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The additive manufacturing of directionally solidified Ni-based superalloys remains a significant challenge due to the formation of stray equiaxed grains and their high susceptibility to cracking, particularly for high-volume γ´-type Ni-based superalloys. In this study, a novel strategy based on temperature field management was proposed to prevent hot cracking and control crystallographic texture during laser powder bed fusion (LPBF) of IN738LC superalloy. The influence of laser parameters and substrate preheating on crack density, melt pool morphology, and texture of IN738LC superalloy was investigated. The fluid dynamics and thermal behavior of melt pool was simulated using the discrete element model (DEM) and volume of fluid (VOF) method. The processing window for achieving defect-free IN738LC samples was established and was found to be highly affected by substrate preheating. Substrate preheating at 350 °C resulted in expanded processing window, with the volume energy density ranging from 42.9 to 62.5 J/mm³ without substrate preheating to 40–75 J/mm³. The enlarged processing window was achieved by reducing cracking susceptibility due to the reduced temperature gradient and cooling rate. A unique crystallographic lamellar microstructure (CLM), comprising a <110>-oriented major layer and <100>-oriented sub-layer along the building direction, was successfully achieved in the LPBF-processed IN738LC superalloy. The solidification conditions for obtaining such a CLM were discussed on the aspects of temperature gradient and solidification rate within the melt pool. This work provides new insights and methods for preparing crack-free γ´-Ni-based superalloys with specific textures, which is favorable for improving the high-temperature properties.

To ensure the safe and stable operation of wireless power transfer (WPT) systems, metal foreign object detection is one of its essential functions. In this paper, a system is designed for detecting and locating small metal foreign objects such as iron clips, coins, and screws. First, simulations are conducted to analyze the mutual inductance between different detection coils and metal foreign objects. The detection coils are determined to have a trapezoidal shape, and the structural parameters, including wire diameter and spacing, are optimized. Next, a dual-channel lock-in amplifier is designed based on the correlation detection principle, and complementary upper computer software is developed to process the output signals from the detection coils. A 5 mV voltage increment test is performed on the conditioning circuit, and the system measurement error is within 5%. Finally, a metal foreign object detection experimental platform is constructed. Through multiple experiments without foreign objects, the maximum value of the digital quantity corresponding to the induced voltage change of the coil is established as the detection threshold for the system. Detection experiments are conducted on common small metal foreign objects such as iron clips, coins, and screws. Results show that the digital quantity change for iron clips can reach up to four times the detection threshold, and the smallest screw exhibits a digital quantity change exceeding 1.2 times the detection threshold. This indicates that the system can effectively detect small metal foreign objects. In addition, the use of orthogonally stacked dual-layer detection coils enables effective positioning of foreign objects.

Fe-Mn-Al-C medium Mn steels were found to reveal extraordinary superplasticity and have significant potential for forming the complex structural parts due to high strength, excellent ductility and material cost. In present study, the effect of tensile deformation temperature on the superplastic deformation behavior of a cold-rolled low Al-added medium Mn steel was studied. A maximum tensile elongation of approximately 1170% was obtained at 745 °C and 10−2s−1, which is to our best knowledge the highest low-temperature-high-strain-rate superplasticity in medium Mn steels. Also, the role mechanism of microalloying elements such as Ti and Mo was revealed to further enhance the strength level of superplastic medium Mn steels. In view of the representative microstructural features, such as equiaxed grains, random texture, and sluggish grain growth, grain boundary sliding is thought to be the dominative mechanism during the high-strain-rate superplastic deformation.

Background: Oxidative stress and mitochondrial dysfunction play a vital role in the pathogenesis of brain aging. Saponins from Panax japonicus (SPJ) have attracted much attention for their potential to attenuate age-related oxidative stress as the main ingredient in rhizomes of Panax japonicus. Objective: This study aimed to investigate the neuroprotective effects of SPJ on natural aging rats as well as the underlying mechanisms regarding oxidative stress and mitochondrial pathway. Methods: Sprague-Dawley rats were divided into control groups (3-, 9-, 15- and 24-month old groups) and SPJ-treated groups. For SPJ-treated groups, SPJ were orally administrated to 18-month old rats at doses of 10 mg/kg, 30 mg/kg and 60 mg/kg once daily. Control groups were given the same volume of saline. After the treatment with SPJ or saline for six months, the cortex and hippocampus were rapidly harvested and deposited at -80°C after the rats were decapitated under anesthesia. The neuroprotective effects of SPJ were estimated by histopathological observation, TUNEL detection, biochemical determination and western blotting. Results: SPJ improved pathomorphological changes in neuronal cells and decreased apoptosis in the cortex and hippocampus of aging rats, increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Na+/K+-ATPase, Ca2+-ATPase and Ca2+/Mg2+-ATPase whereas, decreased malondialdehyde (MDA) contents in the cortex of aging rats. Furthermore, the SPJ increased silent mating type information regulation 2 homolog-1 (SIRT1) protein expression, decreased acetylated level of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in the cortex and hippocampus of aging rats, and reversed the aging-induced decline of Forkhead box O3 (Foxo3a), Superoxide Dismutase 2 (SOD2), microtubule-associated protein light chain 3 (LC3II) and Beclin1 levels in the cortex and hippocampus. Conclusion: Our data showed that SPJ conferred neuroprotection partly through the regulation of oxidative stress and mitochondria-related pathways in aging rats.

ABSTRACTTumorigenic cancer stem cells (CSCs) exist in various tumors including the cutaneous squamous cell carcinoma (cSCC) as a minor subpopulation and are tightly associated with metastasis and therapeutic resistance. Better understanding of CSCs properties is essential for the novel therapeutic strategy targeted toward these cancers. The cSCC stem cells (cSCCSCs) were enriched from a cSCC cell line A431 by repeated sphere culture, and identified via the expression analysis of stemness marker genes and CD44 proteolysis. MiR-199a-5p was previously reported to be related with the proteolysis modulation of CD44, so the specific regulation mechanisms were verified by overexpression in vitroand in vivo. MiR-199a-5p is under-expressed in cSCCSCs and functions as a tumor suppressive molecule. Overexpression of miR-199a-5p reduced the stemness of cSCCSCs and inhibited cell proliferation. By targeting the deacetylase Sirt1, miR-199a-5p inhibited cellular proteolysis of CD44 and reduced the CD44 intracellular domain (CD44ICD) release and nuclear translocation. Overexpression of CD44ICD reversed the effects of miR-199a-5p overexpression or Sirt1 silencing, and increased the transcriptional expression of stemness genes. Our results revealed that the miR-199a-5p/Sirt1/CD44ICD signaling pathway regulates cSCCSCs progression by affecting its migration ability and tumorigenicity, therefore can be utilized to develop a curative approach for cSCC.Abbreviations: CSCs: cancer stem cells; cSCC cutaneous squamous cell carcinoma; cSCCSCs: cSCC stem cells; CD44ICD: CD44 intracellular domain; HA: hyaluronic acid; HNSCC: hand and neck squamous cell carcinoma; ESCC: esophageal squamous cell carcinoma;MMPs: matrix metalloproteinases; SFM: sphere formation medium; EGF: epidermal growth factor; bFGF: basic fibroblast growth factor; BSA: bovine serum albumin; CCK-8: cell counting kit-8

Liquid metal (LM)-based flexible sensors, which utilize advanced liquid conductive materials to serve as sensitive elements, are emerging as a promising solution to measure large deformations. Nowadays, one of the biggest challenges for precise control of soft robots is the detection of their real-time positions. Existing fabrication methods are unable to fabricate flexible sensors that match the shape of soft robots. In this report, we first described a novel 3D printed multifunction inductance flexible and stretchable sensor with LMs, which is capable of measuring both axial tension and curvature. This sensor is fabricated with a developed coaxial LM 3D printer by coprinting of silicone rubber and LMs. Because of the solenoid shape, this sensor can be easily installed on snakelike soft robots and can accurately distinguish different degrees of tensile and bending deformations. We determined the structural parameters of the sensor and proved its excellent stability and reliability. As a demonstration, we used this sensor to measure the curvature of a finger and feedback the position of an endoscope, a typical snakelike structure. Because of its bending deformation form consistent with the actual working status of the soft robot and unique shape, this sensor has better practical application prospects in the pose detection.

Objective: This study aimed to elucidate the antibacterial properties and therapeutic effect in refractory diabetic wound healing of a NanoAg-epidermal growth factor sustained-release carrier(NanoAg-EGF). Methods: as previous publishing, the sustained-release carrier of NanoAg-EGF can be conducted. The antibacterial properties and therapeutic effects of NanoAg-EGF were determined through in vitro bacterial growth inhibition experiments and in vivo wound healing experiments in diabetic rats. Results: In antibacterial experiments, NanoAg-EGF had strong properties of antibacterial which is similar to those of NanoAg (p>0.05). In diabetic wound healing experiments, NanoAg-EGF significantly shortened the wound healing time. Furthermore, at 3 days after wounding, the healing rate of each group was no different (p>0.05). However, at 7 and 13 days after wounding, with being higher than other four groups, the healing rates of sustained-release carrier treated diabetic rats were remarkable (p<0.05). Conclusion: NanoAg-EGF not only has good antibacterial properties, but can also promote rapid wound healing in diabetes.

Myocardial infarction (MI) increased reactive oxygen species (ROS) and cardiomyocyte apoptosis. Saponins from Panax japonicus (SPJ) exerted beneficially cardioprotective effects on myocardial ischemia injury and possess antioxidant properties to scavenge the toxic radicals. Nuclear factor erythroid 2-related factor (Nrf2) is a transcription factor that controls the expression of a large pool of anti-oxidant and protects cells from oxidative damage. The data from this study show that SPJ reduced the production of ROS by increase the expression of antioxidants and restore the balance between prooxidants and antioxidants via activation of the Nrf-2 pathway. Furthermore, SPJ might reduce ROS production and apoptosis in hydrogen peroxide-induced H9c2 cells. The effect of MI apoptotic cells induces generation of ROS in abundance. Taken together, SPJ treatment significantly improved MI-induced injury and this may be attributing to inhibiting ROS related apoptosis via activation of the Nrf-2 pathway.

The flow curve behavior and microstructure evolution of commercially pure titanium (CP-Ti) through uniaxial hot compression was investigated at 850 °C and a strain rate of 0.1/s. Electron back scattered diffraction (EBSD) was employed to characterize the microstructure and crystallographic texture development for different thermomechanical conditions. The stress-strain curves of CP-Ti alloy under hot compression displayed a typical flow behavior of metals undergoing dynamic recrystallization (DRX), which resulted in grain refinement. The critical strain for the onset of DRX was 0.13 using the double differentiation analysis technique. It was also revealed that the texture was markably altered during hot deformation.

Activating mutations in the receptor tyrosine kinase FLT3 are present in up to approximately 30% of acute myeloid leukemia (AML) patients, implicating FLT3 as a driver of the disease and therefore as a target for therapy. We report the characterization of AC220, a second-generation FLT3 inhibitor, and a comparison of AC220 with the first-generation FLT3 inhibitors CEP-701, MLN-518, PKC-412, sorafenib, and sunitinib. AC220 exhibits low nanomolar potency in biochemical and cellular assays and exceptional kinase selectivity, and in animal models is efficacious at doses as low as 1 mg/kg given orally once daily. The data reveal that the combination of excellent potency, selectivity, and pharmacokinetic properties is unique to AC220, which therefore is the first drug candidate with a profile that matches the characteristics desirable for a clinical FLT3 inhibitor.

Abstractβ-N-Acetyl-D-glucosaminidase (NAGase, EC.3.2.1.52), which catalyzes the cleavage of N-acetylglucosamine polymers, is a composition of chitinase and cooperates with endo- chitinase and exo-chitinase to disintegrate chitin into N-acetylglucosamine (NAG). In this investigation, A NAGase from green crab (Scylla serrata)was purified and the effects of dioxane on the enzyme activity for the hydrolysis of p-Nitrophenyl-N-acetyl-β-D- glucosamin- ide (pNP-NAG) were studied. The results show that appropriate concentrations of dioxane can lead to reversible inactivation of the enzyme and the inactivation is classified as mixed type. The value of IC50, the dioxane (inactivator) concentration leading to 50%activity lost, is estimated to be 0.68%. The kinetics of inactivation of NAGase in the appropriate concentrations of dioxane solution has been studied using the kinetic method of the substrate reaction. The rate constants of inactivation have been determined. The results showed that k+ois much larger than k′+o, indicating the free enzyme molecule is more fragile than the enzyme- substrate complex in the dioxane solution. It is suggested that the presence of the substrate offers marked protection of this enzyme against inactivation by dioxane.

In a broiler carcass production conveyor system, inspection, monitoring, and grading carcass and cuts based on computer vision techniques are challenging due to cuts segmentation and ambient light conditions issues. This study presents a depth image-based broiler carcass weight prediction system. An Active Shape Model was developed to segment the carcass into 4 cuts (drumsticks, breasts, wings, and head and neck). Five regression models were developed based on the image features for each weight estimation (carcass and its cuts). The Bayesian-ANN model outperformed all other regression models at 0.9981 R2and 0.9847 R2in the whole carcass and head and neck weight estimation. The RBF-SVR model surpassed all the other drumstick, breast, and wings weight prediction models at 0.9129 R2, 0.9352 R2, and 0.9896 R2,respectively. This proposed technique can be applied as a nondestructive, nonintrusive, and accurate on-line broiler carcass production system in the automation of chicken carcass and cuts weight estimation.

A novel functional monomer containing cyano and propenylphenoxy groups, 2,6‐di{2‐[(E)‐l‐propenyl]phenoxy}benzonitrile (DPPB) was prepared with high stereospecificity by the reaction of 2,6‐dichlorobenzonitrile and 2‐allylphenol in a mixed solvent system of N‐methylpyrrolidone (NMP)/toluene in the presence of anhydrous potassium carbonate. The chemical structure of the product was characterized by FTIR, 1H NMR and 13C NMR. The monomer was then used to modify a popular commercial bismaleimide, 4,4‐bismaleimidodiphenylmethane (BMDPM), for improving the shear strength of the resin. The results showed that the modified resin could attain 4.7 times the shear strength of neat BMDPM and good heat resistance when the composition of DPPB in the modified resin was 45% (by weight).© 2002 Society of Chemical Industry

Adenine deoxynucleosides induce apoptosis in quiescent lymphocytes and are thus useful drugs for the treatment of indolent lymphoproliferative diseases. To explain why deoxyadenosine and its analogs are toxic to a cell that is not undergoing replicative DNA synthesis, several mechanisms have been proposed, including the direct binding of dATP to the pro-apoptotic factor Apaf-1 and the activation of the caspase-9 and -3 pathways. In this study it is shown, by means of several assays on whole cells and isolated mitochondria, that 2-chloro-2'-deoxyadenosine (2CdA) and 2-choloro-2'-ara-fluorodeoxyadenosine (CaFdA) disrupt the integrity of mitochondria from primary chronic lymphocytic leukemia (B-CLL) cells. The nucleoside-induced damage leads to the release of the pro-apoptotic mitochondrial proteins cytochrome c and apoptosis-inducing factor. The other adenine deoxynucleosides tested displayed comparable DNA-damaging potency but did not affect mitochondrial function. Interference with mitochondrial integrity, thus, may be a factor in the potent cytotoxic effects of 2CdA and CaFdA toward nondividing lymphocytes.

We make a detailed study of the three-body decays B(s)→χc1hh′, where h(′) is either a pion or kaon, by taking into account the S-wave states in the hh′ invariant mass distribution within the perturbative QCD approach. The two meson distribution amplitudes are introduced to capture the strong interaction related to the production of the hh′ system. We calculate the branching ratios for the S-wave components and observe large values of order 10−4 for some Cabibbo-favored decays, which are accessible to the LHCb and Belle II experiments. The obtained branching ratio B(B→χc1K∗0(1430)(→K+π−))=(5.1+0.6−0.8)×10−5 consistent with the data from Belle within errors. Moreover, we also predict the differential distributions in the hh′ invariant mass for the decays under consideration, which await the future experimental test. In addition, the corresponding χc1(2P) channels are also investigated, which are helpful to clarify the nature of the X(3872) state. [ABSTRACT FROM AUTHOR]

Additive manufacturing, also known as 3D printing, overcomes many design and manufacturing constraints to allow almost direct production of metals into complicated geometries. However, coarse columnar grain structures, up to the millimeter-scale, are commonly produced in titanium and its alloys through the layer-by-layer process and this causes significant anisotropy in mechanical properties. Here we report an innovative approach for microstructure refinement of an additively manufactured Ti-6Al-4V alloy via directed energy deposition of boron nitride nanotube (BNNT) decorated powders. With only 0.4 wt% BNNT, this process results in unprecedented grain refinement down to a few micrometers and over 50% strength enhancement. A unique texture-weakened structure comprising fine equiaxed grains is achieved via a novel nanoparticle-mediated nucleation mechanism enabled by local hypereutectic precipitation in the rapid solidification process. This mechanism is highly suited to the metallurgical environment of metal additive manufacturing and creates a pathway for screening effective grain refiners in titanium and other alloy systems.

AbstractThe synthesis, stability toward nucleases, and conformational properties of 3′→5′ and 5′→5′ dinucleotides bearing an isomeric nucleoside component is described.

The appearance, size, and weight of poultry meat and eggs are essential for production economics and vital in the poultry sector. These external characteristics influence their market price and consumers' preference and choice. With technological developments, there is an increase in the application and importance of vision systems in the agricultural sector. Computer vision has become a promising tool in the real-time automation of poultry weighing and processing systems. Owing to its noninvasive and nonintrusive nature and its capacity to present a wide range of information, computer vision systems can be applied in the size, mass, volume determination, and sorting and grading of poultry products. This review article gives a detailed summary of the current advances in measuring poultry products' external characteristics based on computer vision systems. An overview of computer vision systems is discussed and summarized. A comprehensive presentation of the application of computer vision-based systems for assessing poultry meat and eggs was provided, that is, weight and volume estimation, sorting, and classification. Finally, the challenges and potential future trends in size, weight, and volume estimation of poultry products are reported.

SDX-101 (R-etodolac), which is currently being evaluated in clinical trials for treatment of chronic lymphocytic leukemia, down regulates the activity of the β-catenin pathway and inhibits the growth of non-Hodgkin's Lymphoma Daudi tumor xenografts in vivowhen dosed orally (AACR PROC 2004 Abs# 2061 and #4574). Initial co-immunoprecipitation experiments conducted on cell nuclear fractions identified a heteromeric nuclear protein complex containing β-catenin and PPAR-γ. Furthermore, we have demonstrated that SDX-101 treatment reduces nuclear β-catenin in the immunoprecipitated complex, indicating that this complex may represent a target of SDX-101 (AACR PROC 2004 Abs# 3672). We recently reported evaluation of novel structural analogs of SDX-101 and have shown that these analogs, whose structures were not disclosed, are 5–10 fold more potent in in vitrocytotoxicity assays than SDX-101 and that they are orally efficacious in vivo(NCI/EORTC 2004 Abs #383). Our current studies further characterize the mechanism of action and safety of these analogs and identify the structures of selected analogs. Novel functional assays were developed to test and compare SDX-101 and the analogs at 4 hours post-treatment, a time before appreciable loss of viability was detected. Best results were obtained using a functional assay co-transfecting a β-catenin-dependent reporter construct (TOPFLASH) and β-catenin and RXR expression vectors. The average IC50 of analogs in this β-catenin reporter system ranged from 50 to 160 μM. These values were approximately five- to ten- fold lower than the IC50 for SDX-101 (~700 μM). Similar results were obtained assessing the inhibition of PPAR-γ-mediated transcription, using a PPAR-dependent reporter and co-transfection with PPAR-γ and RXR expression vectors. The average IC50s of the analogs ranged from 50–150 μM in this functional assay, demonstrating an approximately 10-fold increase in potency of the analogs when compared to SDX-101 (~1000 μM). No effect was observed at the 4 hour time point using a constitutive SV40-based control reporter vector. These results suggest that the primary target for these compounds may be a nuclear complex containing β-catenin, PPAR-γ and RXR, supporting a hypothesis developed upon evaluation of earlier results generated with SDX-101. To evaluate the safety of two SDX-101 analogs in vivo, normal mice were administered each analog at 240, 120 and 60 mg/kg/d (M-F) for four weeks. Mortality, morbidity, clinical signs, hematology/chemistry were monitored. There were no mortalities, overt toxicities or abnormal observations at necropsy with either of the analogs at any of the tested dose levels. There was a transient body weight loss (<5%) and a mild dose-independent increase in platelets and a reversible decrease in total bilirubin. Results of the histopathological examination of critical organs are pending. These results suggest, when given at doses previously shown to be efficacious in a DAUDI murine lymphoma model, these analogs were well tolerated.