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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Additional file 9: Fig. S8. Time-resolved, representative images of the growth and heterogeneity in mPOs. Illustrated are single organoids extracted from three different cultures showing rotation, size oscillation, luminal dynamics, fusion and different cell nucleus sizes. In addition, cell division events at a late stage (day 4, 5, 6) and the formation of differently sized organoid fragments are shown. Besides the luminal dynamics, which are imaged by the use of a bright field microscope, all behaviour patterns and appearances were observed from organoids expressing the nuclei marker Rosa26-nTnG (grey) and grown within the Z.1-FEP-cuvette inside the Z.1 Lightsheet microscope. The red rectangles indicate the corresponding close-up, the red arrows indicate the position within the organoid where the event occurs, the curved arrow indicate the direction of rotation and the red circle indicates the volume change during a size oscillation event. Microscope fluorescence images: Zeiss Lightsheet Z.1; Plan S 1.0x FWD 81 mm, 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; Microscope bright field images: Zeiss Axio Observer Z.1; objective lenses: Plan-Apochromat 5x/0.16, voxel size: 1.26 × 1.26 × 4 μm3, avg. z-projection.

TEM-cells can be used for EMC-measurements or field sensor calibration. For a practical application, the TEM-cell’s resonance behavior over a broad range of frequencies is essential. This paper presents two methods to compute the resonance frequencies of an ideal (perfect electrical conductor) coaxial TEM-cell based on the generalized telegraphist equations. We compare our numerical results with commercially available software and measurements on a coaxial TEM-cell with similar geometric dimensions.

Quantum emitters in hexagonal Boron Nitride (hBN) were recently reported to hol a homogeneous linewidth according to the Fourier-Transform limit up to room temperature. This unusual observation was traced back to decoupling from in-plane phonon modes which can arise if the emitter is located between two planes of the hBN host material. In this work, we investigate the origins for the mechanical decoupling. Improved sample preparation enabled a reduced background and a 70-fold decrease of spectral diffusion which was so far the major drawback of defect center in hBN and allowed us to reveal a gap in the electron-phonon spectral density for low phonon frequencies. This decoupling from phonons persists at room temperature and explains the observed Fourier Transform limited lines up to 300K. Furthermore, we investigate the dipole emission directionality and show a preferred photon emission through the side of the hBN flakes supporting the claim for an out-of-plane distortion of the defect center. Our work lays the foundation to a deeper understanding of the underlying physics for the persistence of Fourier-Transform limit lines up to room temperature. It furthermore provides a description on how to identify the mechanically isolated emitter within the large number of defect centers in hBN. Therefore, it paves the way for quantum optics applications with defect centers in hBN at room temperature., Comment: 9 pages, 5 figures

Additional file 1. Supplementary Material.

Figure S4. Principal coordinate analysis of 235 wheat cultivars. Three sub-populations based on geographical origin were shown in three colors. Blue, red and green indicate the cultivars from Europe, North America and Asia, respectively. The black dots indicatethe mixture gemplasm from three sub-populations. (PDF 42Â kb)

Figure S5. Amino acid alignment and nucleotide divergence rates (dN/dS) of CBF-A5 and nine homologous amino acid sequences. Shownare alignments of two haplotype AA sequences of CBF-A5 and nine homologous plant AA sequences. The numbers above the alignment indicate the sites of AAs. The black line above the alignment illustrates the PKK/RPAGRxKFxETRHP and DSAWR motif, the red line the AP2 domain, the black arrows the β-strands and the black spiral the α-helix. The description of red arrows, black line und red dots is according to Fig. 6. (PDF 54 kb)

Figure S7. Amino acid alignment and nucleotide divergence rates (dN/dS) of CBF-A13 gene and nine homologous amino acid sequences. Illustrated are alignments of two haplotype AA sequences of CBF-A13 and nine homologous plant AA sequences. The numbers above the alignment illustrate the sites of AAs. The black line above the alignment illustrates the PKK/RPAGRxKFxETRHP and DSAWR motif, the red line the AP2 domain, the black arrows the β-strands and the black spiral the α-helix. The description of black line and red dots is according to Fig. 6. (PDF 53 kb)

Figure S3. Localization of 19 candidate genes and corresponding primers in the Chinese Spring Reference assembly v1.0. Next to the gene names, the chromosome number and physical position of the Chinese Spring reference assembly v1.0 are shown in brackets. For each gene the structure is illustrated below. The black lines indicate the genomic sequences, the gray boxes the exons, the black arrows rightward the forward primers and the black arrows leftwards the reverse primers. (PDF 23Â kb)

Figure S6. Amino acid alignment and nucleotide divergence rates (dN/dS) of CBF-A10 gene and nine homologous amino acid sequences. Alignments of two haplotype AA sequences of CBF-A10 and nine homologous plant AA sequences. The numbers above the alignment indicate the sites of AAs. The black line above the alignment illustrates the PKK/RPAGRxKFxETRHP and DSAWR motif, the red line the AP2 domain, the black arrows the β-strands and the black spiral the α-helix. The description of red arrow, black line and red dots is according to Fig. 6. (PDF 53 kb)

Figure S10. Amino acid alignment and nucleotide divergence rates (dN/dS) of CBF-A18 gene and nine homologous amino acid sequences. Illustrated are alignments of two haplotype AA sequences of CBF-A18 and nine homologous plant AA sequences. The numbers above the alignment illustrate the sites of AAs. The black line above the alignment illustrates the PKK/RPAGRxKFxETRHP and DSAWR motif, the red line the AP2 domain, the black arrows the β-strands and the black spiral the α-helix. The description of black line und red dots is according to Fig. 6. (PDF 54 kb)

Figure S14. AA alignment and nucleotide divergence rates (dN/dS) of PPD-D1 gene and nine homologous amino acid sequences. Illustrated are alignments of four haplotype AA sequences of PPD-D1 and nine homologous plant AA sequences. The numbers above the alignment illustrate the sites of AAs. The red line above the alignment illustrates the Pseudo Receiver domain and COSTANS motif. The description of black line and red dots is according to Fig. 6. (PDF 7539 kb)

Figure S12. Amino acid alignment and nucleotide divergence rates (dN/dS) of VRN-B3 gene and nine homologous amino acid sequences. Illustrated are alignments of three haplotype AA sequences of VRN-B3 nine homologous plant AA sequences. The numbers above the alignment illustrate the sites of AAs. The black line above the alignment illustrates the segment B, the red line the flowering time (FT)-family protein, the black arrows the β-strands and the spirals the α-helices. The description of red arrow, black line and red dots is according to Fig. 6. (PDF 51 kb)

Die Gesellschaft für Informatik e.V. (GI) will mit diesen Leitlinien bewirken, dass berufsethische oder moralische Konflikte Gegenstand gemeinsamen Nachdenkens und Handelns werden. Die Leitlinien sollen den GI-Mitgliedern und darüber hinaus allen Menschen, die IT-Systeme entwerfen, herstellen, betreiben oder verwenden, eine Orientierung bieten.

Figure S2. PCA plot of mean winter survival and number of days under − 15 °C from ten environments. (PDF 52 kb)

Figure S13. Amino acid alignment and nucleotide divergence rates (dN/dS) of PPD-B1 gene and nine homologous amino acid sequences. Illustrated are alignments of four haplotype AA sequences of PPD-B1 and nine homologous plant AA sequences. The numbers above the alignment illustrate the sites of AAs. The red line above the alignment illustrates the Pseuodo Receiver domain and COSTANS motif. The description of red arrows, black line and red dots is according to Fig. 6. (PDF 8583 kb)

Figure S11. Amino acid alignment and nucleotide divergence rates (dN/dS) of VRN-A1 gene and nine homologous amino acid sequences. Illustrated are alignments of three haplotype AA sequences of VRN-A1 nine homologous plant AA sequences. The numbers above the alignment illustrate the sites of AAs. The black line above the alignment illustrates the I domain and C domain, the red line the MADS box domain and K domain, the black arrows the β-strands and the spirals the α-helices. The description of red arrow, black line and red dots is according to Fig. 6. (PDF 79 kb)

Figure S8. Amino acid alignment and nucleotide divergence rates (dN/dS) of CBF-A15 gene and nine homologous amino acid sequences. Illustrated are alignments of two haplotype AA sequences of CBF-A15 and nine homologous plant AA sequences. The numbers above the alignment illustrate the sites of AAs. The black line above the alignment illustrates the PKK/RPAGRxKFxETRHP and DSAWR motif, the red line the AP2 domain, the black arrows the β-strands and the black spiral the α-helix. The description of red arrows, black line and red dots is according to Fig. 6. (PDF 52 kb)

The additional material file contains: Figure 1s - Study scheme for inclusion, consent and follow up of UPS patients. Figure 2s - UPS flow during study follow up. Table 1s - Clinical characteristics of 177 patients who chose and received PD (n = 89) or HD (n = 70) or who chose but never received PD (n = 14) or HD (n = 4). (DOCX 89 kb)

Trans* und Inter* Menschen verunsichern die kulturell gesellschaftliche Ordnung der Zweigeschlechtlichkeit. Während Medizin und Sexualwissenschaften sich seit langem mit Inter- und Transsexualität beschäftigen, wird die aktivistische Kritik am gesellschaftlichen und akademischen Umgang mit Trans* und Inter* seit den 2000er Jahren lauter. Der Band versammelt Beiträge aus dem deutschsprachigen Raum, die sich aus Perspektiven kultur- und sozialwissenschaftlich orientierter Geschlechterforschung mit Inter- und Transgeschlechtlichkeit auseinandersetzen. Die Texte entwickeln theoretisch-methodische Zugänge für eine nicht pathologisierende Wissensproduktion über Trans* und Inter* und setzen die eigene Forschung in ein solidarisches Verhältnis mit den politischen Bewegungen von Trans*- und Inter*-Aktivist_innen. Damit liefert der Band vielfältige Einblicke in aktuelle Forschungsdebatten und Denkanstöße für künftige Auseinandersetzungen.