Fusion-based additive manufacturing (AM) has significantly grown to fabricate Nickel-based superalloys with design freedom across multiple length scales. Several phenomena such as feedstock/energy ...source/melt pool interactions, solidification and phase transformations occur during fusion-based AM processes of Nickel-based superalloys, which determine the ultimate microstructure and mechanical performance of the built parts. In this review, we elaborate a comprehensive discussion on AM Nickel-based superalloys and influential factors including feedstock characteristics (powder morphology, chemistry, contamination, flowability, recycling) and AM processing (parameters, and powder spreading/wall/balling/spattering effects) on their microstructure (micro-segregation, phases formations and grain structures), defect generation (sub-surface/internal defects, microcracks, surface roughness, and residual stress). Furthermore, the mechanical properties of AM Nickel-based superalloys such as tensile, creep and fatigue at room/elevated temperatures are analyzed in accordance with the initial, and post processing effects. Additionally, the commonly utilized modeling approaches in literature to predict the microstructure and mechanical behavior of these alloys are highlighted. Finally, the current challenges and mitigation approaches for future research are identified considering the gaps in the AM Nickel-based superalloys.
•A field experiment was conducted on a real steel truss bridge with four artificial damage scenarios.•Changes in the identified modal parameters due to the artificial damage were observed.•A damage ...detection approach in an order of feature extraction and discrimination was practicable.•Multiple modal frequencies were effective features sensitive to damage presence and severity.•Multiple MAC values and COMAC values were also effective features if modes are sufficient.
Bridge damage detection has become increasingly important, but few related techniques have been tested in situ on real bridges. For this study, a field experiment was conducted on an actual simply supported steel truss bridge with four artificial damage scenarios applied sequentially. Preliminary results of modal-parameter identification and vibration-based damage detection are then presented. For each scenario, modal frequencies and mode shapes of the bridge were identified with high precision and accuracy using a stabilization diagram-aided multivariate autoregressive analysis of vehicle-excited bridge vibrations. Changes in the identified modal parameters attributable to the artificial damage were observed. For modal frequencies, they decreased as damage causing high stress redistribution was applied, signifying a global stiffness loss. For mode shapes, both symmetric and anti-symmetric ones were distorted when the damage was applied asymmetrically, but no distortion was observed when damage was applied symmetrically. Moreover, a damage detection approach in an order of feature extraction and discrimination was verified to be practicable if the damage-sensitive feature was properly selected. Multiple modal frequencies, specifically the first three and four modal frequencies, were effective features because they were highly sensitive not only to the presence but also to the severity of the artificial damage. Multiple modal assurance criteria (MAC) values and coordinate modal assurance criteria (COMAC) values were also effective features that were sensitive to damage scenarios examined herein if sufficient modes were considered. However, neither a single frequency nor a single MAC value was as effective as multiple ones because each was sensitive to certain specific damage scenarios only. When damping ratios were taken as features, most of their combinations were slightly sensitive to the asymmetric damage, but none of those combinations, neither single nor multiple damping ratios, was sensitive to the symmetric damage.
The endoplasmic reticulum (ER) has diverse functions, and especially misfolded protein modification is in the focus of this review paper. With a highly regulatory mechanism, called unfolded protein ...response (UPR), it protects cells from the accumulation of misfolded proteins. Nevertheless, not only does UPR modify improper proteins, but it also degrades proteins that are unable to recover. Three pathways of UPR, namely PERK, IRE-1, and ATF6, have a significant role in regulating stress-induced physiological responses in cells. The dysregulated UPR may be involved in diseases, such as atherosclerosis, heart diseases, amyotrophic lateral sclerosis (ALS), and cancer. Here, we discuss the relation between UPR and cancer, considering several aspects including survival, dormancy, immunosuppression, angiogenesis, and metastasis of cancer cells. Although several moderate adversities can subject cancer cells to a hostile environment, UPR can ensure their survival. Excessive unfavorable conditions, such as overloading with misfolded proteins and nutrient deprivation, tend to trigger cancer cell death signaling. Regarding dormancy and immunosuppression, cancer cells can survive chemotherapies and acquire drug resistance through dormancy and immunosuppression. Cancer cells can also regulate the downstream of UPR to modulate angiogenesis and promote metastasis. In the end, regulating UPR through different molecular mechanisms may provide promising anticancer treatment options by suppressing cancer proliferation and progression.
The enthalpy of mixing provides information on the favorability of cross-interactions between two different chemical compounds, and it can be included in the training of activity coefficient models ...to capture the temperature dependence. Recently, Mathias highlighted that certain mixtures of primary and secondary alcohols exhibit exothermic mixing behavior, whereas mixtures of primary alcohols show the more common endothermic mixing behavior (Ind. Eng. Chem. Res. 2019, 58, 12465). Here, we probe the mixing behavior of short-chain alcohols at T = 298 K and p = 1 atm through molecular simulations with the TraPPE–UA force field and molecular modeling with the COSMO–SAC activity coefficient model. Using their predictive modes (i.e., without tuning of the models), neither of these two computational approaches yields the exothermic mixing behavior for primary and secondary alcohols. To capture the exothermic mixing, we explore modifications of the TraPPE–UA force-field parameters to make the secondary CHOH group a better hydrogen bond acceptor (through an increase of the partial charge on the oxygen atom) but also adding steric hindrance for hydrogen bond formation between two secondary alcohols (through an increase of the Lennard-Jones diameter on the α-CH pseudoatom). Detailed analysis of the liquid structures for the neat phases and mixtures indicates that the tuned model yields slightly enhanced cross-association which results in a more significant shift from tetrameric to larger hydrogen-bonded aggregates than for the TraPPE–UA model, whereas neither model exhibits a significant change in the number of hydrogen bonds upon mixing. Thus, the simulations point to a shift from cyclic tetramers and pentamers with strained hydrogen bonds to larger, less strained aggregates as the underlying structural change for the exothermic mixing behavior of primary and secondary alcohols.
Adipocytes are the most abundant stromal partners in breast tissue. However, the crosstalk between breast cancer cells and adipocytes has been given less attention compared to cancer-associated ...fibroblasts. Here we find, through systematic screening, that primary mammary gland-derived adipocytes (MGDAs) promote growth of breast cancer cells that express monocarboxylate transporter 2 (MCT2) both in vitro and in vivo. We show that β-hydroxybutyrate is secreted by MGDAs and is required to enhance breast cancer cells malignancy in vitro. Consistently, β-hydroxybutyrate is sufficient to promote tumorigenesis of a mouse xenograft model of MCT2-expressing breast cancer cells. Mechanistically we observe that upon co-culturing with MGDAs or treatment with β-hydroxybutyrate, breast cancer cells expressing MCT2 increase the global histone H3K9 acetylation and upregulate several tumour-promoting genes. These results suggest that adipocytes promote malignancy of MCT2-expressing breast cancer via β-hydroxybutyrate potentially by inducing the epigenetic upregulation of tumour-promoting genes.
Dispensing micron-scale droplets from a suspended nozzle is important for applications in bioprinting, analytical chemistry, and pharmaceutical formulation. Here, we describe a general approach to ...eject droplets from microfluidic devices using superhydrophobic patterning; this facilitates release of wetted fluids, allowing droplets to break contact with channel surfaces and travel along regular paths to achieve a printing accuracy of ∼3 μm. We demonstrate the utility of the approach by using it to print droplets of varied composition from a microfluidic mixing device. Our approach is compatible with common fabrication techniques making it applicable to devices configured for diverse applications.
Under metabolic stress conditions such as hypoxia and glucose deprivation, an increase in the AMP:ATP ratio activates the AMP-activated protein kinase (AMPK) pathway, resulting in the modulation of ...cellular metabolism. Metformin, which is widely prescribed for type 2 diabetes mellitus (T2DM) patients, regulates blood sugar by inhibiting hepatic gluconeogenesis and promoting insulin sensitivity to facilitate glucose uptake by cells. At the molecular level, the most well-known mechanism of metformin-mediated cytoprotection is AMPK pathway activation, which modulates metabolism and protects cells from degradation or pathogenic changes, such as those related to aging and diabetic retinopathy (DR). Recently, it has been revealed that metformin acts via AMPK- and non-AMPK-mediated pathways to exert effects beyond those related to diabetes treatment that might prevent aging and ameliorate DR. This review focuses on new insights into the anticancer effects of metformin and its potential modulation of several novel types of nonapoptotic cell death, including ferroptosis, pyroptosis, and necroptosis. In addition, the antimetastatic and immunosuppressive effects of metformin and its hypothesized mechanism are also discussed, highlighting promising cancer prevention strategies for the future.
In tribological applications, the degradation of alloy nitride coatings is an issue of increasing concern. The drawbacks of monolayer hard coatings can be overcome using a multilayer coating system. ...In this study, single-layer TiAlNbN and multilayer TiAlNbN/AlCrN coatings with AlCrN layer addition into TiAlNbN were prepared by cathodic arc evaporation (CAE). The multilayer TiAlNbN/AlCrN showed B1 NaCl structure, and the columnar structure continued from the bottom interlayer of CrN to the top multilayers without interruption. After AlCrN addition, the TiAlNbN/AlCrN coating consisted of TiAlNbN and AlCrN multilayers with a periodic thickness of 13.2 nm. The layer thicknesses of the TiAlNbN and AlCrN were 7 nm and 6.2 nm, respectively. The template growth of the TiAlNbN and AlCrN sublayers stabilized the cubic phases. The introduction of bottom CrN and the TiAlNbN/CrN transition layers possessed com-position-gradient that improved the adhesion strength of the coatings. The hardness of the deposited TiAlNbN was 30.2 ± 1.3 GPa. The TiAlNbN/AlCrN had higher hardness of 31.7 ± 3.5 GPa and improved tribological performance (wear rate = 8.2 ± 0.6 × 10−7 mm3/Nm) than those of TiAlNbN, which were because the multilayer architecture with AlCrN addition effectively resisted abrasion wear.
This study focuses on the interaction between the oxide layer area of a transistor and its ferroelectric layer area. An experimental comparison of transistor oxide layer area demonstrates that the ...larger the ratio of oxide to ferroelectric layers, the larger the on/off ratio, thus improving performance. A subsequent experiment aimed to further demonstrate this in different sized devices, and changing the ratio of <inline-formula> <tex-math notation="LaTeX">\text{A}_{\text {HZO}}/\text{A}_{\text {SiO2}} </tex-math></inline-formula> (the area of HfZrO x divided by oxide layer) showed the same tendency as above, but also produced an unexpected finding in that a comparison of on/off ratio exhibits an abnormal electric characteristic. This study discusses this abnormal electric characteristic and proposes an explanatory physical model.
This work presents an activity-based formulation for Langmuir adsorption isotherm. Treating adsorption as a chemical reaction between the gas molecule and the adsorption vacant site, the classical ...Langmuir isotherm model expresses the reaction in terms of the species concentrations. Designed to capture the surface heterogeneity, the proposed thermodynamic Langmuir isotherm model substitutes the species concentrations with the species activities and calculates the species activity coefficients with the adsorption non-random two-liquid activity coefficient model. The resulting isotherm model accurately represents pure component adsorption isotherms for gases with wide varieties of adsorbents including silica gels, activated carbons, zeolites and metal organic frameworks at various temperatures. With three physically meaningful parameters, the model outperforms the classical Langmuir isotherm model for the 98 isotherms of 33 systems examined.
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