Early Detection of Peripheral Blood Cell Signature in Children Developing Beta-Cell Autoimmunity at a Young Age

The appearance of Type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, autoantibodies indicate an active autoimmune reaction, wherein the immune tolerance is already broken. Therefore, there is a clear and urgent need for new biomarkers that predict the onset of the autoimmune reaction preceding autoantibody positivity or reflect progressive beta-cell destruction. Here we report the mRNA-sequencing-based analysis of 306 samples including fractionated samples of CD4+ and CD8+ T cells as well as CD4-CD8- cells fractions and unfractionated PBMC samples longitudinally collected from seven children that developed beta-cell autoimmunity (Cases) at a young age and their matched controls. We identified transcripts, including interleukin-32 (IL32) that were upregulated before T1D-associated autoantibodies appeared. Single-cell RNA-seq studies revealed that high IL32 in Case samples were contributed mainly by activated T cells and NK cells. Further, we showed that IL32 expression can be induced by a virus and cytokines in pancreatic islets and beta-cells, respectively. The results provide a basis for early detection of aberrations in the immune system function before T1D and suggest a potential role for IL32 in the pathogenesis of T1D.</p

Characterization of Friction Stir and TIG Welded CK45 Carbon Steel

The present paper aims to compare the microstructural and mechanical properties of CK45 carbon steel plates, joined by friction stir (FSW) and tungsten inert gas (TIG) welding methods. Besides visual inspection, the welded joints and the base material were subsequently evaluated in respect of optical microstructures, hardness and tensile properties. Sound joints could be accomplished using both the FSW and TIG welding methods through proper selection of process parameters and the filler metal. The influence of a water-cooling system on the FSW and various filler metals on the quality of TIG welding were further assessed. Both the FS welded sample as well as TIG welded samples with two different filler metals ER70S-6 and ER80S-B2 exhibited brittle behavior that could be mitigated through optimized water cooling and use of R60 filler metal. A drastic reduction of brittle martensite phase constituent in the microstructure corroborated significant improvements in mechanical properties of the welded zones for both the FSW sample as well as TIG welded samples with R60 filler metal

Hot deformation characteristic and strain dependent constitutive flow stress modelling of Ti + Nb stabilized interstitial free steel

Abstract An effort has been made to establish a relation between Zener–Hollomon parameter, flow stress and dynamic recrystallization (DRX). In this context, the plastic flow behavior of Ti + Nb stabilized interstitial free (IF) steel was investigated in a temperature range of 650–1100 °C and at constant true strain rates in the range 10−3–10 s−1, to a total true strain of 0.7. The flow stress curves can be categorized into two distinct types, i.e. with/without the presence of steady-state flow following peak stress behavior. A novel constitutive model comprising the strain effect on the activation energy of DRX and other material constants has been established to predict the constitutive flow behavior of the IF steel in both α and γ phase regions, separately. Predicted flow stress seems to correlate well with the experimental data both in γ and α phase regions with a high correlation coefficient (0.982 and 0.936, respectively) and low average absolute relative error (7 and 11%, respectively) showing excellent fitting. A detailed analysis of the flow stress, activation energy of DRX and stress exponent in accord with the modelled equations suggests that dislocation glide controlled by dislocation climb is the dominant mechanism for the DRX, as confirmed by the transmission electron microscopy analysis

Abnormal mechanical response in a silicon bearing medium carbon low alloy steel following quenching and bainitic holding versus quenching and partitioning treatment

Abstract Multiphase advanced high strength low alloy steels having a refined microstructure of hard bainite and/or martensite laths, interspersed with finely divided retained austenite films, are the potential candidate materials for futuristic industrial applications, such as automotive industry, structural parts, crankshafts and shafts, and powertrain components. In this study, a silicon-bearing, medium-carbon low alloy steel grade of DIN 1.5025 was subjected to both quenching and bainitic holding (Q&B), as well as quenching and partitioning (Q&P) isothermal heat treatments at temperatures closely above and below the martensite start temperature (Ms), respectively. The mechanical response of heat treated samples was evaluated by conducting hardness and tensile tests, corroborated by XRD analysis and metallography using both scanning electron microscopy combined with electron backscatter diffraction as well as transmission electron microscopy. The experimental results showed that a number of Q&B heat treated samples displayed a superior combination of high strength levels with good ductility and work hardening capacity in comparison to that of Q&P ones, akin to the requirements for third generation high strength multiphase steels. It was also found that the superior mechanical response of Q&B heat treated samples was rationalized in respect of the formation of tough strong multiphase microstructures involving a fine mixture of hard bainite and/or martensite laths along with thin films of mostly interlath retained austenite that imparted superior combination of ductility and tensile strength through TRIP phenomenon. Moreover, limited tensile test results conducted in this study, supported by XRD and electron microscopy analyses, suggested that the TRIP response was quite effective in the Q&B multiphase samples containing more than 18 vol.% of retained austenite

Characterization of friction stir and TIG welded CK45 carbon steel

Abstract The present paper aims to compare the microstructural and mechanical properties of CK45 carbon steel plates, joined by friction stir (FSW) and tungsten inert gas (TIG) welding methods. Besides visual inspection, the welded joints and the base material were subsequently evaluated in respect of optical microstructures, hardness and tensile properties. Sound joints could be accomplished using both the FSW and TIG welding methods through proper selection of process parameters and the filler metal. The influence of a water-cooling system on the FSW and various filler metals on the quality of TIG welding were further assessed. Both the FS welded sample as well as TIG welded samples with two different filler metals ER70S-6 and ER80S-B2 exhibited brittle behavior that could be mitigated through optimized water cooling and use of R60 filler metal. A drastic reduction of brittle martensite phase constituent in the microstructure corroborated significant improvements in mechanical properties of the welded zones for both the FSW sample as well as TIG welded samples with R60 filler metal

Effect of carbon partitioning and residual compressive stresses on the lattice strains of retained austenite during quenching and isothermal bainitic holding in a high-silicon medium-carbon steel

Abstract The residual compressive stresses and dimensional changes related to the lattice strains of retained austenite (RA) phase in a high-Si, medium-carbon steel (Fe-0.53C-1.67Si-0.72Mn-0.12Cr) are investigated for samples austenitized and quenched for isothermal bainitic transformation (Q&amp;B) in the range 5 s to 1 h at 350 °C. Also, samples are directly quenched in water (DWQ) from the austenitization temperature for comparison with Q&amp;B samples. Field emission scanning electron microscopy (FE-SEM) combined with electron backscatter diffraction (EBSD) analyses, and X-ray diffraction are used to investigate the microstructural evolution, phase distribution, and lattice parameters of RA phase. While the Q&amp;B samples showed formation of bainite and high-carbon fresh martensite in conjunction with stabilization of various fractions of RA, the DWQ samples displayed nearly complete martensitic microstructure. For short holding durations (≪200 s), there was limited formation of bainite and the inadequate carbon partitioning to the adjacent untransformed austenite areas resulted in significant martensite formation and the associated c/a ratio of martensite resulted in high compressive residual stresses within the RA phase. While, at long isothermal holding times (≫ 200 s), there was a significant formation of bainite. The DWQ samples displayed maximum lattice strain in a small fraction of untransformed RA phase

On the decomposition of austenite in a high-silicon medium-carbon steel during quenching and isothermal holding above and below the Mₛ temperature

Abstract The microstructural mechanisms operating during the decomposition of austenite in a high-Si, medium‑carbon steel (Fe-0.53C-1.67Si-0.72Mn-0.12Cr) subjected to quenching and isothermal holding at temperatures above and below the martensite start (Mₛ) temperature for times up to 1 h have been investigated using a Gleeble 3800 thermomechanical simulator. Dilatometry and metallography using laser scanning microscopy, transmission electron microscopy, scanning electron microscopy together with X-ray diffraction and hardness measurements have been employed. Treatment with the quench stop and isothermal hold both above and below Ms lead to the formation of both martensite and bainite. In the case of isothermal treatment above Mₛ, at 350 and 300 °C, high‑carbon martensite is formed during the final cooling to room temperature. In the case of isothermal treatment at temperatures below Mₛ, at 250 and 200 °C, the initial martensite formation and subsequent carbon partitioning to austenite is followed by the formation of bainite containing carbides and high‑carbon martensite that forms during the final cooling to room temperature. Despite the presence of the high silicon content, carbides are able to form even at the lowest temperature studied (200 °C). All treatments led to the presence of carbon enriched retained austenite, which ranged from 4 to 18 vol%. The variation of room temperature hardness as a function of isothermal holding time at the various temperatures is rationalized in terms of the microstructural development

Hot forming of ultra-fine-grained multiphase steel products using press hardening combined with quenching and partitioning process

Abstract Hot forming combined with austempering and quenching and partitioning (QP) processes have been used to shape two cold rolled high silicon steel sheets into hat profiles. Thermal simulation on a Gleeble instrument was employed to optimize processing variables to achieve an optimum combination of strength and ductility in the final parts. Microstructures were characterized using optical and scanning electron microscopy and X-ray diffraction. Tensile strengths (Rₘ) of 1190 and 1350 MPa and elongations to fracture (A₅₀ₘₘ) of 8.5 and 7.4%, were achieved for the two high-silicon steels having 0.15 and 0.26 wt % C, respectively. Preliminary results show that press hardening together with a QP heat treatment is an effective method of producing components with high strength and reasonable tensile ductility from low carbon containing steels that have the potential for carbide free bainite formation. The QP treatment resulted in faster austenite decomposition during partitioning in the steels in comparison with an austempering treatment

Early detection of peripheral blood cell signature in children developing β-cell autoimmunity at a young age

The appearance of type 1 diabetes (T1D)-associated autoantibodies is the first and only measurable parameter to predict progression toward T1D in genetically susceptible individuals. However, autoantibodies indicate an active autoimmune reaction, wherein the immune tolerance is already broken. Therefore, there is a clear and urgent need for new biomarkers that predict the onset of the autoimmune reaction preceding autoantibody positivity or reflect progressive β-cell destruction. Here we report the mRNA sequencing-based analysis of 306 samples including fractionated samples of CD4+ and CD8+ T cells as well as CD4-CD8- cell fractions and unfractionated peripheral blood mononuclear cell samples longitudinally collected from seven children who developed β-cell autoimmunity (case subjects) at a young age and matched control subjects. We identified transcripts, including interleukin 32 (IL32), that were upregulated before T1D-associated autoantibodies appeared. Single-cell RNA sequencing studies revealed that highIL32 in case samples was contributed mainly by activated T cells and NK cells. Further, we showed that IL32 expression can be induced by a virus and cytokines in pancreatic islets and β-cells, respectively. The results provide a basis for early detection of aberrations in the immune system function before T1D and suggest a potential role for IL32 in the pathogenesis of T1D.Peer reviewe