Network evolution towards optimal dynamical performance

Understanding the mutual interdependence between the behavior of dynamical processes on networks and the underlying topologies promises new insight for a large class of empirical networks. We present a generic approach to investigate this relationship which is applicable to a wide class of dynamics, namely to evolve networks using a performance measure based on the whole spectrum of the dynamics' time evolution operator. As an example, we consider the graph Laplacian describing diffusion processes, and we evolve the network structure such that a given sub-diffusive behavior emerges.Comment: 5 pages, 4 figure

The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil

Moraxella catarrhalis is a ubiquitous human-specific bacterium commonly associated with upper and lower respiratory tract infections, including otitis media, sinusitis and chronic obstructive pulmonary disease. The bacterium uses an autotransporter protein UspA1 to target an important human cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Using X-ray crystallography, we show that the CEACAM1 receptor-binding region of UspA1 unusually consists of an extended, rod-like left-handed trimeric coiled-coil. Mutagenesis and binding studies of UspA1 and the N-domain of CEACAM1 have been used to delineate the interacting surfaces between ligand and receptor and guide assembly of the complex. However, solution scattering, molecular modelling and electron microscopy analyses all indicate that significant bending of the UspA1 coiled-coil stalk also occurs. This explains how UspA1 can engage CEACAM1 at a site far distant from its head group, permitting closer proximity of the respective cell surfaces during infection

Using Recursive Logistic Regression to Develop a Patient-reported Outcome in Non-cystic Fibrosis Bronchiectasis

Many patient reported outcomes for non-cystic fibrosis bronchiectasis are time-consuming self-report surveys such as the St. George's Respiratory Questionnaire. Using data from the EMBRACE multi-center RCT, we use recursive logistic regression to develop a new outcome that only requires responses to three simple questions about pulmonary symptoms (sputum volume, sputum purulence, and dyspnoea). The low response burden means that the outcome can be calculated for each day of follow-up in real-time. The new outcome is constructed such that it is a good predictor of event-based exacerbation, a sustained worsening of condition requiring treatment with antibiotics, and validated against self-reported quality of life

Automatic adjudication of symptom-based exacerbations in bronchiectasis patients treated with Azithromycin

The EMBRACE multi-center RCT evaluated the effect of azithromycin on frequency of event-based exacerbations (EBEs), lung function and health-related quality of life in adult patients with non-cystic fibrosis bronchiectasis. The treatment was effective in lowering the rate of EBEs relative to placebo (Wong et al., Lancet 2012 380(9842):660--7). An EBE, a binary outcome, is a sustained worsening of condition requiring treatment with antibiotics. Respiratory condition is defined, partly, in terms of daily sputum volume, sputum purulence, and dyspnoea, recorded daily in diaries kept by participants. Quality of life, as measured by the St. George's respiratory questionnaire, was also recorded in the diaries. Here, we use the daily diary entries to build a statistical model to estimate the probability that an EBE is imminent. A definition of symptom-based exacerbation (SBE) is developed by comparing the ROC curves of logistic regression models with EBE as the response and respiratory condition over different time windows as the predictors. Predictive accuracy is estimated using cross-validation. The new SBE definition is validated against self-reported quality of life

Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study

Background: In the assessment of severity in community acquired pneumonia (CAP), the modified British Thoracic Society (mBTS) rule identifies patients with severe pneumonia but not patients who might be suitable for home management. A multicentre study was conducted to derive and validate a practical severity assessment model for stratifying adults hospitalised with CAP into different management groups. Methods: Data from three prospective studies of CAP conducted in the UK, New Zealand, and the Netherlands were combined. A derivation cohort comprising 80% of the data was used to develop the model. Prognostic variables were identified using multiple logistic regression with 30 day mortality as the outcome measure. The final model was tested against the validation cohort. Results: 1068 patients were studied (mean age 64 years, 51.5% male, 30 day mortality 9%). Age ⩾65 years (OR 3.5, 95% CI 1.6 to 8.0) and albumin <30 g/dl (OR 4.7, 95% CI 2.5 to 8.7) were independently associated with mortality over and above the mBTS rule (OR 5.2, 95% CI 2.7 to 10). A six point score, one point for each of Confusion, Urea >7 mmol/l, Respiratory rate ⩾30/min, low systolic(<90 mm Hg) or diastolic (⩽60 mm Hg) Blood pressure), age ⩾65 years (CURB-65 score) based on information available at initial hospital assessment, enabled patients to be stratified according to increasing risk of mortality: score 0, 0.7%; score 1, 3.2%; score 2, 3%; score 3, 17%; score 4, 41.5% and score 5, 57%. The validation cohort confirmed a similar pattern. Conclusions: A simple six point score based on confusion, urea, respiratory rate, blood pressure, and age can be used to stratify patients with CAP into different management groups

PV-Live. Auswertung satellitenbasierter und gemessener Solarstrahlungsdaten für PV-Hochrechnungen

Photovoltaik (PV) spielt heute eine tragende Rolle im Energiesystem. Mit einer installierten Photovoltaik-Leistung in Deutschland von aktuell rund 46 GW können an sonnigen Tagen mittags Spitzenwerte der Einspeisung von mehr als 50% der Last erreicht werden. Die Erzeugung von PV-Strom ist jedoch abhängig vom Sonnenstand und vom Wetter. Zuverlässige Hochrechnungen und Prognosen der PV-Einspeisung spielen eine wichtige Rolle, um auch bei hohen Anteilen von variablem Solarstrom im Netz eine kosteneffiziente und sichere Stromversorgung zu gewährleisten

Correlation of in situ mechanosensitive responses of the Moraxella catarrhalis adhesin UspA1 with fibronectin and receptor CEACAM1 binding

Bacterial cell surfaces are commonly decorated with a layer formed from multiple copies of adhesin proteins whose binding interactions initiate colonization and infection processes. In this study, we investigate the physical deformability of the UspA1 adhesin protein from Moraxella catarrhalis, a causative agent of middle-ear infections in humans. UspA1 binds a range of extracellular proteins including fibronectin, and the epithelial cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Electron microscopy indicates that unliganded UspA1 is densely packed at, and extends about 800 Å from, the Moraxella surface. Using a modified atomic force microscope, we show that the adhesive properties and thickness of the UspA1 layer at the cell surface varies on addition of either fibronectin or CEACAM1. This in situ analysis is then correlated with the molecular structure of UspA1. To provide an overall model for UspA1, we have determined crystal structures for two N-terminal fragments which are then combined with a previous structure of the CEACAM1-binding site. We show that the UspA1–fibronectin complex is formed between UspA1 head region and the 13th type-III domain of fibronectin and, using X-ray scattering, that the complex involves an angular association between these two proteins. In combination with a previous study, which showed that the CEACAM1–UspA1 complex is distinctively bent in solution, we correlate these observations on isolated fragments of UspA1 with its in situ response on the cell surface. This study therefore provides a rare direct demonstration of protein conformational change at the cell surface