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Sökning: WFRF:(Dinis R)

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  • Pöntinen, M., et al. (författare)
  • Euclid: Identification of asteroid streaks in simulated images using deep learning
  • 2023
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 679
  • Tidskriftsartikel (refereegranskat)abstract
    • The material composition of asteroids is an essential piece of knowledge in the quest to understand the formation and evolution of the Solar System. Visual to near-infrared spectra or multiband photometry is required to constrain the material composition of asteroids, but we currently have such data, especially in the near-infrared wavelengths, for only a limited number of asteroids. This is a significant limitation considering the complex orbital structures of the asteroid populations. Up to 150 000 asteroids will be visible in the images of the upcoming ESA Euclid space telescope, and the instruments of Euclid will offer multiband visual to near-infrared photometry and slitless near-infrared spectra of these objects. Most of the asteroids will appear as streaks in the images. Due to the large number of images and asteroids, automated detection methods are needed. A non-machine-learning approach based on the Streak Det software was previously tested, but the results were not optimal for short and/or faint streaks. We set out to improve the capability to detect asteroid streaks in Euclid images by using deep learning. We built, trained, and tested a three-step machine-learning pipeline with simulated Euclid images. First, a convolutional neural network (CNN) detected streaks and their coordinates in full images, aiming to maximize the completeness (recall) of detections. Then, a recurrent neural network (RNN) merged snippets of long streaks detected in several parts by the CNN. Lastly, gradient-boosted trees (XGBoost) linked detected streaks between different Euclid exposures to reduce the number of false positives and improve the purity (precision) of the sample. The deep-learning pipeline surpasses the completeness and reaches a similar level of purity of a non-machine-learning pipeline based on the StreakDet software. Additionally, the deep-learning pipeline can detect asteroids 0.25–0.5 magnitudes fainter than StreakDet. The deep-learning pipeline could result in a 50% increase in the number of detected asteroids compared to the StreakDet software. There is still scope for further refinement, particularly in improving the accuracy of streak coordinates and enhancing the completeness of the final stage of the pipeline, which involves linking detections across multiple exposures.
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  • Hess, Timo, et al. (författare)
  • Dissecting the genetic heterogeneity of gastric cancer
  • 2023
  • Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. 
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  • Apollonio, Benedetta, et al. (författare)
  • Tumor-activated lymph node fibroblasts suppress T cell function in diffuse large B cell lymphoma
  • 2023
  • Ingår i: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 133:13
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent transcriptomic-based analysis of diffuse large B cell lymphoma (DLBCL) has highlighted the clinical relevance of LN fibroblast and tumor-infiltrating lymphocyte (TIL) signatures within the tumor microenvironment (TME). However, the immunomodulatory role of fibroblasts in lymphoma remains unclear. Here, by studying human and mouse DLBCL-LNs, we identified the presence of an aberrantly remodeled fibroblastic reticular cell (FRC) network expressing elevated fibroblast activated protein (FAP). RNA-Seq analyses revealed that exposure to DLBCL reprogrammed key immunoregulatory pathways in FRCs, including a switch from homeostatic to inflammatory chemokine expression and elevated antigen-presentation molecules. Functional assays showed that DLBCL-activated FRCs (DLBCL-FRCs) hindered optimal TIL and chimeric antigen receptor (CAR) T cell migration. Moreover, DLBCL-FRCs inhibited CD'+ TIL cytotoxicity in an antigen-specific manner. Notably, the interrogation of patient LNs with imaging mass cytometry identified distinct environments differing in their CD'+ TIL-FRC composition and spatial organization that associated with survival outcomes. We further demonstrated the potential to target inhibitory FRCs to rejuvenate interacting TILs. Cotreating organotypic cultures with FAP-targeted immunostimulatory drugs and a bispecific antibody (glofitamab) augmented antilymphoma TIL cytotoxicity. Our study reveals an immunosuppressive role of FRCs in DLBCL, with implications for immune evasion, disease pathogenesis, and optimizing immunotherapy for patients.
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