Search

The biological carbon pump (BCP) is one of the atmospheric CO2 pathways into the ocean and plays a major role in climate regulation. Primary production in the ocean uptakes CO2 to produce organic matter, which enters the food chain and undergoes transformations to become particulate organic carbon (POC). The POC sinks transporting carbon into the ocean, creating a POC flux. As it sinks, POC gets respired and releases CO2 back into the environment, attenuating the flux. The deeper this happens, the longer the released CO2 stays away from the atmosphere. Sediment traps and the Martin's curve, a statistical fit of a power law, are commonly used to describe this flux attenuation with depth. The use of sediment traps assumes the flux captured by traps deployed simultaneously at different depths comes from the same region. The source of the flux plays a key role in understanding observations of the BCP. Unusual/unexpected flux profiles might be caused by variability in fields on the ocean's surface. To know the source region of the flux, one must find its "statistical funnel". A particle backtracking approach can be used to achieve this; however, the currently used approach does not account for uncertainties in ocean currents. Additionally, the existing method for the statistical funnel backtracks particles until they reach the ocean's surface. This is not necessarily accurate as the surface layer of the ocean is well mixed. Particles in the mixed surface layer does not make sense as particles could come from any point within the mixed layer. Here I suggest a method to calculate a statistical funnel considering uncertainties in ocean currents. From this funnel study I also suggest a method to estimate the contributions of spatial variability in the traps' catchment areas to the uncertainty in Martin's "b-value" (which represents the flux attenuation). The method also suggests a spatially adjusted b-value, which considers each trap's catchment area. Finally, I present a case study that found that spatial variability can contribute up to 25% in the uncertainty in a b-value obtained from POC flux observation.

Polymers have developed significantly over the last decade in a variety of fields in order to address challenges in materials science, biotechnology and medicine. Drug delivery is an exemplar application in which linear and dendritic polymers are involved in the design of polymer-drug conjugates. Molecular structure and conformation are key parameters which ensure the physical stability and biological activity of pharmaceutically relevant materials. Electrospray ionisation (ESI) and nanoelectrospray ionisation (nESI) mass spectrometry (MS) techniques have recently evolved to enable high-resolution mass measurements of low concentration samples. The inclusion of ion mobility-mass spectrometry (ESI/nESI-IM-MS) allows for the calculation of collision cross sections (CCSs) that provide insight into the size and shape of gas-phase ions. In addition, this technique can further facilitate the separation of isobaric compounds in the analysis of unknown species and/or complex mixtures. Firstly, linear amino acid-based polymers are studied using MS and IM-MS workflows. The molecular weight distributions of polydisperse polyalanine, polylysine, polyglutamic acid and polyarginine measured by MS and IM-MS are compared to the expected ranges with ESI, nESI and matrix-assisted laser desorption/ionisation (MALDI). Discrepancies are observed in which higher molecular weights are not detected, namely due to peptide fragmentation. The use of a deconvolution algorithm supplements the MS results and provides more detailed information. Secondly, polylysine dendrimers of generation 1 to 6 are structurally investigated with MS and IM-MS techniques. Accurate mass measurements are enabled by nESI-MS analysis through formation of multiply charged ions. Moreover, the charge state dictates gas-phase conformation as evidenced by distinct monomodal CCS distributions. A linear increase in the CCS of high generation dendrimers (4 to 6) is observed with charge. Lastly, the conformational stability of dendrimers is investigated by activated IM-MS and variable temperature (VT) IM-MS. The rigidity observed for these molecules under thermal and collisional activations alongside wide m/z and CCS ranges make them systems of interest for IM-MS calibration purposes. This thesis explores the benefits of using MS and IM-MS techniques to characterise a variety of polymers in structure across a wide range of instrumentation.

Chemotactic cytokines or chemokines are small signalling proteins responsible for the recruitment of leukocytes to sites of inflammation. Although, chemokines are critical to orchestrate effective immune response, many have been associated to several inflammatory disorders. Despite being recognised as therapeutic target, no efficient treatments targeting the chemokine network for inflammatory diseases are available to date. This is attributed with the complexity of the many and varied chemokine interactions with themselves, their receptors and glycosaminoglycans on extracellular matrix. Thus, the pharmaceutical industry dogma of "one molecule, one target" is rendered ineffective against this network. Evasins are small tick saliva proteins that can bind and neutralise several chemokines, therefore allowing the tick to feed on their host for days without sparking an immune response. The potential of Evasins as effective anti-inflammatory agents was proven in many pre-clinical disease models. The interest in Evasins led to the discovery of a novel Evasin, P672, that can bind a wide range of CC chemokines. This work describes the discovery of peptides inspired by the chemokine binding site of P672. These peptides were shown to neutralise several chemokines and exhibited in vivo anti-inflammatory activity. A novel generation of P672-inspired peptides were designed and exhibited multiple chemokine-binding properties with increased human plasma resistance. Finally, P672/chemokine interfaces were mapped using peptide display techniques informing on P672 binding sites and its mode of action to neutralise chemokines. This work demonstrates the exciting potential of utilising Evasin/chemokine interaction studies with informed mode of action as starting points for anti-inflammatory peptide development.

This thesis considers questions pertaining to the discursive constructions of religion(s) as mediated through a primary school. It considers how pupils and teachers make sense of religion(s) in their institutional setting and beyond. The main research questions are: a) How is religion mediated through daily educational practices? b) How do pupils and teachers construct religion(s) at school? For this project, I adopted an ethnographic approach to a case study, and conducted fieldwork at Alexander Parkes Primary School,1 a state-funded non-faith-based primary school in Birmingham, UK. .While most research conducted in Birmingham tends to focus on faith-based schools and/or minority faith communities, this research pays attention to the "missing group"(Davie, 2012: 287), that is to say the 'middle ground' group in the religious life of England "who self-identify as Christians" (Davie, 2015: 169), but "whose way of being religious is captured by the term 'vicarious'" (Davie, 2012: 287).This project considers the place of religion in the everyday lives of children andteachers, and how they encounter religion in mundane ways. The findings of this study shed new light on how pupils and teachers discursively construct religion in education(macro level). The concepts of religion as 'chain of memory' (Hervieu-Léger, 2000),'Golden Rule' Christianity (Ammerman, 1997), and 'vicarious religion' (Davie, 2015)provide the theoretical framework to explore the dialectic relationship between the'religious' and the 'secular,' and the (perceived) role and function of religion in contemporary society (meso level). In order to investigate which discourses were(re)reproduced at Alexander Parkes, I adopted Ipgrave's analytical tools to the "differentapproaches to religion: doxological, sacramental, and instrumental, founded,respectively, on certain faith in God, on openness to the possibility of God, and on adefault scepticism" (2012a: 30). These tools were useful to explore how the school managed religion (micro level). Findings show that while children's agency should notbe underplayed, the school as a structure plays an important role in shaping pupils'construction of religion in general, and of Christianity in particular.

The end of Late Bronze Age in Greece is recognised for its dynamism and shifting patterns of international connections between different regions of the Central and Eastern Mediterranean. Perhaps most significant for this period is the increasing evidence of contacts between Italy and its eastern neighbours. Mycenaean Achaea seems to have held a key role in this “Italian Connection”. A key element in understanding these mobilities is the appearance of handmade burnished ware (HBW) in Mainland Greece, Crete and Cyprus in the Late 13th-12th Century BCE, seemingly transplanted into areas using high quality wheelmade fineware. While it is now becoming widely accepted that the origin of this new class of pottery should be sought in Southern Italy, there is increasing evidence that HBW comprises a more diverse phenomenon. This project looks at this pottery class and its diversity in the specific context of Teichos Dymaion, in Achaea, an important anchorage located at the first landfall for maritime traffic coming from Italy. Based on a chaîne opératoire approach and using thin section petrography to complement the visual assessment of the assemblage, it approaches HBW by the concept of pottery tradition, to produce a localised understanding of the pottery rooted in both technology and style. The results reveal a HBW assemblage that shares a series of common practices distinctively different from the more canonical Mycenaean pottery, which it is suggested correspond to pottery traditions foreign to Achaea. Technological variability within this group, however, suggests a more diverse picture, hinting at evolving practices and perhaps at multiples groups of potters.

Computer-aided engineering methods have been increasingly used in various industries to support the design of complex systems and validate their performance by simulating their physical behaviour. This created a need to generate fit-for-purpose analysis models with a turnaround time comparable to the time required to generate the design model. However, most existing tools for computer-aided design and engineering have been developed independently to address different issues and therefore lack integration. As a consequence, many current simulation workflows rely on experienced users to adapt, or create from scratch, an appropriate analysis model to represent the physics to be solved. Preparing complex multi-physics analysis models for very large assemblies can take up to several person-years, limiting the tools for validation rather than having the maximum impact on design decisions. This thesis builds on previous research on automatic hex-mesh generation and CAD-CAE integration to develop a novel framework for generating CAE analysis models from CAD design models. The framework uses ‘virtual topology’ to bridge the representation gap between CAD and CAE tools, overcome geometric limitations and accommodate the multiple different representations necessary for analysis workflows. Virtual topology is also a key enabler for the flexible modification and updating of the analysis models. Robust information management is achieved by implementing a cellular model within the virtual topology framework, which hosts and interconnects the different representations while capturing the information necessary for downstream processes. In this work, 9 pre-processing reasoners are defined within the virtual topology framework to automatically generate hex-dominant meshes by incrementally identifying and extracting virtual regions for which a simple hex-meshing strategy can be applied. A new translator tool is introduced to query virtual models using virtual geometry curves. Additional reasoners are then used to automatically process the different meshing strategies and generate a conformal mesh, reducing the CAD to mesh time from several hours to several minutes compared to manual decomposition and existing meshing methods. Incorporating meshing constraints early in the pre-processing workflow also enables the enhancement of the pre-processing tools. A new method to propagate design modifications is developed, so that a decomposed analysis model and its associated mesh can be updated after topological changes on the design model. This is up to 95% faster than re-starting the automated pre-processing from the beginning. Finally, examples of aeronautical components are processed using the virtual topology framework developed to demonstrate the benefits of virtual topology based workflows for hex-dominant mesh generation.

Essential tremor and Parkinson’s disease are the most common movement disorders affecting patients globally. When pharmacological treatment options have been exhausted, continuous, high-frequency deep brain stimulation (DBS) is an effective therapy option. Despite its success, DBS is limited by side effects such as speech and motor impairment, as well as impulsivity. Closed-loop DBS could address these limitations by stimulating in a way that is more parsimonious and by targeting the pathology more selectively to spare physiological processing. In closed-loop DBS, pathological activity is recorded, and stimulation is delivered based on the current state and knowledge of its association with symptoms. Experimental closed-loop strategies include phase-locked DBS in essential tremor and adaptive DBS in Parkinson’s disease. In phase-locked DBS, a precise understanding of the phase-dependence of the response to stimulation is difficult to attain experimentally because of patient fatigue. In Parkinson’s disease, refining adaptive DBS likely requires a better understanding of the dynamics of bursts in the recorded beta band activity (13-35 Hz), which have been implicated in motor symptoms. To inform closed-loop DBS strategies, we use patient data as a starting point to formulate and constrain mathematical models of pathological oscillatory activity and of the effects of DBS. In Chapter 2, we model the effects of phase-locked stimulation in essential tremor patient data. Models fitted to patient data can be used to optimise DBS in silico, and provide insights into the pathophysiology of the disease. In Chapter 3, we relate changes in beta oscillation temporal patterning between medication states in Parkinson’s disease to changes in dynamical properties of the system generating beta bursts. In particular, we show that the system generating beta oscillations is more non-linear in the pathological state, which has implications for closed-loop DBS. In Chapter 4, we compare two definitions of amplitude to measure the effects of phase-locked DBS, and to optimise stimulation in models. We demonstrate that a dynamical measure of amplitude, isostable amplitude, can in some cases be more beneficial to optimise stimulation than envelope amplitude. Together, this thesis sheds light on key aspects of Parkinson’s disease and essential tremor, and contributes to advancing closed-loop DBS.

The intra-cluster medium (ICM) plays a key role in galaxy formation. The cooling of hot gas and its recycling due to feedback are key parameters in understanding the regulation of star formation. Semi-analytical models (SAMs) are quick simulations that allow us to test our understanding of galaxy formation processes. Most of them produce results agreeing fairly well with various galaxy observations, however they fail in reproducing the ICM properties. In this work we focus on the active galactic nuclei (AGN) feedback and cooling mechanisms affecting the ICM, by developing new physically motivated methods that give a more accurate ICM description in the L-Galaxies SAM. We start by correcting the baryon content of each halos in the simulation. Due to halo mass fluctuations, halos ended up with an over density of baryons. This problem was resolved by introducing an extra phase for the baryons to keep track of the gas that would be considered leaving the halo (during contractions) or inflating (halo growth). Although this solution solved the baryon problems, it did not answer the question of the excess of hot gas stored inside the virial radius. We investigated different feedback mechanisms, from SNR to black holes and found that ejecting the gas with powerful AGN jets is compulsory to reduce the hot gas content of the halos. In order to reduce the gas content, a new model of AGN feedback was implemented and tuned to reproduce the observational gas fractions available in the literature. The AGN can not only now reheat cold and cooling gas, but also eject it via powerful jets. In addition to this feedback, four new black hole accretion models were compared, based on different gas reservoir. The most accurate agreement with observations for most AGN and galaxy properties came from a model where the AGN was fed by accretion of cold clouds from the ISM of the host galaxy. Finally we investigate the effect of our improved feedback on the ICM itself. In addition to the new AGN feedback, we developed a more physical cooling mechanism based on Bremsstrahlung radiation and a Beta profile of the gas. This change enabled us to give X-ray predictions for our model to compare with observational data, including the most recent XMM results. We found that the change in cooling only slightly affects the results (gas fractions, metallicities), as expected. However the X-ray luminosities of our groups and clusters of galaxies are now in agreement with observations, mainly due to the gas content reduction done by the new feedback mechanism. This new version of L-Galaxies manages to reproduce both galaxies and ICM properties in fairly good agreement with observational data.

In plants, the H3K27me3 modification, established by the subunit of the Polycomb Repressive Complex 2 showing a methyltransferase activity, is present at more than 4400 genes, which are mostly transcription factors involved in major plants developmental processes. The first aim of this thesis is to test whether nascent RNA could be present at PRC2 targeted genes and whether these nascents RNA could act as anchor point for cis-elements to recruit PRC2 to a specific locus. The presence of nascent RNA at Polycomb repressed genes was demonstrated in Arabidopsis before adapting a new innovative chromatin tool, called Chromatin Isolation by RNA Precipitation (ChIRP), to isolate and identify proteins interacting with nascent RNA. The fully optimized method revealed nineteen candidate proteins to interact specifically with the nascent RNA at the FLC locus (Chapter 3) but the link to PRC2 recruitment is yet to be shown and should be investigated in the future. The second aim of this thesis is to determine the effects of the H3K27me3 erasers on plant development. The flowering time, the fertility and the embryo to seedling transition were studied in different Arabidopsis plants lacking the different demethylases, REF6, ELF6 and JMJ13. It showed antagonist phenotype suggesting very distinct roles. Flowering time studies identified four potential targets of JMJ13, FLC, SNZ, AGL24 and SOC1 that require further validation (Chapter 4) while the effect of ELF6 and REF6 on the flowering time have been described several years ago. Fertility studies showed JMJ13 promotes stamen elongation while ELF6 suppresses stamen and promotes pistil elongations. Seed analysis revealed that the seed size and weight are negatively affected by the demethylases and that REF6 and ELF6 share redundancy (Chapter 5). Germination rate analysis showed JMJ13 suppresses germination while ELF6 and REF6 promote it and the embryo-to-seedling transition study revealed ELF6 is partially required to generate true leaves (Chapter 6). The characterisation of the effects of the demethylases on Arabidopsis development has started recently and should be investigated to better understand the regulation of plant life cycle by the histone demethylases.

Sarcopenia negatively impacts physical function and health. Although the mechanisms underpinning sarcopenia are unclear, a blunted response to anabolic stimuli is observed. Accordingly, Chapter 2 explored how dose, timing, distribution and source of dietary protein intake differed between healthy young and older individuals. We showed that, whilst the recommended dietary allowance for protein was met by most individuals, total protein intake was lower and unevenly distributed across meals in old. The observation of sub-optimal protein intakes in older individuals has important implications for skeletal muscle maintenance. Therefore, in Chapter 3 we investigated the muscle anabolic response in young lean, old lean and obese old individuals to a suboptimal protein dose. Whilst young lean and, to a lesser extent, old lean significantly increased postprandial myofibrillar protein synthesis (MyoPS), this response was blunted in obese old. Furthermore, MyoPS correlated significantly with step count and leg fat mass in old. Based on the age-related decrease in MyoPS, we assessed the ability of phosphatidic acid (PA) to increase MyoPS at rest and after exercise in Chapter 4. Compared to a placebo treatment, MyoPS was blunted upon PA consumption in the late phase of resistance exercise recovery and was probably due to impaired anabolic signaling.

With the expansion of digital information and the number of people potentially able to access it, there are increasing demands for efficient, secure systems which authenticate users effectively. At the end of the 1960's, IBM defined three authentication factors: knowledge factor, which relates to "something the entity knows"; ownership factor, relating to "something the entity has/possesses"; inherent factor, which can be summarised as "something the entity is or does". Each of these factors possesses its own limitations: knowledge factors can be forgotten or discovered by a fraudster; ownership factors can be lost, stolen or counterfeited. These nuisances have led to increased use of biometric authentication as a means of increasing security. However, conventional biometrics are static, so if compromised cannot be changed by the user. This has led to interest in techniques that authenticate using changeable multi-factor authentication measures that are influenced by biometrics, rather than being completely reliant on them. Investigating the practicality and security of such techniques provided the motivation for this research. First we needed to identify these "easily changeable biometrics" and it led us to define a new biometric family, which we called the dynamic biometrics. We then studied the security characteristics of this new family. Out of the dynamic biometrics, we chose to focus on one of these elements, authentication based on gesture recognition. We conducted several experiments to assess the ability of this authentication technique to authenticate the genuine user and reject any impostors, either if these impostors do not know the gesture or do random movements. We continued by looking for a secure place to store the gesture recognition's template and run the application. We evaluated the possibility of doing that on a personal limited device, such as a Smart Card. Then we designed a protocol to use a gesture recognition application which we analysed with respect to several threat vectors.

It is known that acidification of reservoirs pore fluids during CO2 subsurface injection leads to fluid-rock interactions. Understanding the effect that these interactions could have on transport and mechanical properties of rocks is particularly relevant for calcite-bearing reservoirs in which rapid pores network evolution could compromise or reinforce the injection operation. In this work, specific experiments were conducted to study the impact of fluid rock interactions on petrophysical properties. The experiments involved the injection into rock cores of CO2-saturated brines to investigate rapid calcite dissolution effects and CO2 plus calcite saturated water to study calcite re-precipitation. Complementary fluid flow modelling at the pore scale was carried out to simulate changes in permeability brought by calcite dissolution. Calcite dissolution directly impacted the permeability and the rock strength in a way that would have been underestimated in classical reservoir simulations. The permeability increase ranged between 50 and 80% while widely used porosity-permeability relationships would predict 10 to 20%, pore scale modelling predictions were found to be more reliable. The change in the rock strength was even more spectacular with a decrease of the shear and bulk moduli of 20% when empirical equations would give a negligible change. Combined experiments and simulations were also used to test the long term CO2 stabilization process known as capillary trapping. The study concluded that CO2 dissolution in brine could give rise to CO2 accumulation in regions of the reservoirs containing larger pores. This could significantly modify CO2 mobility and goes against common belief of capillary trapping stability. This dissertation demonstrate CO2 injection can lead to critical modifications in rock petrophysical properties as well as CO2 trapping processes and that laboratory experiments and pore scale modelling can provide valuable insight into these changes.

Friction is omnipresent in our daily life, and although this phenomenon has been studied for centuries, the fundamental understanding on tribological processes as a whole is still lacking. Reducing friction is beneficial in many applications, from mediating wear to improving the life span of devices, hence improving our knowledge of the parameters affecting frictional forces is of paramount importance. In particular, the miniaturisation of modern devices implies that their reliability and durability become friction limited. Recent advances in the fabrication of nanostructured surfaces with tuneable topographic properties, along with advances in metrological tools such as the atomic force microscope (AFM), now provide the means to systematically study friction on well-defined nanostructured surfaces. This research project is focused on the lubricated and un lubricated frictional behaviour of nanotextured surfaces using the AFM with conventional and colloidal probes. The frictional properties of nanotextured surfaces bearing aluminium oxide nanodomes and zinc oxide nanorods of varying topographic properties in air, as well as the frictional properties in aqueous solutions of ionic and nonionic surfactants on flat and textured surfaces of titanium oxide, are reported. The results show that for the nanodomed-textured surfaces, the ancient Amontons laws of dry friction are obeyed; however, the friction coefficient was insufficient to fully characterise the frictional behaviour of such nanotextured surfaces. Pronounced stick-slip frictional characteristics were observed, with the amplitude of the stick-slip varying linearly with the applied load. On nanorod-textured surfaces, the friction-applied load linear relationship was however lost, due to the bending contributions of the rods to the lateral force experienced by the probe. Finally, the results obtained on flat and pillar-textured titanium oxide surfaces showed that ionic surfactants could mediate effective boundary lubrication with the existence of two frictional regimes, due to load- and shear-induced structural changes in the nanofilms of the adsorbed surfactant molecules.

Combined measurements of velocity and temperature are essential to improve our understanding of turbulent flows involving heat transfer or chemical reactions. However, performing such measurements is a very difficult task. The presence of particles, which are seeded into the flow as tracers for the flow velocity, strongly interferes with classic optical thermometry techniques such as Rayleigh scattering. A review of the current approaches shows that a technique that can measure both quantities simultaneously, in two dimensions and over a wide range of flow conditions is yet to be found. An alternative approach to this problem, presented in this dissertation, uses tracer particles made of temperature-sensitive luminescent material, which are capable of also indicating the gas temperature. Thermographic phosphors are shown to be clear candidates for this concept. Made of ceramic material, they are chemically inert and survive low and high temperature environments. The temperature has a strong influence on the luminescence process allowing various ways to perform thermometry Currently, phosphors are used for surface temperature measurements, but a phosphor suitable for two-dimensional measurements in turbulent flows must meet stringent requirements in terms of luminescence properties. In this respect, the temperature dependence of the emission spectrum, a high quantum efficiency and a short lifetime are essential. Micrometre-size refractory particles are widely used for PIV and are able to follow the fluid motion without slip for a wide range of fluid velocities and turbulence intensities However, for the concept to be valid, the ability of phosphor particles to follow fluctuations in the gas temperature must be demonstrated. Using theoretical heat transfer models, it is shown that the temperature response of a particle is faster than its velocity response irrespective of the gas temperature. These response times have a quadratic dependence on the particle diameter so only small particles can be used. Various aspects of the practical implementation of the flow measurement concept, such as the excitation, particle seeding, detection, image processing and calibration, are considered, tested and developed, with the objective of providing high signal levels and to permit precise, accurate, and highly resolved measurements. In order to determine whether a sufficient signal level can be obtained for a reasonable particle seeding density, i.e. that does not have any effect on the gas properties, a particle counting tool is implemented. This system is used to characterise the phosphorescence intensity of 2 μm diameter particles made of BAM:Eu2+, a phosphor with very advantageous properties for flow measurements. It is shown that a seeding density comparable to that of conventional PIV and relatively small laser fluence provide sufficient signal levels for precise single shot measurements. The technique is demonstrated in a turbulent heated jet from 300 K to 700 K. Single shot measurements of temperature and velocity are presented with a single-shot, single-pixel temperature precision of 2-5 %, a temperature accuracy of 2%, and a spatial resolution of 400 μm. An additional concept is explored. By seeding two streams with different materials, the phosphorescence signal can be used to visualise the turbulent mixing between the streams. This concept is demonstrated in the same turbulent heated jet. Future developments and applications of the thermographic phosphor tracer particle concept are discussed. Owing to the very wide variety of thermographic phosphors, the results presented in this dissertation constitute a solid foundation for the expansion of this promising technique.

This thesis examines attitudes toward infertility in early modern England and colonial New England from c.1620 to 1720 through infertility’s representation in contemporary medical, religious, and literary sources. This study uses an expanded definition of infertility, namely a 'spectrum of infertility', to capture the tensions that arose during periods of infertility and experiences of reproductive failure such as miscarriages, stillbirths, monstrous births, and false conceptions. A spectrum, more than a modern definition, more accurately represents the range of bodily conditions experienced by early modern women and men that indicated reproductive disorder in the body; by extension, the language of infertility expressed fears about disorder in times of social, religious, and political crisis in early modern society. The two societies' relationship was often described through reproductive language and the language of infertility appears in both societies when order - within the body, within marriages, or within and between communities - was threatened. This thesis contributes to a growing body of scholarship on infertility in early modern society by analysing its presence in communications within and between early modern England and colonial New England. It argues that understanding the English origins of the colonists' attitudes toward infertility is fundamental both to understanding the close connection between the two societies and to providing context for the colonists' perceptions about their encounters with new lands, bodies, environments, and reasons for emigration. As a result, this thesis seeks to break new ground in providing an overview of social, medical, and cultural reactions in both England and New England, demonstrating that similar language and tropes were used in both regions to communicate concerns about infertility. Exploring the interplay between the many sources addressing this health issue more accurately represents the complexity of early modern attitudes toward infertility, and the intimacy of the relationship between the fledgling New England colonies and their metaphorical Mother England.

Network traffic monitoring and analysis has several practical implications. It can be used for malicious or legitimate purpose and aimed at improving the quality of communications, enhancing the security of a system or extracting information via side-channels. Such analysis can even deal with the use of encryption and obfuscation and extract meaningful information from huge amounts of Internet traffic. First, tills thesis explores its use to investigate the leakage of information from Skype, a widely used and encrypted VoIP application. VoIP has experienced tremendous growth over the last few years and is now widely used among the public and for business purposes. The security of such VoIP systems is often assumed, creating a false sense of privacy. Experiments have shown that isolated phonemes can be classified and given sentences identified. By using the DTW algorithm, frequently used in speech processing, an accuracy of 60% can be reached. The results can be further improved by choosing specific training data and reach an accuracy of 83% under specific conditions. The initial results being speaker dependent, an approach involving the Kalman filter is proposed to extract the kernel of all training signals. Second, the use of traffic monitoring and analysis for network security is investigated to detect hosts infected with the ZeuS botnet, a recent infamous trojan that steals banking information and one of the most prominent cyber threats to date. Cyber threats are becoming ever more sophisticated, persistent and difficult to detect. As highlighted by recent success stories of malware, such as the ZeuS botnet, current defence solutions are not enough to thwart these threats. Therefore, it is of paramount importance to be able to detect and mitigate these kinds of malware. This work proposes a detailed analysis of the network communications that occur between a bot and its master as part of the command and control traffic. This research identifies six key attributes which provide a reliable way of detecting hosts infected by the Zeus botnet. These discoveries are then used in combination with different machine learning algorithms in order to prove their validity. Finally, the use of IBM QRadar, a commercial SIEM product, to detect ZeuS infected hosts is investigated.

During the decommissioning of nuclear facilities, a range of materials are generated and need careful characterisation in order to segregate them into their appropriate waste stream. The procedures involved demand significant time and investments to accurately determine the radionuclide inventory necessary to proceed. Methodology requires sampling, homogenisation, dissolution and sometimes a separation step to measure radionuclides using their decay properties. The approach proposed here is to spatially resolve the distribution of major and trace elements in concretes, and by inference important neutron activation-induced radionuclides, using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The technique offers the possibility of an onsite sampling tool for the different concrete constituents such as aggregates and sand/cement mixes at the micron scale, with typical detection limits in the ng.g-1 range for most elements. Several shielding concrete samples from Windscale (Cumbria) and CONSORT research reactor hosted by Imperial College (Silwood Park campus) are investigated. Initial work focussed on the identification and main chemistry of the aggregate types involved, using a set of chemical characteristics to fingerprint the ablated phases. Subsequently, available and manufactured calibration materials are evaluated for direct quantification purposes, together with wet chemistry reference values obtained for each concrete constituent for validation. Typical chemistry can thereafter be linked to each phase and build the overall bulk information. Finally, the potential to measure 3H directly using ICP-MS is investigated. This theoretical approach describes the conventional analysis methods and problems with ICP-MS analysis and considers several technological advances from the original instrumentation to overcome these, including the latest instrument available and figures of merit based on practical data.

Calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM) receptors are heterodimeric complexes composed of the calcitonin receptor-like receptor (CLR) and a receptor activity-modifying protein (RAMP). Association with RAMP1 gives a high affinity CGRP receptor, whereas association with RAMP2 or RAMP3 gives high affinity ADM receptors. CGRP and ADM are widely distributed throughout the body and play important roles and are implicated in many diseases including migraine, heart failure and sepsis. Recently, CGRP has been shown to promote nitric oxide (NO) production and inducible NO synthase (iNOS) expression in trigeminal ganglion glial cells via ERK activation. CGRP is known to induce iNOS/NO production in thoracic artery smooth muscle cells (TA-SMC) pretreated with interleukin-1b. However, the molecular mechanism of CGRP-induced iNOS/NO production in TA-SMC is unknown. Therefore, in order to determine if CGRP induces iNOS/NO production via ERK activation, I first investigated the exact mechanisms through which CGRP activates ERK1-2 in HEK cells. By using different inhibitors I showed that CGRPinduced ERK activation is mainly activated through two major pathways. I showed for the first time that CGRP induces ERK activation through transactivation of ErbB1 and as expected through the cAMP/PKA pathway. Then, in order to characterise a suitable model to study CGRP-induced iNOS expression, I used primary TA-SMC and I showed that CGRP induces iNOS upregulation, which is reduced when cells are incubated with U0126, a MEK inhibitor. Thus, these results suggest that CGRP induces iNOS expression via ERK activation in TA-SMC. However, further experimentation is required to determine the exact ERK pathway responsible for iNOS induction. Compared to CLR•RAMP1 and CLR•RAMP3, little is known about the postendocytic sorting of CLR•RAMP2. Using HEK cells stably expressing CLR•RAMP2, I investigated the molecular mechanisms regulating the ADM receptor. I first showed that, unlike CLR•RAMP1, even transient stimulation of CLR•RAMP2 with ADM promotes degradation of both CLR and RAMP2, indicating that this ADM receptor does not recycle to the cell-surface. Moreover, I showed that CLR, not RAMP2, is constitutively ubiquitinated, which was further enhanced upon ADM stimulation. In order to elucidate the role of ADM-mediated ubiquitination of CLR, I made a lysine-less mutant of CLR, named CLRD9KR. I showed that ubiquitination of CLR did not affect ADM-induced trafficking of CLR•RAMP2 to lysosomes, nor did it affect the degradation or the ERK signalling of CLR•RAMP2. However, I showed that ubiquitination of CLR regulated the rate of degradation of the receptor. Together, these results indicate that CLR•RAMP2 does not recycle and is degraded via a molecular mechanism that is accelerated by ADM-induced ubiquitination of CLR.

Mild traumatic brain injury (mTBI) or concussion is the most common form of TBI, and although a single concussion rarely results in long-term neurological dysfunction, repeated mild traumatic brain injury (r-mTBI) is a recognized risk factor for later development of neurodegenerative disease. However, the mechanisms contributing to neurodegeneration following TBI remain obscure. Animal models provide a means to examine the factors and mechanisms involved in TBI in experiments that cannot be conducted using human participants. The purpose of this thesis was to develop and fully characterize a reproducible, non-invasive mTBI model that will facilitate the study of repetitive brain injury. In the present study, male wild type mice received a midline concussive blow via an electromagnetic impactor, tuned to produce an injury without fracturing the skull. The injured mice were used to examine the chronic neurobehavioral, neuropathological and biochemical outcomes following single and r-mTBI up to 18 months following injury. Importantly, our findings recapitulate many aspects of human long term TBI sequelae, in particular persistent neuroinflammation, white matter injury, and axonal pathology in the corpus callosum. Our results provide the first evidence that, whilst a single concussion produces transient neurobehavioral changes and pathology which remains static in the period following injury, r-mTBI produces behavioral and pathological changes which continue to evolve many months post injury. There have been a number of clinical studies implicating tau in TBI pathology. As such, we investigated the relationship between tau pathologies after trauma in a transgenic mouse model expressing all 6 isoforms of human tau protein on a null murine background (hTau). Our results revealed that that single and r-mTBI induced a modest cortical increase in the soluble fraction of three different p-tau epitopes at 24 h post last injury. Moreover, this increase was not associated with worse behavioral performance when compared to wild type animals. Therefore, tau hyperphosphorylation appears to have a contributory, but not primary, role in the acute phase post-injury. Additional prospective studies in both humans and animal models are required to characterize the contribution of tau to TBI sequelae. The experimental data presented here suggest that inflammation and axonal injury (as seen in both wild-type and hTau models) appear to play a role in the events following single or repetitive mTBI and strongly correlates with the behavioral changes post-injury. The relationship between a history of mTBI and neuroinflammation are likely to be complex and warrant further work to elucidate their association with neurodegenerative disease. This work represents the development of a novel model, and the demonstration of its relevance to human TBI. This model can now be used for further exploration of TBI-related effects and for evaluation of potential therapeutic and diagnostic approaches, as is discussed throughout the thesis.

Nowadays, the European automotive market is dominated by Diesel engines. Despite their high efficiency, these produce significant levels of pollutants. Among the various pollutants released, nitrogen oxides and soot are the main issues. Their formation is linked to the combustion process and attempts to reduce one often lead to an increase of the other. Laser diagnostics are among the best tools for experimental, non-intrusive studies inside combustion chambers for a better understanding of the complex combustion processes. Depending on the optical diagnostic, numerous combustion characteristics and processes can be investigated. The work presented here intends initially to develop a quantitative laser technique for characterising soot and, secondly, to further the knowledge on soot formation in Diesel engines by the application of this technique in an optical combustion chamber. Some of the main characteristics describing soot formation are the soot volume fraction, number density and particle sizes. Soot volume fraction is the major one as it is representative of the volume of soot produced. Planar characterisation of soot volume fraction, number density and particle size were achieved for the first time by simultaneous recording laser-induced incandescence (LII), laser scattering and two-colour time-resolved (2C-TiRe) LII signals. Qualitative planar distributions of particle diameter and soot volume fraction were derived from the image ratio of scattering and incandescence signals. 2C- TiRe LII technique allowed the simultaneous recording of the temporal LII signal for two different wavelengths in order to obtain quantitative values of the laser-heated particles temperature, soot volume fraction and particle size for a local or global part of the flame. These were used to recalibrate relative size and soot volume distributions. An initial development of the technique was performed on a laminar diffusion flame (Santoro burner) to validate its viability and performance. Equivalent temperature, soot volume fraction and particle diameter were determined throughout the flame. The results were found to be in good agreement with the ones published in the literature. The diagnostic was subsequently applied to an optical Diesel rapid compression machine, and further refinements were undertaken to cope with the higher soot concentration and lower LII signal. Tests were conducted for in-cylinder pressures ranging from 4 to 10 MPa, and injection pressures up to 160 MPa. A fixed injection timing and injected fuel quantity were used. Effects of in-cylinder pressure, fuel injection pressure and cetane number on soot formation and characteristics were observed. High injection pressure, cetane number and in-cylinder pressure caused a reduction of soot particle size and volume fraction but an increase of the soot particle density.

Highly stereo- and regioselective rhodium-catalysed carbometallations of ynamides using organometallic reagents have been disclosed. The scope of the process was explored, and investigations revealed that Rh(cod)(acac) acts as an effective precatalyst for carbometallation of ynamides using a range of organozinc reagents. A plausible mechanism has been suggested where an alkenylzinc intermediate is formed. This species has been exploited in further transformations with electrophiles and in cross-coupling reactions, thus providing access to multisubstituted enamides in a stereo- and regioselective manner. It was also possible to carry out the carbometallation of ynamides using organoboron reagents by using [Rh(cod)(MeCN)2]BF4 as a precatalyst. This complementary protocol allowed the introduction of a greater diversity of substituents, including those carrying sensitive functional groups. Mechanistic studies, including deuterium labelling, suggested that an alkenylrhodium intermediate was produced during the course of the reaction. With a set of optimised conditions, this species was successfully used in a tandem carbometallation– conjugate addition (or annulation) reaction with bifunctional arylboron reagents. The 2-amidoindene products were obtained in good yields and high regioselectivities. Preliminary studies on the development of an asymmetric variant of this transformation have been undertaken and the initial results have been reported. In addition, highly enantioselective dihydroxylation of the enamide substrates prepared from the developed rhodium-catalysed carbometallations of ynamides was readily accomplished using commercially available AD-mix- . This novel procedure provides an access to a wide range of chiral products that might be difficult to access using existing methods. Finally, as a further exemplification of asymmetric enamide dihydroxylation, this method was applied to a concise total synthesis of the antifugal natural product (+)-Tanikolide.

This study investigates the complex flow structure generated by riparian emergent vegetation along the edge of floodplain. Detailed velocity and boundary shear stress measurements were carried out for various arrangements of emergent rigid cylindric rods of 3 mm, 6 mm and 9 mm diameters and for three different rod densities. In addition, the impact of foliage on the flow field was assessed during a series of experiments where brushes were used instead of smooth rods. The results of these new experiments are first presented. In addition to the laboratory data, field data was obtained through Acoustic Doppler Current Profiler measurements for two flood events in a stretch of the river Rhône that can be approximated to a straight compound channel with vegetated banks. The analysis of the flow structure highlights the presence of strong secondary circulation and increased vorticity on the river banks. The rods on the edge of the floodplain increase significantly flow resistance, reducing velocity and decreasing boundary shear stress. Flow rate was seen to decrease with increasing vegetative density for all cases except when foliage was added. This suggests that an optimum threshold density, for which a smaller density would lead to an increased flow rate might exist. Wakes trailing downstream of the vegetation stem, planform coherent structures advected between the main channel and the floodplain, and eddying motion in the flow due to enhanced turbulence anisotropy are among the defining patterns observed in the studied compound channel flows with one line of emergent vegetation along the edge of the floodplain. The Shiono and Knight Method (SKM) was modified in order to account for the increased turbulence activity due to the rods. The drag force term was introduced in the same way as in the work of Rameshwaran and Shiono (2007). However, a new term was added to the transverse shear stress term in the form of an Elder formulation, incorporating a friction drag coefficient which can be derived from the experimental data. In this proposed version, the advection term was set to zero. Another version of the SKM, similar to Rameshwaran and Shiono (2007), was also tested with the addition of a local drag friction only applied in the rod region. The proposed SKM version without the advection term was favored as it can be more closely related to the experimental data and to physical processes. Finally, the capabilities of Telemac-2D were tested against the experimental data for various turbulence models. The Large Eddy Simulation turbulence model highlighted some unsteady flow patterns that were observed during experiments, while satisfactorily predicting the lateral velocity and boundary shear stress distributions.

The functional organisation of rostral prefrontal cortex (rPFC; approximating Area 10) is largely unknown. On one hand, this region might support processes that are commonly involved in coping with multiple demands. On the other hand, rPFC might be fractionated into functionally specialised subregions. This thesis examines which of these accounts is more plausible. Therefore, four functional MRI studies were conducted, each of which compared two functions. These were hypothesised to share common processing denominators that might be supported by medial rPFC (mrPFC). It was assessed whether the functions are associated with haemodynamic signal changes in overlapping versus segregated subregions. Study I investigated the involvement of rPFC in prospective memory and in stimulus-oriented (i.e. triggered by the environment) versus stimulus-independent (i.e. decoupled from the environment) processing. Study II asked participants to envision future episodes of spending money (e.g., £35 at a Pub). It was hypothesised that subregions supporting such episodic prospection might also exhibit haemodynamic signal changes as a function of the imagined reward value (e.g., £35). In study III, participants first made personality trait judgements about themselves and others (i.e., their best friends), and then tried to remember the target of each judgement. It was investigated whether mrPFC subregions involved in thinking about oneself during those tasks might also support thinking about others to the degree that the other person is perceived as similar. Study IV examined the relationship between mrPFC engagement during self-appraisal and individual differences in the valuation of future rewards. Overall, the data are most consistent with a synthesis of the two accounts: mrPFC seems to be functionally fractionated. However, the specialised subregions appear to be engaged irrespective of the exact task context (e.g., the nature of the stimuli). Thus, these regions may be characterised as supporting central functions that are involved in coping with multiple demands.

ZnO nanostructures have great promise in a wide range of applications such as sensors, optoelectronics, piezoelectronics, healthcare. Preparation of oxide films by electrodeposition from aqueous solution presents several advantages over other techniques such as controlling the rate and morphology through several well-defined parameters (electrode potential, current, temperature, pH, etc.), the fact that electrolytic processing is a well-established technology and readily scalable for production, and the non-equilibrium nature of the electrochemical interface often gives rise to morphologies and compositions not attainable through other, usually high-temperature, routes. Despite a large amount of research in this area the detailed mechanism of nucleation and growth is still controversial. Only a good understanding of it will allow the expected industrial applications to be achieved. One of the main difficulties to overcome is that tiny amounts of material are involved and the required in-situ measurements are thus very delicate. The ability of synchrotron radiation to probe material structure during deposition makes it the ideal tool for the study of nucleation and growth of these materials as a function of the processing parameters. Here we will present two synchrotron-based approaches involving both X-ray absorption and scattering. The first method, together with ex-situ characterisation, provides detailed information about how the kinetics of the growth and/or dissolution is influenced by the electrochemical parameters. The effect of time, potential, zinc ions concentration, oxygen precursor, temperature and electrolyte composition have been studied. Following this understanding of the influence of the parameters, films of desired structure can be synthesised and new structures have been made. Beside the electrochemical parameters, the growth of the film is influenced by the interaction with substrate in the early stage of nucleation. The second synchrotron technique allows the direct observation of the development of the crystal orientation of the films during the deposition. It gives promising results to study how the substrate influences the growth and thus the properties of the films.

In this thesis we consider several questions on harmonic and analytic functions spaces and some of their operators. These questions deal with Carleson-type measures in the unit ball, bi-parameter paraproducts and multipliers problem on the bitorus, boundedness of the Bergman projection and analytic Besov spaces in tube domains over symmetric cones. In part I of this thesis, we show how to generate Carleson measures from a class of weighted Carleson measures in the unit ball. The results are used to obtain boundedness criteria of the multiplication operators and Ces`aro integral-type operators between weighted spaces of functions of bounded mean oscillation in the unit ball. In part II of this thesis, we introduce a notion of functions of logarithmic oscillation on the bitorus. We prove using Cotlar’s lemma that the dyadic version of the set of such functions is the exact range of symbols of bounded bi-parameter paraproducts on the space of functions of dyadic bounded mean oscillation. We also introduce the little space of functions of logarithmic mean oscillation in the same spirit as the little space of functions of bounded mean oscillation of Cotlar and Sadosky. We obtain that the intersection of these two spaces of functions of logarithmic mean oscillation and L1 is the set of multipliers of the space of functions of bounded mean oscillation in the bitorus. In part III of this thesis, in the setting of the tube domains over irreducible symmetric cones, we prove that the Bergman projection P is bounded on the Lebesgue space Lp if and only if the natural mapping of the Bergman space Ap0 to the dual space (Ap) of the Bergman space Ap, where 1 p + 1 p0 = 1, is onto. On the other hand, we prove that for p > 2, the boundedness of the Bergman projection is also equivalent to the validity of an Hardy-type inequality. We then develop a theory of analytic Besov spaces in this setting defined by using the corresponding Hardy’s inequality. We prove that these Besov spaces are the exact range of symbols of Schatten classes of Hankel operators on the Bergman space A2.

This thesis presents a study on the integration of polymer organic materials, onto GaN-based micron-scale light-emitting diodes, or 'micro-LEDs'. Several pertinent micro-patterning techniques are investigated along with their used in the realisation of such hybrid devices. Polymers are an attractive family of materials whose properties can be tailored to the requirements of specific applications. The interest of this thesis focuses on an 'in-house' synthesised transparent polymer ('HTP2') designed for encapsulation of micro-LEDs emitting in the UV-blue region of the spectrum and on conjugated light-emitting materials whose semiconducting properties are used in this work for colour conversion.

Optical lattices make it possible to trap and coherently control large ensembles of ultracold atoms. They provide the possibility to create lattice potentials that mimic the structure of solid-state systems, and to control these potentials dynamically. In this thesis, we study how dynamical manipulations of the lattice geometry can be used to perform different tasks, ranging from quantum information processing to the creation of diatomic molecules. We first examine the dynamical properties of ultracold atoms trapped in a lattice whose periodicity is dynamically doubled. We derive a model describing the dynamics of the atoms during this process, and compute the different interaction parameters of this model. We investigate different ways of using this lattice manipulation to optimise the initialisation time of a Mott-insulating state with one atom per site, and provide a scaling law related to the interaction parameters of the system. We go on to show that entangling operations between the spin of adjacent atoms are realisable with optical lattices forming arrays of double-well potentials. We study the creation of a lattice containing a spin-encoded Bell-pair in each double-well, and show that resilient, highly-entangled many-body states are realisable using lattice manipulations. We show that the creation of cluster-like states encoded on Bell-pairs can be achieved using these systems, and we provide measurement networks that allow the execution of quantum algorithms while maintaining intact the resilience of the system. Finally, we investigate the possibility to create a diatomic molecular state and simulate Fermi systems via the excitation to Rydberg levels of ground-state atoms trapped in optical lattices. We develop a method based on symbolical manipulations to compute the interaction parameters between highly-excited electrons, and evaluate them for different electronic configurations. We use these parameters to investigate the existence of diatomic molecular states with equilibrium distances comparable to typical lattice spacings. Considering the possibility to excite atoms trapped in an optical lattice to Rydberg levels such that the electronic cloud of neighbouring atoms overlap, we propose a model describing their interactions and compute its parameters. If such systems were realised, they would allow the simulation of Fermi systems at a temperature much below the Fermi temperature, thus enabling the observation of quantum phenomena hitherto inaccessible with current technology.

Despite companies' growing interest for customer education (for instance: Nikon, Orange, Sony) and the recent awareness in marketing literature of this concept (Hennig-thurau et al., 2005), research on customer education remains relatively scarce. Thus, the present research study aims to contribute to the development of knowledge on customer education. More specifically, it endeavours to clarify the concept of customer education and to understand and measure its outcomes on customer satisfaction, a key indicator of corporate performance. To achieve this goal, a literature review was conducted in order to provide an original conceptualization of customer education and its outcomes. Then, a reliable and valid scale to measure customer education was developed. Finally, an experimental procedure based on hypothetic-deductive methodology was performed. A structural model was built that depicts the effects of customer education on customer satisfaction and tested a set of hypotheses covering the mediating and moderating effects. The experimental fieldwork was conducted in partnership with the digital camera manufacturer Nikon France, on a sample of 321 customers. Structural Equation Modelling was used to test the hypotheses. The results of this research were twofold. First, a 5-item original scale to measure customer education was developed. The psychometric qualities of this scale were shown, using Churchill's procedure (1979). Second, a model which details the relationships between customer education and customer satisfaction was proposed and validated. The existence of two mediating variables was unveiled: product usage and product-usage related knowledge and skills. The moderating role of customer expertise with a product category was also substantiated. Keywords: customer education, customer satisfaction, product usage, product usage related knowledge and skills.

This work represents a contribution to the rapidly expanding field of microarray technology, which consists in the pooling of a large number of miniaturised biorecognition elements on a single solid substrate so as to allow heterogeneous bioassays to be performed in a highly multiplexed fashion. Numerous applications of life science research and pharmaceutical development, such as diagnostics and molecular medicine, are expected to greatly benefit from the increased levels of throughput provided by the microarray approach. However, most microarray platforms developed as of this writing have merely been based on a two-dimensional configuration in which the biorecognition sites are distributed on the surface of a planar, unpenetrable substrate; this format does not adress the mass-transfer limitations inherent to heterogeneous ligand binding kinetics and thus does not provide optimal assay performance in terms of speed and sensitivity. In this thesis, a novel concept is presented that has been devised to increase the intrinsic analytical performance of microarrays. The approach is based on the use of three-dimensional, uniformly porous substrates featuring a regular array of discrete, ordered, high aspect ratio microchannels. The fabrication of such microstructures, with feature sizes in the micrometre range and aspect ratios in excess of 30:1, was achieved using two subtractive silicon processing techniques, electrochemical etching and deep dry etching, whose relative merits have been assessed. Commercially available microchannel glass substrates were also used. Nucleic acid molecules were immobilised as capture probes on the sidewalls of the microchannels, in a conformation allowing biorecognition through heterogeneous hybridisation. To that end, a chemical strategy was developed for the functional immobilisation of oligonucleotide probes onto silica-rich substrates such as glass and oxidised silicon. Nucleic acid hybridisation was chosen as the model ligand binding process due not only to the relative ease of handling of DNA (including the availability of chemically pure, synthetic oligonucleotides) but also to its relevance, through genomics, to a number of clinical, medical and pharmaceutical applications. The particular wetting properties of microchannel substrates were characterised and subsequently taken into account in the development of a microarraying procedure based on non-contact, ink-jet dispensing technology. In this respect, the physical-chemical processes that control the formation of spots on microchannel substrates, i.e. the wetting properties of the substrates, as well as the main parameters involved in the arraying process, such as the concentration of the capture probe solution and volume of the aliquots dispensed, have been investigated. Medium-density microchannel oligoarrays were produced that comprised as many as 256 probe spots over a 1 cm2 area. Since the effective surface area available for probe immobilisation was increased by expansion into the third dimension, a higher spatial density of probes could be achieved as compared to planar substrates with the same lateral dimensions. Biorecognition events between the immobilised capture probes and solution-borne target molecules were allowed to take place, in a dynamic mode, by convectively pumping sample through the microchannel array. As each microchannel acted as a miniature analytical chamber, probe-target hybridisation kinetics were enhanced by spatial confinement, while recirculation of the sample provided enhanced mass transfer. The feasibility of using electrokinetic transport of the targets was also assessed. Quantitative detection of heterogeneous hybridisation events taking place along the microchannel sidewalls was achieved through a CCD camera-based epifluorescence detection scheme, in a first instance, conventional low magnification microscope objective lenses were used as imaging optics whose depth-of-field characteristics matched the thickness of the microchannel substrate. The suitability of the approach was illustrated by the achievement of detection limits as low as a few attomoles of fluorescent dye per spot. This level of performance was made possible by the remarkable optical properties of the substrate, which were characterised both experimentally and through simulations based on ray-tracing procedures. Since the use of microchannel chips of increased thickness provided a way of increasing the number of capture probe molecules immobilised within each spot without increasing the lateral dimensions of the spots, a range of chip thicknesses were considered in a first step towards optimisation of the substrate geometry. Potential limitations to the benefits associated with an increase in chip thickness were discussed, in terms of the effectiveness of both the fluorescence detection scheme and the process of probe immobilisation on the microchannel sidewalls. Comparative hybridisation experiments were conducted which demonstrated the improved performance of the flow-through microchannel configuration over the conventional planar configuration, with an observed circa 5 times enhancement in hybridisation kinetics and a one to two orders of magnitude higher detectability. A few routes for further improving the performance of flow-through microchannel DNA chips are suggested, along with other possible bioanalytical applications of the microchannel biochip platform.