571 research outputs found
Efficient, Near Complete and Often Sound Hybrid Dynamic Data Race Prediction (extended version)
Dynamic data race prediction aims to identify races based on a single program
run represented by a trace. The challenge is to remain efficient while being as
sound and as complete as possible. Efficient means a linear run-time as
otherwise the method unlikely scales for real-world programs. We introduce an
efficient, near complete and often sound dynamic data race prediction method
that combines the lockset method with several improvements made in the area of
happens-before methods. By near complete we mean that the method is complete in
theory but for efficiency reasons the implementation applies some optimizations
that may result in incompleteness. The method can be shown to be sound for two
threads but is unsound in general. We provide extensive experimental data that
shows that our method works well in practice.Comment: typos, appendi
Laws of the single logarithm for delayed sums of random fields
We extend a law of the single logarithm for delayed sums by Lai to delayed
sums of random fields. A law for subsequences, which also includes the
one-dimensional case, is obtained in passing.Comment: Published in at http://dx.doi.org/10.3150/07-BEJ103 the Bernoulli
(http://isi.cbs.nl/bernoulli/) by the International Statistical
Institute/Bernoulli Society (http://isi.cbs.nl/BS/bshome.htm
Dynamic Interaction and Manipulation of Web Resources
In this thesis we join methods for evaluating queries over interlinked resources via link traversal with approaches for the integration of data over interlinked schemata via reasoning. Our approach allows for the on-the-fly alignment and processing of dynamically retrieved data in a streaming fashion including incremental query answering. We go beyond the simple consumption of exposed information by enabling manipulations of remote resources in a parallel execution system
Evaluation of the Antiviral Effect of Polyglycerols Functionalized with Sialic Acid on Influenza Virus
Ein vielversprechender Ansatz zur Verhinderung von Infektionen mit Influenzavirus ist die kompetitive Inhibition der Virusanhaftung an die Wirtszellen durch Behinderung der Bindung des viralen Hemagglutinin (HA) an sialylierte Glykanrezeptoren. Allerdings erschwert die hohe Variabilität des HA die Entwicklung von universellen Sialinsäure (SA)-basierten Virostatika.
In dieser Arbeit wurde der antivirale Effekt von mit SA funktionalisierten Polyglycerolen (PGs) auf Influenza A Viren (IAV) evaluiert. SA-basierte PGs waren nur bei der Inhibition einer geringen Anzahl an IAV Stämmen effektiv. Um die molekulare Basis für diese Beschränkung zu ergründen, wurden mittels Serienpassagen IAV Mutanten selektiert, die gegen sialyliertes PG resistent waren. Es entwickelten sich drei unabhängige resistente Virusvarianten, die einen einfachen bzw. doppelten Aminosäuren-Austausch in der HA RBS aufwiesen. Durch Hemagglutinations-Elution, Einzel-Virus Kraft-Untersuchungen und Glykanarray Analysen konnte eine verringerte Rezeptorbindungsstabilität sowie ein verändertes Rezeptorbindeprofil für diese Virusvarianten gezeigt werden.
Interessanterweise wurden drei unterschiedliche Fälle von Virusbindung und Inhibition beobachtet: 1) Virales HA wurde vom PG gebunden und die Virusreplikation inhibiert, 2) virales HA wurde vom PG gebunden ohne Inhibition der Virusreplikation und 3) Virales HA wurde nicht vom PG gebunden und es gab keine Inhibition. Diese Ergebnisse suggerieren, dass es eine Mindestanforderung an die Affinität oder Avidität für eine effektive kompetitive Inhibition von HA gibt. Durch modifizierte PGs, die Sialyllaktose statt SA und einen Amidlinker enthielten, konnte das Potential von PGs als breite IAV Inhibitoren demonstriert werden. Zusammenfassend bieten die Ergebnisse dieser Arbeit wertvolle Einblicke in die Entwicklung von Resistenzen in IAV gegen Inhibitoren des HA-Attachment und in das strategische Design von sialylierten mutlivalenten Inhibitoren gegen IAV.A promising approach to block influenza virus infections is competitive inhibition of virus attachment to host cells by interfering with binding of the viral surface protein hemagglutinin (HA) to sialylated glycan receptors. However, the high structural and genetic variability of the viral HA has hampered the development of universal sialic acid (SA)-based antivirals.
Here, the antiviral effect of biocompatible Polyglycerols (PGs) functionalized with SA on influenza A virus (IAV) was evaluated. PG compounds were only effective at inhibiting a narrow spectrum of IAV strains. To elucidate the molecular basis for this restriction, PG-resistant IAV mutants were selected using serial passaging. Three independent resistant variants developed with single or double amino acid changes mapping to the HA RBS. By employing hemagglutination elution, single-virus force measurements and glycan array analyses, a reduced receptor binding stability as well as an altered receptor binding profile of mutant viruses was shown.
Intriguingly, three different cases of virus binding and inhibition were observed using Cy3-labeled compound: 1) viral HA was bound by the compound and resulted in inhibition of replication, 2) viral HA was bound by the compound but replication was not inhibited and 3) viral HA was not bound by the compound and no inhibition occurred. These results suggest that there is an affinity or avidity requirement for effective competitive inhibition of HA attachment. The suitability of PGs as IAV inhibitors with potential for broad activity was demonstrated by a modified PG incorporating sialyllactose instead of SA and an amide linkage covering an extended spectrum of inhibited IAV strains. Taken together, results described in this thesis provide valuable insights into the development of resistance against inhibitors of HA attachment in IAV and into the strategic design of sialylated, multivalent inhibitors aiming at broad activity against influenza viruses
Documentation of mail data collection (Version 1.0)
Transparency and reproducibility are key elements of good science, and this also holds for the process
of data collection in scientific surveys. To conduct analyses based on survey data collected by others,
researchers heavily depend on accurate documentation of all stages in the data collection process, either
for generating new scientific evidence or for reviewing previous research findings (e.g., in replication
studies). In this contribution, we propose documentation guidelines for mail surveys. In doing this,
we not only focus on mail-only surveys but also cover documentation guidelines for self-administered
mixed-mode surveys, thus taking into account their growing importance in the survey landscape
Linear combinations of iterated generalized Bernstein functions with an application to density estimation
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