3,657 research outputs found
Steam Engine Ex Mayor at Steam Fair
Ex G.T. Tuby's Burrell showman's road locomotive steam traction engine 'Ex Mayor' No.4000, registration 'WT8606' (built 1925). Built 1925 for G. T. Tuby. Photographed at a steam fair circa 1972
La Prova di Ascolto
This chapter decribes the objective listening test administered to students with specific learning difficulties (dyslexia) and a control group. Test types used included true/false and MCQ with 3, 4 or 5 options. The test, set at B1 level of he CEFR (the required level for university entrance) involved listening to a monologue (extract from a radio programme) and an interview. An analysis of the results suggests that, whereas T/F items posed considerable difficulty to students with dyslexia, especially those items with greater information load, there seemed to be no difference in difficulty between 3 and 4 option MCQs. More problematic were those items requiring inferencing skills to retrieve information which was not explicit in the text
A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern
The var multicopy gene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variant antigens, which, through their ability to adhere to a variety of host receptors, are thought to be important virulence factors. The predominant expression of a single cytoadherent PfEMP1 type on an infected red blood cell, and the switching between different PfEMP1 types to evade host protective antibody responses, are processes thought to be controlled at the transcriptional level. Contradictory data have been published on the timing of var gene transcription. Reverse transcription-polymerase chain reaction (RT-PCR) data suggested that transcription of the predominant var gene occurs in the later (pigmented trophozoite) stages, whereas Northern blot data indicated such transcripts only in early (ring) stages. We investigated this discrepancy by Northern blot, with probes covering a diverse var gene repertoire. We confirm that almost all var transcript types were detected only in ring stages. However, one type, the well-conserved varCSA transcript, was present constitutively in different laboratory parasites and does not appear to undergo antigenic variation. Although varCSA has been shown to encode a chondroitin sulphate A (CSA)-binding PfEMP1, we find that the presence of full-length varCSA transcripts does not correlate with the CSA-binding phenotype
Effects of rarity form on species’ responses to land use
Anthropogenic land-use change causes substantial changes in local and global biodiversity. Rare and common species can differ in sensitivity to land-use change; rare species are expected to be affected more negatively. Rarity may be defined in terms of geographic range size, population density, or breadth of habitat requirements. How these 3 forms of rarity interact in determining global responses to land use is yet to be assessed. Using global data representing 912 vertebrate species, we tested for differences in responses to land use of species characterized by different types of rarity. Land-use responses were fitted using generalized linear mixed-effects models, allowing responses to vary among groups of species with different forms of rarity. Species considered rare with respect to all 3 forms of rarity showed particularly strong declines in disturbed land uses (>40% of species and 30% of individuals in the most disturbed land uses). In contrast, species common both geographically and numerically and with broad habitat requirements showed strong increases (up to 90% increase in species and 40% in abundance in some land uses). Our results suggest that efforts to understand the vulnerability of species to environmental changes should account for different types of rarity where possible. Our results also have potentially important implications for ecosystem functioning, given that rare species may play unique roles within ecosystems
Visual art festivals and globalisation: the rise of biennials
t is a dynamic and indispensable text for students in arts and festivals management, events, tourism, creative industries, cultural and public policy, music industry and management courses as well as for festival and events managers, public authorities and existing and potential sponsors.
Through the variety of festivals illustrated in this book, the reader will discover that much about the nature of festivals crosses borders, they are a recognisable and growing part of societal and cultural delivery around the globe; their impacts, economic, social and cultural are a major driver in their development; their popularity with audiences, arts organisations and performers is undiminished in this ever-expanding cultural phenomenon of festivals
Functional identification and mapping of a gene that represses telomerase hTERT transcription in prostate cancer cells
This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Telomerase is present in over 90% of tumour tissues and immortalized cells and is tightly regulated in most normal somatic cells. This suggests the existence of regulatory mechanisms repressing telomerase in normal cells that somehow have become inactive during cancer development. In this project, I used genetic complementation in the form of microcell-mediated monochromosome transfer (MMCT) to search for chromosomes that repress telomerase activity in a prostate cancer cell line, PC-3. Microcell hybrids generated by introducing normal human chromosome 11 strongly inhibited telomerase. Telomerase is regulated primarily at the level of hTERT transcription, its catalytic subunit. Consequently, endogenous hTERT mRNA levels were measured by quantitative RT-PCR in microcell hybrids generated by transferring normal human chromosomes into a PC-3 sub-clone (PC- 3/hTERT) ectopically expressing hTERT cDNA to prevent senescence. Only hybrids constructed with transferred chromosome 11 showed strong transcriptional repression of hTERT. Next, hybrids were constructed by the MMCT transfer of chromosome 11 fragments (X-ray-induced). FISH analysis of clones with completely silenced endogenous hTERT transcription revealed in all cases a discrete chromosome 11 fragment with both the p-arm and q-arm material. A randomly selected hTERT-repressed clone was treated with ganciclovir to select against the HyTK marker and reverse the phenotype. hTERT expression in majority of GCV-resistant clones returned to levels comparable to the parent PC-3/hTERT cells.
Collectively, these results provide strong functional evidence for the presence of a powerful telomerase repressor sequence on the fragment. Transfer of one repressive fragment back into mouse A9 cells was then carried out to facilitate fine-structure mapping of its sequence content. High density STS mapping of the fragment in each of the clones revealed a considerable DNA content heterogeneity across the panel. These content maps, together with a further round of MMCT to confirm hTERTrepressive activity, enabled me to identify three candidate regions on the q-arm of chromosome 11 where the repressor sequence may be located: the first region lies between map positions 64.70Mb to 65.42Mb and the other two regions each flank a single positive STS marker at 69.71Mb and 127.32Mb. KAT5, a histone modifying gene has been identified as a potential candidate for repressing hTERT.Professor Robert F Newbol
Behaviour of Dickey-Fuller Unit Root Tests Under Trend Misspecification
We analyse the case where a unit root test is based on a Dickey-Fuller regression whose only deterministic term is a fixed intercept. Suppose, however, as could well be the case, that the actual data generating process includes a broken linear trend. It is shown theoretically, and verified empirically, that under the I(1) null and I(0) alternative hypotheses the Dickey-Fuller test can display a wide range of different characteristics depending on the nature and location of the break.
Expression of shelterin and shelterin-associated genes in breast cancer cell lines
This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Mammalian telomeric DNA consists of tandem repeats of the sequence TTAGGG associated with a specialized set of proteins, known collectively as Shelterin. These telosomal proteins protect the ends of chromosomes against end-to-end fusion and degradation. The objective of this project was to investigate whether expression of Shelterin and Shelterin-associated proteins are altered, and influence the protection and maintenance of telomeres, in breast cancer cells. Initial findings showed that most of the Shelterin and Shelterin-associated genes were significantly down-regulated (at the mRNA expression level) in a panel of ten breast cancer cell lines. Epigenetic alterations to DNA (methylation at CpG Islands) and histones can result in altered expression of genes. Further investigations showed that the promoter region of POT1 was partially methylated in the breast cancer cell line, 21NT. To support these observations, a DNA methylation inhibitor, 5-aza-CdR, and a histone deacetylation inhibitor, TSA, were used in an attempt to reactivate the expression of silenced genes. This work generated novel findings. Treatment with 5-aza-CdR and TSA resulted in the highest recovery of TIN2 and POT1 mRNA levels at both short-term (48 and 72 hours) and long-term (3 weeks) treatment of the breast cancer cell line, 21NT cells. In addition, POT1 promoter methylation was analysed before and after treatment of 21NT cells. Bisulphite sequencing data were consistent with the mRNA expression results, showing up-regulation of POT1, as all methylation sites were demethylated after the treatment of 21NT cells with 5-aza-CdR. These studies also showed for the first time that both the short-term (72 hours) and 3 weeks treatment of 21NT cells with 5-aza-CdR was able to increase telomere lengths (using four measurement methods, i.e. TRF, q-PCR, flow-FISH and iQFISH). Breast cancer cell lines expressed low levels of several telosomal mRNAs and that this down-regulation was found to be due in part to promoter methylation. Methylation was shown to be relieved through treatment of the cells with 5-aza-CdR and TSA; specifically, POT1 was shown to be up-regulated to a higher extent compared with other Shelterin genes. Given that previous studies involved over-expression of POT1 in telomerase-positive cells to demonstrate telomere length elongation, we addressed the possibility that over-expression of POT1 may affect telomere length in 21NT breast cancer cells. The results showed that the average telomere length of the POT1 over-expressing clones was increased by 2 to 3 kb compared with 21NT non-transfected and empty vector controls. The study also demonstrated that increased telomere length (by ectopic over-expression of POT1) is not due to a direct effect of telomerase enzyme activity. One explanation for this could be that POT1 may induce a negative regulator of telomerase activity to maintain telomere length. Taken together, the results generated in this project suggest that POT1 may control a localised activation of telomerase enzyme at the telomere end, and regulate stability of the Shelterin complex
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