TU Braunschweig: LeoPARD - Publications And Research Data
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Messungen der Wasseroberflächenauslenkungen und der bodennahen Geschwindigkeit über Muschelbank- und Austernriffsurrogaten, die regelmäßigen Wellen ausgesetzt sind
No full textThe bioinvasion of the Pacific oyster (Magallana gigas) in the Wadden Sea has led to a system shift of the biogenic structures. Formerly predominant native blue mussel (Mytilus edulis) beds have almost entirely transformed into oyster reefs formed by the Pacific oyster. This ecological shift has substantial implications for topographic roughness and wave-biogenic structure interactions. This dataset provides experimental data on the interactions of surrogate models of mussel beds and oyster reefs with waves, offering critical insights into the mechanisms of wave attenuation induced by these biogenic structures. The data were collected from controlled laboratory experiments in a 2D wave flume, where surrogate models of both biogenic structures were subjected to regular, non-breaking waves. The surrogate models, fabricated using particle bed 3D printing with Selective Cement Activation, replicate natural roughness at a geometric scale of 1:3. The experimental program included varying water depths (d = 0.40; 0.50; 0.60; 0.70; 0.80 m), mean incoming wave heights (Hm,in = 0.05; 0.10; 0.15; 0.20 m), and mean wave periods (Tm = 1.5; 2.0; 2.5; 3.0 s), reflecting realistic conditions in the Wadden Sea considering Froude similitude with a length scaling of 1:3. The dataset comprises time-histories of the water surface elevations, η, and near-bed instantaneous velocity components, ui,, vi, and wi, in x, y, and z directions, respectively, measured along the surrogate models and simultaneously collected reference measurements over a flat surface. This dataset is intended to support further research into the hyrodynamic-biogenic structure interactions and to inform the design of nature-based solutions for coastal protection
PhzF as a potential Pseudomonas pathoblocker target
Full text linkPseudomonas aeruginosa ist ein gram-negativer Krankheitserreger, der vor allem für immungeschwächte Patienten und im Krankenhausumfeld problematisch ist. Antimikrobielle Resistenzen gegen die bei einer Infektion eingesetzten Antibiotika erfordern neue Therapieansätze. Einer dieser Ansätze ist das Pathoblocker-Konzept. Dabei wird die Virulenz eines Krankheitserregers verringert, ohne das Bakterium abzutöten. Aufgrund ihres geringeren Selektionsdrucks kann eine verringerte Resistenzentwicklung gegen diese Pathoblocker erwartet werden. Eine mögliche Zielstruktur für Pathoblocker ist das Enzym PhzF, ein essentieller Katalysator der Phenazinbiosynthese von Pseudomonaden. Das Phenazin Pyocyanin agiert hierbei als Virulenzfaktor und ist aufgrund seiner Redoxaktivität für die Pathogenität von P. aeruginosa erforderlich. Vorherige Untersuchungen haben die Struktur von PhzF mit röntgenkristallographischen Methoden aufgeklärt und gezeigt, dass die Isomerase zwei verschiedene Konfigurationen annehmen kann: Eine offene apo-Konformation und eine geschlossene Konformation, bei der entweder das Substrat 2,3-Dihydro-3-hydroxyanthranilsäure (DHHA) oder das Substratanalogon 3-Hydroxyanthranilsäure (3-HAA) gebunden ist. Auf der Grundlage der Co-Kristallstruktur wurden zunächst 3-HAA-Analoga für die geschlossene Konformation entworfen und anschließend erworben oder synthetisiert. Die Bindung der Liganden an PhzF wurde mit einem nDSF- und einem FRET-Assay untersucht. Keine der untersuchten Verbindungen zeigte eine höhere Affinität zu PhzF als 3-HAA. Eine Co-Kristallstruktur von 3-Ethoxyanthranilsäure mit PhzF zeigte die räumlichen Einschränkungen der geschlossenen Konformation. Eine sinnvolle Weiterentwicklung dieser 3-HAA-Analoga erschien aufgrund dieses beschränkten Platzes zweifelhaft. Deswegen wurden mit einem virtuellen fragment-basierten Designansatz Liganden für die offene PhzF-Konformation entworfen. Von den entwickelten und synthetisierten 5-phenylsubstituierten Anthranilsäuren wurden erstmals Co-Kristallstrukturen mit der offenen Konformation des nativen PhzF aufgeklärt. Die Liganden zeigten einen aus dem Design nicht erwarteten Bindungsmodus. Die Affinität der 5-phenylsubstituierten Anthranilsäuren zu PhzF war wesentlich geringer als die von 3-HAA, die offene Konformation von PhzF bietet aber ausreichend Platz für die weitere Optimierung der Liganden. Keiner der entwickelten Liganden war in der Lage die Pyocyaninproduktion von P. aeruginosa zu verringern. Die negativ geladene Carbonsäurefunktion verhindert vermutlich die Aufnahme in die Bakterienzelle. Ein bioisosterer Austausch gegen eine Nitro- oder Amidgruppe oder die Maskierung der Carbonsäure als Methylester hatte ebenfalls keinen Einfluss auf die bakterielle Pyocyaninproduktion. Aus dem strukturbasierten PhzF-Ligandendesign dieser Arbeit wurden Details der PhzF-Bindetasche und Struktur-Aktivitätsbeziehungen der Liganden gewonnen, die eine rationale Grundlage bieten, die gefundenen Strukturen zu PhzF-Inhibitoren als Pathoblocker für P. aeruginosa weiterzuentwickeln.Pseudomonas aeruginosa is a gram-negative pathogen that is problematic for immunocompromized patients and in the hospital environment. Due to antimicrobial resistance against the antibiotics used to treat an infection new therapeutic approaches are required. One of these approaches is the pathoblocker concept – to reduce the virulence of a pathogen without killing it. Due to their lower selection pressure less development of resistance to these pathoblockers can be expected. A possible target structure for pathoblockers is PhzF, an essential enzyme of the phenazine biosynthesis of pseudomonads. The phenazine pyocyanin acts as a virulence factor and is required for the pathogenicity of P. aeruginosa due to its redox activity. Previous investigations have elucidated the structure of PhzF using X-ray crystallographic methods and showed that the isomerase can adopt two different conformations: An open apo conformation and a closed conformation in which either the substrate 2,3-dihydro-3-hydroxyanthranilic acid (DHHA) or the substrate analogue 3-hydroxyanthranilic acid (3-HAA) is bound. Based on the co-crystal structure, 3-HAA analogs were designed for the closed conformation and subsequently acquired or synthesized. The binding of the ligands to PhzF was investigated using an nDSF and a FRET assay. None of the investigated compounds bound more strongly to PhzF than 3-HAA. A co-crystal structure of 3-ethoxyanthranilic acid with PhzF showed the spatial constraints of the closed conformation. A meaningful further development of these 3-HAA analogs appeared doubtful because of this limited space. Therefore, a virtual fragment-based design approach was used to design ligands for the open PhzF conformation. Of the designed and synthesized 5-phenyl substituted anthranilic acids co-crystal structures with the open conformation of the native PhzF were elucidated for the first time. The ligands showed a binding mode not expected from the design. The affinity of the 5-phenyl-substituted anthranilic acids for PhzF was significantly lower than that of 3-HAA, but the open conformation of PhzF offers sufficient space to optimize the ligands further. None of the developed ligands was able to reduce the pyocyanin production of P. aeruginosa. The negatively charged carboxylic acid function presumably prevents uptake into the bacterial cell. A bioisosteric substitution such as a nitro or amide group or masking the carboxylic acid as a methyl ester also had no effect on the bacterial pyocyanin production. From the structure-based PhzF ligand design of this work, details of the PhzF binding pocket and structure-activity relationships of the ligands were obtained. These provide a rational basis for the further design of PhzF inhibitors as pathoblockers for P. aeruginosa
Abschlussbericht: Quantenchemische Schwingungs-Exzitonmodelle für Biomoleküle
Full text linkVibrational spectroscopy can provide insights into fast processes occurring during protein folding and in disordered or unfolded proteins. In this project, we have developed efficient computational methods for reliably predicting vibrational spectra of biomolecular systems, in particular for two-dimensional infrared (2D-IR) and vibrational Raman optical activity (ROA) spectroscopy of conformationally flexible polypeptides and proteins. The key idea of all these developments is the use of localized vibrational modes as starting point. In this project, we have (a) further developed efficient L-VSCF/L-VCI methods for the calculation of anharmonic vibrational spectra, (b) explored the use of localized modes for constructing efficient vibrational exciton models from quantum-chemical calculations, and (c) pursued the calculation of ROA and 2D-IR spectra based on these novel methods. Specifically, we have (a) performed the first L-VSCF/L-VCI calculation of the anharmonic ROA spectrum of a system as large as (Ala)20, which revealed that anharmonicities do not alter ROA band shapes significantly, (b) performed the first quantum-chemical calculations of 2D-IR spectra of polypeptides, and made the first predictions for 2D-IR spectra in the extended amide III region. The developments made in this project open the door to large-scale computational studies of advanced vibrational spectroscopy for realistic models of biomolecular systems.Schwingungsspektroskopie kann Einblicke in schnelle Prozesse während der Proteinfaltung und in ungeordneten oder entfalteten Proteinen bieten. In diesem Projekt haben wir effiziente Berechnungsmethoden fürr die zuverlässige Vorhersage von Schwingungsspektren biomolekularer Systeme entwickelt, insbesondere für die zweidimensionale Infrarot-Spektroskopie (2D-IR) und Raman optische Aktivitäts-(ROA)-Spektroskopie von konformationell flexiblen Polypeptiden und Proteinen. Die Kernidee all dieser Entwicklungen ist die Verwendung von lokalisierten Schwingungsmoden als Ausgangspunkt. In diesem Projekt haben wir (a) effiziente L-VSCF/L-VCI-Methoden für die Berechnung von anharmonischen Schwingungsspektren weiterentwickelt, (b) die Verwendung lokalisierter Moden zur Konstruktion effizienter Schwingungs-Exzitonenmodelle aus quantenchemischen Berechnungen exploriert und (c) die Berechnung von ROA- und 2D-IR-Spektren auf der Grundlage dieser neuen Methoden verfolgt. Im Einzelnen haben wir (a) die erste L-VSCF/L-VCI-Berechnung des anharmonischen ROA-Spektrums eines Systems mit der Größe von (Ala)20 durchgeführt, wobei sich zeigte, dass Anharmonizitäten die ROA-Bandenformen nicht wesentlich verändern, (b) die ersten quantenchemischen Berechnungen der 2D-IR-Spektren von Polypeptiden durchgeführt und dabei die ersten Vorhersagen für 2D-IR-Spektren in der erweiterten Amid III-Region gemacht. Die in diesem Projekt durchgefuhrten Entwicklungen öffnen die Tür zu groß angelegten Berechnungen von fortgeschrittenen Schwingungsspektroskopien für realistische Modelle von biomolekularen Systemen
Cross-moment reduction in multi-moment matching
Full text linkThis thesis discusses the realisation of cross-moment reduction respectively multi-moment vector reduction in multimoment matching model order reduction against the background of a generic vibroacoustic model to enhance the method’s computational efficiency. In order to reduce the number of multi-moment vectors, which is connected to the number of model parameters, non-influential model parameters are identified via sensitivity analysis by Morris screening and Sobol analysis. The sensitivity analysis enables multi-moment vector reduction based on two working principles: general multi-moment vector reduction and specific multi-moment vector reduction. In the case of general multi-moment vector reduction, the expansion points describing the non-influential parameters’ variation are deleted, and, therefore, also the respective local projection matrices. Then, during the construction of the global reduced-order model by concatenating the local reduced-order models’ projection matrices, fewer local projection matrices are summarised into the global projection matrix; reducing the size of the global reduced order model and, thus increasing the method’s computational efficiency. Specific multi-moment vector reduction deletes the non-sensitive parmeters’ multi-moments from the Taylor series expansion at an expansion point, reducing the size of the local reduced-order models’ projection matrices, which are then concatenated into the global reduced order models’ projection matrix; again, enhancing the method’s computational efficiency due to the smaller size of the global reduced order model. Nonetheless, specific multi-moment vector reduction can only be applied to additive models, where a physical parameter equals a respective affine parameter in the affine decomposition of the system matrix. As the vibroacoustic system is non-additive, this thesis only examines the efficiency of general multi-moment vector reduction in multi-moment matching model order reduction for an undamped and damped vibroacoustic model. Finally, applying sensitivity analysis-based multi-moment matching model order reduction yields accurate parametric reduced order models that allow time-efficient computations. In the case of the undamped vibroacoustic model, the parametric reduced order model is competitive to this derived by standard multi-moment matching. For the application to the damped vibroacoustic model, the parametric reduced order models of the here-proposed method are superior to these computed with standard multi-moment matching as the standard method is unable to find an accurate parametric reduced order model that additionally allows time-efficient computations.In dieser Arbeit wird die Realisierung der Cross-moment-Reduktion, beziehungsweise, Multi-moment-Vektorreduktion in der Multi-moment-matching-basierten Modellordnungsreduktion vor dem Hintergrund eines generischen vibroakustischen Modells diskutiert, um die Recheneffizienz der Methode zu erhöhen. Eine Reduktion der Multi-moment-Vektoren, deren Anzahl mit der der Modellparameter verknüpft ist, wird mithilfe der Sensitivitätsanalysen Morris-Screening und Sobol-Analyse ermöglicht, die nicht-sensitive Modellparameter identifizieren. Die Sensitivitätsanalyse ermöglicht eine Reduktion der Multi-moment-Vektoren auf der Grundlage zweier Prinzipien: erstens, die allgemeine Reduktion der Multi-moment-Vektoren und zweitens, die spezifische Reduktion der Multi-moment-Vektoren. Bei der allgemeinen Multi-moment-Vektorreduktion werden die Expansionspunkte, die die Variation der nicht-sensitiven Parameter beschreiben, eliminiert, und damit auch die entsprechenden lokalen Projektionsmatrizen. Bei der Konstruktion des globalen Modells reduzierter Ordnung durch das Zusammenfügen der Projektionsmatrizen der lokalen Modelle reduzierter Ordnung werden so weniger lokale Projektionsmatrizen in der globalen Projektionsmatrix zusammengefasst, wodurch sich die Größe des globalen Modells reduzierter Ordnung verringert und die Recheneffizienz der Methode erhöht. Die spezifische Multi-moment-Vektorreduktion eliminiert die Multi-moments der nicht-sensitiven Parameter aus der Taylorreihenentwicklung an einem Expansionspunkt, was die Größe der Projektionsmatrizen der lokalen Modelle reduzierter Ordnung, die in die Projektionsmatrix des globalen Modells reduzierter Ordnung zusammengefasst werden, reduziert; dies erhöht wiederum die Recheneffizienz der Methode. Dennoch kann die spezifische Multi-moment-Vektorreduktion nur auf additive Modelle angewendet werden, bei denen ein physikalischer Parameter einem affinen Parameter der affinen Zerlegung der Systemmatrix entspricht. Da das vibroakustische System nicht additiv ist, wird in dieser Arbeit lediglich die Effizienz der allgemeinen Multi-moment-Vektorreduktion im Zuge der Multi-moment-matching-basierten Modellordnungsreduktion eines ungedämpftes und gedämpftes vibroakustisches Modell untersucht. Die Anwendung der auf der Sensitivitätsanalyse gestützen Multi-moment-matching-basierten Modellordnungsreduktion führt schließlich zu genauen parametrischen Modellen reduzierter Ordnung, die zeiteffiziente Berechnungen ermöglichen. Im Falle des ungedämpften vibroakustischen Modells ist das parametrische Modell reduzierter Ordnung konkurrenzfähig zu den Modellen reduzierter Ordnung, die mithilfe der herkömmlichen Multi-moment-matchingbasierten Modellordnungsreduktion berechnet werden. Bei der Anwendung auf das gedämpfte vibroakustische Modell sind die parametrischen Modelle reduzierter Ordnung der hier vorgeschlagenen Methode denen der herkömmlichen Methode überlegen, da die Standardmethode es nicht zulässt, ein genaues parametrisches Modell reduzierter Ordnung zu finden, das zudem zeiteffiziente Berechnungen erlaubt
Bed shear stress measurements in rough beds flows through sparse array of rigid emergent vegetation
No full textThis dataset provides the hydraulic boundary conditions, bed shear stress measurements, and double-averaged velocity measurements collected in flume experiments presented in the article "Bed shear stress model for rough bed flows through rigid emergent vegetation" (Aliaga & Aberle, 2025). This research characterizes bed shear stress and double-averaged flow characteristics in rough-bed flows covered with sparse arrays of rigid emergent cylinders. For this purpose, a novel adaptation of a shear plate was used to directly measure the bed shear stress acting at the canopy scale. These bed shear stress measurements were analyzed in relation to spatially averaged near-bed flow quantities for two array densities and a reference scenario without cylinders. The primary outcome of this research is the formulation of a bed shear stress model for rough-bed flows covered with rigid emergent vegetation
Relationship Between Area and Capacity of Hydrogen Refueling Stations and Derivation of Design Recommendations
Full text linkHydrogen plays a pivotal role in the decarbonization of the transport sector, necessitating the development of an adequate infrastructure in the form of hydrogen refueling stations (HRSs) to support hydrogen-powered vehicles. This study investigates the characteristics of hydrogen refueling stations to optimize their spatial design and provide key performance indicators for spatial efficiency. An overview of HRS components and their operational requirements is provided, alongside the classification of stations into distinct categories. The primary focus is on analyzing the relationship between station area and capacity. Utilizing spatial data from hydrogen stations, areas are determined through Google Maps analysis. Linear and power regression models are applied to quantify the relationship, with both models proving effective for capturing these dynamics. Based on the findings, spatially efficient design recommendations are proposed, supplemented by examples and a conceptual blueprint for optimized HRS construction, which are then summarized in a morphological design catalog
Auflagenerfüllung zur Akkreditierung des Studiengangs "Mathematik für Computational Sciences B.Sc." an der Technischen Universität Braunschweig
No full textBacterial membrane vesicles of Pseudomonas aeruginosa activate adenosine monophosphate-activated protein kinase signaling through inhibition of mitochondrial complex III
Full text linkBacterial membrane vesicles (BMVs) are secreted by many pathogenic bacteria and known to stimulate various host responses upon infection, thereby contributing to the pathogenicity of bacterial pathogens like Pseudomonas aeruginosa. While the effects of BMVs on host immune responses are well studied, little is known about their impact on cell metabolism and mitochondrial respiration. Here, we show that P. aeruginosa BMVs (i) reprogram cell metabolism of human lung cells, (ii) negatively affect mitochondrial respiration by (iii) specifically inhibiting complex III of the electron transport chain, leading to (iv) the activation of adenosine monophosphate-activated protein kinase (AMPK) signaling, which in turn results in (v) AMPK-dependent inhibition of global protein synthesis
A quality-by-design optimized LC method for navigating degradation kinetics and quantification of favipiravir in the presence of degradation products and manufacturing impurities
Full text linkEmergent viruses require effective treatment regimens, and the severe acute respiratory syndrome coronavirus-2 variants are still evolving. Favipiravir has emerged as an effective antiviral medication, especially after its popularity against COVID-2019. Despite its growing popularity, favipiravir has not yet been included in any pharmacopeia, and new dosage forms are being developed to improve its bioavailability for various infections. Therefore, studying its stability and developing methods capable of detecting its impurities and degradation products are essential. An isocratic high-performance liquid chromatography with photodiode array detection method was also designed using the Quality-by-Design approach and validated to determine favipiravir in presence of its hydrolytic degradation products, besides two major manufacturing impurities (namely, 3,6-dichloro pyrazine-2-carbonitrile and 6-fluoro-3-hydroxypyrazine-2-carbonitrile). The separation was achieved using a mobile phase of 25.0 mM phosphate buffer (pH 3.04): acetonitrile (92: 8, v/v) at a 1.0 mL min-1 flow rate. A Hypersil C18-BDS column (5.0 μm, 250.0 × 4.6 mm) was employed at room temperature and detection at 323.0 nm. The method had a linear range (5.0-100.0 µg mL-1) with a limit of detection and quantification of 0.51 and 1.54 µg mL-1. The drug's stability after forced degradation and at different pH levels was explored. Key results proved that FAV is most stable at pH 5.0, with calculated activation energies for the acidic and alkaline degradation processes being 53492.276 and 61896.899 kJ/mole, respectively. Moreover, the analysis of expired favipiravir tablets revealed the presence of the alkaline degradate, thereby demonstrating the efficacy of the method. The proposed method was evaluated for its greenness and blueness to demonstrate its ecological safety and practicality, scoring 0.65 in the Analytical Greenness (AGREE) metric and 85.00 on the Blue Applicability Grade Index (BAGI). It is the first sustainable method developed using the Quality-by-Design to profile favipiravir together with its degradation products and impurities simultaneously
Integrating remote sensing and deep learning for mapping urban housing wealth patterns
Full text linkDisaggregated data on housing and household economic conditions, particularly in developing countries, are often inaccessible to urban planners and local users, and conducting independent in-person surveys is prohibitively expensive. This impedes the development of precisely informed policies and targeted infrastructure investments, services, and incentives that are essential for fostering equitable and sustainable cities. Using Kigali and Musanze cities in Rwanda, this study introduces a novel deep learning-based approach that combines limited expert annotation, self-training, and instance image segmentation to generate building-level housing wealth data. Our experiment included state-of-the-art instance segmentation based on You Only Look Once (YOLO) and Masked-attention Mask Transformer (Mask2former) models. To check the validity of the predictions, over ten thousand samples from the official cadastre-based property taxation database were used to evaluate whether the observed patterns in actual property values align with the model’s predictions. Importantly, our method successfully detected approximately 70% of the existing buildings within their respective perceived wealth classes. Buildings predicted to belong to the high-wealth class exhibited mean property values 2.5-times higher in Kigali and 1.7-times higher in Musanze than those classified as low-wealth, thereby demonstrating the model’s ability to capture spatial patterns of housing wealth. The predicted maps reveal that housing wealth growth in urban cores parallels increased low-wealth housing in peri-urban areas, a likely result of gentrification, an insight that could inform more inclusive urban development strategies and support policies aimed at curbing urban sprawl. Our findings demonstrate that combining minimal expert labeling of economically meaningful visual features with self-training and multi-class instance segmentation offers an effective and rapid approach for generating precise planning data in contexts that lack detailed local census information. Moreover, while leveraging advanced deep networks, our methodology was designed to be simple and easily replicable