Multi-gradient structures by cold extrusion of strongly textured continuously cast commercially pure aluminum

During extrusion, the material is subjected to a heterogeneous deformation that results in the formation of gradients of microstructure and thus mechanical properties. In this study, using continuously cast commercially pure aluminum as a reference material, we show how a cast structure with coarse columnar grains affects the formation of these gradients during extrusion at room temperature. Characterization of the initial material as well as the extruded round bars by optical and electron microscopy, X-ray diffraction as well as by means of mechanical testing documents the formation of four characteristic annular sections. For extrusion along the casting direction there is a / double-fiber textured center with lowest hardness, followed by a single-fiber textured ring with a hardness plateau, a double-fiber textured region with grains arranged alternatingly in an iris-like shape, and an (ultra-)fine grained surface layer with highest hardness. For extrusion opposite to the casting direction we find similar characteristics of the center section. With increasing distance from the center follow another double-fiber textured section with increasing hardness, a single-fiber textured ring with nearly homogeneous hardness and a surface layer with a slightly rotated fiber and highest hardness. The key finding is that the macroscopic anisotropy of the cast material, resulting from the grain size, crystal orientation and growth direction of the columnar grains, determines the local material flow during extrusion and thus leads to the formation of these different complex multi-gradient macrostructures that may provide unique properties for complex applications such as light-weight safety-relevant components

Influence of Extrusion Temperature on the Aging Behavior and Mechanical Properties of an AA6060 Aluminum Alloy

Processing of AA6060 aluminum alloys for semi-products usually includes hot extrusion with subsequent artificial aging for several hours. Processing below the recrystallization temperature allows for an increased strength at a significantly reduced annealing time by combining strain hardening and precipitation hardening. In this study, we investigate the potential of cold and warm extrusion as alternative processing routes for high strength aluminum semi-products. Cast billets of the age hardening aluminum alloy AA6060 were solution annealed and then extruded at room temperature, 120 or 170 °C, followed by an aging treatment. Electron microscopy and mechanical testing were performed on the as-extruded as well as the annealed materials to characterize the resulting microstructural features and mechanical properties. All of the extruded profiles exhibit similar, strongly graded microstructures. The strain gradients and the varying extrusion temperatures lead to different stages of dynamic precipitation in the as-extruded materials, which significantly alter the subsequent aging behavior and mechanical properties. The experimental results demonstrate that extrusion below recrystallization temperature allows for high strength at a massively reduced aging time due to dynamic precipitation and/or accelerated precipitation kinetics. The highest strength and ductility were achieved by extrusion at 120 °C and subsequent short-time aging

Combined Effect of Particle Reinforcement and T6 Heat Treatment on the Compressive Deformation Behavior of an A357 Aluminum Alloy at Room Temperature and at 350 °C

Solid state sintering of cast aluminum powders by resistance heating sintering (RHS), also known as spark plasma sintering or field-assisted sintering technique, creates a very fine microstructure in the bulk material. This leads to high performance material properties with an improved strength and ductility compared to conventional production routes of the same alloys. In this study, the mechanical behavior of an RHS-sintered age-hardenable A357 (AlSi7Mg0.6) cast alloy and a SiCp/A357 aluminum matrix composite (AMC) was investigated. Aiming for high strength and good wear behavior in tribological applications, the AMC was reinforced with a high particle content (35 vol.%) of a coarse particle fraction (d50 = 21 µm). Afterwards, separated and combined effects of particle reinforcement and heat treatment were studied under compressive load both at room temperature and at 350 °C. At room temperature compression, the strengthening effect of precipitation hardening was about twice as high as that for the particle reinforcement, despite the high particle content. At elevated temperatures, the compressive deformation behavior was characterized by simultaneously occurring temperature-activated recovery, recrystallisation and precipitation processes. The occurrence and interaction of these processes was significantly affected by the initial material condition. Moreover, a rearrangement of the SiC reinforcement particles was detected after hot deformation. This rearrangement lead to a homogenized dispersion of the reinforcement phase without considerable particle fragmentation, which offers the potential for secondary thermo-mechanical processing of highly reinforced AMCs

The Association between Neoadjuvant Radio-Chemotherapy and Prolonged Healing of Anastomotic Leakage after Esophageal Resection Treated with EndoVAC Therapy

(1) Background: Endoscopic vacuum therapy (EVT) has become the mainstay in the treatment of early anastomotic leakage (AL) after esophageal resection. The effect of nRCT on the efficacy of EVT is currently unknown. (2) Methods: Data of 427 consecutive patients undergoing minimally invasive esophagectomy between 2013 and 2022 were analyzed. A total of 26 patients received EVT for AL after esophagectomy between 2010 and 2021. We compared a cohort of 13 patients after treatment with EVT for anastomotic leakage after neoadjuvant radiochemotherapy (nRCT) with a control group of 13 patients after neoadjuvant chemotherapy (nCT) using inverse propensity score weighting to adjust for baseline characteristics between the groups. EVT therapy was assessed regarding patient survival, treatment failure as defined by a change in treatment to stent/operation, duration of treatment, and secondary complications. Statistical analysis was performed using linear regression analysis. (3) Results: Time to EVT after initial tumor resection did not vary between the groups. The duration of EVT was longer in patients after nRCT (14.69 days vs. 20.85 days, p = 0.002) with significantly more interventions (4.38 vs. 6.85, p = 0.001). The success rate of EVT did not differ between the two groups (nCT n = 8 (61.54%) vs. nCT n = 5 (38.46%), p = 0.628). The rate of operative revision did not vary between the groups. Importantly, no mortality was reported within 30 days and 90 days in both groups. (4) Conclusions: EVT is a valuable tool for the management of AL after esophageal resection in patients after nRCT. While the success rates were comparable, EVT was associated with a significantly longer treatment duration. Anastomotic leakages after nRCT often require prolonged and multimodal treatment strategies while innovative strategies such as prophylactic endoVAC placement or use of a VAC-Stent may be considered

RPA and Rad51 constitute a cell intrinsic mechanism to protect the cytosol from self DNA.

Immune recognition of cytosolic DNA represents a central antiviral defence mechanism. Within the host, short single-stranded DNA (ssDNA) continuously arises during the repair of DNA damage induced by endogenous and environmental genotoxic stress. Here we show that short ssDNA traverses the nuclear membrane, but is drawn into the nucleus by binding to the DNA replication and repair factors RPA and Rad51. Knockdown of RPA and Rad51 enhances cytosolic leakage of ssDNA resulting in cGAS-dependent type I IFN activation. Mutations in the exonuclease TREX1 cause type I IFN-dependent autoinflammation and autoimmunity. We demonstrate that TREX1 is anchored within the outer nuclear membrane to ensure immediate degradation of ssDNA leaking into the cytosol. In TREX1-deficient fibroblasts, accumulating ssDNA causes exhaustion of RPA and Rad51 resulting in replication stress and activation of p53 and type I IFN. Thus, the ssDNA-binding capacity of RPA and Rad51 constitutes a cell intrinsic mechanism to protect the cytosol from self DNA

Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism

Abstract The Escherichia coli TetR-related transcriptional regulator RutR is involved in the coordination of pyrimidine and purine metabolism. Here we report that lysine acetylation modulates RutR function. Applying the genetic code expansion concept, we produced site-specifically lysine-acetylated RutR proteins. The crystal structure of lysine-acetylated RutR reveals how acetylation switches off RutR-DNA-binding. We apply the genetic code expansion concept in E. coli in vivo revealing the consequences of RutR acetylation on the transcriptional level. We propose a model in which RutR acetylation follows different kinetic profiles either reacting non-enzymatically with acetyl-phosphate or enzymatically catalysed by the lysine acetyltransferases PatZ/YfiQ and YiaC. The NAD+-dependent sirtuin deacetylase CobB reverses enzymatic and non-enzymatic acetylation of RutR playing a dual regulatory and detoxifying role. By detecting cellular acetyl-CoA, NAD+ and acetyl-phosphate, bacteria apply lysine acetylation of transcriptional regulators to sense the cellular metabolic state directly adjusting gene expression to changing environmental conditions

Sensing Acute Cellular Rejection in Liver Transplant Patients Using Liver-Derived Extracellular Particles: A Prospective, Observational Study

Acute cellular rejection (ACR) after liver transplantation (LT) goes along with allograft dysfunction, which is diagnosed by liver biopsy and concomitant histological analysis, representing the gold standard in clinical practice. Yet, liver biopsies are invasive, costly, time-intensive and require expert knowledge. Herein we present substantial evidence that blood plasma residing peripheral liver-derived extracellular particles (EP) could be employed to diagnose ACR non-invasively. In vitro experiments showed organ-specific EP release from primary human hepatocytes under immunological stress. Secondly, analysis of consecutive LT patients (n=11) revealed significant heightened EP concentrations days before ACR. By conducting a diagnostic accuracy study (n = 69, DRKS00011631), we explored the viability of using EP as a liquid biopsy for diagnosing ACR following LT. Consequently, novel EP populations in samples were identified using visualization of t-distributed stochastic neighbor embedding (viSNE) and self-organizing maps (FlowSOM) algorithms. As a result, the ASGR1(+)CD130(+)Annexin V+ EP subpopulation exhibited the highest accuracy for predicting ACR (area under the curve: 0.80, 95% confidence interval [CI], 0.70-0.90), with diagnostic sensitivity and specificity of 100% (95% CI, 81.67-100.0%) and 68.5% (95% CI, 55.3-79.3%), respectively. In summary, this new EP subpopulation presented the highest diagnostic accuracy for detecting ACR in LT patients