Development and validation of opioid ligand–receptor interaction models: The structural basis of mu vs. delta selectivity

Opioid receptor binding conformations for two structurally related, conformationally constrained tetrapeptides, JOM-6 (µ receptor selective) and JOM-13 (δ receptor selective), were deduced using conformational analysis of these ligands and analogs with additional conformational restrictions. Docking of these ligands in their binding conformations to opioid receptor structural models, based upon the published rhodopsin X-ray structure, implicates specific structural features of the µ and δ receptor ligand binding sites as forming the basis for the µ selectivity of JOM-6 and the δ selectivity of JOM-13. In particular, the presence of E229 in the µ receptor (in place of the corresponding D210 of the δ receptor) causes an adverse electrostatic interaction with C-terminal carboxylate-containing ligands, resulting in the observed preference of ligands with an uncharged C-terminus for the µ receptor. In addition, the requirement that the Phe 3 side chain of JOM-13 assume a gauche orientation for optimal δ binding, whereas the Phe 3 side chain of JOM-6 must be in a trans orientation for high-affinity µ binding can be largely attributed to the steric effect of replacement of L300 of the δ receptor by W318 of the µ receptor. Testing this hypothesis by examining the binding of JOM-6 and several of its key analogs with specific µ receptor mutants is described. Our initial results are consistent with the proposed ligand–receptor interaction models.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73528/1/j.1399-3011.2002.21061.x.pd

Experimental investigation of the performance of a fully cooled gas turbine vane with and without mainstream flow and experimental analysis supporting the redesign of a wind tunnel test section

textThis study focused on experimentally determining the cooling performance of a fully cooled, scaled-up model of a C3X turbine vane. The primary objective was to determine the differences in overall effectiveness in the presence and absence of a hot mainstream flowing over the vane. Overall effectiveness was measured using a thermally scaled matched Biot number vane with an impingement plate providing the internal cooling. This is the first study focused on investigating the effect of removing the mainstream flow and comparing the contour and laterally-averaged effectiveness data in support of the development of an assembly line thermal testing method. It was found that the proposed method of factory floor testing of turbine component cooling performance did not provide comparable information to traditional overall effectiveness test methods. A second experiment was performed in which the effect of altering the angle of attack of a flow into a passive turbulence generator was investigated. Measurements in the approach flow were taken using a single wire hot-wire anemometer. This study was the first to investigate the effects such a setup would have on fluctuating flow quantitates such as turbulence intensity and integral length scale rather than simply the mean quantities. It was found that both the downstream turbulence intensity and the turbulence integral length scale increase monotonically with approach flow incidence angle at a specified distance downstream of the turbulence generator.Mechanical Engineerin

Modification of the Phe 3 aromatic moiety in delta receptor-selective dermorphin/deltorphin-related tetrapeptides Effects on opioid receptor binding

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72346/1/j.1399-3011.1992.tb01449.x.pd

Baseline Study on Microplastics in ASEAN

Prosjektleder: France CollardThe ASEAN region has among the highest concentrations of plastic litter globally. The knowledge on microplastic pollution in that region is still limited and needs further investigation for policy implementation. To support the implementation of the Regional Action Plan for combatting marine debris, the proposed Regional ASEAN Baseline Study on Microplastics is intended as a summary report that examines existing studies, sources, knowledge gaps, projects and policies that pertain to microplastics in the ASEAN region. Microplastic pollution is unequally investigated among the 10 countries of the region, constituting a first major knowledge gap. In addition, studies often focused on the same environments or matrices, i.e. marine and freshwaters, beach sediment and marine organisms (mostly fish). Microplastic contamination in top predators, air, river sediment, terrestrial ecosystems (including organisms), and wastewater treatment plants are largely unknown. Modeling and experimental studies are also lacking, resulting in a lack of knowledge on the fate and impacts of microplastic contamination on species and ecosystems. These fields need to be further investigated to implement relevant and efficient mitigation measures.Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) GmbHpublishedVersio

The Power of ‘Know-Who’: Adaptation to Climate Change in a Changing Humanitarian Landscape in Isiolo, Kenya

This article examines adaptation to climate change in view of changing humanitarian approaches in Isiolo County, Kenya. While humanitarian actors are increasingly integrating climate change in their international and national-level strategies, we know less about how this plays out at sub-national levels, which is key to tracking whether and how short-term assistance can support long-term adaptation. The article suggests that increasing attention to resilience and adaptation among humanitarian actors may not lead to reduced vulnerability because resources tend to be captured through existing power structures, directed by who you know and your place in the social hierarchy. In turn, this sustains rather than challenges the marginalisation processes that cause vulnerability to climate shocks and stressors. The article highlights the important role of power and politics both in channelling resources and determining outcomes

Linearized embedding: A new metric matrix algorithm for calculating molecular conformations subject to geometric constraints

There are many methods in the literature for calculating conformations of a molecule subject to geometric constraints, such as those derived from two-dimensional NMR experiments. One of the most general ones is the EMBED algorithm, based on distance geometry, where all constraints except chirality are converted into upper and lower bounds on interatomic distances. Here we propose a variation on this where the molecule is assumed to have fixed bond lengths, vicinal bond angles and chiral centers; and these holonomic constraints are enforced separately from the experimental constraints by being built into the mathematical structure of the problem. The advantages of this approach are: (1) for molecules having large rigid groups of atoms, there are substantially fewer variables in the problem than all the atomic coordinates; (2) rigid groups achieve in the end more accurate local geometry (e.g., planar aromatic rings are truly planar, chiral centers always have their correct absolute chirality); (3) it is easier to detect inconsistencies between the holonomic and the experimental constraints; and (4) when generating a random sampling of conformers consistent with all constraints, the probability of achieving satisfactory structures tends to be greater.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38281/1/540100706_ftp.pd

Flow in knowledge intensive organizations

Masteroppgave i økonomi og administrasjon - Universitetet i Agder 200

At (gen)skabe forbindelser: Økocentriske medieringer

Human-nature connectedness is regarded as an important factor in relation to both pro-environmental behaviour and general well-being. However, within environmental psychology and nature education, digital media technologies are often regarded as direct causes of declining nature connectedness. On the basis of the assumption that media technologies are created to minimize distances of various kinds, the question of whether media technologies may as well be used to foster nature connectedness is being engaged. To that effect, different examples of the use of media technologies for (re)connecting humans with the rest of nature are discussed