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.
PEGylation and its impact on the design of new protein-based medicines. - Ginn, C; Khalili, H; Lever, R; Brocchini, S
PEGylation is the covalent conjugation of PEG to therapeutic molecules. Protein PEGylation is a clinically proven approach for extending the circulation half-life and reducing the immunogenicity of protein therapeutics. Most clinically used PEGylated proteins are heterogeneous mixtures of PEG positional isomers conjugated to different residues on the protein main chain. Current research is focused to reduce product heterogeneity and to preserve bioactivity. Recent advances and possible future directions in PEGylation are described in this review. So far protein PEGylation has yielded more than 10 marketed products and in view of the lack of equally successful alternatives to extend the circulation...
Human corneal stromal stem cells exhibit survival capacity following isolation from stored organ-culture corneas. - Kureshi, AK; Funderburgh, JL; Daniels, JT
To assess the suitability of human donor corneas maintained in long-term organ culture for the isolation and expansion of viable and functional corneal stromal stem cells (CSSCs). These cells display properties similar to mesenchymal stem cells and demonstrate the ability to reproduce an organized matrix in vitro. Therefore, CSSCs have great potential for the development of cell-based therapies for corneal blindness or stromal tissue bioengineering.
Operating RegenMed: development of better in-theater strategies for handling tissue-engineered organs and tissues. - Fishman, JM; Wormald, JC; Lowdell, MW; Coppi, PD; Birchall, MA
Tissue engineering ex vivo and direct cellular application with bioscaffolds in vivo has allowed surgeons to restore and establish function throughout the human body. The evidence for regenerative surgery is growing, and consequently there is a need for the development of more advanced regenerative surgery facilities. Regenerative medicine in the surgical field is changing rapidly and this must be reflected in the design of any future operating suite. The theater environment needs to be highly adaptable to account for future significant advances within the field. Development of purpose built, combined operating suites and tissue-engineering laboratories will provide the facility for...
Comparison of DSM-IV and Proposed ICD-11 Formulations of PTSD Among Civilian Survivors of War and War Veterans. - Morina, N; van Emmerik, AA; Andrews, B; Brewin, CR
The World Health Organization recently proposed a reformulation of posttraumatic stress disorder (PTSD) for the 11(th) edition of the International Classification of Diseases (ICD-11), employing only 6 symptoms. The aim of this study was to investigate the impact of this reformulation of PTSD as compared to criteria according to Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV; American Psychiatric Association, 1994) on the prevalence of current PTSD as well as comorbid major depressive episode and anxiety disorders other than PTSD. Study 1 involved previously collected interviews with 560 Kosovar civilian war survivors; Study 2 employed a previously collected...
Detection and correction of artefacts in estimation of rare copy number variants and analysis of rare deletions in type 1 diabetes. - Cooper, NJ; Shtir, CJ; Smyth, DJ; Guo, H; Swafford, AD; Zanda, M; Hurles, ME; Walker, NM; Plagnol, V; Cooper, JD; Howson, JM; Burren, OS; Onengut-Gumuscu, S; Rich, SS; Todd, JA
Copy number variants (CNVs) have been proposed as a possible source of 'missing heritability' in complex human diseases. Two studies of type 1 diabetes (T1D) found null associations with common copy number polymorphisms, but CNVs of low frequency and high penetrance could still play a role. We used the Log-R-ratio intensity data from a dense single nucleotide polymorphism (SNP) array, ImmunoChip, to detect rare CNV deletions (rDELs) and duplications (rDUPs) in 6808 T1D cases, 9954 controls and 2206 families with T1D-affected offspring. Initial analyses detected CNV associations. However, these were shown to be false-positive findings, failing replication with polymerase chain...
Uncovering many-body correlations in nanoscale nuclear spin baths by central spin decoherence. - Ma, WL; Wolfowicz, G; Zhao, N; Li, SS; Morton, JJ; Liu, RB
Central spin decoherence caused by nuclear spin baths is often a critical issue in various quantum computing schemes, and it has also been used for sensing single-nuclear spins. Recent theoretical studies suggest that central spin decoherence can act as a probe of many-body physics in spin baths; however, identification and detection of many-body correlations of nuclear spins in nanoscale systems are highly challenging. Here, taking a phosphorus donor electron spin in a (29)Si nuclear spin bath as our model system, we discover both theoretically and experimentally that many-body correlations in nanoscale nuclear spin baths produce identifiable signatures in decoherence of...
A role for the outer retina in development of the intrinsic pupillary light reflex in mice. - Vugler, A; Semo, M; Ortín-Martínez, A; Rojanasakul, A; Nommiste, B; Valiente-Soriano, FJ; García-Ayuso, D; Coffey, P; Vidal-Sanz, M; Gias, C
Mice do not require the brain in order to maintain constricted pupils. However, little is known about this intrinsic pupillary light reflex (iPLR) beyond a requirement for melanopsin in the iris and an intact retinal ciliary marginal zone (CMZ). Here, we study the mouse iPLR in vitro and examine a potential role for outer retina (rods and cones) in this response. In wild-type mice the iPLR was absent at postnatal day 17 (P17), developing progressively from P21-P49. However, the iPLR only achieved ∼30% of the wild-type constriction in adult mice with severe outer retinal degeneration (rd and rdcl). Paradoxically, the...
The development and future of reconstructive and microvascular surgery of the hand. - Malahias, M; Jordan, DJ; Hindocha, S; Khan, W; Juma, A
The hand is often thought of as a key discriminator in what makes humans human. The hand is both intricate and fascinating in its design and function, allowing humans to interact with their surroundings, and each other. Due to its use in manipulation of the person's environment, injury to the hand is common. Devastating hand injuries have a profound, physical, psychological, ﬁnancial and socially crippling effect on patients. Advances in operative techniques and improvements in microscopes and instruments allowed Malt &McKhann to perform the first successful arm replantation in 1962 . This was followed by a myriad of autologous free...
Orthopaedic approaches to proximal humeral fractures following trauma. - Mafi, R; Khan, W; Mafi, P; Hindocha, S
Proximal humeral fractures have been a topic of discussion in medical literature dating back as far as 3rd century BC. Today, these fractures are the most common type of humeral fractures and account for about 5-6% of all fractures in adults with the incidence rising rapidly with age. In broad terms the management of proximal humeral fractures can be divided into two categories: conservative versus surgical intervention. The aim of treatment is to stabilize the fracture, aid better union and reduce pain during the healing process. Failure to achieve this can result in impairment of function, and significantly weaken the...
The ortho-plastic approach to soft tissue management in trauma. - Jordan, DJ; Malahias, M; Khan, W; Hindocha, S
Fractures with associated soft tissue injuries, or those termed 'open,' are not uncommon. There has been much discussion regarding there management, with the guidance from the combined British Orthopaedic Association and British Association and Aesthetic Surgeons teams widely accepted as the gold level of therapy. We aim to discuss the current evidence about the initial management of this group of injuries, taking a journey from arrival in the accident and emergency department through to the point of definitive closure. Other modes of therapy are also reviewed.
Relatedness in the post-genomic era: is it still useful? - Speed, D; Balding, DJ
Relatedness is a fundamental concept in genetics but is surprisingly hard to define in a rigorous yet useful way. Traditional relatedness coefficients specify expected genome sharing between individuals in pedigrees, but actual genome sharing can differ considerably from these expected values, which in any case vary according to the pedigree that happens to be available. Nowadays, we can measure genome sharing directly from genome-wide single-nucleotide polymorphism (SNP) data; however, there are many such measures in current use, and we lack good criteria for choosing among them. Here, we review SNP-based measures of relatedness and criteria for comparing them. We discuss...
Interdependence of Utility and Probability Estimates: The Role of Social Power in Distinguishing Theories - De Moliere, L
This thesis aims to identify mechanisms underlying the impact of negative utility on probability estimates (Harris, Corner, & Hahn, 2009). In particular, we investigated evidence for arousal misattribution (Vosgerau, 2010) by examining a moderation by interoceptive ability. Furthermore, we investigated an account of loss function asymmetry (e.g., Weber, 1994) by examining the role of decision-control. Important to the current aims, social power is related to both interoception and control. Power increases interoceptive awareness (Moeini-Jazani, Knöpferle, de Molière, Gatti & Warlop, 2014) and one’s personal sense of control (Fast, Gruenfeld, Sivanathan, & Galinsky, 2009). Thus, we examined whether power moderates the...
A Genetic and Functional Investigation of Inherited Neuropathies: Charcot-Marie Tooth Disease and Brown-Vialetto-Van Laere Syndrome - Pandraud, A
Charcot-Marie-Tooth (CMT) disease and Brown-Vialetto-Van Laere syndrome (BVVL) are two inherited neuropathies. Although most CMT type 1A patients carry the same sized duplication containing the peripheral myelin protein 22 (PMP22) gene, they present with a wide range of severities both within and between families. Some CMT1A patients exhibit chronic inflammatory demyelinating polyneuropathy (CIDP)-like features. An association study was performed in a CMT1A and a CIDP cohort to identify the genetic factors modifying the CMT1A phenotype. Variants associated with CIDP and/or with autoimmune/inflammatory diseases were determined to be unlikely to modulate disease severity in CMT1A, or to contribute to CMT1A pathogenesis....
Bul and Kul are novel components of the Dachsous-Fat planar polarity system - Rodrigues Campos, M
The atypical cadherins Dachsous (Ds) and Fat (Ft) form a system of planar cell polarity that controls the shape of tissues and organs in animals. These cadherins become planar polarised in response to opposing gradients of ds and four jointed (fj) and lead to the downstream polarisation of Dachs, an atypical myosin. Polarisation of Dachs is critical for orientation of cell division and tissue elongation. Even though the proximal-distal gradients are critical, some additional mechanism must exist in order to generate a robust planar polarisation. Via an RNAi screen in the Drosophila wing, we identify two novel components of the...
Next generation sequencing approaches to identify novel susceptibility genes for epithelial ovarian cancer - Hayward, JD
Ovarian cancer is the fifth most common cancer in women in developed countries and is associated with poor survival due to late diagnoses. Strategies focusing on detecting the disease in the earliest stages and/or improving risk prediction may represent effective clinical intervention reducing disease burden. Women at the greatest risk of epithelial ovarian cancer (EOC) can be offered prophylactic risk-reducing salpingo-oopherectomy (RRSO), which is currently only offered to women with mutations in the highly penetrant susceptibility genes BRCA1 or BRCA2. Previous studies show that 46% of familial cases of EOC carry a deleterious mutation in BRCA1 (37%) or BRCA2 (9%)....
Polythiophene nanofibres for optoelectronic applications - Seidler, N
This thesis reports on the fabrication and characterisation of self-assembled nanofibres of poly(3-hexylthiophene) (P3HT), and demonstrates how these nanofibres can be used in applications like thin-film transistors and solar cells. The first results chapter describes a preparation method of P3HT nanofibres in a solution of chlorobenzene by using di-tert butyl peroxide (DTBP) as an additive. This method allows the fabrication of films of P3HT with high molecular order and gives control over the film retention. The films are characterised using a range of experimental techniques, including optical absorption, X-ray diffraction and atomic force microscopy, which also allows to determine the...