The nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome drives many inflammatory processes and mediates IL-1 family cytokine release. ...Inflammasome activators typically damage cells and may release lysosomal and mitochondrial products into the cytosol. Macrophages triggered by the NLRP3 inflammasome activator nigericin show reduced mitochondrial function and decreased cellular ATP. Release of mitochondrial reactive oxygen species (ROS) leads to subsequent lysosomal membrane permeabilization (LMP). NLRP3-deficient macrophages show comparable reduced mitochondrial function and ATP loss, but maintain lysosomal acidity, demonstrating that LMP is NLRP3 dependent. A subset of wild-type macrophages undergo subsequent mitochondrial membrane permeabilization and die. Both LMP and mitochondrial membrane permeabilization are inhibited by potassium, scavenging mitochondrial ROS, or NLRP3 deficiency, but are unaffected by cathepsin B or caspase-1 inhibitors. In contrast, IL-1β secretion is ablated by potassium, scavenging mitochondrial ROS, and both cathepsin B and caspase-1 inhibition. These results demonstrate interplay between lysosomes and mitochondria that sustain NLRP3 activation and distinguish cell death from IL-1β release.
In this study, the effects of internal pores on the tensile behavior of austenitic stainless steel 316L manufactured with laser powder bed fusion (L-PBF) additive manufacturing (AM) were ...investigated. Both fully-dense samples and samples with intentional internal pores of varying diameters were fabricated. For each sample with a pore, the internal pore was deliberately fabricated in the center of the cylindrical tensile sample during AM processing. By varying the diameter of the 180 μm-tall initial penny-shaped pores, from 150 to 4800 μm within 6 mm gauge diameter cylindrical samples, the impact of lack-of-fusion, commonly present in AM, as well as the impact of well-defined pores in general, on tensile mechanical properties was studied. To link the pore size and morphology to the mechanical properties, the sizes of the initial pores were evaluated using non-destructive Archimedes measurements, 2D X-ray radiography, 3D X-ray computed tomography, and destructive 2D optical microscopy. Samples with and without the single, penny-shaped pore were subjected to uniaxial tension to evaluate the defect size dependent mechanical properties. The intentional pore began to impact ultimate tensile strength when the pore diameter was 2400 μm, or 16% of the cross-sectional sample area. Elongation to failure was significantly affected when the pore diameter was 1800 μm or 9% of the cross-sectional sample area. This shows that 316L stainless steel manufactured by additive manufacturing is defect-tolerant under uniaxial tension loading.
Heid E. Erdrich writes from the present into the future where human anxiety lives. Many of her poems engage ekphrasis around the visual work of contemporary artists who, like Erdrich, are ...Anishinaabe. Poems in this collection also curate unmountable exhibits in not-yet-existent museums devoted to the ephemera of communication and technology. A central trope is the mixtape, an ephemeral form that Erdrich explores in its role of carrying the romantic angst of American couples. These poems recognize how our love of technology and how the extraction industries on indigenous lands that technology requires threaten our future and obscure the realities of indigenous peoples who know what it is to survive apocalypse. Deeply eco-poetic poems extend beyond the page in poemeos, collaboratively made poem films accessible in the text through the new but already archaic use of QR codes. Collaborative poems highlighting lessons in Anishinaabemowin also broaden the context of Erdrich's work. Despite how little communications technology has helped to bring people toward understanding one another, these poems speak to the keen human yearning to connect as they urge engagement of the image, the moment, the sensual, and the real.
This study investigates the disparate impact of internal pores on the fracture behavior of two metal alloys fabricated via laser powder bed fusion (L-PBF) additive manufacturing (AM)—316L stainless ...steel and Ti-6Al-4V. Data from mechanical tests over a range of stress states for dense samples and those with intentionally introduced penny-shaped pores of various diameters were used to contrast the combined impact of pore size and stress state on the fracture behavior of these two materials. The fracture data were used to calibrate and compare multiple fracture models (Mohr-Coulomb, Hosford-Coulomb, and maximum stress criteria), with results compared in equivalent stress (versus stress triaxiality and Lode angle) space, as well as in their conversions to equivalent strain space. For L-PBF 316L, the strain-based fracture models captured the stress state dependent failure behavior up to the largest pore size studied (2400 µm diameter, 16% cross-sectional area of gauge region), while for L-PBF Ti-6Al-4V, the stress-based fracture models better captured the change in failure behavior with pore size up to the largest pore size studied. This difference can be attributed to the relatively high ductility of 316L stainless steel, for which all samples underwent significant plastic deformation prior to failure, contrasted with the relatively low ductility of Ti-6Al-4V, for which, with increasing pore size, the displacement to failure was dominated by elastic deformation.
Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged ...either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors.
The aim of this study was to identify processing-microstructure-mechanical property links in additively manufactured Ti-6Al-4V. First, the microstructure and mechanical properties of Ti-6Al-4V ...produced via two laser powder bed fusion (LPBF) additive manufacturing (AM) methods, one using a pulsed laser (P-LPBF) and the other a continuous-wave laser (CW-LPBF), were investigated and compared. Second, existing data from the literature were integrated with the present data in order to identify a general quantitative relationship between anisotropic ductility and grain morphology in additively manufactured Ti-6Al-4V. This revealed that an exponential relationship exists between the anisotropic grain morphology and anisotropic elongation to failure in Ti-6Al-4V. In particular, this relationship shows that a prior-β grain aspect ratio (grain height to grain width) exceeding 6 results in significant anisotropy in elongation. Namely, the columnar grains dominate the fracture mechanics by furnishing significant damage accumulation paths for tension in the longitudinal direction, resulting in higher ductility in the build direction than that in the longitudinal direction. With respect to processing, it was shown that as-built CW-LPBF samples had nearly equiaxed grains while those made by P-LPBF had elongated columnar grains. This resulted in greater yield strength, ultimate tensile strength, and ductility in the CW-LPBF samples compared to P-LPBF samples.
The multiaxial yield and plastic flow behavior of Ti-6Al-4V manufactured in two orientations via laser powder bed fusion (L-PBF) additive manufacturing was investigated. The mechanical properties of ...L-PBF Ti-6Al-4V were evaluated under uniaxial tension, plane strain tension, pure shear, and combined tension/shear loading. The mechanical behavior was found to be stress state dependent and slightly anisotropic. A plasticity model, consisting of a Hill 1948 anisotropic yield criterion, associated flow rule, and an isotropic hardening law was calibrated and used to describe the yield and plasticity behavior of this material. Validation of the plasticity model under multiaxial stress states demonstrated that the model was able to predict the stress state dependent anisotropic plasticity behavior of this material.
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