Simultaneous suppression of disturbing fields and localization of magnetic markers by means of multipole expansion

BACKGROUND: Magnetically marked capsules serve for the analysis of peristalsis and throughput times within the intestinal tract. Moreover, they can be used for the targeted disposal of drugs. The capsules get localized in time by field measurements with a superconducting quantum interference device (SQUID) magnetometer array. Here it is important to ensure an online localization with high speed and high suppression of disturbing fields. In this article we use multipole expansions for the simultaneous localization and suppression of disturbing fields. METHODS: We expand the measurement data in terms of inner and outer multipoles. Thereby we obtain directly a separation of marker field and outer disturbing fields. From the inner dipoles and quadrupoles we compute the magnetization and position of the capsule. The outer multipoles get eliminated. RESULTS: The localization goodness has been analyzed depending on the order of the multipoles used and depending on the systems noise level. We found upper limits of the noise level for the usage of certain multipole moments. Given a signal to noise ratio of 40 and utilizing inner dipoles and quadrupoles and outer dipoles, the method enables an accuracy of 5 mm with a speed of 10 localizations per second. CONCLUSION: The multipole localization is an effective method and is capable of online-tracking magnetic markers

Turbulenzstrukturen in hochbelasteten Transsonik-Verdichtergittern unter besonderer Berücksichtigung der Verdichtungsstoß-Grenzschicht-Interferenz

Zur Senkung der Herstellungs- und Wartungskosten von modernen Triebwerksverdichtern wird die Reduzierung der Schaufel- und Stufenanzahl bei gleich bleibender Gesamtleistung angestrebt. Dies kann nur durch eine gesteigerte aerodynamische Belastung in Form höherer Strömungsgeschwindigkeiten erreicht werden, die zu transsonischen Strömungsverhältnissen mit lokalen Überschallfeldern im Schaufelkanal führen. Die dabei auftretenden Verdichtungsstöße treten in Wechselwirkung mit der Profilgrenzschicht und beeinflussen maßgeblich die weitere Grenzschichtentwicklung und das Verlustverhalten, sodass eine gute Kenntnis der Strömungsvorgänge für die Auslegung wirtschaftlich arbeitender Transsonikverdichter erforderlich ist. Insbesondere ist im Auslegungsprozess eine zuverlässige numerische Strömungssimulation unverzichtbar, sodass eine Validierung der eingesetzten Modelle und Verfahren mit Hilfe geeigneter experimenteller Untersuchungen weiterhin erforderlich ist. Die vorliegende Arbeit gibt durch detaillierte experimentelle Untersuchungen an einem hochbelasteten ebenen Verdichtergitter mit großskaligen Abmessungen einen Einblick in die Mechanismen und Phänomene der Grenzschicht- und Turbulenzentwicklung bei laminarer Verdichtungsstoß-Grenzschicht-Interaktion. Durch den Einsatz des Hochgeschwindigkeits-Gitterwindkanals wird der Forderung nach turbomaschinenähnlichen Bedingungen Rechnung getragen. Unterschiedlichste Messtechniken und Verfahren ermöglichen die Erfassung mittlerer und zeitaufgelöster Strömungsgrößen. Schwerpunkt der Messungen sind die Grenzschichttraversierung an verschiedenen Schnitten stromab des Gebietes der Verdichtungsstoß-Grenzschicht-Interferenz mit der dreidimensionalen Hitzdrahtmesstechnik. Die experimentellen Untersuchungen verdeutlichen den Einfluss des durch die Verdichtungsstöße zusätzlich verstärkten Druckgradienten auf den Anstieg der turbulenten kinetischen Energie innerhalb der Grenzschicht. Die Lage der Verdichtungsstöße ist zeitlich nicht konstant. Begleitend zu den Messungen wurden Strömungssimulationen mit dem Navier-Stokes-Strömungslöser TRACE in Verbindung mit einem Ein-Gleichungsmodell nach Spalart-Allmaras sowie einem Zwei-Gleichungs-k-Omega-Turbulenzmodell durchgeführt. Die Rechnungen zeigen eine gute Übereinstimmung mit den experimentellen Resultaten hinsichtlich der Profilbelastung und der Verdichtungsstoßkonfiguration. Größere Unterschiede ergeben sich bei der Bestimmung der Grenzschichtprofile stromab des Verdichtungsstoßes bei hoher überkritischer Zuströmung, wofür auch die Stoßbewegung mitverantwortlich ist.The present work provides an insight into the mechanism and phenomena of boundary layer and turbulence development in a highly loaded linear transonic compressor cascade with laminar shock boundary layer interaction. Detailed experimental investigations using different measuring techniques were performed in the high-speed cascade wind tunnel at various Mach- and Reynolds numbers representative for real turbomachinery conditions. Numerical investigations were performed using the Navier Stokes flow solver TRACE in connection with an one equation turbulence model according to Spalart-Allmaras as well as a two-equation k-omega model

Improving experimental phases for strong reflections prior to density modification.

Experimental phasing of diffraction data from macromolecular crystals involves deriving phase probability distributions. These distributions are often bimodal, making their weighted average, the centroid phase, improbable, so that electron-density maps computed using centroid phases are often non-interpretable. Density modification brings in information about the characteristics of electron density in protein crystals. In successful cases, this allows a choice between the modes in the phase probability distributions, and the maps can cross the borderline between non-interpretable and interpretable. Based on the suggestions by Vekhter [Vekhter (2005), Acta Cryst. D61, 899-902], the impact of identifying optimized phases for a small number of strong reflections prior to the density-modification process was investigated while using the centroid phase as a starting point for the remaining reflections. A genetic algorithm was developed that optimizes the quality of such phases using the skewness of the density map as a target function. Phases optimized in this way are then used in density modification. In most of the tests, the resulting maps were of higher quality than maps generated from the original centroid phases. In one of the test cases, the new method sufficiently improved a marginal set of experimental SAD phases to enable successful map interpretation. A computer program, SISA, has been developed to apply this method for phase improvement in macromolecular crystallography

PhyloMap: an algorithm for visualizing relationships of large sequence data sets and its application to the influenza A virus genome

<p>Abstract</p> <p>Background</p> <p>Results of phylogenetic analysis are often visualized as phylogenetic trees. Such a tree can typically only include up to a few hundred sequences. When more than a few thousand sequences are to be included, analyzing the phylogenetic relationships among them becomes a challenging task. The recent frequent outbreaks of influenza A viruses have resulted in the rapid accumulation of corresponding genome sequences. Currently, there are more than 7500 influenza A virus genomes in the database. There are no efficient ways of representing this huge data set as a whole, thus preventing a further understanding of the diversity of the influenza A virus genome.</p> <p>Results</p> <p>Here we present a new algorithm, "PhyloMap", which combines ordination, vector quantization, and phylogenetic tree construction to give an elegant representation of a large sequence data set. The use of PhyloMap on influenza A virus genome sequences reveals the phylogenetic relationships of the internal genes that cannot be seen when only a subset of sequences are analyzed.</p> <p>Conclusions</p> <p>The application of PhyloMap to influenza A virus genome data shows that it is a robust algorithm for analyzing large sequence data sets. It utilizes the entire data set, minimizes bias, and provides intuitive visualization. PhyloMap is implemented in JAVA, and the source code is freely available at <url>http://www.biochem.uni-luebeck.de/public/software/phylomap.html</url></p

Irreversible inhibitors of the 3C protease of Coxsackie virus through templated assembly of protein-binding fragments

Small-molecule fragments binding to biomacromolecules can be starting points for the development of drugs, but are often difficult to detect due to low affinities. Here we present a strategy that identifies protein-binding fragments through their potential to induce the target-guided formation of covalently bound, irreversible enzyme inhibitors. A protein-binding nucleophile reacts reversibly with a bis-electrophilic warhead, thereby positioning the second electrophile in close proximity of the active site of a viral protease, resulting in the covalent de-activation of the enzyme. The concept is implemented for Coxsackie virus B3 3C protease, a pharmacological target against enteroviral infections. Using an aldehyde-epoxide as bis- electrophile, active fragment combinations are validated through measuring the protein inactivation rate and by detecting covalent protein modification in mass spectrometry. The structure of one enzyme–inhibitor complex is determined by X-ray crystallography. The presented warhead activation assay provides potent non-peptidic, broad-spectrum inhibitors of enteroviral proteases

The Effect of wake Turbulence Intensity on Transition in a Compressor Cascade

Direct numerical simulations of separating flow along a section at midspan of a low-pressure V103 compressor cascade with periodically incoming wakes were performed. By varying the strength of the wake, its influence on both boundary layer separation and bypass transition were examined. Due to the presence of small-scale three-dimensional fluctuations in the wakes, the flow along the pressure surface undergoes bypass transition. Only in the weak-wake case, the boundary layer reaches a nearly-separated state between impinging wakes. In all simulations, the flow along the suction surface was found to separate. In the simulation with the strong wakes, separation is intermittently suppressed as the periodically passing wakes managed to trigger turbulent spots upstream of the location of separation. As these turbulent spots convect downstream, they locally suppress separation. © 2014 Springer Science+Business Media Dordrecht

The SARS-coronavirus-host interactome

Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock

Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases

The genus Coronavirus contains about 25 species of coronaviruses (CoVs), which are important pathogens causing highly prevalent diseases and often severe or fatal in humans and animals. No licensed specific drugs are available to prevent their infection. Different host receptors for cellular entry, poorly conserved structural proteins (antigens), and the high mutation and recombination rates of CoVs pose a significant problem in the development of wide-spectrum anti-CoV drugs and vaccines. CoV main proteases (M(pro)s), which are key enzymes in viral gene expression and replication, were revealed to share a highly conservative substrate-recognition pocket by comparison of four crystal structures and a homology model representing all three genetic clusters of the genus Coronavirus. This conclusion was further supported by enzyme activity assays. Mechanism-based irreversible inhibitors were designed, based on this conserved structural region, and a uniform inhibition mechanism was elucidated from the structures of M(pro)-inhibitor complexes from severe acute respiratory syndrome-CoV and porcine transmissible gastroenteritis virus. A structure-assisted optimization program has yielded compounds with fast in vitro inactivation of multiple CoV M(pro)s, potent antiviral activity, and extremely low cellular toxicity in cell-based assays. Further modification could rapidly lead to the discovery of a single agent with clinical potential against existing and possible future emerging CoV-related diseases