UCL University College London Eprints
UCL Eprints collects the work of UCL researchers and makes it freely available over the web, helping the worldwide scholarly community to discover UCL research. Institutional repositories like UCL Eprints complement the traditional academic publishing and scholarly communications processes. They raise the visibility of research and help to maximise its impact. UCL researchers are encouraged to deposit a copy of each journal article, conference paper, working paper, and any other research output, in the UCL Eprints at the earliest opportunity, ensuring that their research reaches as wide an audience as possible.
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Solution structure and stabilities of rabbit and human IgG - Rayner, LE
Immunoglobulin G (IgG) is the most abundant antibody class in serum, and in humans is present as four subclasses, IgG1- 4, which have distinct properties. IgG binds to antigens via its two Fab regions, and to its effector ligands via its Fc region. IgG is also widely used as a pharmaceutical due to its specific binding to targets. Solution scattering and constrained modelling, along with analytical ultracentrifugation, were used to determine IgG structures in solution. Rabbit IgG was shown to have an asymmetric solution structure, and these structures explained the ability of its two ligands, the Fc receptor and complement...
In vitro and in vivo studies of RNA recognition by Rna15 - Robertson, LE
For successful gene expression in eukaryotes, mRNA transcripts are processed in the 5’ and 3’ untranslated regions (UTRs) and non-coding mRNA is spliced out. These processes are crucial in determining the fate of the mRNA transcript. Rna14 and Rna15 are subunits of Cleavage factor 1A (CF1A) and required for 3’ end processing in S. cerevisiae. Structural and biophysical data have determined a number of residues within the RNA recognition motif (RRM) of Rna15 that interact directly with RNA. However, although the crystal structure of the RRM revealed a mechanism for the preferential recognition of G/U nucleotides by Rna15 the sequence...
Analysis of HIV-1 Assembly on Intracellular Plasma Membrane-connected Compartments of Primary Human Macrophages - Nkwe, DO
In primary human monocyte-derived macrophages (MDM), HIV assembles on complex intracellular plasma membrane-connected compartments (IPMCs). Currently, it is unclear whether, in addition to assembly at IPMCs, HIV uses the cell surface of MDM, as viruses that bud at the cell surface may dissociate and be lost from the samples. As the endosomal sorting complex required for transport (ESCRT) machinery is required for the final scission events that release assembled virus from the plasma membrane, this question was addressed by depleting the ESCRT components Tsg101 and ALIX, or generating mutant HIV-1 strains defective in recruiting the ESCRT machinery, to arrest HIV...
A values-driven and evidence-based health care psychology for diverse sex development - Liao, L-M; Simmonds, M
The integration of psychology into multidisciplinary care for people affected by 'disorders of sex development' is acknowledged in most recent care standard documents. However, psychological evidence that can inform service development is currently insubstantial for specific reasons, some of which are outlined in this article. We argue for psychological activities and their prioritisation to be equally driven by the professional values embedded in clinical psychology and to seek user input in key activities. These values include critical engagement with research literature, theoretically informed question and problem formulation, development of interventions to boost health and well-being, honouring of personal agency, equality...
Radical Trust Works: An Investigation of Digital Visitor Generated Content and Visitor Engagement in Museum Spaces - Ross, CS
Visitor generated content projects are becoming increasingly significant in the development and delivery of engaging visitor experiences in museums in the UK, but the rationale behind them and the impact they are having on not only visitor engagement but also museum practice are not always clear. There is a requirement to understand and articulate the impact of digital visitor co-creation in the museum environment and to discuss the challenges of implementing digital innovation projects in museums and the implications this has on institutional change. This thesis presents an investigation into the potential of digital visitor generated content applications in museum...
Cultural transmission of lithic artefact traditions: an experimental approach - Page, SN
Experimental methods for exploring the idea that cultural variation can be explained as part of a process analogous to that of biological evolution have been used in psychology to examine how human copying error effects the transmission of simple artefact form. Applying these methods in an archaeological framework, this study is the first of its kind to develop a programme of transmission chain experiments exploring different aspects of skill, social interaction and copying error and their effect on the evolution of artefact form in two different Palaeolithic technologies: blade production and Acheulean handaxe manufacture. In the blade replication experiment, form...
Sequential pregnancies among women living with HIV in the United Kingdom and Ireland - French, CE
This thesis investigates the epidemiology of sequential pregnancies among HIV-positive women in the United Kingdom and Ireland, and explores the health, therapeutic and obstetric management, and pregnancy outcomes, of the women experiencing them. Data from the UK and Ireland’s National Study of HIV in Pregnancy and Childhood (NSHPC) are analysed. This is a well-established, active, comprehensive national surveillance study with over 1500 pregnancies currently reported each year. The findings demonstrate that a substantial and increasing proportion of pregnancies are women’s second or subsequent since their HIV diagnosis (39% in 2009), with a rate of 6.7 (95% CI: 6.5-6.9) per 100...
Multitask and transfer learning for multi-aspect data - Romera Paredes, B
Supervised learning aims to learn functional relationships between inputs and outputs. Multitask learning tackles supervised learning tasks by performing them simultaneously to exploit commonalities between them. In this thesis, we focus on the problem of eliminating negative transfer in order to achieve better performance in multitask learning. We start by considering a general scenario in which the relationship between tasks is unknown. We then narrow our analysis to the case where data are characterised by a combination of underlying aspects, e.g., a dataset of images of faces, where each face is determined by a person's facial structure, the emotion being...
Advance care planning in dementia: understanding the preferences of people with dementia and their carers - Harrison Dening, K
The UK End of Life Care Strategy proposed that all people should identify preferences for end of life care. Aims To explore whether family carers of a person with dementia (PWD) can accurately predict their preferences for end of life care and what factors influence this. Methods: This mixed methods study began with nominal groups to explore if PWD and carers could generate and prioritise preferences for end of life care and how much carers influenced the PWD’s choices. The second phase involved 60 dyad interviews using a modified Life Support Preferences Questionnaire to assess whether carers of PWD could...
Literary transmissions and the fate of a topic: the continental spa in post-1840 British, Russian and American writing - Morgan, BD
Around 1840 the Continental watering place took off as a destination of international appeal—and as a topic in an internationalizing print culture. My thesis, drawing on a broad range of theories of intertextuality, uses the case of the waters to model the farrago of transmissions, contacts and collisions that go into the making of a common-place in discourse. In particular I show how writing from multiple genres and national literatures helped establish the spa's identity as a deeply ambivalent locus of encounter—a venue that both tickled and deflated cosmopolitan ambition. Key points of reference include Dostoevskii'sThe Gambler, Edmund Yates's sensation...
When a close friend or relative dies by suicide: the impact on mental health and social functioning of young adults - Pitman, AL
Introduction: Provision of support for people bereaved by suicide has become a key priority for suicide prevention strategies in many developed countries. Few studies have measured whether suicide bereavement increases risk of suicidal behaviour compared with bereaved controls. Methods: I sampled 659,572 staff and students at 37 UK higher education institutions in 2010. Via mass email, I invited adults who had experienced a sudden bereavement to complete an online survey measuring post-bereavement suicidal ideation and attempts, and other psychosocial outcomes. Inclusion criteria were: current age 18-40 years, and sudden bereavement of a close contact since the age of 10 years....
Improving the quality and security of probabilistic search in peer-to-peer information retrieval systems - Richardson, SA
Commercial web search engines typically use a centralised architecture, where machines are kept at centralised server facilities and are under the control of a central authority. This requires high capital and operating costs, potentially deterring new entrants from offering competing services. A promising alternative is to host the search engine on a peer-to-peer (P2P) network. Volunteers can add their machines as peers, essentially providing computing resources for free. However, search quality and security against malicious behaviour is lower than for a centralised system. This thesis addresses these issues for an unstructured P2P architecture. To improve search quality we develop techniques...
Cross-sectional imaging of metal-on-metal hip arthroplasties. Can we substitute MARS MRI with CT? - Robinson, E; Henckel, J; Sabah, S; Satchithananda, K; Skinner, J; Hart, A
Metal artifact reduction sequence (MARS) MRI is widely advocated for surveillance of metal-on-metal hip arthroplasties (MOM-HAs). However, its use is limited by susceptibility artifact at the prosthesis-bone interface, local availability, patient compliance, and cost (Hayter et al. 2011a). We wanted to determine whether CT is a suitable substitute for MARS MRI in evaluation of the painful MOM-HA.
Body ownership causes illusory self-attribution of speaking and influences subsequent real speaking. - Banakou, D; Slater, M
When we carry out an act, we typically attribute the action to ourselves, the sense of agency. Explanations for agency include conscious prior intention to act, followed by observation of the sensory consequences; brain activity that involves the feed-forward prediction of the consequences combined with rapid inverse motor prediction to fine-tune the action in real time; priming where there is, e.g., a prior command to perform the act; a cause (the intention to act) preceding the effect (the results of the action); and common-sense rules of attribution of physical causality satisfied. We describe an experiment where participants falsely attributed an...
Two-pore channels provide insight into the evolution of voltage-gated Ca2+ and Na+ channels. - Rahman, T; Cai, X; Brailoiu, GC; Abood, ME; Brailoiu, E; Patel, S
Four-domain voltage-gated Ca(2+) and Na(+) channels (CaV, NaV) underpin nervous system function and likely emerged upon intragenic duplication of a primordial two-domain precursor. To investigate if two-pore channels (TPCs) may represent an intermediate in this evolutionary transition, we performed molecular docking simulations with a homology model of TPC1, which suggested that the pore region could bind antagonists of CaV or NaV. CaV or NaV antagonists blocked NAADP (nicotinic acid adenine dinucleotide phosphate)-evoked Ca(2+) signals in sea urchin egg preparations and in intact cells that overexpressed TPC1. By sequence analysis and inspection of the model, we predicted a noncanonical selectivity filter...
A phase II study to determine the efficacy and safety of oral treosulfan in patients with advanced pre-treated Ewing sarcoma ISRCTN11631773. - Michelagnoli, M; Whelan, J; Forsyth, S; OTIS Trial Management Group, Site Investigators,
We report a prospective Phase II study of efficacy and toxicity for oral treosulfan in advanced Ewing sarcoma. Twenty patients, median age 19 years (range 7-39) from five UK sites, were treated with oral treosulfan 1 g/m(2) daily for 7 days in 28. Primary endpoint was objective response rate. Best response was stable disease in one patient. All patients died of progressive disease, after median 6.41 months. Median progression free survival was 1.8 months. Toxicity was minimal. No activity was demonstrated for treosulfan at this dose. Progression free survival data should be able to be used for comparison when planning...
CMV-specific T cell isolation from G-CSF mobilized peripheral blood: depletion of myeloid progenitors eliminates non-specific binding of MHC-multimers. - Beloki, L; Ciaurriz, M; Mansilla, C; Zabalza, A; Perez-Valderrama, E; Samuel, ER; Lowdell, MW; Ramirez, N; Olavarria, E
BackgroundCytomegalovirus (CMV)-specific T cell infusion to immunocompromised patients following allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is able to induce a successful anti-viral response. These cells have classically been manufactured from steady-state apheresis samples collected from the donor in an additional harvest prior to G-CSF mobilization, treatment that induces hematopoietic stem cell (HSC) mobilization to the periphery. However, two closely-timed cellular collections are not usually available in the unrelated donor setting, which limits the accessibility of anti-viral cells for adoptive immunotherapy. CMV-specific cytotoxic T cell (CTL) manufacture from the same G-CSF mobilized donor stem cell harvest offers great regulatory advantages, but...
Atypical parkinsonism: diagnosis and treatment. - Stamelou, M; Bhatia, KP
Atypical parkinsonism comprises typically progressive supranuclear palsy, corticobasal degeneration, and mutilple system atrophy, which are distinct pathologic entities; despite ongoing research, their cause and pathophysiology are still unknown, and there are no biomarkers or effective treatments available. The expanding phenotypic spectrum of these disorders as well as the expanding pathologic spectrum of their classic phenotypes makes the early differential diagnosis challenging for the clinician. Here, clinical features and investigations that may help to diagnose these conditions and the existing limited treatment options are discussed.