376 research outputs found

    Frontline Leadership: Strategies and Tactics for First Responders

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    For the workshop, I plan to provide a comprehensive three to four-hour session focusing on the principles of extreme ownership—a leadership approach that has proven successful, particularly in high-pressure environments. Drawing inspiration from the renowned philosophy advocated by former Navy SEALs Jocko Willink and Leif Babin, the workshop will dive into realistic strategies for effective leadership. To ensure relatability to the First Responder field, I will tailor the content to the unique challenges and environments faced by those in law enforcement at all levels. Real-world examples and personal experiences will be included, making the training not only educational but also highly applicable to their roles and responsibilities in the field, and within their own homes. Realizing the importance of active participation, the workshop will include interactive elements such as fire team exercises and role-playing scenarios. These activities will give recruits opportunities to apply the principles in simulated situations, helping to reinforce their understanding and ability to implement them

    Microfinance and Rural Women Empowerment in the Kpandai District of Ghana: The Role of SEND Ghana Microfinance Scheme

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    The study investigated the extent to which SEND Ghana’s provision of financial resources has improved the livelihoods of poor women in the Kpandai District in the Northern Region of Ghana. It particularly evaluated method and type of financial services that the organization extends, the type of economic activities that clients invest their credit in the informal sector of the economy, the challenges associated with the financial programme and ways that the programme could be improved to address their economic and social problems. It found out through the use of focus group discussions and personal interviews with beneficiary women that there were significant improvement in beneficiaries’ lives. Apart from training in business and loan management that each beneficiary woman benefits; 39% reported improved access to child education, 27% in access to healthcare services and 14% in improved nutrition among others. The study therefore concludes that SEND-Ghana’s unique approach of training women and giving them loans on incremental basis have empowered many women in the Kpandai. We recommend to make the scheme more useful; SEND Ghana should review the loan package for each cycle by about fifty Ghana cedis (Gh? 50), a downward review of the interest rates and an extension of the period for repaying the credit. We further conclude that microfinance could be a tool for vulnerable groups’ empowerment if they are properly targeted and the approach tailored-made to suit them. Keywords: Women, economic empowerment, microfinance, Kpandai District, SEND Ghana

    Structural insights into functional overlapping and differentiation among myosin V motors

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    Orientador: Mário Tyago MurakamiTexto em português e inglêsTese (doutorado) - Universidade Estadual de Campinas, Instituto de BiologiaResumo: As miosina de classe V, amplamente distribuídas em sistemas eucarióticos desde leveduras até vertebrados, são um dos mais caracterizados motores moleculares da superfamília das miosinas e desempenham um papel chave no transporte intracelular de vesículas, organelas e RNA mensageiro. As miosinas V consistem de duas cadeias pesadas idênticas que se dimerizam através da formação de uma estrutura coiled-coil e sua arquitetura tridimensional pode ser dividida em três distintos domínios: a porção N-terminal ou domínio motor que apresenta os sítios de interação com ATP e actina; a porção central ou pescoço formada por 6 domínios IQ, responsável pela regulação e interação com calmodulina; e a porção C-terminal que inclui a região coiled-coil e o domínio de ligação de cargas celulares também conhecido como domínio cauda globular (GTD). Uma das mais importantes questões pertinentes até hoje é como ocorre a sinalização e a interação entre as vesículas/organelas e o domínio globular C-terminal das miosinas V. Neste estudo, foram resolvidas as estruturas dos domínios cauda globular das miosinas Va, Vb e Vc humanas, revelando pequenas mudanças estruturais que levam a diferenciação funcional e, ainda, um novo mecanismo redox que controla a dimerização do GTD de forma independente do coiled-coil, que é exclusivo para a miosina Vc. As alterações estruturais induzidas pela fosforilação do GTD também foram exploradas, mostrando que o estado fosforilado possuí uma flexibilidade menor, podendo estar envolvido na regulação do estado inibido e/ou reconhecimento de cargas nucleares. Além disso, os sítios de ligação a carga e ao domínio motor foram estruturalmente anotados, indicando uma conservação de resíduos envolvidos na interação com adaptadores para o transporte de peroxissomos e proporcionando detalhes da inibição da atividade motora pelo GTD. Estes resultados contribuem para a compreensão dos determinantes estruturais para o transporte de carga, autoinibição e mecanismos de regulação dos motores de miosina V. Além dos resultados obtidos com a cauda globular, alguns problemas cristalográficos como o problema da fase, pseudosimetria e ordem-desordem cristalina foram abordados (descrito nos Apêndices 9.3 e 9.4). Patologias cristalinas como ordem-desordem parcial ou total podem estar relacionadas à valores elevados de Rfactor e Rfree, mesmo após a conclusão do refinamento, ou mesmo à dificuldade de resolução da estrutura. Problemas de ordem-desordem rotacional parcial e pseudosimetria foram observados em cristais de uma hidrolase glicosídica (TpAbn). Nesse caso, valores satisfatórios de Rfactor e Rfree foram obtidos somente após um minucioso processamento dos dados e redução da simetria. Além disso, os dados dos GTDs das miosinas de classe V foram utilizados como caso teste para o desenvolvimento de novas metodologias de faseamento ab initio em média e baixa resolução (2 ¿ 3 Å) em colaboração com o grupo de Prof. Dr. Isabel Usón (IBMB, Barcelona, Espanha). Utilizando o programa ARCIMBOLDO foi possível resolver a estrutura do GTD-MioVb a 2,1 Å utilizando apenas duas hélices de poli-Ala de 22 resíduos (7,5% do conteúdo da unidade assimétrica), mostrando o grande potencial desta metodologia para dados de média a baixa resoluçãoAbstract: The class V myosins (MyoVs) are widely distributed in eukaryotic organisms from yeast to vertebrates, being one of the most characterized molecular motors of the myosin superfamily. MyoVs play a central role in the intracellular transport of vesicles, organelles, messenger RNA and proteins. MyoVs consist of a coiled-coil-stabilized dimer of two identical heavy chains and their general structure can be divided into three distinct domains: the N-terminal portion or motor domain which binds both actin and ATP; the central portion or neck formed by 6 IQ domains, responsible for the regulation and interaction with calmodulin; and the C-terminal portion that includes the coiled-coil region and the cargo-binding domain also known as globular tail domain (GTD). One of the most important issues still obscure so far is how occurs the interaction between the cargoes and the globular C-terminal domain of myosin V. Here, we have solved the globular tail domain structures of the three human MyoV paralogs (Va, Vb and Vc), revealing subtle structural changes that drive functional differentiation and a novel redox mechanism controlling the GTD dimerization process, which is unique for the MyoVc subclass. The structural changes induced by the phosphorylation of GTD have also been explored, showing that the phosphorylated state is less flexible and may be involved in the regulation of the auto-inhibition mechanism and/or in the recognition of nuclear cargoes. Moreover, the cargo- and motor-binding sites were structurally assigned indicating the conservation of residues involved in the recognition of adaptors for peroxisome transport and providing high-resolution insights into motor domain inhibition by GTD. These results contribute to the understanding of the structural requirements for cargo transport, auto-inhibition and regulatory mechanisms in myosin V motors. In addition to the results obtained with the GTD structures, some crystallographic problems, such as the phase problem, pseudosymmetry and lattice order-disorder were discussed (described in Appendices 9.3 and 9.4). Crystal pathologies such as partial or total order-disorder may be related to high values of Rfactor and Rfree, even at late stages of crystallographic refinement, or even hindering the structure determination. Problems of partial rotational order-disorder and pseudosymmetry were found in TpAbn crystals where only after a careful data processing and symmetry reduction was possible to obtain satisfactory values of residuals (Rfactor and Rfree). Moreover, data from MyoV GTDs were used as a test case for the development of new methodologies for ab initio phasing at medium and low resolution (2 ¿ 3 Å) in collaboration with the group of Prof. Dr. Isabel Usón (IBMB, Barcelona, Spain). Using the program ARCIMBOLDO we have solved the GTD-MioVb structure at 2.1 Å using only two 22-residue-long poly-Ala helix fragments (7.5% of asymmetric unit content), showing the great potential of this methodology for data at medium to low resolutionDoutoradoBioquimicaDoutor em Biologia Funcional e Molecula

    Controlling human Oesophagostomiasis in Northern Ghana

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    This thesis describes aspects of the epidemiology and attempts to control infection and pathology due to the nematode parasite Oesophagostomum bifurcum . In northern Ghana and Togo O. bifurcum is an important parasite of humans; elsewhere it is predominantly seen as a parasite of non-human primates. It is shown that frequency and severity of colonic pathology, measured by ultrasound, is associated with the intensity of infection as measured with coproculture. Females are more infected than males but convincing explanations for the gender-dependent difference of infection rates are not found. Details of the route of transmission remain obscure. Mass treatment with Albendazole resulted in a very important reduction of both prevalence and morbidity of infection. Elimination of human oesophagostomiasis is within reach. The impact on hookworms, also effectively killed by the drug, is considerably smaller. Interruption of Albendazole treatment results of rapidly increasing infection rates in hookworm but not in Oesophagostomum. Integration of control activities in the filariasis elimination programme is likely to result in elimination of human oesophagostomiasis but not of human hookworm infection.LEI Universiteit LeidenDBL Institute For Health Research and Development Glaxo-Smith-Kline Dept of Parasitology, LUMC Gratama FoundationImmunologie, moleculaire biologie en epidemiologie van parasitaire infecties, in het bijzonder van schistosomiasis, malaria en filariasi

    FrameNet, Barsalou Frames and the Case of Associative Anaphora

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