渭南地区末次冰期以来的蜗牛化石记录及古气候古环境研究

In this study, 172 mollusk assemblages from the Weinan loess section in the southeast of Loess Plateau, China, were identified quantitatively at relative high resolution. The results show: 1) the history and processes of paleoclimatic and paleoenvironmental changes in Weinan since the last 70 ka; 2) the characteristics of climatic changes during the period of the last glacial maximum (LGM); 3) the spatial pattern of paleoclimate variations at the south and middle parts of the Loess Plateau during the LGM period; 4) the timing of the last deglaciation and the return event of rapid climate change during the last deglaciation. The main conclusions are as follows: 1) 172 mollusk samples taken from the uppermost 9 m deposits cover the past 70 ka, which were sampled at the internals of 5 cm for S_0, 3 cm for L_(1-1) and L_(1-2), and 10 cm for L_(1-3), L_(1-4) and L_(1-5). Author analyzed quantitatively all individuals including broken pieces of snail shells, percentages of 15 species identified from 172 samples. Three main groups were determined according to the ecological requirement of each taxon. Based on the variations of three ecological groups and typical ecological species, The author intended to reconstruct the history of and processes of climate and environment since the last 70 ka in the Weinan region. The climate and environment in this region experienced the following changes: relative warm and humid stage from 67.5-20.3 cal. ka B.P., a period of forest-steppe or steppe developed; cold and arid stage from 20.3-15.5 cal. ka B.P., a dry steppe period, later wetter and colder; cold and humid period once time from 15.5 to 12.3 cal. ka B.P., a typical steppe or forest-steppe stage; cold and humid again from 12.3 cal. ka B.P. to 8.2 cal. ka B.P., a tropical steppe stage; warm and humid climate, a forest-steppe developed. 2) The climate during the period of the last glacial maximum (LGM) in Weinan was characterized by a general cold-humid condition, represented by occurrence of a number of the cool-humidiphilous mollusk species such as Gastocopta amigerella and Vallonia cf. pulchella in the section. 3) Comparison of the variations in abundance of Puncture orphana at Weinan with those at Luochuan and Changwu sections suggests that the summer monsoon intensity influenced differently at the three regions during the LGM period. The Weinan was weaker summer monsoon impact during all the period, the Luochuan was influenced occasionally, and Changwu was only a very short time affected, which indicated it might be located at the western margin of the summer monsoon influence during that period. 4) The ratio of thermo-humidiphilous mollusk group to cold-aridiphilous one shows an increase tendency at about 15 cal. ka B.P., reflecting the climate warming after the deglaciation in Weinan, which is approximately corresponding to the timing of warming period of the last deglaciation, found in the East Atlantic Ocean, the South China Sea and the Loess Plateau (indicated by the phytolith study). 5) A remarkable decrease in the number of thermo-humidiphilous and cool-humidiphilous mollusk species from 12.7 - 11.6 cal. ka B.P. indicates a cooling in climate and might be the reflection of the Younger Dryas event in Weinan. 6) Variations in the ratios of thermo-humidiphilous mollusk species to cold-aridiphilous ones reflect the climate instability in Holocene. There were four warm-humid periods (10-8.1 cal. ka B.P., 6.9-6.1 cal. ka B.P., 5.2-2.6cal. ka B.P., 1.6cal. ka B.P. to the present ) and three relative cold-arid periods (8.1-6.9 cal. ka B.P., 6.1-5.2 cal. ka B.P., 2.6-1.6 cal. ka B.P.), showing about a 1,000 year climatic oscillation.

地理信息系统支持下的滑坡灾害空间分析预测-以云南小江流域为例

As a typical geological and environmental hazard, landslide has been causing more and more property and life losses. However, to predict its accurate occurring time is very difficult or even impossible due to landslide's complex nature. It has been realized that it is not a good solution to spend a lot of money to treat with and prevent landslide. The research trend is to study landslide's spatial distribution and predict its potential hazard zone under certain region and certain conditions. GIS(Geographical Information System) is a power tools for data management, spatial analysis based on reasonable spatial models and visualization. It is new and potential study field to do landslide hazard analysis and prediction based on GIS. This paper systematically studies the theory and methods for GIS based landslide hazard analysis. On the basis of project "Mountainous hazard study-landslide and debris flows" supported by Chinese Academy of Sciences and the former study foundation, this paper carries out model research, application, verification and model result analysis. The occurrence of landslide has its triggering factors. Landslide has its special landform and topographical feature which can be identify from field work and remote sensing image (aerial photo). Historical record of landslide is the key to predict the future behaviors of landslide. These are bases for landslide spatial data base construction. Based on the plenty of literatures reviews, the concept framework of model integration and unit combinations is formed. Two types of model, CF multiple regression model and landslide stability and hydrological distribution coupled model are bought forward. CF multiple regression model comes form statistics and possibility theory based on data. Data itself contains the uncertainty and random nature of landslide hazard, so it can be seen as a good method to study and understand landslide's complex feature and mechanics. CF multiple regression model integrates CF (landslide Certainty Factor) and multiple regression prediction model. CF can easily treat with the problems of data quantifying and combination of heteroecious data types. The combination of CF can assist to determine key landslide triggering factors which are then inputted into multiple regression model. CF regression model can provide better prediction results than traditional model. The process of landslide can be described and modeled by suitable physical and mechanical model. Landslide stability and hydrological distribution coupled model is such a physical deterministic model that can be easily used for landslide hazard analysis and prediction. It couples the general limit equilibrium method and hydrological distribution model based on DEM, and can be used as a effective approach to predict the occurrence of landslide under different precipitation conditions as well as landslide mechanics research. It can not only explain pre-existed landslides, but also predict the potential hazard region with environmental conditions changes. Finally, this paper carries out landslide hazard analysis and prediction in Yunnan Xiaojiang watershed, including landslide hazard sensitivity analysis and regression prediction model based on selected key factors, determining the relationship between landslide occurrence possibility and triggering factors. The result of landslide hazard analysis and prediction by coupled model is discussed in details. On the basis of model verification and validation, the modeling results are showing high accuracy and good applying potential in landslide research.

Resolution prediction and optimization of temperature programme in comprehensive two-dimensional gas chromatography

A model is developed for predicting the resolution of interested component pair and calculating the optimum temperature programming condition in the comprehensive two-dimensional gas chromatography (GC x GC). Based on at least three isothermal runs, retention times and the peak widths at half-height on both dimensions are predicted for any kind of linear temperature-programmed run on the first dimension and isothermal runs on the second dimension. The calculation of the optimum temperature programming condition is based on the prediction of the resolution of "difficult-to-separate components" in a given mixture. The resolution of all the neighboring peaks on the first dimension is obtained by the predicted retention time and peak width on the first dimension, the resolution on the second dimension is calculated only for the adjacent components with un-enough resolution on the first dimension and eluted within a same modulation period on the second dimension. The optimum temperature programming condition is acquired when the resolutions of all components of interest by GC x GC separation meet the analytical requirement and the analysis time is the shortest. The validity of the model has been proven by using it to predict and optimize GC x GC temperature programming condition of an alkylpyridine mixture. (c) 2005 Elsevier B.V. All rights reserved.

Avaliação do teor e produtividade de óleo em genótipos de girassol.

RESUMO: O presente trabalho teve como objetivo avaliar o teor e a produtividade de genótipos de girassol semeados em segunda safra no ano de 2014 em Campo Novo do Parecis ? MT, no campo experimental do Instituto Federal de Educação Ciência e Tecnologia de Mato Grosso. O delineamento experimental utilizado foi o de blocos casualizados, com 16 tratamentos (16 genótipos) e quatro repetições. As parcelas experimentais foram constituídas de 4 linhas com 6,5 m de comprimento, com espaçamento entrelinhas de 0,45 m, contendo área de 11,7 m², totalizando uma área de 748 m². Foi utilizada a população de 45000 plantas por hectare. Os dados foram submetidos à análise de variância e ao teste Scott-Knott, a 5% de probabilidade. Os genótipos que se destacaram em relação à produtividade de aquênios foram o MG 360, AGUARÁ 06, MG 305, AGUARÁ 04, CF 101, SYN 045, GNZ NEON, HELIO 251 e SYN 3950HO. Para o teor de óleo nos aquênios e produtividade de óleo, o genótipo MG 360 apresentou o maior valor e se destacou em relação aos demais genótipos analisados. ABSTRACT: This study aimed to evaluate genotypes of sunflower seeded second harvest in the year 2014 in Campus Campo Novo do Parecis, in the experimental field of the Instituto Federal de Educação Ciência e Tecnologia de Mato Grosso. The experimental design was a randomized block design with treatments 16 (16 genotypes) and four replications. The experimental plots consisted of four rows 6.5 m long with row spacing of 0.45 m, containing area of 11.7 m², totaling an area of 748 m². The population of 45000 plants per hectare is used. Data were subjected to analysis of variance and the Scott-Knott test at 5 % probability. The genotypes that stood out in relation to achenes productivity were MG 360, AGUARÁ 06, MG 305, AGUARÁ 04, CF 101, SYN 045, GNZ NEON, HELIO 251 and SYN 3950HO. For oil content and oil productivity, MG 360 genotype showed the highest value and stood out in relation to other genotypes.

Avaliação de genótipos de girassol (helianthus annuus l.) em Campo Novo Do Parecis - MT.

RESUMO: O presente trabalho teve como objetivo avaliar genótipos de girassol semeados em segunda safra no ano de 2014 em Campo Novo do Parecis ? MT, no campo experimental do Instituto Federal de Educação Ciência e Tecnologia de Mato Grosso. O delineamento experimental utilizado foi o de blocos casualizados, com 16 tratamentos (16 genótipos) e quatro repetições. As parcelas experimentais foram constituídas de 4 linhas com 6,5 m de comprimento, com espaçamento entrelinhas de 0,45 m, contendo área de 11,7 m², totalizando uma área de 748m². Foi utilizada a população de 45000 plantas por hectare. Os dados foram submetidos à análise de variância e ao teste Scott-Knott, a 5% de probabilidade. Para a massa de mil aquênios, os genótipos que se destacaram foram BRS 323, MG 360 e M734 enquanto que as os mais produtivos foram os genótipos MG 360, AGUARÁ 06, MG 305, AGUARÁ 04, CF 101, SYN 045, GNZ NEON, HELIO 251 e SYN 3950HO. ABSTRACT: This study aimed to evaluate genotypes of sunflower seeded second harvest in the year 2014 in Campus Campo Novo do Parecis, in the experimental field of the Instituto Federal de Educação Ciência e Tecnologia de Mato Grosso. The experimental design was a randomized block design with treatments 16 (16 genotypes) and four replications. The experimental plots consisted of four rows 6.5 m long with row spacing of 0.45 m, containing area of 11.7 m², totaling an area of 748 m². The population of 45000 plants per hectare is used. Data were subjected to analysis of variance and the Scott - Knott test at 5 % probability. For the mass of thousand achenes, genotypes that stood out were BRS 323, MG 360 and M734 while the most productive genotypes were the MG 360, AGUARÁ 06, MG 305, AGUARÁ 04, CF 101, SYN 045, GNZ NEON, HELIO 251 and SYN 3950HO.

Desempenho de genótipos de girassol no cerrado do leste Maranhense, ano agrícola 2013/2014.

RESUMO: No ano agrícola 2013/2014, foram conduzidos três ensaios de avaliação de genótipos de girassol, sendo dois no município de Mata Roma e um em Magalhães de Almeida, com o objetivo de identificar materiais promissores para produção de grãos e óleo. O espaçamento utilizado foi de 0,70 m entre linhas com plantas distanciadas de 0,30 m. A adubação de fundação constou de 200 kg ha-1 da fórmula 05-30-15 + micronutrientes e cobertura aos 30 dias após semeadura, usando-se 30 kg ha-1 de N e 30 kg ha-1 de K2O. Em Mata Roma, a produtividade de grãos no ensaio final 01 variou de 1.866 kg ha-1 a 2.567 kg ha-1, obtida nos genótipos Embrapa 122 e BRS G34, respectivamente, ficando a média geral do ensaio em 2.095 kg ha-1. No ensaio final 02 a produtividade de grãos variou de 1.705 kg ha-1 a 2.036 kg ha -1 para os genótipos Helio 250 e MG 360, REspectivamente, com média geral de 1.834 kg ha-1. Em Magalhães de Almeida a produtividade de grãos obtida no ensaio final constou de 1.600 kg ha-1 no genótipo Helio 251, 2.110 kg ha-1 no CF 101 e média Geral do ensaio de 1.908 kg ha -1. Os maiores teores de óleo obtidos nos três ensaios foram 40,1%, 40,6%, 40,9% e 41,4%, respectivamente, nos genótipos CF 101, Paraíso 20, BRS G41 e MG 360. ABSTRACT: In the agricultural year 2013/2014, three sunflowers genotypes tests were conducted in the state of Maranhão: two in the county of Mata Roma and one in Magalhães de Almeida, in order to identify promising materials for the production of grain and oil. The spacing used was 0.70 m between rows with plants spaced of 0.30 m. The foundation of fertilization consisted of 200 kg ha-1 formula 05-30-15 + micro-nutrient and coverage on 30 days after sowing, using 30 kg ha-1 of N and 30 kg ha-1 of K2O. In Mata Roma, grain yield in the final test 01 ranged from 1,866 kg ha-1 to 2,567 kg ha-1, obtained at Embrapa 122 and BRS G34 genotypes, respectively, getting the overall average of the test in 2,095 kg ha-1. In the final test 02, the grain yield ranged from 1,705 kg ha-1 to 2,036 kg ha-1 for Helio 250 and MG 360 genotypes, respectively, with overall average of 1,834 kg ha-1. In Magalhães de Almeida the grain yield obtained in the final test consisted of 1,600 kg ha-1 in the genotype Helio 251, 2,110 kg ha-1 in the CF 101 and overall average test of 1,908 kg ha-1. The highest oil content obtained in the three tests were 40.1%, 40.6%, 40.9% and 41.4%, respectively, in the 101 CF genotypes, Heaven 20, BRS G41 and MG 360.

Avaliação de genótipos de girassol em ambiente de sequeiro e irrigado no Distrito Federal.

RESUMO: O presente trabalho tem por objetivo caracterizar o comportamento de 16 genótipos de girassol em ambiente de sequeiro e ambiente irrigado do Cerrado do Distrito Federal visando aumentar disponibilidade de cultivares mais produtivas e adaptadas. Os ensaios foram conduzidos na área experimental da Embrapa Cerrados, Planaltina, DF. Os ensaios foram arranjados experimentalmente em blocos ao acaso, com quatro repetições. Os genótipos avaliados foram: CF 101, ADV 5504, BRS G42, BRS 323, HELIO 250, HELIO 251, SYN 045, SYN 3950HO, MG 305, MG 360, AGUARÁ 04, AGUARÁ 06, PARAÍSO 20, GNZ NEON, HLA 2012 e M734. Os caracteres avaliados foram rendimento estimado de grãos, tamanho do capítulo, peso de mil aquênios, altura de plantas, teor de óleo e dias para floração inicial. Houve diferenças significativas entre os genótipos para todas as características avaliadas. Dos 16 genótipos avaliados, os híbridos SYN 045 (3.786,2 kg ha-1) e MG 305 (4.987,2 kg ha-1) se sobressaíram quanto ao rendimento estimado de grãos. Quanto ao teor de óleo, os híbridos MG 306 (53,95%) e SYN 3950HO (49,49%) se destacaram. Foram identificados os genótipos mais promissores dentre os avaliados, podendo ser explorados em programas de melhoramento que visam o desenvolvimento de cultivares mais adaptadas.

ROSSI: Emergence of communication in Robots through Sensorimotor and Social Interaction

ROSSI: Emergence of communication in Robots through Sensorimotor and Social Interaction, T. Ziemke, A. Borghi, F. Anelli, C. Gianelli, F. Binkovski, G. Buccino, V. Gallese, M. Huelse, M. Lee, R. Nicoletti, D. Parisi, L. Riggio, A. Tessari, E. Sahin, International Conference on Cognitive Systems (CogSys 2008), University of Karlsruhe, Karlsruhe, Germany, 2008 Sponsorship: EU-FP7

Scattering poles near the real axis for two strictly convex obstacles

Iantchenko, A., (2007) 'Scattering poles near the real axis for two strictly convex obstacles', Annales of the Institute Henri Poincar? 8 pp.513-568 RAE2008

Genetic analysis of bacteriophages from clinical and environmental samples

Bacteriophages, viruses infecting bacteria, are uniformly present in any location where there are high numbers of bacteria, both in the external environment and the human body. Knowledge of their diversity is limited by the difficulty to culture the host species and by the lack of the universal marker gene present in all viruses. Metagenomics is a powerful tool that can be used to analyse viral communities in their natural environments. The aim of this study was to investigate diverse populations of uncultured viruses from clinical (a sputum of patient with cystic fibrosis, CF) and environmental samples (a sludge from a dairy food wastewater treatment plant) containing rich bacterial populations using genetic and metagenomic analyses. Metagenomic sequencing of viruses obtained from these samples revealed that the majority of the metagenomic reads (97-99%) were novel when compared to the NCBI protein database using BLAST. A large proportion of assembled contigs were assignable as novel phages or uncharacterised prophages, the next largest assignable group being single-stranded eukaryotic virus genomes. Sputum from a cystic fibrosis patient contained DNA typical of phages of bacteria that are traditionally involved in CF lung infections and other bacteria that are part of the normal oral flora. The only eukaryotic virus detected in the CF sputum was Torque Teno virus (TTV). A substantial number of assigned sequences from dairy wastewater could be affiliated with phages of bacteria that are typically found in the soil and aquatic environments, including wastewater. Eukaryotic viral sequences were dominated by plant pathogens from the Geminiviridae and Nanoviridae families, and animal pathogens from the Circoviridae family. Antibiotic resistance genes were detected in both metagenomes suggesting phages could be a source for transmissible antimicrobial resistance. Overall, diversity of viruses in the CF sputum was low, with 89 distinct viral genotypes predicted, and higher (409 genotypes) in the wastewater. Function-based screening of a metagenomic library constructed from DNA extracted from dairy food wastewater viruses revealed candidate promoter sequences that have ability to drive expression of GFP in a promoter-trap vector in Escherichia coli. The majority of the cloned DNA sequences selected by the assay were related to ssDNA circular eukaryotic viruses and phages which formed a minority of the metagenome assembly, and many lacked any significant homology to known database sequences. Natural diversity of bacteriophages in wastewater samples was also examined by PCR amplification of the major capsid protein sequences, conserved within T4-type bacteriophages from Myoviridae family. Phylogenetic analysis of capsid sequences revealed that dairy wastewater contained mainly diverse and uncharacterized phages, while some showed a high level of similarity with phages from geographically distant environments.

Cystic fibrosis gene repair: correction of ΔF508 using ZFN and CRISPR/Cas9 guide RNA gene editing tools

Cystic Fibrosis (CF) is an autosomal recessive monogenic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene with the ΔF508 mutation accounting for approximately 70% of all CF cases worldwide. This thesis investigates whether existing zinc finger nucleases designed in this lab and CRISPR/gRNAs designed in this thesis can mediate efficient homology-directed repair (HDR) with appropriate donor repair plasmids to correct CF-causing mutations in a CF cell line. Firstly, the most common mutation, ΔF508, was corrected using a pair of existing ZFNs, which cleave in intron 9, and the donor repair plasmid pITR-donor-XC, which contains the correct CTT sequence and two unique restriction sites. HDR was initially determined to be <1% but further analysis by next generation sequencing (NGS) revealed HDR occurred at a level of 2%. This relatively low level of repair was determined to be a consequence of distance from the cut site to the mutation and so rather than designing a new pair of ZFNs, the position of the existing intron 9 ZFNs was exploited and attempts made to correct >80% of CF-causing mutations. The ZFN cut site was used as the site for HDR of a mini-gene construct comprising exons 10-24 from CFTR cDNA (with appropriate splice acceptor and poly A sites) to allow production of full length corrected CFTR mRNA. Finally, the ability to cleave closer to the mutation and mediate repair of CFTR using the latest gene editing tool CRISPR/Cas9 was explored. Two CRISPR gRNAs were tested; CRISPR ex10 was shown to cleave at an efficiency of 15% and CRISPR in9 cleaved at 3%. Both CRISPR gRNAs mediated HDR with appropriate donor plasmids at a rate of ~1% as determined by NGS. This is the first evidence of CRISPR induced HDR in CF cell lines.

An investigation on the use of SNR distributions for the optimisation of coarse-fine spectrum sensing for cognitive radio

This thesis investigates the optimisation of Coarse-Fine (CF) spectrum sensing architectures under a distribution of SNRs for Dynamic Spectrum Access (DSA). Three different detector architectures are investigated: the Coarse-Sorting Fine Detector (CSFD), the Coarse-Deciding Fine Detector (CDFD) and the Hybrid Coarse-Fine Detector (HCFD). To date, the majority of the work on coarse-fine spectrum sensing for cognitive radio has focused on a single value for the SNR. This approach overlooks the key advantage that CF sensing has to offer, namely that high powered signals can be easily detected without extra signal processing. By considering a range of SNR values, the detector can be optimised more effectively and greater performance gains realised. This work considers the optimisation of CF spectrum sensing schemes where the security and performance are treated separately. Instead of optimising system performance at a single, constant, low SNR value, the system instead is optimised for the average operating conditions. The security is still provided such that at the low SNR values the safety specifications are met. By decoupling the security and performance, the system’s average performance increases whilst maintaining the protection of licensed users from harmful interference. The different architectures considered in this thesis are investigated in theory, simulation and physical implementation to provide a complete overview of the performance of each system. This thesis provides a method for estimating SNR distributions which is quick, accurate and relatively low cost. The CSFD is modelled and the characteristic equations are found for the CDFD scheme. The HCFD is introduced and optimisation schemes for all three architectures are proposed. Finally, using the Implementing Radio In Software (IRIS) test-bed to confirm simulation results, CF spectrum sensing is shown to be significantly quicker than naive methods, whilst still meeting the required interference probability rates and not requiring substantial receiver complexity increases.

Characterising novel anti-biofilm targets for the treatment of chronic Pseudomonas aeruginosa infection in the cystic fibrosis lung

The global rise in antibiotic resistance is a significant problem facing healthcare professionals. In particular within the cystic fibrosis (CF) lung, bacteria can establish chronic infection and resistance to a wide array of antibiotic therapies. One of the principle pathogens associated with chronic infection in the CF lung is Pseudomonas aeruginosa. P. aeruginosa can establish chronic infection in the CF lung partly through the use of the biofilm mode of growth. This biofilm mode of growth offers a considerable degree of protection from a wide variety of challenges such as the host immune system or antibiotic therapy. The threat posed by the emergence of chronic pathogens is prompting the development of next generation antimicrobials. The biofilm mode of growth is often central to the establishment of chronic infection and the development of antibiotic resistance. Thus, targeting biofilm formation has emerged as one of the principle strategies for the development of next generation antimicrobials. In this thesis two separate approaches were used to identify potential anti - biofilm targets. The first strategy focused on the identification of novel genes with a role in a biofilm formation. High throughput screening identified almost 300 genes which had a role in biofilm formation. A number of these genes were characterised at a phenotypic and a molecular level. The second strategy focused on the identification of compounds capable of inhibiting biofilm formation. A collection of marine sponge isolated bacteria were screened for the ability to inhibit the central pathway regulating biofilm formation, quorum sensing. A number of distinct isolates were identified that had quorum sensing inhibition activity from which, a Pseudomonas isolate was selected for further characterisation. A specific compound capable of inhibiting quorum sensing was identified using chemical analytical technologies in the supernatant of this marine isolate.

The role of bacterial interspecies communication in polymicrobial infection of the cystic fibrosis lung

There is an increasing appreciation of the polymicrobial nature of bacterial infections associated with Cystic Fibrosis (CF) and of the important role for interactions in influencing bacterial virulence and response to therapy. Patients with CF are co-infected with Pseudomonas aeruginosa, Burkholderia cenocepacia and Stenotrophomonas maltophilia. These latter bacteria produce signal molecules of the diffusible signal factor (DSF) family, which are cis-2-unsaturated fatty acids. Previous studies showed that DSF from S. maltophilia leads to altered biofilm formation and increased tolerance to antibiotics in P. aeruginosa and that these responses require the P. aeruginosa sensor kinase PA1396. The work in this thesis aims of further elucidate the influence and mechanism of DSF signalling on P. aeruginosa and examine the role that such interspecies signalling play in infection of the CF airway. Next generation sequencing technologies targeting the 16S ribosomal RNA gene were applied to DNA and RNA isolated from sputum taken from cohorts of CF and non-CF subjects to characterise the bacterial community. In parallel, metabolomics analysis of sputum provided insight into the environment of the CF airway. This analysis revealed a number of observations including; that differences in metabolites occur in sputum taken from clinically stable CF patients and those with exacerbation and DNA- and RNA-based methods suggested that a strong relationship existed between the abundance of specific strict anaerobes and fluctuations in the level of metabolites during exacerbation. DSF family signals were also detected in the sputum and a correlation with the presence of DSFproducing organisms was observed. To examine the signal transduction mechanisms used by P. aeruginosa, bioinformatics with site directed mutagenesis were employed to identify signalling partners for PA1396. A pathway suggesting a role for a number of proteins in the regulation of several factors following DSF recognition by PA1396 were observed.

Novel insights into the expression and function of p38δ MAPK in oesophageal squamous cell carcinoma

Oesophageal cancer is an aggressive malignancy which is resistant to conventional therapy and has a poor prognosis. A greater understanding of the underlying molecular biology of oesophageal cancer and the identification of novel targets is necessary for the future treatment of this disease. This thesis focuses specifically on the ill-defined and understudied p38δ mitogen-activated protein kinase (MAPK) and its function(s) in oesophageal squamous cell carcinoma (OESCC). In contrast to the three other p38 isoforms (p38α, -β and –γ which have to-date been relatively well-studied), p38δ MAPK signalling is poorly understood. Thus, this research elucidates some of the role(s) played by p38δ MAPK in cancer progression. This work outlines how loss of p38δ MAPK expression confers greater tumourigenicity in oesophageal cancer. Restoration of p38δ MAPK expression, however, has anti-proliferative and anti-migratory effects and decreases OESCC capacity for anchorageindependent growth. Using a novel application of an enzyme-substrate fusion approach, the effect of phosphorylated p38δ (p-p38δ) MAPK expression is also considered. The work goes onto describe the effect(s) of p38δ MAPK status on the chemosensitivity of OESCC to conventional cisplatin and 5-fluorouracil (CF) versus the effectiveness of doxorubicin, cisplatin and 5-fluorouracil (ACF). ACF treatment of p38δ MAPK-negative OESCC results in decreased proliferation, migration and recovery, and increased apoptosis when compared with CF treatment. This thesis examines the potential mechanisms by which p38δ MAPK expression is lost in OESCC and identifies epigenetic regulation as the probable cause of differential p38δ MAPK expression. Also analysed is the role p38δ MAPK and p-p38δ MAPK play in the cell cycle. In summary, this research identifies p38δ MAPK as a possible molecular target and a potential predictor of response to chemotherapy in OESCC patients.