Shape: automatic conformation prediction of carbohydrates using a genetic algorithm

<p>Abstract</p> <p>Background</p> <p>Detailed experimental three dimensional structures of carbohydrates are often difficult to acquire. Molecular modelling and computational conformation prediction are therefore commonly used tools for three dimensional structure studies. Modelling procedures generally require significant training and computing resources, which is often impractical for most experimental chemists and biologists. <monospace>Shape</monospace> has been developed to improve the availability of modelling in this field.</p> <p>Results</p> <p>The <monospace>Shape</monospace> software package has been developed for simplicity of use and conformation prediction performance. A trivial user interface coupled to an efficient genetic algorithm conformation search makes it a powerful tool for automated modelling. Carbohydrates up to a few hundred atoms in size can be investigated on common computer hardware. It has been shown to perform well for the prediction of over four hundred bioactive oligosaccharides, as well as compare favourably with previously published studies on carbohydrate conformation prediction.</p> <p>Conclusion</p> <p>The <monospace>Shape</monospace> fully automated conformation prediction can be used by scientists who lack significant modelling training, and performs well on computing hardware such as laptops and desktops. It can also be deployed on computer clusters for increased capacity. The prediction accuracy under the default settings is good, as it agrees well with experimental data and previously published conformation prediction studies. This software is available both as open source and under commercial licenses.</p

EUROCarbDB: An open-access platform for glycoinformatics

The EUROCarbDB project is a design study for a technical framework, which provides sophisticated, freely accessible, open-source informatics tools and databases to support glycobiology and glycomic research. EUROCarbDB is a relational database containing glycan structures, their biological context and, when available, primary and interpreted analytical data from high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance experiments. Database content can be accessed via a web-based user interface. The database is complemented by a suite of glycoinformatics tools, specifically designed to assist the elucidation and submission of glycan structure and experimental data when used in conjunction with contemporary carbohydrate research workflows. All software tools and source code are licensed under the terms of the Lesser General Public License, and publicly contributed structures and data are freely accessible. The public test version of the web interface to the EUROCarbDB can be found at http://www.ebi.ac.uk/eurocarb

Human cerebral malaria and Plasmodium falciparum genotypes in Malawi

<p>Abstract</p> <p>Background</p> <p>Cerebral malaria, a severe form of <it>Plasmodium falciparum </it>infection, is an important cause of mortality in sub-Saharan African children. A Taqman 24 Single Nucleotide Polymorphisms (SNP) molecular barcode assay was developed for use in laboratory parasites which estimates genotype number and identifies the predominant genotype.</p> <p>Methods</p> <p>The 24 SNP assay was used to determine predominant genotypes in blood and tissues from autopsy and clinical patients with cerebral malaria.</p> <p>Results</p> <p>Single genotypes were shared between the peripheral blood, the brain, and other tissues of cerebral malaria patients, while malaria-infected patients who died of non-malarial causes had mixed genetic signatures in tissues examined. Children with retinopathy-positive cerebral malaria had significantly less complex infections than those without retinopathy (OR = 3.7, 95% CI [1.51-9.10]).The complexity of infections significantly decreased over the malaria season in retinopathy-positive patients compared to retinopathy-negative patients.</p> <p>Conclusions</p> <p>Cerebral malaria patients harbour a single or small set of predominant parasites; patients with incidental parasitaemia sustain infections involving diverse genotypes. Limited diversity in the peripheral blood of cerebral malaria patients and correlation with tissues supports peripheral blood samples as appropriate for genome-wide association studies of parasite determinants of pathogenicity.</p

Prediction of 3D structures of oligosaccharides. Methodological development and studies on saccharide antigens of interest for vaccine design

This thesis presents 3D structure predictions of five immunologically active surfacepolysaccharides of pathogens, which are of interest as targets for development of glycoconjugatevaccines. Furthermore it describes two methods which have been used for theconformational predictionsThe Shigella dysenteriae type 2 Oantigenwas predicted to form a compact helicalstructure with three repeating pentasaccharide units per turn. Favoured conformations werealso predicted for the Shigella dysenteriae type 4 and Escherichia coli O159 Oantigens,which have been reported to be crossreactivewith antibodies. We propose a commonepitope at the branch region of the repeating units. The conformation of the Burkholderiacepacia exopolysaccharidewas also predicted and was shown to form an extended fibre,with the three branches of the repeating unit packing tightly against the main chain.Furthermore, the 3D structure of a Schistosoma mansoni cercarial surface polysaccharidethat has been reported to be immunologically reactive, was predicted. The fucosyl brancheswrap tightly around the main chain, reducing the molecule's flexibility.The polysaccharides studied are of interest for development of glycoconjugatevaccines,and the results suggest that oligosaccharide 3D structure prediction can be an importanttool for rational vaccine design. These rapid predictions provide detailed information aboutpotential epitopes and the basis of immunological crossreactivityas well as conformationsof the polymer.Methods used for the conformation predictions were filtered systematic search and geneticalgorithm search. The filtered systematic search method thoroughly explores theconformational space below a set filter cutoffenergy. It can be used for structures up totetrasaccharide size with reasonable computational requirements. It is guaranteed to findthe global minimum energy conformation and the results can be used to generate adiabaticenergy maps, clearly describing the conformational restrictions and flexibility of theoligosaccharide. The genetic algorithm search is a very fast conformational search method.It scales well and is suitable for large oligosaccharides approximately up to the size ofdecasaccharides. It finds most local energy minima in the conformational space quickly, butis not guaranteed to find the global minimum conformation

Computational analysis of oligosaccharide conformations – methodological development, applied studies, and design of glycomimetics

Carbohydrates are the most abundant class of biomolecules. Besides their roles as structural elements and energy storage, they are involved in signaling and recognition processes. Their functions and activities depend on their preferred conformations. The software GLYGAL was developed to perform conformational studies of oligosaccharides using a genetic algorithm tailored for carbohydrates. The new method was applied to the highly branched exopolysaccharide of Burkholderia cepacia. The results show that its heptasaccharide repeating units assume a well defined conformation, stabilized by steric interactions between consecutive units. Furthermore, GLYGAL was used to calculate favorable conformations of histo-blood group antigens. The compounds were then fitted in the binding site of the surface protein of the norovirus VA387 strain and their binding affinity was estimated by molecular dynamics and Glide scoring, giving insights into the interaction patterns involved in norovirus infection. Finally, the mimetic properties of thioglycosidic and selenoglycosidic derivatives of the ABH antigens were studied by conformational and dockings studies, indicating potentially bioactive derivatives with increased resistance to hydrolysis. In conclusion, the computational methodologies developed during this study were successfully used, together with existing methods, for the investigation of natural carbohydrates and the rational design of glycomimetics

New concept for hook and leader for longline

Prosjektet «Nytt konsept for krok og forsyn til linefiske" ble igangsatt i 2020 og hadde som mål å (1) utvikle en krok som ikke korroderer og som er mer effektiv og har lengre levetid enn dagens krok, og (2) utvikle et forsyn som ikke avgir mikroplast, kan tilpasses ulike driftsformer og ha lengre levetid enn dagens forsyn. Prosjektet fikk en utfordrende start i koronapandemiåret 2020. Leveringsutfordringer fra underleverandører, men også materialespesifikke utfordringer i utviklingsarbeidet hos MF gjorde det nødvendig å avvike fra målsetningene tidlig i prosjektet. Det ble besluttet å fokusere på en hurtigkobling for krokskifte uten å skifte forsyn. Hurtigkoblinger mellom forsyn og krok hadde en positiv effekt på fangstrate av torsk sammenlignet med en blåkveitekrok med lignende, men ikke helt lik utforming. Fangstøkningen kan forklares utfra økt sviveleffekt fra hurtigkobling. Grunnet utfordringene ble fiskeforsøkene dreid mot testing av visuelle og taktile stimuli. Forsøk med lavenergi LED lys montert på linerygg økte fangstene (antall) av torsk og hyse med henholdsvis med ~75% og ~25% (ikke signifikant). Selvlysende hylser tredd over forsyn endret ikke fangsteffektivitet for torsk og hyse, hylsene var imidlertid ikke fulladet. Hylsene førte til lengdeavhengig seleksjon med høyere andel større fisk. Gummierte kroker førte til en 35% nedgang i hysefangstene, men ikke torskefangstene og forklares med ulik beiteadferd hos torsk og hyse. Prosjektet har frembrakt en rekke interessante innledende funn på visualisering, krokutforming og materialvalg med betydning for både fangsteffektivitet og seleksjon. Funnene kan ha betydning for utviklingsløpene på både krok, forsyn og linerygg både nasjonalt og internasjonalt.Nytt konsept for krok og forsyn til linefiskepublishedVersio

High-power impulse magnetron sputter deposition of TiB\u3csub\u3ex\u3c/sub\u3e thin films: Effects of pressure and growth temperature

© 2019 Elsevier Ltd Titanium boride, TiBx, thin films are grown in pure Ar discharges by high-power impulse magnetron sputtering (HiPIMS) from a compound TiB2 target. Film compositions are determined by time-of-flight elastic recoil detection analysis and Rutherford backscattering spectrometry as a function of deposition temperature (Ts = 25–900 °C) and Ar pressure (pAr = 0.67–2.67 Pa, 5–20 mTorr). For reference, films are also grown by direct current magnetron sputtering (dcMS) under similar conditions. The HiPIMS waveform, average target power PT, and resulting film compositions are strongly dependent not only on pAr, but also on Ts. At high pressures the effect of varying Ts on PT is minimal, while at lower pAr the effect of Ts is more pronounced, due to substrate-temperature-induced gas rarefaction. Films grown by HiPIMS at 0.67 Pa are understoichiometric, with B/Ti = 1.4–1.5, while at 2.67 Pa, B/Ti decreases from 2.4 to 1.4 as Ts increases from 25 to 900 °C. dcMS-deposited films are overstoichiometric (B/Ti ≃ 3) when grown at low pressures, and near-stoichiometric (B/Ti ≃ 1.9–2.2) for higher pAr. All experimental results are explained by differences in the ionization potentials of sputtered Ti and B atoms, together with pAr- and Ts -dependent gas-phase scattering