Dissertations / Theses: 'Toxic factors'

7

Muñoz, Ramos Valentina. "Relationship between toxic cyanobacterial blooms, physico-chemical factors and multiple source excreta contamination in affected watershed." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=117190.

Full text

Abstract:

Missisquoi Bay (MB) is a temperate eutrophic freshwater ecosystem located in an agricultural watershed and it frequently experiences toxic Microcystis-dominated cyanobacterial blooms. Cyanobacterial population dynamics are influenced by a plethora of factors that may differ from system to system, requiring a site-specific assessment of bloom-promoting factors to design more effective bloom prevention or remediation strategies. This is the first biomonitoring study that combined data from high-throughput 16S rRNA gene amplicon sequencing, qPCR and environmental parameters from temporal and spatial samples to identify the main bloom-promoting factors. In addition, high-throughput amplicon sequencing of mitochondrial DNA genes was performed to qualitatively identify potential external sources of nutrients originating from animal excreta. Particular emphasis was placed on 1) determining whether there was a link between nutrients from external sources and cyanobacterial blooms and 2) analyzing in situ the effect of environmental factors (particularly nitrogen (N) and phosphorus (P) concentrations) on the dynamics of cyanobacterial community composition, abundance and toxicity.The concentrations of total P (TP) and total N (TN) in MB in 2009 correlated significantly with the abundance of total cyanobacterial cells, the Microcystis 16S rRNA and mcyD genes and intracellular microcystin. The results suggest that external sources of nutrients, such as surface runoff and animal excreta, played a significant role in the load of nutrients into the bay and thus in the proliferation of toxic cyanobacterial blooms. This was indicated by the detection of non-aquatic mitochondrial DNA hosts in the bay and the relationships between the pattern of surface runoff, nutrient concentrations, E. coli counts and total cyanobacterial abundance. Potential sources of nutrients from non-aquatic animal excreta in the system comprised rodents, birds, cattle and humans, indicating that efforts are required to control pollution from animal excreta in MB. During the growing season, the major cyanobacterial taxa were members of the orders Chroococcales and Nostocales. The genus Microcystis was identified as the main mcyD-carrier and main microcystin producer, hence the most problematic taxon in the cyanobacterial bloom. The correlations observed with environmental parameters suggest that increasing nutrient concentrations and TN:TP (mass) ratios approaching 11:1, coupled with an increase in temperature, promoted Microcystis-dominated toxic cyanobacterial blooms. Although the importance of nutrient ratios and absolute concentrations on cyanobacterial and Microcystis dynamics has been documented, this is the first time that an optimum TN:TP ratio for Microcystis dominance has been observed in the field. This observation provides further support to the theory that nutrient supply ratios are an important determinant of species composition in natural phytoplankton assemblages. Although the validity and prediction potential of this optimum ratio for Microcystis dominance has yet to be verified through longer-term studies, it may provide practical guidelines for nutrient management strategies to avoid the proliferation of this toxin producing cyanobacterial genus in MB. La baie Missisquoi (BM) est un écosystème d'eau douce tempérée situé dans un bassin versant où les activités agricoles sont importantes. La baie est fréquemment exposée à la prolifération de Microcystis, des cyanobactéries qui ont un potentiel toxique. La dynamique des populations de cyanobactéries est influencée par une multitude de facteurs qui peuvent varier d'un site à l'autre. Une caractérisation spécifique des facteurs qui sont responsables des floraisons est donc nécessaire afin de développer des mesures préventives et des stratégies de remédiation efficaces. C'est la première fois qu'une étude de biosurveillance combine des données de séquençage d'amplicons ARN ribosomal 16S à haut débit, la PCR en temps réel et des paramètres environnementaux d'échantillons qui ont été prélevés de façon spatio-temporelle pour identifier les facteurs qui causent les floraisons. De plus, le séquençage à haut débit d'amplicons ciblant l'ADN mitochondrial a été utilisé pour identifier qualitativement les sources potentielles de nutriments qui proviennent d'excréments d'origine animale. Une insistance a été accordée plus spécifiquement à 1) l'évaluation de l'existence d'un lien entre les nutriments provenant de sources externes et les périodes de floraison de cyanobactéries et 2) l'analyse in situ des impacts des facteurs environnementaux (particulièrement les concentrations d'azote (N) et de phosphore (P)) sur la structure des communautés de cyanobactéries, leur abondance et leur toxicité.Les concentrations de P et de N à la baie Missisquoi en 2009 étaient fortement corrélées avec l'abondance des cellules de cyanobactéries, des gènes de Microcystis (ARNr 16S et mcyD) ainsi qu'avec la concentration de microcystine intracellulaire. Les résultats suggèrent que les sources externes de nutriments telles que le ruissellement de surface et les excréments d'origine animale ont contribué de manière importante à la charge d'éléments nutritifs dans la baie et ainsi à la prolifération de cyanobactéries qui produisent des toxines. Ces conclusions ont été corroborées par la présence d'ADN mitochondrial d'hôtes non aquatiques et les liens entre les types de ruissellement de surface, les concentrations de nutriments, et les dénombrements de E.coli et de cyanobactéries. Les sources potentielles de nutriments provenant des excréments animaux dans la baie incluaient les rongeurs, les oiseaux, le bétail et les humains. Ces résultats indiquent que des efforts sont requis dans la baie Missisquoi pour contrôler la pollution provenant des excréments d'origine animale.Pendant la période de floraison, la communauté de cyanobactéries était principalement composée de Chroococcales et Nostocales. Les cyanobactéries du genre Microcystis étaient à la fois les principales porteuses du gène mcyD et les principales productrices de microcystine. Ce taxon a donc été le plus problématique pendant les fleurs d'eau. Les corrélations observées entre les facteurs environnementaux suggèrent que la dominance des Microcystis a été associée à l'augmentation des concentrations en nutriments, à un ratio TN:TP (masse) d'une valeur aux environs de 11:1, combinée à une hausse de température.Même si l'importance des concentrations et des ratios de nutriments sur la dynamique des cyanobactéries et des Microcystis a déjà été documentée, c'est la première fois qu'un ratio optimum pour le genre Microcystis est observé sur le terrain. Cette observation est en accord avec la théorie voulant que les ratios de nutriments soient importants pour déterminer la composition des espèces faisant partie de la communauté phytoplanctonique. La validité et le potentiel de prédiction de ce ratio optimum pour la dominance des Microcystis devraient être vérifiés à l'aide d'études à long terme, car il pourrait devenir un critère important pour développer des stratégies de gestion de nutriments qui permettraient d'éviter la prolifération de ce genre de cyanobactéries nocives.

APA, Harvard, Vancouver, ISO, and other styles

8

Okolo, Bartholomew Ndubuisi. "Alcohol tolerance in yeast : on factors influencing the inhibitory and toxic effects of alcohols on distilling yeast." Thesis, University of Strathclyde, 1986. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=24267.

Full text

Abstract:

An investigation of the factors influencing the inhibitory and toxic effects of ethanol and higher alcohols, byproducts of alcoholic fermentation, on yeast, is presented. The relative potency of alcohols was found to correlate strongly with the carbon chain-length or molecular size and the lipid solubility of the respective alcohols. Higher alcohols act synergistically with each other and with ethanol in causing cell death of suspensions of non-growing Saccharomyces cerevisiae. The presence of higher alcohols in fermented broth, even at low concentrations, and other by-products of alcoholic fermentation, could explain the higher potency of ethanol produced during fermentation compared to added ethanol. The kinetics of uptake of labelled ethanol supplied at different concentrations gave no evidence of enzymic involvement in the ethanol uptake process. The rate of release of labelled ethanol by cells fed labelled glucose paralled the rate of p14sC-C0b2s release. This does not support the view that ethanol accumulates within the cells to higher concentrations than occur in the medium. Supplementation of a basal synthetic medium with various nutrients did not confer additional survival capacity on yeast against the adverse effects of alcohol. Osmotic pressure did not influence alcohol toxicity below 10% (w/v) sorbitol equivalent of osmotic pressure. Alcohol toxicity is not influenced by hydrogen ion concentration (pH) over a range of pH 5.3 to 3.5.

APA, Harvard, Vancouver, ISO, and other styles

9

Ovesen, Jerald Lee. "Aryl Hydrocarbon Receptor Ligands of Widely Different Toxic Equivalency Factors Induce Similar Histone Marks in Target Gene Chromatin." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1291408173.

Full text

APA, Harvard, Vancouver, ISO, and other styles

10

Ястремська, Лариса Сергіївна, І. Прекрасна, О. Таширев, and г. Снєгур. "Resistance of Negev desert microbial community to Cu2+ and Hg2+." Thesis, National Aviation University, 2013. http://er.nau.edu.ua/handle/NAU/38607.

Full text

Abstract:

The aim of the work is to evaluate the ability to keep stabile functioning of microbial community of Negev Desert clay (Israel) in the presence of typical for damaging effect toxic metals - Cu2 + and Hg2+ . The results show the stability of Negev desert microbial community to the extremely high bactericidal concentrations of toxic metals (1000 mg/l Cu2+and 10 mg/l Hg2+), despite the trace concentrations of these metals (0,23 mg/l Cu2+) in the desert ecosystem. This indicates a high resistance and ability of microbial cenosis to adapt to extreme factors. It can be supposed, according to obtained results, that Negev desert microbial community is able to interact with toxic metals and involve them in biogeochemical cycles. On the base of metal resistant microorganisms from Negev desert ecosystem development the technology of industrial heavy metal wastewater purification is available.

APA, Harvard, Vancouver, ISO, and other styles

11

Pförtner, Ramona [Verfasser], Wolfgang [Akademischer Betreuer] Brück, and Mikael [Akademischer Betreuer] Simons. "Astroglial and therapeutic factors affect demyelination in murine models with toxic demyelination / Ramona Pförtner. Gutachter: Wolfgang Brück ; Mikael Simons. Betreuer: Wolfgang Brück." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2013. http://d-nb.info/1048469824/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

12

Chahine, Samir. "Factors enhancing the interactions of lower rim calix[4]arene derivatives towards toxic metal cations in solution : versatile behaviour in the solid state." Thesis, University of Surrey, 2004. http://epubs.surrey.ac.uk/843546/.

Full text

Abstract:

The synthesis of calix[4]arene derivatives, 5,11,17,23-tetra-tert-butyl[25,27-bis(hydroxy)-26,28-bis(ethylthioethoxy)]-calix[4]arene, L3, and 5,11,17,23-tetra-tert-butyl[25,27-bis(ethylethanoate)oxy-26,28-bis(ethylthioethoxy)]-calix[4]arene, L4, are reported. These ligands are structurally (1H, 13C NMR and X-ray crystallography) and thermodynamically (solubility, calorimetry) characterised. In addition to L3 and L4, 5,11,17,23-tetra-tert-butyl[25,26,27,28-tetrakis(ethylethanoate)- calix[4]arene, L1 and 5,11,17,23-tetra-tert-butyl[25,26,27,28-tetrakis(methylketonemethoxy)-calix[4]arene, L2, are included in this study. Therefore, ligands L1, L2, L3 and L4 were investigated by 1H NMR technique to obtain information regarding their conformation in solution and the active sites of interaction with metal cations in different deuterated solvents at 298 K. Conductance measurements were performed to establish the composition of the metal-ion complexes with L1, L3 and L4 in acetonitrile, methanol, N,N-dimethylformamide and propylene carbonate at 298.15 K. Weak or non-existing interaction was observed in the latter solvent. However, complexes of 1:1 stoichiometry are formed in all cases. Potentiometric and calorimetric measurements were carried out to establish the thermodynamic parameters of complexation of these ligands in acetonitrile, methanol, and N,N-dimethylformamide at 298.15 K. L1 and L2 behaved in a parallel fashion in acetonitrile, with a peak selectivity for Ca2+ relative to other bivalent metal cations investigated. Complexation was absent in other media. On the other hand, L4 showed higher discrimination ability towards metal cations relative to L1 in acetonitrile, methanol and N,N-dunethylformamide. In moving to L3, the selectivity of the ligand was improved with respect to L1 and L4 to recognize only Ag+ and Hg2+. The ligand and the medium effects on the complexation process are quantitatively assessed. Solution and transfer thermodynamic parameters for the reactants and the product involved in the complexation of Ag+, Hg2+ with L3 and L4 in acetonitrile (as a reference solvent), methanol and N,N-dimethylformamide (as receiving solvents) are discussed. The complexation and solution data for the reactants and the product were used to calculate the standard enthalpies of coordination as a means of checking the reliability of the data. Extraction affinity of L3 for Ag+ was investigated in the water-dichloromethane saturated system. Crystals of several ligands and their metal-ion complexes were isolated and characterized by X-ray diffraction studies. Conclusions and suggestions for further work in this area are given.

APA, Harvard, Vancouver, ISO, and other styles

13

Ramsay, Bruce A. "The use of complex toxic industrial waste as a fermentation substrate /." Thesis, McGill University, 1987. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75450.

Full text

Abstract:

Two complex wastes were considered for biological conversion into a marketable product. One waste, peat runoff water (the waste-water that remains after the mining of peat), was found to be unsuitable for biological conversion to any product since it contained an insufficient quantity of carbon. The other waste, NVR (non-volatile residue, the major waste from the manufacture of nylon 6$ sp prime 6 sp prime$), was found to be a suitable carbon and energy source for the production of PHB (poly-$ beta$-hydroxybutyric acid) by Pseudomonas cepacia ATCC 17697. A general approach to the development of complex toxic wastes as fermentation substrates was formulated. NVR was found to be toxic to microorganisms. None grew in enrichment culture containing 2.0% NVR. P. cepacia was the most resistant microorganism found. It could grow well in up to 1.3% NVR. It also grew on butanoic, pentanoic, and hexanoic acid as well as 6-hexanolactone. These were found to be the major toxic components of NVR. P. cepacia was grown in a NVR-limited chemostat with a NVR feed concentration well in excess of the toxic NVR concentration. In nitrogen-limited, batch fermentation on fructose, P. cepacia accumulated PHB in excess of 50% of its dry weight. A 2-stage chemostat process for the production of PHB from NVR by P. cepacia was investigated with encouraging results.

APA, Harvard, Vancouver, ISO, and other styles

14

Bäckström, Nils, Hanna Egeman, and Hanna Mattsson. "Why do companies produce vegan and vegetarian products imitated with real meat products? : Exploring a virgin topic on the Swedish market." Thesis, Högskolan i Jönköping, Internationella Handelshögskolan, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-40016.

Full text

Abstract:

With the support of four vegetarian and vegan companies established on the Swedish market, Astrid och Aporna, Ekko Gourmet, Tzay and Quorn, the objective of this study is to understand why companies produce vegan and vegetarian products imitated with real meat products as well as how these companies market these products. The data was collected through interviews with suitable representatives from respective company. The empirical data collected from the interviews have further been analysed together with theories from past researches. The research approaches of this study has been a mixture of inductive and deductive when handling our data. The results from this thesis enlightens that there are contrasting strategies behind the products’ visual appearance, chosen target group and marketing among the different vegetarian and vegan companies on the Swedish market. We have discovered patterns between the companies’ target audiences and how these companies have designed their products depending of target audience Due to time limitations and companies’ unwillingness to participate in interviews, a broader perspective on the topic could not be given. Also, this study only looks at vegan and vegetarian companies operating in Sweden. A suggestion for future research is to investigate the consumer’s perspective and perceptions of vegan and vegetarian products by conducting a quantitative research to distinguish if the companies’ strategies are consistent with the perceptions of consumers on the Swedish market.

APA, Harvard, Vancouver, ISO, and other styles

15

Mitchell, Danielle. "Analysis of interactions between the A1 subunit of cholera toxin and ADP-ribosylation factor 6 /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.

Find full text

Abstract:

Thesis (Ph.D. in Microbiology) -- University of Colorado Denver, 2007. Typescript. Includes bibliographical references (leaves 183-207). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

APA, Harvard, Vancouver, ISO, and other styles

16

Downes-Tettmar, Naomi. "Factors that impact Pseudo-nitzschia spp. occurrence, growth, and toxin production." Thesis, University of Plymouth, 2013. http://hdl.handle.net/10026.1/1588.

Full text

Abstract:

This work investigates, for the first time, the Pseudo-nitzschia (PN) dynamics in the western English Channel (L4) and the environmental factors impacting on domoic acid (DA) production in these waters. This is combined with laboratory studies examining key environmental factors and the multifactorial impact of multiple macronutrient and micronutrient availability on PN growth and DA production. An LC-MS method was established, optimised, and compared with ELISA for the accurate and reproducible extraction and determination of particulate and dissolved DA. The method was used to measure the seasonal variation in DA at L4 during 2009 and this was compared to PN seasonal abundance and diversity. Three groups a P. delicatissima-group, a P. seriata-group, and a P. pungens/multiseries-group were identified and were found to have different ecological distributions with the latter two groups significantly correlating with DA concentration. Macronutrients, in combination with other environmental factors, were found to influence PN populations at L4. Multifactorial laboratory culture experiments investigating the availability of nitrate, phosphate, and silicate, confirmed that the interrelatedness of all these nutrients significantly affected the growth, decline, and DA production of P. multiseries, and highlight the importance of both phosphate and silicate availability for DA production. When the impacts of both macronutrient (phosphate and silicate) and micronutrient (iron and copper) availability were investigated, limited growth and DA production was observed in P. multiseries cultures. Results revealed the complexity and interrelationship of factors affecting both PN growth and DA production. Furthermore, molecular methods were developed to elucidate the PN species present from 2009 Lugol’s-preserved L4 samples. DNA was successfully extracted and amplified from these samples which had been stored for up to 2 years. Initial sequence analysis identified the rbcL DNA marker as an informative site for future work with a number of L4 sequences closely relating to different Pseudo-nitzschia spp.

APA, Harvard, Vancouver, ISO, and other styles

17

Bollinger, Laurie M. "Factors affecting prevalence of Shiga toxin-producing Escherichia coli in cattle /." abstract and full text PDF (UNR users only), 2008. http://0-gateway.proquest.com.innopac.library.unr.edu/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3329564.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

LEÃO, CLÁUDIO. "Desenvolvimento e validação de metodologia para a determinação de monocloroacetato de sódio e dicloroacetato de sódio em cocoamido,N-[(3-dimetilamino)propil],betaína via cromatografia a gás: GC/FID, GC/ECD e GC/MS." reponame:Repositório Institucional do IPEN, 2016. http://repositorio.ipen.br:8080/xmlui/handle/123456789/26796.

Full text

Abstract:

Submitted by Claudinei Pracidelli (cpracide@ipen.br) on 2016-11-11T09:28:13Z No. of bitstreams: 0 Made available in DSpace on 2016-11-11T09:28:13Z (GMT). No. of bitstreams: 0 O monocloroacetato de sódio (MCAS) e o dicloroacetato de sódio (DCAS) são compostos tóxicos e irritantes ao ser humano e nocivos ao meio ambiente, sendo impurezas indesejáveis na cocoamido propil betaína (CAPB), que é um surfactante anfótero utilizado em produtos de consumo dos segmentos cosmético e domiciliar. Diante dos requisitos de concentração em nível de mg/kg exigidos pelos órgãos reguladores de saúde do governo, tornou-se mandatório o emprego de metodologia com limite de quantificação, precisão e exatidão adequados aos rígidos controles de processo pelos fabricantes da CAPB, bem como, dispor de técnicas convencionais com poder de resolução e proficiência pelo controle de qualidade e neste contexto inseriu-se a cromatografia a gás. Neste estudo foram estabelecidos os procedimentos analíticos que definiram as melhores condições para identificar e quantificar as impurezas MCAS e DCAS na matriz CAPB por meio da cromatografia a gás. A preparação das amostras consistiu da derivação das impurezas MCAS e DCAS a ésteres etílicos e a extração líquido-líquido em hexano para separar dos demais constituintes da matriz. Os modos de detecção acoplados à cromatografia a gás foram a ionização pela chama (GC/FID), a captura de elétrons (GC/ECD) e a espectrometria de massas (GC/MS). A validação comprovou que as metodologias são lineares entre 4 e 50 mg/kg com recuperação de 70 a 120%, apresentam limites de quantificação inferiores a 10 mg/kg e produziram médias e incertezas similares na amostra examinada, constituindo-se alternativas para a determinação de cloroacetatos em betaínas. Dissertação (Mestrado em Tecnologia Nuclear) IPEN/D Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

APA, Harvard, Vancouver, ISO, and other styles

19

Finnerty, Gerald Thomas. "Factors determining the transition to seizure in the tetanus toxin model of epilepsy." Thesis, Imperial College London, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361453.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Everling, Nils. "Extending the explanatory power of factor pricing models using topic modeling." Thesis, KTH, Skolan för datavetenskap och kommunikation (CSC), 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-210253.

Full text

Abstract:

Factor models attribute stock returns to a linear combination of factors. A model with great explanatory power (R2) can be used to estimate the systematic risk of an investment. One of the most important factors is the industry which the company of the stock operates in. In commercial risk models this factor is often determined with a manually constructed stock classification scheme such as GICS. We present Natural Language Industry Scheme (NLIS), an automatic and multivalued classification scheme based on topic modeling. The topic modeling is performed on transcripts of company earnings calls and identifies a number of topics analogous to industries. We use non-negative matrix factorization (NMF) on a term-document matrix of the transcripts to perform the topic modeling. When set to explain returns of the MSCI USA index we find that NLIS consistently outperforms GICS, often by several hundred basis points. We attribute this to NLIS’ ability to assign a stock to multiple industries. We also suggest that the proportions of industry assignments for a given stock could correspond to expected future revenue sources rather than current revenue sources. This property could explain some of NLIS’ success since it closely relates to theoretical stock pricing. Faktormodeller förklarar aktieprisrörelser med en linjär kombination av faktorer. En modell med hög förklaringsgrad (R2) kan användas föratt skatta en investerings systematiska risk. En av de viktigaste faktorerna är aktiebolagets industritillhörighet. I kommersiella risksystem bestäms industri oftast med ett aktieklassifikationsschema som GICS, publicerat av ett finansiellt institut. Vi presenterar Natural Language Industry Scheme (NLIS), ett automatiskt klassifikationsschema baserat på topic modeling. Vi utför topic modeling på transkript av aktiebolags investerarsamtal. Detta identifierar ämnen, eller topics, som är jämförbara med industrier. Topic modeling sker genom icke-negativmatrisfaktorisering (NMF) på en ord-dokumentmatris av transkripten. När NLIS används för att förklara prisrörelser hos MSCI USA-indexet finner vi att NLIS överträffar GICS, ofta med 2-3 procent. Detta tillskriver vi NLIS förmåga att ge flera industritillhörigheter åt samma aktie. Vi föreslår också att proportionerna hos industritillhörigheterna för en aktie kan motsvara förväntade inkomstkällor snarare än nuvarande inkomstkällor. Denna egenskap kan också vara en anledning till NLIS framgång då den nära relaterar till teoretisk aktieprissättning.

APA, Harvard, Vancouver, ISO, and other styles

21

Ahn, Kisuh. "Topic indexing and retrieval for open domain factoid question answering." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/3794.

Full text

Abstract:

Factoid Question Answering is an exciting area of Natural Language Engineering that has the potential to replace one major use of search engines today. In this dissertation, I introduce a new method of handling factoid questions whose answers are proper names. The method, Topic Indexing and Retrieval, addresses two issues that prevent current factoid QA system from realising this potential: They can’t satisfy users’ demand for almost immediate answers, and they can’t produce answers based on evidence distributed across a corpus. The first issue arises because the architecture common to QA systems is not easily scaled to heavy use because so much of the work is done on-line: Text retrieved by information retrieval (IR) undergoes expensive and time-consuming answer extraction while the user awaits an answer. If QA systems are to become as heavily used as popular web search engines, this massive process bottle-neck must be overcome. The second issue of how to make use of the distributed evidence in a corpus is relevant when no single passage in the corpus provides sufficient evidence for an answer to a given question. QA systems commonly look for a text span that contains sufficient evidence to both locate and justify an answer. But this will fail in the case of questions that require evidence from more than one passage in the corpus. Topic Indexing and Retrieval method developed in this thesis addresses both these issues for factoid questions with proper name answers by restructuring the corpus in such a way that it enables direct retrieval of answers using off-the-shelf IR. The method has been evaluated on 377 TREC questions with proper name answers and 41 questions that require multiple pieces of evidence from different parts of the TREC AQUAINT corpus. With regards to the first evaluation, scores of 0.340 in Accuracy and 0.395 in Mean Reciprocal Rank (MRR) show that the Topic Indexing and Retrieval performs well for this type of questions. A second evaluation compares performance on a corpus of 41 multi-evidence questions by a question-factoring baseline method that can be used with the standard QA architecture and by my Topic Indexing and Retrieval method. The superior performance of the latter (MRR of 0.454 against 0.341) demonstrates its value in answering such questions.

APA, Harvard, Vancouver, ISO, and other styles

22

Kejuo, Kingsley. "TOPIC: Critical Success Factors: Telecommunication Network equipment Procurement projects. A case study of MTN Nigeria." Thesis, KTH, Tillämpad maskinteknik (KTH Södertälje), 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-118753.

Full text

APA, Harvard, Vancouver, ISO, and other styles

23

Mohammed, Hesham Hamada Taha. "Molecular analysis of adenylyl cyclase : bacillus anthracis edema factor exotoxin." kostenfrei, 2009. http://www.opus-bayern.de/uni-regensburg/volltexte/2010/1411/.

Full text

APA, Harvard, Vancouver, ISO, and other styles

24

Slater, Louise. "Identification of Host Factors Required for Anthrax Lethal Toxin Intoxication Using Chemical Genetic and RNAi Approaches." Thesis, Harvard University, 2011. http://dissertations.umi.com/gsas.harvard:10066.

Full text

Abstract:

Bacterial toxins have co-opted host cell machinery in order to enter cells and exert their deleterious effects. Anthrax toxin is composed of the receptor binding protein protective antigen (PA), and the enzymatic subunits lethal factor (LF) and edema factor (EF), which form the binary toxin complexes lethal toxin, LeTx (PA + LF), and edema toxin, EdTx (PA + EF). PA binds to receptors on the surface of host cells and shuttles LF and EF into cells through the endocytic pathway. Upon endosome acidification, PA oligomers insert into the endosomal membrane and form functional pores that deliver LF and EF into the cytoplasm. Translocation of the N-terminal domain of LF, $LF_N$, through PA pores formed in lipid bilayers in vitro does not require host machinery. However, translocation of the related fusion protein $LF_N$-DTA across the membrane of toxin-loaded endosomes in vitro requires the addition of cytosolic translocation factors that include the COPI coatamer complex. We performed high-throughput small molecule and RNAi screens to identify host factors required for LF translocation, using LeTx-induced cell death as a phenotype. We describe the characterization of small molecule inhibitors of LeTx-induced cell death that inhibit toxin entry. Further, we describe the role of the endosomal chaperone GRP78 and the cytoplasmic CCT chaperonin in toxin translocation. RNAi knockdown of GRP78 and CCT subunits inhibited LeTx and EdTx delivered through the endocytic pathway. CCT knockdown additionally inhibited translocation of LF through PA pores formed directly in the plasma membrane, while GRP78 had no effect. Furthermore, we show that the role of GRP78 in toxin translocation is specific to translocation from the early endosome. Together with biochemical data, we propose that GRP78 facilitates translocation by unfolding LF and EF at near-neutral pH. In addition, we show that in CCT-knockdown cells, lethal levels of toxin reach the endosome, suggesting that CCT has a role in translocation and/or refolding of LF and EF. These studies highlight previously unidentified strategies used by anthrax toxin to hijack host cellular machinery in order to gain access to the cytosol.

APA, Harvard, Vancouver, ISO, and other styles

25

Sittlington, Samuel Brian Kerr. "What are the factors that influence the effectiveness of anti-money laundering policy implementation in the UK? : exploring money laundering crime and policy." Thesis, Northumbria University, 2014. http://nrl.northumbria.ac.uk/36465/.

Full text

Abstract:

Anti-Money Laundering has become the term for many stakeholders including Financial Institutions and law enforcement agencies that attempt to prevent the movement of money obtained from criminal activity. This research combines two important areas within the money laundering arena: Anti-Money Laundering preventative measures and Anti-Money Laundering Policy. This study aims to discover significant determinants that influence the current anti-money laundering policy (AML) by understanding the relationship between criminal activity, stakeholder activity and public policy. This research adopts a pragmatic approach which embraces the use of mixed methods. The strategy using mixed method (triangulation) approach for data collection increase the rigor and robustness of the research in terms of exploration, validation and confirmation of findings. From a pragmatic perspective a better understanding of the research problem could be achieved that overcomes complexities in the context of the research, such as access to key stakeholders. The research question “What are the factors that influence the effectiveness of AML policy implementation in the UK?” is answered using a four phase approach to data collection and analysis that incorporates theme identification from literature, focus group interviews, survey questionnaire and verification of factors through individual participation. The findings of the research point to three areas of activity that could be confirmed as areas in which policy changes can be applied. These are ‘sentencing’ as a deterrent to crime; ‘reporting regime’ for suspicious activity reports, and ‘criminal knowledge’ based on law enforcement tactics’. The methods used also provided an abundance of additional material that set the findings in their appropriate environment.

APA, Harvard, Vancouver, ISO, and other styles

26

Boudreau, Denise M. "The association between HMG-CoA inhibitor use and breast cancer risk & a validation study of patient interview data and pharmacy records for antihypertensive, statin, and antidepressant medication use /." Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/7934.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Alkimin, Gilberto Dias de [UNESP]. "Toxicidade de cádmio e zinco em Danio rerio: comparação entre valores permitidos em legislação para proteção da vida aquática e a potencial atuação como interferentes endócrinos." Universidade Estadual Paulista (UNESP), 2016. http://hdl.handle.net/11449/138031.

Full text

Abstract:

Submitted by GILBERTO DIAS DE ALKIMIN null (gilberto_cdz@hotmail.com) on 2016-04-15T17:08:54Z No. of bitstreams: 1 Dissertação_FINAL.pdf: 6110695 bytes, checksum: c7822bb8a9272890beb5ba8faae113c6 (MD5) Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-04-19T19:40:04Z (GMT) No. of bitstreams: 1 alkimin_gd_me_soro.pdf: 6110695 bytes, checksum: c7822bb8a9272890beb5ba8faae113c6 (MD5) Made available in DSpace on 2016-04-19T19:40:04Z (GMT). No. of bitstreams: 1 alkimin_gd_me_soro.pdf: 6110695 bytes, checksum: c7822bb8a9272890beb5ba8faae113c6 (MD5) Previous issue date: 2016-02-19 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) A contaminação dos ambientes aquáticos por metais é uma preocupação mundial, pois são elementos bioacumulativos e persistentes. Diversos desses compostos possuem a capacidade de alterar o sistema endócrino (denominados interferentes endócrinos – IE), sendo o cádmio (Cd) e o zinco (Zn) suspeitos dessa atuação, segundo a literatura. Para verificação dessa potencialidade algumas análises biológicas são indicadas como: 1) a realização do teste de dessorção no auxílio ao posterior cálculo do fator de bioconcentração (FBC), para detecção do real valor incorporado do contaminante pelo organismo e predição dos efeitos tóxicos causados; 2) análises histológicas de órgãos como as gônadas e o fígado e 3) análise de vitelogenina (VTG) no fígado de machos. Dessa forma o objetivo deste trabalho foi averiguar a atuação endócrina dos metais Cd e Zn em concentrações permitidas em ambientes aquáticos para a proteção da vida aquática por meio de: a) estudo do tempo de dessorção de Cd e Zn da parte externa do organismo; b) determinação do FBC de Cd e Zn em D. rerio após exposição crônica; c) avaliação da possibilidade de Cd e Zn provocarem alterações histológicas em gônada e fígado de machos e fêmeas de D. rerio e d) análise da capacidade de Cd e Zn em induzir a produção de VTG no fígado de machos de D. rerio. Para a realização do teste de dessorção, organismos adultos de D. rerio, foram expostos por 72 horas a Cd (1 µg de Cd/L) e Zn (180 µg de Zn/L) seguindo-se a lavagem do organismo-teste em ácido nítrico 2% por diferentes tempos (0h; 5; 60; 90; 120; 150 e 180 minutos) e posterior construção da curva de dessorção. As análises de FBC, histologia e histoquímica foram realizadas após exposição crônica (21 dias) em regime semi-estático, com troca total da solução a cada 72 horas, em separado a concentrações permitidas por legislação nacional (1 µg de Cd/L e 180 µg de Zn/L) e internacional (0,25 µg de Cd/L e 120 µg de Zn/L) para proteção da vida aquática. Desse modo, após o final da exposição organismos foram levados a digestão, leitura da concentração do contaminante e o FBC foi calculado, bem como machos e fêmeas foram sacrificados e passaram por procedimento de preparo histológico, corados com hematoxilina e eosina e análise qualitativa de gônada e fígado e machos após preparo histológico sofreram marcação histoquímica para detecção de VTG no fígado. Pelos resultados obtidos, verificou-se que a dessorção dos metais apresentou diferença, sendo a dessorção de Cd realizada em 90 minutos e a de Zn em 60 minutos; a bioconcentração de Cd foi semelhante nas duas concentrações de exposição e a de Zn foi inversamente proporcional à concentração exposta. As análises histológicas mostraram que Cd e Zn provocam alterações de forma pronunciada tanto em gônadas quanto em fígados de fêmeas, enquanto gônadas de machos não sofreram graves alterações e os fígados apresentaram lesões que podem comprometer o funcionamento do órgão, além disso, observou-se a produção de VTG no fígado de machos de D. rerio expostos a Cd e Zn. Por fim, a união das técnicas utilizadas comprova que Cd e Zn, mesmo em concentrações permitidas por legislação são capazes de atuarem como IE em D. rerio, necessitando de mudanças na legislação para valores mais restritivos com a finalidade de garantir a saúde endócrina dos organismos aquáticos. The contamination of aquatic environments by metals is a global concern because they are bioaccumulative and persistent elements. Several such compounds have the ability to change the endocrine system (called endocrine disruptors - ED), and cadmium (Cd) and zinc (Zn) that suspicious activity, according to the literature. To verify the potential some biological analyzes are given as: 1) the realization of the desorption test to aid the subsequent calculation of bioconcentration factor (BCF), for determining the real corporate value of the contaminant by the body and prediction of toxic effects; 2) histological analysis of organs such as the gonads and liver and 3) analysis of vitellogenin (VTG) in the liver of males. Thus the aim of this study was to determine the endocrine actions of Cd and Zn in allowed concentrations in aquatic environments for the protection of aquatic life through: a) study time desorption of Cd and Zn from outside the body; b) determination of CBF of Cd and Zn in D. rerio after chronic exposure; c) assessment of the possibility of Cd and Zn cause histological changes in the liver and gonads of males and females of D. rerio d) analysis of the ability of Cd and Zn in inducing the production of VTG in the liver of males of D. rerio. To perform the desorption test, adult organisms of D. rerio were exposed for 72 hours Cd (1 µg/L of Cd) and zinc (180 µg/L of Zn) followed by washing of the organism under test 2% nitric acid for different times (0 h, 5, 60, 90, 120, 150 and 180 minutes) and subsequent construction of desorption curve. The analyses of BCF, histologic and histochemical were performed after chronic exposure (21 days) under semi-static system, with complete exchange of the solution every 72 hours in separat concentrations allowed by national legislation (1 µg of Cd/L and 180 µg of Zn/L) and international (0.25 µg Cd/L and 120 µg Zn/L) for protection of aquatic life. Thus, after the end of exposure organisms were taken digestion, of the contaminant concentration of the reading and the CBF was calculated as well as males and females were euthanized and underwent histological preparation procedure, stained with hematoxylin and eosin and qualitative analysis of gonads and liver histological was performed and males after preparing suffered histochemical staining VTG detection in the liver. This waythe desorption of metals it was different, with desorption of Cd performed in 90 minutes and Zn in 60 minutes, the bioconcentration of Cd was similar in both exposure concentration and the Zn was inversely proportional to the concentration exposed, histological analyzes show that Cd and Zn cause pronounced changes in both gonads, as in female livers, but the gonads of male suffered no serious changes and livers showed lesions that can compromise the function of organ, besides, it was observed VTG production in the liver D. rerio males exposed to Cd and Zn. Finally, the union of techniques shows that Cd and Zn, even at concentrations allowed by law are able to act as IE in D. rerio, requiring changes in legislation for more stringent values in order to ensure the endocrine health organisms water.

APA, Harvard, Vancouver, ISO, and other styles

28

Teixeira, Sergio de Mello Novita. "Caracterização genotípica de cepas de Pasteurella multocida proveniente de suínos." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/10/10134/tde-29062012-135605/.

Full text

Abstract:

Um total de 123 isolados de Pasteurella multocida provenientes de suínos foi avaliado através da PCR para pesquisa de genes codificadores de capsula, toxina dermonecrótica e outros fatores de virulência. As amostras foram caracterizadas como tipo capsular A (78,8 %) e tipo capsular D (21%). Nenhum dos isolados foi positivo para presença de toxina dermonecrótica. Os genes codificadores dos fatores de virulência pesquisados foram observados nas freqüências de 93,5 % para nanB, 92,7% para psl, 91,9% para oma87 e nanH, 87,8% para sodA,87% para hghA,83,7% para ompH, 82,9% para sodC, 79,7% para ptfA e exbBD tonB,73,2% para hgbB, 14,6% para pfhA e 4,9% para tbpA. Estes achados são compatíveis com o descrito na literatura internacional. A total of 123 Pasteurella multocida strains from swine was evaluated through PCR to detect capsular, dermonecrotic toxin codifying genes and others virulence factors. The strains were identified as capsular type A (78.8 %) and capsular type D (21%). None of isolates were positive to dermonecrotic toxin gene. The virulence factors genes were detected in the following frequency: 93.5 % to nanB, 92.7% to psl, 91.9% to oma87 and nanH, 87.8% to sodA, 87% to hghA, 83.7% to ompH, 82.9% to sodC, 79.7% to ptfA and exbBD tonB, 73.2% to hgbB, 14.6% to pfhA and 4.9% to tbpA. These findings were in accordance with international literature.

APA, Harvard, Vancouver, ISO, and other styles

29

Santiesteban, Oscar. "Assessment of molecular interactions via magnetic relaxation: a quest for inhibitors of the anthrax toxin." Doctoral diss., University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/5481.

Full text

Abstract:

Anthrax is severe disease caused by the gram-positive Bacillus anthracis that can affect humans with deadly consequences. The disease propagates via the release of bacterial spores that can be naturally found in animals or can be weaponized and intentionally released into the atmosphere in a terrorist attack. Once inhaled, the spores become activated and the anthrax bacterium starts to reproduce and damage healthy macrophages by the release of the anthrax toxin. The anthrax toxin is composed of three virulent factors: (i) anthrax protective antigen (APA), (ii) anthrax lethal factor (ALF), and (iii) anthrax edema factor (AEF) that work in harmony to effectuate the lethality associated with the disease. Out of the two internalized factors, ALF has been identified to play a critical role in cell death. Studies in animals have shown that mice infected with an anthrax strain lacking ALF survive the infection whereas when ALF is present the survivability of the mice is eliminated. Although the current therapy for anthrax is antibiotic treatment, modern medicine faces some critical limitations when combating infections. Antibiotics have proven very efficient in eliminating the bacterial infection but they lack the ability to destroy or inhibit the toxins released by the bacteria. This is a significant problem since ALF can remain active in the body for days after the infection is eliminated with no way of inhibiting its destructive effects. The use of inhibitors of ALF is an attractive method to treat the pathogenesis of anthrax infections. Over the last decade several inhibitors of the enzymatic activity of ALF have been identified. In order to identify inhibitors of ALF a variety of screening approaches such as library screenings, Mass Spectroscopy- based screenings and scaffold-based NMR screening have been used. Results from these screening have yielded mainly small molecules that can inhibit ALF in low micromolar to nanomolar concentrations. Yet, although valuable, these results have very little significance with regards to treating ALF in a real-life scenario since pharmaceutical companies are not willing to invest in further developing these inhibitors. Furthermore, the low incidence of inhalation anthrax, the lack of a market for an ALF inhibitor, and the expenses associated with the approval process of the FDA, have hindered the motivation of pharmaceutical companies to pursuit these kind of drugs. Therefore we have screened a small-molecule library of FDA approved drugs and common molecules in order to identify currently approved FDA drugs that can also inhibit ALF (Chapter III). The screening revealed that five molecules: sulindac, fusaric acid, naproxen, ketoprofen and ibuprofen bound to either ALF or APA with sulindac binding both. Additionally, we have developed a nanoparticle-based screening method that assesses molecular interactions by magnetic relaxation changes (Chapter II). Using this assay, we were able to accurately measure the dissociation constants of different interactions between several ligands and macromolecules. Moreover, we have used computational docking studies to predict the binding site of the identified molecules on the ALF or APA (Chapter IV). These studies predicted that two molecules sulindac and fusaric acid could be potential inhibitors of ALF since they bind at the enzymatic pocket. As a result, we tested the inhibitory potential of these molecules as well as that of the metabolic derivatives of sulindac (Chapter V). Results from these studies provided conclusive evidence that fusaric acid and sulindac were both strong inhibitors of ALF. Furthermore, the metabolic derivatives of sulindac, sulindac sulfide and sulindac sulfone also inhibited ALF. Overall, taking together these results we have discovered the alternate use of a currently used drug for the treatment of ALF pathogenesis. Ph.D. Doctorate Chemistry Sciences Chemistry

APA, Harvard, Vancouver, ISO, and other styles

30

Laabei, Maisem. "Using phospholipid vesicles to assay bacterial lytic agents, examining factors and identifying virulence loci which alter toxin production in Staphylococcus aureus." Thesis, University of Bath, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.636526.

Full text

Abstract:

Burns represent one of the most devastating forms of injury with infection complications representing the highest risk of mortality. The primary objective of the Bacteriosafe project was the development of a smart wound dressing that would respond to the presence of bacteria in burn wounds. The basis of this sensing system employed the use of phospholipid vesicles, containing a self-quenchable fluorescent dye. These vesicles mimic the eukaryotic cell membrane and as such are susceptible to bacterial cytolytic factors which lyse the vesicles, generating an observable and measurable fluorescent response. My primary role in this project was to identify the vesicle lysing agents secreted from the two most frequent burn wound colonisers, Staphylococcus aureus and Pseudomonas aeruginosa. We identified the small amphipathic alpha helical peptide toxins from S. aureus and glycolipid molecules derived from P. aeruginosa as the agents responsible for vesicle lysis. The identification of these molecules led to the development of two novel phenotypic assays designed to measure these important virulence factors, as discussed in chapter 3 and 4. In chapter 5 we examined the role of toxic shock syndrome toxin-1 (TSST-1) in repressing global exoprotein expression. Our results demonstrate that TSST-1 does not repress toxin secretion and strains expressing TSST-1 retain their ability to lyse vesicles. In chapter 6 we explored the use of subinhibitory oxacillin in inducing the alternative penicillin binding protein 2a (PBP2a) in community-acquired methicillin resistant S. aureus (CA-MRSA) strains to down-regulate toxicity. Previous work in the Massey lab demonstrated that the expression of the mecA gene, which encodes PBP2a, resulted in reduced toxicity in hospital-acquired (HA) -MRSA. CA-MRSA strains are considered highly toxic and have a considerably lower level of PBP2a expression. Treatment of CA-MRSA strains with subinhibitory oxacillin did result in a down-regulation of some toxins but also the up-regulation of others, highlighting the pleiotropic effect oxacillin had on virulence regulation. In chapter 7 we developed an approach that uses the genome sequences of a set of related clinical S. aureus strains to identify novel virulence loci by associating genetic polymorphisms with specific virulence phenotypes using a genome wide association study (GWAS). This analysis resulted in the identification of four novel loci which when mutated lead to a reduction in toxicity. We demonstrate that the GWAS approach is an effective method in identifying candidate SNPs which may be important in altering virulence but do highlight limitations of this approach, primarily the generation of false positives.

APA, Harvard, Vancouver, ISO, and other styles

31

Heltshe, Sonya Lenore. "Quantification of length-bias in screening trials with covariate-dependent test sensitivity /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.

Find full text

Abstract:

Thesis (Ph.D. in Biostatistics, Department of Preventive Medicine and Biometrics) -- University of Colorado Denver, 2007. Typescript. Includes bibliographical references (leaves 89-93). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

APA, Harvard, Vancouver, ISO, and other styles

32

Heine, Wiebke Alexandra Verfasser], and Petra [Akademischer Betreuer] [Dersch. "The influence of the cytotoxic necrotizing factor toxin of Yersinia pseudotuberculosis on pathogenesis / Wiebke Alexandra Heine ; Betreuer: Petra Dersch." Braunschweig : Technische Universität Braunschweig, 2017. http://d-nb.info/1175817325/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

33

Phelps, Christopher. "The Importance of Listeriolysin O in Host Cell Invasion by Listeria monocytogenes and its Use in Vaccine Development." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1555582881156988.

Full text

APA, Harvard, Vancouver, ISO, and other styles

34

Wetzel, Amy Noel. "Studies in Shiga toxin-producing Escherichia coli O157:H7 determination of factors contributing to the dissemination of Escherichia coli O157:H7 among dairy farms /." Columbus, Ohio : Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1133239436.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

Paddock, Zachary Dean. "Shiga toxin producing Escherichia coli (STEC) in cattle: factors affecting fecal shedding of E. coli O157:H7 and detection methods of non-O157 STEC." Diss., Kansas State University, 2013. http://hdl.handle.net/2097/15732.

Full text

Abstract:

Doctor of Philosophy Department of Diagnostic Medicine/Pathobiology T. G. Nagaraja Escherichia coli O157:H7 and over 380 non-O157 serotypes of Shiga toxin producing E. coli (STEC) are human food-borne pathogens that inhabit the hindgut of ruminants and are shed in the feces, which subsequently contaminate food products. Recent epidemiological data have shown that six non-O157 STEC (O26, O103, O111, O121, O45 and O145) account for majority of human STEC infections. Fecal shedding of STEC is influenced by a number of factors, including diets, supplements, and feed additives, because of their potential to alter hindgut ecosystem. Not much is known about the fecal shedding of non-O157 STEC in cattle because of lack of standardized detection methods. Fecal shedding of E. coli O157:H7 was studied to determine the effects of supplemental urea, monensin, an ionophore, and ractopamine, a beta-agonist. Cattle fed monensin at 44 mg/kg of feed had lower (P = 0.05) fecal O157:H7 prevalence than cattle fed 33 mg/kg. Supplemental urea (0.35 or 0.70% of the diet) and inclusion of ractopamine at 200 mg/animal/day had no effect on fecal shedding of E. coli O157:H7. In an experimental inoculation study, inclusion of corn starch to a distiller’s grains (DG)-supplemented diet had no effect on fecal shedding of E. coli O157 suggesting that either the decreased starch content in the DG-supplemented diet is not a factor in the increased shedding of E. coli O157:H7 or inclusion of pure starch in the diet may not have achieved our intended goal to have starch flow into the hindgut similar to that of corn grain. A multiplex PCR to detect O26, O45, O103, O111, O121, O145, and O157 was designed and applicability to detect the seven serogroups in cattle feces was evaluated. A multiplex PCR, designed to detect E. coli O104, feces showed presence of O104 in cattle feces (20.6%), but the isolated strains did not carry genes characteristic of the virulent strain responsible for the 2011 food-borne outbreak in Germany. Two preharvest interventions, a siderophore receptor and porin proteins-based vaccine and a Lactobacillus acidophilus-based direct-fed microbial, intended to control E. coli O157, had no effect on fecal shedding of O26 assessed by culture-based or PCR-based method.

APA, Harvard, Vancouver, ISO, and other styles

36

Jaros, Mark J. "A joint model for longitudinal data and competing risks /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2008.

Find full text

Abstract:

Thesis (Ph.D. in Biostatistics) -- University of Colorado Denver, 2008. Typescript. Includes bibliographical references (leaves 117-119). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;

APA, Harvard, Vancouver, ISO, and other styles

37

Yenikent, Seren [Verfasser], and Joachim [Akademischer Betreuer] Kimmerle. "Understanding the effects of topic factors and threat exposure on motivation to participate in knowledge artefacts : The case of Wikipedia / Seren Yenikent ; Betreuer: Joachim Kimmerle." Tübingen : Universitätsbibliothek Tübingen, 2019. http://d-nb.info/1204880891/34.

Full text

APA, Harvard, Vancouver, ISO, and other styles

38

Kreutz, Philippe. "Les prédicats factifs: une enquête logique et linguistique." Doctoral thesis, Universite Libre de Bruxelles, 1995. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/212508.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Alazzabi, Mufida. "Insulin-like growth factor-II (IGF2) gene of zebrafish and its use as a biogenetic marker for the assay of epigenetic toxin exposure." Thesis, University of Ottawa (Canada), 2004. http://hdl.handle.net/10393/26561.

Full text

Abstract:

The purpose of this research was to determine whether expression analysis of the IGF2 gene in zebrafish, a gene whose transcription is known to be regulated by DNA methylation in mammals, can be used as a marker or indicator of DNA methylation due to toxin exposure in fish embryos. We examined the expression of IGF2, IGF1, and IGFBP-1 in zebrafish embryos treated with sodium arsenite (thought to inhibit DNA methylation), nickel chloride (thought to cause DNA hypermethylation), trichostatin A (a histone deacetylase inhibitor), 5-azaC (thought to cause methyltransferase inhibition), cadmium chloride (thought to cause DNA hypermethylation) and mercury chloride (unknown). (Abstract shortened by UMI.)

APA, Harvard, Vancouver, ISO, and other styles

40

Mercado, Salazar Jorge Anibal, and S. M. Masud Rana. "A Confirmatory Analysis for Automating the Evaluation of Motivation Letters to Emulate Human Judgment." Thesis, Högskolan Dalarna, Institutionen för information och teknik, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:du-37469.

Full text

Abstract:

Manually reading, evaluating, and scoring motivation letters as part of the admissions process is a time-consuming and tedious task for Dalarna University's program managers. An automated scoring system would provide them with relief as well as the ability to make much faster decisions when selecting applicants for admission. The aim of this thesis was to analyse current human judgment and attempt to emulate it using machine learning techniques. We used various topic modelling methods, such as Latent Dirichlet Allocation and Non-Negative Matrix Factorization, to find the most interpretable topics, build a bridge between topics and human-defined factors, and finally evaluate model performance by predicting scoring values and finding accuracy using logistic regression, discriminant analysis, and other classification algorithms. Despite the fact that we were able to discover the meaning of almost all human factors on our own, the topic models' accuracy in predicting overall score was unexpectedly low. Setting a threshold on overall score to select applicants for admission yielded a good overall accuracy result, but did not yield a good consistent precision or recall score. During our investigation, we attempted to determine the possible causes of these unexpected results and discovered that not only is topic modelling limitation to blame, but human bias also plays a role.

APA, Harvard, Vancouver, ISO, and other styles

41

St, Pierre Liam Daniel. "Identification and comparative analysis of novel factors from the venom gland of the coastal taipan (Oxyuranus scutellatus) and related species." Thesis, Queensland University of Technology, 2005. https://eprints.qut.edu.au/16677/1/Liam_St_Pierre_Thesis.pdf.

Full text

Abstract:

Snake venoms are a complex mixture of polypeptide and other molecules that adversely affect multiple homeostatic systems within their prey in a highly specific and targeted manner. Amongst the most potently toxic venoms in the world are those of the Australian venomous snakes, which belong almost exclusively to the elapid family. Their venoms posses a number of unique properties by which they target the mammalian cardiovascular and neuromuscular systems and are the focus for the identification of novel pharmacologically interesting compounds which may be of diagnostic or therapeutic benefit. Although much is known about the biochemical properties of Australia snake venoms as a whole, little research attention has focused upon individual components at the molecular level. This thesis describes the cloning, characterisation and comparative analysis of a number of unique toxins from the venom gland of the coastal taipan (Oxyuranus scutellatus) and a total of seven other related Australian snakes. These include the factor X- and factor V-like components of a prothrombin activator that causes a highly coagulable state in mammals. Comparative analysis of the sequences identified in this study, along with recombinant expression of an active form of the factor X-like component, provides important information on the structural, functional and evolutionary relationships of these molecules. Numerous other toxins were similarly identified and characterised including a pseudechetoxin-like protein, multiple phospholipase A2 enzymes and neurotoxin isoforms as well as vasoactive venom natriuretic peptides. Identified transcripts included not only toxin sequences but also other cellular peptides implicated in toxin processing, including a calglandulin-like protein. This thesis is the first description of the majority of these molecules at either the cDNA or protein level, and provides a means to study the activity of individual components from snake venoms and probe their function within the systems they specifically target. This study represents the most detailed and comprehensive description to date of the cloning and characterisation of different genes associated with envenomation from Australian snakes.

APA, Harvard, Vancouver, ISO, and other styles

42

St, Pierre Liam Daniel. "Identification and comparative analysis of novel factors from the venom gland of the coastal taipan (Oxyuranus scutellatus) and related species." Queensland University of Technology, 2005. http://eprints.qut.edu.au/16677/.

Full text

Abstract:

Snake venoms are a complex mixture of polypeptide and other molecules that adversely affect multiple homeostatic systems within their prey in a highly specific and targeted manner. Amongst the most potently toxic venoms in the world are those of the Australian venomous snakes, which belong almost exclusively to the elapid family. Their venoms posses a number of unique properties by which they target the mammalian cardiovascular and neuromuscular systems and are the focus for the identification of novel pharmacologically interesting compounds which may be of diagnostic or therapeutic benefit. Although much is known about the biochemical properties of Australia snake venoms as a whole, little research attention has focused upon individual components at the molecular level. This thesis describes the cloning, characterisation and comparative analysis of a number of unique toxins from the venom gland of the coastal taipan (Oxyuranus scutellatus) and a total of seven other related Australian snakes. These include the factor X- and factor V-like components of a prothrombin activator that causes a highly coagulable state in mammals. Comparative analysis of the sequences identified in this study, along with recombinant expression of an active form of the factor X-like component, provides important information on the structural, functional and evolutionary relationships of these molecules. Numerous other toxins were similarly identified and characterised including a pseudechetoxin-like protein, multiple phospholipase A2 enzymes and neurotoxin isoforms as well as vasoactive venom natriuretic peptides. Identified transcripts included not only toxin sequences but also other cellular peptides implicated in toxin processing, including a calglandulin-like protein. This thesis is the first description of the majority of these molecules at either the cDNA or protein level, and provides a means to study the activity of individual components from snake venoms and probe their function within the systems they specifically target. This study represents the most detailed and comprehensive description to date of the cloning and characterisation of different genes associated with envenomation from Australian snakes.

APA, Harvard, Vancouver, ISO, and other styles

43

Larsson, Malin. "Computational methods for analyzing dioxin-like compounds and identifying potential aryl hydrocarbon receptor ligands : multivariate studies based on human and rodent in vitro data." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-139487.

Full text

Abstract:

Polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are omnipresent and persistent environmental pollutants. In particular, 29 congeners are of special concern, and these are usually referred to as dioxin-like compounds (DLCs). In the European Union, the risks associated with DLCs in food products are estimated by a weighted sum of the DLCs’ concentrations. These weights, also called toxic equivalency factors (TEFs), compare the DLCs’ potencies to the most toxic congener, 2,3,7,8-tetrachloro-dibenzo-p-dioxin (2378- TCDD). The toxicological effects of PCDD/Fs and PCBs are diverse, ranging from chloracne and immunological effects in humans to severe weight loss, thymic atrophy, hepatotoxicity, immunotoxicity, endocrine disruption, and carcinogenesis in rodents. Here, the molecular structures of DLCs were used as the basis to study the congeneric differences in in vitro data from both human and rodent cell responses related to the aryl hydrocarbon receptor (AhR). Based on molecular orbital densities and partial charges, we developed new ways to describe DLCs, which proved to be useful in quantitative structure-activity relationship modeling. This thesis also provides a new approach, the calculation of the consensus toxicity factor (CTF), to condense information from a battery of screening tests. The current TEFs used to estimate the risk of DLCs in food are primarily based on in vivo information from rat and mouse experiments. Our CTFs, based on human cell responses, show clear differences compared to the current TEFs. For instance, the CTF of 23478-PeCDF is as high as the CTF for 2378-TCDD, and the CTF of PCB 126 is 30 times lower than the corresponding TEF. Both of these DLCs are common congeners in fish in the Baltic Sea. Due to the severe effects of DLCs and their impact on environmental and human health, it is crucial to determine if other compounds have similar effects. To find such compounds, we developed a virtual screening protocol and applied it to a set of 6,445 industrial chemicals. This protocol included a presumed 3D representation of AhR and the structural and chemical properties of known AhR ligands. This screening resulted in a priority list of 28 chemicals that we identified as potential AhR ligands.

APA, Harvard, Vancouver, ISO, and other styles

44

Gauthier, Audrey, and Audrey Gauthier. "Analyse de l'expérience d'hommes qui participent à un groupe psychoéducatif dans le cadre du programme Toxico-Justice offert en milieu carcéral sous l'angle des facteurs d'aide." Master's thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/27962.

Full text

Abstract:

Les groupes de traitement de la toxicomanie en milieu carcéral offrent un contexte d’intervention particulier. Bien que plusieurs études abordent leur efficacité, les processus d’intervention qui y prennent place ont été très peu explorés dans les écrits scientifiques. Il devenait alors pertinent d’entreprendre cette recherche, qui tente de saisir l’expérience des hommes qui participent à un groupe psychoéducatif dans le cadre du programme Toxico-Justice offert en milieu carcéral. S’inscrivant dans la perspective de l’interactionnisme symbolique, l’étude utilise l’entretien qualitatif semi-directif afin d’élaborer un portrait subjectif de l’expérience de groupe ainsi que du rôle des interactions dans cette expérience. L’échantillon est constitué de dix hommes ayant complété le programme Toxico-Justice depuis moins d’un an au moment de l’entrevue. Les résultats obtenus ont permis d’analyser la présence de huit facteurs d’aide au sein du groupe : le partage d’information, la connaissance de soi, la cohésion, l’universalité, l’altruisme, la catharsis, la révélation de soi et l’apprentissage par imitation. La présence de ces facteurs d’aide a été modérée par certaines difficultés qui ont teinté les interactions entre les membres du groupe. Le contexte de groupe ouvert ainsi que le contexte carcéral font partie des facteurs qui auraient rendu les interactions entre les membres du groupe plus difficiles. Néanmoins, les résultats montrent que les participants ont atteint l’objectif du groupe, qui est d’approfondir leur réflexion sur leurs habitudes de consommation et de réduire leur risque de récidive en regard des conduites délinquantes associées à la toxicomanie. Différentes pistes sont explorées afin d’amenuiser l’impact des difficultés vécues dans l’expérience des participants. Les groupes de traitement de la toxicomanie en milieu carcéral offrent un contexte d’intervention particulier. Bien que plusieurs études abordent leur efficacité, les processus d’intervention qui y prennent place ont été très peu explorés dans les écrits scientifiques. Il devenait alors pertinent d’entreprendre cette recherche, qui tente de saisir l’expérience des hommes qui participent à un groupe psychoéducatif dans le cadre du programme Toxico-Justice offert en milieu carcéral. S’inscrivant dans la perspective de l’interactionnisme symbolique, l’étude utilise l’entretien qualitatif semi-directif afin d’élaborer un portrait subjectif de l’expérience de groupe ainsi que du rôle des interactions dans cette expérience. L’échantillon est constitué de dix hommes ayant complété le programme Toxico-Justice depuis moins d’un an au moment de l’entrevue. Les résultats obtenus ont permis d’analyser la présence de huit facteurs d’aide au sein du groupe : le partage d’information, la connaissance de soi, la cohésion, l’universalité, l’altruisme, la catharsis, la révélation de soi et l’apprentissage par imitation. La présence de ces facteurs d’aide a été modérée par certaines difficultés qui ont teinté les interactions entre les membres du groupe. Le contexte de groupe ouvert ainsi que le contexte carcéral font partie des facteurs qui auraient rendu les interactions entre les membres du groupe plus difficiles. Néanmoins, les résultats montrent que les participants ont atteint l’objectif du groupe, qui est d’approfondir leur réflexion sur leurs habitudes de consommation et de réduire leur risque de récidive en regard des conduites délinquantes associées à la toxicomanie. Différentes pistes sont explorées afin d’amenuiser l’impact des difficultés vécues dans l’expérience des participants. Prison-based substance abuse treatment groups provide a specific context for intervention. Although several studies address their effectiveness, the group processes of these groups have been little explored in scientific literature. It became relevant to undertake this research, which attempts to capture the experience of men who participate in a psychoeducational group as part of the Toxico-Justice, a prison-based program. Based on symbolic interactionism, the study uses semi-directive interviews to develop a subjective picture of group experience and the role of interactions in this experience. The sample consisted of ten men who completed the Toxico-Justice program for less than one year at the time of the interview. Results highlighted the presence of eight therapeutic factors within the group: information sharing, self-understanding, cohesion, universality, altruism, catharsis, self-disclosure and interpersonal learning. The presence of these therapeutic factors has been moderated by some difficulties encountered in the interactions between the members of the group. The open group context as well as the prison context are among the factors that would have made interactions between group members more difficult. Nevertheless, the results show that participants met the group's objective of deepening their reflection on their using habits and reducing their risk of recidivism in relation to delinquent behaviors associated with drug addiction. Different avenues are explored in order to reduce the impact of the difficulties encountered in the participants' experience. Prison-based substance abuse treatment groups provide a specific context for intervention. Although several studies address their effectiveness, the group processes of these groups have been little explored in scientific literature. It became relevant to undertake this research, which attempts to capture the experience of men who participate in a psychoeducational group as part of the Toxico-Justice, a prison-based program. Based on symbolic interactionism, the study uses semi-directive interviews to develop a subjective picture of group experience and the role of interactions in this experience. The sample consisted of ten men who completed the Toxico-Justice program for less than one year at the time of the interview. Results highlighted the presence of eight therapeutic factors within the group: information sharing, self-understanding, cohesion, universality, altruism, catharsis, self-disclosure and interpersonal learning. The presence of these therapeutic factors has been moderated by some difficulties encountered in the interactions between the members of the group. The open group context as well as the prison context are among the factors that would have made interactions between group members more difficult. Nevertheless, the results show that participants met the group's objective of deepening their reflection on their using habits and reducing their risk of recidivism in relation to delinquent behaviors associated with drug addiction. Different avenues are explored in order to reduce the impact of the difficulties encountered in the participants' experience.

APA, Harvard, Vancouver, ISO, and other styles

45

Albornoz, Luis Antonio Llanco. "Caracterização molecular dos principais fatores de virulência e genótipos de Clostridium perfringens isolados de frangos com enterite necrótica." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/42/42132/tde-27062014-164523/.

Full text

Abstract:

Clostridium perfringens causa enterite necrótica aviária devido à produção de toxinas que lesam o intestino. Neste estudo, de 94 amostras nove apresentaram C. perfringens, totalizando 22 isolados. Todos exceto um isolado, possuíram os genes nanI (95%) e/ou nanJ (81%), e 19/22, mostraram atividade neuraminidase em hemácias de frango. A atividade hemaglutinante foi observada em poucos isolados (26%). Todos os isolados foram plc positivos (toxina α), sendo classificados como tipo A. Sete isolados (31,8%) abrigaram o gene tpeL que codifica a toxina TpeL. Isolados tpeL+ mostraram efeito citotóxico característico da ação desta toxina. Alguns isolados mostraram capacidade de aderir e invadir células Vero. A maioria dos isolados foi resistente à sulfaquinoxalina (100%), cefalexina (95%) e eritromicina (95%) e sensíveis (100%) à cefoxitina, amoxicilina, enrofloxacina, amoxicilina-ácido clavulânico, penicilina-estreptomicina, cloranfenicol e metronidazol. Todos os isolados foram agrupados geneticamente em sete clusters, apresentando se como um grupo heterogêneo. Clostridium perfringens cause avian necrotic enteritis due to production of toxins that damage the intestine. In this study, nine out of 94 samples had C. perfringens, totaling 22 isolates. All the isolates with exception of one, possessed the genes nanI (95 %) and/or nanJ (81 %), and 19/22 showed neuraminidase activity in chicken erythrocytes. The hemagglutinating activity was observed in a few isolates (26 %). All isolates were plc positive (toxin α) being classified as type A. Seven isolates (31.8%) harbored tpeL gene encoding the toxin TpeL. TpeL + isolates showed characteristic cytotoxic effect of the action of this toxin. Some isolates showed ability to adhere and invade Hep-2 cells. Most of the isolates were resistant sulphaquinoxaline (100%), cephalexin (95%) and erythromycin (95%) and sensitivity (100%) to cefoxitin, amoxicillin, enrofloxacin, amoxicillin - clavulanic acid, penicillin -streptomycin, chloramphenicol and metronidazole. All isolates were genetically grouped into seven clusters, presenting itself as a heterogeneous group.

APA, Harvard, Vancouver, ISO, and other styles

46

Corelli, Barbara. "Investigation of Klebsiella virulence : the role of capsule in Klebsiella rhinoscleromatis pathogenesis and characterization of a Klebsiella pneumoniae capsule mutant unable to produce colibactin toxin." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC265/document.

Full text

Abstract:

L’émergence et la dissémination récentes de clones hypervirulents et multi-résistants de Klebsiella pneumoniae ont renouvelé l'intérêt général envers Klebsiella. Cependant, notre connaissance de la pathogénèse de Klebsiella au niveau moléculaire et cellulaire reste faible. Dans ce travail, nous avons mené deux axes de recherche focalisés sur la pathogénèse de Klebsiella. Le premier projet visait à caractériser un mutant de capsule de K. pneumoniae incapable de produire une toxine colibactine fonctionnelle. La colibactine est un métabolite secondaire génotoxique produit principalement par des souches commensales et extraintestinales pathogènes d’Escherichia coli, mais également par des souches de K. pneumoniae. Elle induit des cassures double brin conduisant à la formation de tumeurs dans des cancers colorectaux et contribue à une virulence accrue de la bactérie. Cependant la structure, les voies de biosynthèse, la sécrétion et le mode d’action de la colibactine restent à définir. Le laboratoire avait préalablement observé qu’un mutant de capsule de K. pneumoniae n’était pas capable de produire une colibactine fonctionnelle, suggérant un rôle de la capsule dans ce processus. Nous avons ensuite démontré qu’en fait la capsule n’est pas impliquée dans la fonction de la colibactine, et que l’incapacité du mutant de la capsule à produire une génotoxicité est due à une mutation avec un fort effet dominant négatif dans la protéine ClbD, une enzyme essentielle de la voie de synthèse de la colibactine. Nous caractérisons actuellement cette mutation pour comprendre comment elle affecte la structure et la fonction de ClbD. Le second projet étudiait le rôle de la capsule dans la pathogénèse de K. rhinoscleromatis. K. rhinoscleromatis est une sous-espèce de K. pneumoniae, responsable du rhinosclérome, une maladie chronique granulomateuse des voies aériennes supérieures spécifiquement humaine, et caractérisée par la formation de macrophages spumeux atypiques appelés cellules de Mikulicz. Or les mécanismes physiopathologiques de cette pathologie sont peu connus. A l’aide d’un modèle murin, nous avons observé qu’un mutant de capsule de K. rhinoscleromatis est atténué in vivo, mais aussi que les cellules de Mikulicz sont recrutées lors d’une infection avec un inoculum élevé du mutant de capsule de K. rhinoscleromatis. Ces données nous indiquent 1) que la capsule est un facteur de virulence de K. rhinoscleromatis qui n’est pas impliqué dans la formation et le recrutement des cellules de Mikulicz, et 2) que des facteurs spécifiques de K. rhinoscleromatis contrôlant la formation de cellules de Mikulicz existent et restent à identifier. Les nouvelles données concernant la pathogénèse de Klebsiella apportées par notre travail représentent une contribution significative dans la connaissance du rhinosclérome et du rôle d’une enzyme impliquée dans la synthèse de la colibactine, tout en ouvrant de nouveaux axes de recherche sur la pathogénèse de K. pneumoniae et K. rhinoscleromatis The recent emergence and global expansion of hypervirulent and multidrug-resistant clones of K. pneumoniae have increased general interest in Klebsiella. However, knowledge of Klebsiella pathogenesis at the molecular and cellular level is still scant. We pursued two lines of research focused on Klebsiella pathogenesis. The first aimed to characterize a K. pneumoniae capsule mutant unable to produce a functional colibactin. Colibactin is a genotoxic secondary metabolite produced mainly by commensals and extraintestinal pathogenic E. coli strains, but also by some K. pneumoniae strains. It induces double-strand DNA breaks leading to tumor formation in colorectal cancer and contributes to increased virulence. However, its structure, biosynthesis, secretion and mode of action have yet to be fully defined. Previous work from our laboratory showed that a K. pneumoniae capsule mutant was unable to produce a functional colibactin, suggesting a role for capsule in this process. We report herein that capsule does not in fact have a role in the colibactin effect and that the inability of the capsule mutant to induce DNA damage is due to a strong dominant negative mutation in ClbD, an essential enzyme of the colibactin biosynthetic pathway. We are currently characterizing this mutation to understand how it deeply affects ClbD structure and function. The second project explored the role of capsule (CPS) in K. rhinoscleromatis pathogenesis. K. rhinoscleromatis is a K. pneumoniae subspecies responsible for rhinoscleroma, a human specific chronic granulomatous disease of the upper airways characterized by the formation of atypical foamy macrophages called Mikulicz cells. However, little is known about the pathophysiological mechanisms underlying this disease. Using our mouse model, we report that a K. rhinoscleromatis CPS mutant is attenuated in vivo but also that Mikulicz cells are observed upon infection with higher doses of K. rhinoscleromatis CPS mutant. Altogether, our data indicate that 1) CPS is a virulence factor of K. rhinoscleromatis, which is not involved in the specific appearance of Mikulicz cells and that 2) the K. rhinoscleromatis specific factors controlling the appearance of Mikulicz cells remain to be identified. The new insights brought to Klebsiella pathogenicity by this work represent a significant contribution to the understanding of rhinoscleroma pathogenesis and of the role of an enzyme implicated in colibactin biosynthesis. This opens new lines of research on K. pneumoniae and K. rhinoscleromatis pathogenesis

APA, Harvard, Vancouver, ISO, and other styles

47

Gauriat, Marie-Anne. "Connaissance des facteurs déterminants dans la conduite d'un procédé pour la production de toxine par Corynebacterium diphteriae utilisée dans la formulation de vaccins." Thesis, Toulouse, INSA, 2012. http://www.theses.fr/2012ISAT0041/document.

Full text

Abstract:

Avec pour problématique une importante variabilité des lots de production vaccinale contre la diphtérie, une analyse intégrative du métabolisme central, du fer et du transcriptome de Corynebacterium diphtheriae, cultivé en conditions les plus proches de la culture industrielle, ont permis d’élargir les connaissances sur le comportement de la bactérie en conditions de production industrielle, et plus particulièrement sur l’existence de corrélations entre activité métabolique et virulence. L'analyse du métabolisme central et la comparaison de l'expression des gènes de C. diphtheriae, ont permis de mettre en évidence l'importance du maltose dans l'établissement de la virulence. Ce sucre, largement présent dans notre alimentation, est ainsi rencontré par la bactérie lors de son processus de colonisation de l'hôte. La consommation du maltose lors de la phase stationnaire, coïncident avec la production de la toxine, semble ainsi liée aux réactions de maintenance et à la production de métabolites secondaires plutôt qu'à la croissance. Plusieurs gènes liés à la capture et au catabolisme du maltose sont liés à la production de la toxine diphtérique. Cependant, les mécanismes de régulation sont complexes, impliquant plusieurs régulateurs. Une étude sur les besoins en fer de la bactérie et les liens avec la pathogénicité a été réalisée. En effet, le gène de la toxine diphtérique est régulé par DtxR, répresseur activé par Fe2+. Elle a permis d'évaluer la capacité de stockage en fer de la bactérie et la limite de concentration intracellulaire pour obtenir une production de toxine. Un effort a été apporté afin de visualiser les ferritines synthétisées par la bactérie par la technique NanoSIMS. Enfin, l'analyse de l'expression des gènes de C.diphtheriae cultivé en condition de limitation en fer et supplémentée en fer a apporté une quantité d'informations sur les liens entre métabolisme central et du fer, virulence et stress oxydatif. Cette démarche a été mise à profit afin de proposer à l'industriel des pistes d'optimisations du procédé et d’améliorations de la productivité en toxine diphtérique. Via l’ajustement de certains paramètres physico-chimiques (visant l'oxygénation et une meilleure métabolisation du maltose), il est possible d'obtenir un gain de production significatif (titre final en toxine multiplié par 2,5). La productivité spécifique en toxine peut être également multipliée par 2,2 par une astucieuse étape de dilution et recyclage de la biomasse en fin de culture Faced with an important variability in production yields of vaccines against diphtheria, a dynamic systemic approach, including central and iron metabolism and transcriptome analysis, led to an improved knowledge of Corynebacterium diphtheriae physiology, notably as regards the connection of central metabolism and virulence. Gene expression analysis coupled to metabolic characterization enabled a correlation between maltose consumption and virulence to be established. Because of the typical human diet, maltose is present in the human oropharynx where it may serve as a key nutrient source for C. diphtheriae. Maltose consumption during stationary phase, coupled with toxin production, seems to be linked to maintenance and secondary metabolites rather than growth. Several genes, including uptake and catabolism of maltose, are related to diphtheria toxin production. However, mechanisms of regulation are complex and may involve several transcriptional regulators. Bacterial iron requirements and its relation to pathogenicity were considered. Indeed, diphtheria toxin gene is regulated by Fe2+ activated DtxR. These studies revealed that C. diphtheriae is able to store an important quantity of intracellular iron within ferritin-like proteins visualized by NanoSIMS microscopy and the definition of an intracellular threshold concentration provoking expression of toxin production. Finally, genome-wide gene expression analysis of C.diphtheriae in iron starvation and iron excess conditions provided information on relations between central and iron metabolism, virulence establishment and oxidative stress. The resulting knowledge was exploited to suggest process optimization strategies to enhance toxin production, currently being assessed by the industrial partner. Adjusting some key physico-chemical parameters (targeting oxygenation and better maltose metabolization) enabled significant gains in toxin production (2.5 fold increase). Specific productivity could be increased by 2.2 thanks to a novel biomass dilution and recycling step at the end of the culture

APA, Harvard, Vancouver, ISO, and other styles

48

Mathevon, Laure. "Analyse des facteurs pronostics d’efficacité du traitement de la spasticité par injection de toxine botulinique. De l’analyse du muscle spastique en imagerie ultrasonore à l’immunisation post injection de toxine botulinique." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSES023/document.

Full text

Abstract:

Notre objectif était de rechercher une méthode d’évaluation musculaire afin de déterminer des facteurs de non réponse tissulaire à une injection de toxine botulique (TB) dans un muscle spastique, chez l’adulte post AVC et chez l’enfant paralysé cérébral (PC). Une étude de reproductibilité et 3 revues systématiques de la littérature ont été réalisées. Les mesures échographiques de l’épaisseur et de l’angle des pennation des fibres du muscle gastrocnémien médial en 2D sont reproductibles. La mesure du module d’élasticité par Shear Wave Ultrasound Elastography délivre une information fiable sur la rigidité du muscle gastrocnémien médial spastique au repos.L’analyse du devenir du muscle post-injection rapporte que la TB participe au remodelage du muscle spastique avec une atrophie persistante, répétition d’injections dépendante.L’étude de l’impact des traitements adjuvants à la TB chez l’enfant PC montre que le renforcement musculaire intensif, y compris des muscles injectés, permet de lutter contre l’atrophie sans renforcer la spasticité. Les plâtres d’allongement permettent d’optimiser le fonctionnement articulaire mais les preuves sur la diminution de la raideur musculaire restent faibles. Dans la description des facteurs pronostics d’efficacité, plus de la moitié des patients identifiés comme secondairement non-répondeurs à la TB dans la spasticité des membres ne sont pas immunisés contre la TB. Les anticorps neutralisants ne sont donc pas la principale cause de non-réponse secondaire. Une évaluation de la qualité musculaire échographique comme facteur pronostic de réponse à la TB et pour mesurer l’impact des traitements adjuvants devrait être réalisée régulièrement afin de déterminer à quel moment ces traitements ne sont plus favorables au système musculaire The aim was to investigate a muscle evaluation method to determine tissue factors leading to non-responsiveness to an injection of botulinum toxin (BTX) into a spastic muscle in adult post stroke and children with cerebral palsy (CP). A reproducibility study and 3 systematic literature reviews were carried out. 2D ultrasound measurements of thickness and pennation angle of medialis gastrocnemius muscle fibers are reproducible. Measurement of the modulus of elasticity by shear wave ultrasound elastography provides a reliable information about the rigidity of the spastic medial gastrocnemius muscle at rest.Analysis of the post-injection muscle fate found that BTX participates in the remodeling of the spastic muscle with persistent atrophy that is dependent on the repetition of the injections.Analysis of the impact of BTX adjuvant therapies in CP children showed that intensive muscle strengthening, including of the injected muscles, may help combat atrophy without increasing spasticity. Stretching casts are used to optimize joint function, but there is little evidence for a reduction in muscle stiffness. In the description of prognostic efficacy factors, more than half of patients identified as secondariy non-responders to BTX in limb spasticity tests were not immunized against BTX. Neutralizing antibodies were therefore not the main cause for secondary non-responsiveness. An ultrasound evaluation of muscle quality as a prognostic factor for BTX response and to measure the impact of adjuvant treatments must be regularly performed to determine when these treatments are no longer favourable for the muscle system

APA, Harvard, Vancouver, ISO, and other styles

49

Haji, mansor Muhammad. "Functionalized polymer implants for the trapping of glioblastoma cells Development of a non-toxic and non-denaturing formulation process for encapsulation of SDF-1α into PLGA/PEG-PLGA nanoparticles to achieve sustained release Reversing the Tumor Target: Establishment of a Tumor Trap". Thesis, Angers, 2019. http://www.theses.fr/2019ANGE0015.

Full text

Abstract:

Le glioblastome (GBM) est la forme de cancer du cerveau la plus courante et la plus meurtrière. Sa nature diffusive entraine une impossibilité d’élimination complète par chirurgie. Une récidive de la tumeur chez ≥ 90% des patients peut être provoqué par des cellules GBM résiduelles se trouvant près du bord de la cavité de résection. Un implant pouvant libérer de manière durable la protéine SDF-1α, qui se lie aux récepteur CXCR4 à la surface des cellules GBM, peut être utile pour induire le recrutement des cellules GBM résiduelles, permettre leur élimination sélective et finalement réduire la récurrence de la tumeur. Dans ce travail, le SDF-1α a été initialement encapsulé dans des nanoparticules à base d'acide poly-lactique-co-glycolique (PLGA). Une efficacité d'encapsulation élevée (76%) a pu être obtenue en utilisant un processus simple de séparation de phase. Les nanoparticules chargées de SDF-1α ont ensuite été incorporées dans un scaffold à base de chitosan par électrofilage pour obtenir des implants nanofibreux imitant la structure de la matrice extracellulaire du cerveau. Une étude de libération in vitro a révélé que l'implant pouvait fournir une libération prolongée de SDF-1α jusqu'à 35 jours, utile pour établir un gradient de concentration de SDF-1α dans le cerveau et induire une attraction des cellules GBM. Une étude de biocompatibilité in vivo à 7 jours a révélé des signes d'inflammation locale sans aucun signe visible de détérioration clinique chez les sujets animaux. Une étude à 100 jours visant à confirmer l'innocuité in vivo des implants avant de passer aux études d'efficacité dans un modèle de résection GBM approprié est actuellement en cours Glioblastoma (GBM) is the most common and lethal form of brain cancer. The diffusive nature of GBM means the neoplastic tissue can not be removed completely by surgery. Often, residual GBM cells can be found close to the border of the resection cavity and these cells can multiply to cause tumor recurrence in ≥90% of GBM patients. An implant that can sustainably release chemoattractant molecules called stromal cell-derived factor-1α (SDF-1α), which bind selectively to CXCR4 receptors on the surface of GBM cells, may be useful for inducing chemotaxis and recruitment of the residual GBM cells. This may then give access to selective killing of the cells and ultimately reduce tumor recurrence. In this work, SDF-1α was initially encapsulated into poly-lactic-coglycolicacid (PLGA)-based nanoparticles. A high encapsulation efficiency (76%) could be achieved using a simple phase separation process. The SDF-1α-loaded nanoparticles were then incorporated into a chitosan-based scaffold by electrospinning to obtain nanofibrous implants that mimic the brain extracellular matrix structure. In vitro release study revealed that the implant could provide sustainedSDF-1α release for 5 weeks. The gradual SDF-1αrelease will be useful for establishing SDF-1α concentration gradients in the brain, which is critical for the chemotaxis of GBM cells. A 7-day in vivo biocompatibility study revealed evidence of inflammation at the implantation site without any visible signs of clinical deterioration in the animal subjects. A long-term study (100 days) aiming to confirm the in vivo safety of the implants before proceeding to efficacy studies in a suitable GBM resection model is currently underway

APA, Harvard, Vancouver, ISO, and other styles

50

Vdovikova, Svitlana. "Roles of membrane vesicles in bacterial pathogenesis." Doctoral thesis, Umeå universitet, Institutionen för molekylärbiologi (Medicinska fakulteten), 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-138714.

Full text

Abstract:

The production of membranous vesicles is observed to occur among organisms from all domains of the tree of life spanning prokaryotes (bacteria, archaea) and eukaryotes (plants, animals and fungi). Bacterial release of membrane-derived vesicles (MVs) has been studied most extensively in cases of Gram-negative species and implicating their outer membrane in formation of extracellular MVs. However, recent studies focusing on Gram-positive bacteria have established that they also undergo MV formation. Membrane vesicles are released during normal bacterial growth, they are derived from the bacterial membrane(s) and may function as transporters of different proteins, DNA and RNA to the neighbouring bacteria or to the cells of a mammalian host. The transport of virulence factors in a condensed manner via MVs to the host cells presumably protects these proteins from degradation and, thereby, targets the host cells in a specific manner. The aim of my thesis is to investigate secretion of MV-associated virulence factors and to study interactions of MVs produced by two selected Gram-negative and Gram-positive bacteria, i.e. Vibrio cholerae and Listeria monocytogenes, with eukaryotic host cells. Depending on whether the bacterium acts as an extracellular or intracellular pathogen, MVs may be considered to have specific functions, which may lead to the different outcomes of MV-host interactions. V. cholerae transport systems for virulence factors include the Type VI secretion system and MVs (also referred to as the “Type 0” secretion system). We have identified that the biologically active form of PrtV protease in different V. cholerae serogroups is transported via MVs. PrtV protease is essential for V. cholerae environmental survival and protection from natural predator grazing. We demonstrated that PrtV is primarily translocated via the inner membrane to the periplasmic space, where it undergoes autoproteolysis, and the truncated version of PrtV protein is packaged inside the MVs and released from the surface of bacteria. MV-associated PrtV protease showed a contribution to bacterial resistance towards the antimicrobial peptide LL-37, thereby, enhancing bacterial survival by avoiding this innate immune defense of the host. We also studied another virulence factor of V. cholerae, the pore-forming toxin VCC, which was found to be transported by MVs. MV-associated VCC is biologically active and triggers an autophagic response in the target cells. We suggested that autophagy serves as a cellular defense mechanism against the MV-associated bacterial virulence factor of V. cholerae. Listeria monocytogenes is a Gram-positive intracellular and facultative anaerobic food-borne pathogen causing listeriosis. It causes only sporadic outbreaks in healthy individuals, however, it is dangerous for a fetus or newborn child, and for pregnant and immunocompromised people, leading to a deadly infection in one third of the cases. We have analyzed MVs produced by L. monocytogenes and their interaction with eukaryotic cells. Confocal microscopy analysis showed that MVs are internalized into HeLa and HEK293 cells and are accumulated in lysosomes. Moreover, L. monocytogenes produces MVs inside the host cells and even inside the phagosomes. We found that the major virulence factor of L. monocytogenes, the cholesterol-dependent pore-forming protein listeriolysin O (LLO), is entrapped inside the MVs and resides there in an oxidized inactive state. LLO is known to induce autophagy by making pores in the phagosomal membrane of targeted eukaryotic cells. In our studies, we have shown that MVs effectively abrogated autophagy induced by Torin1, by purified LLO or by another pore-forming toxin from V. cholerae. We also found that MVs promote bacterial intracellular survival inside mouse embryonic fibroblasts. In addition, MVs have been shown to have a strong protective activity against host cell necrosis initiated by pore-forming toxin. Taken together, these findings suggested that in vivo MVs production from L. monocytogenes might be a relevant strategy of bacteria to manipulate host responses and to promote bacterial survival inside the host cells.

APA, Harvard, Vancouver, ISO, and other styles

Dissertations / Theses on the topic 'Toxic factors'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles