Numerical Simulation and Machine Learning Prediction of the Direct Chill Casting Process of Large-Scale Aluminum Ingots.

The large-scale ingot of the 7xxx-series aluminum alloys fabricated by direct chill (DC) casting often suffers from foundry defects such as cracks and cold shut due to the formidable challenges in the precise controlling of casting parameters. In this manuscript, by using the integrated computational method combining numerical simulations with machine learning, we systematically estimated the evolution of multi-physical fields and grain structures during the solidification processes. The numerical simulation results quantified the influences of key casting parameters including pouring temperature, casting speed, primary cooling intensity, and secondary cooling water flow rate on the shape of the mushy zone, heat transport, residual stress, and grain structure of DC casting ingots. Then, based on the data of numerical simulations, we established a novel model for the relationship between casting parameters and solidification characteristics through machine learning. By comparing it with experimental measurements, the model showed reasonable accuracy in predicting the sump profile, microstructure evolution, and solidification kinetics under the complicated influences of casting parameters. The integrated computational method and predicting model could be used to efficiently and accurately determine the DC casting parameters to decrease the casting defects.

Regulatory T cells use heparanase to access IL-2 bound to extracellular matrix in inflamed tissue.

Although FOXP3+ regulatory T cells (Treg) depend on IL-2 produced by other cells for their survival and function, the levels of IL-2 in inflamed tissue are low, making it unclear how Treg access this critical resource. Here, we show that Treg use heparanase (HPSE) to access IL-2 sequestered by heparan sulfate (HS) within the extracellular matrix (ECM) of inflamed central nervous system tissue. HPSE expression distinguishes human and murine Treg from conventional T cells and is regulated by the availability of IL-2. HPSE-/- Treg have impaired stability and function in vivo, including in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Conversely, endowing monoclonal antibody-directed chimeric antigen receptor (mAbCAR) Treg with HPSE enhances their ability to access HS-sequestered IL-2 and their ability to suppress neuroinflammation in vivo. Together, these data identify a role for HPSE and the ECM in immune tolerance, providing new avenues for improving Treg-based therapy of autoimmunity.

A Novel Allogeneic Rituximab-Conjugated Gamma Delta T Cell Therapy for the Treatment of Relapsed/Refractory B-Cell Lymphoma.

Chimeric antigen receptor T cell (CAR-T) therapy has been applied in the treatment of B-cell lymphoma; however, CAR-T manufacturing requires virus- or non-virus-based genetic modification, which causes high manufacturing costs and potential safety concerns. Antibody-cell conjugation (ACC) technology, which originated from bio-orthogonal click chemistry, provides an efficient approach for arming immune cells with cancer-targeting antibodies without genetic modification. Here, we applied ACC technology in Vγ9Vδ2 T (γδ2 T) cells to generate a novel off-the-shelf CD20-targeting cell therapy ACE1831 (rituximab-conjugated γδ2 T cells) against relapsed/refractory B-cell lymphoma. ACE1831 exhibited superior cytotoxicity against B-cell lymphoma cells and rituximab-resistant cells compared to γδ2 T cells without rituximab conjugation. The in vivo xenograft study demonstrated that ACE1831 treatment strongly suppressed the aggressive proliferation of B-cell lymphoma and prolonged the survival of tumor-bearing mice with no observed toxicity. Mass spectrometry analysis indicated that cell activation receptors including the TCR complex, integrins and cytokine receptors were conjugated with rituximab. Intriguingly, the antigen recognition of the ACC-linked antibody/receptor complex stimulated NFAT activation and contributed to ACE1831-mediated cytotoxicity against CD20-expressing cancer cells. This study elucidates the role of the ACC-linked antibody/receptor complex in cytotoxicity and supports the potential of ACE1831 as an off-the-shelf γδ2 cell therapy against relapsed/refractory B-cell lymphoma.

Efficient extraction of nanocellulose from lignocellulose using aqueous butanediol fractionation to improve the performance of waterborne wood coating.

The highly efficient extraction of cellulose from lignocellulose with an excellent yield of 95.2 % and purity of 96.7 % was demonstrated using acid-catalyzed fractionation with aqueous butanediol. This cellulose was subsequently transformed into cellulose nanofibers (CNFs) and cellulose nanocrystals (CNCs) with specific dimensions and surface functional groups through various chemomechanical treatments. The average diameters of CNFs and CNCs produced by sulfuric acid hydrolysis-ultrasonication and deep eutectic solvent treatment-ultrasonication (DES-CNCs) were 29.7, 21.9 and 17.3 nm, respectively. The DES-CNCs were obtained in a good yield of 71 ± 1.27 wt% and exhibited a high zeta potential of -33.5 ± 2.51 mV following posthydrolysis and esterification during the DES treatment. These CNFs and CNCs were used as nanofillers in a waterborne wood coating (WWC), which significantly improved its dynamic viscosity and storage modulus. The addition of these materials also enhanced the mechanical strength of the WWC but had little effect on transmittance. Glossiness, hardness, abrasion resistance and adhesion strength were evaluated, and the DES-CNCs provided the greatest improvements at a low concentration. A plausible reinforcement mechanism was presented. This work provided an efficient cellulose extraction method and detailed structure elucidation of the nanocellulose together with suggestions for value-added applications of cellulosic nanofillers for reinforcing WWC.

The Effect of Lattice Misfits on the Precipitation at Dislocations: Phase-Field Crystal Simulation.

An atomic-scale approach was employed to simulate the formation of precipitates with different lattice misfits in the early stages of the aging of supersaturated aluminum alloys. The simulation results revealed that the increase in lattice misfits could significantly promote the nucleation rate of precipitates, which results in a larger number and smaller size of the precipitates. The morphologies of the precipitates also vary with the degree of a lattice misfit. Moreover, the higher the lattice misfit, the earlier the nucleation of the second phase occurs, which can substantially inhibit the movement of dislocations. The research on the lattice misfit of precipitation can provide theoretical guidance for the design of high-strength aluminum alloys.

FOXP3+ regulatory T cells use heparanase to access IL-2 bound to ECM in inflamed tissues.

FOXP3+ regulatory T cells (Treg) depend on exogenous IL-2 for their survival and function, but circulating levels of IL-2 are low, making it unclear how Treg access this critical resource in vivo. Here, we show that Treg use heparanase (HPSE) to access IL-2 sequestered by heparan sulfate (HS) within the extracellular matrix (ECM) of inflamed central nervous system tissue. HPSE expression distinguishes human and murine Treg from conventional T cells and is regulated by the availability of IL-2. HPSE-/- Treg have impaired stability and function in vivo, including the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Conversely, endowing Treg with HPSE enhances their ability to access HS-sequestered IL-2 and their tolerogenic function in vivo. Together, these data identify novel roles for HPSE and the ECM in immune tolerance, providing new avenues for improving Treg-based therapy of autoimmunity.

Atomic-Scale Insights into the Self-Assembly of Alternating AlN/TiN Lamellar Nanostructures via Spinodal Decomposition in AlTiN Coating.

The self-assembly mechanism of alternating AlN/TiN nano-lamellar structures in AlTiN coating is still a mystery, though this coating has been widely used in industry. Here, by using the phase-field crystal method, we studied the atomic-scale mechanisms of the formation of nano-lamellar structures during spinodal decomposition transformation of an AlTiN coating. The results show that the formation of a lamella is characterized by four distinct stages including the generation of dislocations (stage I), formation of islands (stage II), merging of islands (stage III), and flattening of lamellae (stage IV). The locally periodic fluctuation of the concentration along the lamella leads to the generation of periodically distributed misfit dislocations and then AlN/TiN islands, while the fluctuation of the composition in the direction normal to the lamella is responsible for the merging of islands and flattening of a lamella and more importantly the cooperative growth between neighboring lamellae. Moreover, we found that misfit dislocations play a crucial role in all the four stages, promoting the cooperative growth of TiN and AlN lamellae. Our results demonstrate that the TiN and AlN lamellae could be produced through the cooperative growth of AlN/TiN lamellae in spinodal decomposition of the AlTiN phase.

Atomic-Scale Insights into the Deformation Mechanism of the Microstructures in Precipitation-Strengthening Alloys.

Clarifying the deformation behaviors of microstructures could greatly help us understand the precipitation-strengthening mechanism in alloys. However, it is still a formidable challenge to study the slow plastic deformation of alloys at the atomic scale. In this work, the phase-field crystal method was used to investigate the interactions between precipitates, grain boundary, and dislocation during the deformation processes at different degrees of lattice misfits and strain rates. The results demonstrate that the pinning effect of precipitates becomes increasingly strong with the increase of lattice misfit at relatively slow deformation with a strain rate of 10-4. The cut regimen prevails under the interaction between coherent precipitates and dislocations. In the case of a large lattice misfit of 19.3%, the dislocations tend to move toward the incoherent phase interface and are absorbed. The deformation behavior of the precipitate-matrix phase interface was also investigated. Collaborative deformation is observed in coherent and semi-coherent interfaces, while incoherent precipitate deforms independently of the matrix grains. The faster deformations (strain rate is 10-2) with different lattice misfits all are characterized by the generation of a large number of dislocations and vacancies. The results contribute to important insights into the fundamental issue about how the microstructures of precipitation-strengthening alloys deform collaboratively or independently under different lattice misfits and deformation rates.

Sensation Seeking and Substance use in Chinese Adolescents: Longitudinal Trajectories and Prospective Within-person Associations.

Sensation seeking has been extensively demonstrated as a risk factor for substance use. Potential bidirectional associations between sensation seeking and substance use at the within-person level are incompletely understood. The present study examined longitudinal trajectories of sensation seeking and substance use and bidirectional longitudinal associations between sensation seeking and substance use in Chinese adolescents during a 3-year period over three time points. A total of 10,138 adolescents (59.8%) male; Mage = 16.77, SD = 0.83 at time (1) were surveyed. Sensation seeking and substance use frequency increased concomitantly over time. At the within-person level, sensation seeking and substance use were reciprocally predictable, and there were no evidence of sex difference in longitudinal associations. This study provides unique data concerning the relationship between sensation seeking and substance use in a sample of Chinese adolescents, and highlights the importance of identifying sensation seeking behaviors to prevent substance use.

Efficient downstream valorization of lignocellulose after organosolv fractionation: Synergistic enhancement of waterborne coatings by co-assembled lignin@cellulose nanocrystals.

The simultaneous downstream valorization of cellulose and lignin is an important aspect of efficiently extracting value from lignocellulose. The present work, we demonstrated the preparation of a novel bio-based filler by the co-assembly of cellulose and lignin obtained from a one-pot ethanosolv lignocellulose fractionation process. The cellulose was valorized by forming cellulose nanocrystals (CNCs) through simple bleaching and ultrasonication processes. The lignin fractions demonstrated greater solubility (19.2 mg/mL) and lower molecular weight (6980 g/mol) than conventional industrial lignins. Various lignin@CNCs specimens were prepared via a facile co-assembly of the lignin and CNCs. These entirely bio-based materials could be used as a multifunctional filler to enhance the properties of a waterborne coating (WBC). Specifically, the mechanical properties, coating performance and ultraviolet resistance of a WBC were all significantly improved, demonstrating a synergistic enhancement effect obtained from the CNCs and lignin. In this manner, both cellulose and lignin components were efficiently transformed to value-added fillers for WBC, demonstrating a highly efficient pathway for lignocellulose utilization and downstream value-added applications.

Effect of Rolling Temperature on Microstructure and Properties of Al-Mg-Li Alloy.

In this study, the effects of hot-rolled processes at different temperatures (420 °C, 450 °C, and 480 °C) and subsequent solid solution and aging treatments on the microstructure, mechanical properties, and corrosion properties of Al-Mg-Li alloys with trace Sc and Zr addition were investigated. The aging treatment of rolled sheets after solid solution treatment could obtain Al3Li particles and Al3(Sc, Zr)/Al3Li core-shell particles to improve the mechanical properties of Al-Mg-Li alloy products effectively. The results showed that, as the rolling temperatures increased from 420 °C to 480 °C, the alloy's ultimate tensile strengths and yield strengths increased, while the corrosion resistance decreased. The increase in rolling temperature increased the precipitation-free zone (PFZ) width of the alloy, which undermined the corrosion resistance of the alloy. Moreover, elevating the hot rolling temperature changes the texture strength of the alloy. Particularly in the 480 °C hot-rolled sample, the decrease in the Brass texture strength and the increase in the S texture and Copper texture strength led to an increase in the Taylor factor (M). The increase in rolling temperature also raised the number density of the Al3(Sc, Zr)/Al3Li core-shell particles. The presence of such particles not only inhibits grain growth but also changes the strength mechanism from dislocation cutting to Orowan bypassing. Due to the combination effect of grain morphology, texture evolution, and precipitation behavior, the 480 °C hot-rolled sample had the highest properties.

Immunoregulatory effects of RGMb in gut inflammation.

Graft-versus-host disease (GvHD) is a major complication after allogeneic hematopoietic cell transplantation (HCT). Current strategies to prevent GvHD with immunosuppressive drugs carry significant morbidity and may affect the graft-versus-tumor (GVT) effect. Inflammatory bowel disease (IBD) is an intestinal inflammatory condition that affects more than 2 million people in the United States. Current strategies to prevent colitis with immunosuppressive drugs carry significant morbidity. Recently, Repulsive Guidance Molecule b (RGMb) has been identified as part of a signaling hub with neogenin and BMP receptors in mice and humans. In addition, RGMb binds BMP-2/4 in mice and humans as well as PD-L2 in mice. RGMb is expressed in the gut epithelium and by antigen presenting cells, and we found significantly increased expression in mouse small intestine after total body irradiation HCT conditioning. We hypothesized that RGMb may play a role in GvHD and IBD pathogenesis by contributing to mucosal inflammation. Using major-mismatched HCT mouse models, treatment with an anti-RGMb monoclonal antibody (mAb) that blocks the interaction with BMP-2/4 and neogenin prevented GvHD and improved survival compared to isotype control (75% versus 30% survival at 60 days after transplantation). The GVT effect was retained in tumor models. Using an inflammatory bowel disease dextran sulfate sodium model, treatment with anti-RGMb blocking monoclonal antibody but not isotype control prevented colitis and improved survival compared to control (73% versus 33% at 21 days after treatment) restoring gut homeostasis. Anti-RGMb mAb (9D1) treatment decreased IFN-γ and significantly increased IL-5 and IL-10 in the gut of the treated mice compared to the isotype control treated mice.

Solid Fe Resources Separated from Rolling Oil Sludge for CO Oxidation.

The efficient recycling of valuable resources from rolling oil sludge (ROS) to gain new uses remains a formidable challenge. In this study, we reported the recycling of solid Fe resources from ROS by a catalytic hydrogenation technique and its catalytic performance for CO oxidation. The solid Fe resources, after calcination in air (Fe2O3-H), exhibited comparable activity to those prepared by the calcinations of ferric nitrate (Fe2O3-C), suggesting that the solid resources have excellent recycling value when used as raw materials for CO oxidation catalyst preparation. Further studies to improve the catalytic performance by supporting the materials on high surface area 13X zeolite and by pretreating the materials with CO atmosphere, showed that the CO pretreatment greatly improved the CO oxidation activity and the best activity was achieved on the 20 wt.%Fe2O3-H/13X sample with complete CO conversion at 250 °C. CO pretreatment could produce more oxygen vacancies, facilitating O2 activation, and thus accelerate the CO oxidation reaction rate. The excellent reducibility and sufficient O2 adsorption amount were also favorable for its performance. The recycling of solid Fe resources from ROS is quite promising for CO oxidation applications.

Food Security: 3D Dynamic Display and Early Warning Platform Construction and Security Strategy.

Since it affects a nation's economy and people's wellbeing, food security is a crucial national security requirement. In order to realize multi-angle grain data presentation and analysis and achieve the goal of deep mining, we propose a 3D dynamic visualization analysis method of multidimensional agricultural spatial-temporal data based on the self-organizing map. This method realizes the multi-angle display and analysis of grain data and achieves the purpose of deep mining. With the outbreak of COVID-19, the global food security situation is not optimistic, so it is necessary to use the food security early warning system to solve the food security issue. Machine learning has emerged widely in recent years and has been applied in various fields. Therefore, it is an excellent way to solve food security to apply the model in machine learning to construct a food security early warning system. Afterward, a food security early warning platform is developed with a support vector regression (SVR) model to ensure food security. Finally, we analyze China's medium and long-term food security policy in line with modernization objectives. The experimental results show that the food security early warning platform based on the SVR model from 2007 to 2016 is effective compared with the actual situation every year. Through analyses, we should improve the stability, reliability, and sustainability of food supply, firmly hold the food security initiative, and construct a national food security guarantee system matching the goal of modernization.

Magnetic, Electrical, and Physical Properties Evolution in Fe3O4 Nanofiller Reinforced Aluminium Matrix Composite Produced by Powder Metallurgy Method.

An investigation into the addition of different weight percentages of Fe3O4 nanoparticles to find the optimum wt.% and its effect on the microstructure, thermal, magnetic, and electrical properties of aluminum matrix composite was conducted using the powder metallurgy method. The purpose of this research was to develop magnetic properties in aluminum. Based on the obtained results, the value of density, hardness, and saturation magnetization (Ms) from 2.33 g/cm3, 43 HV and 2.49 emu/g for Al-10 Fe3O4 reached a maximum value of 3.29 g/cm3, 47 HV and 13.06 emu/g for the Al-35 Fe3O4 which showed an improvement of 41.2%, 9.3%, and 424.5%, respectively. The maximum and minimum coercivity (Hc) was 231.87 G for Al-10 Fe3O4 and 142.34 G for Al-35 Fe3O4. Moreover, the thermal conductivity and electrical resistivity at a high weight percentage (35wt.%) were 159 w/mK, 9.9 × 10-4 Ω·m, and the highest compressive strength was 133 Mpa.

Analyzing the Effects of Heat Treatment on SMAW Duplex Stainless Steel Weld Overlays.

Duplex stainless steel (DSS) has a reasonably high resistance to chloride stress corrosion cracking for offshore and marine applications. However, DSS weld overlay has not been successfully demonstrated due to some inherent problems in achieving pitting and crevice corrosion resistance. In this research work, isothermal heat treatments (350, 650 and 1050 °C) with and different cooling rates have been performed DMR249 Grade A by using shield metal arc welding (SMAW) with an E2209 electrode. Micrographs have shown two phase microstructures of the DSS weld metal, the amounts of austenite phase increased with increment of post-weld heat treatment (PWHT) temperatures. The dilution has maintained consistent values except solution annealing that has shown the disappearance of the heat affected zone in micrographs. The weld metal hardness values increased with PWHT temperatures and remained low at solid solution annealing temperatures. The major alloying elements (C, Mo, Cr, Ni, N, and Fe) were analyzed, as these elements can contribute to intermetallic phases. The results showed that C and Cr content slightly increased with PWHT except for solid solution annealing, Mo showed consistently low content due to dilution effects. Ni maintained higher content, although the heat-treated samples showed slight fluctuations. Nitrogen produced consistent values, as recommended to prevent critical involvement in nitride precipitation.

A Novel off-the-Shelf Trastuzumab-Armed NK Cell Therapy (ACE1702) Using Antibody-Cell-Conjugation Technology.

Natural killer (NK) cells harbor efficient cytotoxicity against tumor cells without causing life-threatening cytokine release syndrome (CRS) or graft-versus-host disease (GvHD). When compared to chimeric antigen receptor (CAR) technology, Antibody-Cell Conjugation (ACC) technology has been developed to provide an efficient platform to arm immune cells with cancer-targeting antibodies to recognize and attack cancer cells. Recently, we established an endogenous CD16-expressing oNK cell line (oNK) with a favorable expression pattern of NK activation/inhibitory receptors. In this study, we applied ACC platform to conjugate oNK with trastuzumab and an anti-human epidermal growth factor receptor 2 (HER2) antibody. Trastuzumab-conjugated oNK, ACE-oNK-HER2, executed in vitro and in vivo cytotoxicity against HER2-expressing cancer cells and showed enhanced T cell-recruiting capability and secretion of IFNγ. The irradiated and cryopreserved ACE-oNK-HER2, designated as ACE1702, retained superior HER2-specific in vitro and in vivo potency with no tumorigenic potential. In conclusion, this study provides the evidence to support the potential clinical application of ACE1702 as a novel off-the-shelf NK cell therapy against HER2-expressing solid tumors.

A novel endogenous CD16-Expressing Natural Killer Cell for cancer immunotherapy.

Natural killer (NK) cells, as a potential source for off-the-shelf cell therapy, attack tumor cells with low risk of severe cytokine release syndrome (CRS) or graft-versus-host disease (GvHD). Fcγ receptor IIIA, also known as CD16, further confers NK cells with antibody-dependent cell-mediated cytotoxicity (ADCC), one mechanism of action of antibody-based immunotherapy. Here, we establish a novel human NK cell line, oNK-1, endogenously expressing CD16 along with high levels of NK activation markers and low levels of NK inhibitory markers. The long-term expansion and CD16 expression of oNK-1 cells were demonstrated. Furthermore, oNK-1 cells elicit superior cytotoxicity against cancer cells than primary NK cells. In conclusion, this study suggests that endogenous CD16-expressing oNK-1 has the potential to develop an effective NK-based therapy.

An atomic scale study of two-dimensional quasicrystal nucleation controlled by multiple length scale interactions.

Formation of quasicrystal structures has always been mysterious since the discovery of these magic structures. In this work, the nucleation of decagonal, dodecagonal, heptagonal, and octagonal quasicrystal structures controlled by the coupling among multiple length scales is investigated using a dynamic phase-field crystal model. We observe that the nucleation of quasicrystals proceeds through local rearrangement of length scales, i.e., the generation, merging and stacking of 3-atom building blocks constructed by the length scales, and accordingly, propose a geometric model to describe the cooperation of length scales during structural transformation in quasicrystal nucleation. Essentially, such cooperation is crucial to quasicrystal formation, and controlled by the match and balance between length scales. These findings clarify the scenario and microscopic mechanism of the structural evolution during quasicrystal nucleation, and help us to understand the common rule for the formation of periodic crystal and quasicrystal structures with various symmetries.

A novel antibody-cell conjugation method to enhance and characterize cytokine-induced killer cells.

BACKGROUND: Cytokine-induced killer (CIK) cells are an ex vivo-expanded cellular therapy product with potent anti-tumor activity in a subset of patients with solid and hematologic malignancies. We hypothesize that directing CIK cells to a specific tumor antigen will enhance CIK cell anti-tumor cytotoxicity. METHODS: We present a newly developed method for affixing antibodies directly to cell surface proteins. First, we evaluated the anti-tumor potential of CIK cells after affixing tumor-antigen targeting monoclonal antibodies. Second, we evaluated whether this antibody-conjugation method can profile the surface proteome of CIK cells. RESULTS: We demonstrated that affixing rituximab or daratumumab to CIK cells enhances cytotoxic killing of multiple lymphoma cell lines in vitro. These 'armed' CIK cells exhibited enhanced intracellular signaling after engaging tumor targets. Cell surface proteome profiling suggested mechanisms by which antibody-armed CIK cells concurrently activated multiple surface proteins, leading to enhanced cytolytic activity. Our surface proteome analysis indicated that CIK cells display enhanced protein signatures indicative of immune responses, cellular activation and leukocyte migration. CONCLUSIONS: Here, we characterize the cell surface proteome of CIK cells using a novel methodology that can be rapidly applied to other cell types. Our study also demonstrates that without genetic modification CIK cells can be rapidly armed with monoclonal antibodies, which endows them with high specificity to kill tumor targets.