Advances in pharmacology, biochemistry and biotechnology are increasingly dependant upon affinity chromatography as a preferred separation technique for the purification and characterisation of specific biomolecules. In the past few years avidin-biotin technology has been widely and successfully used in the fields of medicine, pharmacy, biology and biochemistry. The avidin-biotin complex (ABC) has been used as a mediator for affinity chromatography, affinity cytochemistry, immunoassay, histopathology, bioaffinity sensors, erosslinking and immobilisation studies. The main reason for the popularity of the ABC and its growing usefulness in biotechnology is the exceptionally high affinity (1015 M-l) and stability of the noncovalent interaction between avidin and biotin. The use of the ABC is broadening as different biotin derivatives and avidin-containing conjugates are becoming commercially available. The aim of this work was to evaluate the usefulness of a plutonic" FI 08 and the ABC conjugate to effect affinity separation. Towards this aim, the adsorption of plutonic" F108 onto hydrophobic polysulphone membrane surfaces was studied. This information was used to determine the theoretical maximum amount of pluronic" FI08 that will adsorb onto a unit surface area of the membrane. It is known that the polypropylene oxide (PPO) centre block ofthe pluronic" F I08 surfactant molecule governs the concentration of pluronic" F I 08 molecules that will adsorb onto a given hydrophobic surface. If the maximum coating concentration of plutonic" FI08 is known, one can assume that the maximum coating concentration of any pluronic derivative, with the same PPO centre block size, will be the same. Adsorption studies were carried out, the Langmuir adsorption isotherm was determined, and subsequently the fractional coating was calculated. The end-groups of plutonic" FI08 were modified as follows and the substituted pluronic was adsorbed onto a membrane that was to act as the solid support matrix in the development of an affinity system: Amino pluronic was synthesised by first tosylating pluronic" FI08, followed by azidation with NaN3 then reduction with LiAI~. The synthesised amino pluronic was then biotinylated using N-hydroxysuccinimide biotin ester. The suitability of this synthetic route was first assessed on a model compound, 2-methoxyethylamine, and validated by NMR (Nuclear Magnetic Resonance) spectroscopy. The synthetic protocol was then used to derivatise the larger pluronic molecule. The affinity system was tested on two different hydrophobic surfaces: polystyrene and polysulphone membranes (PSMs). Avidin-conjugated horseradish peroxidase was obtained and used to interact with the immobilised biotin. The enzymatic reaction of the coupled peroxidase converted the substrate, 2, 2'-azino-di-(3-ethyl-benzthiazoline-6-sulphonic acid) (ABTS) to a coloured product. The colour developed is proportional to the amount of biotin that was immobilised on the hydrophobic surfaces studied. Non-covalent immobilisation of the synthesised biotin-pluronic molecule was successfully obtained onto the hydrophobic polystyrene as well as the polysulphone membrane surfaces. / AFRIKAANSE OPSOMMING: Vooruitgang in die farmakologie, biochemie en biotegnologie word al meer afhanklik van affiniteits chromatografie as die verkose tegniek vir die suiwering en karaterisering van spesifieke biomolekules. Oor die afgelope jare het die avidien-biotien tegnologie homself as baie bruikbaar bewys in die mediese, farmakologiese, biologiese en biochemiese velde. Toepassings waar die avidien-biotien kompleks betrokke was sluit in die toepassing as 'n mediator vir affiniteits chromatografie, affiniteits sitologie, immuno bepalings, histopatologie, bioaffiniteits sensors sowel as kruisbinding en immobiliserings studies en vele meer. Die hoofrede vir die gewildheid van die avidien-biotien kompleks en die groeiende bruikbaarheid in die biotegnologie is die buitengewone hoë affiniteit (l015 M-I ) en stabiliteit van die nie-kovalente interaksie tussen avidien en biotien. Die toepassingsveld van die avidien-biotien kompleks word wyer met die verskeidenheid biotien derivate en avidien-bevattende konjugate wat kommersiëel beskikbaar is. Die doel van die werk wat hier gedokumenteer word is om die bruikbaarheid van Plutonic" FI08 en die avidien-biotien kompleks, vir gebruik in 'n affiniteits chromatografie sisteem, te evalueer. Om hierdie doel te bereik is die adsorpsie van Pluronic" FI08 aan hidrofobiese polisulfoon membraan oppervlaktes bestudeer. Die eksperimentele data wat gegenireer is, is gebruik om die teoretiese maksimum hoeveelheid Pluronic wat per eenheids oppervlakte membraan adsorbeer te bepaal. Dit is reeds bekend dat die polipropileen (PPO) middel blok van die Pluronic emulgant die konsentrasie van die geadsorbeerde Pluronic molekules op 'n gegewe hidrofobiese oppervlakte bepaal. Indien die maksimum bedekkingskonsentrasie VIr maksimum oppervlakbedekking van Plutonic" FI08 bekend is, kan teoreties aanvaar word dat die bedekkingskonsentrasie vir enige Pluronic derivaat met dieselfde grootte PPO blok dieselfde sal wees. Adsorpsiestudies was uitgevoer om die Langmuir adsorpsie isoterm te bepaal. Daaropvolgend was die fraksionele bedekking bereken. Amino-pluronic was gesintetiseer deur die eindpunte van Pluronic te derivatiseer. Hierdie Pluronic derivaat was gevolglik geadsorbeer aan 'n membraan wat gedien het as die soliede oppervlakte vir die ontwikkeling van 'n affiniteits chromatografie sisteem. Amino-pluronic was gesintetiseer deur Pluronic eers te tosileer en daarna te asideer met NaN3 en laastens te reduseer met LiAI~. Die produk was gebiotinileer deur gebruik te maak van N-hidroksisuksinimied-biotien-ester. Die bruikbaarheid van hierdie sintetiese roete is eers bepaal deur van 'n model verbinding, 2-metoksiëtielamien, gebruik te maak en dit met behulp van KMR (Kern Magnetiese Resonans) spektroskopie te karakteriseer. Die affiniteits sisteem is getoets op twee verskillende hidrofobiese oppervlaktes naamlik polistireen en polisulfoon membraan oppervlaktes. Avidien gekonjugeerd met 'n peroksiedase ensiem is gebruik om met die geïmmobiliseerde biotien te assosieer. Die ensiematiese reaksie van die gekoppelde peroksiedase het die substraat 2, 2' -azino-di-(3-etiel-benzthiazolien-6-sulfoonsuur) (ABTS) omgesit na 'n gekleurde produk, waar dit teenwoordig is. 'n Reeks wasstappe is gebruik om die gemodifiseerde peroksidase ensiem wat nie aan die hidrofobiese oppervlakte gekoppel nie, weg te spoel. Hierdeur is die mate van binding aan die hirofobiese oppervlakte gekwantifiseer deur die kleur te kwantifiseer wat ontwikkelomdat die kleurontwikkeling direk proporsioneel is aan die hoeveelheid peroksidase wat nog aan die membraan gekoppel is. Nie-kovalente immobilisasie van die gesintetiseerde biotien-pluronic molekule is suksesvolop beide die hidrofobiese polistireen oppervlakte sowel as die polisulfoon membraan verkry.

Thesis (MSc)--Stellenbosch University, 2003. / ENGLISH ABSTRACT: In this study, a number of mono- and di-substituted acyl(aroyl)thioureas were investigated for potential application as specific carriers (ionophores) for the transport and extraction of Ag(l) from a mixture of Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Pb(lI) ions. The experimental arrangement for the transport experiments employed a liquid membrane set up involving a 3-phase system - 2 aqueous phases (source and receiving phase) separated by a chloroform membrane incorporating the ligand. Competitive metal ion transport experiments were conducted using the liquid membrane set up. The aqueous source and receiving phases were analyzed using Atomic Absorption Spectroscopy (AAS) and results were confirmed by Inductively Coupled Plasma-Optical Emission Spectroscopy (ICPOES). The transport results show that the N,N-dialkyl-substituted-N'-acyl(aroyl) (HL) thioureas studied, with the exception of the N,N-di-(2-hydroxyethyl)-N'-benzoylthiourea (HL3 ) and N-piperidyl-N'-4-nitrobenzoylthiourea (HL9 ), were efficient and selective for Ag(I). HL9 was also selective for Ag(l) but not efficient. HL3 was selective for Cu(II). Under the experimental conditions employed, 13% Cu(lI) was transported by HL3 . Among the N,Ndialkyl- N'-aroylthioureas, maximum Ag(l) transport was obtained by using N,N-diethyl-N'-4- chlorobenzoylthiourea (HL5 ) and N,N-di-n-butyl-N'-benzoylthiourea (HL \ Under the experimental conditions employed, the percentages of Ag(l) transported by HL5 and HL 1 were 48% and 42% respectively. The transport selectivity and efficiency of 3,3,3' ,3'-tetraethyl-1 ,1'-isophthaloylbisthiourea (H2L12 ) and N,N-diethyl-N'-camphanoylthiourea (HL13)for Ag(l) were also studied. We were particularly interested, in comparing the Ag(l) transport and extraction efficiency of these ligands with that of the HL and H2L ligands. The experimental results reveal that, of all the ligands we investigated in this study, HL 13 was the most efficient and selective carrier for Ag(l) transport. The interesting result is that, depending on the ligand concentration used, HL 13 transported 71-81% of Ag(I). Competitive two-phase metal ion solvent extraction experiments were also performed under conditions similar to the transport studies. The results show that by varying the ligand concentration in the membrane phase, up to 100% Ag(l) can be selectively and efficiently extracted from the mixture of the seven metal ions. Finally, the N,N-di-(n)-butyl-N'-benzoylthiourea (HL1) ligand and its complex with Ag(l) were synthesized. Single crystals of the complex were grown for X-ray crystallography and the crystal and molecular structure of the complex was determined. The crystal structure showed that Ag(l) is bonded to the deprotonated ligand through the S,O atoms forming interesting cluster [Ag (L - S, 0)] 4 in the solid state. This structure is monoclinic and crystallizes in the space group P21!c with a = 17.805 (4) A, b = 21.759 (4) A, c = 36.438 (7) A, f3= 96.34(3)°, Z = 8 and a final R-factor of 5.4%. / AFRIKAANSE OPSOMMING: In hierdie proefskrif is 'n aantal mono- en di-gesubstitueerde asiel(ariel) tioureums ondersoek vir moontlike gebruik as ionofore (spesifieke draers) vir die transportasie en ekstraksie van Ag(l) vanuit 'n mengsel van Co(ll), Ni(II), Cu(II), Zn(II), Cd(II), Ag(l) en Pb(lI) ione. 'n Drie-fase selsisteem is gebruik vir die transportasie eksperimente, twee waterige fases (bron- en ontvang-fase) wat geskei is met die chloroform membraan fase wat die ligande bevat. Kompeterende metaalioon transportasie eksperimente is uitgevoer met behulp van hierdie vloeistof membraan stelsel. Die twee waterige fases is deur middel van Atoomabsorpsie Spektroskopie (AAS) ge-analiseer en resultate is bevestig met gebruik van Induktief-gekoppelde Plasma-Optiese Emissie Spektroskopie (IGP-OES). Die resultate het getoon dat elkeen van die N,N-dialkiel-gesubstitueerde-N'-asiel(ariel) (HL) tioureums, met uitsondering van N,N-di(2-hidroksie-etiel)-N'-benzieltioureum(HL 3) en Npiperidiel- N'-4-nitrobenzieltioureum(HL9 ), doeltreffend en selektief was vir Ag(l) transportasie. HL9 was selektief vir Ag(I), maar die transportasie waarde was nie hoog nie, dws. dit was nie doeltreffend nie. HL3 was selektief vir Cu(II). Met gebruik van ons eksperimentele kondisies is 13% Cu(lI) getransporteer deur HL 3. Van die N,N-dialkiel-N'- ariel tioureums, is maksimum transportasie van Ag(l) verkry met gebruik van N,N-dietiel- N'-4-chlorobenzieltioureum (HL5) en N,N-di-n-butiel-N'-benzieltioureum (HL1). Met gebruik van ons eksperimentele kondisies was die persentasie transportasie van Ag(l) deur HL5 en HL 1 48% en 42% onderskeidelik. Die selektiwiteit en doeltreffendheid van 3,3,3' ,3'-tetra-etiel-1 ,t-isoftaltelblstioureumtl+L 12) en N,N-di-etiel-N'-kamfonieltioureum (HL13) vir Ag(l) transportasie is ook onderneem. Ons was besonder ge-interesseerd om die Ag(l) transportasie en ekstraksie van hierdie ligande te vergelyk met dié van die HL en H2L tipe ligande. Die eksperimentele resultate het getoon dat van al die ligande wat bestudeer is, HL 13 die doeltreffendste en mees selektiewe ionofoor was. Van besondere, belang was dat, afhangend van die ligand konsentrasie wat gebruik is, HL13 71-81% Ag(l) getransporteer het. Kompeterende twee-fase metaalioon vloeistof-vloeistof ekstraksie eksperimente is ook uitgevoer onder toestande soortgelyk aan dié van die transportasie eksperimente. Die resultate toon dat met varierende ligand konsentrasie, tot soveel as 100% Ag(l) selektief en doeltreffend geëkstrakeer word vanuit 'n mengsel van die sewe metaal ione. N,N-di-n-butiel-N'-benzieltioureum (HL1 ) ligande en die kompleks daarvan met Ag(l) is ook gesintetiseer. Enkel-kristalle van die kompleks is verkry en X-straal kristallografiese analiese is onderneem. Die kristalstruktuur toon hoedat Ag(l) gebind is aan die gedeprotoneerde ligand deur die S en Q atome en toon ook interessante [Ag(L-S,Q)]4 groepe in die vaste toestand. Hierdie struktuur is monoklinies en kristaliseer in die ruimtegroep P21!c met a = 17.805(4) Á, b = 21.759(4)Á, c = 36.438(7)Á, P = 96.34(3t, z = 8 en 'n finale R-faktor van 5.4%.

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Repetitive stress injuries are common in the workplace where workers perform repetitive tasks continuously throughout the day. Muscle fatigue may lead to injury either directly through muscle damage or indirectly through changes in coordination, development of muscle imbalances, kinematic and muscle activation variability, and/or movement instability. To better understand the role of muscle fatigue in changes in movement parameters, we studied how muscle fatigue and muscle imbalances affected the control of movement timing, variability, and stability during a repetitive upper extremity sawing task. Since muscle fatigue leads to delayed muscle and cognitive response times, we might expect the ability to maintain movement timing would decline with muscle fatigue. We compared timing errors pre- and post-fatigue as subjects performed this repetitive sawing task synchronized with a metronome using standard techniques and a goalequivalent manifold (GEM) approach. No differences in basic performance parameters were found. Significant decreases in the temporal correlations of the timing errors and velocities indicated that subjects made more frequent corrections to their movements post-fatigue. Muscle fatigue may lead to movement instability through a variety of mechanisms including delayed muscle response times and muscle imbalances. To measure movement stability, we must first define a state space that describes the movement. We compared a variety of different state space definitions and found that state spaces composed of angles and velocities with little redundant information provide the most consistent results. We then studied the affect of fatigue on the shoulder flexor muscles and general fatigue of the arm on movement stability. Subjects were able to maintain stability in spite of muscle fatigue, shoulder strength imbalance and decreased muscle cocontraction. Little is known about the time course for adaptations in response to fatigue. We studied the effect of muscle fatigue on movement coordination, kinematic variability and movement stability while subjects performed the same sawing task at two work heights. Increasing the height of the task caused subjects to make more adjustments to their movement patterns in response to muscle fatigue. Subjects also exhibited some increases in kinematic variability at the shoulder but no changes in movement stability. These findings suggest that people alter their kinematic patterns in response to fatigue possibly to maintain stability at the expense of increased variability. / text

It has been suggested that Patellofemoral Pain (PFP) may be the result of a coordinate state which exhibits less joint coordination variability. The ability to relate joint coordination variability to PFP pathology could have many clinical uses; however, evidence to support clinical application is lacking. Vector coding’s coupling angle variability (CAV) has been introduced as a possible analysis method to quantify joint coordination variability. The purpose of this study was to assess the clinical usefulness of CAV measures from a dynamical systems perspective. This involved establishing the precision limits of CAV measures when physiological conditions are held constant, altering control parameters of knee pain and population then determining if the observed changes in CAV were clinically meaningful. 20 female recreational runners with PFP and 21 healthy controls performed a treadmill acclimation protocol then ran at a self-selected pace for 15 minutes. 3-D kinematics, force plate kinetics, knee pain and perceived exertion were recorded each minute. CAV were calculated for six knee-ankle combinations for 2 sets of 5 non-consecutive stride cycles at each capture period. Data were selected for the PFP group at a high (=>3) and low (<=high-2) pain level in a non-exhausted state (<14). Healthy data were used from the 11th minute of the running. Levels of agreement were performed between the 2 sets of CAV measures for both populations, a paired t-test compared low to high pain CAV measures and independent t-tests compared populations at the high pain state. Several CAV measures showed a significant increase in value with an increase in pain and were significantly greater for the PFP group. None of the observed changes exceeded the precision limits of all CAV measures investigated. These results do not agree with previous claims that less variability is indicative of pathology but rather the opposite. This suggests that there might be an optimal amount of variability to maintain a healthy coordinate state with deviations in any direction being detrimental. However; due to the volatile nature of CAV measures, the clinical use of CAV is not recommended using current analysis methods since changes observed weren’t considered clinically meaningful.

La chimie de coordination des éléments de transition (d ou f) permet de synthétiser de nombreux matériaux magnétiques moléculaires aux propriétés physico-chimiques très variées (molécules aimants ou complexes à transition de spin). Nous avons choisi certains ligands suivant des objectifs très précis et développé leur chimie de coordination afin d'obtenir des propriétés magnétiques spécifiques.<br /> La voie de synthèse par méthode solvothermale a permis de caractériser des complexes originaux à base de macrocycles. Deux complexes dinucléaires à base de CoII et FeIII où les deux centres métalliques sont pris en « sandwich » entre deux unités calixarènes ont été ainsi isolés. Ces dimères ont été utilisés comme brique moléculaire de départ pour l'élaboration de cluster à plus haute nucléarité. Un complexe associant six ions CoII a pu être isolé et caractérisé.<br /> La synthèse de nouveaux de ligands de type base de Schiff résultant de la condensation de l'acetylacétone avec différents acides aminés a été développée et leur complexation avec différents éléments de la première série de transition a été étudiée. Ainsi, un trimère à base de CuII a été caractérisé et ses propriétés magnétiques ont été modélisées par une série de calculs ab initio. Cette étude théorique a été complétée par un ensemble de mesures RPE en solution en fonction de la température.<br />Enfin, la chimie de coordination de ligands de type β-dicétone, en particulier l'acétylacetonate, avec différents métaux (3d et 4f ) a été revisitée. Ce ligand et certains de ses dérivés permettent de contrôler la nucléarité d'édifices moléculaires à base d'ions 3d et 4f. L'utilisation d'une brique moléculaire préformée de type cubane a permis d'isoler un complexe heptanucléaire de type « double cubane » à base de NiII qui présente les caractéristiques d'une molécule-aimant. En jouant sur l'effet de l'encombrement stérique du ligand, trois familles de complexes polynucléaires Ln5, Ln8 et Ln9 ont été obtenues par auto-assemblage suivant les méthodes de la chimie douce à base d'ions 4f. Des études structurales, magnétiques et une analyse approfondie des caractéristiques spectroscopiques des complexes à base d'europium(III) ont été réalisées. Une étude complète a été menée sur une famille de complexes Y9 dopés en europium (Y9-xEux).

Ce travail est axé vers la compréhension détaillée des propriétés de luminescence de composés de certains métaux lourds. La première partie de ce mémoire décrit la caractérisation spectroscopique d'un radical de type nitronyle nitroxyde, 2-(2-pyridinyl)-4,4,5,5-tétraméthyl-4,5-dihydro-1H-imidazolyl-1-oxyl-3-oxyde, abrégé (NIT2-Py), et de ses complexes avec les cations Tb(III), [Tb(hfac)3NIT2-Py], et Y(III), [Y(hfac)3NIT2-Py]. La variation de la température affecte les spectres de luminescence qui montrent de la structure vibronique résolue. Les maxima de ces transitions vibroniques se rapprochent au fur et à mesure que la température augmente. Ces variations des maxima en fonction de la température ne correspondent pas à des variations de fréquences vibrationnelles et sont de l'ordre de 200 cm-1 entre 80 K et 240 K. La variation de la température n'a pas d'influence significative sur la structure moléculaire, comme atteste la variation mineure des maxima des spectres Raman entre 80 K et 300 K. La comparaison des spectres expérimentaux à des spectres calculés montre que ces variations peuvent être reproduites par l'utilisation d'une combinaison de fréquences vibrationnelles. Le paramètre dont la variation est très significative est la résolution du spectre de luminescence, représentée par la largeur à mi-hauteur des transitions vibroniques qui forment le spectre de luminescence. La deuxième partie de ce mémoire décrit les propriétés de luminescence d'une série de complexes d’or(I). Elles sont comparées aux changements structuraux à pression et température variable. Les interactions aurophiles ont une grande influence sur la luminescence. La variation de la température et de la pression est une approche efficace pour varier la luminescence. Les effets observés dans les spectres d'émission de ces complexes dépendent des changements de structure induits par variation de la température et de la pression. Ces petites variations structurales mènent à des changements importants, à titre d'exemple à un déplacement du maximum de la bande de luminescence de 60 cm-1/ kbar vers les faibles énergies pour un des complexes de l'or(I) étudiés au cours de ce projet. / The overall goal of this work is to contribute to the understanding of luminescence properties of transition metal compounds. The first part of this thesis describes the spectroscopic characterization of a pyridine-substituted nitronyl nitroxyde radical 2-(2-pyridyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazolyl-3-oxide-1-oxyl abbreviated (NIT2-Py) and its complexes with Tb(III) and Y(III), [Tb(hfac)3NIT2-Py] and [Y(hfac)3NIT2-Py], respectively. Their luminescence spectrum show resolved vibronic structure and variations with temperature The energy difference between vibronic luminescence maxima decreases with increasing temperature. This decrease is on the order of 200 cm-1 between 80 K and 240 K and is not due to decreasing Raman frequencies. The variations of temperature do not have a significant influence on the molecular structures, as illustrated by the very small variation of Raman maxima between 80 K and 300 K. Luminescence spectra were calculated using the time dependent theory of spectroscopy. Calculated luminescence spectra show that the variations with temperature are reproduced by using specific combinations of experimental frequencies and by adjusting the width of the vibronic transitions, determining the resolution of the luminescence spectrum. The second part of the thesis describes the luminescence spectroscopic properties of a series of trimetallic gold(I) complexes at variable temperature and pressure. Aurophilic interactions are very important for these compounds and influence the luminescence spectra. The spectroscopic features are compared to structural changes at variable temperature and pressure. Even small changes in structure lead to significant changes in luminescence, for example a shift of the maximum of the luminescence band by 60 cm-1/ kbar to lower energy for one of the gold(I) complexes studied.

As a pedestrian at the roadside, the two most informative cues as to the distance and rate of closure of a vehicle are its optical size and the rate of expansion of the optical image. In addition, the time to arrival of an approaching vehicle can be perceptually estimated by the ratio of these two variables, referred to as tau (Lee, 1976). Sensitivity to optic expansion is critical for collision avoidance and was measured in populations of adults, typically developing children, and in children with Developmental Coordination Disorder (DCD), an idiopathic condition characterised by marked impairments in motor coordination that negatively impact on activities of daily living. A central tendency was found in adults (n = 193) between 18 to 59 years of age to make significant errors in judging the approach rates of two vehicles. Inflated errors were observed in children (n = 136) between 6 to 17 years of age, with decreased sensitivity in the youngest age group (6 to 11 years). Furthermore, a significant decrement was found in children (n = 9) with DCD between 6 to 11 years of age. Across all groups, a systematic vehicle size bias was found, whereby faster small vehicles were perceived as travelling slower than larger vehicles. This pattern of results suggest that in general, observers are not utilising tau in judgments of relative approach rates for speeds typically encountered at the roadside, but instead rely on optical expansion that does not compensate for image size. Errors due to a reliance on optic size were inflated in children with DCD, potentially placing them at significantly greater risk at the roadside. To examine the decreased sensitivity observed in DCD, thresholds for detecting visual looming were measured in children (n = 11) with DCD between 6 to 11 years of age. A significant deficit was found when vehicles were presented in perifoveal vision, whereby children with DCD may perceive vehicles that are 5 seconds away as stationary if they are travelling any faster than ~14 mph. This demonstration of a low-level visual processing deficit could suggest an immaturity in the dorsal stream network and explain some of the difficulties that characterise DCD. Critically, perceptual judgments at the roadside are inextricably linked to the motoric capability of the observer. If a pedestrians crossing time is greater than the time available, collision will occur. Crossing gap thresholds were measured and compared to walking times for a single vehicle approaching at varying speeds. Children (n = 9) with DCD between 6 to 11 years of age left considerably longer temporal crossing gaps than their action capabilities necessitated. However, when children with DCD were presented with multiple vehicles in a virtual reality environment, they accepted crossing gaps at all approach speeds that were shorter than the time it would take them to cross. This suggests that children with DCD may not have the perceptual accuracy to predict their required action gaps in a road crossing situation. One explanation for these findings could be a difference in DCD in how vision is dynamically allocated to facilitate the preparation of goal-directed actions. Dynamic allocation of visual attention was assessed in a series of experiments that measured eye movement latencies and hand movement accuracy in children (n = 5) with DCD between 6 to 11 years of age. Both measures were found to be comparable in DCD with their typically developing peers regardless of task complexity, indicating that the allocation of visual attention is not deficient in children with DCD. The prospective control of movement in our everyday lives is critically depended on estimating the immediacy of approaching objects. Combined, these results indicate that children with DCD may be particularly vulnerable at the roadside due to a visual motion processing deficit, consistent with atypical function across broad neural structures such as the dorsal stream.

Leading philosophical accounts of joint activity, such as Michael Bratman’s account of ‘shared intentional activity’, take joint activity to be the outcome of two or more agents having a ‘shared intention’, where this is a certain pattern of mutually known prior intentions (plans) that are directed toward a common goal. With Bratman’s account as a foil, I address two lacunas that are relatively unexplored in the philosophical literature. The first lacuna concerns how to make sense of the apparently joint cooperative activities of agents that lack the capacities for planning and “mindreading” that one must have in order to be a party to a shared intention (consider, for example, the social play of young children or the cooperative hunting of non-human primates or social carnivores). The second lacuna concerns how participants (including adult human agents) are able to coordinate their actions “online”—that is, during action execution as a joint activity unfolds—without recourse to plans that specify in advance what they should do (consider the coordination involved when two friends meet and do a “high five”). Chapters 2 and 3 focus on the first lacuna, while chapters 4 and 5 focus on the second. In chapter 2, I focus on why participants must have mutual or common knowledge of each other’s intentions and beliefs in order to have a shared intention: Why must these attitudes be “out in the open”? I argue that, if participants lack the concept of belief, then one of the two main motivations for the common knowledge requirement—to filter out certain cases that intuitively aren’t cases of genuine joint activity—actually dissipates. Furthermore, a kind of “openness” that only requires of participants that they have the concept of goal but not that of belief can satisfy the other main motivation, to make sense of the idea that joint activities are non-accidentally coordinated. In chapter 3, I offer an account of a kind of joint activity in which agents such as young children and some non-human primates could participate, given what we know about their socio-cognitive capacities. In chapter 4, I argue that ‘shared intention’-accounts are unable to say much about spontaneous or skilful joint action because of the following widely accepted constraint on what one can intend: while an agent might intend—in the sense of commit to a plan—that “we” do something together, an agent cannot intend to perform “our” joint action. I reject this constraint and argue that some joint actions (such as a joint manoeuvre performed by two figure skaters) are joint in virtue of each participant having what I call ‘socially extended intention-in-action’ that overlap. In chapter 5, I review empirical work on subpersonal enabling mechanisms for the coordination of joint action. The review provides clues to what it is that enables participants to successfully coordinate their actions in the absence of plan-like intentions or beyond what such intentions specify. While what I address are lacunas rather than problems, an upshot of this thesis is that leading philosophical accounts of joint activity may have less explanatory scope than one might otherwise be led to believe. The accounts of joint activity and joint action that are presented in this thesis are arguably applicable to many of the joint activities and joint actions of adult human beings. The account also helps us avoid the false dichotomy between a very robust form of joint activity and a mere concatenation of purely individualistic actions—a dichotomy that accounts such as Bratman’s arguably invite us to adopt.

The task of developing a framework for which agents can communicate reliably and flexibly in open systems is not trivial. This thesis addresses the dichotomy between reliable communication and facilitation of the autonomy of agents to create more flexible and emergent interactions. By the introduction of adaptations to a distributed protocol language, agents benefit from the ability to communicate interaction protocols to elucidate the social norms (thus creating more reliable communication). Yet, this approach also provides the functionality for the agent to unilaterally introduce new paths for the conversation to explore unforeseen opportunities and options (thus restoring more autonomy than possible with static protocols). The foundation of this work is Lightweight Coordination Calculus (LCC). LCC is a distributed protocol language and framework in which agents coordinate their own interactions by their message passing activities. In order to ensure that adaptations to the protocols are done in a reasonable way, we examine the use of two models of communication to guide any transformations to the protocols. We describe the use of FIPA's ACL and ultimately its unsuitability for this approach as well as the more fecund task of implementing dialogue games, an model of argumentation, as dynamic protocols. The existing attempts to develop a model that can encompass the gulf between reliability and autonomy in communication have had varying degrees of success. It is the purpose and the result of the research described in this thesis to develop an alloy of the various models, by the introduction of dynamic and distributed protocols, to develop a framework stronger than its constituents. Though this is successful, the derivations of the protocols can be dificult to reconstruct. To this end, this thesis also describes a method of protocol synthesis inspired by models of human communication that can express the dialogues created by the previous approaches but also have a fully accountable path of construction. Not only does this thesis explore a unique and novel approach to agent communication, it is tested through a practical implementation.