Development of the Sphere Overlap Scale (SOS) : compartmentalization and the spillover hypothesis

The purpose of this study was to create a scale that could measure compartmentalization. In the first of two studies 311 working undergraduates were asked to indicate agreement with 119 items that measured compartmentalization. The resulting scale's reliability and validity were evaluated by having a second sample of 312 working students complete the items that comprise a sphere overlap scale, two measures of spillover, and a measure of personality, coping, and demoralization. Although the study's original goal was not realized, its procedures were successful in developing a short (10-item) measure of work-to-home spillover whose items loaded on a single factor. Structural equation modeling indicated that SOS items were correlated with existing measures of spillover and could be discriminated from related concepts of personality and coping. The SOS was also more highly correlated with demoralization than existing measures of spillover in hierarchical analyses that controlled for demographic factors, personality characteristics, and coping style. It is concluded that the SOS shows enough promise to warrant the cost of its appraisal as an alternative measure of spillover in a longitudinal study.

Development of Innovative Load Transfer Mechanism to Reduce Hurricane-Induced Failures in New and Existing Residential Construction

Implicit in current design practice of minimum uplift capacity, is the assumption that the connection's capacity is proportional to the number of fasteners per connection joint. This assumption may overestimate the capacity of joints by a factor of two or more and maybe the cause of connection failures in extreme wind events. The current research serves to modify the current practice by proposing a realistic relationship between the number of fasteners and the capacity of the joint. The research is also aimed at further development of non-intrusive continuous load path (CLP) connection system using Glass Fiber Reinforced Polymer (GFRP) and epoxy. Suitable designs were developed for stud to top plate and gable end connections and tests were performed to evaluate the ultimate load, creep and fatigue behavior. The objective was to determine the performance of the connections under simulated sustained hurricane conditions. The performance of the new connections was satisfactory.

A model of self-transformative identity development in troubled adolescent youth

Within the Stage II program evaluation of the Miami Youth Development Project's (YDP) Changing Lives Program (CLP), this study evaluated CLP intervention effectiveness in promoting positive change in emotion-focused identity exploration (i.e. feelings of personal expressiveness; PE) and a "negative" symptom of identity development (i.e. identity distress; ID) as a first step toward the investigation of a self-transformative model of identity development in adolescent youth. Using structural equation modeling techniques, this study found that participation in the CLP is associated with positive changes in PE (path = .841, p < .002), but not changes in ID. Increase in ID scores was found to be associated with increases in PE (path = .229, p < .002), as well. Intervention effects were not moderated by age/stage, gender, or ethnicity, though differences were found in the degree to which participating subgroups (African- American/Hispanic, male/female, 14-16 years old/17-19 years old) experience change in PE and ID. Findings also suggest that moderate levels of ID may not be deleterious to identity exploration and may be associated with active exploration.

Development of a triage tool for neurodevelopmental risk in children aged 30 months

Peer reviewed

Development of a triage tool for neurodevelopmental risk in children aged 30 months

Peer reviewed

NGR Tumor-Homing Peptides : Structural Requirements for Effective APN (CD13) Targeting

Acknowledgements We thank The Development Trust, University of Aberdeen, for financial support and a fellowship to M.P.

Development of a triage tool for neurodevelopmental risk in children aged 30 months

Peer reviewed

BDNF-TrkB Signaling in Single-Spine Structural Plasticity

Multiple lines of evidence reveal that activation of the tropomyosin related kinase B (TrkB) receptor is a critical molecular mechanism underlying status epilepticus (SE) induced epilepsy development. However, the cellular consequences of such signaling remain unknown. To this point, localization of SE-induced TrkB activation to CA1 apical dendritic spines provides an anatomic clue pointing to Schaffer collateral-CA1 synaptic plasticity as one potential cellular consequence of TrkB activation. Here, we combine two-photon glutamate uncaging with two photon fluorescence lifetime imaging microscopy (2pFLIM) of fluorescence resonance energy transfer (FRET)-based sensors to specifically investigate the roles of TrkB and its canonical ligand brain derived neurotrophic factor (BDNF) in dendritic spine structural plasticity (sLTP) of CA1 pyramidal neurons in cultured hippocampal slices of rodents. To begin, we demonstrate a critical role for post-synaptic TrkB and post-synaptic BDNF in sLTP. Building on these findings, we develop a novel FRET-based sensor for TrkB activation that can report both BDNF and non-BDNF activation in a specific and reversible manner. Using this sensor, we monitor the spatiotemporal dynamics of TrkB activity during single-spine sLTP. In response to glutamate uncaging, we report a rapid (onset less than 1 minute) and sustained (lasting at least 20 minutes) activation of TrkB in the stimulated spine that depends on N-methyl-D-aspartate receptor (NMDAR)-Ca2+/Calmodulin dependent kinase II (CaMKII) signaling as well as post-synaptically synthesized BDNF. Consistent with these findings, we also demonstrate rapid, glutamate uncaging-evoked, time-locked release of BDNF from single dendritic spines using BDNF fused to superecliptic pHluorin (SEP). Finally, to elucidate the molecular mechanisms by which TrkB activation leads to sLTP, we examined the dependence of Rho GTPase activity - known mediators of sLTP - on BDNF-TrkB signaling. Through the use of previously described FRET-based sensors, we find that the activities of ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42) require BDNF-TrkB signaling. Taken together, these findings reveal a spine-autonomous, autocrine signaling mechanism involving NMDAR-CaMKII dependent BDNF release from stimulated dendritic spines leading to TrkB activation and subsequent activation of the downstream molecules Rac1 and Cdc42 in these same spines that proves critical for sLTP. In conclusion, these results highlight structural plasticity as one cellular consequence of CA1 dendritic spine TrkB activation that may potentially contribute to larger, circuit-level changes underlying SE-induced epilepsy.

Structural and Functional Analysis of the Caspase –dependent and –independent Domains of the X-linked Inhibitor of Apoptosis Protein in Inflammatory Breast Cancer Tumor Biology

Inflammatory breast cancer (IBC) is an extremely rare but highly aggressive form of breast cancer characterized by the rapid development of therapeutic resistance leading to particularly poor survival. Our previous work focused on the elucidation of factors that mediate therapeutic resistance in IBC and identified increased expression of the anti-apoptotic protein, X-linked inhibitor of apoptosis protein (XIAP), to correlate with the development of resistance to chemotherapeutics. Although XIAP is classically thought of as an inhibitor of caspase activation, multiple studies have revealed that XIAP can also function as a signaling intermediate in numerous pathways. Based on preliminary evidence revealing high expression of XIAP in pre-treatment IBC cells rather than only subsequent to the development of resistance, we hypothesized that XIAP could play an important signaling role in IBC pathobiology outside of its heavily published apoptotic inhibition function. Further, based on our discovery of inhibition of chemotherapeutic efficacy, we postulated that XIAP overexpression might also play a role in resistance to other forms of therapy, such as immunotherapy. Finally, we posited that targeting of specific redox adaptive mechanisms, which are observed to be a significant barrier to successful treatment of IBC, could overcome therapeutic resistance and enhance the efficacy of chemo-, radio-, and immuno- therapies. To address these hypotheses our objectives were: 1. to determine a role for XIAP in IBC pathobiology and to elucidate the upstream regulators and downstream effectors of XIAP; 2. to evaluate and describe a role for XIAP in the inhibition of immunotherapy; and 3. to develop and characterize novel redox modulatory strategies that target identified mechanisms to prevent or reverse therapeutic resistance.

Using various genomic and proteomic approaches, combined with analysis of cellular viability, proliferation, and growth parameters both in vitro and in vivo, we demonstrate that XIAP plays a central role in both IBC pathobiology in a manner mostly independent of its role as a caspase-binding protein. Modulation of XIAP expression in cells derived from patients prior to any therapeutic intervention significantly altered key aspects IBC biology including, but not limited to: IBC-specific gene signatures; the tumorigenic capacity of tumor cells; and the metastatic phenotype of IBC, all of which are revealed to functionally hinge on XIAP-mediated NFκB activation, a robust molecular determinant of IBC. Identification of the mechanism of XIAP-mediated NFκB activation led to the characterization of novel peptide-based antagonist which was further used to identify that increased NFκB activation was responsible for redox adaptation previously observed in therapy-resistant IBC cells. Lastly, we describe the targeting of this XIAP-NFκB-ROS axis using a novel redox modulatory strategy both in vitro and in vivo. Together, the data presented here characterize a novel and crucial role for XIAP both in therapeutic resistance and the pathobiology of IBC; these results confirm our previous work in acquired therapeutic resistance and establish the feasibility of targeting XIAP-NFκB and the redox adaptive phenotype of IBC as a means to enhance survival of patients.

Structural and agentic analysis of supply-chains: a social network analysis approach

This research adds to a body of work exploring the role of Social Network Analysis (SNA) in the study of both relational and structural characteristics of supply chain networks. Two contrasting network cases (food enterprises and digital-based enterprises) are chosen in order to elicit structural differences in business networks subject to divergences in local embeddedness and the relative materiality of the goods and services produced. Our analysis and findings draw out differences in network structure as evidenced by metrics of network centralization and cohesion, the presence of components and other sub-groupings, and the position of central actors. We relate these structural features both to the nature of the networks and to the (qualitative) experiences of the actors themselves. We find, in particular, the role of customers as co-creators of knowledge (for the Food network), the central role of infrastructure and services (for the Digital network), the importance of ICT as a source of codified knowledge inputs, along with the continuing importance of geographical proximity for the development and transfer of tacit knowledge and for incremental learning.

Development of nanostructured hydrogel for spatial and temporal controlled release of active compounds

L’utilisation de nanovecteurs pour la livraison contrôlée de principes actifs est un concept commun de nous jours. Les systèmes de livraison actuels présentent encore cependant des limites au niveau du taux de relargage des principes actifs ainsi que de la stabilité des transporteurs. Les systèmes composés à la fois de nanovecteurs (liposomes, microgels et nanogels) et d’hydrogels peuvent cependant permettre de résoudre ces problèmes. Dans cette étude, nous avons développé un système de livraison contrôlé se basant sur l’incorporation d’un nanovecteur dans une matrice hydrogel dans le but de combler les lacunes des systèmes se basant sur un vecteur uniquement. Une telle combinaison pourrait permettre un contrôle accru du relargage par stabilisation réciproque. Plus spécifiquement, nous avons développé un hydrogel structuré intégrant des liposomes, microgels et nanogels séparément chargés en principes actifs modèles potentiellement relargués de manière contrôlé. Ce contrôle a été obtenu par la modification de différents paramètres tels que la température ainsi que la composition et la concentration en nanovecteurs. Nous avons comparé la capacité de chargement et la cinétique de relargage de la sulforhodamine B et de la rhodamine 6G en utilisant des liposomes de DOPC et DPPC à différents ratios, des nanogels de chitosan/acide hyaluronique et des microgels de N-isopropylacrylamide (NIPAM) à différents ratios d’acide méthacrylique, incorporés dans un hydrogel modèle d’acrylamide. Les liposomes présentaient des capacités de chargement modérés avec un relargage prolongé sur plus de dix jours alors que les nanogels présentaient des capacités de chargement plus élevées mais une cinétique de relargage plus rapide avec un épuisement de la cargaison en deux jours. Comparativement, les microgels relarguaient complétement leur contenu en un jour. Malgré une cinétique de relargage plus rapide, les microgels ont démontré la possibilité de contrôler finement le chargement en principe actif. Ce contrôle peut être atteint par la modification des propriétés structurelles ou en changeant le milieu d’incubation, comme l’a montré la corrélation avec les isothermes de Langmuir. Chaque système développé a démontré un potentiel contrôle du taux de relargage, ce qui en fait des candidats pour des investigations futures.

Empowering development: capabilities and Latin American critical traditions

This thesis theoretically and critically examines the move towards people-centred approaches to development. It offers a critical examination of the work of Amartya Sen using theoretical resources emerging from Latin American traditions. Amartya Sen’s calls to understand Development as Freedom (1999) have significantly influenced mainstream development thinking and practice, constituting the clearest example of people-centred approaches to development today. Overcoming the limitations of previous state-centred notions of development articulated around ideas of economic growth, in Sen’s Capability Approach (CA) development is seen as a process of expanding the real freedoms that people enjoy. In this understanding, the agency of development shifts from the state to individuals and the analytic focus moves from economic growth to individual capabilities. In this manner, this framework is structured towards the central goal of empowerment, wherein the expansion of capabilities is seen both as the means and end of development. Since its inception, the widespread support for the CA has allowed for the expansion of ethical considerations within mainstream development thinking. Even while the remarkable advances offered by Sen’s work should be praised, this thesis argues that these have come with new limitations. These limitations stem from, what is termed here, a “Paradox of Empowerment” that effectively encloses Sen’s approach within Western notions of development. While Sen’s approach is poised to provide a theoretical framework that is built on the expansion of freedom and individual agency, there is little agency here to move beyond the ideas of development fundamentally linked to liberal democracies and market economies. This thesis engages with several critical traditions from Latin America, recovering their often undervalued insights for development thinking. Crucially, this engagement provides the critical framework to illustrate the aforementioned paradox and explore multiple dimensions of empowerment central for contemporary development thinking and practice. In this, the thesis engages Sen’s work with the Liberation Theology of Gustavo Gutierrez, with Paulo Freire’s Critical Pedagogy and with the contemporary discussions of ‘Buen Vivir’ associated with Indigenous philosophies of the Andean region. Throughout its chapters,it uncovers the conceptual baggage within the Paradox of Empowerment in Sen’s work and examines the ethical challenges and boundaries of this approach in relation to the collective dimension of development processes, the possibilities for structural transformation and concerns for sustainability. Progressively engaging the different dimensions of this paradox, this thesis advances the recovery of the transformative potential of the ideas of empowerment for development.

Bridge weigh-in-motion system and Structural Health Monitoring using fiber optic sensors

There have been over 3000 bridge weigh-in-motion (B-WIM) installations in 25 countries worldwide, this has led vast improvements in post processing of B-WIM systems since its introduction in the 1970’s. This paper introduces a new low-power B-WIM system using fibre optic sensors (FOS). The system consisted of a series of FOS which were attached to the soffit of an existing integral bridge with a single span of 19m. The site selection criteria and full installation process has been detailed in the paper. A method of calibration was adopted using live traffic at the bridge site and based on this calibration the accuracy of the system was determined.

Field Testing and Development of Novel SHM systems at Queen’s University Belfast

Ageing and deterioration of infrastructure is a challenge facing transport authorities. In
particular, there is a need for increased bridge monitoring in order to provide adequate
maintenance and to guarantee acceptable levels of transport safety. The Intelligent
Infrastructure group at Queens University Belfast (QUB) are working on a number of aspects
of infrastructure monitoring and this paper presents summarised results from three distinct
monitoring projects carried out by this group. Firstly the findings from a project on next
generation Bridge Weight in Motion (B-WIM) are reported, this includes full scale field testing
using fibre optic strain sensors. Secondly, results from early phase testing of a computer
vision system for bridge deflection monitoring are reported on. This research seeks to exploit
recent advances in image processing technology with a view to developing contactless
bridge monitoring approaches. Considering the logistical difficulty of installing sensors on a
‘live’ bridge, contactless monitoring has some inherent advantages over conventional
contact based sensing systems. Finally the last section of the paper presents some recent
findings on drive by bridge monitoring. In practice a drive-by monitoring system will likely
require GPS to allow the response of a given bridge to be identified; this study looks at the
feasibility of using low-cost GPS sensors for this purpose, via field trials. The three topics
outlined above cover a spectrum of SHM approaches namely, wired monitoring, contactless
monitoring and drive by monitoring

Land, Power and Technology : Essays on Political Economy and Historical Development

Land Ownership and Development: Evidence from Postwar Japan This paper analyzes the effect of land ownership on technology adoption and structural transformation. A large-scale land reform in postwar Japan enforced a large number of tenant farmers who were cultivating land to become owners of this land. I find that the municipalities which had many owner farmers after the land reform tended to experience a quick entry of new agricultural machines which became available after the reform. The adoption of the machines reduced the dependence on family labor, and led to a reallocation of labor from agriculture to industries and service sectors in urban centers when these sectors were growing. I also analyze the aggregate impact of labor reallocation on economic growth by using a simple growth model and micro data. I find that it increased GDP by about 12 percent of the GDP in 1974 during 1955-74. I also find a large and positive effect on agricultural productivity. Loyalty and Treason: Theory and Evidence from Japan's Land Reform A historically large-scale land reform in Japan after World War II enforced by the occupation forces redistributed a large area of farmlands to tenant farmers. The reform demolished hierarchical structures by weakening landlords' power in villages and towns. This paper investigates how the change in the social and economic structure of small communities affects electoral outcomes in the presence of clientelism. I find that there was a considerable decrease in the vote share of conservative parties in highly affected areas after the reform. I find the supporting evidence that the effect was driven by the fact that the tenant farmers who had obtained land exited from the long-term tenancy contract and became independent landowners. The effect was relatively persistent. Finally, I also find the surprising result that there was a decrease, rather than an increase, in turnout in these areas after the reform.  Geography and State Fragmentation We examine how geography affects the location of borders between sovereign states in Europe and surrounding areas from 1500 until today at the grid-cell level. This is motivated by an observation that the richest places in this region also have the highest historical border presence, suggesting a hitherto unexplored link between geography and modern development, working through state fragmentation. The raw correlations show that borders tend to be located on mountains, by rivers, closer to coasts, and in areas suitable for rainfed, but not irrigated, agriculture. Many of these patterns also hold with rigorous spatial controls. For example, cells with more rivers and more rugged terrain than their neighboring cells have higher border densities. However, the fragmenting effects of suitability for rainfed agriculture are reversed with such neighbor controls. Moreover, we find that borders are less likely to survive over time when they separate large states from small, but this size-difference effect is mitigated by, e.g., rugged terrain.