The Development of a Tory Ideology and Identity 1760-1832

This thesis examines the ideas which underpinned early nineteenth century Toryism and their development in the late eighteenth century. It argues that a distinct, coherent, refined Tory identity emerged from the Tory splits between 1827 and 1830. This was preceded by a process of renegotiation and consolidation in Tory ideology and identity from 1760 onwards. The period between the accession of George III, in 1760, and the passage of the First Reform Act, in 1832, witnessed consistent and sustained crises regarding the constitution established in Church and state. The outbreak of revolutions in America and France reinvigorated debates regarding the nature and location of political sovereignty as well as the relationship between the crown and parliament. Lengthy wars against each nation were followed by severe economic depressions, the apparent proliferation of domestic political radicalism, and intermittent, but determined, demands for parliamentary reform. In addition, there were persistent attempts to alter the religious basis of the constitution to accommodate both Protestant pluralism and, from 1801, predominantly Catholic Ireland. This thesis contends that the debates surrounding these issues contributed to the rehabilitation and renegotiation of late-seventeenth-century and early-eighteenth-century Tory ideas. It also contends that, in moments of crisis and reaction, old Toryism converged with the conservative elements of an increasingly fractured Whig tradition in defence of the constitutional status quo. This convergence, apparent in the opening decades of George III’s reign, was consolidated in the context of the French Revolution. Consequently, after 1812, a broad, but loose, ideological consensus emerged, labelled as Tory, underpinned by anti-populism, commitment to the preservation of Christian orthodoxy, and the establishment of the Church of England. However, below this broad ideological umbrella, differences persisted which created tensions, contributing to the divisions between 1827 and 1830, and, through them, the refinement of Tory identity

Expression stability of commonly used reference genes in canine articular connective tissues

<p>Abstract</p> <p>Background</p> <p>The quantification of gene expression in tissue samples requires the use of reference genes to normalise transcript numbers between different samples. Reference gene stability may vary between different tissues, and between the same tissue in different disease states. We evaluated the stability of 9 reference genes commonly used in human gene expression studies. Real-time reverse transcription PCR and a mathematical algorithm were used to establish which reference genes were most stably expressed in normal and diseased canine articular tissues and two canine cell lines stimulated with lipolysaccaride (LPS).</p> <p>Results</p> <p>The optimal reference genes for comparing gene expression data between normal and diseased infrapatella fat pad were <it>RPL13A </it>and <it>YWHAZ </it>(M = 0.56). The ideal reference genes for comparing normal and osteoarthritic (OA) cartilage were <it>RPL13A </it>and <it>SDHA </it>(M = 0.57). The best reference genes for comparing normal and ruptured canine cranial cruciate ligament were <it>B2M </it>and <it>TBP </it>(M = 0.59). The best reference genes for normalising gene expression data from normal and LPS stimulated cell lines were <it>SDHA </it>and <it>YWHAZ </it>(K6) or <it>SDHA </it>and <it>HMBS </it>(DH82), which had expression stability (M) values of 0.05 (K6) and 0.07 (DH82) respectively. The number of reference genes required to reduce pairwise variation (V) to <0.20 was 4 for cell lines, 5 for cartilage, 7 for cranial cruciate ligament and 8 for fat tissue. Reference gene stability was not related to the level of gene expression.</p> <p>Conclusion</p> <p>The reference genes demonstrating the most stable expression within each different canine articular tissue were identified, but no single reference gene was identified as having stable expression in all different tissue types. This study underlines the necessity to select reference genes on the basis of tissue and disease specific expression profile evaluation and highlights the requirement for the identification of new reference genes with greater expression stability for use in canine articular tissue gene expression studies.</p

Mixed metal nanoparticle assembly and the effect on surface enhanced raman scattering

Here we report the assembly of mixed metal nanoparticles using an oligonucleotide-templated approach. Substitution of one of the gold nanoparticle probes with an analagous silver probe to produce a hetero-metal duplex permitted surface enhanced Raman scattering of the dye label, exploiting the improved surface enhancement properties of silver nanoparticles whilst maintaining the surface chemistry benefits of gold nanoaprticle

Expression stability of commonly used reference genes in canine articular connective tissues

Background: The quantification of gene expression in tissue samples requires the use of reference genes to normalise transcript numbers between different samples. Reference gene stability may vary between different tissues, and between the same tissue in different disease states. We evaluated the stability of 9 reference genes commonly used in human gene expression studies. Realtime reverse transcription PCR and a mathematical algorithm were used to establish which reference genes were most stably expressed in normal and diseased canine articular tissues and two canine cell lines stimulated with lipolysaccaride (LPS). Results: The optimal reference genes for comparing gene expression data between normal and diseased infrapatella fat pad were RPL13A and YWHAZ (M = 0.56). The ideal reference genes for comparing normal and osteoarthritic (OA) cartilage were RPL13A and SDHA (M = 0.57). The best reference genes for comparing normal and ruptured canine cranial cruciate ligament were B2M and TBP (M = 0.59). The best reference genes for normalising gene expression data from normal and LPS stimulated cell lines were SDHA and YWHAZ (K6) or SDHA and HMBS (DH82), which had expression stability (M) values of 0.05 (K6) and 0.07 (DH82) respectively. The number of reference genes required to reduce pairwise variation (V) to <0.20 was 4 for cell lines, 5 for cartilage, 7 for cranial cruciate ligament and 8 for fat tissue. Reference gene stability was not related to the level of gene expression. Conclusion: The reference genes demonstrating the most stable expression within each different canine articular tissue were identified, but no single reference gene was identified as having stable expression in all different tissue types. This study underlines the necessity to select reference genes on the basis of tissue and disease specific expression profile evaluation and highlights the requirement for the identification of new reference genes with greater expression stability for use in canine articular tissue gene expression studies

Renal peroxiredoxin 6 interacts with anion exchanger 1 and plays a novel role in pH homeostasis.

Peroxiredoxin 6 (PRDX6) is one of the six members of the PRDX family, which have peroxidase and antioxidant activity. PRDX6 is unique, containing only one conserved cysteine residue (C47) rather than the two found in other PRDXs. A yeast two-hybrid screen found PRDX6 to be a potential binding partner of the C-terminal tail of anion exchanger 1 (AE1), a Cl(-)/HCO(3)(-) exchanger basolaterally expressed in renal α-intercalated cells. PRDX6 immunostaining in human kidney was both cytoplasmic and peripheral and colocalized with AE1. Analysis of native protein showed that it was largely monomeric, whereas expressed tagged protein was more dimeric. Two methionine oxidation sites were identified. In vitro and ex vivo pull-downs and immunoprecipitation assays confirmed interaction with AE1, but mutation of the conserved cysteine resulted in loss of interaction. Prdx6 knockout mice had a baseline acidosis with a major respiratory component and greater AE1 expression than wild-type animals. After an oral acid challenge, PRDX6 expression increased in wild-type mice, with preservation of AE1. However, AE1 expression was significantly decreased in knockout animals. Kidneys from acidified mice showed widespread proximal tubular vacuolation in wild-type but not knockout animals. Knockdown of PRDX6 by siRNA in mammalian cells reduced both total and cell membrane AE1 levels. Thus, PRDX6-AE1 interaction contributes to the maintenance of AE1 during cellular stress such as during metabolic acidosis.Human kidney sections were prepared by Suzy Haward, Addenbrooke's Human Research Tissue Bank, which is supported by the Cambridge Biomedical Research Centre. We thank Dr. Aron Fisher (Institute for Environmental Science, University of Pennsylvania) for the kind gift of Prdx6−/− mice and reagents, Carsten Wagner (Zurich) for antisera, Jane Clarke (University of Cambridge) for modified pRSET-A vector, and Kamburapola Jayawardena for mass spectrometry (CIMR). This work was funded by the Wellcome Trust (award 088489/Z/09/Z to FEKF and Strategic award 100140/Z/12/Z to the Cambridge Institute for Medical Research), and the Jack Kent Cooke Foundation (scholarship to SLS).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ki.2015.27

The X-ray reflection spectrum of the radio-loud quasar 4C 74.26

The relativistic jets created by some active galactic nuclei are important agents of AGN feedback. In spite of this, our understanding of what produces these jets is still incomplete. X-ray observations, which can probe the processes operating in the central regions in immediate vicinity of the supermassive black hole, the presumed jet launching point, are potentially particularly valuable in illuminating the jet formation process. Here, we present the hard X-ray NuSTAR observations of the radio-loud quasar 4C 74.26 in a joint analysis with quasi-simultaneous, soft X-ray Swift observations. Our spectral analysis reveals a high-energy cut-off of 183$_{-35}^{+51}$ keV and confirms the presence of ionized reflection in the source. From the average spectrum we detect that the accretion disk is mildly recessed with an inner radius of $R_\mathrm{in}=4-180\,R_\mathrm{g}$. However, no significant evolution of the inner radius is seen during the three months covered by our NuSTAR campaign. This lack of variation could mean that the jet formation in this radio-loud quasar differs from what is observed in broad-line radio galaxies.Comment: Accepted for publication in Ap

Investigating the perceived versus actual gastrointestinal nematode challenge on extensive sheep farms

Extensive farming systems form an integral part of sheep production systems across Europe. However, with innate production handicaps, declining sheep numbers and narrow economic margins, production is becoming increasingly challenging threatening the future sustainability of the industry. Gastrointestinal nematodes (GINs) are a significant cause of production losses to the global sheep industry, with well-established resistance to the major anthelmintic groups. Traditionally, extensive farming systems are not thought to have a significant parasite challenge compared with intensive farms, but there is a need to identify the scale and importance of GINs on extensive farms to inform the need for sustainable control strategies. In this study, a questionnaire of extensive farmers (n=34) was conducted and parasitological data were collected from nine study farms to investigate the perceived versus actual GIN and anthelmintic resistance challenge faced by extensive farms. The results showed a production-limiting challenge on most farms, with a higher GIN challenge observed on improved pastures. Furthermore, over half of the extensive farmers perceived anthelmintic resistance to be a greater problem for intensive farmers, with only 20% of respondents reporting known anthelmintic resistance. However, all study farms had evidence of resistance to at least one group of anthelmintics. Consequently, this study has demonstrated that despite the traditional perception of parasitism on extensive farms, there is a need to increasingly consider its impact and take a proactive approach to sustainable control, with solutions tailored to their unique management