Expensive multi-objective optimization of electromagnetic mixing in a liquid metal

This paper presents a novel trust-region method for the optimization of multiple expensive functions. We apply this method to a biobjective optimization problem in fluid mechanics, the optimal mixing of particles in a flow in a closed container. The three-dimensional time-dependent flows are driven by Lorentz forces that are generated by an oscillating permanent magnet located underneath the rectangular vessel. The rectangular magnet provides a spatially non-uniform magnetic field that is known analytically. The magnet oscillation creates a steady mean flow (steady streaming) similar to those observed from oscillating rigid bodies. In the optimization problem, randomly distributed mass-less particles are advected by the flow to achieve a homogeneous distribution (objective function 1) while keeping the work done to move the permanent magnet minimal (objective function 2). A single evaluation of these two objective functions may take more than two hours. For that reason, to save computational time, the proposed method uses interpolation models on trust-regions for finding descent directions. We show that, even for our significantly simplified model problem, the mixing patterns vary significantly with the control parameters, which justifies the use of improved optimization techniques and their further development

Adaptive Vermittlung digitalisierungsbezogener Kompetenzen in der Eingangsphase des Lehramtsstudiums

Dieser Beitrag beschreibt, wie neue Entwicklungsziele bezüglich digitalisierungsbezogener Kompetenzen von Lehrkräften an den Hochschulen so adressiert werden können, dass adaptiv auf heterogenes Vorwissen von Studienanfängeninnen eingegangen wird. Hierfür wird eine Qualifizierungsmaßname aus dem QLB-geförderten Entwicklungsprojekt CU2RVE an der Stiftung Universität Hildesheim (SUH) in seiner Konzeption vorgestellt. Diese besteht in einer Eingangsdiagnostik, mit der das individuelle Leistungsniveau bezüglich der sechs Kompetenzbereiche aus der KMK-Strategie zur Bildung in der digitalen Welt erfasst wird, und dem darauf aufbauenden, modularen Seminar "Digitalisierungsbezogene Basiskompetenzen". (DIPF/Orig.

Immunosenescence in choroidal neovascularization (CNV) — transcriptional profiling of naïve and CNV-associated retinal myeloid cells during aging

Immunosenescence is considered a possible factor in the development of age-related macular degeneration and choroidal neovascularization (CNV). However, age-related changes of myeloid cells (MCs), such as microglia and macrophages, in the healthy retina or during CNV formation are ill-defined. In this study, Cx3cr1-positive MCs were isolated by fluorescence-activated cell sorting from six-week (young) and two-year-old (old) Cx3cr1(GFP)(/+) mice, both during physiological aging and laser-induced CNV development. High-throughput RNA-sequencing was performed to define the age-dependent transcriptional differences in MCs during physiological aging and CNV development, complemented by immunohistochemical characterization and the quantification of MCs, as well as CNV size measurements. These analyses revealed that myeloid cells change their transcriptional profile during both aging and CNV development. In the steady state, senescent MCs demonstrated an upregulation of factors contributing to cell proliferation and chemotaxis, such as Cxcl13 and Cxcl14, as well as the downregulation of microglial signature genes. During CNV formation, aged myeloid cells revealed a significant upregulation of angiogenic factors such as Arg1 and Lrg1 concomitant with significantly enlarged CNV and an increased accumulation of MCs in aged mice in comparison to young mice. Future studies need to clarify whether this observation is an epiphenomenon or a causal relationship to determine the role of immunosenescence in CNV formation

Transcriptional and distributional profiling of microglia in retinal angiomatous proliferation

Macular neovascularization type 3, formerly known as retinal angiomatous proliferation (RAP), is a hallmark of age-related macular degeneration and is associated with an accumulation of myeloid cells, such as microglia (MG) and infiltrating blood-derived macrophages (MAC). However, the contribution of MG and MAC to the myeloid cell pool at RAP sites and their exact functions remain unknown. In this study, we combined a microglia-specific reporter mouse line with a mouse model for RAP to identify the contribution of MG and MAC to myeloid cell accumulation at RAP and determined the transcriptional profile of MG using RNA sequencing. We found that MG are the most abundant myeloid cell population around RAP, whereas MAC are rarely, if ever, associated with late stages of RAP. RNA sequencing of RAP-associated MG showed that differentially expressed genes mainly contribute to immune-associated processes, including chemotaxis and migration in early RAP and proliferative capacity in late RAP, which was confirmed by immunohistochemistry. Interestingly, MG upregulated only a few angiomodulatory factors, suggesting a rather low angiogenic potential. In summary, we showed that MG are the dominant myeloid cell population at RAP sites. Moreover, MG significantly altered their transcriptional profile during RAP formation, activating immune-associated processes and exhibiting enhanced proliferation, however, without showing substantial upregulation of angiomodulatory factors

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

Helicobacter pylori cag-Pathogenicity Island-Dependent Early Immunological Response Triggers Later Precancerous Gastric Changes in Mongolian Gerbils

Infection with Helicobacter pylori, carrying a functional cag type IV secretion system (cag-T4SS) to inject the Cytotoxin associated antigen (CagA) into gastric cells, is associated with an increased risk for severe gastric diseases in humans. Here we studied the pathomechanism of H. pylori and the role of the cag-pathogenicity island (cag-PAI) for the induction of gastric ulcer and precancerous conditions over time (2–64 weeks) using the Mongolian gerbil model. Animals were challenged with H. pylori B128 (WT), or an isogenic B128ΔcagY mutant-strain that produces CagA, but is unable to translocate it into gastric cells. H. pylori colonization density was quantified in antrum and corpus mucosa separately. Paraffin sections were graded for inflammation and histological changes verified by immunohistochemistry. Physiological and inflammatory markers were quantitated by RIA and RT-PCR, respectively. An early cag-T4SS-dependent inflammation of the corpus mucosa (4–8 weeks) occurred only in WT-infected animals, resulting in a severe active and chronic gastritis with a significant increase of proinflammatory cytokines, mucous gland metaplasia, and atrophy of the parietal cells. At late time points only WT-infected animals developed hypochlorhydria and hypergastrinemia in parallel to gastric ulcers, gastritis cystica profunda, and focal dysplasia. The early cag-PAI-dependent immunological response triggers later physiological and histopathological alterations towards gastric malignancies

Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer‐reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state‐of‐the‐art handbook for basic and clinical researchers.DFG, 389687267, Kompartimentalisierung, Aufrechterhaltung und Reaktivierung humaner Gedächtnis-T-Lymphozyten aus Knochenmark und peripherem BlutDFG, 80750187, SFB 841: Leberentzündungen: Infektion, Immunregulation und KonsequenzenEC/H2020/800924/EU/International Cancer Research Fellowships - 2/iCARE-2DFG, 252623821, Die Rolle von follikulären T-Helferzellen in T-Helferzell-Differenzierung, Funktion und PlastizitätDFG, 390873048, EXC 2151: ImmunoSensation2 - the immune sensory syste

Bewegungslernen und instruktionen : zur effektivitat ausfuhrungs- und effektbezogener aufmerksamkeitsfokussierungen

Efficacité des instructions pour l'apprentissage des mouvements complexes. Faible efficacité des instructions pour l'enseignement des facultés sportivo-motrices qui ont pour but la coordination des mouvements corporels (focalisation interne de l'attention); par contre les instructions qui attirent l'attention de l'apprenant sur l'effet du mouvement entraînent des progrès d'apprentissage beaucoup plus importants (focalisation externe de l'attention). Utilisation de la théorie du 'common coding' (Prinz 1990) pour expliquer ce phénomène

On the automated mapping of snow cover on glaciers and calculation of snow line altitudes from multi-temporal Landsat data

Mapping snow cover (SC) on glaciers at the end of the ablation period provides a possibility to rapidly obtain a proxy for their equilibrium line altitude (ELA) which in turn is a metric for the mass balance. Satellite determination of glacier snow cover, derived over large regions, can reveal its spatial variability and temporal trends. Accordingly, snow mapping on glaciers has been widely applied using several satellite sensors. However, as glacier ice originates from compressed snow, both have very similar spectral properties and standard methods to map snow struggle to distinguish snow on glaciers. Hence, most studies applied manual delineation of snow extent on glaciers. Here we present an automated tool, named ‘ASMAG’ (automated snow mapping on glaciers), to map SC on glaciers and derive the related snow line altitude (SLA) for individual glaciers using multi-temporal Landsat satellite imagery and a digital elevation model (DEM). The method has been developed using the example of the Ötztal Alps, where an evaluation of the method is possible using field-based observations of the annual equilibrium line altitude (ELA) and the accumulation area ratio (AAR) measured for three glaciers for more than 30 years. The tool automatically selects a threshold to map snow on glaciers and robustly calculates the SLA based on the frequency distribution of elevation bins with more than 50% SC. The accuracy of the SC mapping was about 90% and the SLA was determined successfully in 80% of all cases with a mean uncertainty of ±19 m. When cloud-free scenes close to the date of the highest snowline are available, a good to very good agreement of SC ratios (SCR)/SLA with field data of AAR/ELA are obtained, otherwise values are systematically higher/lower as useful images were often acquired too early in the summer season. However, glacier specific differences are still well captured. Snow mapping on glaciers is impeded by clouds and their shadows or when fresh snow is covering the glaciers, so that more frequent image acquisitions (as now provided by Sentinel-2) would improve results