Development of a Cationic Mucic Acid Polymer-Based Nanoparticle siRNA Delivery System

Cancer chemotherapy has advanced from highly toxic drugs to more targeted treatments in the last 70 years. Chapter 1 opens with an introduction to targeted therapy for cancer. The benefits of using a nanoparticle to deliver therapeutics are discussed. We move on to siRNA in particular, and why it would be advantageous as a therapy. Specific to siRNA delivery are some challenges, such as nuclease degradation, quick clearance from circulation, needing to enter cells, and getting to the cytosol. We propose the development of a nanoparticle delivery system to tackle these challenges so that siRNA can be effective.

Chapter 2 of this thesis discusses the synthesis and analysis of a cationic mucic acid polymer (cMAP) which condenses siRNA to form a nanoparticle. Various methods to add polyethylene glycol (PEG) for stabilizing the nanoparticle in physiologic solutions, including using a boronic acid binding to diols on mucic acid, forming a copolymer of cMAP with PEG, and creating a triblock with mPEG on both ends of cMAP. The goal of these various pegylation strategies was to increase the circulation time of the siRNA nanoparticle in the bloodstream to allow more of the nanoparticle to reach tumor tissue by the enhanced permeation and retention effect. We found that the triblock mPEG-cMAP-PEGm polymer condensed siRNA to form very stable 30-40 nm particles that circulated for the longest time – almost 10% of the formulation remained in the bloodstream of mice 1 h after intravenous injection.

Chapter 3 explores the use of an antibody as a targeting agent for nanoparticles. Some antibodies of the IgG1 subtype are able to recruit natural killer cells that effect antibody dependent cellular cytotoxicity (ADCC) to kill the targeted cell to which the antibody is bound. There is evidence that the ADCC effect remains in antibody-drug conjugates, so we wanted to know whether the ADCC effect is preserved when the antibody is bound to a nanoparticle, which is a much larger and complex entity. We utilized antibodies against epidermal growth factor receptor with similar binding and pharmacokinetics, cetuximab and panitumumab, which differ in that cetuximab is an IgG1 and panitumumab is an IgG2 (which does not cause ADCC). Although a natural killer cell culture model showed that gold nanoparticles with a full antibody targeting agent can elicit target cell lysis, we found that this effect was not preserved in vivo. Whether this is due to the antibody not being accessible to immune cells or whether the natural killer cells are inactivated in a tumor xenograft remains unknown. It is possible that using a full antibody still has value if there are immune functions which are altered in a complex in vivo environment that are intact in an in vitro system, so the value of using a full antibody as a targeting agent versus using an antibody fragment or a protein such as transferrin is still open to further exploration.

In chapter 4, nanoparticle targeting and endosomal escape are further discussed with respect to the cMAP nanoparticle system. A diboronic acid entity, which gives an order of magnitude greater binding (than boronic acid) to cMAP due to the vicinal diols in mucic acid, was synthesized, attached to 5kD or 10kD PEG, and conjugated to either transferrin or cetuximab. A histidine was incorporated into the triblock polymer between cMAP and the PEG blocks to allow for siRNA endosomal escape. Nanoparticle size remained 30-40 nm with a slightly negative ca. -3 mV zeta potential with the triblock polymer containing histidine and when targeting agents were added. Greater mRNA knockdown was seen with the endosomal escape mechanism than without. The nanoparticle formulations were able to knock down the targeted mRNA in vitro. Mixed effects suggesting function were seen in vivo.

Chapter 5 summarizes the project and provides an outlook on siRNA delivery as well as targeted combination therapies for the future of personalized medicine in cancer treatment.

River Wyre salmon and sea trout spawning habitat restoration / creation project. Final report April 1995

Adult salmon and sea trout rod catches in the River Wyre have been subject to considerable variability over the years. Annual rod catches ranging from 6 to 401 have been reported since records began in 1905. It has long been suspected that the physical nature of the catchment, combined with anthropogenic influences, has resulted in a deleterious effect on the Wyre fishery. Acidification problems in the head water streams (Marshaw Wyre and Tarnbrook Wyre) have been reported and are thought to threaten salmon juvenile survival. The construction of Abbeystead Reservoir and an increased tendency towards rapidly rising water levels during storms (flashiness) 1 are thought to have a significant impact on spawning gravel quality and quantity, both of which are thought to be deteriorating. As part of an overall desire to maintain and improve the migratory salmonid population in the River Wyre, this project has been commissioned to investigate remedial action which may improve and enhance spawning success, leading to an eventual improvement in the status of adult stocks. The primary objective is to establish whether the quantity and/or quality of available spawning gravels are limiting migratory salmonid productivity. The investigations undertaken confirm the general observation that useable spawning gravels appear to be in short supply in the River Wyre, and may be the limiting factor influencing returning adult stock.

River Wyre salmon and sea trout spawning habitat restoration / creation project. Gravel enhancement schemes.

As part of an overall desire to maintain and improve the migratory salmonid population in the River Wyre, a project was commissioned to investigate remedial action which may improve and enhance spawning success and lead to an eventual improvement in the status of adult stocks. The report, titled "River Wyre Salmon and Sea Trout Spawning Habitat Restoration/Creation Project", concluded that usable spawning gravels appeared to be in short supply in the River Wyre catchment and may be the limiting factor influencing the returning adult stock, as juvenile nursery habitat was not found to be limiting. This report looks at gravel enhancement schemes to improve River Wyre salmon and sea trout spawning habitat restoration. It examines methods for gravel enhancement schemes: mechanical cleaning and construction of gravel addition structures. Includes sites figures of sites identified for enhancement.

Occupational exposure to nano-TiO2 in the life cycle steps of new depollutant mortars used in construction

The present work is focused on the measurement of workers exposure to nano-TiO2 in the life cycle steps of depollutant mortars. It has been done in the framework of the SCAFFOLD project, which aims at the management of potential risks arising from the use of manufactured nanomaterials in construction. Main findings can be summarized as follows: (1) The occupational exposure to nano-TiO2 is below 0.3 mg/m(3) for all measured scenarios. The highest concentrations were measured during the cleaning task (in the nano-TiO2 manufacturing process) and during the application (spraying) of depollutant coatings on a wall. (2) It was found a high release of particles above the background in several tasks as expected due to the nature of the activities performed. The maximum concentration was measured during drilling and during adding powder materials (mean total particle concentration up to 5.591E+04 particles/cm(3) and 5.69E+04 particles/cm(3)). However, considering data on total particle concentration released, no striking differences have been observed when tasks have been performed using conventional materials in the sector (control) and when using materials doped with nano-objects.

Atribuindo significados as enfermeiras obstétricas: uma construção social sob a ótica das usuárias na perspectiva do interacionismo simbólico

O presente estudo teve como objetivos: identificar o significado de Enfermeira Obstétrica para as usuárias; analisar os significados atribuídos à Enfermeira Obstétrica pelas usuárias; e, desenvolver um modelo teórico explicativo da construção do significado de Enfermeira Obstétrica sob a ótica das usuárias. Trata-se de uma pesquisa descritiva com abordagem qualitativa interpretada pelo Interacionismo Simbólico, como referencial teórico e, tendo a Grounded Theory, como referencial metodológico. Foram participantes da pesquisa, 20 (vinte) usuárias atendidas por Enfermeiras Obstétricas em diversos cenários de cuidado, tais como: domicílio, Unidades Básicas de Saúde, Maternidades, Casas de Parto/Centros de Parto Normal de diversos municípios do Estado do Rio de Janeiro - durante o pré-natal, trabalho de parto e parto. A coleta dos dados ocorreu entre setembro de 2012 e julho de 2014, após este projeto ter sido aprovado pelo Comitê de Ética em Pesquisa da Universidade do Estado do Rio de Janeiro/UERJ/SR2 em julho de 2012. Utilizou-se a entrevista semi-estruturada gravada, iniciada com uma questão comum: Fale-me como foi sua gestação, seu acompanhamento pré-natal e seu parto. Os resultados revelam que as usuárias chegam até as enfermeiras obstétricas porque procuram por alguém que atenda seu desejo de vivenciar uma gestação e um parto natural sem intervenções desnecessárias e com a presença de familiares, principalmente os companheiros. Fica evidente, neste estudo, que as usuárias desconhecem, até o estabelecimento da interação social, a profissional enfermeira obstétrica e chegam até elas por: indicação de amigos e/ou familiares; por indicação de outros profissionais de saúde (enfermeiras, fisioterapeutas ou médicos); ou por intermédio de grupos de mulheres nas redes sociais. Vale ressaltar que, as mulheres que optaram por serem atendidas por enfermeiras obstétricas durante o pré-natal, trabalham de parto e parto, buscaram informações sobre gestação, fisiologia do trabalho de parto, atuação e formação as enfermeiras obstétricas, direitos sexuais e reprodutivos, legislação sobre direitos dos usuários dos serviços de saúde, dentre outros, nas redes sociais; compartilharam vivências em grupos na internet e acabaram referenciando as enfermeiras obstétricas a outras mulheres. A análise comparativa dos dados identificou três categorias: Desejando vivenciar o parto natural; Procurando alguém que atenda o desejo de vivenciar o parto natural; e Encontrando e vivenciando os cuidados da Enfermeira Obstétrica. As usuárias agem em relação às Enfermeiras Obstétricas com base no significado que estas têm para ela, ou seja, apresentam como símbolos significantes para o objeto social Enfermeiras Obstétricas: aquela que presta um cuidado concreto, um cuidado abstrato, um cuidado afetivo e um cuidado com conhecimento científico. Os significados retratam que o vínculo estabelecido entre as envolvidas extrapola a competência técnica e ratificam que, a necessidade de vínculo pessoal é imprescindível para que o cuidado humanizado aconteça.

O desempenho da Maternidade da Santa Casa de Angra dos Reis face aos critérios de qualidade do Programa Nacional de Avaliação dos Serviços de Saúde - PNASS.

A Santa Casa de Angra dos Reis é uma Instituição Filantrópica inaugurada em 06 de janeiro de 1839. A Unidade passa por Intervenção Municipal, recomendada pelo Ministério Público, no intuito de garantir o restabelecimento adequado de seus serviços, a eficiência desejável e para resgatar a credibilidade e sustentabilidade do Hospital. Da motivação pelos projetos da nova gestão emergiu a necessidade de conhecer a situação do desempenho desta unidade hospitalar, em especial a Maternidade, ponto de partida do projeto. Este estudo é relevante para a institucionalização da avaliação da qualidade nesta Unidade Hospitalar, bem como condição primária para construção de planos de trabalho. O Programa Nacional de Avaliação dos Serviços de Saúde PNASS é uma proposta do Ministério da Saúde, e é visto como uma ferramenta de gestão para monitoramento e avaliação. O programa pode apontar diversas oportunidades de melhorias e auxiliar a tomada de decisão tornando-se adequado seu emprego no levantamento das informações necessárias para o conhecimento do cenário da Maternidade, como base para um futuro plano de ação. Este estudo tem por objetivo aplicar o programa de avaliação normativa proposto pelo PNASS na Maternidade da Santa Casa, a fim de identificar seu desempenho, como primeiro passo para a construção do plano estratégico de ação em busca do aprimoramento da qualidade em saúde neste setor. Como metodologia, é uma pesquisa quantitativa onde foram utilizados padrões de conformidade, questionários fechados direcionados aos usuários e trabalhadores da Maternidade, e análise de indicadores. Resultados: foram entrevistadas 35 mulheres e 47 profissionais de saúde, num total de 85% da amostra desejada; ficou evidente a necessidade de intervenção e implementação de mudanças na área de Gerenciamento de Risco; e melhorias quanto às condições de trabalho relacionadas à infraestrutura e equipamentos. Os indicadores de internação apontam a necessidade de revisão do número de leitos disponíveis; a taxa de parto cesáreo, 59%, é extremamente alta e muito acima do preconizados pela Organização Mundial de Saúde. Este estudo mostrou um resultado positivo quanto à satisfação das parturientes com o serviço prestado, embora existam áreas carentes de melhorias. Melhorias também são necessárias para o dimensionamento efetivo do quadro de profissionais para atendimento à demanda. A interrupção do lançamento de relatórios sobre atuais avaliações feitas pelo PNASS e a pouca divulgação do mesmo são questões levantadas por este estudo. Considera-se que a aplicação do PNASS na Maternidade da Santa Casa de Angra dos Reis proporcionou embasamento para a elaboração de uma oportuna matriz de intervenção.

Impact of Bashundhara Baridhara Housing Project on the status, abundance and species diversity of fish in Bashundhara Housing lake in Dhaka, Bangladesh

A study on the status of fisheries and environmental impact assessment (EIA) was conducted on Bashundhara Baridhara Housing Project (BBHP), Dhaka, Bangladesh for prediction and measure the effects of housing project related development activities that have already been implemented and planned for future implementation. The project is still under development phase and so far allotted 10,000 plots of different sizes. The study shows that the original water bodies and natural fish production there from have greatly declined due to earth filling carried out for development of land for the housing. The physico-chemical parameters of the existing water body within the project area were found to be suitable for fish farming in the estate. A number of economically important fish species are found available in the existing lake. However, the natural fisheries resources of the existing lake is under great stress due to the changes made in the ecosystem, siltation, construction of building and dumping of house building and household waste materials. This has caused some important fish species of the lake to become critically endangered and vulnerable which have been documented in this paper. Appropriate regulatory and mitigating measures with respect to water management, disposal of construction garbage and other biomedical toxic substances far away from the water bodies are required to be taken to keep the water safe and suitable for fish production as well as for multipurpose use of the lake water.

Comparative feature on design, construction and installation of three different model of low cost solar tunnel dryers

The study was conducted in collaboration with the ECFC project of the FAO (BGD/97/017) in Cox's Bazar to develop a low cost solar tunnel dryer for the production of high quality marine dried fish. The study areas were Kutubdiapara, Maheshkhali and Shahparirdip under Cox's Bazar district. Three different models of low cost solar dryer were constructed with locally available materials such as bamboo, wood, bamboo mat, hemp, canvas, wire, nails, rope, tin, polythene and net. Size of the dryers were: 20x4x3 ft ; 30x3x3 ft and 65x3x3 ft with the costs of Tk. 3060, 3530, 9600 for dryer 1, 2 and 3, respectively having different models. The drying capacities were 50, 150, 500 kg for dryer 1, 2 and 3 respectively. The average temperature range inside the dryers were 29-43°C, 34-51°C and 37-57°C for dryer 1, 2 and 3 respectively as recorded at 8:30h to 16:30h. The relative humidity were in the ranges of 22-42%, 27-39% and 24-41 % in dryer 1, 2 and 3 respectively. The fish samples used were Bombay duck, Silver Jew fish and Ribbon fish. The total drying time was in the range of 30-42, 28-38 and 24-34 hours to reach the moisture content of 12.3-14.5, 11.8-14.3, and 11.6-14.1% in dryer 1, 2 and 3 respectively. Among these three fish samples the drying was faster in Silver Jew fish followed by Bombay duck and Ribbon fish in all the three dryer.

Patterns of interaction in construction team meetingsξ

Sir John Egan’s 1998 report on the construction industry (Construction Task Force 1998) noted its confrontational and adversarial nature. Both the original report and its subsequent endorsement in Accelerating Change (Strategic Forum 2002) called for improved working relationships—so-called ‘integration’—within and between both design and construction aspects. In this paper, we report on our observations of on-site team meetings for a major UK project during its construction phase. We attended a series of team meetings and recorded the patterns of verbal interaction that took place within them. In reporting our findings, we have deliberately used a graphical method for presenting the results, in the expectation that this will make them more readily accessible to designers. Our diagrams of these interaction patterns have already proved to be intuitively and quickly understood, and have generated interest and discussion among both those we observed and others who have seen them. We noted that different patterns of communication occurred in different types of meetings. Specifically, in the problem-solving meeting, there was a richness of interaction that was largely missing from progress meetings and technical meetings. Team members expressed greater satisfaction with this problem-solving meeting where these enriched exchanges took place. By making comparisons between the different patterns, we are also able to explore functional roles and their interactions. From this and other published evidence, we conclude that good teamworking practices depend on a complex interplay of relations and dependencies embedded within the team.

Capture fisheries in Uganda: why Bujagali hydro-power project and ecological monitoring?

Human use of water resow-ces in Uganda has grown and intensified along with population growth and increasing demand to meet the diverse human needs. In the case of Uganda's rivers, the main uses include fisheries, hydropower generation, abstraction for potable water supply, discharge of sewage and navigation. All these uses can disrupt the integrity of the aquatic ecosystem and may affect the survival of the diversity of organisms. In consideration of the need to increase electricity to meet demand, the Bujagali Hydro-power Project (BHPP) and the National Environment Management Authority (NEMA) recognised the importance of safeguards to mitigate impacts of the project. The National Fisheries Resources Research Institute (NaFIRRI) was assigned the role of providing baseline information on the aquatic ecosystem of the Upper Victoria Nile and to follow up the findings with a monitoring framework during construction and post-commissioning phases.

Social sensing in the field: Challenges in detecting social interactions in construction sites

Construction industry is a sector that is renowned for the slow uptake of new technologies. This is usually due to the conservative nature of this sector that relies heavily on tried and tested and successful old business practices. However, there is an eagerness in this industry to adopt Building Information Modelling (BIM) technologies to capture and record accurate information about a building project. But vast amounts of information and knowledge about the construction process is typically hidden within informal social interactions that take place in the work environment. In this paper we present a vision where smartphones and tablet devices carried by construction workers are used to capture the interaction and communication between workers in the field. Informal chats about decisions taken in the field, impromptu formation of teams, identification of key persons for certain tasks, and tracking the flow of information across the project community, are some pieces of information that could be captured by employing social sensing in the field. This information can not only be used during the construction to improve the site processes but it can also be exploited by the end user during maintenance of the building. We highlight the challenges that need to be overcome for this mobile and social sensing system to become a reality. © 2012 ACM.

Automated vision tracking of project related entities

Tracking of project related entities such as construction equipment, materials, and personnel is used to calculate productivity, detect travel path conflicts, enhance the safety on the site, and monitor the project. Radio frequency tracking technologies (Wi-Fi, RFID, UWB) and GPS are commonly used for this purpose. However, on large-scale sites, deploying, maintaining and removing such systems can be costly and time-consuming. In addition, privacy issues with personnel tracking often limits the usability of these technologies on construction sites. This paper presents a vision based tracking framework that holds promise to address these limitations. The framework uses videos from a set of two or more static cameras placed on construction sites. In each camera view, the framework identifies and tracks construction entities providing 2D image coordinates across frames. Combining the 2D coordinates based on the installed camera system (the distance between the cameras and the view angles of them), 3D coordinates are calculated at each frame. The results of each step are presented to illustrate the feasibility of the framework.

Testing in harsh conditions: Tracking resources on construction sites with machine vision

When tracking resources in large-scale, congested, outdoor construction sites, the cost and time for purchasing, installing and maintaining the position sensors needed to track thousands of materials, and hundreds of equipment and personnel can be significant. To alleviate this problem a novel vision based tracking method that allows each sensor (camera) to monitor the position of multiple entities simultaneously has been proposed. This paper presents the full-scale validation experiments for this method. The validation included testing the method under harsh conditions at a variety of mega-project construction sites. The procedure for collecting data from the sites, the testing procedure, metrics, and results are reported. Full-scale validation demonstrates that the novel vision tracking provides a good solution to track different entities on a large, congested construction site.

Identification of Materials from Construction Site Images Using Content Based Image Retrieval Techniques

The capability to automatically identify shapes, objects and materials from the image content through direct and indirect methodologies has enabled the development of several civil engineering related applications that assist in the design, construction and maintenance of construction projects. Examples include surface cracks detection, assessment of fire-damaged mortar, fatigue evaluation of asphalt mixes, aggregate shape measurements, velocimentry, vehicles detection, pore size distribution in geotextiles, damage detection and others. This capability is a product of the technological breakthroughs in the area of Image and Video Processing that has allowed for the development of a large number of digital imaging applications in all industries ranging from the well established medical diagnostic tools (magnetic resonance imaging, spectroscopy and nuclear medical imaging) to image searching mechanisms (image matching, content based image retrieval). Content based image retrieval techniques can also assist in the automated recognition of materials in construction site images and thus enable the development of reliable methods for image classification and retrieval. The amount of original imaging information produced yearly in the construction industry during the last decade has experienced a tremendous growth. Digital cameras and image databases are gradually replacing traditional photography while owners demand complete site photograph logs and engineers store thousands of images for each project to use in a number of construction management tasks. However, construction companies tend to store images without following any standardized indexing protocols, thus making the manual searching and retrieval a tedious and time-consuming effort. Alternatively, material and object identification techniques can be used for the development of automated, content based, construction site image retrieval methodology. These methods can utilize automatic material or object based indexing to remove the user from the time-consuming and tedious manual classification process. In this paper, a novel material identification methodology is presented. This method utilizes content based image retrieval concepts to match known material samples with material clusters within the image content. The results demonstrate the suitability of this methodology for construction site image retrieval purposes and reveal the capability of existing image processing technologies to accurately identify a wealth of materials from construction site images.