Craig Hamilton and Rebecca Moore in a Faculty Recital

This is the program for the faculty recital featuring trumpet player Craig V. Hamilton and pianist Rebecca Moore. Trumpet player Jim Lloyd assisted the performance. This recital took place on September 29, 2003, in the McBeth Recital Hall

New injectable scaffolds for cell and drug delivery

An injectable scaffold system for the delivery of cells and growth factors was developed in this project to enhance healing of bone fractures. The project was focused to meet the clinical need for an off-the-shelf synthetic biodegradable bone graft material. The concept required the injection of a paste to fill defects then rapidly solidify to a mechanically supportive macroporous structure. The injectable paste was developed from a two-component biodegradable microparticle scaffold based on poly(lactic-co-glycolic acid) (PLGA) and comprised of a versatile temperature insensitive (type 1) carrier and an adhesive (type 2) component made temperature sensitive with the addition of poly(ethylene glycol) (PEG) as a plasticizer. The plasticized adhesive type 2 component achieved wet compressive strengths up to 18 MPa at 37 °C after 24 hours. The sintering strategy utilised the changes in viscoelastic and mechanical properties that occur in the glass transition region of amorphous polymers. The specific mechanism devised in this thesis exploited the biocompatibility and diffusivity of PEG to increase polymer glass transition temperature in the wet sintering process. The solidification speed was demonstrated by rheological assessment of storage modulus and wet compressive strengths up to 2 MPa after 15 minutes at 37 °C. Restricting particle size distribution to narrow 100 µm bands controlled porosity between 35-65%. The interconnectivity of the macroporous structures was demonstrated by the invasion of 3T3 cells seeded on the outer surface of the scaffold and evaluated by microcomputed tomography. The innocuous nature of the solidification process was demonstrated by the survival and proliferation of in situ seeded primary human fibroblasts, osteoblasts and murine C2C12 cells. The multifunctional type 1 component acted as a porous spacer, protein delivery vehicle and cell carrier when modified with polyethylenimin. The potential use of the scaffold as a controlled delivery system for recombinant human bone morphogenetic protein-2 (rhBMP-2) was demonstrated by the sustained differentiation of murine C2C12 myoblast to osteogenic alkaline phosphatase positive cells over 28 days. In this thesis a novel sintering mechanism has been developed that facilitates control of pore size and porosity of injectable scaffolds. The benign nature of the process facilitates the potential use of this injectable system as a delivery vehicle for cell and growth factor therapy

Investigating the anti-tumour effects of macrophages in the zebrafish brain

Glioblastoma (GBM) remains an incurable tumour fraught with a high probability of death. One of the key characteristic of GBM is the development of local immunosuppression that promotes immune evasion and lays a solid foundation for the tumour to progress. Breakthroughs in our understanding in cancer biology have shown that GBM have evolved unique mechanisms that influence infiltrating macrophages, a key immune cell type, to facilitate tumour progression. Macrophages have been identified in many studies to promote angiogenesis, extra cellular matrix reorganisation, establishment of local immunosuppression and tumour growth. Thus, there is great need to improve the clinical development of immunotherapeutics that can address tumour-specific immune responses. Herein, we tested the capability of solidly supported Gold and Palladium nanoparticles as biorthogonal catalytic converters of prodrugs in a zebrafish U87 glioblastoma xenograft model. Intriguingly, we report that the implantation of Palladium and Gold bead into the zebrafish brain causes a potent anti-tumour responses that leads to U87 cell clearance, fragmentation and increased macrophage number. Further investigation revealed that Gold and Palladium beads did not cause aberrant necrosis when implanted in the zebrafish brain and that macrophages played a key role in mediating the associated anti-tumour response of Palladium and Gold bead implantation. The role of macrophages was investigated further using Next Generation RNA sequencing of macrophages isolated from Palladium bead implanted zebrafish. RNA sequencing results revealed differentially expressed genes in Palladium bead implanted zebrafish with 389 genes upregulated and 361 genes downregulated. Enrichment analysis of these genes showed significant enrichment of oxidation-reduction processes as a result of Palladium bead implantation. In addition, confirmatory RT-qPCR highlighted two key TLR signalling inflammatory genes, Cxcl8b.1 and TNF-α, to be overexpressed in macrophages of Palladium and Gold bead implanted zebrafish. Since Cxcl8b.1 is a potent attractant of neutrophils, we studied the dynamics of macrophages and neutrophil number in the zebrafish brain. Indeed, we detected an accumulation of neutrophils upon gold bead transplantation. Thus, we analysed the role of Cxcl8b.1 and TNF-α in the initiation of the anti-tumour effect. This was achieved by com- bining CRISPR-Cas9 knock out and genetic overexpression transgenesis techniques of Cxcl8b.1 and TNF-α. The results here conclude that TNF-α were not key genetic mediators of the associated bead induced anti-tumour phenotype. Finally, this study opens new ave- nues for the development of novel cancer immunotherapeutics. RNA sequencing results showed high number of other candidate genes that exploit the intrinsic capabilities of transitions metals to initiate an anti-tumour response

Coherent electronic transfer in quantum dot systems using adiabatic passage

We describe a scheme for using an all-electrical, rapid, adiabatic population transfer between two spatially separated dots in a triple-quantum dot system. The electron spends no time in the middle dot and does not change its energy during the transfer process. Although a coherent population transfer method, this scheme may well prove useful in incoherent electronic computation (for example quantum-dot cellular automata) where it may provide a coherent advantage to an otherwise incoherent device. It can also be thought of as a limiting case of type II quantum computing, where sufficient coherence exists for a single gate operation, but not for the preservation of superpositions after the operation. We extend our analysis to the case of many intervening dots and address the issue of transporting quantum information through a multi-dot system.Comment: Replaced with (approximately) the published versio

Late Glacial to Holocene relative sea level change in Assynt, northwest Scotland, UK

Relative sea-level change (RSL), from the Late Glacial through to the late Holocene, is reconstructed for the Assynt region, northwest Scotland, based on bio- and lithostratigraphical analysis. Four new radiocarbon-dated sea-level index points help constrain RSL change for the Late Glacial to late Holocene. These new data, in addition to published material, capture the RSL fall during the Late Glacial and the rise and fall associated with the mid-Holocene highstand. Two of these index points constrain the Late Glacial RSL history in Assynt for the first time, reconstructing RSL falling from 2.47 ± 0.59 m OD to 0.15 ± 0.59 m OD at c. 14000 - 15000 cal yr BP. These new data test model predictions of glacial isostatic adjustment (GIA), particularly during the early deglacial period which is currently poorly constrained throughout the British Isles. While the empirical data from the mid- to late-Holocene to present matches quite well with recent GIA model output, there is a relatively poor fit between the timing of the Late Glacial RSL fall and early Holocene RSL rise. This mismatch, also evident elsewhere in northwest Scotland, may result from uncertainties associated with both the global and local ice components of GIA models

Goal representation in the infant brain

It is well established that, from an early age, human infants interpret the movements of others as actions directed towards goals. However, the cognitive and neural mechanisms which underlie this ability are hotly debated. The current study was designed to identify brain regions involved in the representation of others’ goals early in development. Studies with adults have demonstrated that the anterior intraparietal sulcus (aIPS) exhibits repetition suppression for repeated goals and a release from suppression for new goals, implicating this specific region in goal representation in adults. In the current study, we used a modified paired repetition suppression design with 9-month-old infants to identify which cortical regions are suppressed when the infant observes a repeated goal versus a new goal. We find a strikingly similar response pattern and location of activity as had been reported in adults; the only brain region displaying significant repetition suppression for repeated goals and a release from suppression for new goals was the left anterior parietal region. Not only does our data suggest that the left anterior parietal region is specialized for representing the goals of others’ actions from early in life, this demonstration presents an opportunity to use this method and design to elucidate the debate over the mechanisms and cues which contribute to early action understanding

Rising numbers of older and female cannabis users seeking treatment in England and Wales

Presentations to specialist drug treatment services in England for cannabis have been rising in recent years. As cannabis is no longer disaggregated in annual reports of drug treatment presentations published by Public Health England, we requested access to a detailed data-set to explore the treatment population in more detail. Analysis of the data revealed two important issues which were not apparent in the published reports. Males and females over the age of 40 are a rapidly growing sub-group. This reflects the parallel growth in those in treatment primarily for problems due to opiates

“The People Who Leave Here Are Not the People Who Arrived.”: A Qualitative Analysis of the Therapeutic Process and Identity Transition in the Offender Personality Disorder Pathway

Individuals with personality disorder are often construed as difficult to treat, and sometimes even “untreatable.” In this study, 24 men who had completed treatment on the offender personality disorder treatment pathway participated in focus groups at a high-security prison in the United Kingdom. The results of the data analysis revealed three superordinate themes that captured the impact and experience of the therapeutic process. The three themes were “A self-reconstructed,” which focused on the reconstruing and reconstructions of participants’ identity and how intervention assisted with a coherent narrative of self. The second superordinate theme, “Relational resilience and dealing with abandonment,” relates to the attachment to therapists and the negotiation of relational boundaries and resilience. The third theme, “Reimagining and re-experiencing trauma,” focuses on participants’ exploration and reliving of trauma, and how group processes allowed for shared understanding and a reconstruing of their trauma. Implications for policy and practice are discussed