Coupling FEM and CFD solvers for continuous casting process simulation using precice

The numerical investigation of continuous casting requires more than just one simulation technique. In continuous casting, liquid metal is continuously poured into a mould while the starting head is slowly moved downwards, which results in a growing metal ingot. Though, the ingot’s outer surface is solidified after the mould, its inside core is still a mixture of liquid and mushy phases. This mixture of physical states requires different numerical schemes to describe the constitutive behaviour and relation. While the liquid region is described in the Eulerian approach, the solid is well described in the Lagrangian approach. Commonly the finite volume method is chosen for the Eulerian and the finite element method for the Lagrangian perspective. Consequently, it is logical to combine a CFD solver with a FEM solver for an ideal numerical representation of the continuous casting process. The coupling of two different solvers communicating in two different programming languages - in the present work OpenFOAM and LS-DYNA - is not an easy task. However, preCICE enables the coupling of the different solvers with a minimum of intrusive functions. The present work deals with the first step towards the coupled simulation routine for the continuous casting process. A first basic simulation of a simple plate was setup consisting of OpenFOAM for the Eulerian approach and LS-DYNA for the Lagrangian approach. OpenFOAM calculates the temperature field due to time-dependent boundary conditions, while the mechanical LS-DYNA solver calculates resulting strains and stresses considering thermal strain. The aim of this simulation was to develop and test the preCICE adapter for LS-DYNA, as the adapter for OpenFOAM is already available and ready to use. The mapping techniques of preCICE did manage to achieve good energy conservation results. The first results showed a good correlation especially in the middle of the domain. The difference at the plates’ ends between the two different methods defined the next steps for the coupling

Vegetationsausstattung und Landschaftsstruktur kontinentaler Tieflandauen am Beispiel der unteren March

An der Marchgrenzstrecke zwischen der Slowakei und Österreich finden sich ausgedehnte kontinentale Tieflandauen von europäischer Bedeutung. Obwohl pflanzensoziologisch schon mehrfach bearbeitet, gibt es nach wie vor Kenntnislücken, insbesondere was den derzeitigen Zustand und die landschaftliche Einbindung der Altarmsysteme und ihrer Vegetation betrifft. Für zukünftige Schutzbemühungen und Adaptionen geplanter flussbaulicher Massnahmen waren neuartige Grundlagen notwendig, die auf einer synoptischen Betrachtung von Landschaft, Vegetation und Tierökologie aufbauen. Aus diesem Grund wurden die Vegetationsdaten mit Hilfe sogenannter Vegetationkomplexen erhoben. Dies resultierte in einer neuartigen Bewertung der Verlandungstendenzen der untersuchten Altwässer durch die Heranziehung des Indikatorpotentials der in den Vegetationskomplexen enthaltenen Pflanzengesellschaften

An S-FSCW Based Multi-Channel Reader System for Beamforming Applications using Surface Acoustic Wave Sensors

Interrogating multiple surface acoustic wave (SAW) sensors located within the same radar beam require techniques to separate the multiple superposing SAW sensor responses. The presented multi-channel reader features four parallel transceiver channels, which are based on the switched frequency-stepped continuous-wave principle and high-speed parallelized baseband electronics. Thus classical beamforming applications including angle of arrival measurement of single SAW tags and the angular separation of multiple SAW sensors are presented and compared to a multiple-input multiple-output (MIMO) approach. Due to the larger virtual array in the MIMO approach a larger aperture can be synthesized, which leads to significantly better angular separation results. The level analysis for the given system is verified by baseband-power measurements at different readout distances, considering the hardware parameters as well as the free-space propagation aspects. Finally measurements assess the maximum interrogation distance for the system

Pediatric Allergy and Immunology / DNA and mRNA vaccination against allergies

Allergen-specific immunotherapy, which is performed by subcutaneous injection or sublingual application of allergen extracts, represents an effective treatment against type I allergic diseases. However, due to the long duration and adverse reactions, only a minority of patients decides to undergo this treatment. Alternatively, early prophylactic intervention in young children has been proposed to stop the increase in patient numbers. Plasmid DNA and mRNA vaccines encoding allergens have been shown to induce T helper 1 as well as T regulatory responses, which modulate or counteract allergic T helper 2-biased reactions. With regard to prophylactic immunization, additional safety measurements are required. In contrast to crude extracts, genetic vaccines provide the allergen at high purity. Moreover, by targeting the encoded allergen to subcellular compartments for degradation, release of native allergen can be avoided. Due to inherent safety features, mRNA vaccines could be the candidates of choice for preventive allergy immunizations. The subtle priming of T helper 1 immunity induced by this vaccine type closely resembles responses of non-allergic individuals and-by boosting via natural allergen exposure-could suffice for long-term protection from type I allergy.W 1213(VLID)286547

Revisiting Glauconite Geochronology: Lessons Learned from In Situ Radiometric Dating of a Glauconite-Rich Cretaceous Shelfal Sequence

The scarcity of well-preserved and directly dateable sedimentary sequences is a major impediment to inferring the Earth’s paleo-environmental evolution. The authigenic mineral glauconite can potentially provide absolute stratigraphic ages for sedimentary sequences and constraints on paleo-depositional conditions. This requires improved approaches for measuring and interpreting glauconite formation ages. Here, glauconite from a Cretaceous shelfal sequence (Langenstein, northern Germany) was characterized using petrographical, geochemical (EMP), andmineralogical (XRD) screening methods before in situ Rb-Sr dating via LA-ICP-MS/MS. The obtained glauconite ages (~101 to 97 Ma) partly overlap with the depositional age of the Langenstein sequence (±3 Ma), but without the expected stratigraphic age progression, which we attribute to detrital and diagenetic illitic phase impurities inside the glauconites. Using a novel age deconvolution approach, which combines the new Rb-Sr dataset with published K-Ar ages, we recalculate the glauconite bulk ages to obtain stratigraphically significant ‘pure’ glauconite ages (~100 to 96 Ma). Thus, our results show that pristine ages can be preserved in mineralogically complex glauconite grains even under burial diagenetic conditions (T < 65 ◦C; <1500 m depth), confirming that glauconite could be a suitable archive for paleo-environmental reconstructions and direct sediment dating.Esther Scheiblhofer, Ulrike Moser, Stefan Löhr, Markus Wilmsen, Juraj Farkaš, Daniela Gallhofer, Alice Matsdotter Bäckström, Thomas Zack, and Andre Balderman

Laser‐facilitated epicutaneous immunotherapy with depigmented house dust mite extract alleviates allergic responses in a mouse model of allergic lung inflammation

Background Skin-based immunotherapy of type 1 allergies has recently been re-investigated as an alternative for subcutaneous injections. In the current study, we employed a mouse model of house dust mite (HDM)-induced lung inflammation to explore the potential of laser-facilitated epicutaneous allergen-specific treatment. Methods Mice were sensitized against native Dermatophagoides pteronyssinus extract and repeatedly treated by application of depigmented D pteronyssinus extract via laser-generated skin micropores or by subcutaneous injection with or without alum. Following aerosol challenges, lung function was determined by whole-body plethysmography and bronchoalveolar lavage fluid was analyzed for cellular composition and cytokine levels. HDM-specific IgG subclass antibodies were determined by ELISA. Serum as well as cell-bound IgE was measured by ELISA, rat basophil leukemia cell assay, and ex vivo using a basophil activation test, respectively. Cultured lymphocytes were analyzed for cytokine secretion profiles and cellular polarization by flow cytometry. Results Immunization of mice by subcutaneous injection or epicutaneous laser microporation induced comparable IgG antibody levels, but the latter preferentially induced regulatory T cells and in general downregulated T cell cytokine production. This effect was found to be a result of the laser treatment itself, independent from extract application. Epicutaneous treatment of sensitized animals led to induction of blocking IgG, and improvement of lung function, superior compared to the effects of subcutaneous therapy. During the whole therapy schedule, no local or systemic side effects occurred. Conclusion Allergen-specific immunotherapy with depigmented HDM extract via laser-generated skin micropores offers a safe and effective treatment option for HDM-induced allergy and lung inflammation

Journal of Immunology Research / Prophylactic mRNA vaccination against allergy confers long-term memory responses and persistent protection in mice

Recently, mRNA vaccines have been introduced as a safety-optimized alternative to plasmid DNA-based vaccines for protection against allergy. However, it remained unclear whether the short persistence of this vaccine type would limit memory responses and whether the protective immune response type would be maintained during recurrent exposure to allergen. We tested the duration of protective memory responses in mice vaccinated with mRNA encoding the grass pollen allergen Phl p 5 by challenging them with recombinant allergen, 3.5, 6, and 9 months after vaccination. In a second experiment, vaccinated mice were repeatedly challenged monthly with aerosolized allergen over a period of 7 months. Antibody and cytokine responses as well as lung inflammation and airway hyperresponsiveness were assessed. mRNA vaccination induced robust TH1 memory responses for at least 9 months. Vaccination efficiently suppressed TH2 cytokines, IgE responses, and lung eosinophilia. Protection was maintained after repeated exposure to aerosolized allergen and no TH1 associated pathology was observed. Lung function remained improved compared to nonvaccinated controls. Our data clearly indicate that mRNA vaccination against Phl p 5 induces robust, long-lived memory responses, which can be recalled by allergen exposure without side effects. mRNA vaccines fulfill the requirements for safe prophylactic vaccination without the need for booster immunizations.(VLID)179427

In silico design of Phl p 6 variants with altered Fold-Stability significantly impacts antigen processing, immunogenicity and immune polarization

Introduction: Understanding, which factors determine the immunogenicity and immune polarizing properties of proteins, is an important prerequisite for designing better vaccines and immunotherapeutics. While extrinsic immune modulatory factors such as pathogen associated molecular patterns are well-understood, far less is known about the contribution of protein inherent features. Protein fold-stability represents such an intrinsic feature contributing to immunogenicity and immune polarization by influencing the amount of peptide-MHC II complexes (pMHCII). Here, we investigated how modulation of the fold-stability of the grass pollen allergen Phl p 6 affects its ability to stimulate immune responses and T cell polarization. Methods: MAESTRO software was used for in silico prediction of stabilizing or destabilizing point mutations. Mutated proteins were expressed in E. coli, and their thermal stability and resistance to endolysosomal proteases was determined. Resulting peptides were analyzed by mass spectrometry. The structure of the most stable mutant protein was assessed by X-ray crystallography. We evaluated the capacity of the mutants to stimulate T cell proliferation in vitro, as well as antibody responses and T cell polarization in vivo in an adjuvant-free BALB/c mouse model. Results: In comparison to wild-type protein, stabilized or destabilized mutants displayed changes in thermal stability ranging from −5 to +14°. While highly stabilized mutants were degraded very slowly, destabilization led to faster proteolytic processing in vitro. This was confirmed in BMDCs, which processed and presented the immunodominant epitope from a destabilized mutant more efficiently compared to a highly stable mutant. In vivo, stabilization resulted in a shift in immune polarization from TH2 to TH1/TH17 as indicated by higher levels of IgG2a and increased secretion of TNF-α, IFN-γ, IL-17, and IL-21. Conclusion: MAESTRO software was very efficient in detecting single point mutations that increase or reduce fold-stability. Thermal stability correlated well with the speed of proteolytic degradation and presentation of peptides on the surface of dendritic cells in vitro. This change in processing kinetics significantly influenced the polarization of T cell responses in vivo. Modulating the fold-stability of proteins thus has the potential to optimize and polarize immune responses, which opens the door to more efficient design of molecular vaccines

Laser‐facilitated epicutaneous immunotherapy with hypoallergenic beta‐glucan neoglycoconjugates suppresses lung inflammation and avoids local side effects in a mouse model of allergic asthma

Background Allergen-specific immunotherapy via the skin targets a tissue rich in antigen-presenting cells, but can be associated with local and systemic side effects. Allergen-polysaccharide neoglycogonjugates increase immunization efficacy by targeting and activating dendritic cells via C-type lectin receptors and reduce side effects. Objective We investigated the immunogenicity, allergenicity, and therapeutic efficacy of laminarin-ovalbumin neoglycoconjugates (LamOVA). Methods The biological activity of LamOVA was characterized in vitro using bone marrow-derived dendritic cells. Immunogenicity and therapeutic efficacy were analyzed in BALB/c mice. Epicutaneous immunotherapy (EPIT) was performed using fractional infrared laser ablation to generate micropores in the skin, and the effects of LamOVA on blocking IgG, IgE, cellular composition of BAL, lung, and spleen, lung function, and T-cell polarization were assessed. Results Conjugation of laminarin to ovalbumin reduced its IgE binding capacity fivefold and increased its immunogenicity threefold in terms of IgG generation. EPIT with LamOVA induced significantly higher IgG levels than OVA, matching the levels induced by s.c. injection of OVA/alum (SCIT). EPIT was equally effective as SCIT in terms of blocking IgG induction and suppression of lung inflammation and airway hyperresponsiveness, but SCIT was associated with higher levels of therapy-induced IgE and TH2 cytokines. EPIT with LamOVA induced significantly lower local skin reactions during therapy compared to unconjugated OVA. Conclusion Conjugation of ovalbumin to laminarin increased its immunogenicity while at the same time reducing local side effects. LamOVA EPIT via laser-generated micropores is safe and equally effective compared to SCIT with alum, without the need for adjuvant

Accuracy Bounds and Measurements of a Contactless Permittivity Sensor for Gases Using Synchronized Low-Cost mm-Wave Frequency Modulated Continuous Wave Radar Transceivers

A primary concern in a multitude of industrial processes is the precise monitoring of gaseous substances to ensure proper operating conditions. However, many traditional technologies are not suitable for operation under harsh environmental conditions. Radar-based time-of-flight permittivity measurements have been proposed as alternative but suffer from high cost and limited accuracy in highly cluttered industrial plants. This paper examines the performance limits of low-cost frequency-modulated continuous-wave (FMCW) radar sensors for permittivity measurements. First, the accuracy limits are investigated theoretically and the Cramér-Rao lower bounds for time-of-flight based permittivity and concentration measurements are derived. In addition, Monte-Carlo simulations are carried out to validate the analytical solutions. The capabilities of the measurement concept are then demonstrated with different binary gas mixtures of Helium and Carbon Dioxide in air. A low-cost time-of-flight sensor based on two synchronized fully-integrated millimeter-wave (MMW) radar transceivers is developed and evaluated. A method to compensate systematic deviations caused by the measurement setup is proposed and implemented. The theoretical discussion underlines the necessity of exploiting the information contained in the signal phase to achieve the desired accuracy. Results of various permittivity and gas concentration measurements are in good accordance to reference sensors and measurements with a commercial vector network analyzer (VNA). In conclusion, the proposed radar-based low-cost sensor solution shows promising performance for the intended use in demanding industrial applications