Improving the biological activity of pyrrole-imidazole polyamides

DNA is nature’s blueprint, holding within it the genetic code that defines the structure and function of an organism. A complex network of DNA-binding proteins called transcription factors can largely control the flow of information from DNA, so modulating the function of transcription factors is a promising approach for treating many diseases. Pyrrole-imidazole (Py-Im) polyamides are a class of DNA-binding oligomers, which can be synthetically programmed to bind a target sequence of DNA. Due to their unique shape complementarity and a series of favorable hydrogen bonding interactions that occur upon DNA-binding, Py-Im polyamides can bind to the minor groove of DNA with affinities comparable to transcription factors. Previous studies have demonstrated that these cell-permeable small molecules can enter cell nuclei and disrupt the transcription factor-DNA interface, thereby repressing transcription. As the use of Py-Im polyamides has significant potential as a type of modular therapeutic platform, the need for polyamides with extremely favorable biological properties and high potency will be essential. Described herein, a variety of studies have been performed aimed at improving the biological activity of Py-Im polyamides. To improve the biological potency and cellular uptake of these compounds, we have developed a next-generation class of polyamides bearing aryl-turn moieties, a simple structural modification that allows significant improvements in cellular uptake. This strategy was also applied to a panel of high-affinity cyclic Py-Im polyamides, again demonstrating the remarkable effect minor structural changes can have on biological activity. The solubility properties of Py-Im polyamides and use of formulating reagents with their treatment have also been examined. Finally, we describe the study of Py-Im polyamides as a potential artificial transcription factor.

Improving the chances for developing coastal country success in adapting to climate change

There is an unequivocal scientific consensus that increases in greenhouse gases in the atmosphere drive warming temperatures of air and sea, and acidification of the world’s oceans from carbon dioxide absorbed by the oceans. These changes in turn can induce shifts in precipitation patterns, sea level rise, and more frequent and severe extreme weather events (e.g. storms and sea surge). All of these impacts are already being witnessed in the world’s coastal regions and are projected to intensify in years to come. Taken together, these impacts are likely to result in significant alteration of natural habitats and coastal ecosystems, and increased coastal hazards in low-lying areas. They can affect fishers, coastal communities and resource users, recreation and tourism, and coastal infrastructure. Approaches to planned adaptation to these impacts can be drawn from the lessons and good practices from global experience in Integrated Coastal Management (ICM). The recently published USAID Guidebook on Adapting to Coastal Climate Change (USAID 2009) is directed at practitioners, development planners, and coastal management professionals in developing countries. It offers approaches for assessing vulnerability to climate change and climate variability in communities and outlines how to develop and implement adaptation measures at the local and national levels. Six best practices for coastal adaptation are featured in the USAID Guidebook on Adapting to Coastal Climate Change and summarized in the following sections. (PDF contains 3 pages)

On-farm feed: the potential for improving profitability in aquaculture

The urge to develop a standard practical diet for farmed fish in Nigeria has been on the increase since the last decade. Since ages diets has ever represent the largest single cost item of most fish farm operations. This is the reason why careful selection of feed ingredients for use in aqafeed plays a vital role in the resultant nutritional and economic success of farmed fish. In an attempt to meet the objectives of culturing fish two main sources of fish feed have been identified for meeting the nutritional requirements of fish. These include 'on-farm feeds' and 'commercial feeds'. However, 'on-farm feed' takes the lion share out of the total annual national aquafeed product which amounts to about 70% of the estimated total of 3,570 tones of fish feed produced in year 2000. This paper takes a look at the important of non-conventional feed resource in 'on-farm feed', the place of vitamins in 'on-farm feed', the need to develop and encourage on-farm feed production and feeding strategies if aquaculture will grow further to meet the projected million metric tones production within this decade

Improving aquaculture through increased fisheries extension research

The present study was conducted, as an attempt to disabuse minds of practicing fish farmers and also encourage prospective farmers who are of the opinion that fish culture is not as profitable as it is widely reported. The study was carried out in an abandoned concrete water fountain tank (20m super(2)) made primarily for recreational purposes. The tank was stocked initially with 125 post fingerlings (Heterobtranchus bidorsalis) bought at rate of N30 each. Cost of feeding was N3, 149.85. Gross and net profits for the passive 2- year culture stood at N27, 149.85 and N20, 000.00 respectively. The longest fish (L sub(max)) was 64.0 com TL while the smallest 41.5cm TL (64.8%L sub(max)) and weight 1.9kg (W sub(max)) and 0.5kg 26.3%W sub(max)). Weight and length data generated from the study were examined

The Economic Impacts of Biodiversity Policy for Improving the Climate Regulating Services Provided by EU Natura 2000 Habitats

22 p.

The Voting Rights Act, Shelby County, and Redistricting: Improving Estimates of Racially Polarized Voting in a Multiple-Election Context

The Supreme Court’s decision in Shelby County has severely limited the power of the Voting Rights Act. I argue that Congressional attempts to pass a new coverage formula are unlikely to gain the necessary Republican support. Instead, I propose a new strategy that takes a “carrot and stick” approach. As the stick, I suggest amending Section 3 to eliminate the need to prove that discrimination was intentional. For the carrot, I envision a competitive grant program similar to the highly successful Race to the Top education grants. I argue that this plan could pass the currently divided Congress.

Without Congressional action, Section 2 is more important than ever before. A successful Section 2 suit requires evidence that voting in the jurisdiction is racially polarized. Accurately and objectively assessing the level of polarization has been and continues to be a challenge for experts. Existing ecological inference methods require estimating polarization levels in individual elections. This is a problem because the Courts want to see a history of polarization across elections.

I propose a new 2-step method to estimate racially polarized voting in a multi-election context. The procedure builds upon the Rosen, Jiang, King, and Tanner (2001) multinomial-Dirichlet model. After obtaining election-specific estimates, I suggest regressing those results on election-specific variables, namely candidate quality, incumbency, and ethnicity of the minority candidate of choice. This allows researchers to estimate the baseline level of support for candidates of choice and test whether the ethnicity of the candidates affected how voters cast their ballots.

O Protocolo de Kyoto e o mercado de crédito de carbono: estudo de caso das emissões de gases de efeito estufa da fábrica de combustível nuclear pertencente às Indústrias Nucleares do Brasil no ano de 2008

A presente dissertação discute as questões relacionadas à intensificação das mudanças climáticas por causas antrópicas conforme a evolução no uso dos recursos naturais, inovações nos processos produtivos, transformações econômicas, sociais, culturais, políticas e, especialmente ambientais. Aborda a comercialização dos créditos de carbono através de projetos de Mecanismo de Desenvolvimento Limpo (MDL), um dos mecanismos de flexibilização criados pelo Protocolo de Kyoto. No contexto de mudanças climáticas, uma matriz energética que utilize fontes de energia que não emitam gases causadores do efeito estufa (GEE) se mostra uma importante estratégia de desenvolvimento sustentável. Sob essa perspectiva, a energia nucleoelétrica é apresentada como uma alternativa viável aos combustíveis fósseis, considerando que esta é uma energia limpa e compatível com a perspectiva de desenvolvimento sustentável. A Fábrica de Combustível Nuclear (FCN), localizada em Resende (Rio de Janeiro), pertencente às Indústrias Nucleares do Brasil (INB), é um conjunto de sofisticadas fábricas nas quais se processam etapas importantes do ciclo do combustível nuclear. Na FCN, o Centro Zoobotânico realiza a gestão das atividades voltadas para a conservação da natureza tais como o Programa de Recuperação de Mata Ciliar, Reflorestamento e Fauna. O Relatório de inventário das emissões diretas e indiretas de GEE da FCN, elaborado pela INB para o ano de 2008, permite a auto-avaliação da empresa, retratando a preocupação corporativa com as questões relativas às mudanças climáticas. Segundo este Relatório, o total de emissões de GEE quantificado corresponde a 12,14% da capacidade total de sequestro de dióxido de carbono, no período de Janeiro a Dezembro de 2008. A proteção de florestas e a plantação de árvores são componentes essenciais de qualquer estratégia global para mitigação da mudança climática, e a participação da INB no mercado de crédito de carbono pode proporcionar externalidades positivas, tais como ganhos de imagem, adequação a padrões ambientais e melhoria do relacionamento com a sociedade.

The scope for biomanipulation in improving water quality

Biomanipulation is a form of biological engineering in which organisms are selectively removed or encouraged to alleviate the symptoms of eutrophication. Most examples involve fish and grazer zooplankton though mussels have also been used. The technique involves continuous management in many deeper lakes and is not a substitute for nutrient control. In some lakes, alterations to the lake environment have given longer-term positive effects. And in some shallow lakes, biomanipulation may be essential, alongside nutrient control, in re- establishing former aquatic-plant-dominated ecosystems which have been lost through severe eutrophication. The emergence of biomanipulation techniques emphasises that lake systems are not simply chemical reactors which respond simply to engineered chemical changes, but very complex and still very imperfectly understood ecosystems which require a yet profounder understanding before they can be restored with certainty.