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Organic semiconductors : optical amplification, lasing and soft lithography
Get PDFThis thesis presents an investigation of optical amplification and lasing in con jugated polymers and novel dendritic organic semiconductors. Novel methods of producing useful wavelength scale microstructure in these materials are also examined. Conjugated materials are a new class of semiconductors that show great potential for tuneable lasers, displays and photovoltaics.
Conjugated polymers have received interest as novel laser gain media be cause they exhibit optical gain over broad spectral ranges and are easy to process. However, there had been no demonstration of an polymer optical amplifier. A broadband solution based optical amplifier is demonstrated. The effect of pump energy, probe energy and solution concentration are examined. Progress towards a solid state polymer amplifier is discussed. Such devices would be useful in ultrafast data communications due to the possibility of gain over a broad spectral range.
Wavelength scale microstructure can be used to control and manipulate light. To realise microstructured organic semiconductor devices, complex fabrication methods are used which remove the ease of processability that is a key advantage of organic materials. Simple techniques to pattern organic semiconductors directly are demonstrated. Solvent assisted micromoulding is used to fabricate polymer distributed feedback lasers in less than two minutes.
Recently a new class of materials have been developed called dendrimers. Their branched modular architecture allows for the independent tuning of the electrical, optical and processing properties. Strong amplification in both solutions and thin films of a bis-fluorene cored dendrimer have been demonstrated. DFB lasers were also fabricated and lower threshold and higher output power were achieved by increasing the dendrimer generation and by changing from etched silica substrates to directly imprinted DFB structures. These advances in organic semiconductor materials and device fabrication should lead to new applications in optoelectronics
DEER measurements of calmodulin : novel spin labels and structural insights
No full textDouble electron-electron resonance (DEER) spectroscopy is a biophysical technique used in structural biology. It allows nanometre scale distance measurements between spin labels containing unpaired electrons. In this thesis, DEER was employed to investigate the structure and behaviour of calmodulin, a calcium binding protein with significant functional and physiological importance.
Following an introduction to the theoretical background and methodologies, the experimental work is organised around three main research questions. The first experimental chapter explores the use of bifunctional spin labelling of vicinal cysteines with a next-generation maleimide spin label. This approach aimed to reduce linker flexibility and to establish a viable labelling strategy for cysteine rich proteins.
The second experimental section investigates the DEER characteristics of five Gd(III) spin labels, both well established and new molecules, measured on two calmodulin mutants, engineered to yield a short and respectively a long distance distribution. This study also compares sensitivity between two home-built W-band spectrometers and a commercial Q-band instrument.
The final part examines the behaviour of calmodulin in a synthetic macromolecular crowding environment, combining DEER measurements of four apo and holo calmodulin mutants with computational modelling to assess the structural changes."The work presented in this thesis was funded by Engineering and Physical Sciences Research Council (EPSRC) EP/ N509759/1. The part of work conducted in collaboration with Weizmann Institute of Science, Israel was sponsored by the Bluston Making Connections (UK-WIS) scheme, The Royal Society (International Exchanges) and the Carnegie Trust."--Fundin
Machine learning whole slide image analysis for the prediction of colorectal cancer biomarkers
No full textColorectal cancer (CRC) is the second leading cause of cancer death worldwide, and incidence is predicted to rise sharply in the next decade. Precision oncology requires the identification of clinically actionable biomarkers such as MMR/MSI status and KRAS, NRAS and BRAF mutations, however immunohistochemistry and sequencing are slow and costly. This thesis shows that machine learning algorithms can rapidly and inexpensively predict these biomarkers directly from routine haematoxylin and eosin whole slide images (WSI), potentially accelerating triage for confirmatory testing and shortening the route to targeted therapy.
Baseline tissue segmentation and slide-level tumour detection are established using fully supervised convolutional networks. A data constrained experiment then evaluates three foundation models (CTransPath, Phikon and UNI) on 423 CRC slides, confirming that self-supervised representations support reliable biomarker prediction when data are scarce. Next, the thesis introduces SurGen, a public dataset of 1020 slides from 843 patients with genetic and survival annotations, released with fully reproducible code exemplars, lowering the barrier to entry for future researchers.
An extensive generalisation study trains transformer aggregators on embeddings from UNI, UNI2-h and Virchow2 across five cohorts: TransSCOT, SurGen, TCGA-CRC, CPTAC-COAD and ORION. Models achieve state-of-the-art AUROC of 0.81778 for KRAS, 0.72108 for NRAS 0.92828 for BRAF, and 0.9559 for MSI within individual cohorts, and retain high accuracy when applied to unseen datasets. A two stage hyper-parameter search reduces computation by a factor of twenty without sacrificing performance.
The thesis supplies the first openly accessible large scale CRC WSI resource with genomics and outcomes, rigorous baselines for both data-rich and data-scarce settings, and the most extensive evaluation to date of foundation model transfer in colorectal pathology. Combining open data with extensive experimentation and thorough benchmarking, this thesis advances WSI biomarker detection towards clinical triage workflow, potentially expediting access to personalised care for colorectal cancer patients."I would like to thank NHS Lothian for funding the work carried out in this thesis. This work is supported in part by the Industrial Centre for AI Research in Digital Diagnostics (iCAIRD) which is funded by Innovate UK on behalf of UK Research and Innovation (UKRI) (project number 104690)."--Fundin
An investigation into some characteristics of the rainfall-subsurface runoff system in an upland catchment : Glendevon, Scotland
Get PDFThe study was aimed at investigating certain aspects of the subsurface hydrology in the Upper Frandy Catchment, Glendevon, Scotland. Examination was directed towards an understanding of the rainfall- throughflow and overlandflow processes as they operate upon the undisturbed slopes of this area.
From a review of the pertinent literature two forms of theoretical analysis were considered. Queueing theory was found to provide a useful conceptualisation of the processes included, but the underlying assumptions of this form of analysis could not be satisfied. Spectral analysis of time series was carried out using the B.M.D. package; however, although the technique appeared a priori to be appropriate, the extremely long runs of observations with value zero which occured in the data undermined its validity.
Data loggers and their ancillary computer programs were developed. Data collection was frought with problems and only one month of usable data was finally available. Due to the discrete nature of the process as recorded, time-series analysis was found to be inappropriate, but even with the underlying unstationarity certain tentative conclusions as to the relative importance of the processes and the delays incorporated in these processes could be drawn.
The spatial makeup of the Upper Frandy was also investigated with an aim to the extension of any models developed for the point process studies. It was shown that this area possesses a highly variable hydrologic space and that any models developed would have to encompass this.
The main aim of the thesis was not met, but instead various forms of analysis have been examined and their limitations to this type of study demonstrated with better data collection techniques, the principles laid down in this study should go a long way to answering the questions posed
Reimagining better addiction treatment services through telemedicine : a complex systems approach
No full textIn 2022, the United States, Scotland and Canada had among the highest drug-related death rates in the world, at 329 per million, 193.3 per million, and 190 per million of the population respectively. The use of Telemedicine to provide Medications for Opioid Use Disorder (TMOUD), such as buprenorphine or methadone, has been identified as an innovation which could increase access to evidence-based treatment. The COVID-19 pandemic saw a sharp rise in the use of TMOUD in North America. In Scotland, despite national efforts to drive telemedicine uptake during the pandemic, the number of addiction-related telemedicine consults fell by 67%. Three peer reviewed publications are presented in this thesis to inform a complex systems understanding of this discrepancy and to identify ways of maximising the potential of TMOUD in mitigating the DRD crisis in Scotland. Paper 1 synthesises the peer-reviewed literature to conceptualise TMOUD as a multifaceted healthcare delivery system. Paper 2 applies Normalisation Process Theory (NPT) to the peer-reviewed literature to understand the work required of stakeholders to embed and normalise TMOUD into routine practice. Paper 3 uses the Successful Healthcare Improvement From Translating Evidence in complex systems (SHIFT-Evidence) framework, collating evidence from Paper 1 and 2 with practice-based knowledge and expert opinion to develop a TMOUD implementation model. This thesis applies the accumulated knowledge from these three papers to make the case for TMOUD in re-imagining addiction treatment services in Scotland. Key findings applicable to both the Scottish and international contexts include the potential for telemedicine to enable low-barrier access, continuity of care, complex care management and improved service resilience. Further, the uptake and spread of TMOUD requires health equity driven, multi-level whole-systems policy and practice interventions which address structural stigma, siloed funding, data and services and power imbalances between clinicians and people who use drugs
Comparison of fluorescent, phosphorescent and TADF luminophores for explosive detection
No full textThe detection of nitroaromatic compounds is crucial for protecting people from explosive hazards, as well as for preserving ecosystems from their toxic effects. Photoluminescence-based sensors offer one approach to detect trace levels of explosives. The detection mechanism is commonly based on a bimolecular interaction between the luminophore and explosive molecule, in which a photoinduced electron transfer (PET) from the luminophore to the analyte causes a quenching of the photoluminescence. The sensitivity and quenching behaviour of the sensor is closely related to the interaction strength between these two compounds, and the emission mechanism of the luminophore.
In this thesis, the influence of the emission mechanisms (fluorescence, phosphorescence, and thermally activated delayed fluorescence - TADF) on the photoluminescent response towards the detection of nitroaromatic explosives was investigated. To evaluate the luminescence quenching kinetics of representative emitters, steady-state and time-resolved photoluminescence measurements are applied in solution and vapour sensing experiments.
The quenching behaviour exhibited by the TADF compounds in solution, was found to deviate from a linear Stern-Volmer relationship, and to be strongly dependent on the intrinsic parameters of the TADF emitter: the product of the initial ISC and RISC quantum yields; the sum of all singlet rate constants; and the sum of all triplet rate constants; with the singlet and triplet populations being quenched with different efficiencies. To model the quenching dynamics of this class of emitters, modified Stern–Volmer equations were derived and applied to different TADF molecules when used as luminophores for sensing a range of PET quenchers.
Vapour sensing was investigated through a combination of steady-state and time-resolved luminescence measurements, showing for the first time that TADF molecules can be used as a sensor for nitroaromatic vapours. These results indicate that in the solid state, the singlet and triplet populations are each quenched by the analyte, and that the temporal response may be modified by blending the luminophore in different polymer hosts.
In summary, the results presented in this thesis demonstrate for the first time the advantages of applying TADF materials as photoluminescent sensors of nitroaromatic compounds and, more broadly, PET quenchers, in both solution and vapour sensing. Besides offering a promising route to significantly increase the sensitivity of PET quencher, the careful monitoring of the singlet and triplet population of TADF quenching systems can be a valuable tool to achieve selectivity in photoluminescence sensors."This work was supported by the University of St Andrews Centre for Doctoral Training in Quantum Materials (QM-CDT) and Edinburgh Instruments Ltd."--Fundin
The SDSS-V Black Hole Mapper Reverberation Mapping project : light echoes of the coronal-line region in a luminous quasar
Get PDFFunding: T.B.S. acknowledges support from a UConn SURF award. L.B.F., J.R.T., M.C.D., and H.W.S. acknowledge support from NSF grants CAREER-1945546 and AST-2007993. Y.S. acknowledges support from NSF grant AST-2009947. F.E.B. acknowledges support from ANID-Chile BASAL CATA FB210003, FONDECYT Regular 1241005, and Millennium Science Initiative, AIM23-0001. J.D.M.’s research was supported by an appointment to the NASA Postdoctoral Program at the NASA Goddard Space Flight Center, administered by Oak Ridge Associated Universities under contract with NASA.We present a reverberation mapping (RM) analysis of the coronal line [Ne v] λ3427-emitting region of the quasar COS168 (SDSS J095910.30+020732.2). [Ne v] λ3427 is known as one of the “coronal lines,” which are a species of emission lines present in active galactic nuclei (AGN) spectra with high ionization potentials (≥ 100 eV) that can serve as tracers for AGN activity. The spatial extent of the coronal line region has been studied with only spatial resolving techniques that are not sensitive to the innermost regions of AGN. Through our RM analysis of [Ne v] λ3427, we measure a nominal “optimal emission radius” for [Ne v] λ3427 of 381.1+16-22 lt-day (observed frame). We place the coronal line region in context with other AGN regions by comparing it with the characteristic radius of Hα, the dust-sublimation radius, and the dusty torus. The coronal line region is located at a larger radius from the black hole than the characteristic radius of the dusty torus, measured using a torus–radius luminosity relationship. The virial product (v2R/G) of both Hα and [Ne v] λ3427 is consistent within the uncertainties, implying that the coronal line region, as probed by the [Ne v] λ3427 line, may be in a virialized orbit that is dominated by the gravitational potential of the black hole. This plausibly suggests that coronal lines could be an effective method for estimating black hole masses.Peer reviewe
Surgical fixation versus non-surgical care for children with a displaced medial epicondyle fracture of the elbow (the SCIENCE study) : a multicentre, randomised controlled, superiority trial and economic evaluation
Get PDFFunding: National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (17/18/02), with additional support from the NIHR Academy, Oxford NIHR Biomedical Research Centre, and the Starship Foundation (New Zealand).Background: Displaced medial epicondyle fractures are among the most controversial injuries in children, with increasing trends towards surgical fixation despite little supporting evidence. Approximately half of affected children undergo surgical fixation, while others receive non-surgical care. The SCIENCE trial aimed to determine whether surgical fixation to restore the position of the bone provides superior functional outcomes and is cost-effective compared with non-surgical care. Methods: We conducted a pragmatic multicentre, randomised, superiority trial across 59 hospitals in the UK, Australia, and New Zealand. Recruiting sites were secondary or tertiary care hospitals providing acute paediatric trauma care. Eligible participants were aged 7-15 years with a displaced medial epicondyle fracture and patients were excluded if the injury occurred more than 2 weeks prior, they had a medial epicondyle fragment that was incarcerated (trapped) within the joint, the injury was part of a complex elbow fracture (ie, extending into the joint), or there were additional fractured bones outside of the elbow. Participants were randomly assigned (1:1) to either surgical fixation or non-surgical care using a web-based randomisation software from Oxford Clinical Trials Research Unit, with minimisation (including a random element) stratified by centre and elbow dislocation status at presentation. Participants and their parents and carers could not be masked to treatment. Surgical fixation was performed under general anaesthesia and involved a surgical incision, restoration of the anatomical alignment, and fixing the fragment, typically with a screw or wires. Non-surgical care involved immobilisation of the elbow at approximately 90° of flexion using a cast, splint, or sling. Both groups were allowed mobilisation as pain allowed, although cast immobilisation beyond 4 weeks was discouraged. The primary outcome was upper limb function at 12 months, measured using the Patient Report Outcomes Measurement System (PROMIS) Upper Extremity Score for Children in the intention-to-treat population, which included all participants in the groups to which they were randomly assigned, irrespective of treatment received. Complications and serious adverse events were summarised in a safety (as-treated) population defined by treatment received. A within-trial economic evaluation was undertaken from the perspective of the UK National Health Service and Personal Social Services over a 12-month time period. The trial was registered with ISRCTN, ISRCTN16619778; recruitment is complete and extended follow-up to age 16 years is ongoing. Findings: Between June 10, 2019, and Sept 22, 2023, 647 patients from 59 sites met the inclusion criteria. 146 patients were excluded (64 due to the injury being more than 2 weeks old and 24 because the epicondyle fragment was incarcerated within the joint), 161 families of children meeting the eligibility criteria declined to participate, and for five patients there was no clinician equipoise. 335 participants were randomly assigned to an intervention (166 to the non-surgical care group and 168 to the surgical fixation group) and one was immediately excluded due to a randomisation error. Primary outcome data were collected from 285 (85%) participants. 170 (51%) participants were female and 164 (49%) were male. Mean participant age at baseline was 11·7 years (SD 2·3). At 12 months post-randomisation, the PROMIS Upper Extremity score was 53·1 (SD 7·8) in the non-surgical care group and 54·3 (5·7) in the surgical fixation group (mean treatment difference, 1·57 [95% CI -0·01 to 3·14; p=0·052]). This estimate of treatment effect was below the clinically important difference specified (4 points), supporting the conclusion that a clinically important effect is unlikely. Additional episodes of surgery, either planned or related to complications, occurred in 24 participants in the surgical group and three in the non-surgical group. Among the 150 participants who underwent surgical fixation, there were 14 intraoperative complications from 13 (9%) participants, and seven participants had a postoperative complication (5% participants) each requiring surgery. Routine screw or wire removal was undertaken in a further 17 (11%) participants. From the 184 participants in the non-surgical group, there were five complications among four (2%) participants, three (2%) of which required additional surgery. The mean per patient cost from the NHS and Personal Social Services perspective was £2435 (95% CI 1812 to 3057) more for participants in the surgical fixation group with a mean per patient quality-adjusted life year difference of -0·008 (95% CI -0·039 to 0·024). The probability that surgical fixation is cost-effective at the £20 000 or £30 000 per quality-adjusted life year willingness-to-pay threshold was 0%. Interpretation: The SCIENCE trial demonstrates that surgical fixation offers no clinical benefit and is not cost-effective compared with non-surgical care, while exposing children to avoidable surgical risks. These findings suggest that non-surgical care should be adopted as the default management strategy for these injuries, regardless of initial elbow dislocation status.Peer reviewe
Mixing and diffusion in protoplanetary disc chemistry
Get PDFFunding: P.W. acknowledges funding from the European Union H2020-MSCA-ITN-2019 under Grant Agreement no. 860470 (CHAMELEON).We develop a simple iterative scheme to include vertical turbulent mixing and diffusion in PRODIMO thermo-chemical models for protoplanetary discs. The models are carefully checked for convergence towards the time-independent solution of the reaction-diffusion equations, as, for example, used in exoplanet atmosphere models. A series of five TTauri disc models is presented where we vary the mixing parameter αmix from zero to 10−2 and take into account: (a) the radiative transfer feedback of the opacities of icy grains that are mixed upwards; and (b) the feedback of the changing molecular abundances on the gas temperature structure caused by exothermic reactions, and increased line heating and cooling. We see considerable changes in the molecular and ice concentrations in the disc. The most abundant species (H2, CH4, CO, the neutral atoms in higher layers, and the ices in the midplane) are transported both up and down, and at the locations where these abundant chemicals finally decompose, for example by photo processes, the release of reaction products has important consequences for all the other molecules. This generally creates a more active chemistry, with a richer mixture of ionised, atomic, molecular, and ice species, and new chemical pathways that are not relevant in the unmixed case. We discuss the impact on three spectral observations caused by mixing and find that: (i) icy grains can reach the observable disc surface where they cause ice absorption and emission features at IR to far-IR wavelengths; (ii) mixing increases the concentrations of certain neutral molecules observable by mid-IR spectroscopy, in particular OH, HCN, and C2H2; and (iii) mixing can change the optical appearance of CO in ALMA line images and channel maps, where strong mixing would cause the CO molecules to populate the distant midplane.Peer reviewe
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