The long-range goal of this project is to investigate the protective effects of conjugated linoleic acid (CLA) against carcinogenesis. In this dissertation, we demonstrate the mechanisms of CLA action on cell cycle progression and repression of polycyclic aromatic hydrocarbon (PAH)-induced Cyclooxygenase-2 (COX-2) in breast and colon cancer cells. CLA reduced the expression of factors required for G1 to S-phase transition including cyclins D1 and E, and hyperphoshorylated retinoblastoma Rb protein. In contrast, the over-expression of mutant p53 (175Arg to His) in MCF-7 cells prevented the CLA-dependent accumulation of p21 and the reduction of cyclin E levels suggesting that the expression of wild-type p53 is required for CLA-mediated activation of the G1 restriction point. We also report, CLA reduced the expression of COX-2 promoter activity induced by the aromatic hydrocarbon receptor (AhR)-ligand benzo[a]pyrene (B[a]P). Mutagenesis or deletion of potential xenobiotic responsive elements (XREs) within the COX-2 promoter abrogated its ability to be induced by the high affinity AhR-ligand TCDD. In addition, promoter studies using a XRE-dependent CYP1A1 plasmid revealed CLA can inhibit PAH-induced AhR/XRE-driven genes. In both studies, the t10,c12-CLA isomer was more effective than c9,t11-CLA in inhibiting cell proliferation and AhR/XRE-dependent genes. Taken together, these data suggest that the anti-cancerous properties of CLA appear to be a function, at least in part, of the relative content of specific isomers and their 1) ability to elicit a p53 response that leads to the accumulation of pRb and cell growth arrest, and 2) ability to inhibit PAH-induced cyclooxygenase-2 promoter activity through an AhR-dependent mechanism.

Im Rahmen dieser Arbeit sollte geprüft werden, welchen Einfluss die Aufnahmewege Wasser und Nahrung auf die Toxikokinetik der 14C-markierten Testsubstanzen Terbutryn und Benzo[a]pyren bei den aquatischen Invertebraten Gammarus fossarum, Asellus aquaticus und Lumbriculus variegatus haben. Es wurden die toxikokinetischen Parameter zur Aufnahme und Elimination von 14C-Terbutryn und 14C-Benzo[a]pyren in Biokonzentrations- und Biomagnifikationsexperimenten untersucht. Die Verwendung der Tracertechnik ermöglichte Untersuchungen zum Metabolismus mittels Hochleistungsflüssigkeitschromatographie (HPLC). Hierzu wurden Extraktionsmethoden und Trennsysteme für den Nachweis der Metabolite in den Organismen, in Blattscheiben und im Hälterungswasser entwickelt. Für 14C-Terbutryn und 14C-B[a]P konnte das Wasser als Hauptaufnahmeweg für die untersuchten Invertebraten identifiziert werden. Die beiden Testsubstanzen wurden bei den untersuchten Invertebraten über die Nahrung aufgenommen. Es fand jedoch keine Anreicherung über die Nahrung statt. Die Aufnahme von 14C-Terbutryn und 14C-B[a]P erfolgte bei den untersuchten Invertebraten über das Wasser schneller als über die Nahrung. Die Elimination von 14C-Terbutryn nach Aufnahme über die Nahrung erfolgte mit Ausnahme von A. aquaticus bei den untersuchten Organismen langsamer als nach Aufnahme über das Wasser. 14C-B[a]P wurde durch die untersuchten Organismen mit Ausnahme von G. fossarum nicht wieder eliminiert. Für die untersuchten aquatischen Invertebraten wurden Korrelationen zwischen dem log Kow und dem log BCF durchgeführt. Dabei zeigte sich, dass es eine lineare Beziehung zwischen log Kow und log BCF gibt. Jedoch bestehen in Abhängigkeit von der Spezies und der Substanz Unterschiede in den Eigenschaften der Regressionsgeraden sowie in der Güte der Anpassung.

Im Rahmen dieser Arbeit sollte geprüft werden, welchen Einfluss die Aufnahmewege Wasser und Nahrung auf die Toxikokinetik der 14C-markierten Testsubstanzen Terbutryn und Benzo[a]pyren bei den aquatischen Invertebraten Gammarus fossarum, Asellus aquaticus und Lumbriculus variegatus haben. Es wurden die toxikokinetischen Parameter zur Aufnahme und Elimination von 14C-Terbutryn und 14C-Benzo[a]pyren in Biokonzentrations- und Biomagnifikationsexperimenten untersucht. Die Verwendung der Tracertechnik ermöglichte Untersuchungen zum Metabolismus mittels Hochleistungsflüssigkeitschromatographie (HPLC). Hierzu wurden Extraktionsmethoden und Trennsysteme für den Nachweis der Metabolite in den Organismen, in Blattscheiben und im Hälterungswasser entwickelt. Für 14C-Terbutryn und 14C-B[a]P konnte das Wasser als Hauptaufnahmeweg für die untersuchten Invertebraten identifiziert werden. Die beiden Testsubstanzen wurden bei den untersuchten Invertebraten über die Nahrung aufgenommen. Es fand jedoch keine Anreicherung über die Nahrung statt. Die Aufnahme von 14C-Terbutryn und 14C-B[a]P erfolgte bei den untersuchten Invertebraten über das Wasser schneller als über die Nahrung. Die Elimination von 14C-Terbutryn nach Aufnahme über die Nahrung erfolgte mit Ausnahme von A. aquaticus bei den untersuchten Organismen langsamer als nach Aufnahme über das Wasser. 14C-B[a]P wurde durch die untersuchten Organismen mit Ausnahme von G. fossarum nicht wieder eliminiert. Für die untersuchten aquatischen Invertebraten wurden Korrelationen zwischen dem log Kow und dem log BCF durchgeführt. Dabei zeigte sich, dass es eine lineare Beziehung zwischen log Kow und log BCF gibt. Jedoch bestehen in Abhängigkeit von der Spezies und der Substanz Unterschiede in den Eigenschaften der Regressionsgeraden sowie in der Güte der Anpassung.

Air pollution cause approximately 5000 premature deaths in Sweden each year. Residential wood combustion of solid biomass (RWC) is responsible for at least 1000 based on a relative risk coefficient of 17 % per 10 μg/m3 exposure. The carcinogenic properties of RWC emissions is linked to their content of particulates and polycyclic aromatic hydrocarbons (PAH’s). The ambition of this study is to answer whether cancer risk may be used as indicator for out dated heating technology with high emissions of carcinogenic air pollutants, and which socioeconomic costs that can be linked to such a scenario. The efficacy of different instruments that are discussed in Swedish environmental policy is also discussed. A transdisciplinary approach, constituting of a literature review, statistical analysis, gap analysis and multi criteria analysis was applied as study design. A literature review resulted in a mapping of the state of the art concerning RWC particulates and their impact on cancer in Sweden together with its related socioeconomic costs. The study is focused on PM2,5 and B(a)P emissions. A statistical analysis examined the potential relationship between short-lived micro nuclei (MN) in Swedish 12-year old school children, and their exposure to the carcinogenic PAH Benzo(a)pyrene (B(a)P) from RWC in Sweden. The results suggest that higher rates of lung cancer incidence, and socioeconomic costs may be found in areas burdened with high rates of RWC emissions from outdated heating technology. The MCA suggest that a combination of instruments is most suitable to achieve the targeted specification for B(a)P in the Clean Air objective, as found in previous CBA’s, and that other instrument may lack efficacy. / Varje år orsakar luftföroreningar omkring 5000 prematura dödsfall i Sverige. Småskalig vedeldning (RWC) ansvarar för åtminstone 1000 av dessa, baserat på den relativa risk-koefficienten 17 % per 10 μg/m3 exponering. De cancerogena egenskaperna hos vedeldningsutsläpp beror bland annat på dess partiklar som bland annat innehåller polycykliska aromatiska kolväten (PAH:er). Ambitionen med denna studie är att besvara hur framtida cancerrisk kan användas som indikator för luftföroreningar från omodern uppvärmningsteknik och vilka samhällsekonomiska följder som kan länkas till en sådan. Dessutom undersöktes styrkraften hos de styrmedel som diskuteras i svensk miljöpolicy. Med hjälp av ett tvärvetenskapligt tillvägagångssätt, bestående av litteraturgenomgång, statistisk analys, gapanalys och multikriterieanalys besvarades frågorna. Litteraturgenomgången resulterade i en kartläggning av det nuvarande kunskapsläget om vedpartiklars påverkan på cancer i Sverige och dess relaterade samhällskostnader. Studien är fokuserad på PM2,5 och B(a)P emissioner. En statistisk analys undersökte korrelationen mellan en biomarkor för framtida cancerrisk, kortlivade mikrokärnor (MN), hos svenska 12-åriga skolelever, och deras vedröksexponering. Resultaten indikerar svagt att större risk för lungcancer kan spås i områden med relativt högre exponering för vedrökskomponenten B(a)P, alltså områden med omodern uppvärmningsutrustning. Multikriterieanalysen visar, liksom i tidigare kostnad-effektivitetsanalyser, att en kombination av olika styrmedel har störst potential att uppnå specifikationerna för PM2,5 och B(a)P i det svenska miljökvalitetsmålet Ren luft. Andra styrmedel kan sakna styrkraft.

The aim of this study was to determine the effects of the heavy metal pollution on microbial diversity along the gradient from a platinum mine tailings dam using culture-dependent (plating methods) and molecular methods. Tailings and soil samples were collected from seven sites (6 samples per site) at increasing distances from the tailings dam. Samples were collected over a two year period and included two rainy and two dry periods. Concentrations of various heavy metals were determined using an inductively coupled plasma mass spectrometer (ICP-MS). The results demonstrated that seasonal variations in metal concentrations occurred and also that concentrations were significantly different'(P < 0.05) between the experimental sites for each metal. The relative relationship between metals was in the following order: Al > Ni > Cu > Cr. Since soil metal concentration benchmarks for South Africa are lacking, the concentrations were compared to the Canadian microbial benchmarks (MB) and Netherlands maximum permissible concentrations (MPC). Concentrations of most of the heavy metals exceeded the MB and MPC. Levels and diversity of culturable fungi and bacteria at each site were determined using plate count methods. Results indicated that levels of bacteria and fungi were not suppressed by high concentrations of heavy metals. Significantly higher levels (P < 0.05) of fungi were found at the sites on the tailings dam (higher concentrations of heavy metals), compared to sites more than 300 m away. A commonly used soil health index (Shannon-Weaver diversity index) was used to compare microbial community diversity at each site and to evaluate whether or not the heavy metal contamination impacted negatively on these soil bacterial and fungal communities. Shannon-Weaver diversity indices were higher at sites on and close to the tailings dam than sites more than 300 m away. However, ratio of fungal to bacterial levels as determined by plate counts was inconsistent. Representatives of bacterial species that were grouped using colony morphology and whole cell protein profiles were identified by 16S rDNA sequences as Bacillus barbaricus (B. barbaricus) and -Paenibacillus lautus {P. Lautus). Restriction enzyme digest, SDS-PAGE and random amplified polymorphic DNA (RAPD) analyses provided supporting evidence that representatives were correctly grouped. Cluster analysis results demonstrated that the RAPD profiles of the metal tolerant P. lautus representatives were sufficiently dissimilar to discriminate between individuals from the spatially separated sites. The spatially separated sites also represented sites with high and low heavy metal concentrations. Observed genetic variability was thus also associated with varying levels of heavy metals. In conclusion, this study demonstrated the potential of using RAPD analysis as biomarkers for genotoxic effects of heavy metals on bacterial genomes. / Masters / Thesis (M.Sc. (Microbiology))--North-West University, Potchefstroom Campus, 2009.

The aim of this study was to determine the effects of the heavy metal pollution on microbial diversity along the gradient from a platinum mine tailings dam using culture-dependent (plating methods) and molecular methods. Tailings and soil samples were collected from seven sites (6 samples per site) at increasing distances from the tailings dam. Samples were collected over a two year period and included two rainy and two dry periods. Concentrations of various heavy metals were determined using an inductively coupled plasma mass spectrometer (ICP-MS). The results demonstrated that seasonal variations in metal concentrations occurred and also that concentrations were significantly different'(P < 0.05) between the experimental sites for each metal. The relative relationship between metals was in the following order: Al > Ni > Cu > Cr. Since soil metal concentration benchmarks for South Africa are lacking, the concentrations were compared to the Canadian microbial benchmarks (MB) and Netherlands maximum permissible concentrations (MPC). Concentrations of most of the heavy metals exceeded the MB and MPC. Levels and diversity of culturable fungi and bacteria at each site were determined using plate count methods. Results indicated that levels of bacteria and fungi were not suppressed by high concentrations of heavy metals. Significantly higher levels (P < 0.05) of fungi were found at the sites on the tailings dam (higher concentrations of heavy metals), compared to sites more than 300 m away. A commonly used soil health index (Shannon-Weaver diversity index) was used to compare microbial community diversity at each site and to evaluate whether or not the heavy metal contamination impacted negatively on these soil bacterial and fungal communities. Shannon-Weaver diversity indices were higher at sites on and close to the tailings dam than sites more than 300 m away. However, ratio of fungal to bacterial levels as determined by plate counts was inconsistent. Representatives of bacterial species that were grouped using colony morphology and whole cell protein profiles were identified by 16S rDNA sequences as Bacillus barbaricus (B. barbaricus) and -Paenibacillus lautus {P. Lautus). Restriction enzyme digest, SDS-PAGE and random amplified polymorphic DNA (RAPD) analyses provided supporting evidence that representatives were correctly grouped. Cluster analysis results demonstrated that the RAPD profiles of the metal tolerant P. lautus representatives were sufficiently dissimilar to discriminate between individuals from the spatially separated sites. The spatially separated sites also represented sites with high and low heavy metal concentrations. Observed genetic variability was thus also associated with varying levels of heavy metals. In conclusion, this study demonstrated the potential of using RAPD analysis as biomarkers for genotoxic effects of heavy metals on bacterial genomes. / Masters / Thesis (M.Sc. (Microbiology))--North-West University, Potchefstroom Campus, 2009.

A fusion protein composed of antibody fragments and β-lactamase was earlier created by Kojima et al. (2011), with antigen specificities against a bone disease marker and a pesticide. The enzyme was circularly permutated and fused to the variable heavy and light chain antibody fragments, thereby ensuring inactivity until binding of the target antigen triggered enzyme activation. Upon activation, the β-lactamase produced a colorimetric signal, which indicated antigen presence. In this work, a similar strategy was used to create two novel fusion proteins composed of circularly permuted β-lactamase and superfolder green fluorescent protein with anti-benzo[a]pyrene variable antibody fragments. The fusion proteins were designed and expressed in E. coli for the development of a single-step visual immunoassay. It was hypothesized that the cp reporter proteins would be activated once the binding of B[a]P to the variable antibody fragments occurred, and this interaction was expected to produce a detectable colorimetric or fluorescent signal. Although positive results were obtained in one instance, substantial supportive evidence in favour of the hypothesis could not be obtained. / SENTINEL Bioactive Paper Network, Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Research Chairs Program.

Area navigation RNAV and reducing vertical separation minimum RVSM methods are both considerable phase of high air traffic density issue solution. By implementation of these methods the optimization of airspace is achieved. In present the RNAV and RVSM procedures are implemented in European airspace and the procedures of these metods are valid. Thesis sumarizes the substance of these methods, its implementation and especially procedures they are connected with. The purpose of this thesis is to form qualified analysis of RNAV and RVSM methods and to desctibe its feasibility and its trends in European airspace. The thesis is intended as an educational aid for pilots and aerospace engineering students self-study.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2015-10-14T13:23:22Z No. of bitstreams: 1 MariaAparecidaDosSantosFerreira_TESE.pdf: 5562083 bytes, checksum: 4db48c755d03181550da95a8c119ac27 (MD5) / Approved for entry into archive by Maria Maia (aniolly@bczm.ufrn.br) on 2015-10-14T14:32:32Z (GMT) No. of bitstreams: 1 MariaAparecidaDosSantosFerreira_TESE.pdf: 5562083 bytes, checksum: 4db48c755d03181550da95a8c119ac27 (MD5) / Made available in DSpace on 2015-10-14T14:32:32Z (GMT). No. of bitstreams: 1 MariaAparecidaDosSantosFerreira_TESE.pdf: 5562083 bytes, checksum: 4db48c755d03181550da95a8c119ac27 (MD5) Previous issue date: 2014-02-28 / O presente estudo analisa os efeitos da pol?tica de financiamento da educa??o b?sica, por interm?dio dos Fundos cont?beis - Fundef e Fundeb e sua proposi??o de valoriza??o do magist?rio, considerando as dimens?es da carreira e da remunera??o dos professores da rede p?blica estadual de ensino do Rio Grande do Norte, no per?odo de 1996 a 2010. Para entender os condicionantes da avalia??o das pol?ticas p?blicas, recorreu-se ?s contribui??es em Marx (1996) segundo o qual ?o concreto ? concreto? e que a dial?tica do concreto pode auxiliar na tentativa de captar o fen?meno estudado. Utilizou-se, ainda, do referencial bibliogr?fico relacionado ao financiamento da educa??o e ? valoriza??o do magist?rio, com base na literatura referente ?s dimens?es do objeto (Fundef e Fundeb) e (carreira e remunera??o). Na pesquisa documental, al?m das legisla??es, diretrizes nacionais e locais pertinentes, utilizaram-se ainda, dados referentes aos recursos, dispon?veis na Finbra, Tesouro Nacional, SIOPE/RN, INEP/MEC, dados do resumo da folha e da folha de pagamento da Secretaria de Estado, da Educa??o e da Cultura (SEEC) e 289 contracheques de 21 professores. Realizou-se entrevista semiestruturada com nove professores, referente ? carreira, al?m de um question?rio aplicado com 12 professores relacionado ? remunera??o. Considera-se que, nos resultados referentes aos indicadores educacionais, no per?odo Fundef, ocorreu uma redu??o tanto nas matr?culas, como nas fun??es docentes do ensino fundamental da rede estadual de ensino, correspondente a 37%. A partir da vig?ncia do Fundeb (2007-2010), esses indicadores foram equacionados. Em todo o per?odo, 1996 a 2010, ocorre um aumento nas matr?culas de 119,03% e, nas fun??es docentes de 77,44%. Quanto aos dados de financiamento, constatou-se que, do m?nimo exigido (60%) dos recursos dos Fundos foram aplicados na remunera??o do magist?rio, no per?odo dos dois Fundos entre 83,29% a 98,89% dos recursos. Os efeitos dos Fundos na carreira dos nove professores, considerando a promo??o e a progress?o, n?o foram satisfat?rios. Na promo??o dos nove docentes, apenas um evoluiu o seu N?vel (titula??o), mas retroagiu na progress?o. Na progress?o desses nove professores, oito se encontram com a sua progress?o atrasada, entre duas e cinco classes, acumulando um preju?zo que varia de 10% a 45% na sua remunera??o. A diferen?a de uma classe para a outra corresponde a 5% no vencimento. Observou-se que as vantagens pecuni?rias contribuem com a remunera??o em um percentual maior que o vencimento, diminuindo essa diferen?a no per?odo do Fundeb. Quanto ? remunera??o, um professor, com 24 anos de carreira, com forma??o (magist?rio), n?o consegue, depois de anos de profiss?o ganhar, sequer, dois sal?rios m?nimos. O professor com 30 anos de carreira, com mestrado tem um vencimento, em 2010, correspondente a menos de tr?s sal?rios m?nimos, isto ?, 2,82 e uma remunera??o que equivale a pouco mais de tr?s sal?rios m?nimos, ou seja, 3,66. Comparando a profiss?o do magist?rio com outras que exigem forma??o superior, a primeira tem sido baixa, causando efeito negativo sobre a procura da profiss?o do magist?rio. Quanto aos efeitos na remunera??o, conclui-se que houve uma melhoria, mas ainda insuficiente, principalmente, ao comparar com o sal?rio m?nimo anual. Avalia-se, pois, que os Fundos - Fundef e Fundeb - n?o foram capazes de promover a valoriza??o do magist?rio nas dimens?es da carreira e da remunera??o. Constataram-se alguns resultados negativos na pol?tica de Fundo pois teria a ver, principalmente, com a incapacidade de a referida pol?tica promover a valoriza??o do magist?rio, sendo, uma das causas, o financiamento com restri??o or?ament?ria. / Este estudio analiza los efectos de la pol?tica de financiamiento de la educaci?n b?sica, por intermedio de los Fundos contables, Fundef y Fundeb, y su proposici?n en valorar el magisterio, considerando las dimensiones de carrera y de la remuneraci?n de los profesores de la red p?blica estadal de ense?anza del estado de Rio Grande do Norte, en el per?odo entre 1996 y 2010. Para entender las condicionantes de la evaluaci?n de las pol?ticas p?blicas, se busc? tambi?n las contribuciones de Marx (1996) segundo qui?n ?el concreto es concreto? y que la dial?ctica del concreto se puede auxiliar en el intento de captar el fen?meno estudiado. Se utiliz? a?n, el referencial te?rico bibliogr?fico relacionado al financiamiento de la educaci?n y a la valoraci?n del magisterio, a partir de la literatura referente a las dimensiones del objeto (fundef y Fundeb) y (carrera y remuneraci?n). En la investigaci?n documental, adem?s de las legislaciones, directrices nacionales y locales pertinentes, se utilizaron datos referentes a los recursos disponibles en la Finbra. Tesoro Nacional, SIOPE/RN, INEP/MEC, datos de resumen del folio y folio de pagamiento de Secretaria de Estado, de la Educaci?n e de la Cultura (SEEC), y 289 sueldos de 21 profesores. Se realiz? entrevista semi estructurada con nueve profesores, referente a la carrera, adem?s de un cuestionario aplicado a 12 profesores relacionado a remuneraci?n. Se considera que en los resultados referentes a los indicadores educacionales, en el per?odo Fundef ocurri? una reducci?n en las inscripciones de la red p?blica de ense?anza, como tambi?n en las funciones docentes, de la ense?anza base (fundamental), que corresponde a 37%. A partir de la vigencia del Fundeb (2007 ? 2010), estos indicadores fueron puestos en ecuaci?n. En todo el per?odo entre 1996 a 2010, ocurre un aumento en las inscripciones de 119,03% y en las funciones docentes de 77,44%. Sobre los datos de financiamiento, se constat? que, del m?nimo exigido (60%) en la aplicaci?n de recursos de los Fundos en la remuneraci?n del magisterio se aplica en el per?odo de los dos Fundos, pero el m?nimo exigido, o sea, 83,29% a 98,89% de los recursos. Los efectos de los Fundos en la carrera de los nueve profesores, considerando la promoci?n y la progresi?n, no han sido satisfactorios. En la promoci?n de los nueve de estos docentes, apenas uno evolucion? el Nivel (titulaci?n), pero retrocedi? en la progresi?n. En la progresi?n de los nueve profesores, ocho se hallan con la progresi?n retrasada, entre dos y cinco clases, acumulando un perjuicio que var?a de 10% a 45% en su ganancia. La diferencia de una clase a otra corresponde a 5% en la renta anual. Se observa que las ventajas pecuniarias contribuyen con la remuneraci?n con porcentaje m?s alto que la renta, disminuyendo esta diferencia en el per?odo de Fundeb. Sobre la remuneraci?n, un profesor con 24 a?os de carrera, con formaci?n (magisterio), no consigue, despu?s de a?os de profesi?n, ganar ni siquiera dos salarios m?nimos. El profesor con 30 a?os de carrera, con maestr?a, tiene una renta, en 2010, correspondiente a menos de tres salarios m?nimos, o sea, 2,82 y una remuneraci?n que equivale a poco m?s de tres salarios m?nimos, o sea, 3,66. Si comparamos la profesi?n de magisterio con otras que igual exigen formaci?n superior, la primera es, en general, de bajo nivel, causando un resultado negativo sobre la b?squeda de la profesi?n del magisterio. Por los efectos en la remuneraci?n, se concluye que hubo una mejor?a, pero a?n insuficiente, sobre todo al comparar con el Salario M?nimo Anual. Se eval?a, una vez que los fundos ? Fundef y Fundeb ? no fueron capaces de promover la valoraci?n del magisterio en las dimensiones de la carrera y de la remuneraci?n. Se constatan algunos resultados negativos en la pol?tica de Fundo ya que tendr?a que ver, principalmente, con la incapacidad de la referida pol?tica a valoraci?n de magisterio, siendo una de las causas, o financiamiento con restricci?n de presupuesto.