Structural similarity between dry and wet sphere packings

The mechanical properties of granular materials change significantly in the presence of a wetting liquid which creates capillary bridges between the particles. Here we demonstrate, using X-ray tomographies of dry and wet sphere packings, that this change in mechanical properties is not accompanied by structural differences between the packings. We characterize the latter by the average numbers of contacts of each sphere $\langle Z\rangle$ and the shape isotropy $\langle \beta_0^{2,0} \rangle$ of the Voronoi cells of the particles. Additionally, we show that the number of liquid bridges per sphere $\langle B\rangle$ is approximately equal to $\langle Z\rangle + 2$, independent of the volume fraction of the packing. These findings will be helpful in guiding the development of both particle-based models and continuum mechanical descriptions of wet granular matter.Comment: slightly revised versio

Pomelo, a tool for computing Generic Set Voronoi Diagrams of Aspherical Particles of Arbitrary Shape

We describe the development of a new software tool, called "Pomelo", for the calculation of Set Voronoi diagrams. Voronoi diagrams are a spatial partition of the space around the particles into separate Voronoi cells, e.g. applicable to granular materials. A generalization of the conventional Voronoi diagram for points or monodisperse spheres is the Set Voronoi diagram, also known as navigational map or tessellation by zone of influence. In this construction, a Set Voronoi cell contains the volume that is closer to the surface of one particle than to the surface of any other particle. This is required for aspherical or polydisperse systems. Pomelo is designed to be easy to use and as generic as possible. It directly supports common particle shapes and offers a generic mode, which allows to deal with any type of particles that can be described mathematically. Pomelo can create output in different standard formats, which allows direct visualization and further processing. Finally, we describe three applications of the Set Voronoi code in granular and soft matter physics, namely the problem of packings of ellipsoidal particles with varying degrees of particle-particle friction, mechanical stable packings of tetrahedra and a model for liquid crystal systems of particles with shapes reminiscent of pearsComment: 4 pages, 9 figures, Submitted to Powders and Grains 201

MorphoCluster: Efficient Annotation of Plankton Images by Clustering

In this work, we present MorphoCluster, a software tool for data-driven, fast, and accurate annotation of large image data sets. While already having surpassed the annotation rate of human experts, volume and complexity of marine data will continue to increase in the coming years. Still, this data requires interpretation. MorphoCluster augments the human ability to discover patterns and perform object classification in large amounts of data by embedding unsupervised clustering in an interactive process. By aggregating similar images into clusters, our novel approach to image annotation increases consistency, multiplies the throughput of an annotator, and allows experts to adapt the granularity of their sorting scheme to the structure in the data. By sorting a set of 1.2 M objects into 280 data-driven classes in 71 h (16 k objects per hour), with 90% of these classes having a precision of 0.889 or higher. This shows that MorphoCluster is at the same time fast, accurate, and consistent; provides a fine-grained and data-driven classification; and enables novelty detection

Berechnung individualisierter Intraokularlinsen

1.1 Berechnung individualisierter Intraokularlinsen Fragestellungen: Ziel der Arbeit war die Entwicklung numerischer Ray-Tracing-Modelle für die Berechnung von Intraokularlinsen (IOL) zur Korrektur der individuellen Aberrationen des Auges (individualisierte IOL). Anhand dieser Modelle wurden IOL-Brechwerte berechnet, die Vorderflächen der individualisierten IOL angepasst, der Einfluss von IOL-Ausrichtungsfehlern untersucht, Messunsicherheiten und die Vorteile von individualisierten IOL gegenüber aberrationsneutralen IOL für Normalaugen und Keratokonusaugen diskutiert. Methoden: Für die Ray-Tracing-Modelle wurden Messungen der Hornhauttomographie und der Biometrie des jeweiligen Auges verwendet. Die Wiederholbarkeit der Hornhauttomographie wurde anhand von 34 Normalaugen analysiert. Die IOL wurde gemäß der Haigis-Formel positioniert. Die zugehörigen IOL-Konstanten wurden durch Minimierung des mittleren quadratischen (RMS) Fehlers der Vorhersage der postoperativen Refraktion ermittelt. Die Vorhersage des IOL-Brechwerts basierend auf der minimalen gewichteten RMS (wRMS) Spot-Größe in den Ray-Tracing-Modellen wurde an 50 Normalaugen mit der Vorhersage der Haigis-Formel verglichen. Individualisierte IOL wurden in den Ray- Tracing-Modellen für zwölf Normalaugen und zwölf Keratokonusaugen berechnet. Die Berechnung berücksichtigte vier Dezentrierungs-Szenarien, um den Einfluss von Ausrichtungsfehlern der IOL zu reduzieren. Eine Monte-Carlo-Analyse mit 500 Iterationen pro Auge wurde dazu verwenden, den Einfluss von IOL-Ausrichtungsfehlern auf die wRMS Spot-Größe zu untersuchen. Schließlich wurden die Parameter des Berechnungsmodells variiert, um die Messunsicherheiten zu analysieren. Ergebnisse: Die in azimutale Richtung gemittelte Wiederholbarkeit der Hornhauttomographie war, innerhalb eines Durchmessers von 8mm, 3;0 μm für die Hornhautvorder- fläche und 10;6 μm für die Hornhautrückfläche. Korrektur von Ausrichtungsfehlern reduzierte die Wiederholbarkeit auf 1;6 μm für die Hornhautvorderfläche und 7;4 μm für die Hornhautrückfläche. Die IOL-Brechwerte gemäß der Haigis-Formel und den Ray-Tracing-Modellen unterschieden sich um 0;16 dpt 0;56 dpt (Mittelwert Standardabweichung). Die individualisierten IOL reduzierten die mittlere wRMS Spot-Größe bei der Monte-Carlo-Analyse verglichen mit aberrationsneutralen IOL um etwa 6;8 μm für Normalaugen und 69;3 μm für Keratokonusaugen. IOL-Ausrichtungsfehler hatten einen stärkeren Einfluss auf die wRMS Spot-Größe mit individualisierten IOL als mit aberrationsneutralen IOL. Durch Einbeziehung von vier Dezentrierungs-Szenarien in die IOL-Berechnung konnte der Einfluss von IOL-Ausrichtungsfehlern minimal reduziert werden. Neben Ausrichtungsfehlern der IOL hatten Fluktuationen der Hornhautform und die Unsicherheit der Abschätzung der Position der Fovea den größten Einfluss auf die Berechnung der individualisierten IOL. Sie resultierten in Berechnungsunsicherheiten der IOL-Oberfläche von bis zu 7 μm. Schlussfolgerung: Die wRMS Spot-Größen konnten durch individualisierte IOL im Vergleich zur Standard-IOL deutlich reduziert werden. Die Verbesserung war für Keratokonusaugen besonders groß. Individualisierte IOL könnten ein erfolgversprechendes Werkzeug zur Aberrationskorrektur bei stabilem Keratokonus werden.1.2 Calculation of Custom Intraocular Lenses Purpose: Purpose of this thesis was to develop numerical ray tracing models that can be used to calculate intraocular lenses (IOLs) that correct the individual eye’s aberrations (custom IOLs). The ray tracing models were used to calculate IOL power, optimize anterior IOL surface shape for custom IOLs, evaluate the impact of IOL misalignment, discuss sources of uncertainty, and discuss the benefits of custom IOLs over aberration-neutral IOLs for normal and keratoconic eyes. Methods: The ray tracing models were set up based on the individual corneal tomography and biometry. The repeatability of corneal tomography was analyzed based on measurements on 34 normal eyes. The IOL was placed according to the Haigis formula whose IOL constants were optimized to minimize the root-mean-square (RMS) error of the prediction of the postoperative refraction. The IOL power was calculated based on the minimum weighted RMS (wRMS) spot-size for 50 normal eyes and compared with calculations of the Haigis formula. Custom IOLs were calculated for twelve normal and twelve keratoconic eyes. To reduce the impact of IOL decentration, four decentration scenarios were included in the calculations. Monte Carlo analysis with 500 iterations per eye was used to study the impact of IOL misalignement on the wRMS spot-size. Finally, the parameters of the calculation model were varied to analyze its uncertainties. Results: The repeatability of corneal tomography, averaged in azimuthal direction, was 3:0 μm for the anterior and 10:6 μm for the posterior cornea within the central 8mm diameter. After correction of misalignment, the repeatability improved to 1:6 μm for the anterior and 7:4 μm for the posterior cornea. The diffences between the IOL power according to the Haigis formula and the ray tracing models were 0:16D 0:56D (mean standard deviation). Custom IOLs reduced the average wRMS spot-size in the Monte Carlo analysis compared to aberration-neutral IOLs by approximately 6:8 μm in normal and 69:3 μm in keratoconic eyes. IOL misalignment had a larger impact on the wRMS spot-size for custom IOLs compared to aberration-neutral IOLs. Inclusion of four decentration scenarios in the calculation of the custom IOLs slightly reduced the impact of IOL misalignment. Aside from IOL-misalignment, fluctuations of corneal shape and the uncertainty of the estimation of the fovea’s position had the largest impact on the calculation of custom IOLs. They resulted in IOL-surface uncertainties of up to 7 μm. Conclusion: The wRMS spot-size was reduced with custom IOLs compared to Standard- IOLs. The improvement for keratoconic eyes was particularly large. Custom IOLs could become a promising tool for the correction of advanced aberrations associated with stable keratoconus

Development of an API production platform by using CRISPR/Cas9 on basis of a CHO cel line

Der Markt monoklonaler Antikörper (mAb) ist in Bezug auf Vielfalt und Produktionsmenge in den letzten Jahren stark gewachsen [1]. Um die daraus resultierende steigende Nachfrage nach mAbs bedienen zu können, ist es notwendig gute Produktionsplattformen, die den qualitativen Ansprüchen in ausreichender Quantität gerecht werden, für den Markt bereit zu stellen [2]. Diese Dissertation zeigt, wie mit Hilfe der clustered regularly interspaced short palindromic repeats (CRISPR) Methode, durch Ausschalten eines Gens der Wirtzelle, eine Produktionsplattform generiert werden kann, mit der es möglich ist therapeutische Proteine in guter Qualität und ausreichender Quantität herzustellen. Die Produktionsleistung der aus dieser Plattform entstandenen Zelllinien kann durch Zugabe von Methotrexat (MTX), einem reversiblen Inhibitor des Enzyms Dihydrofolatreduktase (DHFR), zu dem Zellkulturmedium, gesteigert werden. Die erreichten Produktivitäten der entstandenen Zellklone bewegten sich dabei im dreistelligen Milligramm-Bereich. Die der Produktionsplattform zugrundeliegende Zelllinie wurde genetisch durch den Einsatz der CRISPR-Cas9-Methode so verändert, dass sie nicht in der Lage ist das Enzym DHFR, das eine wichtige Rolle in der DNA Synthese spielt, zu exprimieren. Zelllinien, bei denen das DHFR-Gen ausgeschaltet wurde, können nur durch Zugabe von Hypoxanthin und Thymidin (HT) in das Zellkulturmedium proliferieren. Durch die Verwendung eines DHFR-Gens als Selektionsgen, das an ein gene of interst (GOI) gekoppelt ist, während einer Zelllinienentwicklung, erlangen die Zellen wieder die Fähigkeit ohne den Zusatz von HT zu überleben. Zusätzlich kann durch Zugabe von MTX zu der Zellkultur erreicht werden, dass sich das DHFR und somit auch das daran gekoppelte GOI amplifiziert. Dadurch kann die Produktivität der entstandenen Produktionszellen gesteigert werden. Es wurde gezeigt, dass unterschiedliche Transfektionsansätze bei der Produktivität stark variieren (3.2.4), was z.B. durch die Kopienzahl und den Integrationsort zustande kommen kann. Daher ist es für die Entwicklung eines Hochproduzentenzellklons zu empfehlen möglichst viele Transfektionsansätze durchzuführen und eine große Menge an Klonen zu screenen.The market for monoclonal antibodies (mAb) has grown massively in the past decades [1]. To serve the resultant increased demand of mAbs, it is necessary to provide production platforms which fulfill both the high quality and quantity objectives of active pharmaceutical ingredient (API) production [2]. This dissertation describes how a production platform was generated with help of the clustered regularly interspaced short palindromic repeats (CRISPR) method, with which it is possible to produce therapeutic proteins in a high quality and sufficient quantity. The productivity of production cell lines applying this production platform can be increased by adding methotrexate (MTX), a reversible inhibitor of the enzyme dihydrofolate reductase, to the cultivation media. The productivity of the cell clones achieved by this method lies in a three-digit milligram range. The cell line of the production platform was genetically modified by the CIRSPR/Cas9 method. The dihydrofolate reductase (DHFR) gene was knocked out to prevent cell proliferation without supplementation of the cell culture media with hypoxanthine and thymidine. Because of the usage of a DHFR gene as selection gene, which is linked to a gene of interest (GOI), during the cell line development, the cells regain the ability to grow without the supplement. Furthermore the productivity of these cells can be increased by adding MTX to the cell culture media, which causes a amplification of the DHFR gene and the linked GOI. The cell line development experiments showed that the productivity of different transfections lead to various productivities, which can be caused by different copy numbers and integration locations. It is therefore important to perform a large number of transfections to get a adequately high producing cell line. This also applies to the number of cell clones which are screened

Curvature driven motion of a bubble in a toroidal Hele-Shaw cell

We investigate the equilibrium properties of a single area-minimizing bubble trapped between two narrowly separated parallel curved plates. We begin with the case of a bubble trapped between concentric spherical plates. We develop a model which shows that the surface energy of the bubble is lower when confined between spherical plates than between flat plates. We confirm our findings by comparing against Surface Evolver simulations. We then derive a simple model for a bubble between arbitrarily curved parallel plates. The energy is found to be higher when the local Gaussian curvature of the plates is negative and lower when the curvature is positive. To check the validity of the model, we consider a bubble trapped between concentric tori. In the toroidal case, we find that the sensitivity of the bubble’s energy to the local curvature acts as a geometric potential capable of driving bubbles from regions with negative to positive curvature

The Development of Environmental Productivity: the Case of Danish Energy Plants

The Danish “Klima 2020” plan sets an ambitious target for the complete phasing-out of fossil fuels by 2050. The Danish energy sector currently accounts for 40% of national CO 2 emissions. Based on an extended Farrell input distance function that accounts for CO 2 as an undesirable output, we estimate the environmental productivity of individual generator units based on a panel data set for the period 1998 to 2011 that includes virtually all fuel-fired generator units in Denmark. We further decompose total environmental energy conversion productivity into conversion efficiency, best conversion practice ratio, and conversion scale efficiency and use a global Malmquist index to calculate the yearly changes. By applying time series clustering, we can identify high, middle, and low performance groups of generator units in a dynamic setting. Our results indicate that the sectoral productivity only slightly increased over the fourteen years. Furthermore, we find that there is no overall high achiever group, but that the ranking, although time consistent, varies between the different productivity measures. However, we identify steam turbines and combustion engines for combined heat and power production as potential high performers, while combustion engines that only produce electricity are clearly low performers

Generic Model Checking for Modal Fixpoint Logics in COOL-MC

We report on COOL-MC, a model checking tool for fixpoint logics that is parametric in the branching type of models (nondeterministic, game-based, probabilistic etc.) and in the next-step modalities used in formulae. The tool implements generic model checking algorithms developed in coalgebraic logic that are easily adapted to concrete instance logics. Apart from the standard modal $\mu$-calculus, COOL-MC currently supports alternating-time, graded, probabilistic and monotone variants of the $\mu$-calculus, but is also effortlessly extensible with new instance logics. The model checking process is realized by polynomial reductions to parity game solving, or, alternatively, by a local model checking algorithm that directly computes the extensions of formulae in a lazy fashion, thereby potentially avoiding the construction of the full parity game. We evaluate COOL-MC on informative benchmark sets.Comment: Full Version of VMCAI 2024 publicatio

Disfluencies in German adult- and infant-directed speech

Bellinghausen C, Betz S, Zahner K, Sasdrich A, Schröer M, Schröder B. Disfluencies in German adult- and infant-directed speech. In: Proceedings of SEFOS: 1st International Seminar on the Foundations of Speech. Breathing, Pausing and The Voice. 2019: 44-46