144 research outputs found

    Further insights regarding oral bioavailability of peptides

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    The presentation introduces latest improvements on oral uptake of peptides. The concept of H-bond internalization, and an in-silico assessment on the basis of solvent accessible polar surface area (SAPSA) is explained. In this context, supercritical fluid chromatography (SFC), a recently described methodology to sense exposed polar groups, is compared to in-silico work, other assays, and in vivo results. Furthermore, evidence for 1st pass liver metabolism is provided on the basis of a hepatic portal vein study in rats

    Construction and Molecular-Dynamics Simulation of Calmodulin in the Extended and in a Bent Conformation

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    Analysis of sequence similarity and comparison of the three-dimensional (3D) structures of troponin C and calmodulin have revealed a sequence in the central helix of calmodulin with a high probability for bending. The three amino acids known to form a bend in the N-terminal portion of troponin C are also found in the central helix of calmodulin. The modelling of a bent calmodulin structure, using the dihedral angles of the three residues in the bend of troponin C as a 3D template, results in a conformation of calmodulin where the N- and C-terminal domains are able to form contacts. Dynamics simulations starting from the X-ray structure of calmodulin and from the modelled bent calmodulin were carried out to compare flexibility and correlated movements of Ca2+ in the binding loops. Both conformations of calmodulin remained stable during the period of simulation. In the simulation of calmodulin in the extended form, the motions of the Ca2+ atoms in the two domains (Ca(2+)1 and Ca(2+)2 in one domain, and Ca(2+)3 and Ca(2+)4 in the other) are correlated. In the simulation of the bent form, an additional correlation between the Ca atoms in the two different domains is observed. The results are compatible with the occurrence of a bent conformation of calmodulin in the presence of targets, and with increased Ca2+ affinity and cooperativity of the Ca2+-binding loops in the calmodulin-peptide complexes

    APPROACHES TO SYNTHETIC VACCINES - DESIGN OF EPITOPE-CONTAINING AMPHIPHILIC PEPTIDES MATCHING THE ANTIGENIC STRUCTURE IN THE NATIVE PROTEIN

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    Syftet Ă€r att identifiera de faktorer som pĂ„verkar utbudet av bostĂ€der, samt analysera vilka policies som verkningsfullt skulle kunna minska bostadsbristen. Detta genomfördes med en studie gjord av Aida Caldera och Åsa Johansson som utgĂ„ngspunkt. Faktorerna som undersöktes var priset pĂ„ bostĂ€der, byggkostnad, regleringar och geografi. Dessa analyserades sedan ur ett empiriskt och teoretiskt perspektiv. De ökade bostadspriserna hade en positiv pĂ„verkan pĂ„ investeringar i bostĂ€der medan de ökade byggkostnader hade en marginell negativ pĂ„verkan. Regleringar verkar ur teoretisk synpunkt och enligt tidigare forskning kunnat haft en negativ pĂ„verkan pĂ„ utbudet, men detta kunde inte faststĂ€llas med hjĂ€lp av regressionen. Geografiska förutsĂ€ttningar verkar inte begrĂ€nsa utbudet för Sverige som helhet, dock kan geografin lokalt begrĂ€nsa byggbar mark som i sin tur begrĂ€nsar utbudet. Utbudets priselasticitet visade sig vara 1,641 i regressionen, vilket innebĂ€r att den Ă€r elastisk. Det Ă€r en högre elasticitet jĂ€mfört med de tidigare studier som undersökts. Priselasticiteten skall dock tolkas med försiktighet dĂ„ det visat sig att priselasticiteten för utbudet i hög grad Ă€r ett lokalt fenomen och inte nödvĂ€ndigtvis Ă€r representativt för alla delar av landet. Policies som skulle kunna öka priselasticiteten för utbudet Ă€r lĂ€ttande av restriktioner kring bevarande av stadsbilden dĂ€r bland annat höjdrestriktioner och kulturskyddade byggnader ingĂ„r, men Ă€ven strandskydd och skogsskydd. Mer resurser till att minska processtiden för detaljplaner och överklaganden av bygglov, samt införande av avgift pĂ„ överklagande skulle Ă€ven höja priselasticiteten och utbudet. Ett slopat hyrestak skulle ge fler hyresrĂ€tter men inte öka utbudet av bostĂ€der totalt.The purpose of this paper is to identify the factors that affect investments in dwellings and to analyze which policies would be effective in reducing the housing shortage. This was conducted with a study made by Aida Caldera and Åsa Johansson as a reference paper. The factors examined were the price of housing, construction costs, regulations and geography. These were then analyzed from an empirical and theoretical perspective. The rise in housing prices had a positive impact on investment in dwellings, while the increased construction costs had a marginal negative impact. Regulations should from a theoretical perspective and according to previous research have had a negative impact on supply of dwellings, but this could not be determined in the regression. Geographical conditions do not seem to limit supply for Sweden as a whole, however, geography can locally limit constructible land, which in turn limits the supply. The price elasticity of supply proved to be 1,641 in the regression, which means that it is elastic. The found elasticity was higher compared to the previous studies investigated. However, the elasticity should be interpreted with caution since previous studies have shown that the price elasticity of supply is largely a local phenomenon and not necessarily representative for all local parts of a country. Policies that could increase the price elasticity for supply are easing of restrictions regarding the conservation of the cityscape which includes height restrictions and conservation of buildings with a cultural heritage, but also shoreland and forest protection. More resources to reduce the processing time for zoning plans and the appeals of building permits, as well as an introduction of a fee for appeal would also increase the price elasticity and the supply. A removed rent control would give more rental units but would not increase the total housing supply
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