Nanotechnology and microfluidics:formulation design and on-chip manufacture of nanoparticles

Nanoparticles offer an ideal platform for the delivery of small molecule drugs, subunit vaccines and genetic constructs. Besides the necessity of a homogenous size distribution, defined loading efficiencies and reasonable production and development costs, one of the major bottlenecks in translating nanoparticles into clinical application is the need for rapid, robust and reproducible development techniques. Within this thesis, microfluidic methods were investigated for the manufacturing, drug or protein loading and purification of pharmaceutically relevant nanoparticles. Initially, methods to prepare small liposomes were evaluated and compared to a microfluidics-directed nanoprecipitation method. To support the implementation of statistical process control, design of experiment models aided the process robustness and validation for the methods investigated and gave an initial overview of the size ranges obtainable in each method whilst evaluating advantages and disadvantages of each method. The lab-on-a-chip system resulted in a high-throughput vesicle manufacturing, enabling a rapid process and a high degree of process control. To further investigate this method, cationic low transition temperature lipids, cationic bola-amphiphiles with delocalized charge centers, neutral lipids and polymers were used in the microfluidics-directed nanoprecipitation method to formulate vesicles. Whereas the total flow rate (TFR) and the ratio of solvent to aqueous stream (flow rate ratio, FRR) was shown to be influential for controlling the vesicle size in high transition temperature lipids, the factor FRR was found the most influential factor controlling the size of vesicles consisting of low transition temperature lipids and polymer-based nanoparticles. The biological activity of the resulting constructs was confirmed by an invitro transfection of pDNA constructs using cationic nanoprecipitated vesicles. Design of experiments and multivariate data analysis revealed the mathematical relationship and significance of the factors TFR and FRR in the microfluidics process to the liposome size, polydispersity and transfection efficiency. Multivariate tools were used to cluster and predict specific in-vivo immune responses dependent on key liposome adjuvant characteristics upon delivery a tuberculosis antigen in a vaccine candidate. The addition of a low solubility model drug (propofol) in the nanoprecipitation method resulted in a significantly higher solubilisation of the drug within the liposomal bilayer, compared to the control method. The microfluidics method underwent scale-up work by increasing the channel diameter and parallelisation of the mixers in a planar way, resulting in an overall 40-fold increase in throughput. Furthermore, microfluidic tools were developed based on a microfluidics-directed tangential flow filtration, which allowed for a continuous manufacturing, purification and concentration of liposomal drug products.

System design and resource management in the next-generation integrated WLAN and 3G cellular networks

Next-generation integrated wireless local area network (WLAN) and 3G cellular networks aim to take advantage of the roaming ability in a cellular network and the high data rate services of a WLAN. To ensure successful implementation of an integrated network, many issues must be carefully addressed, including network architecture design, resource management, quality-of-service (QoS), call admission control (CAC) and mobility management. ^ This dissertation focuses on QoS provisioning, CAC, and the network architecture design in the integration of WLANs and cellular networks. First, a new scheduling algorithm and a call admission control mechanism in IEEE 802.11 WLAN are presented to support multimedia services with QoS provisioning. The proposed scheduling algorithms make use of the idle system time to reduce the average packet loss of realtime (RT) services. The admission control mechanism provides long-term transmission quality for both RT and NRT services by ensuring the packet loss ratio for RT services and the throughput for non-real-time (NRT) services. ^ A joint CAC scheme is proposed to efficiently balance traffic load in the integrated environment. A channel searching and replacement algorithm (CSR) is developed to relieve traffic congestion in the cellular network by using idle channels in the WLAN. The CSR is optimized to minimize the system cost in terms of the blocking probability in the interworking environment. Specifically, it is proved that there exists an optimal admission probability for passive handoffs that minimizes the total system cost. Also, a method of searching the probability is designed based on linear-programming techniques. ^ Finally, a new integration architecture, Hybrid Coupling with Radio Access System (HCRAS), is proposed for lowering the average cost of intersystem communication (IC) and the vertical handoff latency. An analytical model is presented to evaluate the system performance of the HCRAS in terms of the intersystem communication cost function and the handoff cost function. Based on this model, an algorithm is designed to determine the optimal route for each intersystem communication. Additionally, a fast handoff algorithm is developed to reduce the vertical handoff latency.^

O olhar das instituições de previdência sobre a casa e a cidade: promoção, financiamento e avaliação de imóveis

The investments of Caixas and Institutos de Aposentadoria e Pensões (CAP and IAP) in homes of Natal, between the decades of 1930-60, helped to boost up the local real estate market in consolidation at the time. Inserted in the first national policy on social housing in the country, these operations have demanded the creation of a wide qualified organizational structure, which would be from the "Central Offices" of Rio de Janeiro to the decentralized units of the federal states. The professionals linked to the Local Agencies have developed, on this matter, from activities related to the design and construction of residential complexes, to the daily study of financing proposals in isolated units. As from these studies, the evaluation of shelters was essential to the effectiveness of the policy, resulting in the production of data on the market value of the properties by observing and issuing judgments upon the living quarters of different social groups. Given these considerations, the aim here is to contribute to the understanding on how to operate these real estate actions in the legitimization of boundaries about the urban space and dwellings available to workers in Natal. Therefore, the views of the city and constructions expressed by the evaluating engineers in their technical reports have been taken as the focus. Being the main primary sources of work, these reports are part of the edifices process of CAP/IAP regarding Natal, whose content is systematized in the database "Enterprises", the HCUrb Research Group. In addition, there were used local newspapers at the time and interviews with professionals as complementary sources. It was found that, in general, the evaluations have configured – in a more everyday dimension of bureaucratic routines - a vehicle, among others, circulating ideas about "home" within the social security institutions, being imbued with assumptions historically constructed about the "modern habitat". Filled in loco, the reports expose the clash between modernizing ideals in vogue and clear limitations in the city scenario at the time. Fragmented images of the town are given to read through the labels assigned to the evaluated sites – these being coated of certain "scientific" character - which both legitimated and contributed to the dynamics of appreciation/depreciation of the soil and to the socio-spatial differentiation. Contradictions were evident in the endorsement given by the technicians when financing of admittedly precarious homes for insured disadvantaged categories at the local level - such as industrial workers - while strict regulations were imposed to new construction, designed, above all, to better paid categories. By identifying raters engineers as urban agents, members of a technical-focused operating system for safety and efficiency in the real estate investments of those authorities corporatist, it is desired the usefulness of further studies on these characters, their training, professional activity and participation in the construction of discourses and practices of intervention about the city and its buildings, discussing individual and grouped interests that were left behind.

Design and implementation of a relative localization system for ground and aerial robotic teams

The main focus of this thesis is to address the relative localization problem of a heterogenous team which comprises of both ground and micro aerial vehicle robots. This team configuration allows to combine the advantages of increased accessibility and better perspective provided by aerial robots with the higher computational and sensory resources provided by the ground agents, to realize a cooperative multi robotic system suitable for hostile autonomous missions. However, in such a scenario, the strict constraints in flight time, sensor pay load, and computational capability of micro aerial vehicles limits the practical applicability of popular map-based localization schemes for GPS denied navigation. Therefore, the resource limited aerial platforms of this team demand simpler localization means for autonomous navigation. Relative localization is the process of estimating the formation of a robot team using the acquired inter-robot relative measurements. This allows the team members to know their relative formation even without a global localization reference, such as GPS or a map. Thus a typical robot team would benefit from a relative localization service since it would allow the team to implement formation control, collision avoidance, and supervisory control tasks, independent of a global localization service. More importantly, a heterogenous team such as ground robots and computationally constrained aerial vehicles would benefit from a relative localization service since it provides the crucial localization information required for autonomous operation of the weaker agents. This enables less capable robots to assume supportive roles and contribute to the more powerful robots executing the mission. Hence this study proposes a relative localization-based approach for ground and micro aerial vehicle cooperation, and develops inter-robot measurement, filtering, and distributed computing modules, necessary to realize the system. The research study results in three significant contributions. First, the work designs and validates a novel inter-robot relative measurement hardware solution which has accuracy, range, and scalability characteristics, necessary for relative localization. Second, the research work performs an analysis and design of a novel nonlinear filtering method, which allows the implementation of relative localization modules and attitude reference filters on low cost devices with optimal tuning parameters. Third, this work designs and validates a novel distributed relative localization approach, which harnesses the distributed computing capability of the team to minimize communication requirements, achieve consistent estimation, and enable efficient data correspondence within the network. The work validates the complete relative localization-based system through multiple indoor experiments and numerical simulations. The relative localization based navigation concept with its sensing, filtering, and distributed computing methods introduced in this thesis complements system limitations of a ground and micro aerial vehicle team, and also targets hostile environmental conditions. Thus the work constitutes an essential step towards realizing autonomous navigation of heterogenous teams in real world applications.

Design and Implementation of a Cloud Infrastructure for Distributed Scientific Calculation

Cloud computing enables independent end users and applications to share data and pooled resources, possibly located in geographically distributed Data Centers, in a fully transparent way. This need is particularly felt by scientific applications to exploit distributed resources in efficient and scalable way for the processing of big amount of data. This paper proposes an open so- lution to deploy a Platform as a service (PaaS) over a set of multi- site data centers by applying open source virtualization tools to facilitate operation among virtual machines while optimizing the usage of distributed resources. An experimental testbed is set up in Openstack environment to obtain evaluations with different types of TCP sample connections to demonstrate the functionality of the proposed solution and to obtain throughput measurements in relation to relevant design parameters.

Design and protocol for the Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial : a randomised controlled trial

Acknowledgements Thank you to all the participants who agreed to take part in the trial. This study was supported NHS Research Scotland (NRS), through Chief Scientist Office (CSO) and the Scottish Mental Health Research Network, and the Clinical Research Network-Mental Health. We are grateful to the Psychosis Research Unit (PRU) Service User Reference Group (SURG) for their consultation regarding the design of the study and contribution to the developments of study related materials. We are grateful to our Independent Trial Steering Committee and Independent Data Monitoring Committee for provided oversight of the trial. Funding This project was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) programme (project number10/101/02) and will be published in full in Health Technology Assessment. Visit the HTA programme website for further project information. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health.

Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers

The aim of this work was to investigate alternative safe and effective permeation enhancers for buccal peptide delivery. Basic amino acids improved insulin solubility in water while 200 and 400 µg/mL lysine significantly increased insulin solubility in HBSS. Permeability data showed a significant improvement in insulin permeation especially for 10 µg/mL of lysine (p < 0.05) and 10 µg/mL histidine (p < 0.001), 100 µg/mL of glutamic acid (p < 0.05) and 200 µg/mL of glutamic acid and aspartic acid (p < 0.001) without affecting cell integrity; in contrast to sodium deoxycholate which enhanced insulin permeability but was toxic to the cells. It was hypothesized that both amino acids and insulin were ionised at buccal cavity pH and able to form stable ion pairs which penetrated the cells as one entity; while possibly triggering amino acid nutrient transporters on cell surfaces. Evidence of these transport mechanisms was seen with reduction of insulin transport at suboptimal temperatures as well as with basal-to-apical vectoral transport, and confocal imaging of transcellular insulin transport. These results obtained for insulin is the first indication of a possible amino acid mediated transport of insulin via formation of insulin-amino acid neutral complexes by the ion pairing mechanism.

Retrieval of grassland biophysical parameters using multitemporal optical and radar satellite data

The amount and quality of available biomass is a key factor for the sustainable livestock industry and agricultural management related decision making. Globally 31.5% of land cover is grassland while 80% of Ireland’s agricultural land is grassland. In Ireland, grasslands are intensively managed and provide the cheapest feed source for animals. This dissertation presents a detailed state of the art review of satellite remote sensing of grasslands, and the potential application of optical (Moderate–resolution Imaging Spectroradiometer (MODIS)) and radar (TerraSAR-X) time series imagery to estimate the grassland biomass at two study sites (Moorepark and Grange) in the Republic of Ireland using both statistical and state of the art machine learning algorithms. High quality weather data available from the on-site weather station was also used to calculate the Growing Degree Days (GDD) for Grange to determine the impact of ancillary data on biomass estimation. In situ and satellite data covering 12 years for the Moorepark and 6 years for the Grange study sites were used to predict grassland biomass using multiple linear regression, Neuro Fuzzy Inference Systems (ANFIS) models. The results demonstrate that a dense (8-day composite) MODIS image time series, along with high quality in situ data, can be used to retrieve grassland biomass with high performance (R2 = 0:86; p < 0:05, RMSE = 11.07 for Moorepark). The model for Grange was modified to evaluate the synergistic use of vegetation indices derived from remote sensing time series and accumulated GDD information. As GDD is strongly linked to the plant development, or phonological stage, an improvement in biomass estimation would be expected. It was observed that using the ANFIS model the biomass estimation accuracy increased from R2 = 0:76 (p < 0:05) to R2 = 0:81 (p < 0:05) and the root mean square error was reduced by 2.72%. The work on the application of optical remote sensing was further developed using a TerraSAR-X Staring Spotlight mode time series over the Moorepark study site to explore the extent to which very high resolution Synthetic Aperture Radar (SAR) data of interferometrically coherent paddocks can be exploited to retrieve grassland biophysical parameters. After filtering out the non-coherent plots it is demonstrated that interferometric coherence can be used to retrieve grassland biophysical parameters (i. e., height, biomass), and that it is possible to detect changes due to the grass growth, and grazing and mowing events, when the temporal baseline is short (11 days). However, it not possible to automatically uniquely identify the cause of these changes based only on the SAR backscatter and coherence, due to the ambiguity caused by tall grass laid down due to the wind. Overall, the work presented in this dissertation has demonstrated the potential of dense remote sensing and weather data time series to predict grassland biomass using machine-learning algorithms, where high quality ground data were used for training. At present a major limitation for national scale biomass retrieval is the lack of spatial and temporal ground samples, which can be partially resolved by minor modifications in the existing PastureBaseIreland database by adding the location and extent ofeach grassland paddock in the database. As far as remote sensing data requirements are concerned, MODIS is useful for large scale evaluation but due to its coarse resolution it is not possible to detect the variations within the fields and between the fields at the farm scale. However, this issue will be resolved in terms of spatial resolution by the Sentinel-2 mission, and when both satellites (Sentinel-2A and Sentinel-2B) are operational the revisit time will reduce to 5 days, which together with Landsat-8, should enable sufficient cloud-free data for operational biomass estimation at a national scale. The Synthetic Aperture Radar Interferometry (InSAR) approach is feasible if there are enough coherent interferometric pairs available, however this is difficult to achieve due to the temporal decorrelation of the signal. For repeat-pass InSAR over a vegetated area even an 11 days temporal baseline is too large. In order to achieve better coherence a very high resolution is required at the cost of spatial coverage, which limits its scope for use in an operational context at a national scale. Future InSAR missions with pair acquisition in Tandem mode will minimize the temporal decorrelation over vegetation areas for more focused studies. The proposed approach complements the current paradigm of Big Data in Earth Observation, and illustrates the feasibility of integrating data from multiple sources. In future, this framework can be used to build an operational decision support system for retrieval of grassland biophysical parameters based on data from long term planned optical missions (e. g., Landsat, Sentinel) that will ensure the continuity of data acquisition. Similarly, Spanish X-band PAZ and TerraSAR-X2 missions will ensure the continuity of TerraSAR-X and COSMO-SkyMed.

The geographies of encounter: investigating the spatiality and construction of 'meaningful' encounters with difference through the experiences of international students at University College Cork, Ireland

The purpose of this research is to investigate how international students negotiate encounters with Irish students and construct ‘meaning’ from those encounters in the spaces of the university and city. As cities are increasingly characterised by a multiplexity of diversity, the issue of living with difference is becoming more and more pertinent. In the wake of escalating socio-spatial polarisation, inter-cultural tension, racism, and xenophobia, the geographies of encounter seek to untangle the interactions that occur in the quotidian activities and spaces of everyday life to determine whether such encounters might reduce prejudice, antipathy and indifference and establish common social bonds (Amin 2002; Valentine 2008). Thus far, the literature has investigated a number of sites of encounter; public space, the home, neighbourhoods, schools, sports clubs, public transport, cafes and libraries (Wilson 2011; Schuermans 2013; Hemming 2011; Neal and Vincent 2011; Mayblin, Valentine and Anderrson 2015; Laurier and Philo 2006; Valentine and Sadgrove 2013; Harris, Valentine and Piekut 2014; Fincher and Iveson 2008). While these spaces produce a range of outcomes, the literature remains frustrated by a lack of clarity of what constitutes a ‘meaningful’ encounter and how such encounters might be planned for. Drawing on survey and interview data with full-time international students at University College Cork, Ireland, this study contributes to understanding how encounters are shaped by the construction and reproduction of particular identities in particular spaces, imbuing spaces with uneven power frameworks that produce diverse outcomes. Rather than identifying a singular ‘meaningful’ outcome of encounter as a potential panacea to the issues of exclusion and oppression, the contention here is to recognise a range of outcomes that are created by individuals in a range of ways. To define one outcome of encounter as ‘meaningful’ is to overlook the scale of intensity of diverse interactions and the multiplicity of ways in which people learn to live with difference.

(Table 1) Sample locations and clay mineral data of sediment surface samples from the Barents Sea region

A new surface sediment sample set gained in the western Barents Sea by the MAREANO program has been analysed for basic clay mineral assemblages. Distribution maps including additional samples from earlier German research cruises to and off Svalbard are compiled. Some trends in the clay mineral assemblages are related to the sub-Barents Sea geology because the Quaternary sediment cover is rather thin. Additionally, land masses like Svalbard and northern Scandinavia dominate the clay mineral signal with their erosional products. Dense bottom water, very often of brine origin, that flows within deep troughs, such as the Storfjorden or Bear Island Trough, transport the clay mineral signal from their origin to the Norwegian-Greenland Sea.

Sample locations, stratigraphic information and listing of carbon and oxygen isotope data of the measured planktonic foraminifera of surface sediments in the western South Atlantic Ocean (Table 1)

We explored the potential to use the stable isotopic compositions of planktonic foraminifera as a proxy for the position of the Brazil-Malvinas Confluence (BMC) in the Argentine Basin. For this purpose, we measured the oxygen and carbon isotopic compositions of Globigerinoides ruber (pink and white varieties measured separately), Globigerinoides trilobus, Globigerina bulloides, Globorotalia inflata and Globorotalia truncatulinoides (left- and right-coiling forms measured separately) from a latitudinal transect of 56 surface sediment samples from the continental slope off Brazil, Uruguay and Argentina between 20 and 48°S. Lowest oxygen isotopes values were found in G. ruber (pink), followed by G. ruber (white) and G. trilobus reflecting the highly stratified near surface water conditions north of the BMC. Globigerina bulloides was present mainly south of the BMC and records subsurface conditions supporting earlier plankton tow studies. Globorotalia inflata and G. truncatulinoides (left and right) were both available over the whole transect and calcify in the depth level with the steepest temperature change across the BMC. Accordingly, the delta18O of these species depict a sharp gradient of 2? at the confluence with remarkably stable values north and south of the BMC. Our data show that the oxygen isotopic composition of G. inflata and G. truncatulinoides (left and right) are the most reliable indicators for the present position of the BMC and can therefore be used to define the past migration of the front if appropriate cores are available.

A case study on a design-informed developmental evaluation

Developmental evaluation (DE) is an evaluation approach that aims to support the development of an innovation (Patton, 1994, 2011). This aim is achieved through supporting clients’ information needs through evaluative inquiry as they work to develop and refine the innovation. While core concepts and principles are beginning to be articulated and refined, challenges remain as to how to focus a developmental evaluation beyond those knowledge frameworks most immediate to clients to support innovation development. Anchoring a DE in knowledge frameworks other than those of the clients might direct attention to issues not yet obvious to clients, but which might further the goal of supporting innovation development if attended to. Drawing concepts and practices from the field of design may be one avenue with which to inform developmental evaluation in achieving its aim. Through a case study methodology, this research seeks to understand the nuances of operationalizing the guiding principles of DE as well as to investigate the utility, feasibility, and consequences of integrating design concepts and practices into developmental evaluation (design-informed developmental evaluation, “DI-DE”). It does so by documenting the efforts of a design-informed developmental evaluator and a task force of educators and researchers in a Faculty of Education as they work to develop a graduate-level education program. A systematic review into those purposeful efforts made to introduce DI-DE thinking into task force deliberations, and an analysis into the responses and consequences of those efforts shed light on what it had meant to practice DI-DE. As a whole, this research on evaluation is intended to further contemporary thinking about the closely coupled relationship between program development and evaluation in complex and dynamic environments.

Sites of Excavation and Construction

For his first solo show in Belgium, British artist Neal White presents a range of recent and new work – some of them in collaboration with artist Tina O’Connell – that reflect his ongoing preoccupations with deep time and the spaces of art. OBJECTIF EXHIBITIONS is a not-for-profit institution devoted to the presentation of contemporary art, supported by the Flemish Community. Curated by Antony Hudek