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- Rekonstruktion (12)
- Replikation (12)
- Risikofaktor (12)
- Rotatorenmanschette (12)
- Ruthenium (12)
- SMN (12)
- SNP (12)
- Schule (12)
- Siliciumorganische Verbindungen (12)
- Spracherwerb (12)
- Sprachwissenschaft (12)
- Toll-like-Rezeptoren (12)
- Ubiquitin (12)
- Ultrakurzer Lichtimpuls (12)
- Validierung (12)
- Zelladhäsion (12)
- age (12)
- amygdala (12)
- biofabrication (12)
- blood–brain barrier (12)
- carbenes (12)
- catalysis (12)
- colorectal carcinoma (12)
- complications (12)
- database (12)
- dementia (12)
- drug delivery (12)
- dynamics (12)
- emotions (12)
- endothelium (12)
- enzyme replacement therapy (12)
- fear conditioning (12)
- head and neck cancer (12)
- lymphocytes (12)
- malignant hyperthermia (12)
- measles (12)
- meiosis (12)
- microarray (12)
- molecular beam epitaxy (12)
- monoclonal antibodies (12)
- neurology (12)
- neuropathy (12)
- optimization (12)
- pollen (12)
- polymers (12)
- proteomics (12)
- rats (12)
- recombination (12)
- review (12)
- screening (12)
- synaptic plasticity (12)
- systematic review (12)
- tinnitus (12)
- topological insulator (12)
- total knee arthroplasty (12)
- ubiquitin (12)
- ultrasound (12)
- vitamin D (12)
- vorsprachliche Entwicklung (12)
- zebrafish (12)
- ++ (11)
- 3D (11)
- Altern (11)
- Alzheimer’s disease (11)
- Anorexia nervosa (11)
- Antigen CD8 (11)
- Arabidopsis (11)
- B-Zelle (11)
- Bioisosterie (11)
- Biosynthese (11)
- Bioverfügbarkeit (11)
- Blazar (11)
- Bruchpilot (11)
- CRISPR/Cas-Methode (11)
- CRISPR/Cas9 (11)
- Candida (11)
- Chromatin (11)
- Click-Chemie (11)
- Computertomografie (11)
- Durchflusscytometrie (11)
- Dynamik (11)
- EGFR (11)
- Elektronentransfer (11)
- Enzym (11)
- Epidemiologie (11)
- Epidermaler Wachstumsfaktor-Rezeptor (11)
- Flavonoide (11)
- Fließverhalten (11)
- Fotovoltaik (11)
- Genom (11)
- Hypoxie (11)
- Immuncytochemie (11)
- Immunology (11)
- Japankärpfling (11)
- Knochen (11)
- Knochenersatz (11)
- Kolorektales Karzinom (11)
- LPS (11)
- Laser (11)
- Längsschnittuntersuchung (11)
- MS (11)
- Mais (11)
- Mathematik (11)
- Megakaryozyt (11)
- Mensch-Maschine-Kommunikation (11)
- Mesenchymale Stammzellen (11)
- Mesenchymzelle (11)
- Model (11)
- NIRS (11)
- Nanodiamant (11)
- Neuropathie (11)
- Niereninsuffizienz (11)
- Nigeria (11)
- Parathormon (11)
- Perylenbisimid (11)
- Phylogenie (11)
- Proteaseinhibitor (11)
- Proteasen (11)
- Pulmonale Hypertonie (11)
- Quality of Experience (11)
- Quality of life (11)
- Quanten-Hall-Effekt (11)
- Religion (11)
- Reperfusion (11)
- Risikofaktoren (11)
- Salmonella (11)
- Schizophrenia (11)
- Schlafapnoe (11)
- Schließzelle (11)
- Schultergelenk (11)
- Schädel-Hirn-Trauma (11)
- Silicate (11)
- Skala (11)
- Small RNA (11)
- Sphingolipide (11)
- Squark (11)
- Stammzellen (11)
- Sterblichkeit (11)
- Supraleitung (11)
- Symbiose (11)
- T cell (11)
- TWEAK (11)
- Training (11)
- Tuberkelbakterium (11)
- Tumor-Nekrose-Faktor <alpha> (11)
- USA (11)
- Vasodilatator-stimuliertes Phosphoprotein (11)
- Wahrnehmung (11)
- Westafrika (11)
- Zelltod (11)
- adhesion (11)
- allergy (11)
- antibody (11)
- atrial fibrillation (11)
- biocompatibility (11)
- biofilm (11)
- cancer treatment (11)
- cell adhesion (11)
- cochlear implant (11)
- coping (11)
- dosimetry (11)
- emotion regulation (11)
- fear (11)
- fluorescence microscopy (11)
- gender (11)
- genome (11)
- genomics (11)
- glioblastoma multiforme (11)
- heart rate (11)
- hypoxia (11)
- immunology (11)
- interaction (11)
- kinetics (11)
- lung (11)
- mechanism (11)
- membrane proteins (11)
- microbiome (11)
- microglia (11)
- molecular dynamics (11)
- molecular imaging (11)
- nervous system (11)
- neural networks (11)
- neuroendocrine tumor (11)
- next generation sequencing (11)
- nuclear envelope (11)
- oncology (11)
- oncolytic virus (11)
- periodontitis (11)
- plasticity (11)
- pollination (11)
- randomized controlled trial (11)
- reactive oxygen species (11)
- relapse (11)
- safety (11)
- signaling (11)
- thrombosis (11)
- tight junctions (11)
- trabeculectomy (11)
- transport (11)
- tumor microenvironment (11)
- university (11)
- water oxidation (11)
- Alkohol (10)
- Alzheimer's disease (10)
- Antigen CD28 (10)
- Arzneimittelüberwachung (10)
- Atherosclerosis (10)
- BERA (10)
- BMP-2 (10)
- Bacteria (10)
- Bakterielle Infektion (10)
- Beschichtung (10)
- Bildverarbeitung (10)
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- Biokompatibilität (10)
- Borole (10)
- Cadherine (10)
- Calciumphosphate (10)
- Carbene (10)
- Children (10)
- Chronische Niereninsuffizienz (10)
- Churritisch (10)
- Cochlear-Implantat (10)
- Coronaviren (10)
- Cyclo-GMP (10)
- Depressivität (10)
- Diamant (10)
- Digital Humanities (10)
- Dimerisierung (10)
- Dotierung (10)
- Echokardiographie (10)
- Eierstockkrebs (10)
- Elektrochemie (10)
- Elektronenkorrelation (10)
- Enzyminhibitor (10)
- Erbkrankheit (10)
- Ereigniskorreliertes Potenzial (10)
- Erwachsener (10)
- Frau (10)
- Funktionalisierung <Chemie> (10)
- Funktionelle Kernspintomografie (10)
- Förderung (10)
- Geldpolitik (10)
- Geschlecht (10)
- Glatter Krallenfrosch (10)
- Globalisierung (10)
- Grenzfläche (10)
- Herzmuskelzelle (10)
- Honigbiene (10)
- Hypophosphatasie (10)
- Impfstoff (10)
- Induzierte pluripotente Stammzelle (10)
- Interleukin 4 (10)
- JNK (10)
- Klassifikation (10)
- Kniegelenk (10)
- Kohlenstoff (10)
- Komplikation (10)
- Kultur (10)
- LASP1 (10)
- LC-MS (10)
- Ladungstransfer (10)
- Ligand (10)
- Lokalisation (10)
- Magnesiumphosphate (10)
- Magnetismus (10)
- Mathematikunterricht (10)
- Mathematisches Modell (10)
- Metakognition (10)
- Metallocene (10)
- Methylphenidat (10)
- Mikrokerne (10)
- Mittelalter (10)
- Multiple Myeloma (10)
- Mutagenität (10)
- Nahrungserwerb (10)
- Nebennierenrindenkarzinom (10)
- Neuropathischer Schmerz (10)
- Niger (10)
- Operation (10)
- Osteosynthese (10)
- PD-1 (10)
- Pain (10)
- Panikstörung (10)
- Parasit (10)
- Parodontitis (10)
- Pathogenität (10)
- Plattenepithelkarzinom (10)
- Prevalence (10)
- Prostaglandine (10)
- Präfrontaler Cortex (10)
- Psychotherapie (10)
- Pädagogik (10)
- Qualitätskontrolle (10)
- RNA interference (10)
- RNA-seq (10)
- RNS-Spleißen (10)
- Radiotherapy (10)
- Remote Sensing (10)
- Rhodium (10)
- Rituximab (10)
- SAR (10)
- Schilddrüse (10)
- Sentinel-1 (10)
- Silaanaloga (10)
- Silber (10)
- Silicon (10)
- South Africa (10)
- Sprachverstehen (10)
- Starke Kopplung (10)
- Stickstoffmonoxid-Synthase (10)
- Stressreaktion (10)
- Stroke (10)
- Struktur (10)
- T-Lymphozyten (10)
- T-Lymphozyten-Rezeptor (10)
- Tagesrhythmus (10)
- Theologie (10)
- Totalsynthese (10)
- Toxizität (10)
- Transplantat-Wirt-Reaktion (10)
- Transthorakale Echokardiographie (10)
- Treg (10)
- Trypanosomen (10)
- Vitamin D (10)
- Vor- und Frühgeschichte (10)
- Vorschulkind (10)
- Wachstum (10)
- X-ray crystallography (10)
- Zebrabärbling (10)
- aldosterone (10)
- amino acids (10)
- antimicrobial resistance (10)
- biosynthesis (10)
- boranes (10)
- chemokines (10)
- chronic heart failure (10)
- circadian rhythms (10)
- clinical trial (10)
- comparison (10)
- complex (10)
- coronary artery disease (10)
- decision-making (10)
- density functional calculations (10)
- eNOS (10)
- electronic properties and materials (10)
- fatigue (10)
- genome-wide association (10)
- global change (10)
- hydrogels (10)
- immunomodulation (10)
- induced pluripotent stem cells (10)
- injury (10)
- insect (10)
- knockout (10)
- leaf-cutting ants (10)
- leukemia (10)
- lymph nodes (10)
- mapping (10)
- membrane potential (10)
- motivation (10)
- oncolytic virotherapy (10)
- oxidativer Stress (10)
- phenotype (10)
- quality assurance (10)
- regulatorische T-Zellen (10)
- remodeling (10)
- senescence (10)
- silicon (10)
- social interaction (10)
- stem cell transplantation (10)
- tDCS (10)
- tumors (10)
- vaccination (10)
- vertigo (10)
- walking (10)
- Östrogene (10)
- 3 (9)
- Adenosin (9)
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- Afrika (9)
- Alps (9)
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- Aorta (9)
- Aortenstenose (9)
- Bauchspeicheldrüsenkrebs (9)
- Beyond Standard Model (9)
- Biotransformation (9)
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- Computational chemistry (9)
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- Diagnose (9)
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- - (6)
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- Overlay-Netz (4)
- Oxidative Stress (4)
- Oxidative stress (4)
- PAK (4)
- PBMC (4)
- PEG (4)
- PER (4)
- PI3K (4)
- PSA (4)
- PSMA-RADS (4)
- PTCA (4)
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- Phosphatidylinositolkinase <Phosphatidylinositol-3-Kinase> (4)
- Phosphoglykolatphosphatase (4)
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- Graduate School of Life Sciences (1005)
- Physikalisches Institut (788)
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Schriftenreihe
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- Alter Orient und Altes Testament : Sonderreihe Veröffentlichungen zur Kultur und Geschichte des Alten Orients ; 3 (1)
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- European Journal of Clinical Nutrition ; 70 (1)
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- Grundzüge ; 45 (1)
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Sonstige beteiligte Institutionen
- Johns Hopkins School of Medicine (18)
- Fraunhofer-Institut für Silicatforschung ISC (8)
- IZKF Nachwuchsgruppe Geweberegeneration für muskuloskelettale Erkrankungen (7)
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- DFG Forschungsgruppe 2757 / Lokale Selbstregelungen im Kontext schwacher Staatlichkeit in Antike und Moderne (LoSAM) (6)
- Clinical Trial Center (CTC) / Zentrale für Klinische Studien Würzburg (ZKSW) (5)
- Helmholtz Institute for RNA-based Infection Research (HIRI) (5)
- Johns Hopkins University School of Medicine (5)
- Universität Leipzig (5)
- Universitätsklinikum Würzburg (5)
ResearcherID
- B-1911-2015 (1)
- B-4606-2017 (1)
- C-2593-2016 (1)
- D-1221-2009 (1)
- D-1250-2010 (1)
- D-3057-2014 (1)
- I-5818-2014 (1)
- J-8841-2015 (1)
- M-1240-2017 (1)
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There is a great need for valuable ex vivo models that allow for assessment of cartilage repair strategies to reduce the high number of animal experiments. In this paper we present three studies with our novel ex vivo osteochondral culture platform. It consists of two separated media compartments for cartilage and bone, which better represents the in vivo situation and enables supply of factors pecific to the different needs of bone and cartilage. We investigated whether separation of the cartilage and bone compartments and/or culture media results in the maintenance of viability, structural and functional properties of cartilage tissue. Next, we valuated for how long we can preserve cartilage matrix stability of osteochondral explants during long-term culture over 84 days. Finally, we determined the optimal defect size that does not show spontaneous self-healing in this culture system. It was demonstrated that separated compartments for cartilage and bone in combination with tissue-specific medium allow for long-term culture of osteochondral explants while maintaining cartilage viability, atrix tissue content, structure and mechanical properties for at least 56 days. Furthermore, we could create critical size cartilage defects of different sizes in the model. The osteochondral model represents a valuable preclinical ex vivo tool for studying clinically relevant cartilage therapies, such as cartilage biomaterials, for their regenerative potential, for evaluation of drug and cell therapies, or to study mechanisms of cartilage regeneration. It will undoubtedly reduce the number of animals needed for in vivotesting.
Politische Bildung übt nicht nur einen großen Einfluss auf die zukünftige Konstellation des politischen Systems aus, sondern beeinflusst ebenfalls das soziale Miteinander prägend. Damit werden entscheidende Weichen für die Entwicklung der Gesellschaft, der Nation und des Staates gestellt. Im Zuge dieses Prozesses durchläuft jeder junge Bürger einen politischen Bildungsweg an Schulen. Die Vorgaben darüber, wie schulische politische Bildung auszusehen hat und welche Kompetenzen Schüler in diesem Zusammenhang erwerben sollen, geben die Kultus- bzw. Bildungsministerien in Curricula vor, verbindlich für alle Lehrer. Durch eine komparative Analyse der Curricula kann damit eindeutig die staatlich vorgegebene politische, gesellschaftliche und soziale Richtung festgestellt werden, die junge Menschen einschlagen sollen. Welche edukativen Ziele der politischen Bildung werden verfolgt? Was sollen Schüler lernen, um mit diesen Kompetenzen die Zukunft ihres Kollektivs zu gestalten? Wo liegen die Gemeinsamkeiten und Unterschiede zweier Staaten, in unserem Fall Deutschlands und Polens, im Hinblick auf die schulische politische Bildung? Beantwortet werden diese Fragestellungen durch das Anwenden zweier Methoden der qualitativen Sozialforschung, der komparativen Inhaltsanalyse, zum einen der strukturierenden zum anderen der induktiven. Davor erfolgt eine komparativ quantitative Untersuchung, die den Umfang der Unterrichtszeit in den Leitfächern für politische Bildung in allen Bundesländern und in Polen vergleicht, was einer empirischen Totalerhebung der komplex umfangreichen Daten entspricht. Die quantitativen Forschungsergebnisse zeigen deutliche Differenzen zwischen Deutschland und Polen, in einem der beiden Staaten wird signifikant mehr Zeit für politische Bildung im Leitfach dieser Disziplin investiert als im anderen. Anhand der qualitativen Daten ist zu erkennen, dass einerseits eine gemeinsame Grundbasis von Kompetenzen der politischen Bildung zwischen Deutschland und Polen besteht. Anderseits stechen in beiden Ländern eindeutige Unterschiede hervor, deren Ursprung zum einen historische Erfahrungen der Nationen und Staaten abbildet, zum anderen aktuell gegensätzliche politische Interessen untermauert.
SMART (Simple Modular Architecture Research Tool) is a web resource (https://smart.embl.de) for the identification and annotation of protein domains and the analysis of protein domain architectures. SMART version 9 contains manually curatedmodels formore than 1300 protein domains, with a topical set of 68 new models added since our last update article (1). All the new models are for diverse recombinase families and subfamilies and as a set they provide a comprehensive overview of mobile element recombinases namely transposase, integrase, relaxase, resolvase, cas1 casposase and Xer like cellular recombinase. Further updates include the synchronization of the underlying protein databases with UniProt (2), Ensembl (3) and STRING (4), greatly increasing the total number of annotated domains and other protein features available in architecture analysis mode. Furthermore, SMART's vector-based protein display engine has been extended and updated to use the latest web technologies and the domain architecture analysis components have been optimized to handle the increased number of protein features available.
Hintergrund
Ein neues Rahmenkonzept hat die flexible Ableitung und Nutzung von rheumatologischen Schulungsprogrammen für unterschiedliche Versorgungsbereiche ermöglicht. Auf dieser Grundlage wurde eine 5‑stündige Basisschulung für Patienten mit rheumatoider Arthritis (RA) entwickelt, es wurden rheumatologische Fachärzte und Psychologen trainiert, und dann wurde die Wirksamkeit nach dem Wirkmodell der Patientenschulung evaluiert.
Methoden
Mit dem Studiendesign einer extern randomisierten Wartekontrollgruppenstudie mit 3 Messzeitpunkten wurde geprüft, wie sich die 5‑stündige Basisschulung auf das Erkrankungs- und Behandlungswissen sowie auf die Gesundheitskompetenz von RA-Patienten (n = 249) auswirkt. Weitere Fragen betrafen Einstellungsparameter, Kommunikationskompetenz, Erkrankungsauswirkungen und die Zufriedenheit mit der Schulung. Die Auswertungen erfolgten auf Intention-to-treat-Basis mit Kovarianzanalysen für die Hauptzielgrößen unter Berücksichtigung des Ausgangswertes.
Ergebnisse
Die Analysen zeigen, dass die Basisschulung RA wirksam ist. Noch 3 Monate nach der Schulung verfügten die Schulungsteilnehmer über mehr Wissen und Gesundheitskompetenz als die Wartekontrollgruppe mit kleinem bis mittelgroßem Effekt (d = 0,37 bzw. 0,38). In den Nebenzielgrößen zeigten sich mit Ausnahme der Krankheitskommunikation keine weiteren Schulungseffekte.
Diskussion
Die Basisschulung bietet eine gute Grundlage, auf der weitere Interventionen zur Verbesserung von Einstellungs- und Erkrankungsparametern aufbauen können. Sie eignet sich damit als zentraler Baustein für die rheumatologische Versorgung auf verschiedenen Ebenen.
Interpreting gaze behavior is essential in evaluating interaction partners, yet the ‘semantics of gaze’ in dynamic interactions are still poorly understood. We aimed to comprehensively investigate effects of gaze behavior patterns in different conversation contexts, using a two-step, qualitative-quantitative procedure. Participants watched video clips of single persons listening to autobiographic narrations by another (invisible) person. The listener’s gaze behavior was manipulated in terms of gaze direction, frequency and direction of gaze shifts, and blink frequency; emotional context was manipulated through the valence of the narration (neutral/negative). In Experiment 1 (qualitative-exploratory), participants freely described which states and traits they attributed to the listener in each condition, allowing us to identify relevant aspects of person perception and to construct distinct rating scales that were implemented in Experiment 2 (quantitative-confirmatory). Results revealed systematic and differential meanings ascribed to the listener’s gaze behavior. For example, rapid blinking and fast gaze shifts were rated more negatively (e.g., restless and unnatural) than slower gaze behavior; downward gaze was evaluated more favorably (e.g., empathetic) than other gaze aversion types, especially in the emotionally negative context. Overall, our study contributes to a more systematic understanding of flexible gaze semantics in social interaction.
Background
Deregulated expression of MYC is a driver of colorectal carcinogenesis, suggesting that decreasing MYC expression may have significant therapeutic value. CIP2A is an oncogenic factor that regulates MYC expression. CIP2A is overexpressed in colorectal cancer (CRC), and its expression levels are an independent marker for long-term outcome of CRC. Previous studies suggested that CIP2A controls MYC protein expression on a post-transcriptional level.
Methods
To determine the mechanism by which CIP2A regulates MYC in CRC, we dissected MYC translation and stability dependent on CIP2A in CRC cell lines.
Results
Knockdown of CIP2A reduced MYC protein levels without influencing MYC stability in CRC cell lines. Interfering with proteasomal degradation of MYC by usage of FBXW7-deficient cells or treatment with the proteasome inhibitor MG132 did not rescue the effect of CIP2A depletion on MYC protein levels. Whereas CIP2A knockdown had marginal influence on global protein synthesis, we could demonstrate that, by using different reporter constructs and cells expressing MYC mRNA with or without flanking UTR, CIP2A regulates MYC translation. This interaction is mainly conducted by the MYC 5′UTR.
Conclusions
Thus, instead of targeting MYC protein stability as reported for other tissue types before, CIP2A specifically regulates MYC mRNA translation in CRC but has only slight effects on global mRNA translation. In conclusion, we propose as novel mechanism that CIP2A regulates MYC on a translational level rather than affecting MYC protein stability in CRC.
Formation and treatment of biofilms present a great challenge for health care and industry. About 80% of human infections are associated with biofilms including biomaterial centered infections, like infections of prosthetic heart valves, central venous catheters, or urinary catheters. Additionally, biofilms can cause food and drinking water contamination. Biofilm research focusses on application of experimental biofilm models to study initial adherence processes, to optimize physico-chemical properties of medical materials for reducing interactions between materials and bacteria, and to investigate biofilm treatment under controlled conditions. Exploring new antimicrobial strategies plays a key role in a variety of scientific disciplines, like medical material research, anti-infectious research, plant engineering, or wastewater treatment. Although a variety of biofilm models exist, there is a lack of standardization for experimental protocols, and designing experimental setups remains a challenge. In this study, a number of experimental parameters critical for material research have been tested that influence formation and stability of an experimental biofilm using the non-pathogenic model strain of Pseudomonas fluorescens. These parameters include experimental time frame, nutrient supply, inoculum concentration, static and dynamic cultivation conditions, material properties, and sample treatment during staining for visualization of the biofilm. It was shown, that all tested parameters critically influence the experimental biofilm formation process. The results obtained in this study shall support material researchers in designing experimental biofilm setups.
In this work, we present a multimodal approach to three-dimensionally quantify and visualize fiber orientation and resin-rich areas in carbon-fiber-reinforced polymers manufactured by vacuum infusion. Three complementary image modalities were acquired by Talbot–Lau grating interferometer (TLGI) X-ray microcomputed tomography (XCT). Compared to absorption contrast (AC), TLGI-XCT provides enhanced contrast between polymer matrix and carbon fibers at lower spatial resolutions in the form of differential phase contrast (DPC) and dark-field contrast (DFC). Consequently, relatively thin layers of resin, effectively indiscernible from image noise in AC data, are distinguishable. In addition to the assessment of fiber orientation, the combination of DPC and DFC facilitates the quantification of resin-rich areas, e.g., in gaps between fiber layers or at binder yarn collimation sites. We found that resin-rich areas between fiber layers are predominantly developed in regions characterized by a pronounced curvature. In contrast, in-layer resin-rich areas are mainly caused by the collimation of fibers by binder yarn. Furthermore, void volume around two adjacent 90°-oriented fiber layers is increased by roughly 20% compared to a random distribution over the whole specimen.
The article deals with the pedagogical content knowledge of mathematical modelling as part of the professional competence of pre-service teachers. With the help of a test developed for this purpose from a conceptual model, we examine whether this pedagogical content knowledge can be promoted in its different facets—especially knowledge about modelling tasks and about interventions—by suitable university seminars. For this purpose, the test was administered to three groups in a seminar for the teaching of mathematical modelling: (1) to those respondents who created their own modelling tasks for use with students, (2) to those trained to intervene in mathematical modelling processes, and (3) participating students who are not required to address mathematical modelling. The findings of the study—based on variance analysis—indicate that certain facets (knowledge of modelling tasks, modelling processes, and interventions) have increased significantly in both experimental groups but to varying degrees. By contrast, pre-service teachers in the control group demonstrated no significant change to their level of pedagogical content knowledge.
In 2020, cancer was the leading cause of death worldwide, accounting for nearly 10 million deaths. Lung cancer was the most common cancer, with 2.21 million cases per year in both sexes. This non-homogeneous disease is further subdivided into small cell lung cancer (SCLC, 15%) and non-small cell lung cancer (NSCLC, 85%). By 2023, the American Cancer Society estimates that NSCLC will account for 13% of all new cancer cases and 21% of all estimated cancer deaths. In recent years, the treatment of patients with NSCLC has improved with the development of new therapeutic interventions and the advent of targeted and personalised therapies. However, these advances have only marginally improved the five-year survival rate, which remains alarmingly low for patients with NSCLC. This observation highlights the importance of having more appropriate experimental and preclinical models to recapitulate, identify and test novel susceptibilities in NSCLC. In recent years, the Trp53fl/fl KRaslsl-G12D/wt mouse model developed by Tuveson, Jacks and Berns has been the main in vivo model used to study NSCLC. This model mimics ADC and SCC to a certain extent. However, it is limited in its ability to reflect the genetic complexity of NSCLC. In this work, we use CRISPR/Cas9 genome editing with targeted mutagenesis and gene deletions to recapitulate the conditional model. By comparing the Trp53fl/fl KRaslsl- G12D/wt with the CRISPR-mediated Trp53mut KRasG12D, we demonstrated that both showed no differences in histopathological features, morphology, and marker expression. Furthermore, next-generation sequencing revealed a very high similarity in their transcriptional profile. Adeno-associated virus-mediated tumour induction and the modular design of the viral vector allow us to introduce additional mutations in a timely manner. CRISPR-mediated mutation of commonly mutated tumour suppressors in NSCLC reliably recapitulated the phenotypes described in patients in the animal model. Lastly, the dual viral approach could induce the formation of lung tumours not only in constitutive Cas9 expressing animals, but also in wildtype animals. Thus, the implementation of CRISPR genome editing can rapidly advance the repertoire of in vivo models for NSCLC research. Furthermore, it can reduce the necessity of extensive breeding.
Optimization problems with composite functions consist of an objective function which is the sum of a smooth and a (convex) nonsmooth term. This particular structure is exploited by the class of proximal gradient methods and some of their generalizations like proximal Newton and quasi-Newton methods. The current literature on these classes of methods almost exclusively considers the case where also the smooth term is convex. Here we present a globalized proximal Newton-type method which allows the smooth term to be nonconvex. The method is shown to have nice global and local convergence properties, and some numerical results indicate that this method is very promising also from a practical point of view.
In der Dissertation „Zwei Burschenschafter als Bürgermeister im Dritten Reich. Theo Memmel in Würzburg und Paul May in Halle im Vergleich.“ steht die Untersuchung der Lebenswege der beiden Wahlbeamten Dr. Paul May und Theodor Memmel anhand ihrer Biographien im Fokus. May glitt dank seiner sich stetig erweiternden Fachkenntnisse sowie seiner Anpassungsfähigkeit durchweg in Leistungspositionen problemlos durch vier politische Systeme - vom Kaiserreich bis zur DDR. Seiner bürgerlichen politischen Ausrichtung blieb er hierbei stets treu. Memmel hingegen machte bedingt durch seine an-dere und gravierendere Weltkriegserfahrung einen Prozess vom politisch des-interessierten Front- und Freikorpskämpfer über die Bayerische Volkspartei hin zum überzeugten Nationalsozialisten. Nach dem Untergang des Dritten Reichs stand er vor dem Nichts, sowohl in beruflicher als auch in politischer Hinsicht. In seiner Studentenverbindung fand er jedoch einen Raum, in dem er sich engagieren und Anerkennung finden konnte.
Da May und Memmel durch ihre gemeinsame studentische Korporation gleich sozialisiert wurden und sie sich auf unterschiedliche Weise wie ein ro-ter Faden durch ihr Leben zog, erfuhr diese ebenfalls eine Untersuchung. Hierbei ergab sich, dass die Wandlung von der toleranten Progressverbindung Adelphia zur pflichtschlagenden Burschenschaft in der Deutschen Burschen-schaft im Jahr 1933 keinen plötzlichen Bruch darstellte, sondern vielmehr die Folge einer langjährigen Entwicklung war, wobei der Erste Weltkrieg als be-sonders einschneidender Faktor zu bewerten ist. Am letztendlichen Art- und Dachverbandswechsel hatte auch Memmel einen entscheidenden Anteil. Dass nach der Umwandlung der waffenstudentischen Verbindungen in NS-Kameradschaften diese (auch Adelphia) während des Zweiten Weltkriegs teil-weise in Würzburg im Verborgenen wiedererstehen konnten, hing auch mit der Patronage durch Memmel und sein imposantes Netzwerk zusammen.
Den dritten Untersuchungskomplex dieser Arbeit bildet die kommunale Entwicklung von Groß- und Gauhauptstädten im Dritten Reich, da sowohl Würzburg als auch Halle eine solche verkörperten. Ein Vergleich mit anderen Städten unter denselben Voraussetzungen lässt darauf schließen: Wer 1933/34 Oberbürgermeister einer Groß- und Gauhauptstadt wurde, verdank-te dies nicht seiner Qualifikation. Die Nationalsozialisten, die dieses Amt er-hielten, bemühten sich noch nicht einmal darum, es zu bekommen. Vielmehr stellten sie einen Kompromiss aus den jeweiligen lokalen Macht- und Interes-senskonstellationen dar. Eine Ausnahme hiervon bilden nur die wenigen Städte, in denen bereits vor 1933 ein NSDAP-Angehöriger als Stadtoberhaupt kandidiert hatte. Der Status der Gauhauptstadt führte für die jeweiligen Oberbürgermeister zu einem ganz besonderen Unterstellungsverhältnis, das sich als zweiseitiges Schwert entpuppte: Einerseits erhielt ihre Kommune spezielle Förderung, andererseits standen sie unter einem hohem Erwar-tungsdruck, der sich vielerorts in einem schlechten Verhältnis von Oberbür-germeister und Gauleiter manifestierte. Das Oberbürgermeisteramt im Drit-ten Reich stellte aus beruflicher Sicht einen doppelten Bruch mit der Zeit vor 1933 dar: Zum einen konnte man ohne die bis dahin üblichen Qualifikationen zum Wahlbeamten einer Großstadt aufsteigen, andererseits bedeutete dies auch gleichzeitig das Karriereende.
Abstract
To compare intravenous contrast material (CM) injection protocols for dual-energy CT pulmonary angiography (CTPA) in patients with suspected acute pulmonary embolism with regard to image quality and pulmonary perfused blood volume (PBV) values. A total of 198 studies performed with four CM injection protocols varying in CM volume and iodine delivery rates (IDR) were retrospectively included: (A) 60 ml at 5 ml/s (IDR = 1.75gI/s), (B) 50 ml at 5 ml/s (IDR = 1.75gI/s), (C) 50 ml at 4 ml/s (IDR = 1.40gI/s), (D) 40 ml at 3 ml/s (IDR = 1.05gI/s). Image quality and PBV values at different resolution settings were compared. Pulmonary arterial tract attenuation was highest for protocol A (397 ± 110 HU; p vs. B = 0.13; vs. C = 0.02; vs. D < 0.001). CTPA image quality of protocol A was rated superior compared to protocols B and D by reader 1 (p = 0.01; < 0.001), and superior to protocols B, C and D by reader 2 (p < 0.001; 0.02; < 0.001). Otherwise, there were no significant differences in CTPA quality ratings. Subjective iodine map ratings did not vary significantly between protocols A, B, and C. Both readers rated protocol D inferior to all other protocols (p < 0.05). PBV values did not vary significantly between protocols A and B at resolution settings of 1, 4 and 10 (p = 0.10; 0.10; 0.09), while otherwise PBV values displayed a decreasing trend from protocol A to D (p < 0.05). Higher CM volume and IDR are associated with superior CTPA and iodine map quality and higher absolute PBV values.
Purpose
Radiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques reduce radiation exposure of the heart, but some exposure remains unavoidable. In a retrospective cohort study, we investigated cardiac mortality and morbidity of breast cancer survivors treated with recent RT in Germany.
Methods
A total of 11,982 breast cancer patients treated between 1998 and 2008 were included. A mortality follow-up was conducted until 06/2018. In order to assess cardiac morbidity occurring after breast cancer treatment, a questionnaire was sent out in 2014 and 2019. The effect of breast cancer laterality on cardiac mortality and morbidity was investigated as a proxy for radiation exposure. We used Cox Proportional Hazards regression analysis, taking potential confounders into account.
Results
After a median follow-up time of 11.1 years, there was no significant association of tumor laterality with cardiac mortality in irradiated patients (hazard ratio (HR) for left-sided versus right-sided tumor 1.09; 95% confidence interval (CI) 0.85–1.41). Furthermore, tumor laterality was not identified as a significant risk factor for cardiac morbidity (HR = 1.05; 95%CI 0.88–1.25).
Conclusions
Even though RT for left-sided breast cancer on average incurs higher radiation dose to the heart than RT for right-sided tumors, we found no evidence that laterality is a strong risk factor for cardiac disease after contemporary RT. However, larger sample sizes, longer follow-up, detailed information on individual risk factors and heart dose are needed to assess clinically manifest late effects of current cancer therapy.
Across Europe, calcareous grasslands become increasingly fragmented and their quality deteriorates through abandonment and land use intensification, both affecting biodiversity. Here, we investigated local and landscape effects on diversity patterns of several taxonomic groups in a landscape of highly fragmented calcareous grassland remnants. We surveyed 31 grassland fragments near Göttingen, Germany, in spring and summer 2017 for vascular plants, butterflies and birds, with sampling effort adapted to fragment area. Through regression modelling, we tested relationships between species richness and fragment size (from 314 to 51,395 m\(^2\)), successional stage, habitat connectivity and the per cent cover of arable land in the landscape at several radii. We detected 283 plant species, 53 butterfly species and 70 bird species. Of these, 59 plant species, 19 butterfly species and 9 bird species were grassland specialists. Larger fragments supported twice the species richness of plants than small ones, and hosted more species of butterflies, but not of birds. Larger grassland fragments contained more grassland specialist plants, but not butterfly or bird specialists. Increasing amounts of arable land in the landscape from 20 to 90% was related to the loss of a third of species of plants, and less so, of butterflies, but not of birds. Per cent cover of arable land negatively correlated to richness of grassland specialist plants and butterflies, but positively to grassland specialist birds. We found no effect by successional stages and habitat connectivity. Our multi-taxa approach highlights the need for conservation management at the local scale, complemented by measures at the landscape scale.
Physical regimes characterized by low Mach numbers and steep stratifications pose severe challenges to standard finite volume methods. We present three new methods specifically designed to navigate these challenges by being both low Mach compliant and well-balanced. These properties are crucial for numerical methods to efficiently and accurately compute solutions in the regimes considered.
First, we concentrate on the construction of an approximate Riemann solver within Godunov-type finite volume methods. A new relaxation system gives rise to a two-speed relaxation solver for the Euler equations with gravity. Derived from fundamental mathematical principles, this solver reduces the artificial dissipation in the subsonic regime and preserves hydrostatic equilibria. The solver is particularly stable as it satisfies a discrete entropy inequality, preserves positivity of density and internal energy, and suppresses checkerboard modes.
The second scheme is designed to solve the equations of ideal MHD and combines different approaches. In order to deal with low Mach numbers, it makes use of a low-dissipation version of the HLLD solver and a partially implicit time discretization to relax the CFL time step constraint. A Deviation Well-Balancing method is employed to preserve a priori known magnetohydrostatic equilibria and thereby reduces the magnitude of spatial discretization errors in strongly stratified setups.
The third scheme relies on an IMEX approach based on a splitting of the MHD equations. The slow scale part of the system is discretized by a time-explicit Godunov-type method, whereas the fast scale part is discretized implicitly by central finite differences. Numerical dissipation terms and CFL time step restriction of the method depend solely on the slow waves of the explicit part, making the method particularly suited for subsonic regimes. Deviation Well-Balancing ensures the preservation of a priori known magnetohydrostatic equilibria.
The three schemes are applied to various numerical experiments for the compressible Euler and ideal MHD equations, demonstrating their ability to accurately simulate flows in regimes with low Mach numbers and strong stratification even on coarse grids.