Synthesis of substituted imidazoles that stabilizes Survival Motor Neuron Protein for treatment of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a common autosomal recessive disorder and the leading cause of infant mortality. Patients with this disorder are missing the SMN1 gene that is producing 80-90 % of the Spinal motor neuron (SMN) protein. The SMN2 gene is not able to produce the full-length protein, due to a small difference in the splicing pattern. This leads to loss of muscle function and physical disability. Different treatments ave been performed on patients with SMA, and one of them is to increase the SNM2 gene. In 2012 Androphy et al., in collaboration with Dr. Hodgetts at the LDDN, discovered two hit compounds that increase the SMN protein. Based on one of these compounds, the research group at LDDN optimized the molecule and produced a better probe for the treatment of SMA. In this project, the synthesized probe will be optimized by changing the heterocycle, with the same substituents and amide linker. Different synthesis has been performed, before reaching the target molecule. Amidation with acid chloride and an amine is the main reaction leading to the target molecule. In addition to the target molecule, different analogs have also been made. The substituents on the heterocycle and the amide linker have been modified, leading to several new compounds. All of the compounds that were synthesized, were also sent for testing at the Department of Dermatology, Indiana University School of Medicine. The main reason for the testing is to see if the compounds are active or not in the treatment for SMA. The % activation and the EC50 value for each compound in mouse models were determined. Based on the previously synthesized molecule, the target molecule was expected to be active. This turned out to be wrong, and the target molecule was inactive. However, one of the other compounds showed good activity.Masteroppgave i kjemiKJEM399MAMN-KJE

Collaborative dynamics in a practice of increasing utility cycling : understanding prerequisites for collaboration between bicycle planners and mobility managers in a Norwegian municipality

This study explores prerequisites for closer collaboration between practitioners who in different ways work to increase the cycle share of all travels in a Norwegian municipality. Attention is given to how practitioners make sense of the practice where they work. Within the practice, the focus is targeted at collaboration. I ask: What is characterising the practice in terms of meanings, materials and competences? What prerequisites for closer collaboration can be identified for the practice to meet the goal of increasing the cycle share of all travels? The analysis draws on practice theory and an integrative framework for collaborative dynamics. The data originate from interviews and observations with practitioners working with bicycle planning or mobility management. The results show that meaning, material and competence characterising the practice, contain prerequisites for closer collaboration in different ways. In relation to collaboration, the practitioners of the practice share meanings of making it easy and safe to cycle, benefits and challenges of closer collaboration. Material aspects related to collaboration concerns shared information and the workspace, which enable the practitioners to be updated on each other’s work. In addition, competences to ask and transmit high-quality knowledge characterise the practice in relation to closer collaboration. The study indicates that the practitioners’ relationship and shared aspirations are the main prerequisites for closer collaboration. Today, the practice in question contains little collaboration between practitioners with different work tasks, specifically bicycle planners and mobility managers. The study indicates that the practice’s capacity for joint action is limited, suggesting that a key management priority should be to enable practitioners, working with physical and social factors, to consider the knowledge they rely on and engage in closer collaboration

Prospects for Security on the European Continent. EU Diplomacy Paper 05/2015.

This collective EU Diplomacy Paper on relations between the North Atlantic Treaty Organisation (NATO) and the European Union (EU) consists of essays written by students of the EU International Relations and Diplomacy Studies programme at the College of Europe in the class on EU-NATO relations taught by Fulbright Professor Mark Sheetz in the academic year 2014-15. It seeks to provide a blueprint of what the near future of the transatlantic alliance and of the European security framework might look like. Special attention will be given to the possible effects of Finland joining NATO, Swedish-NATO relations, the question whether NATO should continue to exist at all, and finally the use of the Common Foreign and Security Policy (CFSP) and the Common Security and Defence Policy (CSDP) in relation with the transatlantic military alliance