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abstract: The demand for portland cement concrete is expected to increase over time. There is a need to develop a more sustainable cementitious systems in order to reduce the negative environmental impacts associated with ordinary portland cement (OPC) production. An attempt is made to investigate sustainable binder solutions through the use of alternative cementitious materials at high levels of volume replacement. Limestone, an abundant material is used as a filler in low water-to-powder concretes where a substantial fraction of the portland cement remains unhydrated. At high volume OPC replacement, 20% and 35%, the combination of limestone and an alumina source has been shown to improve mechanical and durability performance. At 20% OPC replacement levels the migration coefficient which is an indication of chloride penetration in concrete is lower than the OPC control mixture at 28 and 56 days of hydration. The use of limestone with a similar particle size distribution to that of the OPC is used in each of these blended systems. A 20% binary limestone blend provide similar strength to an OPC mortar at all ages and comparable transport properties to that of the OPC concrete. Fly ash and metakaolin are the two alumina sources for the ternary blended mixes with concrete. The metakaolin shows the highest increase in the amount of hydration products formed out of all the mixes, including calcium-silicate-hydrate and carboaluminate phases in combination with limestone powder. At both levels of replacement the metakaolin blends show a substantially lower migration coefficient which is contributed to the smaller pore sizes found in the metakaolin blends. The fracture response of these systems show that at all replacement levels the ductility of the systems increase indicated by the large critical crack tip opening displacement. The fracture toughness is the highest for the blend containing metakaolin indicative of the smaller pore sizes allowing more dissipation of energy. An attempt is made to relate all mechanical and durability parameters to the reaction products and pore-structure developing at later ages. / Dissertation/Thesis / M.S. Civil and Environmental Engineering 2014

Thesis advisor: Rudolph Hon / Thesis advisor: Yvette Kuiper / Chloride-based deicers (NaCl, CaCl₂, MgCl₂), also referred to as road salt, are the most common substances used in maintaining safe roadway surfaces during the winter months. Upon application, road salt reacts with the accumulated snow or ice to form brine equilibrium solutions along the liquidus line in the salt-water system. Dissolved salts dissociate, leading to increased concentrations of the respective ions in nearby soils, surface water, and groundwater. Of the ions present in road salt, chloride has the advantage of tracking all chloride deicers at the same time and since chloride ions are conservative tracers in soils it stays unaffected by ionic exchange interferences. This study explores the mechanisms of chloride return flows by investigating chloride dissolved loads, chloride concentrations in stream waters, seasonal patterns, and changes over the course of four years in two separate watersheds in Massachusetts with differing degrees of urbanization. The chloride tracking technique used in this study is based on calibrated chloride concentrations obtained from specific conductance signals recorded every 15 minutes by automatic recording systems at two locations, one in rural central Massachusetts and the other in urban eastern Massachusetts. These systems are maintained by the USGS, which also provide the simultaneously recorded stream flow datasets. The dissolved chloride load carried by each river is calculated for each single 15-minute interval by multiplying water volume with the corresponding chloride concentration, resulting in a total of over 34,000 data points per annum per site. Hydrograph separation techniques were used to separate dissolved load transported by each river into two separate flow components, event flow resulting from precipitation events, and baseflow resulting from groundwater discharge. Well defined hydrograph baseflow supported periods yield consistent chloride concentrations independent of the season at either urban or rural study sites. Comparison of direct runoff dissolved chloride loads with the total annual dissolved loads suggests that only a small fraction of the deicers actually removed during the overland runoff events and that a minimum of 60% of the total load discharged each year in both urban and rural systems is transported by groundwater. From groundwater recharge by brines rural watersheds are currently retaining as much as 95% of the total chloride applied to roadways each year while urban and suburban watersheds may only retain 75% of the total chloride applied to roadways each year. The increased retention of chloride in rural areas is likely due to the decreased amount of chloride transported during winter seasons as event flow compared to urban watersheds. / Thesis (MS) — Boston College, 2009. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Geology and Geophysics.

<p>The cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP activated chloride channel in the apical membrane of epithelial cells, is defective in patients with cystic fibrosis (CF). Research efforts are focused on chloride channel function in order to find a cure for the disease.</p><p>Genistein increased chloride transport in normal and delF508-CFTR cultured airway epithelial cells without cAMP stimulation. Prior pretreatment with phenylbutyrate did not affect the rate of the genistein-stimulated chloride efflux in these cells.</p><p>S-nitrosoglutathione is an endogenous bronchodilator, present in decreased amounts in the lungs of CF patients. We studied the effect of GSNO on chloride (Cl-) transport in primary nasal epithelial cells from CF patients homozygous for the delF508-CFTR mutation, as well as in two CF cell lines, using a fluorescent Cl- indicator and X-ray microanalysis. GSNO increased chloride efflux in the CF cell lines and in primary nasal epithelial cells from CF patients. This effect was partly mediated by CFTR. If the cells were exposed to GSNO in the presence of L-cysteine, Cl- transport was enhanced after 5 min, but not after 4 h. GSNO may be a candidate for pharmacological treatment of CF patients. </p><p>Chloride transport properties of cultured NCL-SG3 sweat gland cells were investigated. The CFTR protein was neither functional nor expressed in these cells. Ca2+-activated chloride conductance was confirmed and the putative Ca2+-activated chloride channel (CaCC) was further characterized in term of its pharmacological sensitivity.</p><p>Corticosteroids, the primary treatment for asthma, cause necrosis/apoptosis of airway epithelial cells. It was investigated whether a newer generation of drugs used in asthma, leukotriene receptor antagonists, had similar effects. Both montelukast and dexamethasone, but not beclomethasone or budesonide induced apoptosis/necrosis in superficial airway epithelial cells. Montelukast and corticosteroids also caused decreased expression of intercellular adhesion molecule -1 (ICAM-1) in epithelial but not endothelial cells.</p>

The cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP activated chloride channel in the apical membrane of epithelial cells, is defective in patients with cystic fibrosis (CF). Research efforts are focused on chloride channel function in order to find a cure for the disease. Genistein increased chloride transport in normal and delF508-CFTR cultured airway epithelial cells without cAMP stimulation. Prior pretreatment with phenylbutyrate did not affect the rate of the genistein-stimulated chloride efflux in these cells. S-nitrosoglutathione is an endogenous bronchodilator, present in decreased amounts in the lungs of CF patients. We studied the effect of GSNO on chloride (Cl-) transport in primary nasal epithelial cells from CF patients homozygous for the delF508-CFTR mutation, as well as in two CF cell lines, using a fluorescent Cl- indicator and X-ray microanalysis. GSNO increased chloride efflux in the CF cell lines and in primary nasal epithelial cells from CF patients. This effect was partly mediated by CFTR. If the cells were exposed to GSNO in the presence of L-cysteine, Cl- transport was enhanced after 5 min, but not after 4 h. GSNO may be a candidate for pharmacological treatment of CF patients. Chloride transport properties of cultured NCL-SG3 sweat gland cells were investigated. The CFTR protein was neither functional nor expressed in these cells. Ca2+-activated chloride conductance was confirmed and the putative Ca2+-activated chloride channel (CaCC) was further characterized in term of its pharmacological sensitivity. Corticosteroids, the primary treatment for asthma, cause necrosis/apoptosis of airway epithelial cells. It was investigated whether a newer generation of drugs used in asthma, leukotriene receptor antagonists, had similar effects. Both montelukast and dexamethasone, but not beclomethasone or budesonide induced apoptosis/necrosis in superficial airway epithelial cells. Montelukast and corticosteroids also caused decreased expression of intercellular adhesion molecule -1 (ICAM-1) in epithelial but not endothelial cells.

Cystic fibrosis (CF) is an inborn, hereditary disease, due to mutations in the gene for a cAMP-activated chloride (Cl-) channel, the cystic fibrosis transmembrane conductance regulator (CFTR). As a result of impaired ion and water transport,the airway mucus is abnormally viscous, which leads to bacterial colonization.Recurrent infections and inflammation result in obstructive pulmonary disease.Similar changes in the pancreas lead to pancreatic insufficiency.Several compounds have been tested to improve transepithelial ion transport in CF patients, either via activation of the mutant CFTR, or via stimulation of alternative chloride channels. The main purpose of this thesis was to find substances that might correct the defective ion transport in epithelial cells in CFand could be useful for the pharmacological treatment of CF patients. Long-term treatment with the macrolide antibiotic azithromycin (AZM)improved clinical parameters and lung function in CF patients and increased Cl- transport in CF bronchial epithelial cells (CFBE) (Paper I); although mRNA expression of the CFTR gene remained unchanged.In contrast, pre-exposure to the mucolytic antioxidant N-acetylcysteine (NAC) increased CFTR protein expression and was associated with increased Cl- efflux from CFBE cells (Paper II). Clinical trials of this substance might be warranted. Duramycin has been the subject of clinical trials that finished in June2009. Up till now, no results from this study are available. The effect of this substance on Cl- efflux from three CF and three non-CF cell lines (Paper III) was disappointing. An effect was found only in CFBE cells, the effect was minimal, occurred in a narrow concentration range, and was not associated with an increase in the intracellular calcium concentration [Ca2+]i. The fact that NO-donors stimulated Cl- efflux from CFBE cells (but did notchange [Ca2+]i) after several hours of preincubation suggests that these substances may be a potentially interesting group of compounds for the treatment of CF (Paper IV). A model for the effect of NO-donors on Cl- efflux is presented. / Cystisk fibros (CF) är en medfödd, ärftlig, sjukdom, som förorsakas av en mutation i en gen som innehåller koden för en kloridkanal som aktiveras av cykliskt AMP (cystic fibrosis transmembrane conductance regulator, CFTR). Som en följd av otillräcklig transport av joner och vatten är slemmet i luftvägarna onormalt segt, vilket leder till att det koloniseras av bakterier. Upprepade infektioneroch inflammation av luftvägarna leder slutligen till obstruktiv lungsjukdom.Liknande förändringar i bukspottkörteln leder till att också detta organ inte fungerar. Flera kemiska ämnen har testats för sin förmåga att förbättra jontransporten över epitelet hos CF-patienter. Detta skulle kunna göras antingen genom aktivering av det muterade CFTR-proteinet, eller genom stimulering av alternativa kloridkanaler. Huvudsyftet med den forskning som beskrivs i denna avhandling var att hitta kemiska substanser som skulle kunna korrigera den defekta jontransporten i epitelceller hos CF-patienter, och därför vara nyttiga för behandlingen av patienterna. Behandling under längre tid med azithromycin (AZM), ett makrolidantibiotikum,förbättrade CF-patienternas kliniska status och lungfunktion,samt ökade kloridutflödet från CF bronkialepitelceller (CFBE-celler) (Arbete I).Däremot ändrades inte uttrycket av mRNA för CFTR-genen. I kontrast till detta ökade uttrycket av CFTR-proteinet om CFBE-cellerna utsattes för den slemlösande anti-oxidanten N-acetylcystein (NAC), vilket ledde till ökat kloridutflöde från denna cellinje (Arbete II). Det vore rimligt att utföra kliniska prövningar av detta ämne. Duramycin har testats i kliniska prov som slutade i juni 2009, men några resultatfrån dessa prov har inte offentliggjorts än. Effekten av detta ämne på kloridutflödet från tre CF-cellinjer och tre icke-CF cellinjer (Arbete III) var en besvikelse. Duramycin hade endast effekt på CFBE-celler, effekten var mycket liten, förekom endast i ett litet koncentrationsområde av duramycin, och var inte kopplad till en ökning av den intracellulära kalciumkoncentrationen [Ca2+]i. Att ämnen som avger kväveoxid (NO) stimulerade kloridutflödet från CFceller (men inte påverkade [Ca2+]i) efter några timmar, visar att denna grupp av ämnen kan vara potentiellt intressant för behandlingen av CF (arbete IV). En modell för effekten av NO på kloridtransporten i CF-celler presenteras.

Made available in DSpace on 2015-05-14T12:09:28Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2555415 bytes, checksum: 47844393899714edc61c7ace2fa21fd0 (MD5) Previous issue date: 2008-03-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Taking into account the research carried out in João Pessoa City, Paraíba State, Brazil, a significant number of concrete structures in urban environments and subjected to marine influence are covered by mortar. This way, it was studied the relationship between chloride transport in mortar covering and its influence on protection of covered structures. Prismatic concrete specimens were cast with 8x8x8cm and water to cement ratio of 0,55. A thin spatterdash layer was applied in these specimens and, after the curing period, a mortar covering layer done using four different mixtures and two thicknesses. Reference concrete specimens were also cast. After 28 days f curing in laboratory environment, the specimens were painted with epoxy resin in five of their six faces, with the purpose to simulate unidirectional chloride flux. Afterwards, the specimens were put under natural diffusion and wetting and drying cycles in sodium chloride solutions (1M) for 49 days. At the end of this period, chloride profiles were obtained with powered samples extracted each five millimetres from surface to bulk specimen. Results show that there is a chloride accumulation in the interface between mortar and concrete, followed by a chloride content decrease in concrete. This effect is called resistance effect . The mixture and the thickness of covering mortars significantly influence chloride transport in concrete. In a general way, covering mortars can play a complementary protection role in concrete structures. However, as these results were taken under accelerated conditions, they may be taken with caution. / De acordo com pesquisa de campo realizada na cidade de João Pessoa - Paraíba - Brasil, grande parte das estruturas de concreto armado inseridas em ambiente urbano e sujeitas a influência marinha possuem revestimento externo, desta forma, optou-se por estudar a relação entre o transporte de cloretos em argamassas de revestimento e a sua influência na proteção da estrutura revestida. Para tanto foram moldados corpos-de-prova (CP) prismáticos em concreto nas dimensões de 8x8x8cm e relação água/cimento 0,55. Nestes CP, aplicou-se uma fina camada de chapisco e, vencido o seu período de cura, revestiu-se com quatro diferentes dosagens de argamassa, sendo que para cada dosagem foram utilizadas duas espessuras de revestimento. Além destes CP, também foram moldados CP de referência, ou seja, só em concreto. Passados 28 dias de cura ao ar em ambiente de laboratório, os CP tiveram cinco de suas seis faces isoladas com resina epóxi para que, quando submetidos aos ensaios acelerados, simulasse um fluxo unidirecional dos cloretos. Em seguida, os CP foram submetidos aos ensaios acelerados de difusão natural e ciclos semanais de imersão/secagem, ambos em solução de cloreto de sódio 1,0M e durante um período de 49 dias. Ao final dos ensaios, foram obtidos perfis de cloretos, com amostras extraídas a cada cinco milímetros, na direção superfície-interior. De acordo com os resultados obtidos, observa-se que existe um acúmulo de cloretos na interface argamassa-concreto seguida de uma redução no teor de cloretos no concreto, o chamado efeito resistência. Além disso, a dosagem e a espessura utilizadas nestas argamassas influenciam de forma significativa o transporte de Cl- no concreto. De uma maneira geral, os resultados indicam que a argamassa de revestimento externo pode exercer um papel de proteção complementar sobre as estruturas de concreto. Contudo, estes resultados devem ser tomados com cautela uma vez que estão relacionados a um ambiente particular promovido pelos ensaios acelerados.

<p>S-nitrosogluthatione is an endogenous substance, present at decreased levels in the lungs of CF patients and was recently found to induce mature CFTR in airway epithelial CF cell lines. We show that S-nitrosoglutathione in physiological concentrations increases the presence of ΔF508 CFTR in the cell membrane and induces cAMP dependent chloride transport in cystic fibrosis airway epithelial cells. The properties of S-nitrosoglutathione include other potential benefits for the CF patient and make this agent an interesting candidate for pharmacological treatment of CF that needs to be further evaluated.</p><p>Genistein was found to increase the chloride efflux in both normal and ΔF508 cells without stimulation of cAMP elevating agents and without prior treatment with phenylbutyrate. Genistein, in concentrations close to those that can be detected in plasma after a high soy diet, could induce chloride efflux in cells with the ΔF508 CFTR mutation and its possible use in the treatment of CF should therefore be further investigated.</p><p>Studies on nasal epithelial cells from CF patients showed cAMP dependent chloride efflux in some of the patients with severe genotypes. This may complicate <i>in vitro</i> evaluation of clinical treatment of these patients. The presence of cAMP dependent chloride transport did not necessarily lead to a milder phenotype. Other factors than CFTR may influence the clinical development of the disease.</p><p>Cystic fibrosis (CF) is the most common monogenetic disease among Caucasians. A defective cAMP regulated chloride channel (cystic fibrosis transmembrane conductance regulator, CFTR) in epithelial cells leads to viscous mucus, bacterial infections, inflammation and tissue damage in the lungs that cause death in 95% of the cystic fibrosis patients. There is no cure for the disease although existing treatment has dramatically prolonged the life expectancy. The aim of this thesis was to study pharmacological agents for their ability to restore the cellular deficiency in CF airway epithelial cells. X-ray microanalysis, MQAE fluorescence and immunocytochemistry were used to evaluate the effects.</p>

<p>Cystic fibrosis (CF) is the most common lethal genetic disease in the white population. It is due to mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR), a protein that functions mainly as a cAMP-activated chloride channel. The disease impairs ion and water transport in epithelia-lined organs such as airways, digestive tract, reproductive epithelium and sweat glands. At present the only therapy is symptomatic and development of curative treatment depends on uncovering the links between the defective CFTR and the disease, as well as on improving end-point measurements. </p><p>A method has been established for studying ion transport in an easily accessible cell type (nasal epithelial cells) from normal and cystic fibrosis patients by X-ray microanalysis. This method represents a rather simple and direct way of measuring simultaneously several chemical elements of biological interest.</p><p>Studies of chloride transport by means of a fluorescent indicator (MQAE) in nasal epithelial cells from CF patients showed that the phenotype cannot exclusively be explained by the CFTR activity in patients with severe genotype. </p><p>A common Portuguese CFTR mutation (A561E) causes protein mislocalization in the endoplasmic reticulum similar to the most common CF mutation (ΔF508) and thus it should be possible to treat it with the same pharmacological strategies.</p><p>Chronic treatment of CF airway epithelial cells with nanomolar concentrations of colchicine increased the chloride efflux via chloride channels other than CFTR, strengthening the notion that colchicine could be beneficial to CF patients.</p><p>Successful <i>in vitro </i>transfection of CF airway epithelial cells with cationic vectors was possible with short incubation times. Heparin added at the end of the transfection incubation time could help to maintain the viability of the cells, without interfering with the transfection efficiency. It seems possible that heparin could be an adjuvant for non-viral mediated gene therapy.</p>

S-nitrosogluthatione is an endogenous substance, present at decreased levels in the lungs of CF patients and was recently found to induce mature CFTR in airway epithelial CF cell lines. We show that S-nitrosoglutathione in physiological concentrations increases the presence of ΔF508 CFTR in the cell membrane and induces cAMP dependent chloride transport in cystic fibrosis airway epithelial cells. The properties of S-nitrosoglutathione include other potential benefits for the CF patient and make this agent an interesting candidate for pharmacological treatment of CF that needs to be further evaluated. Genistein was found to increase the chloride efflux in both normal and ΔF508 cells without stimulation of cAMP elevating agents and without prior treatment with phenylbutyrate. Genistein, in concentrations close to those that can be detected in plasma after a high soy diet, could induce chloride efflux in cells with the ΔF508 CFTR mutation and its possible use in the treatment of CF should therefore be further investigated. Studies on nasal epithelial cells from CF patients showed cAMP dependent chloride efflux in some of the patients with severe genotypes. This may complicate in vitro evaluation of clinical treatment of these patients. The presence of cAMP dependent chloride transport did not necessarily lead to a milder phenotype. Other factors than CFTR may influence the clinical development of the disease. Cystic fibrosis (CF) is the most common monogenetic disease among Caucasians. A defective cAMP regulated chloride channel (cystic fibrosis transmembrane conductance regulator, CFTR) in epithelial cells leads to viscous mucus, bacterial infections, inflammation and tissue damage in the lungs that cause death in 95% of the cystic fibrosis patients. There is no cure for the disease although existing treatment has dramatically prolonged the life expectancy. The aim of this thesis was to study pharmacological agents for their ability to restore the cellular deficiency in CF airway epithelial cells. X-ray microanalysis, MQAE fluorescence and immunocytochemistry were used to evaluate the effects.