Artificial intelligence based deconvolving on megavoltage photon beam profiles for radiotherapy applications

Objective. The aim of this work is an AI based approach to reduce the volume effect of ionization chambers used to measure high energy photon beams in radiotherapy. In particular for profile measurements, the air-filled volume leads to an inaccurate measurement of the penumbra. Approach. The AI-based approach presented in this study was trained with synthetic data intended to cover a wide range of realistic linear accelerator data. The synthetic data was created by randomly generating profiles and convolving them with the lateral response function of a Semiflex 3D ionization chamber. The neuronal network was implemented using the open source tensorflow.keras machine learning framework and a U-Net architecture. The approach was validated on three accelerator types (Varian TrueBeam, Elekta VersaHD, Siemens Artiste) at FF and FFF energies between 6 MV and 18 MV at three measurement depths. For each validation, a Semiflex 3D measurement was compared against a microDiamond measurement, and the AI processed Semiflex 3D measurement was compared against the microDiamond measurement. Main results. The AI approach was validated with dataset containing 306 profiles measured with Semiflex 3D ionization chamber and microDiamond. In 90% of the cases, the AI processed Semiflex 3D dataset agrees with the microDiamond dataset within 0.5 mm/2% gamma criterion. 77% of the AI processed Semiflex 3D measurements show a penumbra difference to the microDiamond of less than 0.5 mm, 99% of less than 1 mm. Significance. This AI approach is the first in the field of dosimetry which uses synthetic training data. Thus, the approach is able to cover a wide range of accelerators and the whole specified field size range of the ionization chamber. The application of the AI approach offers an quality improvement and time saving for measurements in the water phantom, in particular for large field size

Analysis of connexin 43, connexin 45 and N-cadherin in the human sertoli cell line FS1 and the human seminoma-like cell line TCam-2 in comparison with human testicular biopsies

Background: Germ cell tumors are relatively common in young men. They derive from a non-invasive precursor, called germ cell neoplasia in situ, but the exact pathogenesis is still unknown. Thus, further understanding provides the basis for diagnostics, prognostics and therapy and is therefore paramount. A recently developed cell culture model consisting of human FS1 Sertoli cells and human TCam-2 seminoma-like cells offers new opportunities for research on seminoma. Since junctional proteins within the seminiferous epithelium are involved in cell organization, differentiation and proliferation, they represent interesting candidates for investigations on intercellular adhesion and communication in context with neoplastic progression. Methods: FS1 and TCam-2 cells were characterized regarding gap-junction-related connexin 43 (Cx43) and connexin 45 (Cx45), and adherens-junction-related N-cadherin using microarray, PCR, Western blot, immunocytochemistry and immunofluorescence. Results were compared to human testicular biopsies at different stages of seminoma development via immunohistochemistry to confirm the cell lines’ representativeness. Furthermore, dye-transfer measurements were performed to investigate functional cell coupling. Results: Cx43, Cx45 and N-cadherin mRNA and protein were generally detectable in both cell lines via qualitative RT-PCR and Western blot. Immunocytochemistry and immunofluorescence revealed a mainly membrane-associated expression of N-cadherin in both cell lines, but gene expression values were higher in FS1 cells. Cx43 expression was also membrane-associated in FS1 cells but barely detectable in TCam-2 cells. Accordingly, a high gene expression value of Cx43 was measured for FS1 and a low value for TCam-2 cells. Cx45 was primary located in the cytoplasm of FS1 and TCam-2 cells and revealed similar low to medium gene expression values in both cell lines. Overall, results were comparable with corresponding biopsies. Additionally, both FS1 and TCam-2 cells showed dye diffusion into neighboring cells. Conclusion: The junctional proteins Cx43, Cx45 and N-cadherin are expressed in FS1 and TCam-2 cells at mRNA and/or protein level in different amounts and localizations, and cells of both lines are functionally coupled among each other. Concerning the expression of these junctional proteins, FS1 and TCam-2 cells are largely representative for Sertoli and seminoma cells, respectively. Thus, these results provide the basis for further coculture experiments evaluating the role of junctional proteins in context with seminoma progression

On the Benefit of Dual-domain Denoising in a Self-supervised Low-dose CT Setting

Computed tomography (CT) is routinely used for three-dimensional non-invasive imaging. Numerous data-driven image denoising algorithms were proposed to restore image quality in low-dose acquisitions. However, considerably less research investigates methods already intervening in the raw detector data due to limited access to suitable projection data or correct reconstruction algorithms. In this work, we present an end-to-end trainable CT reconstruction pipeline that contains denoising operators in both the projection and the image domain and that are optimized simultaneously without requiring ground-truth high-dose CT data. Our experiments demonstrate that including an additional projection denoising operator improved the overall denoising performance by 82.4-94.1%/12.5-41.7% (PSNR/SSIM) on abdomen CT and 1.5-2.9%/0.4-0.5% (PSNR/SSIM) on XRM data relative to the low-dose baseline. We make our entire helical CT reconstruction framework publicly available that contains a raw projection rebinning step to render helical projection data suitable for differentiable fan-beam reconstruction operators and end-to-end learning.Comment: This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessibl

ExoS/ChvI two-component signal-transduction system activated in the absence of bacterial phosphatidylcholine

Sinorhizobium meliloti contains the negatively charged phosphatidylglycerol and cardiolipin as well as the zwitterionic phosphatidylethanolamine (PE) and phosphatidylcholine (PC) as major membrane phospholipids. In previous studies we had isolated S. meliloti mutants that lack PE or PC. Although mutants deficient in PE are able to form nitrogen-fixing nodules on alfalfa host plants, mutants lacking PC cannot sustain development of any nodules on host roots. Transcript profiles of mutants unable to form PE or PC are distinct; they differ from each other and they are different from the wild type profile. For example, a PC-deficient mutant of S. meliloti shows an increase of transcripts that encode enzymes required for succinoglycan biosynthesis and a decrease of transcripts required for flagellum formation. Indeed, a PC-deficient mutant is unable to swim and overproduces succinoglycan. Some suppressor mutants, that regain swimming and form normal levels of succinoglycan, are altered in the ExoS sensor. Our findings suggest that the lack of PC in the sinorhizobial membrane activates the ExoS/ChvI two-component regulatory system. ExoS/ChvI constitute a molecular switch in S. meliloti for changing from a free-living to a symbiotic life style. The periplasmic repressor protein ExoR controls ExoS/ChvI function and it is thought that proteolytic ExoR degradation would relieve repression of ExoS/ChvI thereby switching on this system. However, as ExoR levels are similar in wild type, PC-deficient mutant and suppressor mutants, we propose that lack of PC in the bacterial membrane provokes directly a conformational change of the ExoS sensor and thereby activation of the ExoS/ChvI two-component system.Fil: Geiger, Otto. Universidad Nacional Autónoma de México; MéxicoFil: Sohlenkamp, Christian. Universidad Nacional Autónoma de México; MéxicoFil: Vera-Cruz, Diana. Universidad Nacional Autónoma de México; MéxicoFil: Medeot, Daniela Beatriz. Universidad Nacional Autónoma de México; México. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Martínez-Aguilar, Lourdes. Universidad Nacional Autónoma de México; MéxicoFil: Sahonero-Canavesi, Diana X.. Universidad Nacional Autónoma de México; MéxicoFil: Weidner, Stefan. Universitaet Biehlefeld; AlemaniaFil: Pühler, Alfred. Universitaet Biehlefeld; AlemaniaFil: López Lara, Isabel M.. Universidad Nacional Autónoma de México; Méxic

Noise2Contrast: Multi-Contrast Fusion Enables Self-Supervised Tomographic Image Denoising

Self-supervised image denoising techniques emerged as convenient methods that allow training denoising models without requiring ground-truth noise-free data. Existing methods usually optimize loss metrics that are calculated from multiple noisy realizations of similar images, e.g., from neighboring tomographic slices. However, those approaches fail to utilize the multiple contrasts that are routinely acquired in medical imaging modalities like MRI or dual-energy CT. In this work, we propose the new self-supervised training scheme Noise2Contrast that combines information from multiple measured image contrasts to train a denoising model. We stack denoising with domain-transfer operators to utilize the independent noise realizations of different image contrasts to derive a self-supervised loss. The trained denoising operator achieves convincing quantitative and qualitative results, outperforming state-of-the-art self-supervised methods by 4.7-11.0%/4.8-7.3% (PSNR/SSIM) on brain MRI data and by 43.6-50.5%/57.1-77.1% (PSNR/SSIM) on dual-energy CT X-ray microscopy data with respect to the noisy baseline. Our experiments on different real measured data sets indicate that Noise2Contrast training generalizes to other multi-contrast imaging modalities

Comprehensive biomarker analysis of long-term response to trastuzumab in patients with HER2-positive advanced gastric or gastroesophageal adenocarcinoma

Background A subgroup of patients with HER2-positive metastatic gastric and gastroesophageal junction cancers shows long-term response under trastuzumab maintenance monotherapy. Obviously, HER2 status alone is not able to identify these patients. We performed this study to identify potential new prognostic biomarkers for this long-term responding patient group. Patients and methods Tumor samples of 19 patients with HER2-positive metastatic gastric and gastroesophageal junction cancer who underwent trastuzumab treatment were retrospectively collected from multiple centers. Patients were divided into long-term responding (n=7) or short-term responding group (n=12) according to progression-free survival (PFS≥12 months vs. PFS<12 months). Next generation sequencing and microarray-based gene expression analysis were performed along with HER2 and PD-L1 immunohistochemistry. Results Long-term responding patients had significantly higher PD-L1 combined positive scores (CPS) and CPS correlated with longer progression-free survival. PD-L1 positivity (CPS≥1) was further associated with an increased CD4+ memory T-cell score. The ERBB2 copy number as well as the tumor mutational burden could not discriminate between short-term and long-term responding patients. Genetic alterations and co-amplifications in HER2 pathway associated genes such as EGFR, which were connected to trastuzumab resistance, were present in 10% of the patients and equally distributed between the groups. Conclusion The study highlights the clinical relevance of PD-L1 testing also in the context of trastuzumab treatment and offers a biological rational by demonstrating elevated CD4+ memory T-cells scores in the PD-L1-positive group

Modeling the Effects of Star Formation Histories on Halpha and Ultra-Violet Fluxes in Nearby Dwarf Galaxies

We consider the effects of non-constant star formation histories (SFHs) on Halpha and GALEX far ultra-violet (FUV) star formation rate (SFR) indicators. Under the assumption of a fully populated Chabrier IMF, we compare the distribution of Halpha-to-FUV flux ratios from ~ 1500 simple, periodic model SFHs with observations of 185 galaxies from the Spitzer Local Volume Legacy survey. We find a set of SFH models that are well matched to the data, such that more massive galaxies are best characterized by nearly constant SFHs, while low mass systems experience bursts amplitudes of ~ 30 (i.e., an increase in the SFR by a factor of 30 over the SFR during the inter-burst period), burst durations of tens of Myr, and periods of ~ 250 Myr; these SFHs are broadly consistent with the increased stochastic star formation expected in systems with lower SFRs. We analyze the predicted temporal evolution of galaxy stellar mass, R-band surface brightness, Halpha-derived SFR, and blue luminosity, and find that they provide a reasonable match to observed flux distributions. We find that our model SFHs are generally able to reproduce both the observed systematic decline and increased scatter in Halpha-to-FUV ratios toward low mass systems, without invoking other physical mechanisms. We also compare our predictions with those from the Integrated Galactic IMF theory with a constant SFR. We find that while both predict a systematic decline in the observed ratios, only the time variable SFH models are capable of producing the observed population of low mass galaxies ($M_{*}$ < 10$^{7}$ Msun) with normal Halpha-to-FUV ratios. These results demonstrate that a variable IMF alone has difficulty explaining the observed scatter in the Halpha-to-FUV ratios. We conclude by considering the limitations of the model SFHs, and discuss the use of additional empirical constraints to improve future SFH modeling efforts.Comment: 15 pages, 11 Figures. Accepted for publication in Ap

Neue Rechte und Universität

Prof. Dr. Jens Schröter, Dr. Pablo Abend und Prof. Dr. Benjamin Beil sind Herausgeber der Reihe. Die Herausgeber*innen der einzelnen Hefte sind renommierte Wissenschaftler*innen aus dem In- und Ausland. AG Siegen Denken: Pablo Abend, Armin Beverungen, Marcus Burkhardt, Timo Kaerlein, Tatjana Seitz, Nadine TahaIn dieser Ausgabe der "Navigationen" sammeln wir Ressourcen gegen die Vereinnahmung der Universität durch die so genannte Neue Rechte. Auslöser für das Themenheft sind die Geschehnisse rund um ein Seminar, das im Wintersemester 2018/19 unter dem Titel „Denken und Denken lassen. Zur Philosophie und Praxis der Meinungsfreiheit“ an der Universität Siegen angeboten wurde.Das Seminar wurde von einer Vorlesungsreihe flankiert, in der „dezidiert konservative oder rechte Denker“ eine Bühne bekamen, u.a. Marc Jongen von der AfD, und der Autor Thilo Sarrazin. Ein zentrales Anliegen dieser Ausgabe ist es, die Siegener Ereignisse zu dokumentieren, wissenschaftlich aufzuarbeiten und in verschiedenen Hinsichten zu kontextualisieren: diskursstrategisch, geographisch, historisch und politisch. Hierzu versammelt das Heft Beiträge diverser Forschungsdisziplinen – explizit auch von Vertreter*innen derjenigen Disziplinen, deren Existenzrecht von Teilen der Siegener Vortragenden in Zweifel gezogen wird. Um die Diversität der betroffenen Zugänge zu repräsentieren, sind über die Medienwissenschaft hinaus Beiträge aus der Islamwissenschaft, den Gender Studies, der Linguistik und der Soziologie im Heft vertreten

Reset of inflammatory priming of joint tissue and reduction of the severity of arthritis flares by bromodomain inhibition

OBJECTIVE: We have recently shown that priming of synovial fibroblasts (SFs) drives arthritis flares. Pathogenic priming of SFs is essentially mediated by epigenetic reprogramming. Bromodomain and extra-terminal motif (BET) proteins translate epigenetic changes into transcription. Here we used a BET inhibitor to target inflammatory tissue priming and reduce flare severity in experimental arthritis. METHODS: BALB/c mice were treated intraperitoneally or locally into the paw with I-BET151, which blocks interaction of BET proteins with acetylated histones. Effect of I-BET151 on acute arthritis and/or inflammatory tissue priming was assessed in a model of repeated injections of monosodium urate crystals or zymosan into the paw. I-BET151 was given either from before arthritis induction, at peak inflammation, or after healing of the first arthritis bout. Transcriptomic (RNA-Seq), epigenomic (ATAC-Seq) and functional analysis (invasion, cytokine production, migration, senescence, metabolic flux) was performed on murine and human SFs treated with I-BET151 in vitro or in vivo. RESULTS: Systemic I-BET151 administration did not affect acute inflammation but abolished inflammatory tissue priming and diminished flare severity in both preventive and therapeutic treatment settings. I-BET151 was also effective when applied locally in the joint. BET inhibition also inhibited osteoclast differentiation, while macrophage activation in the joint was not affected. Flare reduction after BET inhibition was mediated, at least in part, by rolling back the primed transcriptional, metabolic and pathogenic phenotype of SFs. CONCLUSION: Inflammatory tissue priming is dependent on transcriptional regulation by BET proteins, which makes them promising therapeutic targets for preventing arthritis flares in previously affected joints

Comparison of H-alpha and UV Star Formation Rates in the Local Volume: Systematic Discrepancies for Dwarf Galaxies

(abridged) Using a complete sample of ~300 star-forming galaxies within 11 Mpc, we evaluate the consistency between star formation rates (SFRs) inferred from the far ultraviolet (FUV) non-ionizing continuum and H-alpha nebular emission, assuming standard conversion recipes in which the SFR scales linearly with luminosity at a given wavelength. Our analysis probes SFRs over 5 orders of magnitude, down to ultra-low activities on the order of ~0.0001 M_sun/yr. The data are drawn from the 11 Mpc H-alpha and Ultraviolet Galaxy Survey (11HUGS), which has obtained H-alpha fluxes from ground-based narrowband imaging, and UV fluxes from imaging with GALEX. For normal spiral galaxies (SFR~1 M_sun/yr), our results are consistent with previous work which has shown that FUV SFRs tend to be lower than H-alpha SFRs before accounting for internal dust attenuation, but that there is relative consistency between the two tracers after proper corrections are applied. However, a puzzle is encountered at the faint end of the luminosity function. As lower luminosity dwarf galaxies, roughly less active than the Small Magellanic Cloud, are examined, H-alpha tends to increasingly under-predict the SFR relative to the FUV. Although past studies have suggested similar trends, this is the first time this effect is probed with a statistical sample for galaxies with SFR~<0.1 M_sun/yr. A range of standard explanations does not appear to be able to account for the magnitude of the systematic. Some recent work has argued for an IMF which is deficient in high mass stars in dwarf and low surface brightness galaxies, and we also consider this scenario.Comment: 29 pages, 10 figures, 2 tables, accepted for publication in Ap