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Photon counting of extreme ultraviolet high harmonics using a superconducting nanowire single-photon detector
No full textLaser-driven light sources in the extreme ultraviolet range (EUV) enable nanoscopic imaging with unique label-free elemental contrast. However, to fully exploit the unique properties of these new sources, novel detection schemes need to be developed. Here, we show in a proof-of-concept experiment that superconducting nanowire single-photon detectors (SNSPD) can be utilized to enable photon counting of a laser-driven EUV source based on high harmonic generation (HHG). These detectors are dark-count free and accommodate very high count rates—a perfect match for high repetition rate HHG sources. In addition to the advantages of SNSPDs for classical imaging applications with laser-driven EUV sources, the ability to count single photons paves the way for very promising applications in quantum optics and quantum imaging with high energetic radiation like, e.g., quantum ghost imaging with nanoscale resolution
Fast harmonic tetrahedral mesh optimization
No full textMesh optimization is essential to enable sufficient element quality for numerical methods such as the finite element method (FEM). Depending on the required accuracy and geometric detail, a mesh with many elements is necessary to resolve small-scale details. Sequential optimization of large meshes often imposes long run times. This is especially an issue for Delaunay-based methods. Recently, the notion of harmonic triangulations [1] was evaluated for tetrahedral meshes, revealing significantly faster run times than competing Delaunay-based methods. A crucial aspect for efficiency and high element quality is boundary treatment. We investigate directional derivatives for boundary treatment and massively parallel GPUs for mesh optimization. Parallel flipping achieves compelling speedups by up to 318×. We accelerate harmonic mesh optimization by 119× for boundary preservation and 78× for moving every boundary vertex, while producing superior mesh quality
Learning Generalized Nash Equilibria in a Class of Convex Games
No full textWe consider multiagent decision making where each agent optimizes its convex cost function subject to individual and coupling constraints. The constraint sets are compact convex subsets of a Euclidean space. To learn Nash equilibria, we propose a novel distributed payoff-based algorithm, where each agent uses information only about its cost value and the constraint value with its associated dual multiplier. We prove convergence of this algorithm to a Nash equilibrium, under the assumption that the game admits a strictly convex potential function. In the absence of coupling constraints, we prove convergence to Nash equilibria under significantly weaker assumptions, not requiring a potential function. Namely, strict monotonicity of the game mapping is sufficient for convergence. We also derive the convergence rate of the algorithm for strongly monotone game maps
GPU-Accelerated Solution of Many Small ODE Systems for High-Temperature Component Lifetime Modeling
No full textAccurate lifetime prediction of critical components in steam and gas turbines is essential for optimizing maintenance strategies and ensuring safe operation under demanding conditions. Traditional engineering methods, though quick, lack the flexibility and precision required for complex scenarios. Advanced continuum damage mechanics models, such as the Chaboche model, offer greater accuracy but are computationally intensive.
This thesis investigates the potential of GPU acceleration to significantly reduce the computational cost of lifetime estimation using the Chaboche model. By leveraging the parallel processing capabilities of GPUs, the study enables efficient simulation of numerous load cases and parameter configurations, addressing uncertainties inherent in such models. We evaluate the suitability of SUNDIALS, a state-of-the-art ODE solver, for GPU-accelerated simulations, highlighting its limitations. Simpler numerical methods, including the Forward Euler method, are also explored to balance accuracy and computational efficiency. Performance enhancements are achieved by optimizing data types and step sizes, improving the efficiency of both SUNDIALS and the Forward Euler method on GPU platforms.
The results demonstrate substantial computational speedups of 40 to 60 times with GPU-accelerated solvers compared to CPU-based implementations. Additionally, optimizing the simplified Chaboche model with tailored data types and step sizes yields a further 23% performance improvement without compromising accuracy. This research offers key insights into the effective application of GPU acceleration for lifetime prediction, contributing to more efficient and reliable design and maintenance practices for critical components in energy systems
Wechselwirkungen zwischen nanoskaligen Füllstoffen und Stabilisatoren in Polyolefin-Anwendungen
No full textIm Rahmen dieser Arbeit wurden diejenigen Wechselwirkungen zwischen Füllstoffen, Stabilisatoren und Polymeren in einem flammgeschützten Polyolefinkomposit untersucht, die zu einer Reduktion der Langzeitstabilität beitragen. Der Fokus lag dabei auf den Faktoren, die ein zusätzlich zu einem Metallhydroxid eingebrachtes Schichtsilikat mit sich bringt. Es konnte gezeigt werden, dass die Destabilisierung des Komposits primär ein oberflächengetriebenes Phänomen darstellt und daher die Anpassung der Grenzfläche sowie das Einstellen der Stärke von Stabilisator-Silikat-Wasserstoffbrückenbindungen effektive Stellschrauben zur Langzeitstabilisierung darstellen. Die Verwendung einer chemometrischen Methode erbrachte neue Erkenntnisse über Alterungsdynamiken verglichen mit klassischen Analysemethoden der Polymerdegradierung und konnte weiterhin genutzt werden, um ein Modell zur Versagensvorhersage von Polymerproben zu generieren
Genome Replication Progression and Epigenetic Regulation in Mammalian Cells
No full textAmong all mammalian cellular organelles, the nucleus gets special attention as it contains the genetic information of the cell, the DNA. This is also the site where all DNA-dependent functions, such as genome duplication prior to cell division, DNA transcription, and damage repair upon various DNA breakages undergo. The nucleus also contains the subcompartment, an assembly site for the ribosome, the nucleolus. Among all the DNA-templated events, genome duplication is the most eventful, involving a large array of proteins simultaneously unwinding and synthesizing a new pair of DNA at thousands of locations of the same long polymer, yet tightly regulated in time and space. It is an event on a scale hitherto undreamt of.
While the faithful reconstitution of cellular identity involves the accurate inheritance of epigenetics, the information that sits atop the genetic information, the dynamic nature of epigenetics also influences the chromatin structure and regulates various aspects of DNA-templated events, including genome replication programs. The progression of development also triggers changes in the epigenetic landscape, thereby influencing the replication program. During genome replication, the chromatin decondenses, the DNA unwinds, and new DNA is synthesized and rewrapped around the histone core. The spatio-temporal regulation of the replication program also ensures the faithful inheritance of the epigenetic nature, specifically the histone post-translational modifications. However, the intricate interplay between epigenetics and the genome replication program remains a mystery, awaiting further exploration.
The present work first sheds light on the developmental changes in genome replication programs, features of replication forks, and underlying chromatin dynamics in human cells. It also uncovered the change in replication time of less-studied tandem and interspersed repeats, which constitute a large chunk of the genome, using repli-FISH. As a prerequisite, a novel approach to analyze the repli-FISH was developed. A switch in the replication timing of ribosomal DNA and differential replication program of Alu, LINE1, and Centromere were observed. Interactions between genome replication machinery and RNA polymerase I responsible for rDNA transcription were observed in pluripotent stem cells. Overall, the study also complements and expands our understanding of the developmentally regulated genome replication program in human cells.
High-throughput image analysis was used to quantify the histone modification marks in different cell cycle phases to characterize the relationship between genome replication and epigenetics. Furthermore, the statistical tool nucim was used to map the dynamic localization of histone marks to different compaction classes with cell cycle and sub-S phase progression in pluripotent stem cells. Dynamic localization in constitutive heterochromatin and its replication timing regulation by H3K36me3 was unveiled. Furthermore, genome-wide dynamics of H3K27me3 and H3K4me3, which also mark the poised/bivalent chromatin in embryonic stem cells, unveiled a peculiar pattern. Using synthetic biology, the replication program was disrupted by localizing the constitutive heterochromatin next to nuclear lamin, and its effect on epigenetics was studied.
Furthermore, the earliest replication origins and their (epi)genetic/chromatin characteristics are explored to validate the Domino model of replication progression. The approach to finding the cells with the earliest origins is developed in living and fixed cells was established for a detailed exploration. The ribosomal DNA tandem repeat was discovered as one of the preferred locations to start the replication across mammalian cell lines/species. To investigate the genetic nature of these origins, methods to identify, collect, and amplify single-cell genomes linearly were established to measure the micro-copy number gain.
Finally, a model was presented describing the genome replication progression and interaction of epigenetic and replication programs
Structure of the Dispase Autolysis-inducing Protein from Streptomyces mobaraensis and Glutamine Cross-linking Sites for Transglutaminase
No full textTransglutaminase from Streptomyces mobaraensis (MTG) is an important enzyme for cross-linking and modifying proteins. An intrinsic substrate of MTG is the dispase autolysis-inducing protein (DAIP). The amino acid sequence of DAIP contains 5 potential glutamines and 10 lysines for MTG-mediated cross-linking. The aim of the study was to determine the structure and glutamine cross-linking sites of the first physiological MTG substrate. A production procedure was established in Escherichia coli BL21 (DE3) to obtain high yields of recombinant DAIP. DAIP variants were prepared by replacing four of five glutamines for asparagines in various combinations via site-directed mutagenesis. Incorporation of biotin cadaverine revealed a preference of MTG for the DAIP glutamines in the order of Gln-39 ≫ Gln-298 > Gln-345 ∼ Gln-65 ≫ Gln-144. In the structure of DAIP the preferred glutamines do cluster at the top of the seven-bladed β-propeller. This suggests a targeted cross-linking of DAIP by MTG that may occur after self-assembly in the bacterial cell wall. Based on our biochemical and structural data of the first physiological MTG substrate, we further provide novel insight into determinants of MTG-mediated modification, specificity, and efficiency
Spontaneous Isopeptide Bond Formation as a Powerful Tool for Engineering Site-Specific Antibody-Drug Conjugates
No full textSpontaneous isopeptide bond formation, a stabilizing posttranslational modification that can be found in gram-positive bacterial cell surface proteins, has previously been used to develop a peptide-peptide ligation technology that enables the polymerization of tagged-proteins catalyzed by SpyLigase. Here we adapted this technology to establish a novel modular antibody labeling approach which is based on isopeptide bond formation between two recognition peptides, SpyTag and KTag. Our labeling strategy allows the attachment of a reporting cargo of interest to an antibody scaffold by fusing it chemically to KTag, available via semi-automated solid-phase peptide synthesis (SPPS), while equipping the antibody with SpyTag. This strategy was successfully used to engineer site-specific antibody-drug conjugates (ADCs) that exhibit cytotoxicities in the subnanomolar range. Our approach may lead to a new class of antibody conjugates based on peptide-tags that have minimal effects on protein structure and function, thus expanding the toolbox of site-specific antibody conjugation
Extrem neutronenreicher Sauerstoffkern: Erstmalige Erzeugung von ²⁸O
No full textEinem internationalen Forschungsteam ist es gelungen, den neutronenreichsten Sauerstoff Kern ²⁸O mit 20 Neutronen an der Forschungsanlage RIKEN in Japan zu erzeugen. Dies gibt entscheidende Einblicke in die starke Wechselwirkung unter den neutronenreichsten Bedingungen, die im Labor erreicht werden können. Diese wichtigen Tests der starken Wechselwirkung erlauben es, verlässliche Vorhersagen für neutronenreiche Materie in Neutronensternen zu entwickeln
Need a Good Book about Privacy? Evaluating Dictionary-Based Corpus Query for Detecting the Topic of Privacy in Literary Texts
No full textThis paper evaluates the usefulness of querying Vasalou et al.’s Privacy
Dictionary (2011), a dictionary of 600+ words and phrases, in 131 canonical
English-language novels from the long 19th century. We evaluate the word
frequencies compared with a classification of the novels based on scholarly
attention to the topic of privacy in each particular text. We report evidence of
low- to low/medium strength of correlation between 3 of the 8 categories of
the Privacy Dictionary and this classification. As a final step, by identifying the
novels in our corpus which score highest in relative word frequency in these 3
categories, we suggest novels which have not yet received scholarly study on
the topic of privacy but which may be promising for such studies. The highest
scoring novel by our method, Maria Edgeworth’s Castle Rackrent (1800), seems
indeed to be highly concerned with the topic of privacy, which is discussed in
its author’s preface and opening pages