Mother-Infant Reciprocity and the Development of Joint Attention in 12 Month Old Infants

Social contingency is the ability to connect social stimuli, such as those behaviors performed by oneself and those performed by others. Detecting social contingencies occurs by means of reciprocity through shared experiences with others. Reciprocity denotes a circumstance in which two individuals participate in a collaborative exchange, and is distinguished from an event in which two individuals engage in separate, unrelated activities. Specifically, reciprocity incorporates joint attention (JA), which occurs when two individuals simultaneously and visually attend to the same item. JA is facilitated by gazing and pointing, whereby one individual initiates the action and the second individual follows suit by, for example, gaze-following. However, little is known about the role the mother may play in the development of JA. The purpose of our study was to investigate social contingency between mothers and infants engaging in dyadic interactions. Thirty-three 12-month-old typically developing infants (M = 12.2, SD = .19; N = 19 males) were filmed for 10 minutes during free play with their mothers and toys provided by an experimenter. Reciprocity was measured by coding mother-infant interactions when a precise chain of events occurred: (1) mother initiated a bid by introducing a toy/activity or request to the infant, (2) infant accepted the bid/request by engaging in play with the given toy/activity, and (3) mother persisted by continuing to engage in play with said toy/activity. We computed a Pearson Correlation to assess the relation between the mothers��� initiations of JA and their infants��� responses to JA. We found a moderately positive correlation between the two variables (r= 0.37, p<.05). Our findings suggest that reciprocity, an important component of social relationships, during parent-infant dyads may serve as a scaffold for joint attention abilities, which have been linked to social and language development.

Sedimentology of cores from the Iberian margin

Bioturbation in marine sediments has basically two aspects of interest for palaeo-environmental studies. First, the traces left by the burrowing organisms reflect the prevailing environmental conditions at the seafloor and thus can be used to reconstruct the ecologic and palaeoceanographic situation. Traces have the advantage over other proxies of practically always being preserved in situ. Secondly, for high- resolution stratigraphy, bioturbation is a nuisance due to the stirring and mixing processes that destroy the stratigraphic record. In order to evaluate the applicability of biogenic traces as palaeoenvironmental indicators, a number of gravity cores from the Portuguese continental slope, covering the period from the last glacial to the present were investigated through X-ray radiographs. In addition, physical and chemical parameters were determined to define the environmental niche in each core interval. A number of traces could be recognized, the most important being: Thalassinoides, Planolites, Zoophycos, Chondrites, Scolicia, Palaeophycus, Phycosiphon and the generally pyritized traces Trichichnus and Mycellia. The shifts between the different ichnofabrics agree strikingly well with the variations in ocean circulation caused by the changing climate. On the upper and middle slope, variations in current intensity and oxygenation of the Mediterranean Outflow Water were responsible for shifts in the ichnofabric. Larger traces such as Planolites and Thalassinoides dominated in coarse, well oxygenated intervals, while small traces such as Chondrites and Trichichnus dominated in fine grained, poorly oxygenated intervals. In contrast, on the lower slope where calm steady sedimentation conditions prevail, changes in sedimentation rate and nutrient flux have controlled variations in the distribution of larger traces such as Planolites, Thalassinoides, and Palaeophycus. Additionally, distinct layers of abundant Chondrites correspond to Heinrich events 1, 2, and 4, and are interpreted as a response to incursions of nutrient rich, oxygen depleted Antarctic waters during phases of reduced thermohaline circulation. The results clearly show that not one single factor but a combination of several factors is necessary to explain the changes in ichnofabric. Furthermore, large variations in the extent and type of bioturbation and tiering between different settings clearly show that a more detailed knowledge of the factors governing bioturbation is necessary if we shall fully comprehend how proxy records are disturbed. A first attempt to automatize a part of the recognition and quantification of the ichnofabric was performed using the DIAna image analysis program on digitized X-ray radiographs. The results show that enhanced abundance of pyritized microburrows appears to be coupled to organic rich sediments deposited under dysoxic conditions. Coarse grained sediments inhibit the formation of pyritized burrows. However, the smallest changes in program settings controlling the grey scale threshold and the sensitivity resulted in large shifts in the number of detected burrows. Therefore, this method can only be considered to be semi-quantitative. Through AMS-^C dating of sample pairs from the Zoophycos spreiten and the surrounding host sediment, age reversals of up to 3,320 years could be demonstrated for the first time. The spreiten material is always several thousands of years younger than the surrounding host sediment. Together with detailed X-ray radiograph studies this shows that the trace maker collects the material on the seafloor, and then transports it downwards up to more than one meter in to the underlying sediment where it is deposited in distinct structures termed spreiten. This clearly shows that age reversals of several thousands of years can be expected whenever Zoophycos is unknowingly sampled. These results also render the hitherto proposed ethological models proposed for Zoophycos as largely implausible. Therefore, a combination of detritus feeding, short time caching, and hibernation possibly combined also with gardening, is suggested here as an explanation for this complicated burrow.

Annotated record of the detailed examination of Mn deposits recovered by the Geological Survey of Japan (GSJ) during the 1971-1974 period in the Pacific Ocean

In 1974, the Geological Survey of Japan began its systematic investigation of manganese nodules in the Central Pacific Basin on the new geological research vessel Hakurei Maru. The first cruise (GH 74-5) was carried out over an eastern part area of the Basin (6��-10��30'N, 164��30'-171��30'W), and the authors report here the preliminary results on the occurrence of manganese nodule deposits, paying particular consideration to their relationship to submarine topography and surficial and sub-bottom sedimentary facies. The surveyed area comprises a deep-sea basin at 5,000-5,400 m, defined to the north and east by the chain of seamounts and guyots of the Christmas Ridge. The deep-sea basin is divided roughly into 2 contrasting topographic features. The eastern part is characterised by flattened topography resulting from continuous deposition of turbidities; the meridian and western parts are characterised by gently rolling topography and the existence of a large number of deep-sea hills. Manganese nodules are almost lacking in the former flattened eastern area, whereas they are widely distributed in the latter rolling meridian and western parts. The population density of nodules varies from less than 1 Kg/m�� to 26 kg/m�� and the higher density is found in the siliceous-calcareous ooze zone of rather small, flat basins surrounded by deep-sea hills. The density is closely related to the thickness of the transparent layer obtained by 3.5 kHz PDR profiling over the whole area. Considering the various data of grab sampling, 3.5 kHz PDR profiling and to a lesser extent of deep-sea television and camera observations, the most promising manganese field in the present area seems to be confined to the north of the western sector of the area.

Computational fluid dynamics (CFD) based approach to consequence assessment of accidental release of hydrocarbon during storage and transportation

This thesis investigated the risk of accidental release of hydrocarbons during transportation and storage. Transportation of hydrocarbons from an offshore platform to processing units through subsea pipelines involves risk of release due to pipeline leakage resulting from corrosion, plastic deformation caused by seabed shakedown or damaged by contact with drifting iceberg. The environmental impacts of hydrocarbon dispersion can be severe. Overall safety and economic concerns of pipeline leakage at subsea environment are immense. A large leak can be detected by employing conventional technology such as, radar, intelligent pigging or chemical tracer but in a remote location like subsea or arctic, a small chronic leak may be undetected for a period of time. In case of storage, an accidental release of hydrocarbon from the storage tank could lead pool fire; further it could escalate to domino effects. This chain of accidents may lead to extremely severe consequences. Analyzing past accident scenarios it is observed that more than half of the industrial domino accidents involved fire as a primary event, and some other factors for instance, wind speed and direction, fuel type and engulfment of the compound. In this thesis, a computational fluid dynamics (CFD) approach is taken to model the subsea pipeline leak and the pool fire from a storage tank. A commercial software package ANSYS FLUENT Workbench 15 is used to model the subsea pipeline leakage. The CFD simulation results of four different types of fluids showed that the static pressure and pressure gradient along the axial length of the pipeline have a sharp signature variation near the leak orifice at steady state condition. Transient simulation is performed to obtain the acoustic signature of the pipe near leak orifice. The power spectral density (PSD) of acoustic signal is strong near the leak orifice and it dissipates as the distance and orientation from the leak orifice increase. The high-pressure fluid flow generates more noise than the low-pressure fluid flow. In order to model the pool fire from the storage tank, ANSYS CFX Workbench 14 is used. The CFD results show that the wind speed has significant contribution on the behavior of pool fire and its domino effects. The radiation contours are also obtained from CFD post processing, which can be applied for risk analysis. The outcome of this study will be helpful for better understanding of the domino effects of pool fire in complex geometrical settings of process industries. The attempt to reduce and prevent risks is discussed based on the results obtained from the numerical simulations of the numerical models.

A tight-binding analysis of the electronic properties of III-nitride semiconductors

This thesis divides into two distinct parts, both of which are underpinned by the tight-binding model. The first part covers our implementation of the tight-binding model in conjunction with the Berry phase theory of electronic polarisation to probe the atomistic origins of spontaneous polarisation and piezoelectricity as well as attempting to accurately calculate the values and coefficients associated with these phenomena. We first develop an analytic model for the polarisation of a one-dimensional linear chain of atoms. We compare the zincblende and ideal wurtzite structures in terms of effective charges, spontaneous polarisation and piezoelectric coefficients, within a first nearest neighbour tight-binding model. We further compare these to real wurtzite structures and conclude that accurate quantitative results are beyond the scope of this model but qualitative trends can still be described. The second part of this thesis deals with implementing the tight-binding model to investigate the effect of local alloy fluctuations in bulk AlGaN alloys and InGaN quantum wells. We calculate the band gap evolution of Al1_xGaxN across the full composition range and compare it to experiment as well as fitting bowing parameters to the band gap as well as to the conduction band and valence band edges. We also investigate the wavefunction character of the valence band edge to determine the composition at which the optical polarisation switches in Al1_xGaxN alloys. Finally, we examine electron and hole localisation in InGaN quantum wells. We show how the built-in field localises the carriers along the c-axis and how local alloy fluctuations strongly localise the highest hole states in the c-plane, while the electrons remain delocalised in the c-plane. We show how this localisation affects the charge density overlap and also investigate the effect of well width fluctuations on the localisation of the electrons.

From Pro-Franco to Anti-Government. The Evolution of the "Sur" regarding National Politics during the Spanish Transition (1975-1978)

The Spanish transition, the political process through which Spain ceased to be a dictatorship to become a democracy, was accompanied by the dissolution of the National Movement, the institutional support for the chain of the Movement Press from its beginnings, in April 1977. This fact, among others, contributed to the /Sur/, the regional reference newspaper for the chain in Andalusia, evolving both structurally and ideologically to adapt itself to the new political regime. This study applies content analysis to editorials, articles and columns published by the newspaper between 1975 and 1978, exploring the process through which the regional newspaper edited in M��laga abandoned its propaganda function with regard to the Government, considering it undemocratic, and supported the PSOE, presenting it as the best alternative to the UCD in the Spanish Executive, thus taking on its role as a political agent.

A parallel method for solving pentadiagonal systems of linear equations

A new parallel approach for solving a pentadiagonal linear system is presented. The parallel partition method for this system and the TW parallel partition method on a chain of P processors are introduced and discussed. The result of this algorithm is a reduced pentadiagonal linear system of order P \Gamma 2 compared with a system of order 2P \Gamma 2 for the parallel partition method. More importantly the new method involves only half the number of communications startups than the parallel partition method (and other standard parallel methods) and hence is a far more efficient parallel algorithm.

Between Bacchus and Dionysus: European Union policies on rural development: the cases of Nemea and Basto wine regions

A actividade vitivin��cola possui um conjunto diverso de caracter��sticas presentes no solo, territ��rio e comunidade que fazem parte do patrim��nio cultural de uma determinada regi��o. Quando a tradi����o se traduz num conceito como terroir que �� formado por caracter��sticas territoriais, sociais e culturais de uma regi��o rural, o vinho apresenta uma ���assinatura��� que se escreve ���naturalmente��� no paladar regionalmente identificado. Os vinhos da Regi��o de Nemea, na Gr��cia e de Basto (Regi��o dos Vinhos Verdes) em Portugal, est��o ambos sob a prote����o dos regulamentos das Denomina����es de Origem. No entanto, apesar de ambos serem regulados por sistemas institucionais de certifica����o e controlo de qualidade, afigura-se a necessidade de questionar se o patrim��nio cultural e a identidade territorial espec��fica, ���impressa��� em ambos os terroirs, pode ser protegida num sentido mais abrangente do que apenas origem e qualidade. Em Nemea, a discuss��o entre os produtores diz respeito ao estabelecimento de sub-zonas, isto �� incluir na regula����o PDO uma diferente categoriza����o territorial com base no terroir. Ou seja, para al��m de estar presente no r��tulo a designa����o PDO, as garrafas incluir��o ainda informa����o certificada sobre a ��rea espec��fica (dentro do mesmo terroir) onde o vinho foi produzido. A acontecer resultaria em diferentes status de qualidade de acordo com as diferentes aldeias de Nemea onde as vinhas est��o localizadas. O que teria poss��veis impactos no valor das propriedades e no uso dos solos. Para al��m disso, a n��o participa����o da Cooperativa de Nemea na SON (a associa����o local de produtores de vinho) e como tal na discuss��o principal sobre as mudan��as e os desafios sobre o terroir de Nemea constitui um problema no sector vitivin��cola de Nemea. Em primeiro lugar estabelece uma rela����o de n��o-comunica����o entre os dois mais importantes agentes desse sector ��� as companhias vin��colas e a Cooperativa. Em segundo lugar porque constituiu uma possibilidade real, n��o s�� para os viticultores ficarem arredados dessa discuss��o, como tamb��m (porque n��o representados pela cooperativa) ficar impossibilitado um consenso sobre as mudan��as discutidas. Isto poder�� criar um ���clima��� de desconfian��a levando a discuss��o para ���arenas��� deslocalizadas e como tal para decis��es ���desterritorializadas��� Em Basto, h�� v��rios produtores que come��aram a vender a sua produ����o para distribuidoras localizadas externamente �� sub-regi��o de Basto, mas dentro da Regi��o dos Vinhos Verdes, uma vez que essas companhias tem um melhor estatuto nacional e internacional e uma melhor rede de exporta����es. Isto est�� ainda relacionado com uma competi����o por uma melhor rede de contactos e status mais forte, tornando as discuss��es sobre estrat��gias comuns para o desenvolvimento rural e regional de Basto mais dif��cil de acontecer (sobre isto a palavra imposs��vel foi constantemente usada durante as entrevistas com os produtores de vinho). A rela����o predominante entre produtores �� caracterizada por rela����es individualistas. Contudo foi observado que essas posi����es s��o ainda caracterizadas por uma desconfian��a no interior da rede interprofissional local: conflitos para conseguir os mesmos potenciais clientes; comprar uvas a viticultores com melhor r��cio qualidade/pre��o; estrat��gias individuais para conseguir um melhor status pol��tico na rela����o com a Comiss��o dos Vinhos Verdes. Para al��m disso a inexist��ncia de uma activa intermedia����o institucional (autoridades municipais e a Comiss��o de Vinho Verde), a inexist��ncia entre os produtores de Basto de uma associa����o ou mesmo a inexist��ncia de uma cooperativa local tem levado a regi��o de Basto a uma posi����o de subpromo����o nas estrat��gias de promo����o do Vinho Verde em compara����o com outras sub-regi��es. �� tamb��m evidente pelos resultados que as mudan��as no sector vitivin��colas na regi��o de Basto t��m sido estimuladas de fora da regi��o (em resposta tamb��m ��s necessidades dos mercados internacionais) e raramente de dentro ��� mais uma vez, ���arenas��� n��o localizadas e como tal decis��es desterritorializadas. Nesse sentido, toda essa discuss��o e planeamento estrat��gico, ter��o um papel vital na preserva����o da identidade localizada do terroir perante os riscos de descaracteriza����o e desterritorializa����o. Em suma, para ambos os casos, um dos maiores desafios parece ser como preservar o terroir vitivin��cola e como tal o seu car��cter e identidade local, quando a rede interprofissional em ambas as regi��es se caracteriza, tanto por rela����es n��o-consensuais em Nemea como pelo modus operandi de isolamento sem comunica����o em Basto. Como tal h�� uma necessidade de envolvimento entre os diversos agentes e as autoridades locais no sentido de uma rede localizada de governan��a. Assim sendo, em ambas as regi��es, a exist��ncia dessa rede �� essencial para prevenir os efeitos negativos na identidade do produto e na sua produ����o. Uma estrat��gia de planeamento integrado para o sector ser�� vital para preservar essa identidade, prevenindo a sua desterritorializa����o atrav��s de uma restrutura����o do conhecimento tradicional em simult��neo com a democratiza����o do acesso ao conhecimento das t��cnicas modernas de produ����o vitivin��cola.

The grand challenge of food security - general lessons from a comprehensive approach to protecting stored grain from insect pests in Australia and India

We outline a philosophical approach to Grand Challenge projects, with particular reference to our experience in our food security project involving the protection of stored grain from insect attack in two countries on different continents. A key consideration throughout has been the management of resistance in these pests to the valuable fumigant phosphine. Emphasis is given to the chain of research issues that required solution and the assembly of a well-integrated team, overlapping in skills for effective communication, in each country to solve the problems identified along that chain. A crucial aspect to maintaining direction is the inclusion of key end users in all deliberations, as well as the establishment and maintenance of effective outlets for the dissemination of practical recommendations. We finish with a summary of our achievements with respect to our approach to this food security Grand Challenge.

Early post-fledgling survival in a fragmented population of a tropical cooperative breeding passerine

During the last years tropical forest has been a target of intense study especially due to its recent big scale destruction. Although a lot still needs to be explored, we start realizing how negative can the impact of our actions be for the ecosystem. Subsequently, the living community have been developing strategies to overcome this problem avoiding bottlenecks or even extinctions. Cooperative breeding (CB) has been recently pointed out as one of those strategies. CB is a breeding system where more than two individuals raise one brood. In most of the cases, extra individuals are offspring that delay their dispersal and independent breeding what allows them to help their parents raising their siblings in the subsequent breeding season. Such behavior is believed to be due, per example, to the lack of mates or breeding territories (ecological constraints hypothesis), a consequence of habitat fragmentation and/or disturbance. From this point, CB is easily promoted by a higher reproductive success of group vs pairs or single individuals. Accordingly, during this thesis I explore the early post-fledging survival of a cooperative breeding passerine, namely the impact of individual/habitat quality in its survival probability during the dependence period of the chicks. Our study species is the Cabanis���s greenbul (Phyllastrephus cabanisi), a medium-sized, brownish passerine, classified within the Pycnonotidae family. It is found over part of Central Africa in countries such as Angola, Democratic Republic of the Congo, Mozambique and Kenya, inhabiting primary and secondary forests, as well as woodland of various types up to 2700m of altitude. Previous studies have concluded that PC is a facultative cooperative breeder. This study was conducted in Taita Hills (TH) at the Eastern Arc Mountains (EAM), a chain of mountains running from Southeast Kenya to the South of Tanzania. TH comprises an area of 430 ha and has been suffering intense deforestation reflecting 98% forest reduction over the last 200 years. Nowadays its forest is divided in fragments and our study was based in 5of those fragments. We access the post-fledging survival through radio-telemetry. The juvenile survey was done through the breeding females in which transmitters were placed with a leg-loop technique. Ptilochronology is consider to be the study of feather growth bars and has been used to study the nutritional state of a bird. This technique considers that the feather growth rate is positively proportional to the individual capability of ingesting food and to the food availability. This technique is therefore used to infer for individual/habitat quality. Survival was lowest during the first 5 days post-fledging representing 53.3%. During the next 15 days, risk of predation decreased with only 14.3% more deceased individuals. This represents a total of only 33% survived individuals in the end of the 50 days. Our results showed yet a significant positive relationship between flock size and post-fledging survival as well as between ptilochronology values and post-fledgling survival. In practice, these imply that on this population, as bigger the flock, as greater the post fledging survival and that good habitat quality or good BF quality, will lead to a higher juvenile survival rate. We believe that CB is therefore an adaptive behaviour to the lack of mates/breeding territory originated from the mass forest destruction and disturbance. Such results confirms the critical importance of habitat quality in the post-fledging survival and, for the first time, demonstrates how flock size influences the living probability of the juveniles and therefore how it impacts the (local) population dynamics of this species. In my opinion, future research should be focus in disentangle individual and habitat quality from each other and verify which relationship exist between them. Such study will allow us to understand which factor has a stronger influence in the post-fledging survival and therefore redirect our studies in that direction. In order to confirm the negative impact of human disturbance and forest fragmentation, it would be of major relevance to compare the reproductive strategies and reproductive success of populations living in intact forests and disturbed patches.

Fish handling, processing and storage in Uganda: the role of the extension worker

The handling and processing of fish in Uganda has until recently been carried out exclusively by the artisanal fishermen and fish processors. Their operations have left much to be desired as the product is often of low quality 'and its keeping time is limited. The handling of fresh fish has been without refrigeration but with the recent establishment of commercial fish processing plants a cold chain of fish distribution is being set up for domestic and export markets. Some of the fishermen are beginning to ice their catch immediately after reaching the shore. It is hoped that fishmongers will increasingly find it more profitable to market their products iced. This will make fish available to a large sector of the population and in the process there will be reduced post-harvest losses.

Running on Rooftops: a novel and critical reflection on writing from an identity of expatriation with an examination of West-meets-East encounters and attitudes depicted in literature

This thesis is in two parts: a creative work of fiction and a critical reflection on writing from an identity of expatriation. The creative work, a novel entitled Running on Rooftops, revolves around a fictitious community of expatriates living and working in China. As a new college graduate, Anne Henry, the novel���s protagonist and narrator, decides to spend a year teaching English in China. Twelve years later, though still unsure of how to make sense of the chain of events and encounters that left her with an X-shaped scar on her knee, she nevertheless tells the story, revealing how ���just a year��� can be anything but. The critical reflection, entitled Writing on Rooftops, explores the nature of expatriation as it relates to identity and writing, specifically in how West-meets-East encounters and attitudes are depicted in literature. In it, I examine the challenges and benefits of writing from an identity and mindset of expatriation as illustrated in the works of Western writers who themselves experienced and wrote from viewpoints of expatriation, particularly those Western writers who wrote of expatriation in China and Southeast Asia. The primary question addressed is how expatriation influences perception and how those perceptions among Western foreigners in China and Southeast Asia have been and can be reflected in literature. In the end, I argue that expatriation can be a valuable viewpoint to write from, offering new ways of seeing and describing our world, ourselves and the connections between the two.

Privity of Contract and Third Party Rights in European Construction Projects

Privity of contract has lately been criticized in several European jurisdictions, particu-larly due to the onerous consequences it gives rise to in arrangements typical for the modern exchange such as chains of contracts. Privity of contract is a classical premise of contract law, which prohibits a third party to acquire or enforce rights under a contract to which he is not a party. Such a premise is usually seen to be manifested in the doctrine of privity of contract developed under common law, however, the jurisdictions of continental Europe do recognize a corresponding starting point in contract law. One of the traditional industry sectors affected by this premise is the construction industry. A typical large construction project includes a contractual chain comprised of an employer, a main contractor and a subcontractor. The employer is usually dependent on the subcontractor's performance, however, no contractual nexus exists between the two. Accordingly, the employer might want to circumvent the privity of contract in order to reach the subcontractor and to mitigate any risks imposed by such a chain of contracts. From this starting point, the study endeavors to examine the concept of privity of con-tract in European jurisdictions and particularly the methods used to circumvent the rule in the construction industry practice. For this purpose, the study employs both a com-parative and a legal dogmatic method. The principal aim is to discover general principles not just from a theoretical perspective, but from a practical angle as well. Consequently, a considerable amount of legal praxis as well as international industry forms have been used as references. The most important include inter alia the model forms produced by FIDIC as well as Olli Norros' doctoral thesis "Vastuu sopimusketjussa". According to the conclusions of this study, the four principal ways to circumvent privity of contract in European construction projects include liability in a chain of contracts, collateral contracts, assignment of rights as well as security instruments. The contempo-rary European jurisdictions recognize these concepts and the references suggest that they are an integral part of the current market practice. Despite the fact that such means of circumventing privity of contract raise a number of legal questions and affect the risk position of particularly a subcontractor considerably, it seems that the impairment of the premise of privity of contract is an increasing trend in the construction industry.

A biochemical analysis into the co-translational folding of a G protein-coupled receptor; GPR35

The folding and targeting of membrane proteins poses a major challenge to the cell, as they must remain insertion competent while their highly hydrophobic transmembrane (TM) domains are transferred from the ribosome, through the aqueous cytosol and into the lipid bilayer. The biogenesis of a mature membrane protein takes place through the insertion and integration into the lipid bilayer. A number of TM proteins have been shown to gain some degree of secondary structure within the ribosome tunnel and to retain this conformation throughout maturation. Although studies into the folding and targeting of a number of membrane proteins have been carried out to date, there is little information on one of the largest class of eukaryotic membrane proteins; the G-protein-coupled receptors (GPCRs). This project studies the early folding events of the human ortholog of GPR35. To analyse the structure of the 1st TM domain, intermediates were generated and assessed by the biochemical method of pegylation (PEG-MAL). A structurally-similar microbial opsin (Bacterioopsin) was also used to investigate the differences in the early protein folding within eukaryotic and prokaryotic translation systems. Results showed that neither the 1st TM domain of GPR35 nor Bacterioopsin were capable of compacting in the ribosome tunnel before their N-terminus reached the ribosome exit point. The results for this assay remained consistent whether the proteins were translated in a eukaryotic or prokaryotic translation system. To examine the communication mechanism between the ribosome, the nascent chain and the protein targeting pathway, crosslinking experiments were carried out using the homobifunctional lysine cross-linker BS3. Specifically, the data generated here show that the nascent chain of GPR35 reaches the ribosomal protein uL23 in an extended conformation and interacts with the SRP protein as it exits the ribosome tunnel. This confirms the role of SRP in the co-translational targeting of GPR35. Using these methods insights into the early folding of GPCRs has been obtained. Further experiments using site-directed mutagenesis to reduce hydrophobicity in the 1st TM domain of GPR35, highlighted the mechanisms by which GPCRs are targeted to the endoplasmic reticulum. Confirming that hydrophobicity within the signal anchor sequence is essential of SRP-dependent targeting. Following the successful interaction of the nascent GPR35 and SRP, GPR35 is successfully targeted to ER membranes, shown here as dog pancreas microsomes (DPMs). Glycosylation of the GPR35 N-terminus was used to determine nascent chain structure as it is inserted into the ER membrane. These glycosylation experiments confirm that TM1 has obtained its compacted state whilst residing in the translocon. Finally, a site-specific cross-linking approach using the homobifunctional cysteine cross-linker, BMH, was used to study the lateral integration of GPR35 into the ER. Cross-linking of GPR35 TM1 and TM2 could be detected adjacent to a protein of ~45kDa, believed to be Sec61��. The loss of this adduct, as the nascent chain extends, showed the lateral movement of GPR35 TM1 from the translocon was dependent on the subsequent synthesis of TM2.

Synchronization of Heteroclinic Circuits Through Learning in Chains of Neural Motifs

The synchronization of oscillatory activity in networks of neural networks is usually implemented through coupling the state variables describing neuronal dynamics. In this study we discuss another but complementary mechanism based on a learning process with memory. A driver network motif, acting as a teacher, exhibits winner-less competition (WLC) dynamics, while a driven motif, a learner, tunes its internal couplings according to the oscillations observed in the teacher. We show that under appropriate training the learner motif can dynamically copy the coupling pattern of the teacher and thus synchronize oscillations with the teacher. Then, we demonstrate that the replication of the WLC dynamics occurs for intermediate memory lengths only. In a unidirectional chain of N motifs coupled through teacher-learner paradigm the time interval required for pattern replication grows linearly with the chain size, hence the learning process does not blow up and at the end we observe phase synchronized oscillations along the chain. We also show that in a learning chain closed into a ring the network motifs come to a consensus, i.e. to a state with the same connectivity pattern corresponding to the mean initial pattern averaged over all network motifs.