Activated Heat Shock Transcription Factor 1 (HSF1) has received attention in recent literature as a therapeutic effector in diseases of protein misfolding, as an immune modulating adjuvant in tumor regression, and as a trigger for gene therapy transcription. In its normal function, activated HSF1 enhances heat shock protein (Hsp) expression when additional molecular chaperoning is required (i.e., in situations of proteotoxic stress, including thermal stress) in a process known as the heat shock (HS) response. Thus, HSF1 acts as an environmental sensor, and a harness based on the biology of this capability enables transcription of genes for engineered purposes. The hypothesis of this thesis is that a harness of the heat shock response, when paired with a therapeutic mechanism, will refine novel therapies. Extensions to the concept of deliberately activating HSF1's normal functions for therapeutic purposes are examined through in vitro trials and in vivo preliminary studies that feature the use of HSF1 as a regulator of therapy. Successful in vitro work translated to pioneering preclinical studies, launched at the University of Florida's Center for Environmental and Human Toxicology. Collaboration supported the development of an innovative project to treat solid tumors using a recombinant virus system. The system was designed to facilitate intratumoral delivery of a previously characterized molecular switch, which was newly engineered to control cytotoxic gene transcription that produced dramatic consequences in cells of human origin. Central to the targeting of the in vivo therapy, is a transient, initial trigger: a thermal dose, delivered to solid tumors, which localizes HSF1 activation (a constitutively active mouse HSF1 construct was also produced to aid clarification of physiological consequences associated with deliberately upregulating HSF1 activity in vivo). Gene transcription was expected to ensue to both cause and sustain tumor regression through other regulatory elements of the molecular switch. Results demonstrated practical potential to achieve a therapeutic outcome of solid tumor regression and define contemporary challenges that continuing research directions (e.g.: production of additional viral vectors, an improved animal model, and a refined heat system) now confront in order to target and safely regulate even more potent, novel therapeutic agents.

Wetlands are one of the most productive ecosystems in the world, housing diverse biota and serving important functions as nursery habitat and feeding grounds. However, nearly 70% of coastal wetlands, including 21% of the salt marshes in Texas, have been lost since 1950, due primarily to coastal development and declines in water quality. Restoration of wetlands is essential to reestablish lost functions, but there is no standard method to assess the ecological health of restored salt marshes in Texas. Numerous recent salt marsh restoration projects in Galveston Bay have made it an ideal model system to develop and implement an ecosystem health assessment, known as a rapid assessment method (RAM). In this study, I modified an established RAM, the Mid-Atlantic Tidal Fringe Assessment, to compare the ecological health of representative reference salt marshes to restored marshes around Galveston Bay. I measured 14 biotic and abiotic characteristics at 12 restored and 6 reference sites around Galveston Bay, and then grouped those measurements into four functional groups: landscape/site characteristics, hydrology, wildlife habitat, and soil characteristics. I then developed a scoring system (minimum 0, maximum 100) to summarize the overall health of each site. Most of the restored salt marshes in this study scored lower than reference marshes. The average reference site score was 81.8 and the average restored site score was 69.7. Functional group values for landscape/site characteristics, soil, and wildlife habitat were significantly lower in restored than in reference sites. In particular, restored sites had more hydrological modifications, more fill material, and fewer macrobenthos than reference wetlands. The Galv-RAM effectively and efficiently identified restoration successes and weaknesses. With this information, management agencies can address restoration shortcomings by adapting management goals. The Galv-RAM will streamline monitoring protocols and facilitate long-term examination of restored wetland health. As a result, management decisions can be modified based on the scores received in different categories or variables to improve and or meet the goals of the project.

Made available in DSpace on 2014-12-17T15:01:30Z (GMT). No. of bitstreams: 1 AlfredoJFS_DISSERT.pdf: 1130528 bytes, checksum: d7a64b847a80a2de8b89250f09f06bd0 (MD5) Previous issue date: 2012-11-05 / Copper is one of the most used metals in platingprocesses of galvanic industries. The presence of copper, a heavy metal, in galvanic effluents is harmful to the environment.The main objective of this researchwas the removal ofcopperfromgalvanic effluents, using for this purpose anionic surfactants. The removal process is based on the interaction between the polar head group of the anionic surfactant and the divalent copper in solution. The surfactants used in this study were derived from soybean oil (OSS), coconut oil (OCS), and sunflower oil (OGS). It was used a copper synthetic solution (280 ppm Cu+2) simulating the rinse water from a copper acid bath of a galvanic industry. It were developed 23and 32 factorial designs to evaluate the parameters that have influence in theremoval process. For each surfactant (OSS, OCS, and OGS), the independent variables evaluated were: surfactant concentration (1.25 to 3.75 g/L), pH (5 to 9) and the presence of an anionic polymer (0 to 0.0125 g/L).From the results obtained in the 23 factorial design and in the calculus for estimatingthe stoichiometric relationship between surfactants and copper in solution, it were developed new experimental tests, varying surfactant concentration in the range of 1.25 to 6.8 g/L (32 factorial design).The results obtained in the experimental designs were subjected to statistical evaluations to obtain Pareto charts and mathematical modelsfor Copper removal efficiency (%). The statistical evaluation of the 23 and 32factorial designs, using saponifiedcoconut oil (OCS), presented the mathematical model that best described the copper removal process.It can be concluded that OCS was the most efficient anionic surfactant, removing 100% of the copper present in the synthetic galvanic solution / O cobre ? um dos metais mais utilizados nos processos decorativos das ind?strias galv?nicas. A presen?a do cobre nos efluentes galv?nicos, por ser um metal pesado, compromete a vida das pessoas e dos animais. O principal objetivo deste trabalho ? remover o cobre destes efluentes, utilizando para este prop?sito tensoativos ani?nicos. O processo de remo??o consiste em utilizar a partepolar do tensoativo ani?nico para interagir com o cobre bivalente em solu??o. Os tensoativos utilizados neste estudo foram derivados dos ?leos de soja, coco e girassol. Utilizou-se a ?gua de lavagem do processo de cobre ?cido de uma ind?stria galv?nica como base para a obten??o do efluente sint?tico (280 ppm Cu+2). Para avaliar os par?metros que influenciam no processo foram desenvolvidos planejamentos experimentais fatoriais 23 e 32.Para cada tensoativo derivado dos ?leos vegetais avaliados (OSS, OCS e OGS) as vari?veis independentes utilizadas no planejamento foram: a concentra??o de tensoativo (1,25 a 3,75 g/L), pH (5 a 9) e presen?a de um pol?mero ani?nico (0 a 0,0125 g/L).A partir dos resultados colhidos neste primeiro planejamento experimental e dos c?lculos obtidos atrav?s da rela??o estequiom?trica entre os tensoativos e o cobre em solu??o foram realizados novos ensaios experimentais, variando a concentra??o do tensoativo na faixa de 1,25 a 6,8 g/L. Os resultados obtidos atrav?s do planejamento experimental foram submetidos a avalia??o estat?stica para obten??o de gr?ficos de pareto e do modelo matem?tico que descreve a efici?ncia do processo na remo??o do cobre. A avalia??o estat?stica dos planejamentos experimentais fatoriais 23 e 32,onde se utilizou ?leo de coco saponificado, apresentou o modelo matem?tico que melhor descreveu o processo de remo??o do cobre. Conclui-se que, atrav?s da utiliza??o de metodologias de planejamento experimental e da varia??o da concentra??o dos 3tensoativos(1,25 a 6,8g/L), o OCS foi o tensoativo mais eficiente, chegando a remover 100% do cobre presente na solu??o