| 1. |
- He, Fei, et al.
(författare)
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FPR2 Shapes an Immune-Excluded Pancreatic Tumor Microenvironment and Drives T-cell Exhaustion in a Sex-Dependent Manner
- 2023
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Ingår i: Cancer Research. - : American Association for Cancer Research (AACR). - 0008-5472 .- 1538-7445. ; 83:10, s. 1628-1645
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Tidskriftsartikel (refereegranskat)abstract
- Sex-driven immune differences can affect tumor progression and the landscape of the tumor microenvironment. Deeper understanding of these differences in males and females can inform patient selection to improve sex-optimized immunotherapy treatments. In this study, single-cell RNA sequencing and protein analyses uncovered a subpopulation of myeloid cells in pancreatic lesions associated with an immune-excluded tumor phenotype and effector T-cell exhaustion exclusively in females. This myeloid subpopulation was positively correlated with poor survival and genetic signatures of M2-like macrophages and T-cell exhaustion in females. The G-protein coupled receptor formyl peptide receptor 2 (FPR2) mediated these immunosuppressive effects. In vitro, treatment of myeloid cells with a specific FPR2 antagonist prevented exhaustion and enhanced cytotoxicity of effector cells. Proteomic analysis revealed high expression of immunosuppressive secretory proteins PGE2 and galectin-9, enriched integrin pathway, and reduced proinflammatory signals like TNFα and IFNγ in female M2-like macrophages upon FPR2 agonist treatment. In addition, myeloid cells treated with FPR2 agonists induced TIM3 and PD-1 expression only in female T cells. Treatment with anti-TIM3 antibodies reversed T-cell exhaustion and stimulated their ability to infiltrate and kill pancreatic spheroids. In vivo, progression of syngeneic pancreatic tumors was significantly suppressed in FPR2 knockout (KO) female mice compared with wild-type (WT) female mice and to WT and FPR2 KO male mice. In female mice, inoculation of tumors with FPR2 KO macrophages significantly reduced tumor growth compared with WT macrophages. Overall, this study identified an immunosuppressive function of FPR2 in females, highlighting a potential sex-specific precision immunotherapy strategy.
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| 2. |
- Sahl, Mikael, et al.
(författare)
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Experimental verification of phased array annular probe in ultrasonic immersion setting : Papers of the ECNDT 2023
- 2023
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Ingår i: Research and Review Journal of Nondestructive Testing. - : NDT.net. - 2941-4989. ; 1:1, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- With the ongoing development of materials and manufacturing techniques, new product design opportunities manifest themselves. However, care must be taken when applying techniques and material where there is less inherent knowledge about different parameters’ effect on the integrity of the final component. In conjunction with destructive testing of components, non-destructive evaluation (NDE) provides valuable insight into the manufacturing process reliability, as well as the possibility for subsequent future in-service inspection. Phased array ultrasonic testing (PAUT) facilitates the inspection of complex geometries on a wide set of material. Mathematical modelling of ultrasonic signal facilitates the optimization of inspection procedures by e.g., maximizing the probability of detection (POD) of specific defect types. In this paper, the response from an immersion annular phased array probe is experimentally validated to the output of the simulation software simSUNDT. In order to only validate the probe model (as both transmitter and receiver) a set of well-defined defects are used. The validity of the simulated amplitude response from side-drilled holes at a depth range of 20-115 mm is investigated. A total of 14 SDH holes in one test piece of is used as cases for validation. The results show a good correspondence between simulated and experimental data for the case where the probe is normal to the component surface.
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| 3. |
- Sahl, Mikael, et al.
(författare)
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Nondestructive evaluation of additively manufactured components
- 2023. - 1.
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Ingår i: Additive Manufacturing of High-Performance metallic Materials. - : Elsevier. - 9780323918855 - 9780323913829 ; , s. 639-675
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Bokkapitel (refereegranskat)abstract
- Lightweight and optimized designs through modern metal additivemanufacturing (AM) require reliable manufacturing processes and put highdemands on quality assessment and control. This part addressesnondestructive testing (NDT) technologies and their industrial AMapplications with a focus on process monitoring, control, and development.Data derived from NDT can be used for process monitoring (as sensors), inprocess nondestructive evaluation (NDE), or postprocess NDE. This chapteraims to define and point out the distinction between these differentframeworks. The methods and techniques addressed include (a) Defectsintroduced during manufacturing, welding (pores, lack of fusion, etc.) withthe NDT perspective in focus; (b) in-service inspection (ISI) andmanufacturing control (in-process and postprocess NDE); (c) NDT methodsand associated physics; (d) standards related to NDT for AM, includingprobability of detection (POD); and (e) mathematical modeling andapplication of NDE simulations.
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