http://www.dspace.cam.ac.uk:80 The DSpace digital repository system captures, stores, indexes, preserves, and distributes digital research material. Fri, 24 May 2013 01:43:14 GMT 2013-05-24T01:43:14Z http://www.dspace.cam.ac.uk:80/handle/1810/244608 Title: Functional modelling of planar cell polarity: an approach for identifying molecular function Authors: Hazelwood, Lee D; Hancock, John M Abstract: Abstract Background Cells in some tissues acquire a polarisation in the plane of the tissue in addition to apical-basal polarity. This polarisation is commonly known as planar cell polarity and has been found to be important in developmental processes, as planar polarity is required to define the in-plane tissue coordinate system at the cellular level. Results We have built an in-silico functional model of cellular polarisation that includes cellular asymmetry, cell-cell signalling and a response to a global cue. The model has been validated and parameterised against domineering non-autonomous wing hair phenotypes in Drosophila. Conclusions We have carried out a systematic comparison of in-silico polarity phenotypes with patterns observed in vivo under different genetic manipulations in the wing. This has allowed us to classify the specific functional roles of proteins involved in generating cell polarity, providing new hypotheses about their specific functions, in particular for Pk and Dsh. The predictions from the model allow direct assignment of functional roles of genes from genetic mosaic analysis of Drosophila wings. Mon, 13 May 2013 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244608 2013-05-13T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244606 Title: Lignin biosynthesis perturbations affect secondary cell wall composition and saccharification yield in Arabidopsis thaliana Authors: Van Acker, Rebecca; Vanholme, Ruben; Storme, Véronique; Mortimer, Jennifer C; Dupree, Paul; Boerjan, Wout Abstract: Abstract Background Second-generation biofuels are generally produced from the polysaccharides in the lignocellulosic plant biomass, mainly cellulose. However, because cellulose is embedded in a matrix of other polysaccharides and lignin, its hydrolysis into the fermentable glucose is hampered. The senesced inflorescence stems of a set of 20 Arabidopsis thaliana mutants in 10 different genes of the lignin biosynthetic pathway were analyzed for cell wall composition and saccharification yield. Saccharification models were built to elucidate which cell wall parameters played a role in cell wall recalcitrance. Results Although lignin is a key polymer providing the strength necessary for the plant’s ability to grow upward, a reduction in lignin content down to 64% of the wild-type level in Arabidopsis was tolerated without any obvious growth penalty. In contrast to common perception, we found that a reduction in lignin was not compensated for by an increase in cellulose, but rather by an increase in matrix polysaccharides. In most lignin mutants, the saccharification yield was improved by up to 88% cellulose conversion for the cinnamoyl-coenzyme A reductase1 mutants under pretreatment conditions, whereas the wild-type cellulose conversion only reached 18%. The saccharification models and Pearson correlation matrix revealed that the lignin content was the main factor determining the saccharification yield. However, also lignin composition, matrix polysaccharide content and composition, and, especially, the xylose, galactose, and arabinose contents influenced the saccharification yield. Strikingly, cellulose content did not significantly affect saccharification yield. Conclusions Although the lignin content had the main effect on saccharification, also other cell wall factors could be engineered to potentially increase the cell wall processability, such as the galactose content. Our results contribute to a better understanding of the effect of lignin perturbations on plant cell wall composition and its influence on saccharification yield, and provide new potential targets for genetic improvement. Thu, 25 Apr 2013 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244606 2013-04-25T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244605 Title: Preparation, characterization and in vitro evaluation of nanostructured chitosan/apatite and chitosan/Si-doped apatite composites Authors: Solis, Yaimara; Davidenko, Natalia; Carrodeguas, Raul G; Cruz, Jeny; Hernandez, Andy; Tomas, Miriela; Cameron, Ruth; Peniche, Carlos Abstract: Chitosan/apatite composites are attracting great attention as biomaterials for bone repair and regeneration procedures. The reason is their unique set of properties: bioactivity and osteoconductivity provided by apatite and resorbability supplied by chitosan among others. Thus, in this work chitosan/apatite and chitosan/Si-doped apatite composites were prepared and characterized. Particle size, surface area, in vitro physiological stability, enzymatic biodegradation and bioactivity were evaluated. Unimodal particle size distribution was obtained for composites with high chitosan/apatite ratios while bimodal distribution was present in composites with low chitosan/apatite ratio. Physiological stability decreased with Si-doping and with the chitosan content. Acetylation degree and molecular weight of chitosan did not affect in vitro stability. Rate of enzymatic degradation increased with the chitosan content in composites. Si-doped apatite composites also showed increased degradation with respect to non-doped ones. The bioactivity of the composites was evidenced by the deposition on their surface of a calcium phosphate layer with apatite morphology after immersion in simulated body fluid. Both, biodegradation and bioactivity were dependent on the molecular weight of the polymeric chitosan matrix. These results suggest that the chitosan/apatite composites obtained are promising materials for bone regeneration applications Tue, 01 Jan 2013 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244605 2013-01-01T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244604 Title: Photograph of memorial medallion of Alfred Russel Wallace Authors: Bruce-Joy, Albert; Spencer, Arthur Description: Photograph by Arthur Spencer of memoral medallion of Alfred Russel Wallace by Albert Bruce-Joy (1915) placed in Westminster Abbey. Also accompanying list of subscribers and advertisement. Fri, 01 Jan 1915 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244604 1915-01-01T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244603 Title: The histone deacetylase inhibitor sodium valproate causes limited transcriptional change in mouse embryonic stem cells but selectively overrides Polycomb-mediated Hoxb silencing Authors: Boudadi, Elsa; Stower, Hannah; Halsall, John A; Rutledge, Charlotte E; Leeb, Martin; Wutz, Anton; O’Neill, Laura P; Nightingale, Karl P; Turner, Bryan M Abstract: Abstract Background Histone deacetylase inhibitors (HDACi) cause histone hyperacetylation and H3K4 hypermethylation in various cell types. They find clinical application as anti-epileptics and chemotherapeutic agents, but the pathways through which they operate remain unclear. Surprisingly, changes in gene expression caused by HDACi are often limited in extent and can be positive or negative. Here we have explored the ability of the clinically important HDACi valproic acid (VPA) to alter histone modification and gene expression, both globally and at specific genes, in mouse embryonic stem (ES) cells. Results Microarray expression analysis of ES cells exposed to VPA (1 mM, 8 h), showed that only 2.4% of genes showed a significant, >1.5-fold transcriptional change. Of these, 33% were down-regulated. There was no correlation between gene expression and VPA-induced changes in histone acetylation or H3K4 methylation at gene promoters, which were usually minimal. In contrast, all Hoxb genes showed increased levels of H3K9ac after exposure to VPA, but much less change in other modifications showing bulk increases. VPA-induced changes were lost within 24 h of inhibitor removal. VPA significantly increased the low transcription of Hoxb4 and Hoxb7, but not other Hoxb genes. Expression of Hoxb genes increased in ES cells lacking functional Polycomb silencing complexes PRC1 and PRC2. Surprisingly, VPA caused no further increase in Hoxb transcription in these cells, except for Hoxb1, whose expression increased several fold. Retinoic acid (RA) increased transcription of all Hoxb genes in differentiating ES cells within 24 h, but thereafter transcription remained the same, increased progressively or fell progressively in a locus-specific manner. Conclusions Hoxb genes in ES cells are unusual in being sensitive to VPA, with effects on both cluster-wide and locus-specific processes. VPA increases H3K9ac at all Hoxb loci but significantly overrides PRC-mediated silencing only at Hoxb4 and Hoxb7. Hoxb1 is the only Hoxb gene that is further up-regulated by VPA in PRC-deficient cells. Our results demonstrate that VPA can exert both cluster-wide and locus-specific effects on Hoxb regulation. Tue, 30 Apr 2013 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244603 2013-04-30T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244602 Title: Genetic architecture and ecological speciation in Heliconius butterflies Authors: Merrill, Richard Abstract: It is now widely accepted that adaptation to different ecological niches can result in the evolution of new species. However, when gene flow persists speciation must overcome the antagonism between selection and recombination: Specifically, if gene flow persists, recombination will break down the genetic associations between alleles that characterise emerging species and cause reproductive isolation. Accordingly, genetic architectures that impede recombination can slow the breakdown of linkage disequilibrium and facilitate speciation. Mimicry in tropical butterflies has long been championed as an example of adaptation driving speciation. In the Neotropical genus Heliconius, distantly related pairs of unpalatable species often converge on the same bright warning-pattern to more efficiently advertise their distastefulness to predators. In contrast, closely related taxa often belong to different mimicry rings. The sister species, Heliconius melpomene and H. cydno are sympatric across much of Central and northern South America. Using artificial butterflies I reveal selection against non-mimetic hybrid colour patterns between these two species. These colour patterns are also used as mating cues and mimetic shifts may cause both pre-mating and post-mating isolation. However, shifts in colour pattern cannot drive reproductive isolation alone; rather, they must be accompanied by corresponding mate preferences. Associations between trait and preference loci may be broken down by mating and subsequent recombination. I demonstrate a genetic linkage between loci for both male and female mate preference and wing colour pattern in Heliconius cydno and H. melpomene. In addition, I present evidence for further associations between alleles affecting hybrid sterility and host-plant use and colour pattern loci. All this implies that linkage between traits that contribute to reproductive and ecological isolation is a general phenomenon in Heliconius with an underlying adaptive basis. Overall these results expose a genetic mechanism that, by impeding recombination, can facilitate speciation in the face of gene flow. Description: Second half of final page redacted as it contained the beginning of the following article in 'Current Biology' Sat, 27 Apr 2013 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244602 2013-04-27T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244601 Title: Sir Robert Ball Authors: Downey, William; Downey, Daniel Description: b/w portrait of astronomer Sir Robert Ball (1840-1913) by W.&D. Downey, London. Thu, 01 Jan 1891 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244601 1891-01-01T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244600 Title: A metadata-aware application for remote scoring and exchange of tissue microarray images Authors: Morris, Lorna; Tsui, Andrew; Crichton, Charles; Harris, Steve; Maccallum, Peter H; Howat, William J; Davies, Jim; Brenton, James D; Caldas, Carlos Abstract: Abstract Background The use of tissue microarrays (TMA) and advances in digital scanning microscopy has enabled the collection of thousands of tissue images. There is a need for software tools to annotate, query and share this data amongst researchers in different physical locations. Results We have developed an open source web-based application for remote scoring of TMA images, which exploits the value of Microsoft Silverlight Deep Zoom to provide a intuitive interface for zooming and panning around digital images. We use and extend existing XML-based standards to ensure that the data collected can be archived and that our system is interoperable with other standards-compliant systems. Conclusion The application has been used for multi-centre scoring of TMA slides composed of tissues from several Phase III breast cancer trials and ten different studies participating in the International Breast Cancer Association Consortium (BCAC). The system has enabled researchers to simultaneously score large collections of TMA and export the standardised data to integrate with pathological and clinical outcome data, thereby facilitating biomarker discovery. Tue, 30 Apr 2013 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244600 2013-04-30T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244599 Title: Political theologies in late colonial Buganda Authors: Earle, Jonathon Lynn Abstract: This thesis is an intellectual history of political debate in colonial Buganda. It is a history of how competing actors engaged differently in polemical space informed by conflicting histories, varying religious allegiances and dissimilar texts. Methodologically, biography is used to explore three interdependent stories. First, it is employed to explore local variance within Buganda’s shifting discursive landscape throughout the longue durée. Second, it is used to investigate the ways that disparate actors and their respective communities used sacred text, theology and religious experience differently to reshape local discourse and to re-imagine Buganda on the eve of independence. Finally, by incorporating recent developments in the field of global intellectual history, biography is used to reconceptualise Buganda’s late colonial past globally. Due to its immense source base, Buganda provides an excellent case study for writing intellectual biography. From the late nineteenth century, Buganda’s increasingly literate population generated an extensive corpus of clan and kingdom histories, political treatises, religious writings and personal memoirs. As Buganda’s monarchy was renegotiated throughout decolonisation, her activists—working from different angles—engaged in heated debate and protest. This debate resulted in massive literary output preserved in the Luganda press, party pamphlets and personal correspondence. Written evidence is taken from private papers, institutional archives and the local and international press. This project is shaped further by oral ethnography. By suggesting that Buganda’s past is well interpreted polemically, the result of this study is a more comprehensive understanding of the life of the mind than has been offered thus far by historians of Uganda. More broadly, by exploring the theological and political within the same analytic framework, this thesis contributes to our understanding of political theology in the history of Africa. Finally, by using biography to rethink Uganda’s past globally, this project furthers the use of global intellectual history in the history of modern Africa. Description: This thesis is embargoed until May 2015. Please contact the author on jonathon.earle at centre.edu if you have any enquiries Mon, 11 Jun 2012 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244599 2012-06-11T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244598 Title: Study of thin metal films and oxide materials for nanoelectronics applications Authors: De Los Santos Valladares, Luis Abstract: Different types of thin metal films and oxide materials are studied for their potential application in nanoelectronics: gold and copper films, nickel nanoelectrodes, oxide nanograin superconductors, carboxyl ferromagnetic microspheres and graphene oxide flakes. The crystallization and surface morphology of gold and copper films on SiO2/Si substrates is investigated as a function of annealing temperature. Annealing arranges the Au crystallites in the [111] direction and changes the morphology of the surface. Relaxation of the Au layer at high temperatures is responsible for the initial stages of cluster formation. These may form at disordered points on the surface and become islands when the temperature is increased. In the case of Cu/SiO2/Si films, oxides are formed after thermal oxidation at different temperatures up to 1000 °C. The phase evolution Cu -> Cu + Cu2O -> Cu2O -> Cu2O + CuO -> CuO is detected. Pure Cu2O films are obtained at 200 °C, whereas uniform CuO films without structural surface defects are obtained in the temperature range 300 - 550 °C. A resistivity phase diagram, which is obtained from the current-voltage response of the copper oxides, is presented. In the case of thin nickel films, the necessary reagents, conditions and processes required to obtain nano and atomic gaps between soft and clean nickel electrodes are described by using a conventional electrochemical cell. Current-voltage characteristics are also presented to evaluate possible applications of the nanogap electrodes in electronic nanodevices. In addition to the metal surfaces, oxides materials such as the superconductor LaCaBaCu3O7 (La1113), carboxyl ferromagnetic microparticles and graphene oxide flakes are studied. La1113 is a high critical temperature superconductor with TC(onset) = 80 K and its structure is similar to the tetragonal YBCO. This thesis explores the attachment of La1113 nanograins on Au(111) surfaces through selfassembled monolayers of HS-C8H16-HS [octane (di)thiol] for their potential application in nanotransistors. It is found that La1113 particles (100 nm mean diameter) can be functionalized by octane (di)thiol without affecting their superconducting critical temperature (TC = 80 K). A design for a superconducting transistor fabricated by immobilized La1113 nanograins in between two gold electrodes which could be controlled by an external magnetic field gate is suggested. Furthermore, the mechanical reorientation of thiolated ferromagnetic microspheres bridging a pair of gold electrodes under an external magnetic field is studied. Finally, a flexible film made of graphene oxide flakes is prepared and characterized by X ray diffraction. It is achieved by the chemical oxidation of commercial graphite and the subsequent reaction with NaOH. It is found that the interlayer distance between graphene increases upon oxidation due to the formation of chemical groups and results in the delamination and flexibility of the flakes. Description: Appendix A Pages 132-134 have been removed from this online version of the thesis for publisher copyright reasons. These had contained page images from the cover of Nanotechnology, Vol. 21, Nov 2010 and its corresponding web alert Tue, 10 Jan 2012 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244598 2012-01-10T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244597 Title: A combination of mutations in AKR1D1 and SKIV2L in a family with severe infantile liver disease Authors: Morgan, Neil V; Hartley, Jane L; Setchell, Kenneth DR; Simpson, Michael A; Brown, Rachel; Tee, Louise; Kirkham, Sian; Pasha, Shanaz; Trembath, Richard C; Maher, Eamonn R; Gissen, Paul; Kelly, Deirdre A Abstract: Abstract Infantile cholestatic diseases can be caused by mutations in a number of genes involved in different hepatocyte molecular pathways. Whilst some of the essential pathways have a well understood function, such as bile biosynthesis and transport, the role of the others is not known. Here we report the findings of a clinical, biochemical and molecular study of a family with three patients affected with a severe infantile cholestatic disease. A novel homozygous frameshift germline mutation (c.587delG) in the AKR1D1 gene; which encodes the enzyme Δ 4-3-oxosteroid 5β–reductase that is required for synthesis of primary bile acids and is crucial for establishment of normal bile flow, was found in all 3 patients. Although the initial bile acid analysis was inconclusive, subsequent testing confirmed the diagnosis of a bile acid biogenesis disorder. An additional novel homozygous frameshift mutation (c.3391delC) was detected in SKIV2L in one of the patients. SKIV2L encodes a homologue of a yeast ski2 protein proposed to be involved in RNA processing and mutations in SKIV2L were recently described in patients with Tricohepatoenteric syndrome (THES). A combination of autozygosity mapping and whole-exome-sequencing allowed the identification of causal mutations in this family with a complex liver phenotype. Although the initial 2 affected cousins died in the first year of life, accurate diagnosis and management of the youngest patient led to successful treatment of the liver disease and disease-free survival. Wed, 15 May 2013 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244597 2013-05-15T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244596 Title: Empirical Bayesian analysis of paired high-throughput sequencing data with a beta-binomial distribution Authors: Hardcastle, Thomas J; Kelly, Krystyna A Abstract: Abstract Background Pairing of samples arises naturally in many genomic experiments; for example, gene expression in tumour and normal tissue from the same patients. Methods for analysing high-throughput sequencing data from such experiments are required to identify differential expression, both within paired samples and between pairs under different experimental conditions. Results We develop an empirical Bayesian method based on the beta-binomial distribution to model paired data from high-throughput sequencing experiments. We examine the performance of this method on simulated and real data in a variety of scenarios. Our methods are implemented as part of the RbaySeq package (versions 1.11.6 and greater) available from Bioconductor (http://www.bioconductor.org). Conclusions We compare our approach to alternatives based on generalised linear modelling approaches and show that our method offers significant gains in performance on simulated data. In testing on real data from oral squamous cell carcinoma patients, we discover greater enrichment of previously identified head and neck squamous cell carcinoma associated gene sets than has previously been achieved through a generalised linear modelling approach, suggesting that similar gains in performance may be found in real data. Our methods thus show real and substantial improvements in analyses of high-throughput sequencing data from paired samples. Mon, 22 Apr 2013 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244596 2013-04-22T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244595 Title: Detection of specific HPV subtypes responsible for the pathogenesis of condylomata acuminata Authors: Hawkins, Matthew G; Winder, David M; Ball, Siolian L R; Vaughan, Katie; Sonnex, Christopher; Stanley, Margaret A; Sterling, Jane C; Goon, Peter K C Abstract: Abstract Background The low-risk human papillomavirus types 6 and 11 are responsible for approximately 90% of anogenital wart cases, with approximately 190,000 new and recurrent cases reported in the UK in 2010. The UK has recently selected the quadrivalent HPV vaccine, which conveys protection against both HPV6 and HPV 11, as part of its immunisation programme for 2012 and it is expected that this will reduce disease burden in the UK. The aims of the study were to evaluate current strategies used for the monitoring of HPV infection in genital warts and to assess the suitability of laser-capture microdissection (LCM) as a technique to improve the understanding of the natural history of HPV types associated with genital wart lesions. Methods DNA and RNA were extracted from whole wart, surface swabs and LCM sections from 23 patients. HPV types present were determined using the Linear Array HPV Genotyping Test (Roche), with HPV DNA viral load and mRNA expression investigated using qPCR and qRT-PCR, respectively. Results Results indicated that swabbing the surface of warts does not accurately reflect potential causative HPV types present within a wart lesion, multiple HPV types being present on the surface of the wart that are absent in the lower layers of tissue isolated by LCM. Although it was shown that HPV DNA viral load does not directly correlate with HPV mRNA load, the presence of both DNA and mRNA from a single HPV type suggested a causative role in lesion development in 8/12 (66.6%) of patients analysed, with dual infections seen in 4/12 (33.3%) cases. HPV 6 and HPV 11 were present in more than 90% of the lesions examined. Conclusions Surface swabbing of warts does not necessarily reflect the causative HPV types. HPV type specific DNA and mRNA loads do not correlate. HPV 6 and 11 were likely to be causally involved in over 90% of the lesions. Dual infections were also found, and further studies are required to determine the biological and clinical nature of dual/multiple infections and to establish the relationship of multiple HPV types within a single lesion. Tue, 30 Apr 2013 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244595 2013-04-30T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244594 Title: Dissemination of metabolomics results: role of MetaboLights and COSMOS Authors: Salek, Reza M; Haug, Kenneth; Steinbeck, Christoph Abstract: Abstract With ever-increasing amounts of metabolomics data produced each year, there is an even greater need to disseminate data and knowledge produced in a standard and reproducible way. To assist with this a general purpose, open source metabolomics repository, MetaboLights, was launched in 2012. To promote a community standard, initially culminated as metabolomics standards initiative (MSI), COordination of Standards in MetabOlomicS (COSMOS) was introduced. COSMOS aims to link life science e-infrastructures within the worldwide metabolomics community as well as develop and maintain open source exchange formats for raw and processed data, ensuring better flow of metabolomics information. Thu, 16 May 2013 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244594 2013-05-16T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244593 Title: Cooling an electron gas using quantum dot based electronic refrigeration Authors: Prance, Jonathan Robert Abstract: Studies of two-dimensional electron gases (2DEGs) in semiconductors form an active and productive field of condensed matter physics research. As well as having interesting inherent properties, they are used as the foundation for constructing various nano-scale electronic devices, such as quantum wires and quantum dots. Conventionally, low temperature measurements of 2DEGs are made by cooling the sample to 1.5 K with liquid Helium-4, to 300 mK with liquid Helium-3, or even down to a few mK using a dilution refrigerator. However, at lower temperatures the electron gas becomes increasingly decoupled from the lattice in which it resides. Below ~ 1 K the coupling can be weak enough for the electron gas to be significantly elevated in temperature due to parasitic heating. In this thesis we present the experimental and theoretical investigation of a refrigeration scheme that has the potential to cool 2DEGs below the temperatures currently available. Cooling to ever lower temperatures would be beneficial for studying fragile fractional quantum Hall states, non-Fermi-liquid behaviour in bilayer 2DEGs, or interactions like the Kondo effect that occur between quantum dots and 2DEGs. The scheme we investigate is called the Quantum Dot Refrigerator (or QDR) and is based upon the energy selective transport of electrons through the singleparticle states of quantum dots. By using a pair of dots, both hot electrons and hot holes can be selectively removed from an otherwise electrically isolated 2DEG. The result is a net current that continuously removes heat. This type of refrigerator is best suited to be used in conjunction with a dilution fridge or Helium-3 system to provide a final stage of cooling. The scheme was first investigated theoretically in 1993 by Edwards et al. but, to our knowledge, has never before been demonstrated experimentally. We detail the fabrication and measurement of a QDR device that is designed to cool an isolated 6 µm2 2DEG. In order to interpret the behaviour of the device, a model was developed to take account of electrostatic interactions between the components of the system (the quantum dots and the isolated 2DEG). Electrostatic interactions were found to be significant for our design, but were neglected in previous work. Our model predicts that their presence complicates, but does not invalidate, the principle of operation of a QDR. By comparing measurements of the current through the QDR with predictions of the model, we show that the observed behaviour is consistent with cooling of the isolated 2DEG by up to 100 mK at ambient temperatures around 250 mK. Although these temperatures are well within the reach of conventional refrigeration techniques, the results are a compelling proof-of-concept demonstration that the QDR principle is sound and can achieve significant refrigeration in the right conditions. Finally, we discuss future directions for improving QDR performance and characterisation, and for lowering the achievable base temperature. We also suggest how QDRs could be used to provide cold reservoirs for a nano-scale electronic device, and explore the limitations that would apply to such an experiment. Mon, 12 Oct 2009 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244593 2009-10-12T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244592 Title: Plates from "An account of the Aurora Borealis, seen near Cambridge,..." Authors: Morgan, John Holdsworth; Barber, John Thomas; Chabot, C.; Andrews, J. Description: "An account of the Aurora Borealis, seen near Cambridge, October the 24th, 1847: together with those of September 21, 1846, and March 19, 1847, seen at the Cambridge Observatory" by John H. Morgan and John T. Barber. Cambridge: Macmillan, Barclay, and Macmillan, London: G. Bell, Fleet Street. 1848? Scans of 12 plates, printed by C. Chabot, plates II-X by J. Andrews. Sat, 01 Jan 1848 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244592 1848-01-01T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244591 Title: Understanding Hospital Admissions Close to the End of Life (ACE) Study Authors: Morris, Zoë S; Fyfe, Miranda; Momen, Natalie; Hoare, Sarah; Barclay, Stephen Abstract: Abstract Background Palliative care is a policy priority internationally. In England, policymakers are seeking to develop high quality care for all by focusing on reducing the number of patients who die in acute hospitals. It is argued that reducing ‘inappropriate’ hospital admissions will lead to an improvement in the quality of care and provide cost savings.Yet what is meant by an ‘inappropriate’ admission is unclear and is unlikely to be shared by all stakeholders. The decision process that leads to hospital admission is often challenging, particularly when patients are frail and elderly. The ACE study reopens the idea of ‘inappropriate’ hospital admissions close to the end of life. We will explore how decisions that result in inpatient admissions close to death are made and valued from the perspective of the decision-maker, and will consider the implications of these findings for current policy and practice. Design/Methods The study focuses on the admission of patients with advanced dementia, chest disease or cancer who die within 72 hours of admission to acute hospitals. The study uses mixed methods with three data collection phases. Phase one involves patient case studies of admissions with interviews with clinicians involved in the admission and next-of-kin. Phase two uses vignette-based focus groups with clinical professionals and patients living with the conditions of interest. Phase three uses questionnaires distributed to clinical stakeholders. Qualitative data will be explored using framework analysis whilst the questionnaire data will be examined using descriptive statistical analysis. Findings will be used to evaluate current policy and literature. Discussion Significant ethical and validity issues arise due to the retrospective nature of phase one of the study. We are not able to gain consent from patients who have died, and the views of the deceased patients cannot be included directly, which risks privileging professional views. This phase also relies on the memories of the participants which may be unreliable. Later phases of the study attempt to compensate for the “absent voices” of the deceased patients by including next-of-kin and patient focus groups. Mon, 11 Mar 2013 00:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244591 2013-03-11T00:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244590 Title: The use of electrochemical sensors for monitoring urban air quality in low-cost, high-density networks. Authors: Mead, M I; Popoola, O A M; Stewart, G B; Landshoff, P; Calleja, M; Hayes, M; Baldovi, J J; Hodgson, T F; McLeod, M W; Dicks, J; Lewis, A; Cohen, J; Baron, R; Saffell, J R; Jones, R L Abstract: Measurements at appropriate spatial and temporal scales are essential for understanding and monitoring spatially heterogeneous environments with complex and highly variable emission sources, such as in urban areas. However, the costs and complexity of conventional air quality measurement methods means that measurement networks are generally extremely sparse. In this paper we show that miniature, low-cost electrochemical gas sensors, traditionally used for sensing at parts-per-million (ppm) mixing ratios can, when suitably configured and operated, be used for parts-per-billion (ppb) level studies for gases relevant to urban air quality. Sensor nodes, in this case consisting of multiple individual electrochemical sensors, can be low-cost and highly portable, thus allowing the deployment of scalable high-density air quality sensor networks at fine spatial and temporal scales, and in both static and mobile configurations. Tue, 30 Apr 2013 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244590 2013-04-30T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244589 Title: Sex-biased gene expression in the developing brain: implications for autism spectrum disorders Authors: Ziats, Mark N; Rennert, Owen M Abstract: Abstract Autism spectrum disorders affect significantly more males than females. Understanding sex differences in normal human brain development may provide insight into the mechanism(s) underlying this disparity; however, studies of sex differences in brain development at the genomic level are lacking. Here, we report a re-analysis of sex-specific gene expression from a recent large transcriptomic study of normal human brain development, to determine whether sex-biased genes relate to specific mechanistic processes. We discovered that male-biased genes are enriched for the processes of extracellular matrix formation/glycoproteins, immune response, chromatin, and cell cytoskeleton. We highlight that these pathways have been repeatedly implicated in autism and demonstrate that autism candidate genes are also enriched for these pathways. We propose that the overlap of these male-specific brain transcriptional modules with the same pathways in autism spectrum disorders may partially explain the increased incidence of autism in males. Mon, 06 May 2013 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244589 2013-05-06T23:00:00Z http://www.dspace.cam.ac.uk:80/handle/1810/244588 Title: Deletions within COL11A1 in Type 2 stickler syndrome detected by multiplex ligation-dependent probe amplification (MLPA) Authors: Vijzelaar, Raymon; Waller, Sarah; Errami, Abdellatif; Donaldson, Alan; Lourenco, Teresa; Rodrigues, Marcia; McConnell, Vivienne; Fincham, Gregory; Snead, Martin; Richards, Allan Abstract: Abstract Background COL11A1 is a large complex gene around 250 kb in length and consisting of 68 exons. Pathogenic mutations in the gene can result in Stickler syndrome, Marshall syndrome or Fibrochondrogenesis. Many of the mutations resulting in either Stickler or Marshall syndrome alter splice sites and result in exon skipping, which because of the exon structure of collagen genes usually leaves the message in-frame. The mutant protein then exerts a dominant negative effect as it co-assembles with other collagen gene products. To date only one large deletion of 40 kb in the COL11A1, which was detected by RT-PCR, has been characterized. However, commonly used screening protocols, utilizing genomic amplification and exon sequencing, are unlikely to detect such large deletions. Consequently the frequency of this type of mutation is unknown. Case presentations We have used Multiplex Ligation-Dependent Probe Amplification (MLPA) in conjunction with exon amplification and sequencing, to analyze patients with clinical features of Stickler syndrome, and have detected six novel deletions that were not found by exon sequencing alone. Conclusion Exon deletions appear to represent a significant proportion of type 2 Stickler syndrome. This observation was previously unknown and so diagnostic screening of COL11A1 should include assays capable of detecting both large and small deletions, in addition to exon sequencing. Thu, 25 Apr 2013 23:00:00 GMT http://www.dspace.cam.ac.uk:80/handle/1810/244588 2013-04-25T23:00:00Z