Oxidative protein folding in the mitochondrial intermembrane space

Disulfide bond formation is a crucial step for oxidative folding and necessary for the acquisition of a protein's native conformation. Introduction of disulfide bonds is catalyzed in specialized subcellular compartments and requires the coordinated action of specific enzymes. The intermembrane space of mitochondria has recently been found to harbor a dedicated machinery that promotes the oxidative folding of substrate proteins by shuttling disulfide bonds. The newly identified oxidative pathway consists of the redox-regulated receptor Mia40 and the sulfhydryl oxidase Erv1. Proteins destined to the intermembrane space are trapped by a disulfide relay mechanism that involves an electron cascade from the incoming substrate to Mia40, then on to Erv1, and finally to molecular oxygen via cytochrome c. This thiol–disulfide exchange mechanism is essential for the import and for maintaining the structural stability of the incoming precursors. In this review we describe the mechanistic parameters that define the interaction and oxidation of the substrate proteins in light of the recent publications in the mitochondrial oxidative folding field

A detection theoretical approach to digital communications using autoregressive process shift keying

I klassisk digital kommunikasjon overføres en bitstrøm gjennom en kanal ved å modulere parametrene til en deterministisk bærebølge. Noen kjente eksempler er amplitudemodulasjon (AM), frekvensmodulasjon (FM) og fasemodulasjon (PM). Mottakeren estimerer parametrene til det informasjonsbærende signalet og bruker en deteksjonsregel til å klassifisere den mottatte bølgeformen som en av flere mulige parametriske signaler. Konvensjonelle metoder gir ingen beskyttelse mot at ikke-autoriserte mottakere avlytter og dekoder signalet. Blant ferske metoder som tilbyr en viss beskyttelse mot avlytting finner vi såkalte spredt spektrum-teknikker og kaotiske digitale kodere. Slike teknikker krever nøyakig synkronisering mellom sender og mottaker. Selv små synkroniseringsfeil kan føre til store bitfeilrater hos mottakeren. Denne oppgaven har undersøkt et nytt konsept innen digital kommunikasjon, som er basert på å bruke realisasjoner av stokastiske prosesser som informasjonsbærende signaler. Teknikken har innebygd sikkerhet mot avlytting. Samtidig er det mulig å konstruere dekodere som er enklere enn de som brukes i spredt spektrum og kaotisk kommunikasjon. Målet med prosjektet er å undersøke noen fundamentale egenskaper ved den nye teknikken: 1) Hvordan kan vi finne et statistisk mål på avstand mellom de informasjonsbærende stokastiske prosessene? 2) Hvilken detektor skal vi bruke for å dekode informasjonssekvensen, og hvor god ytelse gir denne? 3) Hvordan skal vi velge de stokastiske prosessene

Behavior of E. coli ST131 regarding the acquisition of a blaOXA-48 encoding plasmid

Antimicrobial resistance has been a challenge ever since the discovery of antibiotics. The rising challenge of resistance has led to the increased use of last-resort antibiotics: carbapenems. It is predicted that a successful E. coli clone, ST131 is apt for the acquisition of carbapenem-resistance encoding plasmids. In this study, we aim to understand how E. coli ST131 respond to acquisition of carbapenemase-encoding plasmids p50579417_3_OXA-48 and pK71-77-1-NDM, also comparing the response to other common E. coli: ST69, ST73 and ST95. We therefore conducted conjugation and plasmid persistence assays for clinical strains of ST131, ST69, ST73 and ST95. Conjugation efficiency, relative fitness and the plasmid persistence were measured and then analyzed with statistical analyses to investigate difference among E. coli ST131 clades and between ST131 the other E. coli clones

Non-pharmacological Treatment of Atrial Fibrillation

In selected patients with atrial fibrillation and severe symptoms, non-pharmacological treatment may be an alternative or supplement to drug therapy. Atrioventricular nodal radiofrequency ablation (requires pacemaker implantation), or atrial pacing for sick sinus syndrome, are established treatment modalities. All other non-pharmacological therapies for atrial fibrillation are still experimental. After the Maze operation, atrial depolarization has to follow one specific path determined by surgical scars in the myocardium. This prevents new episodes of atrial fibrillation, but at a cost of perioperative morbidity and mortality. Catheter-based "Maze-like" radiofrequency ablation is technically difficult, and thrombo-embolic complications may occur. Paroxysmal atrial fibrillation sometimes is initiated by spontaneous depolarizations in a pulmonary vein inlet. Radio frequency ablation against such focal activity has been reported with high therapeutic success, but the results await confirmation from several centres. For ventricular rate control, most electrophysiologists presently prefer ablation to induce a complete atrioventricular conduction block (with pacemaker) rather than trying to modify conduction by incomplete block. Atrial or dual chamber pacing may prevent atrial fibrillation induced by bradycardia. It remains to confirm that biatrial or multisite right atrial pacing prevents atrial fibrillation more efficiently than ordinary right atrial pacing. An atrial defibrillator is able to diagnose and convert atrial fibrillation. The equipment is expensive, and therapy without sedation may be unpleasant beyond tolerability

Epidemiological, aetiological and prognostic aspects of canine primary bone cancer, with a view to its human counterpart

Osteosarcoma (OSA) is the most common histological subtype of primary bone cancer in both humans and dogs. The importance of this relatively rare malignancy in humans is underlined by the fact that it typically affects children and adolescents, constituting about 5% of paediatric cancers (<15 years (y) of age). Although a rare disease in the canine population as well, certain breeds of dogs have a lifetime risk approaching 10%, thereby affecting a large proportion of these dogs. Hence, OSA has a major impact on the health within such breeds. The overall incidence rate in canines outnumbers that of the human population, inspiring the use of dogs with naturally occurring OSA as models for its human counterpart. Furthermore, similar clinical and epidemiological features of this disease are seen in the 2 species. Knowledge regarding risk factors for developing OSA is scarce in both dogs and humans. A better understanding of the aetiology and pathogenesis could generate ideas for novel treatment options, and identifying markers for progression of the disease may help optimise individualised therapy.Osteosarkom (OSA) er den vanligste histologiske formen for primær benkreft hos både mennesker og hunder. Viktigheten av denne relativt sjeldne kreftformen understrekes av at den hovedsakelig rammer barn og ungdom; den utgjør omtrent 5 % av kreftsykdommene som rammer barn under 15 år. Osteosarkom er sjelden hos hunder også, men rammer opp til 10 % av hunder innen visse raser i løpet av livet. Sykdommen får derfor store konsekvenser for helsen til disse rasene. Alt i alt er OSA vanligere hos hund enn menneske, noe som har ført til bruk av hunder med naturlig forekomst av OSA som modeller for tilsvarende sykdom hos mennesker. Dette komparative aspektet styrkes av kliniske og epidemiologiske likheter ved denne kreftformen hos de to artene. Kunnskap om risikofaktorer for utviklingen av denne sykdommen er mangelfull hos både hund og menneske. En bedre forståelse av årsaksfaktorer for utvikling av OSA kan generere hypoteser som fører til nye behandlingsformer, samt identifisere markører som kan indikere progresjon av sykdommen og tilrettelegge for individuelle behandlingsprotokoller

Urinary and faecal N-methylhistamine concentrations do not serve as markers for mast cell activation or clinical disease activity in dogs with chronic enteropathies

This study sought to correlate faecal and urinary N-methylhistamine (NMH) concentrations with resting versus degranulated duodenal mast cell numbers in dogs with chronic enteropathies (CE), and investigate correlations between intestinal mast cell activation and clinical severity of disease as assessed by canine chronic enteropathy clinical activity index (CCECAI), and between urinary and faecal NMH concentrations, mast cell numbers, and histopathological scores. Twenty-eight dogs with CE were included. Duodenal biopsies were stained with haematoxylin and eosin (H&E), toluidine blue, and by immunohistochemical labelling for tryptase. Duodenal biopsies were assigned a histopathological severity score, and duodenal mast cell numbers were counted in five high-power fields after metachromatic and immunohistochemical staining. Faecal and urinary NMH concentrations were measured by gas chromatography–mass spectrometry

Analytical and experimental assessment of the connection in a CLT-Steel dissipating system

To achieve the long-term climate and energy goals set by the EU, the housing stock in Europe is in need of renovation. This thesis is part of a four-year long European project called e-SAFE: energy and Seismic AFfordable rEnovation solutions. The project aims to renovate existing buildings by considering different aspects, in particular the seismic retrofitting system called e-CLT. A CLT panel is attached to the exterior buildings and connected with an innovative friction connection, in order to provide energy dissipation and limit the damage to the building. Throughout this thesis, the focus will be on the friction connection. Five different designs of the friction connection were provided to be tested and analyzed. Each design has two versions with different bolt size. The goal of the design was to provide a stable and repeatable behavior with a predetermined slip friction force. The connections were analyzed using FEManalysis software as well as tested experimentally in a press.For å oppnå de langsiktige klima- og energimålene satt av EU, må bygningsmassen i Europa renoveres. Denne masteroppgaven er del av et fireårig europeisk prosjekt kalt e-SAFE: energy and Seismic AFfordable rEnovation solutions. Prosjektets mål er å rehabilitere eksisterende bygninger med fokus på forskjellige aspekter. Et viktig aspekt er rehabilitering av bygningers evne til å tåle jordskjelv med et system kalt e-CLT. Systemet består av en massivtreplate som monteres på utsiden av eksisterende bygninger med en innovativ friskjonsforbindelse. Dette systemet vil kunne dempe kreftene og begrense skadeomfanget på bygninger i et jordskjelv. Gjennom denne oppgaven er fokuset på friksjonsforbindelsen. Fem forskjellige design av friskjonsforbindelsen ble testet og analysert. Hvert design hadde to forskjellige versjoner med forskjellig boltestørrelse. Målet med forbindelsen var å oppnå en stabil og repetitiv oppførsel med en forhåndsbestemt glidekraft. Forbindelsen ble analysert med bruk av FEM-analyse og testet eksperimentelt i en presse.M-B

Ensemble Conformalized Quantile Regression for Probabilistic Time Series Forecasting

This article presents a novel probabilistic forecasting method called ensemble conformalized quantile regression (EnCQR). EnCQR constructs distribution-free and approximately marginally valid prediction intervals (PIs), which are suitable for nonstationary and heteroscedastic time series data. EnCQR can be applied on top of a generic forecasting model, including deep learning architectures. EnCQR exploits a bootstrap ensemble estimator, which enables the use of conformal predictors for time series by removing the requirement of data exchangeability. The ensemble learners are implemented as generic machine learning algorithms performing quantile regression (QR), which allow the length of the PIs to adapt to local variability in the data. In the experiments, we predict time series characterized by a different amount of heteroscedasticity. The results demonstrate that EnCQR outperforms models based only on QR or conformal prediction (CP), and it provides sharper, more informative, and valid PIs

Highly Designable Protein Structures and Inter Monomer Interactions

By exact computer enumeration and combinatorial methods, we have calculated the designability of proteins in a simple lattice H-P model for the protein folding problem. We show that if the strength of the non-additive part of the interaction potential becomes larger than a critical value, the degree of designability of structures will depend on the parameters of potential. We also show that the existence of a unique ground state is highly sensitive to mutation in certain sites.Comment: 14 pages, Latex file, 3 latex and 6 eps figures are include

Power Flow Balancing With Decentralized Graph Neural Networks

We propose an end-to-end framework based on a Graph Neural Network (GNN) to balance the power flows in energy grids. The balancing is framed as a supervised vertex regression task, where the GNN is trained to predict the current and power injections at each grid branch that yield a power flow balance. By representing the power grid as a line graph with branches as vertices, we can train a GNN that is accurate and robust to changes in topology. In addition, by using specialized GNN layers, we are able to build a very deep architecture that accounts for large neighborhoods on the graph, while implementing only localized operations. We perform three different experiments to evaluate: i) the benefits of using localized rather than global operations and the tendency of deep GNN models to oversmooth the quantities on the nodes; ii) the resilience to perturbations in the graph topology; and iii) the capability to train the model simultaneously on multiple grid topologies and the consequential improvement in generalization to new, unseen grids. The proposed framework is efficient and, compared to other solvers based on deep learning, is robust to perturbations not only to the physical quantities on the grid components, but also to the topology