Marathon: An open source software library for the analysis of Markov-Chain Monte Carlo algorithms

In this paper, we consider the Markov-Chain Monte Carlo (MCMC) approach for random sampling of combinatorial objects. The running time of such an algorithm depends on the total mixing time of the underlying Markov chain and is unknown in general. For some Markov chains, upper bounds on this total mixing time exist but are too large to be applicable in practice. We try to answer the question, whether the total mixing time is close to its upper bounds, or if there is a significant gap between them. In doing so, we present the software library marathon which is designed to support the analysis of MCMC based sampling algorithms. The main application of this library is to compute properties of so-called state graphs which represent the structure of Markov chains. We use marathon to investigate the quality of several bounding methods on four well-known Markov chains for sampling perfect matchings and bipartite graph realizations. In a set of experiments, we compute the total mixing time and several of its bounds for a large number of input instances. We find that the upper bound gained by the famous canonical path method is several magnitudes larger than the total mixing time and deteriorates with growing input size. In contrast, the spectral bound is found to be a precise approximation of the total mixing time

The Transitivity of Trust Problem in the Interaction of Android Applications

Mobile phones have developed into complex platforms with large numbers of installed applications and a wide range of sensitive data. Application security policies limit the permissions of each installed application. As applications may interact, restricting single applications may create a false sense of security for the end users while data may still leave the mobile phone through other applications. Instead, the information flow needs to be policed for the composite system of applications in a transparent and usable manner. In this paper, we propose to employ static analysis based on the software architecture and focused data flow analysis to scalably detect information flows between components. Specifically, we aim to reveal transitivity of trust problems in multi-component mobile platforms. We demonstrate the feasibility of our approach with Android applications, although the generalization of the analysis to similar composition-based architectures, such as Service-oriented Architecture, can also be explored in the future

The yeast expression system for recombinant glycosyltransferases

Glycosyltransferases are increasingly being used for in vitro synthesis of oligosaccharides. Since these enzymes are difficult to purify from natural sources, expression systems for soluble forms of the recombinant enzymes have been developed. This review focuses on the current state of development of yeast expression systems. Two yeast species have mainly been used, i.e. Saccharomyces cerevisiae and Pichia pastoris. Safety and ease of fermentation are well recognized for S. cerevisiae as a biotechnological expression system; however, even soluble forms of recombinant glycosyltransferases are not secreted. In some cases, hyperglycosylation may occur, P. pastoris, by contrast, secrete soluble orthoglycosylated forms to the supernatant where they can be recovered in a highly purified form. The review also covers some basic features of yeast fermentation and describes in some detail those glycosyltransferases that have successfully been expressed in yeasts. These include β1,4galactosyltransferase, α2,6sialyltransferase, α2,3sialyltransferase, α1,3fucosyltransferase III and VI and α1,2mannosyltransferase. Current efforts in introducing glycosylation systems of higher eukaryotes into yeasts are briefly addresse

Entwicklung von Verfahren zur Erzeugung anisotroper Mikrostrukturen und VEGF-Gradienten auf Collagen Typ I-Scaffolds für Zellkulturanwendungen

Die Versorgung mit Nährstoffen und Sauerstoff in artifiziellen, 3D Scaffolds für das Tissue Engineering ist Grundvoraussetzung für die Viabilität darin kultivierter Zellen. Die Kombination aus definierter Architektur und biomimetischer Zusammensetzung ist dabei entscheidend, sodass neben dem Stofftransport auch die Adhäsion, Proliferation, Migration und Morphologie von Zellen gesteuert werden können. Die Verwendung von Komponenten der nativen Extrazellulären Matrix, wie Collagen Typ I (COL I), als Scaffold-Material wird dafür als optimal angesehen. Jedoch stellt die Gestaltung der Architektur und Bereitstellung instruktiver Elemente zur Steuerung der Zellverhaltens bei COL I-basierten Scaffolds, aufgrund der mechanischen und biochemischen Eigenschaften des COL I, besondere Ansprüche an die Bearbeitungsverfahren. Ziel dieser Arbeit war es daher, Verfahren zur Ausstattung von modularisierbaren, COL I-basierten Membranen mit einer instruktiven biochemischen Zusammensetzung, Mikroarchitekturen als Basis für ein initiales vaskuläres System und Gradienten des Vascular Endothelial Growth Factors (VEGF) zu entwickeln. Diese Scaffolds sollten anschließend hinsichtlich der Beeinflussung des Wachstums, der Orientierung und der gerichteten Migration von humanen Endothelzellen aus der Nabelschnurvene (HUVEC) charakterisiert werden. COL I-Scaffolds konnten durch Plastic Compression in Membranform hergestellt und mit Fibronectin (FN) und Hyaluronsäure (HA, mit hohem Molekulargewicht) ausgestattet werden. Die Inkorporation von FN erhöhte die HUVEC-Proliferation, während die Proliferationsrate bei der verwendeten HA konstant blieb. Anisotrope Mikrostrukturen als Basis für ein vaskuläres System und zur HUVECOrientierung wurden durch einen 3-stufigen Prozess auf den COL I-Membranen erzeugt. Dabei wurde die Mikrostrukturübertragung durch mikrostrukturierte Polystyren-Stempel in einem Druckumformprozess realisiert. Die erhaltenen Mikrogräben mit Breiten von 10-40 µm beeinflussten die Orientierung der HUVEC deutlich. Für die Erzeugung von VEGF-Gradienten zur Steuerung der gerichteten Migration von HUVEC wurde ein Immersionsverfahren mit Hilfe der Modellproteine Bovines Serumalbumin und Hyaluronidase entwickelt. Dieses ermöglichte die Erzeugung eines linearen, graduellen Konzentrationsverlaufs der Modellproteine auf der Membranoberfläche. Der entwickelte Prozess konnte auf VEGF mit einem minimalen Gradientenprofil von 3,8-11,8 pg/mm² nach Immersion in 100 ng/mL VEGF-Lösung übertragen werden. Erste Versuche zur Induktion der HUVEC-Migration zeigten, dass ein erfolgreiches Gradientenprofil jedoch noch gefunden werden muss. Die erzeugten COL I-Membranen bilden eine gute Ausgangsposition für die Bereitstellung modularer, biomimetischer Tissue-Engineering-Scaffolds, mit initialer Vaskularisierung und zellinstruktiven Elementen. Außerdem besitzen sie das Potential, durch eine Vielzahl von Bio-Engineering-Methoden modifiziert und biochemisch den Anforderungen an das zelluläre Mikromilieu ausgestattet zu werden.The supply of nutrients and oxygen in artificial, three-dimensional scaffolds for tissue engineering is a basic prerequisite for the viability of cells cultivated therein. The combination of defined architecture and biomimetic composition are crucial in this context, so that besides the metabolic transport, the adhesion, proliferation, migration and morphology of cells can also be controlled. The use of native extracellular matrix components, such as collagen type I (COL I), as scaffold material is considered optimal for this purpose. However, designing the architecture and providing instructive elements to control cell behavior in COL I-based scaffolds poses special challenges to processing methods due to the mechanical and biochemical properties of COL I. Therefore, the aim of this work was to develop basic procedures to equip modularizable COL I-based membranes with instructive biochemical composition, microarchitectures as initial vascular system, and vascular endothelial growth factor (VEGF) gradients and to characterize the obtained scaffolds with respect to influencing human umbilical vein endothelial cell (HUVEC) growth, orientation, and migration. It was shown that COL I scaffolds can be prepared by Plastic Compression in membrane form and equipped with fibronectin (FN) and hyaluronic acid (HA, with high molecular weight). Incorporation of FN increased HUVEC proliferation, whereas the proliferation rate remained constant with the HA used. Anisotropic microstructures as a basis for a vascular system and for HUVEC orientation were generated by a 3-step process on the COL I membranes. In this process, the microstructure transfer was realized by microstructured polystyrene stamps in a pressure forming process. The obtained microtrenches with widths of 10-40 µm significantly affected the orientation of HUVEC. For the generation of VEGF gradients to control the directional migration of HUVEC, an immersion technique was developed using the model proteins bovine serum albumin and hyaluronidase. This allowed the generation of a linear, gradual concentration gradient of the model proteins on the membrane surface. The developed process could be applied to VEGF with a minimum gradient profile of 3.8-11.8 pg/mm² after immersion in 100 ng/mL VEGF solution. Initial experiments to induce HUVEC migration showed that a successful gradient profile still needs to be found, however. The generated COL I membranes provide a good starting point for the provision of modular, biomimetic tissue engineering scaffolds, with initial vascularization and cell-instructive elements. They also possess the potential to be modified by a variety of bioengineering methods and biochemically equipped to meet the requirements of the cellular microenvironment

Postoperative sepsis in infants below 6 months of age

Background: Sepsis is a threatening postoperative complication especially in small infants. Regarding the advances in perinatal medicine, its incidence is unknown to date. We aimed to investigate the incidence, risk factors, laboratory findings and outcome of postoperative sepsis in infants younger than 6 months old. Methods: We examined postoperative sepsis in babies below 6 months of age during a 4-year period at a tertiary pediatric institution. Results: The rate of postoperative sepsis was 6.9%. Laparotomy with enterotomy, thoracotomy and diaphragmatic hernia repair (P<0.05, respectively) as well as low postnatal age and long operation time (P<0.001, respectively) were correlated with the incidence of sepsis. Significant independent predictors for the development of sepsis were the presence of a central venous catheter and perioperative antibiotic treatment (P<0.001, respectively). Coagulase negative Staphylococci were the major infecting organism associated with postoperative sepsis, accounting for 53% of monomicrobial infections. Complete blood counts with differential were not different between infants with sepsis and controls, who had undergone the same surgical procedures. Outcome was favorable in all cases; however, the length of hospital stay was significantly longer in sepsis patients (P<0.05). Conclusions: Postoperative sepsis syndrome is a frequent complication in infants below 6 months of age and causes significant prolongation of hospital stay. Adequate prevention and therapeutic strategies warrant further prospective investigation

Geometric phases in superconducting qubits beyond the two-level-approximation

Geometric phases, which accompany the evolution of a quantum system and depend only on its trajectory in state space, are commonly studied in two-level systems. Here, however, we study the adiabatic geometric phase in a weakly anharmonic and strongly driven multi-level system, realised as a superconducting transmon-type circuit. We measure the contribution of the second excited state to the two-level geometric phase and find good agreement with theory treating higher energy levels perturbatively. By changing the evolution time, we confirm the independence of the geometric phase of time and explore the validity of the adiabatic approximation at the transition to the non-adiabatic regime.Comment: 5 pages, 3 figure

Accuracy of the Berger-Exner test for detecting third-order selection bias in randomised controlled trials: a simulation-based investigation

BACKGROUND: Randomised controlled trials (RCT) are highly influential upon medical decisions. Thus RCTs must not distort the truth. One threat to internal trial validity is the correct prediction of future allocations (selection bias). The Berger-Exner test detects such bias but has not been widely utilized in practice. One reason for this non-utilisation may be a lack of information regarding its test accuracy. The objective of this study is to assess the accuracy of the Berger-Exner test on the basis of relevant simulations for RCTs with dichotomous outcomes. METHODS: Simulated RCTs with various parameter settings were generated, using R software, and subjected to bias-free and selection bias scenarios. The effect size inflation due to bias was quantified. The test was applied in both scenarios and the pooled sensitivity and specificity, with 95% confidence intervals for alpha levels of 1%, 5%, and 20%, were computed. Summary ROC curves were generated and the relationships of parameters with test accuracy were explored. RESULTS: An effect size inflation of 71% - 99% was established. Test sensitivity was 1.00 (95% CI: 0.99 – 1.00) for alpha level 1%, 5%, and 20%; test specificity was 0.94 (95% CI: 0.93 – 0.96); 0.82 (95% CI: 0.80 – 0.84), and 0.56 (95% CI: 0.54 – 0.58) for alpha 1%, 5%, and 20%, respectively. Test accuracy was best with the maximal procedure used with a maximum tolerated imbalance (MTI) = 2 as the randomisation method at alpha 1%. CONCLUSIONS: The results of this simulation study suggest that the Berger-Exner test is generally accurate for identifying third-order selection bias. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2288-14-114) contains supplementary material, which is available to authorized users