Dissertations / Theses on the topic 'Substances of photoinitiator system'

This master's thesis deals with a present problem of alternative dental fillings, which should replace amalgam fillings. Although there are health concerns about these alternative materials, especially resin composite fillings raise concerns, because they release potentionally harmful substances into the oral cavity. Accordingly even this medical device subjects various tests before releasing to the commercial market and one of these tests was carried out according to ČSN EN ISO 10993 and available scientific literature in the experimental part of this thesis. The amalgam controversy, substances used for manufacturing of resin dental fillings and analytical methods are described in the theoretical part of the thesis. In the experimental part of the thesis, 30 days long cumulative extraction experiments were carried out into various extraction mediums in order to assess suitability of new dental resin filling from ADM, a.s. by comparison with commercially available dental material from company GC EUROPE N.V. These samples were analysed by LC-MS and the amount of eluted substances from dental composites to extraction medium was quantified.

The purpose of this research was to develop a test system for screening toxic substances by predicting their aquatic ecosystem effects. The system studied was a static, one liter microcosm with a diverse species assemblage. Teh microcosm was composed of biotic inoculum, chemically defined medium and sediment. The biotic inoculum cotained primary producers, grazers, carnivores and decomposers. The chemical medium used was Taub #82 modified by adding sodium bicarbonate. Three different types of sediment were studied: sand, clay and clay plus sand. Four organic chemicals: phenol, triethylene glycol (TEG), quinoline and naphtoquinone were evaluated with this test system. The toxicities of TEG, quinoline and naphthoquinone were compared for each sediment type. Toxicity was evluated in terms of the chemicals' effects on primary productivity and heterotrophic activity though other effects are also noted. The toxicity of the chemicals in this study was compared to those from other toxicological evaluations based on threshhold toxicity values (EC20 and LC50). The screening test sytem evaluated in this study did not demonstrate significanly different threshhold toxicity values than the other screening systems to which it was compared. The ranking of the toxicants based on EC20 values was different for the two ecosystem properties, net production and heterotrophic activity. Naphthoquinone concentration exhibited no correlation between ecosystems property values and therefore, could not be ranked. Phenol exhibited the greatest toxicity to net production immediately after the toxicant addition. Quinoline was most toxic to net production over the longer time scale. TEG exhibited the least toxicity to net production, however, TEG exhibited higher toxicity to heterotrophic activity than either quinoline or phenol. Although the type of sediment used in the nicrocosms did not change the relative toxicities of the chemicals, the microcosms with clay sediment always were observed to exhibit lower net production and higher variability. Nonparametric statistical analyses are recommended for microcosm studies because of the lack of normally distributed data. Confidence limits of 80% are recommended because of the need for biologically conservative estimates of ecosystem toxicity.
Ph. D.
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Thesis (M.S.D.)--Indiana University School of Dentistry, 2009.
Title from PDF t. p. (viewed Feb. 9, 2010) Advisor(s): Jeffrey A. Platt, Chair of the Research Committee, Carl J. Andres, Suteena Hovijitra, David Brown, John A. Levon. Curriculum vitae. Includes abstract. Includes bibliographical references (leaves 56-59).

Integrated algae pond systems (IAPS) combine the use of anaerobic and aerobic bioprocesses to effect wastewater treatment. Although, IAPS as a technology process offers many advantages including efficient and simultaneous N and P removal, no requirement for additional chemicals, O2 generation, CO2 mitigation, and a biomass with potential for valorization, a lack of technological advancement and the need for large land area, has limited the reach of this technology at industrial scale. In mitigation, peroxonation was introduced as a tertiary treatment unit and its effect on COD and TSS of IAPS treated water investigated. An effort was made to characterize the soluble but persistent COD in IAPS treated water and, productivity of the HRAOP mixed liquor was investigated to gain insight into the potential use of this biomass. Results show that peroxone treatment effectively reduced COD, TSS, and nutrient load of IAPS water without any significant impact on land area requirement. Indeed, summary data describing the effect of peroxone on quality of IAPS-treated water confirmed that it complies with the general limit values for either irrigation or discharge into a water resource that is not a listed water resource for volumes up to 2 ML of treated wastewater on any given day. Extraction followed by FT-IR spectroscopy was used to confirm albeit tentatively, the identity of the soluble but persistent COD in IAPS treated water as MaB-floc EPS. Results show that MaB-flocs from HRAOPs are assemblages of microorganisms produced as discrete aggregates as a result of microbial EPS production. A relationship between photosynthesis and EPS production was established by quantification of the EPS following exposure of MaB-flocs to either continuous light or darkness. Several novel strains of bacteria were isolated from HRAOP mixed liquor and 16S ribosomal genomic sequence analysis resulted in the molecular characterization of Planococcus maitriensis strain ECCN 45b. This is the first report of Planococcus maitriensis from a wastewater treatment process. Productivity and change in MaB-flocs concentration, measured as mixed liquor suspended solids (MLSS) between morning and evening were monitored and revealed that MLSS is composed of microalgae and bacteria but not fungi. Concentration varied from 77 mg L-1 in September (winter) to 285 mg L-1 in November (spring); pond productivity increased from 5.8 g m-2 d-1 (winter) to 21.5 g m-2 d-1 (spring); and, irrespective of MLSS concentration in late afternoon, approximately 39% was lost overnight, which presumably occurred due to passive removal by the algae settling pond. The outcomes of this research are discussed in terms of the quality of treated water, and the further development of IAPS as a platform technology for establishing a biorefinery within the wastewater treatment sector.

Orientador: Mário Alexandre Coelho Sinhoreti
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: O objetivo neste estudo foi determinar a influência da concentração e proporção de canforoquinona (CQ) e etil-dimetilaminobenzoato (amina terciária - DABE) em propriedades de compósitos microhíbridos experimentais. Foram testados o Grau de Conversão (GC), Amarelamento (AM), Módulo de Elasticidade (ME), Resistência à Flexão (RF), Sorção de Água (SO) e Solubilidade (SL). Para tanto, 10 compósitos experimentais com a mesma composição monomérica (Bis-GMA, UDMA, BisEMA e TEGDMA) foram manipulados, variando-se apenas as concentrações e proporções de CQ/DABE (% em peso): 0,4/0,4 (C1); 0,4/0,8 (C2); 0,6/0,6 (C3); 0,6/1,2 (C4); 0,8/0,8 (C5); 0,8/1,6 (C6); 1/1 (C7); 1/2 (C8); 1,5/1,5 (C9) e 1,5/3 (C10). Para o ensaio de GC, 8 espécimes de cada material foram confeccionados, a partir de uma matriz de silicone em forma de barra (comprimento = 7 mm; largura = 2mm e espessura = 1mm), os quais foram fotoativados com um aparelho LED (Radii Cal, SDI, 800 mW/cm2), durante 20 segundos. Após 24 horas, o GC foi analisado por Espectroscopia de Infravermelho Transformada de Fourier (FTIR). Posteriormente, as mesmas amostras foram submetidas ao ensaio de flexão de 3 pontos em máquina de ensaio universal (Instron), e a RF e ME calculados. Para os testes de AM, SO e SL, foi utilizada uma matriz de silicone cilíndrica (diâmetro = 6 mm e espessura = 0,5 mm), e confeccionadas 5 amostras de cada material para cada teste. Todas as amostras foram armazenadas em estufa a 37º C, até que fossem submetidas aos seus respectivos testes. O AM foi mensurado após 24 horas de armazenamento em água, utilizando o espectrofotômetro Chroma Meter CR-400 (Konica Minolta). A análise se baseou no eixo b* (+b = amarelo; -b = azul). Para os testes de SO e SL, as amostras foram dissecadas por 1 semana e pesadas diariamente até que a variação máxima de massa fosse de 0,0001 g de um dia para o outro, obtendo m1. Para obter m2, as amostras foram armazenadas em água por 1 semana e pesadas novamente, uma única vez. Por último, m3 foram obtidas do mesmo modo em que m1, após recondicionamento das amostras. Para o cálculo foram utilizadas as fórmulas: SO = (m2-m3) / V e SL = (m1-m3) / V. Após os testes, os dados foram submetidos ao ANOVA one-way e teste Tukey (5%). As diferentes concentrações e proporções de CQ e DABE não alteraram significativamente as propriedades de RF e SO. Por outro lado, o GC foi influenciado positivamente, seguindo a ordem crescente da concentração CQ/DABE (C1 a C10). A SL foi inversamente proporcional à concentração do sistema CQ/DABE. Já relacionado ao ME, observou-se valores diretamente proporcionais à porcentagem em volume de CQ/DABE. Os compósitos 9 e 10, com maiores concentrações de CQ, apresentaram maior AM, comparados aos demais. Pode-se concluir que as altas concentrações de CQ/DABE levaram às melhores propriedades, porém ao maior AM. O aumento na proporção do co-iniciador (DABE) não influenciou nas propriedades de todas as formulações experimentais
Abstract: The aim of this study was to determine the influence of the concentration and ratio of camphorquinone (CQ) and ethyl-dimethylaminobenzoic (tertiary amine - DABE) on properties of microhybrids experimental composites. It was tested Degree of Conversion (DC), Yellowing (YL), Elastic Modulus (EM), Flexural Strength (FS), Water Sorption (WSP) and Solubility (SL). For this, 10 experimental composites with the same monomer composition (Bis-GMA, UDMA, BisEMA and TEGDMA) were manipulated by varying the concentration and ratio of CQ / DABE (wt%): 0.4 / 0.4 (C1); 0.4 / 0.8 (C2); 0.6 / 0.6 (C3); 0.6 / 1.2 (C4); 0.8 / 0.8 (C5); 0. 8 / 1. 6 (C6); 1 / 1 (C7); 1 / 2 (C8); 1.5 / 1.5 (C9); 1.5 / 3 (C10). For DC testing, 8 specimens of each material were prepared from a matrix of silicone-shaped bar (length = 7 mm, width = 2 mm and thickness = 1mm), which were photoactivated with one LED unit (Radii Cal, SDI, 800 mW/cm²) for 20 seconds . After 24 hours, the DC was analyzed by Infrared Fourier Transformed (FTIR). Subsequently, the same samples were subjected to bending test of three points on a universal testing machine (Instron), and the FS and EM calculated. For testing of YL, WSP and SL was used an array of cylindrical silicon (diameter = 6 mm and thickness = 0.5 mm), and made 5 samples of each material for each test. All samples were stored at 37 º C until they were subjected to their respective tests. The YL was measured after 24 hours of storage in water using the spectrophotometer Chroma Meter CR-400 (Konica Minolta). The analysis was based on the axis b * (+ b = yellow,-b = blue). For testing WSP and SL, the samples were dissected for 1 week and weighed daily until the maximum variation in weight was 0.0001 g of an overnight, obtaining m1. For m2, the samples were stored in water for 1 week and weighed once again. Finally, m3 were obtained in the same manner in which m1, after reconditioning of samples. For the calculation, were used: WSP = (m2-m3) / V and SL = (m1-m3) / V. After the tests, the data were subjected to one-way ANOVA and Tukey test (5%). The different concentration and ratio of CQ and DABE not significantly altered the properties of FS and WSP. Moreover, the DC was influenced positively in the order of increasing concentration of CQ / DABE (C1 to C10). The SL was inversely proportional to the concentration of the system CQ / DABE. Related to EM, was observed values directly proportional to the percentage by volume of CQ / DABE. The composites 9 and 10, with higher concentration of CQ showed higher YL, compared to the others. It can be concluded that high concentrations of CQ / DABE took the best properties, but the larger YL. The increase in the proportion of co-initiator (DABE) did not affect the properties of all experimental formulations
Mestrado
Materiais Dentarios
Mestre em Materiais Dentários

Norrvatten är den fjärde största dricksvattenproducenten i Sverige. De producerar och distribuerar dricksvatten till 14 kommuner norr om Stockholm. Norrvatten har under en tid studerat alternativa processer för att optimera och öka produktionskapaciteten och effektiviteten i deras dricksvattenreningsverk vid Görvälnverket.  I detta projekt har en pilotanläggning använts för att studera och optimera ett hybridprocessteg bestående av ett koagulerings- och ultrafiltreringssteg med syfte att avlägsna humusämnen från ytvatten. Effekten av pH, reaktionstid och olika matarvattenkvaliteter (Görväln, Fyrisån och sandfiltrat) analyserades genom en serie experiment utförda med pilotanläggningen. Den mest optimala placeringen av ett eventuellt ultrafiltreringssteg i reningsprocessen studerades även.   Resultaten från experimenten påvisade att pH mellan 6.1 och 6.7 inte hade någon effekt på reningen av fDOM. Mer signifikanta skillnader i rening kunde observeras mellan de olika koaguleringsdoserna, vilket indikerar att denna parameter är viktigare än pH. Reaktionstiden hade ingen märkbar effekt på anläggningens reningseffektivitet. Däremot ökade transmembrantrycket tio gånger snabbare under experimenten med den kortare reaktionstiden. Dessa resultat antyder att de bildade flocken var mindre och därmed blev mer tätt packade i ultrafiltret vilket i sin tur lett till det snabbt ökande trycket i membranet. En avskiljning av minst 50 %, men inte mer än 60 %, av det ingående fDOM kunde uppnås med alla matarvatten utom sandfiltratet, som hade en reningseffektivitet på 18 %. Vattnet från Fyrisån visade sig vara en utmaning för anläggningen att hantera, då trycket snabbt byggdes upp i membranet vilket tyder på att anläggningen inte klarar för starkt förorenade vatten. Resultaten från sandfiltratexperimenten visade att ett ultrafiltreringssteg efter sandfiltren skulle kunna vara en möjlig placering av ultrafiltren. Ytterligare studier krävs dock för att med säkerhet kunna bestämma den mest optimala placeringen.   Sammanfattningsvis visar resultaten från experimenten lovande tecken på att en ultrafiltreringsprocess är ett möjligt alternativ för att öka Norrvattens dricksvattenreningsverks effektivitet och kapacitet.
Norrvatten is the fourth largest drinking water producer in Sweden. They produce and distribute drinking water to 14 municipalities north of Stockholm. For some time, Norrvatten has studied alternative processes in order to optimise and increase the production capacity and efficiency of their drinking water treatment plant at Görvälnverket.   In this project, a small-scale pilot plant has been used to study and optimise a coagulation and ultrafiltration hybrid process step in order to remove humic substances from surface water. The effect of pH, reaction time, and different feed water qualities (Görväln, Fyrisån and Görväln full scale sand filtrate) were analysed through a series of experiments performed with the pilot plant. The most optimal placement of an eventual ultrafiltration step was also studied.  The results from the experiments suggested that pH in the range 6.1 to 6.7 had no large effect on the removal efficiency of fluorescent dissolved organic matter (fDOM). Instead, differences in removal efficiency could be observed between coagulant dosages which indicates that this parameter is of more importance than pH. At higher pH (> 7) removal was significantly lower. The reaction time had no effect on the removal efficiency of the plant. However, the transmembrane pressure increased ten times faster during the experiments with a shorter reaction time. These results suggested that the floc formed were smaller and thereby more tightly packed in the ultrafilter which in turn increased the pressure in the membrane. An fDOM removal of at least 50 %, though no more than 60 %, was achieved with all feed waters except for the sand filtrate which had a removal efficiency of 18 %. However, highly concentrated humic waters such as Fyrisån proved to be challenging for the plant to handle since the pressure built up rather quickly in the membrane. The sand filtrate feed water experiments indicated that an ultrafiltration step after a sand filtration process would be effective. However, further studies are required to be able to determine the most optimal placement of the ultrafiltration process.  In conclusion, the results achieved with the pilot plant show promising signs of an ultrafiltration process being a viable alternative for Norrvatten to increase their drinking water treatment plant’s efficiency and capacity.

Hazardous waste management demands detailed planning due to the risks posed by hazardous wastes on public and environment and high investments required. This study aims to provide a framework that leads Ministry of Environment and Forestry (MoEF) in planning of hazardous waste facilities to be built. This framework considers the facility and transport cost along with impacts of hazardous waste management. The linear optimization models for several scenarios are developed in order to evaluate possible approaches in management of hazardous wastes. During cost calculations economy of scale principle is considered. Estimation of impact includes not only population impact but also environmental impact for which a methodology is developed in the scope of this study. This methodology considers the effect of hazardous waste transportation on lakes, rivers, dams, seashores, forests and agricultural areas, which are defined as vulnerable environmental elements. Evaluation of the results suggests that establishment of designated hazardous waste facilities with co-incineration practices and use of transfer stations give most satisfactory outcome. Co-incineration practices decrease incineration costs, which has the highest contribution to overall cost while transfer stations provide great improvement in total impact. Locations for recovery, treatment, incineration facilities and landfills are selected. These selections both confirm decisions made in the past regarding existing locations and become suggestions for locations for new facilities. It is observed that integrated facilities are favored. The importance of countrywide planning should also be underlined. It is believed that results of this study provides a basis to evaluate possible alternatives for further improvement of hazardous waste management system in Turkey that would be most useful to MoEF.

The environmental risk assessment of substances is introduced and the various controls used to protect the environment are outlined. The European notification system and the risk assessments required as part of the system are detailed. Through an examination of the existing European Union System for the Evaluation of Substances tool and sensitivity analyses based on variability in the measurement of physico-chemical properties for a substance, a spreadsheet model was developed to allow multiple risk assessments for the same substance to be calculated simultaneously. The development and testing of the NECXES spreadsheet tool are documented in detail. Data for the capacity and dilution factor at Sewage Treatment Plants (STPs) in England and Wales were collated and statistically analysed and compared to European default values used for generic risk assessments. The default capacity value for STPs (10,000 population equivalents) was protective of 70% of the STPs sampled. The remaining 30% however, a small number of large works, contributed 94% of the total effluent discharged from STPs in England and Wales. The STP data were used with the NEXCES tool to perform and compare probabilistic risk assessments to those calculated using deterministic methods for a number of test substances. The probabilistic calculations produced a lower median exposure concentration for water than the generic assessment for all of the test substances. Regression analysis allowed the probability of adverse effects to be quantified for the various deterministic risk values. The NEXCES tool was also used to develop a rapid assessment tool for new substances in the form of contour plots, which can be used to assess the risk of substances using minimal data. The main conclusions and contributions to the academic and industrial fields, as well as the field of environmental technology are presented. Areas where there are opportunities for further research are also outlined.

Comparaison au moyen d'une approche comportementale et electrophysiologique de l'efficacite analgesique de la morphine, d'agonistes des recepteurs mu , delta , kappa , et d'inhibiteurs de l'enkephalinase dans un modele de douleur experimentale, l'arthrite induite par adjuvant de freund chez le rat. Etude de la reactivite des systemes opioides endogenes au moyen de la naloxone

Climate change scenarios predict that seawater temperature and precipitation will increase in the Baltic Sea region during the next century. In the northern part of the Baltic Sea, increasing inflows of the terrestrial allochthonous dissolved organic matter (ADOM) are expected to be a major consequence of elevated rainfall, which can alter light and nutrient availability for phytoplankton. The aim of my thesis was to elucidate effects of ADOM on phytoplankton production, community, size-structure and nutritional strategy along offshore south-north gradients in the Baltic Sea, as well as in estuarine systems exposed to seasonal variation in river discharge. Field studies, a mesocosm experiment and a modeling study were used to explore these issues. Results from the field studies and mesocosm experiment illustrated that the nutritional strategy, size-structure and cellular pigment content of the phytoplankton were governed by changes in ADOM, and thus in light and nutrient availability. A summer study along an offshore south-north gradient showed that the proportion of mixotrophic phytoplankton increased towards the north. In this area the concentrations humic substances (proxy for ADOM) were high, while the light availability and phosphorus concentrations were relatively low. The phytoplankton cells responded to reduced light availability by increasing their chlorophyll a: carbon ratio. Additionally, the levels of photoprotective pigments decreased from south to north, as a result of acclimation to a low-light environment and reduced exposure to ultraviolet radiation. According to ecological assumptions picophytoplankton should be favored in light- and nutrient-limited environments. However, the results did not follow that pattern, the proportion of picophytoplankton being highest in the relatively nutrient rich Baltic Proper. The study was performed during the decline of an extensive bloom of filamentous cyanobacteria, a successional phase in which picophytoplankton often dominate the phytoplankton community. The estuarine studies performed in the Bothnian Bay (Råne estuary) and in the Bothnian Sea (Öre estuary) showed different successions. In the Råne estuary no spring phytoplankton bloom occurred and highest primary production was observed during the summer. This absence of a spring bloom was explained by low phosphorus and high ADOM concentrations, while the summer maximum could be explained by higher temperature and nutrient concentrations. In the Öre estuary a marked phytoplankton spring bloom was observed as well as an ADOM sustained bacterial production phase. The later secondary peak of bacterial production observed in summer, concomitant with an extended secondary primary production peak, suggests that autochthonous dissolved organic matter supported the bacterial growth Furthermore, the photosynthetic efficiency (i.e. phytoplankton growth rates) was lower during spring, indicating that high ADOM, and thus lower light and phosphorus availability, disfavored phytoplankton growth. Our modeling study showed that climate change can impact the food web; however effects will be different between basins. In the southern Baltic Sea elevated temperature and nutrient discharge may promote nutrient recycling and oxygen consumption, potentially extending anoxic areas, sediment nutrient release and cyanobacteria blooms. In the north, increased inflow of ADOM may promote heterotrophic bacterial production and decrease primary production due to light attenuation and lower phosphorus availability. This will favor the heterotrophic microbial food web and consequently lead to lower food web efficiency of the ecosystem.

The United Nations has, during many years, developed a model for a globally harmonized system for classification and labeling of chemicals, with the aim of it becoming a global standard. This system is implemented in the European Union through the CLP-regulation and is now working parallel to the existing directives until 1st of June 2015, when all the new classifications of substances and mixtures must be completed. The aim of this project was to adjust the laboratory to the new legislation, through inventory of stored chemicals, update the list of chemicals and perform self-classifications of mixtures. The work included handling of about 650 different chemicals with varying hazard classifications and search for information in corporate websites and chemical databases. This resulted in a new and complete list of chemicals stored and used in the laboratory and, in addition, an example of how to make a self classification of a mixture. Through this work using web based search for chemical classification according to the CLP-regulation, many difficulties were encountered and one of the conclusions is that due to the many noticed uncertainties and inconsistencies in self classification of mixtures the aim of keeping the globally harmonized system harmonized will be nearly impossible to fulfill.

The development of new therapeutical approaches, devised to foster the regeneration of neuronal circuits after injury and/or in neurodegenerative diseases, is of great importance. The impairment of dopaminergic projections is especially severe, because these projections are involved in crucial brain functions such as motor control, reward and cognition. In the work presented here, organotypic brain slice co-cultures of (a) the mesostriatal and (b) the mesocortical dopaminergic projection systems consisting of tissue sections of the ventral tegmental area/substantia nigra (VTA/SN), in combination with the target regions of (a) the striatum (STR) or (b) the prefrontal cortex (PFC), respectively, were used to evaluate different approaches to stimulate neurite outgrowth: (i) inhibition of cAMP/cGMP turnover with 3’,5’ cyclic nucleotide phosphodiesterase inhibitors (PDE-Is), (ii) blockade of calcium currents with nimodipine, and (iii) the co-cultivation with bone marrow-derived mesenchymal stromal/stem cells (BM-MSCs). The neurite growth-promoting properties of the tested substances and cell populations were analyzed by neurite density quantification in the border region between the two brain slices, using biocytin tracing or tyrosine hydroxylase labeling and automated image processing procedures. In addition, toxicological tests and gene expression analyses were conducted. (i) PDE-Is were applied to VTA/SN+STR rat co-cultures. The quantification of neurite density after both biocytin tracing and tyrosine hydroxylase labeling revealed a growth promoting effect of the PDE2A-Is BAY60-7550 and ND7001. The application of the PDE10-I MP-10 did not alter neurite density in comparison to the vehicle control. (ii) The effects of nimodipine were evaluated in VTA/SN+PFC rat co-cultures. A neurite growth-promoting effect of 0.1 µM and 1 µM nimodipine was demonstrated in a projection system of the CNS. In contrast, the application of 10 µM nimodipine did not alter neurite density, compared to the vehicle control, but induced the activation of the apoptosis marker caspase 3. The expression levels of the investigated genes, including Ca2+ binding proteins (Pvalb, S100b), immediate early genes (Arc, Egr1, Egr2, Egr4, Fos and JunB), glial fibrillary acidic protein, and myelin components (Mal, Mog, Plp1) were not significantly changed (with the exception of Egr4) by the treatment with 0.1 µM and 1 µM nimodipine. (iii) Bulk BM-MSCs that were classically isolated by plastic adhesion were compared to the subpopulation Sca-1+Lin-CD45--derived MSCs (SL45-MSCs). The neurite growth-promoting properties of both MSC populations were quantified in VTA/SN+PFC mouse co-cultures. For this purpose, the MSCs were seeded on glass slides that were placed underneath the co-cultures. A significantly enhanced neurite density within the co-cultures was induced by both bulk BM-MSCs and SL45-MSCs. SL45-MSCs increased neurite density to a higher degree. The characterization of both MSC populations revealed that the frequency of fibroblast colony forming units (CFU-f ) is 105-fold higher in SL45-MSCs. SL45-MSCs were morphologically more homogeneous and expressed higher levels of nestin, BDNF and FGF2 compared to bulk BM-MSCs. Thus, this work emphasizes the vast potential for molecular targeting with respect to the development of therapeutic strategies in the enhancement of neurite regrowth.

Objective of this project was the study of interaction processes between humic substances, U(VI), Np(V) and kaolinite KGa-1b. It contributed to the attainment of a better process understanding, the improvement of the knowledge on the interaction of humic substances and metal ions and the enhancement of the thermodynamic database. With a synthetic humic acid (HA), N-containing functional groups of HA were characterized by 15N-NMR spectroscopy. Based on these results, model studies of the influence of amino groups on the complexation behavior of HA were performed. Spectroscopic studies with amino acids show that the amino group do not contribute to the U(VI) complexation at pH 4. The impact of kaolinite on the formation of HA and humic substance-kaolinite-sorbates was studied in model syntheses. The results exhibit that the presence of kaolinite during the syntheses mainly influences the yields on HA and their elemental compositions. Synthetic humic substance-kaolinite-sorbates were isolated. Under exclusion of CO2, the U(VI) complexation by HA was investigated at pH 7 by means of the conventional time-resolved laser-induced fluorescence spectroscopy (TRLFS) and TRLFS with ultrafast pulses. Complexation parameters for the ternary complex UO2(OH)HA(I) were determined. Studies of the Np(V) reduction in presence of HA with different functionalities under anaerobic conditions have shown that Np(V) is reduced to Np(IV) by HA. The redox capacity depends on the HA functionality. Applying a modified HA it was verified that phenolic/acidic OH groups play a dominating role in the Np(V) reduction. The influence of HA on the U(VI) and Np(V) sorption onto kaolinite was investigated in batch experiments. In dependence on the experimental conditions, HA effects the sorption and consequently the mobility of U(VI) and Np(V). From studies of the U(VI) sorption onto synthetic humic substance-kaolinite-sorbates it was concluded that the structure and functionality of sorbed/associated humic substances considerably influence the sorption behavior of U(VI). The structure of U(VI)-kaolinite-surface complexes in presence of HA was studied by means of X-ray absorption spectroscopy and TRLFS and compared to those of U(VI)-kaolinite-complexes. Investigations of the migration of HA and U(VI) in the laboratory system kaolinite-water were carried out in diffusion experiments. The migration of HA in compacted clay is governed by diffusion and influenced by its colloidal properties. Humic substances exert an immobilizing effect on the U(VI) transport in compacted kaolinite.

Objective of this project was the study of interaction processes between humic substances, U(VI), Np(V) and kaolinite KGa-1b. It contributed to the attainment of a better process understanding, the improvement of the knowledge on the interaction of humic substances and metal ions and the enhancement of the thermodynamic database. With a synthetic humic acid (HA), N-containing functional groups of HA were characterized by 15N-NMR spectroscopy. Based on these results, model studies of the influence of amino groups on the complexation behavior of HA were performed. Spectroscopic studies with amino acids show that the amino group do not contribute to the U(VI) complexation at pH 4. The impact of kaolinite on the formation of HA and humic substance-kaolinite-sorbates was studied in model syntheses. The results exhibit that the presence of kaolinite during the syntheses mainly influences the yields on HA and their elemental compositions. Synthetic humic substance-kaolinite-sorbates were isolated. Under exclusion of CO2, the U(VI) complexation by HA was investigated at pH 7 by means of the conventional time-resolved laser-induced fluorescence spectroscopy (TRLFS) and TRLFS with ultrafast pulses. Complexation parameters for the ternary complex UO2(OH)HA(I) were determined. Studies of the Np(V) reduction in presence of HA with different functionalities under anaerobic conditions have shown that Np(V) is reduced to Np(IV) by HA. The redox capacity depends on the HA functionality. Applying a modified HA it was verified that phenolic/acidic OH groups play a dominating role in the Np(V) reduction. The influence of HA on the U(VI) and Np(V) sorption onto kaolinite was investigated in batch experiments. In dependence on the experimental conditions, HA effects the sorption and consequently the mobility of U(VI) and Np(V). From studies of the U(VI) sorption onto synthetic humic substance-kaolinite-sorbates it was concluded that the structure and functionality of sorbed/associated humic substances considerably influence the sorption behavior of U(VI). The structure of U(VI)-kaolinite-surface complexes in presence of HA was studied by means of X-ray absorption spectroscopy and TRLFS and compared to those of U(VI)-kaolinite-complexes. Investigations of the migration of HA and U(VI) in the laboratory system kaolinite-water were carried out in diffusion experiments. The migration of HA in compacted clay is governed by diffusion and influenced by its colloidal properties. Humic substances exert an immobilizing effect on the U(VI) transport in compacted kaolinite.

Petroleum products, which are required to keep the 'wheels' of industry and commerce turning, are distributed from the various refineries to their destinations throughout the country on a daily basis and the mode and extent of transportation or conveyance of these products is varied. This distribution activity predominantly takes place by means of road tanker, pipeline as well as rail tanker and quantities during transit could vary from a few hundred litres to many thousands of litres per trip. Road tanker transportation is considered to be the most vulnerable form of distribution means and this poses a high risk in terms of the potential for being involved in an accident. The risk potential associated with the road transportation of these fuels, from an environmental point of view, is aggravated due to: *The conveyance of bulk loads, *non-roadworthiness of many vehicles, *inconsistency in vehicle condition checking systems and in the application of *safety systems, *poor road conditions, *driver fatigue, *hi-jacking threats, *the level of incompetence or unsuitability of drivers, *the inconsistency in driver training programs, *the vulnerability of the tankers being subject to collision and accidents. The potential exists for road tankers involved in accidents to leak or spill large quantities of petroleum products which in turn could result in catastrophic environmental consequences (such as leaking large quantities of fuel into sewers, plantations, rivers and streams thus causing much ground and water pollution). Also, during an accident the fuel leaking from a road tanker may ignite causing it to burn for several hours before it is finally brought under control and extinguished. This may result in much air pollution as well as damage to the surrounding ecological systems. Subsequent explosions could further result in severe loss of life and associated fires which in turn could cause more environmental degradation and damage. For the purpose of this dissertation, focus was specifically placed on the introduction of internal company control measures that a "supplier” company (such as Natref (Pty) Ltd) could implement to check whether petroleum product distributors are complying with predetermined criteria aimed at reducing the potential for accidents involving road tankers. The measuring of how these controls have an effect in the bigger scheme of things in terms of reducing accidents and environmental degradation was very difficult to determine because it was not possible to extract from the distributors how many of their vehicles were actually involved in incidents during the study period. As a result it was not possible to determine whether the improved control measures had an effect on the number of accidents incurred by the vehicles that were effected by the improved application of the standards. The study thus focused primarily on the effect that the implementation of an inspection system could have in progressively reducing the number of defects found on road tankers wanting to gain access to Natrefs site as well as measuring whether an improvement in compliance to standards actually took place. This study was conducted over a period of 22 months and involved the development and implementation of a new procedure and training course, implementation of an inspection checklist, improved reporting methods as well as improved the overall environmental awareness of the employees involved in the checking and inspection process. It is however assumed that the implementation and ongoing enforcement of the company standards has assisted in contributing towards minimising the potential for pollution exposures arising from accidents and in so doing minimising environmental degradation to a larger or lesser extent.
Thesis (M. Environmental Management)--North-West University, Potchefstroom Campus, 2004.

Inflammatory Bowel Disease (IBD) is a chronic disorder that affects millions of peopleworldwide. Although the etiology behind the disease is yet unknown, current theoriespropose a complex interplay between genetic susceptibility, exposure to environmentalfactors and exacerbated immune responses. While important efforts have been made to linkgenetics and environmental factors to IBD pathogenesis, a major challenge remains to assignthem a causative role. Particularly since most of the IBD-risk genetic polymorphisms arefound in non-coding regions (NCRs) with unknown regulatory activity, and for the lack ofknowledge about how environmental factors can modulate the function of these elements invivo . A main problem to address this challenge in IBD research is the lack of an appropriatemodel system in vivo that allows for high-throughput experiments with combinations ofdifferent IBD-risk factors, while keeping the in vivo context. In this work, we sought toovercome this issue by using a zebrafish reporter for a specific human IBD-risk NCR, inorder to investigate the modulation of this element by two groups of common environmentalfactors: pollutants, such as PolyFluoroAlkyl Substances (PFASs); and diet, by activation ofdietary sensors. We found that the activity of the WT-NCR in zebrafish larvae was increased in the presenceof PFAS, while the activation of the dietary sensor PPAR δ decreased the activity. These datalead us to suggest that the function of PFAS can be counteracted by PPARδ activation.Therefore, we propose zebrafish as a suitable in vivo model in which we can screen forpotentially harmful or beneficial effects of environmental factors in the activity of humannon-coding regions.
Inflammatorisk tarmsjukdom (IBD) är en kronisk störning som drabbar miljontals människorvärlden över. Även om etiologin bakom sjukdomen fortfarande är okänd, föreslår nuvarandeteorier ett komplext samspel mellan genetisk mottaglighet, exponering av miljöfaktorer ochförvärrat immunförsvar. Även om stora ansträngningar har gjorts för att koppla genetik ochmiljöfaktorer till IBD-patogenes, återstår en stor utmaning att tilldela dem en orsakande roll.Särskilt eftersom de flesta av IBD-riskgenetiska polymorfismer finns i icke-kodande regioner(NCR) med okänd reglerande aktivitet samt för bristen på kunskap om hur miljöfaktorer kanmodulera funktionen hos dessa element in vivo . Ett huvudproblem för att möta dennautmaning i IBD-forskning är avsaknaden av ett lämpligt modellsystem in vivo som möjliggörexperiment med hög kapacitet och kombinationer av olika IBD-riskfaktorer in vivo . I dettaarbete försökte vi få svar på denna fråga genom att använda en zebrafiskreporter för ettspecifikt humant IBD-risk icke-kodande område. Detta möjliggjorde att vi kunde undersökamodulering av två gemensamma miljöfaktorer: föroreningar, såsom PolyFluoroAlkyl-ämnen(PFASs); och diet, genom aktivering av dietsensorer. Vi fann att aktiviteten i WT-NCR hos zebrafisklarver ökade i närvaro av PFAS, medanaktiveringen av dietsensorn PPARδ minskade aktiviteten. Denna data leder till att vi antyderatt funktionen för PFAS kan motverkas genom PPARδ-aktivering. Därför föreslår vizebrafisk som en lämplig in vivo -modell, i vilken vi kan screena för potentiellt skadliga ellergynnsamma effekter av miljöfaktorer i mänskligt icke-kodande DNA.

La progression rapide de l’obésité en Europe est en partie due à un déséquilibre de l’homéostasie énergétique lié à une consommation excessive d’aliments gras et sucrés, et à des modes de vie sédentaires. Cette consommation excessive d'aliments riches en calories, à fort impact hédonique,dépend en partie de la libération de dopamine dans le système mésocorticolimbique, autrement nommé circuit de la récompense. La libération de dopamine dans le système mésocorticolimbique est un facteur nécessaire aux comportements compulsifs liés à la nourriture, et les aliments riches pourraient être responsables d’une alimentation trop excessive, assimilable aux dysfonctionnements du système mésocorticolimbique relatifs aux drogues d’abus. En particulier, la majorité des lipides issus de notre alimentation circulent sous forment de triglycérides devant être hydrolysés en acides gras libres pour pouvoir être oxydés par la cellule, et s'accumulent en condition obèse (hypertriglycéridémie). Les neurones du système mésocorticolimbique expriment certaines enzymes liées au métabolisme de ces triglycérides, notamment la lipoprotéine lipase, ce qui suggère qu’ils peuvent les détecter et moduler en conséquence leur activité, et donc la libération de dopamine. Le but de cette thèse est d'étudier les mécanismes moléculaires et cellulaires qui relient prise alimentaire et signalisation induite par les lipides dans le système nerveux central, et en particulier dans le système dopaminergique
Obesity spreading is due to an imbalance of energy homeostasis, with excessive consumption of sweet and fat food, and sedentary lifestyles. Food intake partly depends on dopamine release in the mesocorticolimbic system, and calorie-rich hedonic food, among other objects of desire, stimulate this reward circuit. Dopaminergic release in the mesocorticolimbic system is a main factor for compulsive feeding, and calorie-rich food could be responsible for abnormal feeding behaviours, where excessive food intake is assimilated to MCL malfunctions similar to drugs addiction. More particularly, postprandial triglycerides represent a major source of dietary lipids, and obesity is often associated with hypertriglyceridemia, but also with dopaminergic signalling impairments. Mesocorticolimbic system neurons express several enzymes involved in triglycerides hydrolysis, such as the lipoprotein lipase, suggesting an ability to sense triglycerides and modulate their activity accordingly. The aim of this thesis is to identify cellular and molecular mechanisms by which dietary triglycerides act onto dopaminergic structures and control food intake

The electrical and optical properties of boron doped hydrogenated amorphous silicon thin films (a-Si) were investigated to determine the effect of boron and hydrogen incorporation on carrier transport. The a-Si thin films were grown by plasma enhanced chemical vapor deposition (PECVD) at various boron concentrations, hydrogen dilutions, and at differing growth temperatures. The temperature dependent conductivity generally follows the hopping conduction model. Above a critical temperature, the dominant conduction mechanism is Mott variable range hopping conductivity (M-VRH), where p = ¼, and the carrier hopping depends on energy. However, at lower temperatures, the coulomb interaction between charge carriers becomes important and Efros-Shklosvkii variable hopping (ES-VRH) conduction, where p=1/2, must be included to describe the total conductivity. To correlate changes in electrical conductivity to changes in the local crystalline order, the transverse optical (TO) and transverse acoustic (TA) modes of the Raman spectra were studied to relate changes in short- and mid-range order to the effects of growth temperature, boron, and hydrogen incorporation. With an increase of hydrogen and/or growth temperature, both short and mid-range order improve, whereas the addition of boron results in the degradation of short range order. It is seen that there is a direct correlation between the electrical conductivity and changes in the short and mid-range order resulting from the passivation of defects by hydrogen and the creation of trap states by boron. This work was done under the ARO grant W911NF-10-1-0410, William W. Clark Program Manager. The samples were provided by L-3 Communications.

A Amazônia representa a maior biodiversidade do mundo e representa um reservatório enorme e dinâmico de carbono, não só na biomassa, mas também no solo. O ciclo do carbono neste bioma é muito importante, principalmente para questões abordadas às mudanças climáticas. Avaliar e compreender a dinâmica do carbono e outros elementos no solo da Amazônia pode ajudar os cientistas a melhorar os modelos e antecipar cenários. Novos métodos, que permitem medições de carbono do solo in situ, são uma abordagem fundamental para este tipo de região, devido aos custos financeiros para a coleta e envio de amostras de solo da floresta para o laboratório, e demanda muito tempo nesta atividade. No presente estudo, uma topossequência de um sistema Latossolo-Espodossolo com caulim associado, desenvolvido a partir de rochas granito gnáissicas do embasamento cristalino, foi estudada. As amostras foram coletadas em São Gabriel da Cachoeira, estado do Amazonas. Dois perfis de solo: Espodossolo Humilúvico (P1) no topo e Latossolo Amarelo (P2) na meia encosta da topossequência foram descritos e amostrados em um total de dezoito amostras. Os objetivos principais foram avaliar e caracterizar através de métodos químicos e espectroscópicos a matéria orgânica e a composição elementar nestes solos arenosos utilizando a análise elementar (CHNS), espectroscopia de emissão ótica com plasma induzido por laser (LIBS), espectrometria de emissão ótica com plasma acoplado indutivamente (ICP OES), espectroscopia de fluorescência induzida por laser (FIL), fluorescência de luz UVVisível e absorção de radiação na região no UV-Visível. Através dos resultados obtidos pela análise elementar foi possível notar que para o Espodossolo Humilúvico houve variações diferenciadas nos teores de carbono, mas para o Latossolo Amarelo, não se pode inferir uma tendência de incremento ou decréscimo do teor de carbono ao longo do perfil, pois o teor de carbono para a maioria das amostras de solo foi inferior a 0,3%, o limite de detecção do CHNS. A espectroscopia de matrizes de fluorescência de excitação-emissão (MEE) foi uma técnica mais seletiva e sensível do que a fluorescência bidimensional para os ácidos húmicos (AH), mostrando informações interessantes, variações estruturais e grande diferença entre os cromóforos que emitem fluorescência nos extratos de ácido fúlvico 2 (EAF2) e AH. A combinação dos espectros de MEE com a análise de fatores paralelos (PARAFAC) permitiu caracterizar qualitativamente os EAF2, podendo identificar e associar com mais clareza os três fluoróforos obtidos, com seus respectivos componentes, ácidos fúlvicos (grupos de fluoróforos simples e complexos) e proteína, com diagnóstico de consistência do tensor núcleo (CORCONDIA) de 85,8%. Esta combinação permitiu caracterizar quantitativamente os AH, identificando a contribuição das intensidades de dois fluoróforos, associados aos AH, grupos de fluoróforos mais complexos e simples, com CORCONDIA de 84,2%. A partir dos resultados de LIBS, uma forte correlação foi encontrada e os coeficientes de correlação de Pearson\'s obtidos para o ajuste logarítmico foi de R = 0,98 e R = 0,99 para o carbono e o alumínio, respectivamente, entre os valores obtidos por LIBS e as técnicas de referências (CHNS e ICP OES) para o Espodossolo Humilúvico. Nenhuma relação foi observada para o ferro, provavelmente devido aos teores estarem abaixo do limite de detecção. A técnica FIL mostrou para o Espodossolo Humilúvico que o horizonte de transição (Tr) estaria funcionando como uma \"peneira molecular\", acumulando a matéria orgânica pouco humificada, permitindo a passagem para os horizontes de caulim (K1 e K2) de compostos com estruturas mais humificadas, mais complexas, de difícil degradação (mais recalcitrantes), mas de menor tamanho molecular, como anéis aromáticos condensados e/ou conjugação de anéis aromáticos simples, corroborando com a eficiência da extração do AH. Para o Latossolo Amarelo, observou-se um aumento no grau de humificação do horizonte superficial BA em relação ao A2. Logo, estes resultados contribuem para um melhor entendimento sobre a quantificação de carbono, grau de humificação e alterações estruturais da matéria orgânica dos solos arenosos da região de São Gabriel da Cachoeira na Amazônia.
The Amazon represents the world\'s biggest biodiversity, comprehending a large and dynamic carbon pool, considering its biomass and soil, as well. The carbon cycle in this biome is very important, especially in questions regarding climatic changes. To evaluate and to understand the carbon and other elements cycles in Amazonian soil can help scientists to improve models and foresee scenarios. New methods, allowing carbon measurements on site, are a crucial approach for this kind of region, due to the financial costs to collect and ship soil samples from forest to laboratory, and the time spent in this activity. In the present study, it was analyzed a topsequence of an Oxisol-Spodosol system with kaolin associated, generated from granitic-gneiss rocks of crystalline basement. The soil samples were collected in São Gabriel da Cachoeira, Amazonas state, Brazil, considering two different soil profiles: Spodosols (P1), at the top layer, and yellow Oxisols (P2) at the topsequence hillside, representing a total of eighteen samples. The main purpose of this study was to evaluate and characterize the organic matter content and elemental composition by chemical and spectroscopic methods using elemental analysis (CHNS), laserinduced breakdown spectroscopy (LIBS), inductively coupled plasma optical emission spectrometry (ICP OES), laser-induced fluorescence spectroscopy (LIFS), fluorescence spectroscopy and UV-Visible spectroscopy. The CHNS results showed differences in the carbon content for the Spodosol (P1) samples; however, it was not observed any differences for the Oxisol (P2) samples, once the carbon content data obtained for these samples were lower than the equipment detection limit (0.3%). The excitation-emission matrix (EEM) fluorescence spectroscopy was more sensitive for detecting humic acids (HA) than the two-dimensional fluorescence spectroscopy, showing interesting information, structural variations and large difference among chromophores that emit fluorescence in fulvic acid extracts 2 (EAF2) and HA. The EAF2 were qualitatively characterized by combining the EEM spectra with parallel factor analysis (PARAFAC), which allowed to identify clearly the three fluorophores obtained and their respective components, fulvic acids (simple and complex groups of fluorophores) and protein, with core consistency diagnostic (CORCONDIA) of 85.8%. These data also allowed to quantify the HA, identifying contributions of intensities from two fluorophores associated with HA, complex groups and simple fluorophores, presenting CORCONDIA of 84.2%. Regarding the carbon and aluminum content results for the Spodosol samples, a strong correlation was found between the LIBS values and the standard techniques (CHNS and ICP OES). The Pearson\'s coefficients obtained by logarithmic fit were R = 0.98 and R = 0.99 for carbon and aluminum, respectively. It was not observed any differences for the iron contents from the analyzed samples, probably due to the low content observed regarding the detection limit this element presents. The LIFS technique indicated that the transition horizon (Tr) would be acting as a \"molecular sieve\" in the Spodosol soil (P1), accumulating less humified organic matter, and allowing passage to kaolin horizons (K1 and K2) of compounds with more humified, more complex, difficult to degrade (recalcitrant) structures, but with lower molecular size, such as condensed aromatic rings and/or combination of simple aromatic rings. These results were in accordance to the HA extraction efficiency. For the yellow Oxisol (P2) samples, it was observed a humification degree increase in the surface horizon BA compared to the A2 horizon. This way, the data obtained contribute to a better understanding regarding carbon quantification, humification degree and organic matter structural alterations on sandy soils in São Gabriel da Cachoeira, at the Amazonian region.

Injury to bone is one of the most prevalent and costly medical conditions. Clinical treatment of volumetric bone loss or hard-to-heal bony lesions often requires the use of proper bone grafting materials, with or without adjuvant anabolic therapeutics. Despite significant problems associated with autografting (donor site morbidity, limited supplies) and allografting (disease transmissions, high graft failure rates) procedures, synthetic bone grafts remain the least utilized clinically. Existing synthetic orthopaedic biomaterials rarely possess a combination of bone-like structural and biochemical properties required for robust osteointegration, scalable and user-friendly characteristics indispensable for successful clinical translations. This thesis tests the hypothesis that by recapitulating key structural elements and biochemical components of bone in 3- and 2-dimensional biomaterials, scalable synthetic bone grafts can be designed to enable expedited healing of hard-to-heal volumetric bone loss. Specifically, FlexBone, a 3-dimensional hydrogel scaffold encapsulating 50 wt% of structurally well integrated nanocrylstalline hydroxyapatite, the main inorganic component of bone, was developed. The large surface area of nanocrystalline hydroxyapatite combined with its intrinsic affinity to proteins and its excellent structural integration with the hydrogel matrix enabled FlexBone to both sequester endogenous protein signals upon press-fitting into an area of skeletal defect and to deliver exogenous protein therapeutics in a localized and sustained manner. We demonstrated that FlexBone enabled the functional healing of critical-size long bone defects in rats in 8 – 12 weeks with the addition of a very low dose of osteogenic growth factor BMP-2/7. This promising synthetic bone graft is now being explored for the delivery of multiple growth factors to expedite the healing of diabetic bony lesions. In addition, a 2-dimensional electrospun cellulose fibrous mesh was chemically modified with sulfate residues to mimic sulfated polysaccharide ECM components of skeletal tissues to enabled progenitor cell attachment and differentiation as well as controlled retention and localized/sustained delivery of protein therapeutics. This sulfated fibrous mesh is currently explored as synthetic periosteum to augment the osteointegration of devitalized structural allografts. Finally, a rat subcutaneous implantation model developed to examine the biocompatibility of newly developed biodegradable shape memory polymer bone substitutes is also presented.

Orientador: Leonardo Fernandes Fraceto
Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Os defensivos agrícolas tornaram-se alguns dos mais importantes compostos utilizados no mundo e são os principais responsáveis pelo aumento da produção agrícola. O Paraquat, um herbicida não seletivo de contato utilizado em diversas culturas no mundo, apresenta alta toxicidade para os seres vivos e considerável persistência no solo, o que fez com que ele fosse banido em alguns países. Embora os defensivos agrícolas possuam uma importante função no aumento da produção de alimentos, através do controle de pragas, eles podem gerar sérios impactos ambientais, através da contaminação dos recursos hídricos e do solo. Com o crescimento da nanotecnologia, diversos mecanismos estão sendo estudados a fim de minimizar estes danos, tais como o desenvolvimento de sistemas de liberação modificada, utilizando polímeros biodegradáveis, o qual permite um aumento no desempenho/eficiência do produto. Estudos indicam que a matéria orgânica natural presente no solo, sedimento e água podem interagir com os defensivos agrícolas e nanopartículas e consequentemente modificar o destino destas substâncias no ambiente. A presente Tese tem como objetivo principal mostrar resultados do desenvolvimento e caracterização de nanopartículas poliméricas de quitosana/tripolifosfato para liberação modificada do herbicida Paraquat, bem como, estudar a estabilidade e a toxicidade deste sistema nanoparticulado com a presença ou ausência de matéria orgânica natural (na forma de substâncias húmicas). A atividade herbicida e a sorção do herbicida nanoparticulado no solo também foram avaliados. Nanopartículas de quitosana/tripolifosfato (com ou sem Paraquat) foram preparadas pelo método de gelificação iônica e apresentaram tamanho médio, índice de polidispersão e potencial zeta de ~ 300 nm, 0,250 e 45 mV, respectivamente. A eficiência de encapsulação do Paraquat foi de 62,6 ± 0,7 % e as nanopartículas apresentaram-se esféricas e com boa estabilidade coloidal. A cinética de liberação e o ensaio de sorção no solo mostraram que as nanopartículas retardaram a difusão e a liberação do herbicida e o modelo matemático que melhor descreveu a cinética de sorção foi o de pseudo-segunda ordem. Ensaios de citotoxicidade, genotoxicidade e ecotoxicidade indicaram que a associação do Paraquat às nanopartículas reduziram o efeito tóxico, uma vez que menos herbicida foi liberado para o ambiente em função do tempo, e ainda assim a atividade herbicida foi preservada ou aumentada. A presença de substâncias húmicas naturais não alterou os parâmetros físico-químicos estudados; entretanto, mostrou que pode reduzir a genotoxicidade e a ecotoxicidade do herbicida quando associado às nanopartículas, através de modificações na dinâmica do sistema. Este trabalho possui resultados inovadores e promissores que abrem novas discussões e perspectivas para o desenvolvimento de sistemas de liberação modificada para defensivos agrícolas
Abstract: Agrochemicals have become one of the most important compounds used in the world and are the main responsible for the increase in agricultural production. Paraquat, a non-selective herbicide used in several crops in the world, has high toxicity to living beings and considerable persistence in the soil, which led to its banishment in some countries. Although agrochemicals have an important function in increasing food production by minimizing pests, they can cause serious environmental impacts through contamination of soil and water resources. With the nanotechnology growth, several mechanisms have been studied in order to minimize these damages, such as the development of modified release systems using biodegradable polymers, which allows an increase in performance/efficiency of the product. Studies indicate that the natural organic matter present in the soil, sediment and water can interact with agrochemicals and nanoparticles, and therefore, modify the destination of these substances in the environment. The purpose of the present Thesis is to show results of the development and characterization of chitosan/trypolyphosphate polymeric nanoparticles for modified release of the Paraquat herbicide, as well as to study the stability and toxicity of this nanoparticles with the presence or absence of natural organic matter (mainly in the form of humic substances). Herbicide activity and sorption of the nanoparticulate herbicide in the soil were also evaluated. Chitosan/Trypolyphosphate nanoparticles (with or without Paraquat) have been prepared by ionic gelation method and presented average size, polydispersity index and zeta potential of ~ 300 nm, 0.250 and 45 mV, respectively. The Paraquat encapsulation efficiency was 62.6 ± 0.7 % and the nanoparticles showed themselves spherical and good colloidal stability. The release kinetics and sorption test in the soil showed that the nanoparticles modified the diffusion and release of herbicide and the mathematical model that best described the sorption kinetics was pseudo-second order. Cytotoxicity, genotoxicity and ecotoxicity tests indicated that the association of Paraquat with the nanoparticles reduced the toxic effect, since less herbicide was released into the environment as function of time, but even so, the herbicidal activity was preserved or enhanced. The presence of humic substances in the medium altered the dynamic equilibrium of the herbicide in solution, and diminished the toxicity of the nanoparticle/paraquat system. This study has innovative and promising results that open new discussions and perspectives for the development of modified release systems for agrochemicals
Doutorado
Bioquimica
Doutor em Biologia Funcional e Molecular

The primary goal of my thesis research was to characterize the basis for the hypersensitive response of glycogen phosphorylase to catecholamine stimulation in primary culture diabetic cardiomyocytes. Toward this goal, I have investigated several key regulatory sites in this signaling pathway which could promote the hypersensitive activation of phosphorylase. Specifically, I investigated (1) which adrenergic receptors are involved in mediating the hypersensitive response of glycogen phosphorylase to epinephrine stimulation; (2) whether the presence of fatty acid metabolites affects phosphorylase activation; (3) whether the hypersensitive response of phosphorylase results from altered signal transduction through the β-adrenergic receptor system or from a post-receptor defect; and (4) the potential role for phosphorylase kinase in mediating the hypersensitive response of phosphorylase to catecholamine stimulation. The basis for adrenergic receptor mediation of the catecholamine-induced activation of glycogen phosphorylase was investigated in adult rat cardiomyocytes isolated from normal and alloxan-diabetic animals. Cells derived from diabetic animals exhibited a hypersensitive response to epinephrine stimulation which was apparent 3 hours after cell isolation and was further enhanced upon maintenance of the myocytes in culture for 24 hours. Normal cells initially lacked the hypersensitive response to epinephrine stimulation although upon maintenance of these cells in culture for 24 hours, the hypersensitive response was acquired in vitro. To assess alpha- and beta- adrenergic mediation of the response, normal and diabetic cardiomyocytes were incubated with propranolol, a β-receptor antagonist, prior to direct α1receptor stimulation with phenylephrine. Both normal and diabetic myocytes failed to undergo activation of phosphorylase in 3 or 24 hour cell cultures. In addition, the effects of epinephrine on phosphorylase activation were completely inhibited by propranolol whereas prazosin, an α-receptor antagonist, was unsuccessful. This data suggests that the hypersensitive response of glycogen phosphorylase in normal and diabetic cardiomyocytes is solely mediated through β-adrenergic receptor activation. Since the accumulation of various fatty acid metabolites can affect certain enzymes and signal transduction pathways within the cell, the potential effect of various fatty acid metabolites on phosphorylase activation was investigated. To determine the potential effects of fatty acid metabolites on phosphorylase activation in cultured cardiomyocytes, normal and alloxan-diabetic cells were incubated with either carnitine or palmitoylcarnitine prior to stimulation with epinephrine. Pretreatment of cardiomyocytes with or without carnitine or palmitoylcarnitine for 3 or 24 hours before epinephrine stimulation failed to alter phosphorylase activation. The addition of exogenous carnitine in the absence and presence of insulin was also unsuccessful in attenuating the hypersensitive phosphorylase activation response in 3 and 24 hour, normal and alloxan-diabetic derived cardiomyocytes. To determine if carnitine palmitoyltransferase 1 (CPT-1) activity was responsible for the hypersensitive response of phosphorylase in the diabetic myocytes, both normal and diabetic myocytes were maintained for 3 and 24 hours in the absence and presence of etomoxir, a CPT-1 inhibitor. Subsequent activation of phosphorylase by epinephrine in normal and diabetic myocytes was unaltered in the presence of etomoxir. Collectively, these data fail to support a critical role for fatty acid metabolite involvement in the hypersensitive activation of glycogen phosphorylase in acute, alloxan-diabetic cardiomyocytes. To assess potential G-protein involvement in the response, normal and diabetic-derived myocytes were incubated with either cholera or pertussis toxin prior to hormonal stimulation. Pretreatment of cardiomyocytes with cholera toxin resulted in a potentiated response to epinephrine stimulation whereas pertussis toxin did not affect the activation of this signaling pathway. To determine if the enhanced response of phosphorylase activation resulted from an alteration in adenylyl cyclase activation, the cells were challenged with forskolin. After 3 hours in primary culture, diabetic cardiomyocytes exhibited a hypersensitive response to forskolin stimulation relative to normal cells. However, after 24 hours in culture, both normal and diabetic myocytes responded identically to forskolin challenge. The present data suggest that a cholera toxin sensitive G-protein mediates the hypersensitive response of glycogen phosphorylase to catecholamine stimulation in diabetic cardiomyocytes. This response, which is present in alloxan-diabetic cells, and is induced in vitroin normal cardiomyocytes, is primarily due to a defect at a post-receptor site. To assess the role of phosphorylase kinase in the hypersensitive activation of glycogen phosphorylase in the diabetic heart, phosphorylase kinase activity was measured initially in perfused hearts (to optimize the assay parameters) and subsequently in primary culture cardiomyocytes. Results from these experiments demonstrate that the present method for measuring phosphorylase kinase activity is a reliable indicator of the enzyme's activity in the heart, although the assay conditions must be further optimized before this system can be applied to the measurement of phosphorylase kinase activity in primary cultured cardiomyocytes.

During heart valve remodeling, and in many disease states, valvular interstitial cells (VICs) shift to an activated myofibroblast phenotype which is characterized by enhanced synthetic and contractile activity. Pronounced alpha smooth muscle actin (αSMA)-containing stress fibers, the hallmark of activated myofibroblasts, are also observed when VICs are placed under tension due to altered mechanical loading in vivo or during in vitro culture on stiff substrates or under high mechanical loads and in the presence of transforming growth factor-beta1 (TGF-β1). The work presented herein describes three distinct model systems for application of controlled mechanical environment to VICs cultured in vitro. The first system uses polyacrylamide (PA) gels of defined stiffness to evaluate the response of VICs over a large range of stiffness levels and TGF-β1 concentration. The second system controls the boundary stiffness of cell-populated gels using springs of defined stiffness. The third system cyclically stretches soft or stiff two-dimensional (2D) gels while cells are cultured on the gel surface as it is deformed. Through the use of these model systems, we have found that the level of 2D stiffness required to maintain the quiescent VIC phenotype is potentially too low for a material to both act as matrix to support cell growth in the non-activated state and also to withstand the mechanical loading that occurs during the cardiac cycle. Further, we found that increasing the boundary stiffness on a three-dimensional (3D) cell populated collagen gel resulted in increased cellular contractile forces, αSMA expression, and collagen gel (material) stiffness. Finally, VIC morphology is significantly altered in response to stiffness and stretch. On soft 2D substrates, VICs cultured statically exhibit a small rounded morphology, significantly smaller than on stiff substrates. Following equibiaxial cyclic stretch, VICs spread to the extent of cells cultured on stiff substrates, but did not reorient in response to uniaxial stretch to the extent of cells stretched on stiff substrates. These studies provide critical information for characterizing how VICs respond to mechanical stimuli. Characterization of these responses is important for the development of tissue engineered heart valves and contributes to the understanding of the role of mechanical cues on valve pathology and disease onset and progression. While this work is focused on valvular interstitial cells, the culture conditions and methods for applying mechanical stimulation could be applied to numerous other adherent cell types providing information on the response to mechanical stimuli relevant for optimizing cell culture, engineered tissues or fundamental research of disease states.

Creating the proposition of the specific database of the hazardous chemical substances for the necessity the integrated rescue system of the Czech Republic. The basic properties of the hazardous chemical substances. The integrated rescue system and its components. The brief view of the selected databases from CR and abroad concerning the hazardous chemical substances. The proposed structure, content and range of the possible communal database of the hazardous chemical substances on the basis of the necessities and the requirements the particular components of the integrated rescue system and possibilities of the utilization.

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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior
Corrosion inhibition efficiency of saponified coconut oil (SCO) and sodium dodecilbenzene sulfonate (DBS) surfactants in AISI 1020 carbon steel was evaluated by electrochemical methods. These surfactants were also evaluated as microemulsion systems (SCO-ME and DBS-ME), of O/W type (water-rich microemulsion), in a Winsor IV region. They were obtained according to the following composition: 15% SCO, 15% butanol (30% Co-surfactant/Surfactant C/T), 10% organic phase (FO, kerosene) and 60% aqueous phase (FA). These systems were also used to solubilize the following nitrogenated substances: Diphenylcarbazide (DC), 2,4-dinitro-phenyl-thiosemicarbazide (TSC) and the mesoionic type compound 1,3,4-triazolium-2-thiolate (MI), that were investigated with the purpose of evaluating their anticorrosive effects. Comparative studies of carbon steel corrosion inhibition efficiencies of free DBS and DBS-ME, in brine and acidic media (0.5%), showed that DBS presents better inhibition results in acidic media (free DBS, 89% and DBS-ME, 93%). However, the values obtained for DBS in salted solution (72% free DBS and 77% DBS-ME) were similar to the ones observed for the SCO surfactant in brine (63% free SCO and 74% SCO-ME). Analysis of corrosion inhibition of the nitrogenated substances that were solubilized in the SCO-ME microemulsion system by the linear polarization method in brine (0.5% NaCl) showed that such compounds are very efficient an corrosion inhibitors [DC-ME-SCO (92%), TSC-ME-SCO (93%) and MI-ME-SCO (94%)]
A efici?ncia de inibi??o ? corros?o em a?o AISI 1020 dos tensoativos ?leo de coco saponificado (OCS) e dodecilbenzeno sulfonato de s?dio (DBS), foi avaliada por m?todos eletroqu?micos. Estes tensoativos foram tamb?m avaliados em sistemas microemulsionados (OCS-ME e DBS-ME), do tipo O/A (microemuls?o rica em ?gua) com regi?o de trabalho Winsor IV, e foram obtidos na seguinte composi??o: 15% de OCS, 15% de butanol (30% de Cotensoativo/tensoativo - C/T), 10% de fase org?nica (FO, querosene) e 60% de fase aquosa (FA), tendo sido utilizados, ainda, para a solubiliza??o das subst?ncias nitrogenadas difenilcarbazida (DC), 2,4-dinitro-fenil-tiossemicarbazida (TSC) e do heterociclo do tipo mesoi?nico 1,3,4-triaz?lio-2-tiolato (MI), que foram disponibilizadas para avalia??o dos seus efeitos anticorrosivos. Os estudos comparativos das efici?ncias dos tensoativos DBS livre e DBS-ME na inibi??o da corros?o de a?o carbono, em meios salino e ?cido (0,5%), mostraram que o DBS apresenta melhores resultados de inibi??o em meio ?cido (DBS livre, 89% e DBS-ME, 93%). No entanto, os valores obtidos para o DBS em meio salino (72% DBS livre e 77% DBS-ME) foram semelhantes aos valores observados para o tensoativo OCS em meio salino (63% OCS livre e 74% OCS-ME). A an?lise de inibi??o ? corros?o das subst?ncias nitrogenadas solubilizadas no sistema microemulsionado OCS-ME, pelo m?todo de curvas de polariza??o linear em meio salino (NaCl 0,5%) mostrou que tais compostos s?o muito eficazes na inibi??o ? corros?o [DC-ME-OCS (92%), TSC-ME-OCS (93%) e MI-ME-OCS (94%)]

L’exploitation de l’énergie nucléaire pour la production d’électricité présente un défi de gestion des e˜uents radiotoxiques pour les générations présentes et futures. Face à ce constat, la communauté des chimistes recherche continument à améliorer les solutions de traitement et de recyclage du combustible usé. Dans le contrôle de ces procédés, les opérations d’analyse jouent un rôle primordial. La miniaturisation des procédés est un des enjeux principaux de la recherche en sûreté nucléaire, dans un e˙ort de réduction des risques, des délais et des coûts des activités de laboratoire. Dans ce contexte, les travaux présentés ici sont issus d’une collaboration entre le CEA de Marcoule et l’IMEP-LAHC et traitent de la mise au point d’un microsystème optofluidique sur verre, adapté à la mesure de concentration de plutonium (VI) en acide nitrique. Une source de lumière sonde est confinée dans un guide d’onde obtenu par échange d’ions et interagit par onde évanescente avec un canal microfluidique. La raie d’absorption à 832 nm du Pu(VI) dans la solution à analyser devient donc observable dans le spectre de la lumière après une certaine longueur d’interaction. Un des enjeux principaux est de fabriquer un capteur très robuste, fonctionnel en boîte à gants. L’assemblage du dispositif est e˙ectué par collage moléculaire avec un procédé permettant d’atteindre une énergie de surface > 2, 5 J·m2 suÿsante à garantir la tenue du dispositifs à des pressions testées jusqu’à 2 bars dans les canaux. Les fonctions optiques et fluidiques du dispositif sont complètement interfacées avec des fibres optiques et des capillaires fluidiques. Des mesures spectrales d’une solution de plutonium (VI) en acide nitrique ont permis de vérifier la compatibilité de la solution technologique abordée pour la manipulation d’acides forts et la résistance à l’irradiation. Le système présente une limite de détection de 1,6·10−2 mol·L−1 Pu(VI) pour un volume sondé inférieur à 1 nano-litre, au sein d’un microcanal de 21 micro-litres. Une structure permettant d’optimiser la sensibilité du capteur ainsi que le volume du canal est étudiée en perspective du travail de thèse, afin d’atteindre les performances équivalentes à des outils commerciaux pour des volumes sondés de l’ordre de quelques nano-litres
.The use of nuclear energy for electricity production presents an important concern with radiotoxic waste management for present and future generations. In view of this fact, the chemists’ community has been searching for solutions to treat and recycle nu-clear fuel. The miniaturization of chemical processes is extensively sought out nowerdays, in an attempt to reduce laboratory acivity risks, delays and costs. The researched ana-lytical innovation requires subsequent development of appropriate analysis tools. In this respect, the work presented here addresses the development of co-integrated optofluidic micro-systems on borosilicate glass, compatible with nuclear e˜uent analysis constraints. A spectrometric sensor is designed, fabricated, interfaced and characterized in a nuclear environement. An optical waveguide and a microfluidic channel are designed adjacent to one another in order to obtain wide-spectrum absorption spectroscopy measurements by light/fluid evanescent interaction. Both ion-exchange technology and wet-etching tech-nologies were used to create the optical and fluidic planar functions. The device is assem-bled by direct molecular bonding with an optimized protocole which withstands surface energies > 2, 5 J·m2. Sensor optical and fluidic functions are interfaced with fiber optics and fluid capillaries in order for the chip to be used within a plug-and-play detection chain. Spectral measurements of a plutonium(VI) in nitric acid solution have allowed to verify the technological solution’s compatibility with harsh acid manipulation and irra-diation resistance. The system put together for the detection of plutonium(VI) displays a detection limit of 1.6×10−2 mol·L−1 for a probed volume below 1 nano-liter, inside a 21 micro-liter channel. A new sensor design is studied in the thesis work perspectives in order to optimize sensor detection limit and channel volume and reach industrial tools analytical performances with nano-liter sample volumes

The importance of insulin delivery and action is best characterized in Type 2 Diabetes, a disease that is becoming a pandemic both nationally and globally. Obesity is a principal risk factor for Type 2 Diabetes, and adipocyte function abnormalities due to adipose hypertrophy and hyperplasia, have been linked to obesity. Numerous reports suggest that the intracellular and systemic consequences of adipocyte function abnormalities include adipocyte insulin resistance, enhanced production of free fatty acids, and production of inflammatory mediators. A hallmark of adipocyte insulin sensitivity is the stimulation of glucose transporter isoform 4 (GLUT4) trafficking events to promote glucose uptake. In the Type 2 diabetic and insulin resistant states the mechanism behind insulin-stimulated GLUT4 trafficking is compromised. Therefore, understanding the role of factors involved in glucose-uptake in adipose tissue is of great importance. Studies from our laboratory suggest an important role for the unconventional myosin, Myo1c, in promoting insulin-mediated glucose uptake in cultured adipocytes. Our observations suggest that depletion of Myo1c in cultured adipocytes results in a significant reduction in the ability of adipocytes to take up glucose following insulin treatment, suggesting Myo1c is required for insulin-mediated glucose uptake. A plausible mechanism by which Myo1c promotes glucose uptake in adipocytes has been suggested by further work from our laboratory in which expression of fluorescently-tagged Myo1c in cultured adipocytes induces significant membrane ruffling at the cell periphery, insulin-independent GLUT4 translocation to the cell periphery, and accumulation of GLUT4 in membrane ruffling regions. Taken together Myo1c seems to facilitate glucose uptake through remodeling of cortical actin. In the first part of this thesis I, in collaboration with others, uncovered a possible mechanism through which Myo1c regulates adipocyte membrane ruffling. Here we identified a novel protein complex in cultured adipocytes, comprising Myo1c and the mTOR binding partner, Rictor. Interestingly our studies in cultured adipocytes suggest that the Rictor-Myo1c complex is biochemically distinct from the Rictor-mTOR complex of mTORC2. Functionally, only depletion of Rictor but not Myo1c results in decreased Akt phosphorylation at serine 473, but depletion of either Rictor or Myo1c results in compromised cortical actin dynamic events. Furthermore we observed that whereas the overexpression of Myo1c in cultured adipocytes causes remarkable membrane ruffling, Rictor depletion in cells overexpressing Myo1c significantly reduces these ruffling events. Taken together our findings suggest that Myo1c, in conjunction with Rictor, modulates cortical actin remodeling events in cultured adipocytes. These findings have implications for GLUT4 trafficking as GLUT4 has been previously observed to accumulate in Myo1c-induced membrane ruffles prior to fusion with the plasma membrane. During our studies of adipocyte function we noticed that current siRNA electroporation methods present numerous limitations. To silence genes more effectively we employed a lentivirus-mediated shRNA delivery system, and to standardize this technology in cultured adipocytes we targeted Myo1c and MAP4K4. Using this technology we were able to achieve clear advantages over siRNA oligonucleotide electroporation techniques in stability and permanence of gene silencing. Furthermore we showed that the use of lentiviral vectors in cultured adipocytes did not affect insulin signaling or insulin-mediated glucose uptake events. Despite our inability to use lentiviral vectors to achieve gene silencing in mice we were able to achieve adipose tissue-specific gene silencing effects in mice following manipulation of the lentiviral conditional silencing vector, and then crossing resulting founders with aP2-Cre mice. Interestingly however, only founders from the MAP4K4 conditional shRNA vector, but not founders from the Myo1c conditional shRNA vector, showed gene knockdown, possibly due to position-effect variegation. Taken together, findings from these studies are important because they present an alternative means of achieving gene silencing in cultured adipocytes, with numerous advantages not offered by siRNA oligonucleotide electroporation methods. Furthermore, the in vivo, adipose tissue-specific RNAi studies offer a quick, inexpensive, and less technically challenging means of achieving adipose tissue-specific gene ablations relative to traditional gene knockout approaches.

Connor O’Hara July 29, 2019 Inhibition of Cancer Stem Cells by Glycosaminoglycan Mimetics In the United States cancer is the second leading cause of death, with colorectal cancer (CRC) being the third deadliest cancer and expected to cause over 51,000 fatalities in 2019 alone.1 The current standard of care for CRC depends largely on the staging, location, and presence of metastasis.2 As the tumor grows and invades nearby lymph tissue and blood vessels, CRC has the opportunity to invade not only nearby tissue but also metastasize into the liver and lung (most commonly).3 The 5-year survival rate for metastasized CRC is <15%, and standard of care chemotherapy regimens utilizing combination treatments only marginally improve survival.3-5 Additionally, patients who have gone into remission from late-stage CRC have a high risk of recurrence despite advances in treatment.6-7 The Cancer Stem-like Cell (CSC) paradigm has grown over the last 20 years to become a unifying hypothesis to support the growth and relapse of tumors previously regressed from chemotherapy (Figure 1).8 The paradigm emphasizes the heterogeneity of a tumor and its microenvironment, proposing that a small subset of cells in the tumor are the source of tumorigenesis with features akin to normal stem cells.9 The CSCs normally in a quiescent state survive this chemotherapy and “seed” tumor redevelopment.10 First observed in acute myeloid lymphoma models, CSCs have since been identified in various other cancers (to include CRC) by their cell surface antigens and unique properties characterizing them from normal cancer cells.11-12 These include tumor initiation, limitless self-renewal capacity to generate clonal daughter cells, as well as phenotypically diverse, mature, and highly differentiated progeny.13-14 Previously our lab has identified a novel molecule called G2.2 (Figure 2) from a unique library of sulfated compounds showing selective and potent inhibition of colorectal CSCs in-vitro.15 G2.2 is a mimetic of glycosaminoglycans (GAGs) and belongs to a class of molecules called non-saccharide GAG mimetics (NSGMs). Using a novel dual-screening platform, comparisons were made on the potency of G2.2 in bulk monolayer cells, primary 3D tumor spheroids of the same cell line, and subsequent generations of tumor spheroids. This work has shown in-vitro the fold-enhancement of CSCs when culturing as 3D tumor spheroids. Spheroid culture serves as a more accurate model for the physiological conditions of a tumor, as well as the functional importance of upregulating CSCs. Evaluation of G2.2 and other NSGMs was performed in only a few cell lines, developing a need to better understand the ability of G2.2 to inhibit spheroids from a more diverse panel of cancer cells to better understand G2.2’s mechanism. The last few decades have seen the advancement in fundamental biological and biochemical knowledge of tumor cell biology and genetics.16 CRC, in particular, has served as a useful preclinical model in recapitulating patient tumor heterogeneity in-vitro.17 Recent work has characterized the molecular phenotypes of CRC cell lines in a multi-omics analysis, stratifying them into 4 clinically robust and relevant consensus molecular subtypes (CMS).18-19 Our work was directed to screen a panel of cells from each of the molecular subtypes and characterize the action of G2.2 and 2nd generation lipid-modified analogs, synthesized to improve the pharmacokinetic properties of the parent compound. Four NSGMs, namely G2.2, G2C, G5C, and G8C (Figure 2) were studied for their ability to inhibit the growth of primary spheroids across a phenotypically diverse panel. Compound HT-29 IC50 (μM) Panel Average IC50 (μM) G2.2 28 ± 1 185 ± 55 G2C 5 ± 2 16 ± 15 G5C 8 ± 2 63 ± 19 G8C 0.7 ± 0.2 6 ± 3 Primary spheroid inhibition assays were performed comparing the potency of new NSGMs to G2.2. Fifteen cell lines were evaluated in a panel of colorectal adenocarcinoma cell lines with several cell lines representing each CMS. Primary spheroid inhibition assays revealed 3 distinct response with regard to G2.2’s ability to inhibit spheroid growth. Cells from CMS 3 and 4, which display poor clinical prognosis, metabolic dysregulation, and enhanced activation of CSC pathways, showed the most sensitivity to G2.2 (mean IC50 = 89 ± 55 μM). Mesenchymal CMS 4 cell lines were over 3-fold more sensitive to treatment with G2.2 when compared to CMS 1 cell lines. Resistant cell lines were composed entirely of CMS 1 and 2 (mean IC50 = 267 ± 105 μM). In contrast, all lipid-modified analogs showed greater potency than the parent NSGM in almost every CRC cell line. Of the three analogs, G8C showed the greatest potency with a mean IC50 of less than 15 μM. Of the CRC spheroids studied, HT-29 (CMS 3) was most sensitive to G8C (IC50 = 0.73 μM). To evaluate the selectivity of NSGMs for CSC spheroid inhibition, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) cytotoxicity assays were performed on monolayer cell culture, and the fold-selectivity of NSGM for spheroids was analyzed. Data shows that NSGMs preferentially target CSC-rich spheroids compared with monolayer cellular growth, with G2.2 having over 7-fold selectivity for spheroid conditions. This fold selectivity was enhanced in CMS 3/4, supporting the idea that G2.2 targets a mesenchymal and stem-like phenotype. To further validate this selectivity, limiting dilution assays were performed across the panel to determine the tumor-initiating capacity of each cell line. Cell lines which showed a sensitive response to G2.2 were over 2-fold more likely to develop into spheroids, validating the previous hypothesis. Further characterization was performed analyzing the changes G2.2 induced on CSC markers, as well as the basal expression of a unique pair of cancer cells. Western blots showed a reduction in self-renewal marker across all CMS after treatment with G2.2, and that cell lines sensitive to G2.2-treatment overexpress mesenchymal and stem-like markers. G2.2-resistant cell lines show an epithelial phenotype, lacking this expression. The positive results observed in these studies enhance the understanding of G2.2 and analogs, and further evaluation with additional cell lines of various tissues would improve the knowledge thus far gained. However, all experiments described take valuable time to perform and analyze. Thus, there became a need to develop a high-throughput screening (HTS) platform for our assays that standardized analysis and enhanced productivity. Initial development of the method for this assay are underway, and recent evidence from these evaluations of breast cancer spheroids suggests that G2.2 and analogs may be tissue-specific compounds for the treatment of cancer. Future work entails refining the application of this method for evaluation of the NCI-60 (National Cancer Institute) tumor cell panel. Overall, these results make several suggestions concerning the NSGMs evaluated against the panel. First, G2.2 selectively targets CSCs with limited toxicity to monolayer cells of the same cell line. Further, G2.2 has the greatest potency with CMS 3/4, whose mesenchymal phenotypes are associated with poor clinical prognosis and enrichment of CSCs. Supporting evidence include that sensitive cell lines are highly tumorigenic and show enhanced expression of mesenchymal/CSC markers compared to resistant cell lines. Lipid-modification of G2.2 enhances in-vitro potency against spheroid growth, with nM potency reached in the most sensitive cell lines. Evidence in the development of a HTS platform also suggests these NSGMs show tissue specificity to cancers of the intestine. Further work characterizing the mechanism of NSGMs in a broader multi-tissue panel will enhance our understanding of the compounds as a potential therapy to dramatically improve patient survival through specific targeting of tumorigenesis. References 1. Colorectal Cancer Facts & Figures 2017-2019. American Cancer Society 2017. 2. Compton, C. C.; Byrd, D. R.; Garcia-Aguilar, J.; Kurtzman, S. H.; Olawaiye, A.; Washington, M. K. Colon and rectum. In AJCC Cancer Staging Atlas, 2nd ed.; Ed. Springer Science: New York, 2012; pp 185–201. 3. Van Cutsem, E.; Cervantes, A.; Adam, R.; Sobrero, A.; Van Krieken, J. H.; Aderka, D.; Aranda Aguilar, E.; Bardelli, A.; Benson, A.; Bodoky, G.; et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann. Oncol. 2016, 27, 1386–422. 4. Siegel, R. L.; Miller, K. D.; Fedewa, S. A.; Ahnen, D. J.; Meester, R. G. S.; Barzi, A.; Jemal, A. Colorectal cancer statistics, 2017. CA Cancer J. Clin. 2017, 67, 177–193. 5. Moriarity, A.; O'Sullivan, J.; Kennedy, J.; Mehigan, B.; McCormick, P. Current targeted therapies in the treatment of advanced colorectal cancer: a review. Ther. Adv. Med. Oncol. 2016, 8, 276–293. 6. Seidel, J.; Farber, E.; Baumbach, R.; Cordruwisch, W.; Bohmler, U.; Feyerabend, B.; Faiss, S. Complication and local recurrence rate after endoscopic resection of large high-risk colorectal adenomas of >/=3 cm in size. Int. J. Colorectal Dis. 2016, 31, 603–611. 7. Pugh, S. A.; Shinkins, B.; Fuller, A.; Mellor, J.; Mant, D.; Primrose, J. N. Site and stage of colorectal cancer influence the likelihood and distribution of disease recurrence and postrecurrence survival: data from the FACS randomized controlled trial. Ann. Surg. 2016, 263, 1143–1147. 8. Batlle, E.; Clevers, H. Cancer stem cells revisited. Nat. Med. 2017, 23, 1124–1134. 9. Hanahan, D.; Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 2011, 144, 646–674. 10. Tirino, V.; Desiderio, V.; Paino, F.; De Rosa, A.; Papaccio, F.; La Noce, M.; Laino, L.; De Francesco, F.; Papaccio, G. Cancer stem cells in solid tumors: an overview and new approaches for their isolation and characterization. FASEB J. 2013, 27, 13–24. 11. Bonnet, D.; Dick, J. E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. 1997, 3, 730–737. 12. Desai, A.; Yan, Y.; Gerson, S. L. Concise reviews: cancer stem cell targeted therapies: toward clinical success. Stem Cells Transl. Med. 2019, 8, 75–81. 13. Munro, M. J.; Wickremesekera, S. K.; Peng, L.; Tan, S. T.; Itinteang, T. Cancer stem cells in colorectal cancer: a review. J. Clin. Pathol. 2018, 71, 110–116. 14. Zhou, Y.; Xia, L.; Wang, H.; Oyang, L.; Su, M.; Liu, Q.; Lin, J.; Tan, S.; Tian, Y.; Liao, Q.; Cao, D. Cancer stem cells in progression of colorectal cancer. Oncotarget 2018, 9, 33403–33415. 15. Patel, N. J.; Karuturi, R.; Al-Horani, R. A.; Baranwal, S.; Patel, J.; Desai, U. R.; Patel, B. B. Synthetic, non-saccharide, glycosaminoglycan mimetics selectively target colon cancer stem cells. ACS Chem. Biol. 2014, 9, 1826–1833. 16. Punt, C. J.; Koopman, M.; Vermeulen, L. From tumour heterogeneity to advances in precision treatment of colorectal cancer. Nat. Rev. Clin. Oncol. 2017, 14, 235–246. 17. Mouradov, D.; Sloggett, C.; Jorissen, R. N.; Love, C. G.; Li, S.; Burgess, A. W.; Arango, D.; Strausberg, R. L.; Buchanan, D.; Wormald, S.; et al. Colorectal cancer cell lines are representative models of the main molecular subtypes of primary cancer. Cancer Res. 2014, 74, 3238–3247. 18. Guinney, J.; Dienstmann, R.; Wang, X.; de Reynies, A.; Schlicker, A.; Soneson, C.; Marisa, L.; Roepman, P.; Nyamundanda, G.; Angelino, P.; et al. The consensus molecular subtypes of colorectal cancer. Nat. Med. 2015, 21, 1350–1356. 19. Berg, K. C. G.; Eide, P. W.; Eilertsen, I. A.; Johannessen, B.; Bruun, J.; Danielsen, S. A.; Bjornslett, M.; Meza-Zepeda, L. A.; Eknaes, M.; Lind, G. E.; et al. Multi-omics of 34 colorectal cancer cell lines - a resource for biomedical studies. Mol. Cancer 2017, 16, 116–132.

El reactor anaerobio de membranas sumergidas (SAnMBR) está considerado como tecnología candidata para mejorar la sostenibilidad en el sector de la depuración de aguas residuales, ampliando la aplicabilidad de la biotecnología anaerobia al tratamiento de aguas residuales de baja carga (v.g. agua residual urbana) o a condiciones medioambientales extremas (v.g. bajas temperaturas de operación). Esta tecnología alternativa de tratamiento de aguas residuales es más sostenible que las tecnologías aerobias actuales ya que el agua residual se transforma en una fuente renovable de energía y nutrientes, proporcionando además un recurso de agua reutilizable. SAnMBR no sólo presenta las principales ventajas de los reactores de membranas (i.e. efluente de alta calidad, y pocas necesidades de espacio), sino que también presenta las principales ventajas de los procesos anaerobios. En este sentido, la tecnología SAnMBR presenta una baja producción de fangos debido a la baja tasa de crecimiento de los microorganismos implicados en la degradación de la materia orgánica, presenta una baja demanda energética debido a la ausencia de aireación, y permite la generación de metano, el cual representa una fuente de energía renovable que mejora el balance energético neto del sistema. Cabe destacar el potencial de recuperación de nutrientes del agua residual bien cuando el efluente es destinado a irrigación directamente, o bien cuando debe ser tratado previamente mediante tecnologías de recuperación de nutrientes. El objetivo principal de esta tesis doctoral es evaluar la viabilidad de la tecnología SAnMBR como núcleo en el tratamiento de aguas residuales urbanas a temperatura ambiente. Por lo tanto, esta tesis se centra en las siguientes tareas: (1) implementación, calibración y puesta en marcha del sistema de instrumentación, control y automatización requerido; (2) identificación de los parámetros de operación clave que afectan al proceso de filtración; (3) modelación y simulación del proceso de filtración; y (4) desarrollo de estrategias de control para la optimización del proceso de filtración minimizando los costes de operación. En este trabajo de investigación se propone un sistema de instrumentación, control y automatización para SAnMBR, el cual fue esencial para alcanzar un comportamiento adecuado y estable del sistema frente a posibles perturbaciones. El comportamiento de las membranas fue comparable a sistemas MBR aerobios a escala industrial. Tras más de dos años de operación ininterrumpida, no se detectaron problemas significativos asociados al ensuciamiento irreversible de las membranas, incluso operando a elevadas concentraciones de sólidos en el licor mezcla (valores de hasta 25 g·L-1 ). En este trabajo se presenta un modelo de filtración (basado en el modelo de resistencias en serie) que permitió simular de forma adecuada el proceso de filtración. Por otra parte, se propone un control supervisor basado en un sistema experto que consiguió reducir el consumo energético asociado a la limpieza física de las membranas, un bajo porcentaje de tiempo destinado a la limpieza física respecto al total de operación, y, en general, un menor coste operacional del proceso de filtración. Esta tesis doctoral está integrada en un proyecto nacional de investigación, subvencionado por el Ministerio de Ciencia e Innovación (MICINN), con título ¿Modelación de la aplicación de la tecnología de membranas para la valorización energética de la materia orgánica del agua residual y la minimización de los fangos producidos¿ (MICINN, proyecto CTM2008-06809- C02-01/02). Para obtener resultados representativos que puedan ser extrapolados a plantas reales, esta tesis doctoral se ha llevado a cabo utilizando un sistema SAnMBR que incorpora módulos comerciales de membrana de fibra hueca. Además, esta planta es alimentada con el efluente del pre-tratamiento de la EDAR del Barranco del Carraixet (Valencia, España).
Robles Martínez, Á. (2013). Modelling, simulation and control of the filtration process in a submerged anaerobic membrane bioreactor treating urban wastewater [Tesis doctoral]. Editorial Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/34102
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Chaque jour des milliers de camions transportant des centaines de milliers de tonnes de marchandises dangereuses par diverses modalités. Toutefois, le terme “dangereux” indique une adversité intrinsèque qui caractérise ces produits transportés, et qui peuvent se manifester lors d'un accident entraînant la fuite d'une substance dangereuse. Dans une telle situation, les conséquences peuvent nuire à l'environnement et létal pour l'humain.L'importance des marchandises dangereuses revient aux bénéfices économiques considérables générés. En fait, on ne peut nier la contribution du transport des produits dérivés de combustibles fossiles, ce qui représente plus de 60% des marchandises dangereuses transportées en Europe. Eni, la société italienne leader de pétrochimie, gère chaque jour une flotte d'environ 1.500 camions, qui effectuent de nombreuses expéditions. Pourtant la distribution de produits pétroliers est une activité à grande risques, et tout accident lors du transport peut entraîner de graves conséquences.Consciente des enjeux, la division Eni R&M - Logistique Secondaire, historiquement actif au siège de Gênes, collabore depuis 2002 avec le DIBRIS à l'Université de Gênes, et le CRC à Mines ParisTech, dans le but d'étudier les améliorations possibles en matière de sûreté dans le transport de marchandises dangereuses. Au fil des ans, cette collaboration a permis le développement d'un système d'information et décisionnel. Le composant principal de ce système est une plate-forme de surveillance de la flotte Eni appelé TIP (Transport Integrated Platform), pour livrer les produits vers les points de distributions. Ces véhicules sont équipés d'un dispositif capable de transmettre des flux de données en temps réel en utilisant un modem GPRS. Les données transmises peuvent être de nature différente et contenir des informations sur l'état du véhicule, le produit et les événements détectés durant l'expédition. Ces données sont destinées à être reçues par des serveurs centralisés puis traitées et stockées, afin de soutenir diverses applications du TIP.Dans ce contexte, les études menées tout au long de la thèse sont dirigés vers le développement d'une proposition visant à réduire davantage les risques liés au transport de marchandises dangereuses. En d'autres termes, un modèle basé sur le compromis entre les facteurs économiques et sûretés pour le choix de l'itinéraire. L'objectif est motivé par la nécessité de soutenir les règlements et les normes de sécurité existantes, car ils ne garantissent pas totalement contre les accidents entrainant des marchandises dangereuses.L'objectif est effectué en prenant en compte le système existant comme base pour l'élaboration d'un système de transport intelligent (STI) regroupant plusieurs plates-formes logicielles. Ces plates-formes doivent permettre aux planificateurs et aux décideurs de suivre en temps réel leur flotte, à évaluer les risques et tous les itinéraires possibles, de simuler et de créer différents scénarios, et d'aider à trouver des solutions à des problèmes particuliers.Tout au long de cette thèse, je souligne la motivation pour ce travail de recherche, les problématiques, et les défis de transport de marchandises dangereuses. Je présente le TIP comme le noyau de l'architecture proposée du STI. Pour les besoins de la simulation, les véhicules virtuels sont injectés dans le système. La gestion de la collecte des données a été l'objet d'une amélioration technique pour plus de fiabilité, d'efficacité et d'évolutivité dans le cadre de la surveillance en temps réel. Enfin, je présente une explication systématique de la méthode d'optimisation des itinéraires considérant les critères économiques et de risques. Le risque est évalué en fonction de divers facteurs notamment la fréquence d'accidents entrainant des marchandises dangereuses, et ses conséquences. La quantification de l'incertitude dans l'évaluation des risques est modélisée en utilisant la théorie des ensembles flous
Everyday thousands of trucks transporting hundreds of thousands of tons of dangerous goods by various modalities and both within and across nations. However, the term “dangerous” indicates an intrinsic adversity that characterize these products, which can manifest in an accident leading to release of a hazardous substance (e.g. radioactive, flammable, explosive etc.). In this situation, the consequences can be lethal to human beings, other living organisms and damage the environment and public/private properties.The importance of dangerous goods boils down to the significant economic benefits that generates. In fact, one cannot deny the contribution of the transport of all fossil fuel derived product, which represents more than 60% of dangerous goods transported in Europe. Eni, the Italian leading petrochemical company, every day operates a fleet of about 1,500 trucks, which performs numerous trips from loading terminals to filling stations. Distribution of petroleum products is a risky activity, and an accident during the transportation may lead to serious consequences.Aware of what is at stake, the division Eni R&M - Logistics Secondary, historically active in Genoa headquarters, is collaborating since 2002 with the DIBRIS department at University of Genoa, and the CRC at Mines ParisTech, with the purpose of studying possible improvements regarding safety in transport of dangerous goods, particularly petroleum products. Over years, this collaboration has led to the development of different technologies and mainly to an information and decision support system. The major component of this system is a platform for monitoring Eni fleet, at the national level, to deliver the products to the distribution points, called the Transport Integrated Platform (TIP). These vehicles are equipped with a device capable of transmitting data stream in real-time using a GPRS modem. The data transmitted can be of different nature and contain information about the state of the vehicle and occurred events during the trip. These data are intended to be received by centralized servers then get processed and stored, in order to support various applications within the TIP.With this in mind, the studies undertaken throughout the thesis are directed towards the development of a proposal to further minimize the risk related to the transportation of dangerous goods. In other words, a trade-off based model for route selection taking into consideration economic and safety factors. The objective is prompted by the need to support existent regulations and safety standards, which does not assure a full warranty against accidents involving dangerous goods.The goal is carried out by considering the existent system as basis for developing an Intelligent Transportation System (ITS) aggregating multiple software platforms. These platforms should allow planners and decision makers to monitor in real-time their fleet, to assess risk and evaluate all possible routes, to simulate and create different scenarios, and to assist at finding solutions to particular problems.Throughout this dissertation, I highlight the motivation for such research work, the related problem statements, and the challenges in dangerous goods transport. I introduce the TIP as the core for the proposed ITS architecture. For simulation purposes, virtual vehicles are injected into the system. The management of the data collection was the subject of technical improvement for more reliability, efficiency and scalability in real-time monitoring of dangerous goods shipment. Finally, I present a systematic explanation of the methodology for route optimization considering both economic and risk criteria. The risk is assessed based on various factors mainly the frequency of accident leading to hazardous substance release and its consequences. Uncertainty quantification in risk assessment is modelled using fuzzy sets theory

Indiana University-Purdue University Indianapolis (IUPUI)
Objectives: A new technology has been introduced into the field of dental resin composites that professes to enhance light-curing efficiency. Rapid amplified photopolymerization (RAP) initiator technology has not yet been fully compared with resin composites with conventional initiators such as camphorquinone (CQ). The purpose of this study was to compare and contrast the effects of this novel technology (RAP) on properties of two light-cured resin composites. Flowable (EFQ) and microfilled (ESQ) experimental composites were fabricated and supplied from Tokuyama Dental with (w/RAP) and without RAP (w/o RAP). The flexural strength (MPa) and flexural modulus (MPa) were obtained using a three-point bending apparatus (Sintech Renew 1123, Instron Engineering Corp., Canton, MA). Polymerization stress curves were created using a tensometer (American Dental Association Health Foundation, NIST, Gaithersburg, MD) which were then used to calculate the maximum stress rate. Finally, the degree of conversion was measured using infrared spectroscopy (Jassco FT-IR spectrometer, Model: 4100, Jasco Corporation, Tokyo, Japan). When evaluating the flexural strength, the peak stress for EFQ w/RAP was significantly higher than EFQ w/o RAP (p = 0.0001). This was statistically not significant for the ESQ group, even though ESQ w/RAP did have a higher peak stress then ESQ w/o RAP (p = 0.28). The interaction between resin type and RAP was not significant when evaluating the flexural modulus (p = 0.21). Formulations with RAP had a significantly higher flexural modulus then w/o RAP (p = 0.0001). Experimental resins with RAP had significantly higher maximum stress rates than those w/o RAP when evaluating polymerization stress (p = 0.0001). Finally, groups w/ RAP appeared to have a higher degree of conversion than groups without (p = 0.0057). This study showed that the experimental composites with RAP had greater mechanical properties than those without. Unfortunately, the increase in polymerization stress causes concern clinically due to the chance of leakage at the restoration/tooth interface. One of the main potential disadvantages of this new RAP technology is an increase in the polymerization stress. Deciding if this amount of polymerization stress is clinically acceptable is yet to be accomplished.

碩士
吳鳳科技大學
消防研究所
106
At manufacturing, processing, storage and other places, the “Class 4 flammable and combustible liquids” of “Public Hazardous Substances”, the foam fire extinguishing equipment usually is the major fire protection equipment. Foam fire extinguishing equipment is composed of foam concentrate storage tank, foam proportioner, foam nozzle, foam discharge outlet, swivel joint, Y-type strainer, foam hydrant, foam monitor and etc. Currently, except foam nozzle, all other components are not including in the “Fire Safety Technical Review Committee of the Ministry of the Interior” as "safety equipment items that must be approved before using." The author has personally engaged in firefighting design, installation, supervision, inspection and repair of such sites for more than 30 years and often encounter and often encountered some factors such as improper design, improper equipment selection, improper equipment manufacturing, etc., which caused the foam fire extinguishing system to fail to exert its due function. Therefore, the author wants to through this research and foam-water discharge test to analyze and clarify the “improper design, improper equipment selection” and other incorrect factors whether cause “the foam concentrate cannot be effectively released” and “cannot extinguish the fire effectively”, and “pollute the environmental” or not. The author obtained the following conclusions from the actual test results and calculation verification during this study: When water flow through the foam proportioner is lower than the specified minimum flow rate of the proportioner, the "REDUCTION OF THE FLOW RATE" causes "BACK PRESSURE GENERATED IN THE PIPE" and "LOW PRESSURE AREA OF PROPORTIONER CANNOT BE FORMED"! This in turn leads to "FOAM CONCENTRATE CANNOT BE SMOOTHLY AND EFFICIENTLY ENTERED INTO THE FOAM PROPORTIONER"! Therefore, “THE CONCENTRATE CANNOT REACH THE DESIGN RATIO," and "FAILED TO PRODUCE FOAM BUBBLE OR LACK OF EXPANSION RATIO"! Currently, the "National Federation of Fire Equipment Traders and Merchants Association of the Republic of China" and the "Taiwan Fire Equipment Industry Association" drafted the "Points for the Implementation of Autonomous Cognizance of Fire Safety Equipment” together. The author hope this time research can provide the “Fire Safety Equipment Autonomy Accreditation Committee” to refer for and can provide the fire professional technicians to refer during they design new foam fire extinguishing systems and/or improving existing foam fire extinguishing equipment. The author also expects that this time research have assistance for "Fire Control Department" during the revision of "Standards of Inspection and Reporting" and " Standards of Fire Safety Equipment Approval ". Keywords: Foam concentrate storage tank, foam proportioner, foam proportion.

碩士
嘉南藥理科技大學
產業安全衛生與防災研究所
100
The aim of this study was to design a test to investigate the cognition of classification and labeling of Hazardous Substances on Globally Harmonized System. There were 171 college students participating in this study. Two parts of this test were carried out, including the classification of hazardous substances matching hazardous symbol test, and hazardous symbol matching the classification of hazardous substances test. The results showed that the highest matching rates were the symbol of “Environment” and the symbol of “Skull and crossbones”. The secondly high matching rates were the symbol of “Gas cylinder”, the symbol of “Corrosion”, and the symbol of “Skull and crossbones”. The thirdly high matching rates were the symbol of “Exploding bomb” and the symbol of “Flame”. The lowest matching rates were the symbol of “Flame over circle” and the symbol of “Exclamation mark”. The results of matching between 27 hazardous classification of chemicals showed that the matching rate of ten hazard classifications were over 67%. However, the matching rate of six hazardous classifications were lower than 20%. They were “Self-heating of substance”, “Oxidizing liquid”, “Oxidizing gases”, “Organic peroxides”, “Skin sensitization”, and “Substances, which in contact with water, emit flammable gases”. The most difficult understanding to matching between hazardous classification and hazardous symbol was the chemical of “Substances, which in contact with water, emit flammable gases”.

Lead concentrations in drinking water were found to exceed the provincial standard of 10 µg/L in Brandon, Portage la Prairie and Winnipeg, in some locations. Lead dioxide was identified in the scale coating the interior of lead pipes in the Brandon water distribution system. However, during periods of stagnation, free chlorine is used up by the elevated concentrations of natural organic matter (NOM) in the treated water, and lead dioxide is reduced back to more soluble divalent lead, resulting in release of dissolved lead. The removal of NOM and the targeted removal of aquatic humic substances (AHS), thought to be the most reactive fraction of NOM, were investigated as a means of decreasing the reduction of lead dioxide. Contrary to expected results, targeted removal of AHS was not found to have a significant impact on reduction of lead dioxide, while removal of 50% of the NOM non-preferentially was found to significantly decrease the reduction of lead dioxide. This indicates that AHS are not the most reductant fraction of natural organic matter in this particular water.

Neurological disorders are a major public health concern due to prevalence, severity of symptoms, and impact on caregivers and economic losses. While genetic susceptibility likely has a role in most cases, exposure to toxicants can lead to neurotoxicity, including potentially developmental origins of adult disease or increased risk of disease onset. These exposures are not necessarily large, acute exposures, but could accumulate, with a chronic low-dose exposure, causing toxicity. This research focuses on the potential neurotoxicity of two classes of dietary toxins/toxicants, heterocyclic aromatic amines (HAAs) and per- and polyfluoroalkyl substances (PFAS). HAAs, such as PhIP, harmane, and harmine, are formed in charred or overcooked meat, coffee, tobacco, and other foods. PFAS are largely used in making household materials, but are found in small amounts in eggs and dairy products and largely in contaminated water. While these two classes are diverse in terms of structure, common neurotoxic targets and mechanisms often exist. Therefore, we tested the effects of these chemicals on cell viability and neurotoxicity. In the first aim, we aimed to elucidate the mechanism of toxicity of harmane and harmine, focusing on their ability to cause mitochondrial dysfunction. The second aim was to determine the effects of either harmane or PhIP on the nigrostriatal motor systems and motor function of rats and mice, respectively. The third aim determined the effects of PFAS on neurodevelopment of Northern leopard frogs, focusing on changes in neurotransmitter levels and accumulation in the brain. Harmane did not cause motor dysfunction, but potentially affected the nigro-striatal motor system in an age- or sex-dependent manner. PhIP had differential effects on dopamine levels over time and caused motor dysfunction after subchronic exposure in mice. Perfluorooctane sulfonate (PFOS) accumulated in the brains of frogs and PFAS caused changes in neurotransmitter levels that were dose- and time-dependent. Overall, this research shows that toxins/toxicants humans are exposed to over their whole lives through their diet and contaminated water can cause neurotoxicity, potentially leading to or increasing risk of disease states.

At he beginning of my thesis some basic notions are explained and there is a brief survey and conditions of the creation of legislation regulating the discussed problems, i.e. emergency laws, laws regarding dangerous substances handling and Nuclear Act above all. In the second part I analyze the readiness of state and community bodies for non-military critical situations (emergency legislation, documents of emergency planning) and for the solution of extraordinary events, I emphasize the task and activities of the integrated emergency system. In the following text I focus in detail on the legislation related to the way of securing and handling dangerous substances and radioactive substances. These are the following acts above all: Act on the Prevention of Serious Accidents (duties of operators handling dangerous substances, participation of public and its informing, state administration), Act on Chemical Substances and Chemical Agents (classification, testing and registration, marking and packaging of chemical substances and agents, transport of dangerous substances), Act on Waste and problems of nuclear energy and ionizing radiation are regulated by the Nuclear Act (nuclear safety and readiness for accidents, measures in the zone of emergency planning). This legislation is completed and detailed by some orders and regulations. The practical part is focused mainly on realizing the level of public knowledge and public awareness, mostly in the surroundings of institutions handling dangerous substances, about the risks connected with the operation of these institutions and about the suitable behaviour of inhabitants in case of an emergency connected with dangerous substances leakage. In the introduction of the practical part I state the characteristics of the survey as a whole, I define the basic file of respondents (from the point of view of identification marks), I describe methods used. In the next part I briefly state the examined regions from the point of view of the occurance of emergencies of dangerous substances leakage. I used the form of a questionnaire for handling this. The questionnaire was focused on questions about real knowledge (toxic effects of some substances, marking dangerous substances, emergency numbers knowledge, axioms of the behaviour of public in case of en emergency of dangerous substances leakage, nuclear problems). In an enclosure to the questionnaire I ask about the interest of the respondents in these problems and their preferences as for a suitable way to be informed about the risks connected with the operation of these institutions. The results of the survey are detailed in the chapter with this title. At the end of my thesis I state some recommended forms how to improve the know-how of public in emergency of dangerous substances leakage. The end of my thesis and the discussion focus on results summary and comparison of the results of my thesis with the results of other authors.

Nowadays more and more new chemicals are used for numerous technologies and ap-plications by diverse chemical, plastic processing and other companies. Are all such companies fit to manage and solve chemical breakdowns, extraordinary events and critical or even emergency situations? Surely a very interesting question. Therefore I have decided for my study to analyse a crisis management system of a plastic processing company located in the City of Liban, region Hradec Kralove. Current status of coordination of the integrated rescue system (hereinafter referred to as the "IZS"). Classification of hazardous chemical substances. Simulating of extraordinary events using the software tool TerEx with respect to diverse chemicals operated by and within the Company. Evaluation of selected chemical substances according to hazards induced. Risk analysis, Analysis of occurrance of extraordinary events like e. g. windstorm, fire or escape of dangerous chemical substance, disconnecting of supply medium (heat, energy, power, water) and their treatment. Methods of actions at threat of bomb attack. Determination whether the IZS coordination including of the documentation elaborated are satisfactory with respect to the plastic processing company as well as with respect to successful mastering of extraordinary and emergency situations. Crisis management of business economics and economic distress.