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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 1,063 records · Page 59
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Fenofibrate activates Nrf2 through p62-dependent Keap1 degradation

Peroxisome proliferator-activated receptor α (PPARα) activates the β-oxidation of fatty acids in the liver. Fenofibrate is a potent agonist of PPARα and is used in the treatment of hyperlipidemia. Fenofibrate treatment often induces the production of intracellular reactive oxygen species (ROS), leading to cell death. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is an essential component of the defense mechanism against oxidative stress. However, the molecular mechanism underlying the regulation of the Nrf2-Keap1 pathway in fenofibrate-induced cell death is not known. In this study, we demonstrated that fenofibrate induces Keap1 degradation and Nrf2 activation. This fenofibrate-mediated Keap1 degradation is partly dependent on autophagy. Furthermore, fenofibrate-induced Keap1 degradation followed by Nrf2 activation is mainly mediated by p62, which functions as an adaptor protein in the autophagic pathway. Consistent with these findings, ablation of p62 increased fenofibrate-mediated apoptotic cell death associated with ROS accumulation. These results strongly suggest that p62 plays a crucial role in preventing fenofibrate-induced cell death. - Highlights: • Fenofibrate induces cell death by increasing ROS production. • The underlying defense mechanism against this effect is unknown. • Fenofibrate induces autophagy-dependent Keap1 degradation and Nrf2 activation. • This process is p62-dependent; lack of p62 enhanced fenofibrate-mediated apoptosis. • p62 plays a crucial role in preventing fenofibrate-induced cell death.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to inhibit hepatocellular carcinoma cells

The aim of the present study is to investigate the potential anti-hepatocellular carcinoma (HCC) cell activity by 4SC-202, a novel class I HDAC inhibitor (HDACi). The associated signaling mechanisms were also analyzed. We showed that 4SC-202 treatment induced potent cytotoxic and proliferation–inhibitory activities against established HCC cell lines (HepG2, HepB3, SMMC-7721) and patient-derived primary HCC cells. Further, adding 4SC-202 in HCC cells activated mitochondrial apoptosis pathway, which was evidenced by mitochondrial permeability transition pore (mPTP) opening, cytochrome C cytosol release and caspase-3/-9 activation. Inhibition of this apoptosis pathway, by caspase-3/-9 inhibitors, mPTP blockers, or by shRNA-mediated knockdown of cyclophilin-D (Cyp-D, a key component of mPTP), significantly attenuated 4SC-202-induced HCC cell death and apoptosis. Reversely, over-expression of Cyp-D enhanced 4SC-202's sensitivity in HCC cells. Further studies showed that 4SC-202 induced apoptosis signal-regulating kinase 1 (ASK1) activation, causing it translocation to mitochondria and physical association with Cyp-D. This mitochondrial ASK1-Cyp-D complexation appeared required for mediating 4SC-202-induced apoptosis activation. ASK1 stable knockdown by targeted-shRNAs largely inhibited 4SC-202-induced mPTP opening, cytochrome C release, and following HCC cell apoptotic death. Together, we suggest that 4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to potently inhibit human HCC cells. - Highlights: • 4SC-202 exerts potent anti-proliferative and cytotoxic activity against established/primary HCC cells. • SC-202-induced anti-HCC cell activity relies on caspase-dependent apoptosis activation. • 4SC-202 activates Cyp-D-dependent mitochondrial apoptosis pathway in HCC cells. • 4SC-202 activates ASK1 in HCC cells, causing it translocation to mitochondria. • Mitochondrial ASK1-Cyp-D complexation mediates 4SC-202's activity in HCC cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Both H4K20 mono-methylation and H3K56 acetylation mark transcription-dependent histone turnover in fission yeast

Nucleosome dynamics facilitated by histone turnover is required for transcription as well as DNA replication and repair. Histone turnover is often associated with various histone modifications such as H3K56 acetylation (H3K56Ac), H3K36 methylation (H3K36me), and H4K20 methylation (H4K20me). In order to correlate histone modifications and transcription-dependent histone turnover, we performed genome wide analyses for euchromatic regions in G2/M-arrested fission yeast. The results show that transcription-dependent histone turnover at 5′ promoter and 3′ termination regions is directly correlated with the occurrence of H3K56Ac and H4K20 mono-methylation (H4K20me1) in actively transcribed genes. Furthermore, the increase of H3K56Ac and H4K20me1 and antisense RNA production was observed in the absence of the histone H3K36 methyltransferase Set2 and histone deacetylase complex (HDAC) that are involved in the suppression of histone turnover within the coding regions. These results together indicate that H4K20me1 as well as H3K56Ac are bona fide marks for transcription-dependent histone turnover in fission yeast.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

pH-dependent electron transfer reaction and direct bioelectrocatalysis of the quinohemoprotein pyranose dehydrogenase

A pyranose dehydrogenase from Coprinopsis cinerea (CcPDH) is an extracellular quinohemoeprotein, which consists a b-type cytochrome domain, a pyrroloquinoline-quinone (PQQ) domain, and a family 1-type carbohydrate-binding module. The electron transfer reaction of CcPDH was studied using some electron acceptors and a carbon electrode at various pH levels. Phenazine methosulfate (PMS) reacted directly at the PQQ domain, whereas cytochrome c (cyt c) reacted via the cytochrome domain of intact CcPDH. Thus, electrons are transferred from reduced PQQ in the catalytic domain of CcPDH to heme b in the N-terminal cytochrome domain, which acts as a built-in mediator and transfers electron to a heterogenous electron transfer protein. The optimal pH values of the PMS reduction (pH 6.5) and the cyt c reduction (pH 8.5) differ. The catalytic currents for the oxidation of L-fucose were observed within a range of pH 4.5 to 11. Bioelectrocatalysis of CcPDH based on direct electron transfer demonstrated that the pH profile of the biocatalytic current was similar to the reduction activity of cyt c characters. - Highlights: • pH dependencies of activity were different for the reduction of cyt c and DCPIP. • DET-based bioelectrocatalysis of CcPDH was observed. • The similar pH-dependent profile was found with cyt c and electrode. • The present results suggested that IET reaction of CcPDH shows pH dependence.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2016

MiR-132 regulates osteogenic differentiation via downregulating Sirtuin1 in a peroxisome proliferator-activated receptor β/δ–dependent manner

MicroRNAs (miRNAs) play significant roles in multiple diseases by regulating the expression of their target genes. Type 2 diabetes mellitus (T2DM) is a chronic endocrine and metabolic disease with complex mechanisms. T2DM can result in diabetic osteoporosis (DO), which is characterized by bone loss, decreased bone mineral density and increased bone fractures. The promotion of osteogenic differentiation of osteoblasts is an effective way to treat osteoporosis. In the present study, high glucose (HG) and free fatty acids (FFA) were employed to mimic T2DM in MC3T3-E1 cells. To induce osteogenic differentiation, MC3T3-E1 cells were cultured in osteogenic medium. The results showed that osteogenic differentiation was significantly suppressed by HG and FFA. We found that miR-132 expression was significantly upregulated and much higher in HG-FFA–induced cells than other selected miRNAs, indicating that miR-132 might play an important role in DO. Furthermore, overexpression of miR-132 markedly inhibited the expression of key markers of osteogenic differentiation and alkaline phosphatase (ALP) activity. Reciprocally, inhibition of miR-132 restored osteogenic differentiation, even under treatment with HG-FFA. We also showed that Sirtuin 1 (Sirt1) was one of the target genes of miR-132, whose expression was controlled by miR-132. Ectopic expression of Sirt1 reversed the decrease in osteogenic differentiation caused by miR-132 and HG-FFA. These results demonstrated the direct role of miR-132 in suppressing osteogenic differentiation through downregulating Sirt1. Moreover, we demonstrated that peroxisome proliferator-activated receptor β/δ (PPARβ/δ) was a downstream molecule of Sirt1, and its knockout by PPARβ/δ siRNA significantly abolished the promotive effects of Sirt1 on osteogenic differentiation, indicating that Sirt1 functioned in a PPARβ/δ–dependent manner. Taken together, we provide crucial evidence that miR-132 plays a key role in regulating osteogenic differentiation through Sirt1 in a PPARβ/δ–dependent manner, indicating that miR-132 and Sirt1-PPARβ/δ may act as potential therapeutic targets for T2DM–induced osteoporosis. - Highlights: • MiR-132 participates in regulating osteogenic differentiation of MC3T3-E1 cells. • Sirt1 is a target gene of miR-132. • Sirt1 is the effector of miR-132 in regulating osteogenic differentiation. • MiR-132-Sirt1 regulates osteogenic differentiation in a PPARβ/δ–dependent manner.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Pulsed electromagnetic field inhibits RANKL-dependent osteoclastic differentiation in RAW264.7 cells through the Ca{sup 2+}-calcineurin-NFATc1 signaling pathway

Pulsed electromagnetic field (PEMF) has been reported to improve bone healing in osteoporosis patients. However, the precise mechanism has remained largely unknown. This study aimed to investigate the effects of PEMF on nuclear factor κB ligand (RANKL)-dependent osteoclastic differentiation and the Ca{sup 2+}-calcineurin-NFATc1 signaling pathway in RAW264.7 cells in vitro. Treating RAW264.7 cells with RANKL for 4 days induced osteoclastic differentiation in vitro, and the formation of multinucleated osteoclasts, bone resorption-pit formation, tartrate-resistant acid phosphatase (TRAP) activity and the protein levels of cathepsin K, TRAP, Nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and matrix metalloproteinase 9 (MMP-9) were significantly decreased. The mRNA levels of specific genes related to osteoclastogenesis (TRAP, NFATc1, CTSK and MMP-9) were also reduced. Moreover, the oscillations of intracellular Ca{sup 2+} in RANKL-dependent RAW264.7 cells were suppressed by PEMF, as well as by inhibitors of membrane and store-operated Ca{sup 2+} channels. Meanwhile, calcineurin activity was increased, although its protein level was not changed. PEMF increased phospho-NFATc1 in the cytosol while suppressing the nuclear translocation of NFATc1, thus inhibiting osteoclastic differentiation by suppressing the Ca{sup 2+}-calcineurin-NFATc1 signaling pathway. Although many questions remain unresolved, to our knowledge, this is the first report demonstrating that PEMF is beneficial against RANKL-dependent osteoclastic differentiation in RAW264.7 cells in vitro via inhibiting the Ca{sup 2+}-calcineurin-NFATc1 signaling pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Indispensable role of Notch ligand-dependent signaling in the proliferation and stem cell niche maintenance of APC-deficient intestinal tumors

Ligand-dependent activation of Notch signaling is required to maintain the stem-cell niche of normal intestinal epithelium. However, the precise role of Notch signaling in the maintenance of the intestinal tumor stem cell niche and the importance of the RBPJ-independent non-canonical pathway in intestinal tumors remains unknown. Here we show that Notch signaling was activated in LGR5{sup +ve} cells of APC-deficient mice intestinal tumors. Accordingly, Notch ligands, including Jag1, Dll1, and Dll4, were expressed in these tumors. In vitro studies using tumor-derived organoids confirmed the intrinsic Notch activity-dependent growth of tumor cells. Surprisingly, the targeted deletion of Jag1 but not RBPJ in LGR5{sup +ve} tumor-initiating cells resulted in the silencing of Hes1 expression, disruption of the tumor stem cell niche, and dramatic reduction in the proliferation activity of APC-deficient intestinal tumors in vivo. Thus, our results highlight the importance of ligand-dependent non-canonical Notch signaling in the proliferation and maintenance of the tumor stem cell niche in APC-deficient intestinal adenomas. - Highlights: • Notch signaling is activated in LGR5{sup +ve} cells of APC-deficient intestinal tumors. • Lack of Jag1 but not RBPJ disrupts stem cell niche formation in those tumors. • Lack of Jag1 reduces the proliferation activity of APC-deficient intestinal tumors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Human soluble thrombomodulin-induced blockade of peripheral HMGB1-dependent allodynia in mice requires both the lectin-like and EGF-like domains

Highlights: • Thrombomodulin alfa promotes the degradation of distinct HMGB1 by thrombin. • Thrombomodulin alfa blocks the allodynia caused by all-thiol and disulfide HMGB1. • The anti-allodynic activity requires both the lectin-like and EGF-like domains. • Thrombomodulin alfa is useful for treatment of HMGB1-dependent pain. Thrombomodulin (TM), an endothelial protein with anti-coagulant activity, is composed of 5 domains, D1-D5. Recombinant human soluble TM (TMα) consisting of D1-D3, which is generated in CHO cells, suppresses inflammatory and nociceptive signals by inactivating high mobility group box 1 (HMGB1), one of damage-associated molecular patterns. TMα sequesters HMGB1 with the lectin-like D1 and promotes its degradation by thrombin binding to the EGF-like D2. We prepared TM's D123, D1 and D2 by the protein expression system of yeast, and evaluated their effects on HMGB1 degradation in vitro and on the allodynia caused by HMGB1 in distinct redox forms in mice in vivo. TMα and TM's D123, but not D1, promoted the thrombin-dependent degradation of all-thiol (at-HMGB1) and disulfide HMGB1 (ds-HMGB1), an effect mimicked by TM's D2, though to a lesser extent. Intraplantar administration of TMα and TM's D123, but not D1, D2 or D1 plus D2, strongly prevented the mechanical allodynia caused by intraplantar at-HMGB1, ds-HMGB1 or lipopolysaccharide in mice. Our data suggest that, apart from the role of D3, TMα and TM's D123 require both lectin-like D1 capable of sequestering HMGB1 and EGF-like D2 responsible for thrombin-dependent degradation of HMGB1, in abolishing the allodynia caused by exogenous or endogenous HMGB1.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Pulsed electromagnetic field induces Ca2+-dependent osteoblastogenesis in C3H10T1/2 mesenchymal cells through the Wnt-Ca2+/Wnt-β-catenin signaling pathway

Highlights: • C3H10T1/2 cell proliferation can be greatly promoted by PEMF exposure. • C3H10T1/2 cell differentiation into osteoblast can be induced upon the stimulation of PEMF. • Intracellular [Ca2+]i up-regulation was observed during the process of PEMF-induced C3H10T1/2 cell differentiation. • PEMF-induced C3H10T1/2 cell differentiation was Ca2+-dependent. • PEMF-induced [Ca2+]i elevation suggested a combination of Wnt/Ca2+ and Wnt/β-catenin signaling pathways. Pulsed electromagnetic fields (PEMFs) are effective in healing fractures and improving osteoporosis. However, their effect on mesenchymal cells remains largely unknown. In this study, the effects of PEMF on osteoblastogenesis and its underlying molecular signaling mechanisms were systematically investigated in C3H10T1/2 cells. C3H10T1/2 mesenchymal cells were exposed to 30-Hz PEMF bursts at various intensities for 3 consecutive days. The optimal PEMF exposure (30 Hz, 1 mT, 2 h/day) was applied in subsequent experiments. Our results suggest that intracellular [Ca{sup 2+}]i in C3H10T1/2 cells can be upregulated upon exposure to PEMF and that PEMF-induced C3H10T1/2 cell differentiation was Ca{sup 2+}-dependent. The pro-osteogenic effect of PEMF on Ca{sup 2+}-dependent osteoblast differentiation was then verified by alkaline phosphatase (ALP) and von Kossa staining. Furthermore, PEMF promoted the gene expression and protein synthesis of the Wnt/β-catenin pathway. Increased [Ca{sup 2+}]i in the nucleoplasm was followed by the mobilization and translocation of β-catenin into the nucleus in C3H10T1/2 cells. A model of Wnt/β-catenin signaling and the Wnt/Ca2+ signaling network is proposed. Taken together, these findings indicated for the first time that PEMF induces osteoblastogenesis through increased intracellular [Ca{sup 2+}]i and the Wnt-Ca2+/Wnt-β-catenin signaling pathway in C3H10T1/2 mesenchymal cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

SPATULA regulates floral transition and photomorphogenesis in a PHYTOCHROME B-dependent manner in Arabidopsis

Highlights: • SPT promotes floral transition in Arabidopsis. • SPT promotes flowering via FLC, SVP, FT and SOC1. • SPT regulates photomorphogenesis in a PHYB-dependent manner. Light is the most important exogenous stimulus regulating plant growth and various developmental processes. Phytochromes, especially PHYTOCHROME B (PHYB) mediates the various light-mediated processes in Arabidopsis. SPATULA (SPT) is an important transcription factor, which has been reported previously to participate in temperature-mediated transition from seed dormancy to germination. Here we investigate the function of SPT in the floral transition under long day conditions and photomorphogenesis in Arabidopsis. In this study, spt-2 shows significantly delayed flowering time. But mutation of SPT in the background of phyb-1 rescues the phenotype of spt-2. The flowering time of double mutant of spt-2/phyb-1 is similar with the wild type. These results indicate that SPT promotes the transition from vegetative stage to floral stage and it regulates this transition in a PHYB-dependent manner. With qRT-PCR analysis, it is found that SPT regulates flowering time via FLC, SVP, FT and SOC1. Furthermore, SPT also controls photomorphogenesis. spt-2 displays shortened hypocotyls and increased chlorophylls contents compared with the wild type. These phenotypes are also rescued in the double mutant of spt-2/phyb-1. These results indicate that SPT is also involved in photomorphogenic development in Arabidopsis and SPT regulates photomorphogenesis in a PHYB-dependent manner. Collectively, SPT is not only a temperature responder but it is also an important light regulator during plant growth and development.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

c-Myc-driven glycolysis via TXNIP suppression is dependent on glutaminase-MondoA axis in prostate cancer

Highlights: • c-Myc suppresses TXNIP transcription in a glutamine-dependent manner. • c-Myc induction of GLS1 is necessary for TXNIP suppression. • TXNIP represses glycolytic target genes broadly in c-Myc-driven cancers. • c-Myc and TXNIP levels are negatively associated in PCA tissues and predict patient outcome. Oncogenic c-Myc-induced metabolic reprogramming triggers cellular dependency on exogenous glucose and glutamine. Understanding how nutrients are used may provide new target for therapeutic intervention. We previously provided an alternate route to c-Myc-driven glucose metabolism via the repression of thioredoxin-interacting protein (TXNIP), which is a potent negative regulator of glucose uptake. Herein, we demonstrate that c-Myc suppression of TXNIP is predominantly through the activation of glutaminolysis via glutaminase (GLS1) in prostate cancer cells. Glutamine depletion blocked c-Myc-dependent reductions of TXNIP and its principal regulator MondoA transcriptional activity. Further, GLS1 inhibition by either siRNA or CB-839 resumed TXNIP expression that was repressed by c-Myc. The TXNIP promoter with mutant E-Box region, which was recognized by MondoA, failed to respond to c-Myc or GLS1, indicating c-Myc repression of TXNIP by GLS1 is predominantly through the blockage of MondoA activity. Especially, ectopic TXNIP expression decreased c-Myc-induce glucose uptake and lead to a broad range of glycolytic target gene suppressions. Thus TXNIP is a key adaptor for c-Myc-driven aerobic glycolysis. Supporting the biological significance of c-Myc and TXNIP, their reciprocal relationship are correlates with patient outcome and contributes to the aggressive phenotype in PCAs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies

Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. Antibody CH540-VRC40.01 (named for donor-lineage.clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Elucidating the temperature and density dependence of silver chloride hydration numbers in high-temperature water vapor: A first-principles molecular simulation study

Hydration numbers of metal complexes in low-density aqueous solutions are required for developing geochemical models for ore-forming metals and for designing supercritical desalination processes. In this study, we investigate the temperature and density dependence of the hydration numbers of silver chloride at 623 K, 673 K, and 713 K and densities of 10–100 kg/m 3 . Experimental estimates of the hydration number in the literature for AgCl at these conditions are inconclusive and possibly contradictory as to the temperature and density dependence. First-principles molecular simulation presents an attractive alternative to experimental measurements. Specifically, recent work shows that machine-learning-accelerated nested Monte Carlo simulations provide reliable estimates for the hydration numbers of CuCl at 623 K from 10 to 100 kg/m 3 . Using the same technique, we find a monotonic temperature dependence, with the hydration number decreasing slightly with increasing temperature. In addition, the simulation-predicted hydration numbers steadily increase with increasing density. These temperature and density trends are in agreement with certain experimental data sets. Therefore, this work demonstrates how first-principles Monte Carlo simulations assist in resolving discrepancies between experimental data sets. Our simulation results also correctly predict that the hydration number, and thus also the solubility, of AgCl is lower than that of CuCl under the same conditions. Furthermore, the bond length and angle formed between the water complex and AgCl differ from those for CuCl, consistent with the lower solubility of AgCl.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2019

A configurational force for adaptive re-meshing of gradient-enhanced poromechanics problems with history-dependent variables

Here, we introduce a mesh-adaption framework that employs a multi-physical configurational force and Lie algebra to capture multiphysical responses of fluid-infiltrating geological materials while maintaining the efficiency of the computational models. To resolve sharp gradients of both displacement and pore pressure, we introduce an energy-estimate-free re-meshing criterion by extending the configurational force theory to consider the energy dissipation due to the fluid diffusion and the gradient-dependent plastic flow. To establish new equilibria after remeshing, the local tensorial history-dependent variables at the integration points are first decomposed into spectral forms. Then, the principal values and directions are projected onto smooth fields interpolated by the basis function of the finite element space via the Lie-algebra mapping. Our numerical results indicate that this Lie algebra operator in general leads to a new trial state closer to the equilibrium than the ones obtained from the tensor component mapping approach. A new configurational force for dissipative fluid-infiltrating porous materials that exhibit gradient-dependent plastic flow is introduced such that the remeshing may accommodate the need to resolve the sharp pressure gradient as well as the strain localization. The predicted responses are found to be not influenced by the mesh size due to the micromorphic regularization, while the adaptive meshing enables us to capture the width of deformation bands without the necessity of employing fine mesh everywhere in the domain.

42 ENGINEERING↗
DOE OSTI2020

Intrinsic size dependent plasticity in BCC micro-pillars under uniaxial tension and pure torsion

The mechanical behavior of submicron body-centered cubic (BCC) micro-pillars is investigated by three-dimensional dislocation dynamics (DD) simulations to better understand the governing mechanisms for size dependent plasticity under uniaxial tension and pure torsion. A formula is developed to compute the incremental plastic twist due to dislocation motion in DD simulations. The DD simulations show that different dislocation microstructures are created depending on the loading conditions, which leads to different size dependent mechanical behavior. While in tension plasticity is mainly governed by the kinetics of dislocation motion controlled partly by the surface dislocation sources, plastic flow in torsion is controlled by dislocation pile-ups associated with strain gradients. The simulation results also reveal a Bauschinger effect and plastic recovery under cyclic twist, which have been observed in recent experiments.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Dependence of the kinetic energy absorption capacity of bistable mechanical metamaterials on impactor mass and velocity

Using an alternative mechanism to dissipation or scattering, bistable structures and mechanical metamaterials have shown promise for mitigating the detrimental effects of impact by reversibly locking energy into strained material. Herein, we extend prior works on impact absorption via bistable metamaterials to computationally explore the dependence of kinetic energy transmission on the velocity and mass of the impactor, with strain rates exceeding 10 2 s –1 . We observe a large dependence on both impactor parameters, ranging from significantly better to worse performance than a comparative linear material. We then correlate the variability in performance to solitary wave formation in the system and give analytical estimates of idealized energy absorption capacity under dynamic loading. In addition, we find a significant dependence on damping accompanied by a qualitative difference in solitary wave propagation within the system. The complex dynamics revealed in this study offer potential future guidance for the application of bistable metamaterials to applications including human and engineered system shock and impact protection devices.

42 ENGINEERING↗
DOE OSTI2020

Constitutive modeling of δ-phase zircaloy hydride based on strain rate dependent nanoindentation and nano-scale impact dataset

In this work, a constitutive model for zircaloy-4 embedded with δ-phase hydride rim/blister structures (δ-phase zircaloy hydride) is presented. Nanoindentation and nano-scale impact experiments were performed on the δ-hydride blisters as a function of temperature in order to obtain strain rate dependent location specific constitutive response. A power law viscoplastic constitutive model was chosen to represent the strain rate dependent behavior. The strength coefficient and the strain hardening exponent in the power law relation were found to decrease with increase in temperature indicating softening behavior at higher temperatures. The strain rate exponent remained constant with increase in temperature indicating that the rate dependent ductility does not change significantly at higher temperatures. A finite element method based model was created to analyze the failure behavior and the ductile to brittle transition in zircaloy hydride. The model predicted that fracture strength of δ-phase zircaloy hydride decreases linearly with increase in temperature.

36 MATERIALS SCIENCE↗
DOE OSTI2023

Multi-level Force-dependent Allosteric Enhancement of αE-catenin Binding to F-actin by Vinculin

Classical cadherins are transmembrane proteins whose extracellular domains link neighboring cells, and whose intracellular domains connect to the actin cytoskeleton via β-catenin and α-catenin. The cadherin-catenin complex transmits forces that drive tissue morphogenesis and wound healing. In addition, tension-dependent changes in αE-catenin conformation enables it to recruit the actin-binding protein vinculin to cell-cell junctions, which contributes to junctional strengthening. How and whether multiple cadherin-complexes cooperate to reinforce cell-cell junctions in response to load remains poorly understood. Here, we used single-molecule optical trap measurements to examine how multiple cadherin-catenin complexes interact with F-actin under load, and how this interaction is influenced by the presence of vinculin. We show that force oriented toward the (-) end of the actin filament results in mean lifetimes 3-fold longer than when force was applied towards the barbed (+) end. We also measured force-dependent actin binding by a quaternary complex comprising the cadherin-catenin complex and the vinculin head region, which cannot itself bind actin. Binding lifetimes of this quaternary complex increased as additional complexes bound F-actin, but only when load was oriented toward the (-) end. In contrast, the cadherin-catenin complex alone did not show this form of cooperativity. Furthermore, these findings reveal multi-level, force-dependent regulation that enhances the strength of the association of multiple cadherin/catenin complexes with F-actin, conferring positive feedback that may strengthen the junction and polarize F-actin to facilitate the emergence of higher-order cytoskeletal organization.

59 BASIC BIOLOGICAL SCIENCES↗