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Modifying light fields at the single-photon level is a key challenge for upcoming quantum technologies and can be realized in a scalable manner through integrated quantum photonics. Laser-written diamond photonics offers 3D fabrication capabilities and large mode-field diameters matched to fiber optic technology, though limiting the cooperativity at the single-emitter level. To realize large coupling efficiencies, we combine excitation of single shallow-implanted silicon vacancy centers via high numerical aperture optics with detection assisted by laser-written type-II waveguides. We demonstrate single-emitter extinction measurements with a cooperativity of 0.0050 and a relative beta factor of 13%. The transmission of resonant photons reveals single-photon subtraction from a quasi-coherent field resulting in super-Poissonian light statistics. Our architecture enables light field engineering in an integrated design on the single quantum level although the intrinsic cooperativity is low. Laser-written structures can be fabricated in three dimensions and with a natural connectivity to optical fiber arrays.

Rezension zu: Angel Montenegro Duque, Historia de España. Edad antigua I. España prerromana. Editorial Gredos, Madrid 1972. 615 Seiten, 172 Abbildungen und 2 Tabellen., Germania : Anzeiger der Römisch-Germanischen Kommission des Deutschen Archäologischen Instituts, Bd. 53 Nr. 1/2 (1975)

IntroductionThe objective of this study was to determine whether postoperative additive systemic steroid administration in chronic rhinosinusitis with nasal polyps (CRSwNP) impacted selected endoscopic, subjective and objective outcome measures.MethodsThis was a prospective, randomized, double-blind, placebo-controlled, noninferiority multicenter trial of n=106 patients with CRSwNP. All patients underwent primary functional endoscopic sinus surgery (FESS) followed by topical nasal steroids. Patients were randomized to a systemic steroid or placebo for 1 month. Patients were followed up for 2 years over 9 time points. The primary outcome measures were the differences between groups with respect to the nasal polyp score (NPS) and sinonasal quality of life (SNQoL). Secondary outcome measures included interactions with respect to the Lund-Kennedy score (LKS), sinonasal symptoms, general quality of life (GQoL), 16-item odor identification test scores, recurrence rates, need for revision surgery and mucus biomarker levels.Results106 patients were randomized to either the placebo or the systemic steroid group (n=53 per group). Postoperative systemic steroids were not superior to placebo with respect to all primary (p= 0.077) and secondary outcome measures (p>0.05 for all). Reported adverse events were similar between the two groups.ConclusionIn conclusion, the addition of postoperative systemic steroids after primary FESS did not confer a benefit over topical steroid nasal spray alone with respect to NPS, SNQOL, LKS, GQOL, sinonasal symptoms, smell scores, recurrence rates, the need for revision surgery or biomarkers over a short-term follow-up of up to 9 months and a long-term follow-up of up to 24 months in CRSwNP patients. Functional endoscopic surgery did, however, show a strong effect on all outcome measures, which remained relatively stable up to the endpoint at 2 years.

Haplotype blocks might carry additional information compared to single SNPs and have therefore been suggested for use as independent variables in genomic prediction. Studies in different species resulted in more accurate predictions than with single SNPs in some traits but not in others. In addition, it remains unclear how the blocks should be built to obtain the greatest prediction accuracies. Our objective was to compare the results of genomic prediction with different types of haplotype blocks to prediction with single SNPs in 11 traits in winter wheat. We built haplotype blocks from marker data from 361 winter wheat lines based on linkage disequilibrium, fixed SNP numbers, fixed lengths in cM and with the R package HaploBlocker. We used these blocks together with data from singleyear field trials in a cross-validation study for predictions with RR-BLUP, an alternative method (RMLA) that allows for heterogeneous marker variances, and GBLUP performed with the software GVCHAP. The greatest prediction accuracies for resistance scores for B. graminis, P. triticina, and F. graminearum were obtained with LD-based haplotype blocks while blocks with fixed marker numbers and fixed lengths in cM resulted in the greatest prediction accuracies for plant height. Prediction accuracies of haplotype blocks built with HaploBlocker were greater than those of the other methods for protein concentration and resistances scores for S. tritici, B. graminis, and P. striiformis. We hypothesize that the trait-dependence is caused by properties of the haplotype blocks that have overlapping and contrasting effects on the prediction accuracy. While they might be able to capture local epistatic effects and to detect ancestral relationships better than single SNPs, prediction accuracy might be reduced by unfavorable characteristics of the design matrices in the models that are due to their multi-allelic nature.

Recurrent and residual laryngeal cancer after organ-preserving radio- or radiochemotherapy is associated with a poor prognosis. Salvage surgery is the most important therapeutic option in these cases.The study assessed rates of recurrence and residual tumor as well as survival and complication rates after salvage laryngectomy at the authors' academic cancer center.A retrospective examination of all patients receiving laryngectomy between 2001 and 2019 due to tumor residuals or recurrence after primary radio- and radiochemotherapy was conducted.A total of 33 salvage procedures were performed. Defect reconstruction was performed by free flap surgery in 30.3% (n = 10) and regional flap surgery in 15.2% (n = 5) . One patient received regional flap surgery and free flap surgery simultaneously. Overall survival after 1, 2, and 5 years was 68.7, 47.9, and 24.2%, and disease-free survival was 81.6, 47.8, and 24.2%, respectively, with 48.5% (n = 16) postoperative tumor recurrences overall. Disease-free survival was significantly shorter for tumor extension into or onto the hypopharynx (p = 0.041). Postoperatively, 72.7% of patients developed a pharyngocutaneous fistula, of which 24.2% required surgical treatment. The hospital stay was 28.0 ± 16.1 days.Salvage laryngectomy is associated with a high rate of treatable complications and high morbidity. Nevertheless, considering the advanced tumor stages treated, it allows for respectable oncological results.HINTERGRUND: Das rezidivierende und residuelle Larynxkarzinom nach organerhaltender Radio- bzw. Radiochemotherapie ist mit einer schlechten Prognose verbunden. Die Salvage-Operation stellt in diesen Fällen die wichtigste therapeutische Option dar.Erfasst wurden die Rate an Rezidiv- und Residualtumoren sowie die Überlebensraten und die Komplikationsrate nach Salvage-Chirurgie des Kehlkopfs an dem akademischen Tumorzentrum der Autor(inn)en.Retrospektiv wurden alle Patienten untersucht, bei denen zwischen 2001 und 2019 eine Salvage-Operation aufgrund eines Tumorresiduums oder Rezidivs nach primärer nichtchirurgischer Therapie erfolgt war.Es wurden 33 Salvage-Operationen durchgeführt. Die Defektrekonstruktion erfolgte in 30,3 % der Fälle (n = 10) mittels freier und in 15,2 % (n = 5) mittels regionaler Lappenplastik. Ein Patient hat sowohl eine freie als auch gleichzeitig eine gestielte Lappenplastik erhalten. Das Gesamtüberleben nach einem, 2 und 5 Jahren betrug 68,7 %; 47,9 % bzw. 24,2 %, das krankheitsfreie Überleben 81,6 %; 47,8 % bzw. 24,2 % bei insgesamt 48,5 % (n = 16) postoperativen Tumorrezidiven. Das krankheitsfreie Überleben war signifikant kürzer bei Tumorausdehnung im bzw. auf den Hypopharynx (p = 0,041). Postoperativ entwickelten 72,7 % der Patienten eine pharyngokutane Fistel unabhängig von einer simultanen Defektrekonstruktion. Nur 24 % der der aufgetretenen Fisteln mussten operativ therapiert werden. Der Krankenhausaufenthalt betrug 28,0 ± 16,1 Tage.Die Salvage-Laryngektomie ist mit vielen, aber beherrschbaren Komplikationen und einer hohen Morbidität verbunden. In Anbetracht der behandelten fortgeschrittenen Tumorkategorien und der Gesamtsituation des Patienten sind respektable onkologische Ergebnisse zu erreichen.

This paper investigates the technological bias of robot adoption using a rich panel data set of Spanish manufacturing firms over a 25-year period. We apply the production function estimation when productivity is multidimensional to the case of an automating technology, to reveal the Hicks-neutral and labor-augmenting technological change brought about by robot adoption within firms. Our results indicate a causal effect of robots on Hicks-neutral and labor-augmenting components of productivity. The biased technological change turns out to be an important determinant of the decline in the aggregate share of labor in the Spanish manufacturing sector.

The development, homeostasis, and repair of intrahepatic and extrahepatic bile ducts are thought to involve distinct mechanisms including proliferation and maturation of cholangiocyte and progenitor cells. This study aimed to characterize human extrahepatic cholangiocyte organoids (ECO) using canonical Wnt-stimulated culture medium previously developed for intrahepatic cholangiocyte organoids (ICO). Paired ECO and ICO were derived from common bile duct and liver tissue, respectively. Characterization showed both organoid types were highly similar, though some differences in size and gene expression were observed. Both ECO and ICO have cholangiocyte fate differentiation capacity. However, unlike ICO, ECO lack the potential for differentiation towards a hepatocyte-like fate. Importantly, ECO derived from a cystic fibrosis patient showed no CFTR channel activity but normal chloride channel and MDR1 transporter activity. In conclusion, this study shows that ECO and ICO have distinct lineage fate and that ECO provide a competent model to study extrahepatic bile duct diseases like cystic fibrosis.

This paper investigates the effects of mergers on the product mix of multiproduct firms. Thus, we open the black box of post-merger efficiency improvements to reveal a new margin of adjustment along the product dimension. We analyze horizontal mergers in a theoretical model where oligopolistic firms employ a flexible manufacturing technology and allocate assets between differentiated varieties. After a merger, acquirers drop products from their consolidated domestic product portfolio and reallocate assets towards core varieties. We further demonstrate that such merger-induced efficiency gains imply greater activity in foreign markets. Using detailed Danish register data, we document novel facts regarding mergers and multiproduct firms and find empirical evidence strongly supporting the model's predictions. Our results show that the number of domestic products of the post-merger acquirer falls relative to the sum of the premerger acquirer and target, that skewness of domestic sales rises towards core products, and that export activity increases.

Iberia Archaeologica, Band 12, Inhaltlich unveränderte digitale Reproduktion der Printausgabe (publiziert 2009), Unchanged digital reproduction of the print edition (published 2009)

Public displays have become more and more ubiquitous in recent years. Both for managing public display networks and for doing research in this field it is an important issue to automatically detect what is happening in front of these screens. This often is done with the help of depth cameras. However, measurement errors can occur due to occlusion or underexposure. In our research we looked into the idea to support the detection of concealed persons using audio information. A se-ries of laboratory experiments showed that audio recordings can be used to detect concealed per-sons. This can be used in existing installations to minimize occlusion error in visual recordings.

Madrider Beiträge, Buch 38,2, Der »Monte do Facho« (O Hío/Cangas), ein mächtiger Hügel, erhebt sich nordwestlich der »ría de Vigo« unmittelbar über dem Ufer des atlantischen Ozeans mit Blick nach Westen. Auf dem Hügelkamm und an seinen Flanken wurden seit Jahrzehnten prähistorische und antike Überreste vermutet, begründet durch Ringwälle und eine Reihe von epigraphischen Streufunden in unmittelbarer Nähe des Hügels. Aber erst die systematische Grabung durch ein deutsch-galicisches Forscherteam ab 2003 erbrachte Gewissheit über sowohl eine prähistorische Besiedlung als auch ein eisenzeitliches »castro« und vor allem ein schlichtes, aber umfangreiches Heiligtum zu Ehren einer bis dahin unbekannten keltischen Gottheit aus der mittleren und späteren Kaiserzeit, deren Name DEUS LAR BERUS BREUS gelautet haben muss. Die Grabung ergab die Existenz von nahezu fünfzig Weihaltären, die zusammen mit früheren epigraphischen Funden aus der Umgebung des Hügels, heute in den Museen von Pontevedra und Vigo, rund einhundert und dreißig Weihaltäre und Altarfragmente zu Ehren dieser Gottheit ausmachen. Aus epigraphischer Sicht handelt es sich um die bislang zahlenmäßig größte Weihung für eine einheimische Gottheit auf der Iberischen Halbinsel. Die Weihaltäre sind im Bild vorgestellt, gelesen und transkribiert sowie epigraphisch interpretiert. Der historische Kontext ist, soweit es der heutige Forschungsstand erlaubt, dargestellt. Die Publikation bedeutet einen Meilenstein in der Erforschung der außerordentlich komplexen Religiosität des keltisch-römischen Nordwestens Hispaniens., Inhaltlich unveränderte digitale Reproduktion der Printausgabe (publiziert 2019), Unchanged digital reproduction of the print edition (published 2019)

CA extern - in press

Madrider Forschungen, Band 14, Inhaltlich unveränderte digitale Reproduktion der Printausgabe (publiziert 1984), Unchanged digital reproduction of the print edition (published 1984)

ICOMOS ��� Hefte des Deutschen Nationalkomitees, Bd. 77 (2020): ICOMOS ��� Hefte des Deutschen Nationalkomitees

Modifying light fields at single-photon level is a key challenge for upcoming quantum technologies and can be realized in a scalable manner through integrated quantum photonics. Laser-written diamond photonics offers three-dimensional fabrication capabilities and large mode-field diameters matched to fiber optic technology, though limiting the cooperativity at the single-emitter level. To realize large cooperativities, we combine excitation of single shallow-implanted silicon vacancy centers via large numerical aperture optics with detection assisted by laser-written type-II waveguides. We demonstrate single-emitter extinction measurements with a cooperativity of 0.153 and a beta factor of 13% yielding 15.3% as lower bound for the quantum efficiency of a single emitter. The transmission of resonant photons reveals single-photon subtraction from a quasi-coherent field resulting in super-Poissonian light statistics. Our architecture enables single quantum level light field engineering in an integrated design which can be fabricated in three dimensions and with a natural connectivity to optical fiber arrays., 8 pages, 4 figures

Supplemental Digital Content is available in the text., Objectives The RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19). Cell entry is mediated by the human angiotensin-converting enzyme II (ACE2). ACE2 and its close homolog angiotensin-converting enzyme I (ACE) are currently discussed candidate genes, in which single-nucleotide polymorphisms (SNPs) could alter binding or entry of SARS-CoV-2 and enhance tissue damage in the lung or other organs. This could increase the susceptibility for SARS-CoV-2 infection and the severity of COVID-19. Patients and methods We performed genotyping of SNPs in the genes ACE2 and ACE in 297 SARS-CoV-2-positive and 253 SARS-CoV-2-negative tested patients. We analyzed the association of the SNPs with susceptibility for SARS-CoV-2 infection and the severity of COVID-19. Results SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding demographics and clinical characteristics. For ACE2 rs2285666, the GG genotype or G-allele was significantly associated with an almost two-fold increased SARS-CoV-2 infection risk and a three-fold increased risk to develop serious disease or COVID-19 fatality. In contrast, the ACE polymorphism was not related to infection risk or severity of disease. In a multivariable analysis, the ACE2 rs2285666 G-allele remained as an independent risk factor for serious disease besides the known risk factors male gender and cardiovascular disease. Conclusions In summary, our report appears to be the first showing that a common ACE2 polymorphism impacts the risk for SARS-CoV-2 infection and the course of COVID-19 independently from previously described risk factors.

Madrider Mitteilungen, Vol. 61 (2020), Der vorliegende Beitrag bespricht Roms m��gliche Motive f��r die Eroberung der gesamten Iberischen Halbinsel nach der Niederlage der kolonialen Verwaltung Karthagos in S��dspanien, dem heutigen Andalusien. Er res��miert die moderne kontroverse Diskussion dar��ber, ob die Annektion Spaniens eine notwendige Ma��nahme zur Selbstverteidigung oder im Gegenteil eine Chance der Bereicherung darstellte. Die Schlu��folgerung des Autors ist, dass nach der Niederlage von Hannibal Spanien keine Bedrohung mehr darstellte und die Annektion daher sowohl in Roms ideologischer ��berzeugung der Eroberung und Dominanz, als auch dem Ehrgeiz der r��mischen Aristokratie nach Ehre, Ruhm und Beute begr��ndet liegt.

Background Organoids are morphologically heterogeneous three-dimensional cell culture systems and serve as an ideal model for understanding the principles of collective cell behaviour in mammalian organs during development, homeostasis, regeneration, and pathogenesis. To investigate the underlying cell organisation principles of organoids, we imaged hundreds of pancreas and cholangiocarcinoma organoids in parallel using light sheet and bright-field microscopy for up to 7 days. Results We quantified organoid behaviour at single-cell (microscale), individual-organoid (mesoscale), and entire-culture (macroscale) levels. At single-cell resolution, we monitored formation, monolayer polarisation, and degeneration and identified diverse behaviours, including lumen expansion and decline (size oscillation), migration, rotation, and multi-organoid fusion. Detailed individual organoid quantifications lead to a mechanical 3D agent-based model. A derived scaling law and simulations support the hypotheses that size oscillations depend on organoid properties and cell division dynamics, which is confirmed by bright-field microscopy analysis of entire cultures. Conclusion Our multiscale analysis provides a systematic picture of the diversity of cell organisation in organoids by identifying and quantifying the core regulatory principles of organoid morphogenesis. Supplementary Information The online version contains supplementary material available at 10.1186/s12915-021-00958-w.

Madrider Mitteilungen, Vol. 17 (1976), Deutsche Zusammenfassung folgt.

Additional file 7: Fig. S6. Representative overview images of three different mPO cultures grown in Z.1-FEP-cuvettes. (a) mPO grown within the Z.1-FEP-cuvette were kept in an incubator as a control for organoids grown within the Z.1 microscope. Images were taken directly after seeding, after 6 days and 10 days. (b) Two representative mPO cultures expressing the nuclei marker Rosa26-nTnG (grey) were imaged with the Zeiss Z.1 microscope over 6 days. Dependent on the number of views, tiles, z-planes and the temporal resolution, the amount of data which is generated and needs to be processed varies between hundreds of gigabyte and tens of terabyte (cuvette 1: total acquisition time: 6 days, temporal resolution: 30 min, views: 1, tiles: 1, total size: 220 GB; cuvette 2: total acquisition time: 6 days, temporal resolution: 30 min, views: 4 (only one is shown), tiles: 1, total size: 1054 GB). Microscope: (a) Zeiss Axio Imager, (b) Zeiss Lightsheet Z.1; objective lenses: (a) Plan S 1.0x FWD 81 mm, (b) detection: W Plan-Apochromat 20x/1.0, illumination: Zeiss LSFM 10x/0.2; laser lines: 561 nm; filters: laser block filter (LBF) 405/488/561; voxel size: 1.02 × 1.02 × 2.00 μm3, recording interval: 30 min; scale bar: 100 μm.

Additional file 14: Fig. S13. Bright field pipeline allows detailed analysis of polycystic hCCAOs. (a) Polycystic hCCAOs display a dense phenotype. Microscope: Zeiss Axio Observer Z.1; objective lenses: Plan-Apochromat 5x/0.16, avg. z-projection, voxel size: 1.29 × 1.29 × 65 μm3, scale bar overview: 500 μm, close-up: 25 μm. (b) The average circularity is around 0.8 over time. (c) Similarly to monocystic organoid cultures, the detected projected luminal areas and growth behaviours are heterogeneous. Box plot analysis, median in green (n = 87) (d) While the median projected luminal areas of three different wells (technical replicates) vary, the normalised projected area increase is similar (n = 87, 34, 63). (e) The initial projected area correlates with the final projected area (R2 = 0.8744) with a linear regression slope m = 1.5857. (f) The organoids display a similar average expansion factor independent of their initial size with an average of 0.02 and outliers (red) lying above 0.078.

Designing human-computer interaction for non-personal computing devices in ur-ban space poses different challenges than designing for personal devices. In this paper we summarize the findings from a project developing smart urban objects to help elderly people participate in urban life. We present four key challenges that have been identified designing such objects, and present first ideas for how to ad-dress these challenges. The four key challenges are adaptability (and data privacy), multi-user usage, walk-up-and-use and joy of use.

Quantum random number generation is a key ingredient for quantum cryptography and fundamental quantum optics and could advance Monte-Carlo simulations and machine learning. An established generation scheme is based on single photons impinging on a beam splitter. Here, we experimentally demonstrate quantum random number generation solely based on the spontaneous emission process in combination with the symmetric emission profile of a dipole aligned orthogonal to the laboratory frame. The demonstration builds on defect centers in hexagonal boron nitride and benefits from the ability to manipulate and align the emission directionality. We prove the randomness in the correlated photon detection events making use of the NIST randomness test suite and show that the randomness remains for two independently emitting defect centers. The scheme can be extended to random number generation by coherent single photons with potential applications in solid-state based quantum communication at room temperature., Comment: 7 pages, 4 figures

Additional file 3: Fig. S2. Ultra-thin FEP-foil cuvette holders for live recordings with the Zeiss Lightsheet Z.1 microscope system. (a) Illustration of the general setup of the Zeiss Lightsheet Z.1 microscope. (b) Close-up of the microscope chamber with the downwards directed Z1-FEP-cuvette enclosing the sample. (c) Close-up of the sample holder. The shrinking tube that seals the FEP cuvette and connects it with the glass capillary is depicted in black. (d) CAD-derived drawings of positive moulds of the FEP cuvette and the glass capillary needed to produce the Z1-FEP-cuvette. (e) Printed mould with a glass capillary used to form the Z1-FEP-cuvette in the vacuum forming process. (f) Ready-to-use Z1-FEP-cuvette. (g) mPOs grown for 7 days in the Z1-FEP-cuvette.

Additional file 5: Fig. S4. Validation of the pH properties of the Zeiss Lightsheet Z.1 microscope. (a) Illustration of the pH-value distribution inside the chamber of the Zeiss Lightsheet Z.1 microscope and the corresponding measurement landmarks. After filling the chamber with buffered media, the pH-value is evenly distributed at 7.5 throughout the chamber. (b) The constant CO2 fumigation that is directed over the liquid column is not able to recover a lower pH-value over time. The pH-value of the medium changes from 8.5 to 8 but it never reaches the physiologically necessary 7.5 (liquid depth: 3 cm). The same is observed at 1 cm and 2 cm liquid depth. At the bottom of the chamber, the pH-value does not change within 48 h. (c) Once the inserted medium has the right pH-value, the incubation system is able to keep it on the same level for more than 2 days.

Madrider Mitteilungen, Vol. 23 (1982), Deutsche Zusammenfassung folgt.

Zeitschrift f��r Hochschulentwicklung, Zeitschrift f��r Hochschulentwicklung (Journal for Higher Education Development), Durch die einheitliche Aufbereitung der Studierenden- und Pr��fungsdaten wird eine vergleichende Analyse von Studienverl��ufen innerhalb des Verbunds Norddeutscher Universit��ten m��glich. Die Gegen��berstellung fachgleicher Studieng��nge anhand von Erfolgsindikatoren soll dazu dienen, fachspezifische Diskurse zur Qualit��tsentwicklung an den Mitgliedsuniversit��ten anzusto��en. Auf Basis eines Arbeitsmodells wird davon ausgegangen, dass sich die Studierbarkeit aus dem Zusammenwirken und der Passf��higkeit von institutionellen und individuellen Faktoren ergibt und Unterschiede zwischen den Studienorten mittelbar auf Unterschiede in der Studierbarkeit der Studienprogramme verweisen., The Association of North German Universities is developing standards for the processing of student and examination data. This will enable comparative analyses of study progress within the alliance. These comparisons on the basis of success indicators are intended to initiate subject-specific discourses on quality development. It is assumed that the studyability results from the interaction and the adaptability of institutional and individual factors. Differences between the results therefore indirectly refer to differences in the studyability of the study programs.

Additional file 23: Table S1. Used settings for the segmentation and post-processing of the data obtained with the light-sheet pipeline. Table S2. Evaluation of segmentation performance for different organoids. The performance was measured against a manually determined ground truth for organoid I (red), II (blue) and III (green). The performance metrics recall, precision and F score are determined from the number of true positives, false negatives and false positives. Values range from 0 (worst performance) to 1 (optimal performance). GT: number of cell nuclei in the ground truth; SC: number of cell nuclei determined by segmentation; TP: true positives; FN: false negatives; FP: false negatives.

Additional file 12: Fig. S11. Analysis of simulated monocystic mPOs. Simulations starting with heterogenous initial cell numbers confirm an influence of organoid size onto the number of oscillation events. The colour code signals the number of registered size oscillation events. The amount of size oscillations is dependent on the initial size of the organoids. While small organoids tend to show frequent inflation-deflation oscillations, initially larger organoids seem less prone to oscillation events.

Madrider Mitteilungen, Vol. 23 (1982), Deutsche Zusammenfassung folgt.

Additional file 11: Fig. S10. Illustration of the input, the assumptions and the output of the model. Measured cell counts and cell division dynamics are used to initialise the simulations. Organoid behaviour is based on the following main assumptions [1]. Each cell produces a substance with constant rate Jin, the substance leads to increase of internal pressure [2]. Cell displacement is driven by mechanical cell-cell-interactions, internal pressure and a surface energy of the organoid [3]. If the organoid shell ruptures, substance is released to the outside with flux Jout, releasing pressure and leading to a contraction of the sphere until the cell-cell connections are restored. The output of the model is the volume data as a function of time of the simulated organoids.

Madrider Mitteilungen, Vol. 28 (1987), Deutsche Zusammenfassung folgt.

Additional file 8: Fig. S7. Dynamic processes observed in organoid morphogenesis. hCCAOs expressed the nuclei marker H2B-eGFP (magenta) and the F-actin cytoskeletal marker LifeAct-mCherry (green) and were cultured in Z1-FEP-cuvettes for long-term live observation. The figure shows excerpts of maximum intensity z-projections. Manual tracking of cell nuclei was performed using the Manual Tracking plugin in Fiji. Microscope: Zeiss Lightsheet Z.1; objective lenses: detection: W Plan-Apochromat 20x/1.0, illumination: Zeiss LSFM 10x/0.2; laser lines: 488 nm, 561 nm; filters: laser block filter (LBF) 405/488/561; voxel size: 1.02 × 1.02 × 2.00 μm3; recording interval: 30 min; scale bars: 50 μm, 25 μm (inset).

Additional file 4: Fig. S3. Validation of the temperature properties of the Zeiss Lightsheet Z.1 microscope. (a) Illustration of the temperature distribution inside of the Zeiss Lightsheet Z.1 microscope chamber and the corresponding measurement landmarks. Beside the open, upper part with a slightly lower value, the temperature is equally distributed throughout the chamber. (b) Results of the measurement of the heating-up time. The included heating unit of the microscope needs to heat up the medium starting from room temperature (21 °C). After 12 min the medium reaches the physiological temperature of 37 °C.

Madrider Mitteilungen, Vol. 19 (1978), Deutsche Zusammenfassung folgt.

Die Einstein’schen Feldgleichungen der allgemeinen Relativitätstheorie können unter bestimmten Umständen als ein Anfangswertproblem formuliert werden. Auf diese Weise wird die enge Verbindung zwischen der Allgemeinen Relativitätstheorie und der Theorie der hyperbolischen Differentialgleichungen sichtbar. Durch die Formulierung der Feldgleichungen als ein Cauchy Problem wird klar, dass die Anfangswerte nicht beliebig gew¨ahlt werden können, sondern gewissen Einschränkungen unterworfen sind. Am Ende stehen nicht-lineare partielle Differentialgleichungen auf Mannigfaltigkeiten. Es zeigt sich weiters, dass die Existenz einer maximalen Entwickung eines Cauchy-Problems in der allgemeinen Relativitätstheorie aufgrund von Nichteindeutigkeiten der Lösungen schwierig zu beweisen ist. So muss man sich let- zten Endes auf eine bestimmte Klasse von Entwicklungen beschränken, um zu einer maximalen und eindeutigen Entwicklung zu kommen. Es ist also möglich, bei gegebenen Anfangswerten, die Existenz einer maximalen gobalen hyperbolischen Entwicklung zu zeigen. In dieser Masterarbeit wird gezeigt wie man das Cauchy Problem der allgemeinen Relativitätstheorie auf das Problem der Lösung von hyperbolischen Differentialgleichungen reduzieren kann (Kapitel 1). Danach wird die Eindeutigkeit/Existenz der Lösung von symmetrischen hyperbolischen Systemen bewiesen und anschließend deren Verbindung zu linearen Wellengleichungen. Danach wird die Eindeutigkeit/Existenz der Lösung von nichtlinearen Wellengleichungen gezeigt (Kapitel 2) und dies auf Mannigfaltigkeiten mit Lorentz-Signaltur erweitert. An Ende wird der Beweis zur Existenz einer maximalen globalen hyperbolischen Entwicklung erläutert (Kapitel 3)., Einstein’s field equations can be, under suitable boundary conditions, formulated as an initial value problem. In this way one can see the strong relation between Einstein’s general theory of relativity and the theory of hyperbolic PDE’s. By the formulation of Einstein’s equation as an IVP it became clear that the initial data cannot be chosen freely, they have to fulfill some constraints. This also leads to non-linear PDE’s on manifolds. It turns out that it is not trivial to show the existence of a maximal development due to the fact that it is not unique. To handle this problem one has to restrict to a specific class of developments in order to get a maximal and unique development. With given initial data, it is possible to show that there is a unique maximal globally hyperbolic development (MGHD). In this Master’s thesis we show how one can reduce the Cauchy problem in General Relativity to that of solving a system of hyperbolic differential equations. Next we prove the existence and uniqueness of a solution for symmetric hyperbolic systems and make the connection to linear wave equations (Chapter 1). Afterwards the existence and uniqueness of a solution to non-linear wave equations is shown (Chapter 2), which then is extended to manifolds of Lorentzian signature. At the end there is a proof for the existence of a maximal globally hyperbolic development (Chapter 3).

Additional file 6: Fig. S5. Overview of entire hCCAO cultures within one Z1-FEP-cuvette and observation of isolated single-cell dynamics. hCCAOs expressed the nuclei marker H2B-eGFP (magenta) and the F-actin cytoskeletal marker LifeAct-mCherry (green). (a) Maximum intensity z-projection of the entire field of view in the Lightsheet Z1 microscope. One cuvette (i) with low organoid density and one cuvette (ii) with high organoid density are displayed. We counted about 120 organoids in the cuvette (ii) with high organoid density. Organoids show different sizes and isolated cell nuclei are visible in the interspaces. Scale bar: 250 μm. (b) Excerpts of the maximum intensity z-projections shown in (a). Isolated single organoid cells show signs of polarisation and undergo cell division. Scale bars: Cell division, Polarisation - 10 μm, Formation – 20 μm. Microscope: Zeiss Lightsheet Z.1; objective lenses: detection: W Plan-Apochromat 20x/1.0, illumination: Zeiss LSFM 10x/0.2; laser lines: 488 nm, 561 nm; filters: laser block filter (LBF) 405/488/561; voxel size: 1.02 × 1.02 × 2.00 μm3; recording interval: 30 min.

HNO : Hals-Nasen-Ohren-Heilkunde, Kopf- und Halschirurgie 69(2), 47-52 (2021). doi:10.1007/s00106-021-01030-3 special issue: "Oropharynxkarzinome. - Teil 1", Published by Springer, New York

Additional file 2: Fig. S1. Light sheet and bright field time-resolved observation allow quantitative analyses of micro-, meso- and macroscale dynamics. Using a light sheet-based fluorescent microscope time-resolved image stack of organoids are recorded. The high-resolution images are subjected to nuclei segmentation [22] for the quantification of dynamics on single cell level (microscale). Besides that, dynamics, such as size oscillation events, of individual organoids (mesoscale) can be analysed. The restricted throughput of this pipeline is matched with the analyses based on time-resolved bright field images. Here, the dynamics of high numbers of organoids are quantified based on the normalised (norm.) projected (proj.) luminal areas. The pipeline also enables the observation of entire organoid cultures (macroscale) within individual wells.