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This study evaluated the effects of the light intensity of curing and the post-curing duration on the mechanical properties and accuracy of the interim dental material. After designing the specimen, 3D printing was performed, and the light intensity was divided into groups G20, G60, G80, and G120 (corresponding to 1.4–1.6, 2.2–3.0, 3.8–4.4, and 6.4–7.0 mW/cm2, respectively), with no post-curing or 5, 10, or 20 min of post-curing being performed. The flexural properties, Vickers microhardness, degree of conversion (DC), and 3D accuracy were then evaluated. The flexural properties and Vickers microhardness showed a sharp increase at the beginning of the post-curing and then tended to increase gradually as the light intensity and post-curing time increased (p < 0.001). On the other hand, there was no significant difference between groups in the accuracy analysis of a 3D-printed three-unit bridge. These results indicate that the light intensity of the post-curing equipment influences the final mechanical properties of 3D-printed resin and that post-curing can be made more efficient by optimizing the light intensity and post-curing time.

Background: Trastuzumab deruxtecan (T-DXd) has been approved in various types cancer and recently expanded its indication to cancers with various HER2 expressions, such as HER2-low breast cancer. Since the effect of T-DXd is based on toxin payload, topoisomerase I inhibitor, the emergence of toxin-resistant cancer cells is unavoidable. Clinical cases of Primary, or secondary resistance to T-DXd have been reported. Therefore, it is necessary to develop novel drugs that can effectively exhibit antitumor effects against T-DXd-resistant carcinoma. Interferon beta (IFN-β), a promising potent cytokine, has been attracting attention for treatment of cancer. It is one of the few cytokines that induce tumor cell killing directly. Importantly, it could be an alternative to conventional drug-resistant cancer, because it regulates tumor growth in a way different from cytotoxic agents. Here, GNP101, an IFN-β mutein-based immunocytokine, exhibits antitumor properties against HER2-positive cancers, including T-DXd-resistant cancer. Method: A panel of human HER2-positive cancer cell lines derived from breast, stomach and lung were treated with GNP101 or HER2 therapeutics (trastuzumab, T-DM1, T-DXd) to compare direct antitumor effects. To generate a T-DXd-resistant cells, HCC1954, NCI-N87 and Calu-3 were exposed to the IC50, IC80 or IC90 of T-DXd by cyclic treatment. After 4 months, HCC1954-R cells were established and IFN-β signaling was assessed by STAT1-phosphorylation. The direct antitumor effect of GNP101 in vivo was tested in HER2-positive cancer xenograft models. Result: GNP101 showed superior potency compared to existing HER2 therapies (trastuzumab, T-DM1, and T-DXd) in all HER2-positive cancers regardless of tissue origin. To investigate the antitumor effect of GNP101 against T-DXd resistant cancer, we first generated T-DXd-resistant cell line (HCC1954-R). These HCC1954-R cells were strongly resistant to T-DXd, and showed no antitumor effect even at 100 nM of T-DXd. However, they were sensitive to GNP101, suggesting that GNP101 maintained its antitumor effect in T-DXd resistant cells. In addition, there was no difference in IFN-β-induced STAT1 phosphorylation between the parent cell and HCC1954-R. Taken together, these results indicate that HCC1954-R cells maintain IFN-β signaling and are selectively resistant to T-DXd. The activities of GNP101, T-DM1 and T-DXd on HER2-positive cancer cells were compared in vivo. GNP101 inhibited the growth of tumor by 90%, with no difference from that of T-DXd or T-DM1. Conclusion: We have evaluated the antitumor properties of GNP101, a trastuzumab-IFN-β mutein in HER2-expressing cancer. Given that GNP101 retains its antitumor properties in T-DXd-resistant cancer cells, the study suggests that anti-HER2-IFN-β mutein is a promising candidate for the treatment of HER2-positive and T-DXd resistant cancers. Citation Format: Chan Gyu Lee, Minkyung Park, Hyun Kyung Lee, Na Young Kim, Jun Young Choi, Sungyoul Hong, Young Kee Shin, Hae Min Jeong. GNP101, anti-HER2-IFN-β mutein immunocytokine, for the treatment of Trastuzumab deruxtecan-resistant HER2-positive cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1803.

In this work, α-Fe2O3 nanocrystals are synthesized by co-precipitation method and used as adsorbent to remove Cr6+, Cd2+, and Pb2+ from wastewater at room temperature. The prepared sample is evaluated by XRD, BET surface area, and FESEM for structural and morphological characteristics. XRD patterns confirm the formation of a pure hematite structure of average particle size of ~ 40 nm, which is further supported by the FESEM images of the nanocrystals. The nanocrystals are found to have BET specific surface area of ~ 39.18 m2 g−1. Adsorption experiments are carried out for the different values of pH of the solutions, contact time, and initial concentration of metal ions. High efficiency Cr6+, Cd2+, and Pb2+ removal occur at pH 3, 7, and 5.5, respectively. Equilibrium study reveals that the heavy metal ion adsorption of the α-Fe2O3 nanocrystals followed Langmuir and Freundlich isotherm models. The Cr6+, Cd2+, and Pb2+ adsorption equilibrium data are best fitted to the Langmuir model. The maximum adsorption capacities of α-Fe2O3 nanocrystals related to Cr6+, Cd2+, and Pb2+ are found to be 15.15, 11.63, and 20 mg g−1, respectively. These results clearly suggest that the synthesized α-Fe2O3 nanocrystals can be considered as potential nano-adsorbents for future environmental and health related applications.

Two new triarylmethane-based dye molecules with a dimeric structure, TAM-1 and TAM-2, were designed and synthesized as potential blue color filter materials for liquid-crystal displays. The dimeric structure of TAM-1 was designed to improve the thermal stability of a well-known blue dye, Victoria Blue BO. TAM-2 was designed to further improve the solubility of TAM-1 by introducing long alkyl ester groups. The synthesized dyes TAM-1 and TAM-2 were transmissive in the wavelength range of 410-460 nm and showed good thermal stability with 5% weight degradation temperatures (T5d) of 259 °C and 289 °C, respectively, and less than 1% of weight loss at 230 °C. Moreover, TAM-2 showed excellent solubility (20.1 wt%) as opposed to Victoria Blue BO (0.03 wt%) and TAM-1 (3.5 wt%) in PGMEA.

Type I interferon (IFN) has been approved as an anticancer agent to treat some malignancies. However, IFNs have a short in vivo half-life, systemic toxicity, and poor biophysical properties, which prevent it from being widely used for cancer therapy. This study aimed to construct recombinant IFN-β-1a mutein immunocytokines that comprise a human epidermal growth factor receptor 2 (HER2)-targeting antibody and IFN-β muteins with an additional glycosylation, which can overcome the limitation of the cytokine itself. Hence, the molecular design aims to 1) enhance productivity and biophysical properties by adding secondary glycosylation in IFN-β, 2) increase the therapeutic index of IFN-β therapy by preferential retention at the tumor by possessing high affinity for HER2-expressing cancer cells, and 3) improve the pharmacokinetics and, thus, the convenience of IFN-β administration. The yield of trastuzumab-IFN-β mutein was higher than that of trastuzumab-wild-type IFN-β in the mammalian cell culture system. Trastuzumab-IFN-β mutein showed similar IFN activity and HER2-targeting ability equivalent to that of IFN-β mutein and trastuzumab, respectively. Trastuzumab-IFN-β mutein directly inhibited the growth of HER2-positive gastric cancer cell lines and was more effective than trastuzumab or IFN-β mutein alone. Trastuzumab-IFN-β mutein and IFN-β mutein displayed enhanced immune cell-mediated cytotoxicity. Collectively, trastuzumab-IFN-β mutein may have indirect immune cell-mediated antitumor effects and direct cell growth inhibitory effects. Tumor-targeting effect of trastuzumab-IFN-β mutein was analyzed using in vivo fluorescence imaging. The accumulation of trastuzumab-IFN-β mutein was observed in HER2-positive tumors rather than other tissues except the liver. To evaluate the both direct tumor growth inhibition effect and indirect immune cell-mediated antitumor effect, we tested the effect of trastuzumab-IFN-β mutein in HER2-positive cancer xenograft models using nude mice or humanized mice. Trastuzumab-IFN-β mutein could significantly enhance tumor regression when compared with trastuzumab or IFN-β mutein. In addition, an increase in tumor-infiltrating lymphocytes was observed in the trastuzumab-IFN-β mutein-treated group, implying that the tumor-targeting IFN-β may have an enhanced antitumor effect through increased immune response. Therefore, targeting IFN-β with an anti-HER2 monoclonal antibody makes the immunocytokine more potent than either agent alone. These novel findings suggest that trastuzumab-IFN-β mutein merits clinical evaluation as a new candidate of anticancer therapeutics.

Background: Interferon beta (IFN-β), a promising potent cytokine, has been attracting attention for treatment of cancer. The pleiotropic antitumor effects of IFN-β have been studied, with specific reference to their direct role on cancer cells and indirect action through the immune effector cells. However, its systemic toxicities and poor biophysical properties prevent IFN-β from being widely used for cancer therapy. Since the potential of cytokine therapies are impaired due to dose-limiting systemic toxicities, novel treatment methods should be developed to safely deliver effective drug quantities at the tumor sites. Like antibody-drug conjugates (ADCs), immunocytokine can be attempted to induce cytokine's organ-targeting and alleviate its systemic side effects. Here, we designed recombinant IFN-β mutein immunocytokines that comprise a HER2-targeting antibody and IFN-β mutein, and evaluate the antitumor properties against HER2-positive cancers.Method: A panel of human gastric cancer cell lines was treated with trastuzumab-IFN-β mutein to evaluate direct antitumor effect. In addition, to test the immune cell-mediated antitumor effect, cancer cells were co-cultured with effector cells (e.g. PBMC) in the absence or drug. The antitumor efficacy of trastuzumab-IFN-β mutein in vivo was tested in HER2-positive cancer xenograft models using nude mice or humanized mice. Result: Trastuzumab-IFN-β mutein directly inhibited the growth of HER2-positive gastric cancer cell lines and was more effective than trastuzumab or IFN-β mutein alone. Trastuzumab-IFN-β mutein also displayed enhanced immune cell-mediated cytotoxicity. Collectively, trastuzumab-IFN-β mutein may have indirect immune cell-mediated antitumor effects and direct cell growth inhibitory effects. Moreover, trastuzumab-IFN-β mutein significantly suppress tumor growth in HER2-positive cancer xenograft models. Tumor-infiltration of lymphocytes was enhanced by trastuzumab-IFN-β mutein, implying that the tumor-targeting IFN-β may have an antitumor effect through increased immune response. Conclusion: We have characterized and evaluated the antitumor properties of trastuzumab-IFN-β mutein in HER2-expressing cancers. Since IFN-β activates antitumor immune responses, it is expected to be administered in combination with immunotherapeutic drugs. Therefore, the study suggests that trastuzumab-IFN-β mutein is a promising candidate for the treatment of HER2-positive carcinoma. Citation Format: Chan Gyu Lee, Tae Eun Kim, Sungyoul Hong, Jongwan Chu, Ju Eun Kang, Hae Min Jeong, Young Kee Shin. HER2-targeted interferon-beta-1a mutein, a potent immunocytokine for the treatment of HER2-positive cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB170.

La1-xBaxMnO3 (x = 0.30, 0.35 and 0.40) samples have been prepared by solid-state reaction method. The X-ray diffraction (XRD) study showed that all the samples crystallized in a rhombohedral structure with an R-3c space group. Variation of the magnetization as a function of the temperature and applied magnetic field was carried out. All the samples revealed ferromagnetic to paramagnetic (FM-PM) phase transition at the Curie temperature TC ~ 342 K. The magnetic entropy change was also studied through examination of the measured magnetic isotherms M(H, T) near TC. The magnetocaloric effect was calculated in terms of the isothermal magnetic entropy change. The maximum entropy change reaches a value of 1.192 J/ kgK under a magnetic field change of 2.5T for the La0.6Ba0.4MnO3 composition. The relative cooling power (RCP) is 79.31 J/ kg for the same applied magnetic field.

It is now well known that there are experimental results of bifurcate, trifurcate or more Kirkendall marker planes (K-plane) in a multiple phase diffusion couple (M-couple). In the case of Au-Zn binary alloy system, for example, even in a β’/β’ single phase diffusion couple (S-couple) there is a possibility of the bifurcate K-planes because the ratio R = D Zn/D Au of the intrinsic diffusion coefficients in the β’ phase is smaller than 1 in the Au rich side and larger than 1 in the Zn rich side. It has been reported that the positions of the K-planes in a diffusion zone can be found graphically as intersections between the plot of marker moving distance $$2t\upsilon_{\text{k}}^{\text{D}}$$ versus X k and the plot of a straight line $$2t\upsilon_{\text{k}}^{\text{EX}}$$ versus X k. Here, $$\upsilon_{\text{k}}^{\text{D}}$$ is the marker velocity with respect to the volume fixed frame of reference (V-frame) defined by, $$\upsilon_{\text{k}}^{\text{D}} = \upsilon_{\text{k}} - \upsilon_{\text{V}} = V_{\text{B}} \left( {D_{\text{B}}^{\text{V}} - D_{\text{A}}^{\text{V}} } \right)\left( {\frac{{\partial C_{\text{B}} }}{\partial X}} \right),$$ and $$\upsilon_{\text{k}}^{\text{Ex}}$$ is that determined experimentally by the following equation, $$\upsilon_{\text{k}}^{\text{Ex}} = \upsilon_{\text{k}} - \upsilon_{0} = \frac{{X_{k} - X_{0} }}{2t}.$$ In this work, we studied the alignments of multiple markers (M-Ms) after diffusion anneal embedded in a S-couple for widely different constant values of ratio of intrinsic diffusion coefficients, R = D B /D A, with respect to the mole fixed frame of reference (N-frame) by our numerical technique taking the change in molar volume into account. For this purpose, new two plots to know the K-plane(s) for the N-flame were derived. A possibility was indicated that Kirkendall markers can locate not only at the intersection(s) between these new two plots but also at an unexpected place where the intersection cannot be found.

Movement of multiple markers (M-Ms) embedded in the Cu end member of a Cu/Zn multiple phases diffusion couple (M-couple) has been experimentally investigated at 623 K and the alignment of the M-Ms after diffusion anneal was reproduced by the numerical analysis that the authors have previously reported. Two intermediate phases, γ and ɛ, were found in the Cu/Zn M-couple. The M-Ms bent toward Zn side at Cu/γ phase interface and show almost a linear line in the γ phase. They again bent at γ/ɛ interface toward Zn side. The Kirkendall marker position, X k, locates in the ɛ phase layer. From this result, ratio, R = D Zn/D Cu, of the intrinsic diffusion coefficients with respect to the mole fixed frame of reference was determined to be about 46 at X k. On the assumption of a constant value of R = 46 in the ɛ phase and appropriate constant values of R = 10-1000 in the γ phase, alignments of M-Ms after diffusion anneal were numerically reproduced. By fitting the alignment of M-Ms obtained numerically on the experimental result, the value R in γ phase is estimated to be very large value of 500.

The p53 protein is an important transcription factor that modulates signaling pathways for both cell death and survival. Its antiapoptotic mechanisms that correlate with necrotic and apoptotic cell death are not well understood. Here, we report that etoposide promotes progression of the DNA damage response as well as necrotic morphological changes including plasma membrane rupture using carbon nanotube-tipped/atomic force microscopy (CNT/AFM) probes in human kidney proximal tubule (HK-2) cells. Inhibition of p53 abrogated cell cycle arrest and led to a decrease in the expression levels of repair proteins that were induced by DNA damage. Mitochondrial biogenesis and cytosolic production of reactive oxygen species were also reduced after p53 inhibition; the latter change induced mitochondrial superoxide accumulation and mitochondrial damage, which triggered the activation of caspase 3. Inhibition of p53 also led to a loss of cell adhesion and converted necrotic cell death to apoptotic cell death, with appreciable cell shrinkage and appearance of apoptotic bodies that were observed using CNT/AFM probes. Thus, our study demonstrated that p53 protects against apoptosis, and leads to etoposide-induced necrosis. These results are expected to aid in the understanding of mechanism of antiapoptosis and its relationship to cell death.

MicroRNA-122 (miR-122) is implicated as a regulator of physiological and pathophysiological processes in the liver. Overexpression of Gα12 is associated with overall survival in patients with hepatocellular carcinoma (HCC). Array-based miRNA profiling was performed on Huh7 stably transfected with activated Gα12 to find miRNAs regulated by the Gα12 pathway; among them, miR-122 was most greatly repressed. miR-122 directly inhibits c-Met expression, playing a role in HCC progression. Gα12 destabilized HNF4α by accelerating ubiquitination, impeding constitutive expression of miR-122. miR-122 mimic transfection diminished the ability of Gα12 to increase c-Met and to activate ERK, STAT3, and Akt/mTOR, suppressing cell proliferation with augmented apoptosis. Consistently, miR-122 transfection prohibited tumor cell colony formation and endothelial tube formation. In a xenograft model, Gα12 knockdown attenuated c-Met expression by restoring HNF4α levels, and elicited tumor cell apoptosis but diminished Ki67 intensities. In human HCC samples, Gα12 levels correlated to c-Met and were inversely associated with miR-122. Both miR-122 and c-Met expression significantly changed in tumor node metastasis (TNM) stage II/III tumors. Moreover, changes in Gα12 and miR-122 levels discriminated recurrence-free and overall survival rates of HCC patients. Collectively, Gα12 overexpression in HCC inhibits MIR122 transactivation by inactivating HNF4α, which causes c-Met induction, contributing to cancer aggressiveness.

Measurable indicators of renal injury are required for the assessment of kidney function after toxicant challenge. In our previous study, pleckstrin homology-like domain, family A, member 3 (Phlda3) was a most greatly up-regulated molecule downstream from p53, culminating with kidney tubular injury. This study investigated the positive feedforward effect of Phlda3 on p53 in an effort to explain the largest increase of Phlda3 in injured tubules and the potential of its urine excretion. qRT-PCR assays confirmed a rapid and substantial increase in Phlda3 messenger RNA (mRNA) in the kidney cortex of mice treated with a single dose of cisplatin. Cisplatin overexpression of Phlda3 was verified by gene set analyses of three different microarray databases. In the immunohistochemistry, Phlda3 staining intensities were augmented in the tubules as kidney injury worsened. Moreover, the urinary content of Phlda3 was increased after cisplatin treatment, as were those of other kidney injury markers (Kim-1 and Timp-1). By contrast, cisplatin failed to increase Phlda3 mRNA in the liver despite hepatocyte necrosis and ensuing increases in serum transaminase activities. In NRK52E tubular cells, siRNA knockdown of Phlda3 enhanced the ability of cisplatin to increase p-Mdm2 presumably via Akt, enforcing the interaction between Mdm2 and p53. Consistently, a deficiency in Phlda3 abrogated p53 increase by cisplatin, indicating that Phlda3 promotes p53 accumulation. Phlda3 overexpression had the opposite effect. In addition, treatment with cyclosporine A or CdCl2, other nephrotoxicants, increased Phlda3 mRNA and protein levels in NRK52E cells, as did cisplatin treatment. Overall, Phlda3 may cause p53 accumulation through a feedforward pathway, facilitating tubular injury and its urine excretion.

// Jung Min Lee 1 , Mi Jeong Heo 1 , Chan Gyu Lee 1 , Yoon Mee Yang 1 , Sang Geon Kim 1 1 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea Correspondence to: Sang Geon Kim, e-mail: sgk@snu.ac.kr Keywords: E2F3, protoporphyrin IX, miR-199a-5p, chemotherapeutic agent, hepatocellular carcinoma Received: September 22, 2014 Accepted: December 15, 2014 Published: February 24, 2015 ABSTRACT Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths. Protoporphyrin IX (PPIX) has been used for photodynamic therapy. Mesenchymal cancer cells adapt to tumor microenvironments for growth and metastasis possibly in association with miRNA dysregulation. In view of the effect of PPIX on cancer-related genes, and its potential to inhibit tumor growth and migration/invasion, this study investigated whether PPIX enables mesenchymal liver tumor to restore dysregulated miRNAs, and if so, whether it sensitizes the cancer cells to chemotherapy. In addition, we explored new target(s) of the miRNA(s) that contribute to the anti-cancer effects. Of the ten miRNAs predicted by the 3′-UTR of HIF-1α mRNA, PPIX treatment increased miR-199a-5p, leading to the inhibition of E2F3 expression which is upregulated in mesenchymal liver tumor. miR-199a-5p levels were downregulated in HCC with E2F3 overexpression. An approach modulating epithelial-mesenchymal transition provided the expected changes in miR-199a-5p and E2F3 in vivo . PPIX prevented tumor cell growth and migration/invasion, and had a synergistic anti-cancer effect when combined with chemotherapeutics. In a xenograft model, PPIX treatment decreased overall growth and average tumor volume, which paralleled E2F3 inhibition. Overall, PPIX inhibited growth advantage and migratory ability of cancer cells and sensitized mesenchymal liver tumor cells to chemotherapeutics.

A series of amorphous electron beam evaporated Ta and TaN films with N/Ta ratio from 0 to 1.15 were deposited on Si/SiO2 substrates at 200°C. As N/Ta ratio increases, the TaN films undergo phase changes from pure metallic Ta to a mixture of Ta, Ta2N, and nitrogen-rich TaN films. The electrical resistivity of the Ta and TaN films increased from 242 µΩ-cm to 1126 µΩ-cm with increasing N/Ta ratio. X-ray diffraction patterns revealed the development of different phases of TaN that are in agreement with the TaN phase diagram. The presence of different phases on the film surface was also confirmed by x-ray photo-emission spectroscopy (XPS) analysis. Groups of Ta4f doublet related to different TaN phases were observed in the core-level spectra of TaN films. Field-emission scanning electron microscopy images revealed that surface morphology also varied with the phase change in TaN films. The N/Ta ratios from energy-dispersive x-ray generally agreed with those from the XPS analysis.

Background and Purpose Methylene blue (MB) has recently been considered for new therapeutic applications. In this study, we investigated whether MB has antioxidant and mitochondria-protecting effects and can prevent the development of toxicant-induced hepatitis. In addition, we explored the underlying basis of its effects. Experimental Approach Blood biochemistry and histopathology were assessed in mice injected with CCl4 (0.5 mL·kg−1) following MB administration (3 mg·kg−1·day−1, 3 days). Immunoblottings were performed to measure protein levels. Cell survival, H2O2, and mitochondrial superoxide and membrane permeability transition were determined in HepG2 cells. Key Results MB protected cells from oxidative stress induced by arachidonic acid plus iron; it restored GSH content and decreased the production of H2O2. It consistently attenuated mitochondria dysfunction, as indicated by inhibition of superoxide production and mitochondrial permeability transition. MB inhibited glycogen synthase kinase-3β (GSK3β) and protected the liver against CCl4. Using siRNA, the inhibition of GSK3β was shown to depend on AMPK. MB increased the activation of AMPK in vitro (3–24 h) and in vivo. MB also increased the phosphorylation of liver kinase B1 (LKB1) via cAMP-dependent PKA. SiRNA knockdown of LKB1 eliminated phosphorylation of AMPK and inhibited MB activation of AMPK. In addition, MB treatment (≤1 h) facilitated PKA-mediated GSK3β serine phosphorylation independently of AMPK. Conclusions and Implications MB has antioxidant and mitochondria-protecting effects and protects the liver from toxicants, which results from the dual inhibition of GSK3β by AMPK downstream of PKA-activated LKB1, and PKA itself. Our findings reveal a novel pharmacological effect of MB and its molecular basis.

In this work, the effect of deposition power on the structural, morphological, and electrical properties of e-beam evaporated tantalum films was investigated. The as-deposited tantalum films were characterized using x-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy dispersive x-ray (EDX) and four-point probe resistivity measurements. The XRD patterns revealed the growth of a tetragonal crystalline structure (β-Ta), and the crystallinity of the films increased with increased deposition power. The FESEM images showed that the tantalum film morphology was smooth with fine spherical particles on the surface, and the grain size was found to increase with deposition power. The resistivity of the tantalum films decreased with increased deposition power.

In this work, the effect of substrate temperature (room temperature — 250 °C) on the structural, morphological and electrical properties of tantalum films deposited on Si/SiO 2 (100) substrate by electron beam evaporation technique was presented. The structural analysis of the deposited films was done using X-ray diffraction (XRD). The XRD patterns revealed the growth of tetragonal crystalline structure (β-Ta) and that the crystallinity of the films increased with the increase of substrate temperature. The field emission scanning electron microscopy (FESEM) images showed that the film morphology was smooth with fine spherical particles on the surface. The film thickness measured using a cross-sectional FESEM was found to increase from 97 nm to 165 nm with the increase in substrate temperature. The resistivity of tantalum films was found to decrease from ~ 350 μΩ-cm to ~ 220 μΩ-cm with increasing substrate temperature from room temperature — 250 °C respectively.

This paper reports effect of thickness on the properties of titanium (Ti) film deposited on Si/SiO2 (100) substrate using two different methods: d.c. magnetron sputtering and electron beam (e-beam) evaporation technique. The structural and morphological characterization of Ti film were performed using X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM). XRD pattern revealed that the films deposited using d.c. magnetron sputtering have HCP symmetry with preferred orientation along (002) plane, while those deposited with e-beam evaporation possessed fcc symmetry with preferred orientation along (200) plane. The presence of metallic Ti was also confirmed by XPS analysis. FESEM images depicted that the finite sized grains were uniformly distributed on the surface and AFM micrographs revealed roughness of the film. The electrical resistivity measured using four-point probe showed that the film deposited using d.c. magnetron sputtering has lower resistivity of ∼13 μΩcm than the film deposited using e-beam evaporation technique, i.e. ∼60 μΩcm. The hardness of Ti films deposited using d.c. magnetron sputtering has lower value (∼7·9 GPa) than the film deposited using e-beam technique (∼9·4 GPa).

Background and Purpose Oltipraz, a cancer chemopreventive agent, has an anti-steatotic effect via liver X receptor-α (LXRα) inhibition. Here we have assessed the biological activity of a major metabolite of oltipraz (M2) against liver steatosis and steatohepatitis and the underlying mechanism(s). Experimental Approach Blood biochemistry and histopathology were assessed in high-fat diet (HFD)-fed mice treated with M2. An in vitro HepG2 cell model was used to study the mechanism of action. Immunoblotting, real-time PCR and luciferase reporter assays were performed to measure target protein or gene expression levels. Key Results M2 treatment inhibited HFD-induced steatohepatitis and diminished oxidative stress in liver. It increased expression of genes encoding proteins involved in mitochondrial fuel oxidation. Mitochondrial DNA content and oxygen consumption rate were enhanced. Moreover, M2 treatment repressed activity of LXRα and induction of its target genes, indicating anti-lipogenic effects. M2 activated AMP-activated protein kinase (AMPK). Inhibition of AMPK by over-expression of dominant negative AMPK (DN-AMPK) or by Compound C prevented M2 from inducing genes for fatty acid oxidation and repressed sterol regulatory element binding protein-1c (SREBP-1c) expression. M2 activated liver kinase B1 (LKB1) and increased the AMP/ATP ratio. LKB1 knockdown failed to reverse target protein modulations or AMPK activation by M2, supporting the proposal that both LKB1 and increased AMP/ATP ratio contribute to its anti-steatotic effect. Conclusion and Implications M2 inhibited liver steatosis and steatohepatitis by enhancing mitochondrial fuel oxidation and inhibiting lipogenesis. These effects reflected activation of AMPK elicited by increases in LKB1 activity and AMP/ATP ratio.

An understanding of the effects of hypergravity on energy homeostasis is necessary in managing proper physiological countermeasures for aerospace missions. This study investigated whether a single or multiple load(s) of mice to hypergravity has an effect on molecules associated with energy metabolism. In the liver, AMPKα level and its signaling were repressed 6 h after a load to +9 Gz hypergravity for 1 h, and then gradually returned toward normal. AMPKα level was restored after 3 loads to +9 Gz, suggestive of preconditioning adaptation. In cDNA microarray analyses, 221 genes were differentially expressed by +9 Gz, and the down-regulated genes included Nrf2 targets. Nrf2 gene knockout abrogated the recovery of AMPKα elicited by 3 loads to +9 Gz, indicating that Nrf2 plays a role in the adaptive increase of AMPKα. In addition, +9 Gz stress decreased STAT3, FOXO1/3 and CREB levels, which was attenuated during the resting time. Similarly, apoptotic markers were enhanced in the liver, indicating that the liver may be vulnerable to hypergravity stress. Preconditioning loads prevented hepatocyte apoptosis. Overall, a load of mice to +9 Gz hypergravity causes AMPKα repression with liver injury, which may be overcome by multiple loads to hypergravity as mediated by Nrf2.

Background Binge alcohol consumption elicits mitochondrial dysfunction in hepatocytes. An understanding of the effect of ethanol (EtOH) exposure after hypergravity stress on liver function may assist in the implementation of pathophysiological countermeasures for aerospace missions. This study investigated whether a combination of hypergravity stress and binge alcohol intake has a detrimental effect on AMP-activated protein kinase (AMPK) and other molecules necessary for hepatocyte survival. Methods The mice were orally administered a single dose of EtOH (5 g/kg body weight, 20% EtOH) immediately after a load to +9 Gz hypergravity for 1 hour using a small animal centrifuge and sacrificed 24 hours after treatment. For the multiple-dose model, 3 consecutive daily treatments were carried out. Immunoblottings were carried out on liver homogenates. Results Binge alcohol intake in mice immediately after a 1-hour exposure to a +9 Gz hypergravity load repressed hepatic Akt and PARP-1 levels at 24 hours posttreatment. Moreover, it sustainably diminished the level of AMPKα, a key regulator of energy metabolism, as compared to each individual treatment. Similarly, the combination of alcohol and hypergravity suppressed the levels of STAT3, FOXO1/3, C/EBPβ, and CREB, transcription factors necessary for cell survival. Similar changes were not detected after 3 consecutive daily combinatorial treatments, indicating that repetitive training with hypergravity loads provides hepatoprotective effects in a binge alcohol model. Conclusions These results show that binge alcohol exposure in mice immediately following a +9 Gz hypergravity stress persistently decreased AMPKα and other key molecules required for hepatocyte survival, and these changes may be reversed by repetitive hypergravity loads.

In this work, nanocrystalline titanium nitride (TiN) films have been deposited by reactive DC magnetron sputtering technique on the Si/SiO2 (100) substrates. The influence of nitrogen gas flow rate [0, 3, 5, 7 and 9 sccm (standard cubic centimeter per minute)] on the structural, morphological and electrical properties of the nanocrystalline TiN films has been studied. As-deposited TiN films have been characterized by using X-ray diffraction (XRD), XPS (X-ray photoelectron spectroscopy), FESEM (field emission scanning electron microscopy) and four point probe resistivity measurement, respectively. The XRD patterns revealed the HCP symmetry for pure Ti (N2 = 0 sccm) with (002) preferred orientations, and the FCC symmetry for TiN (N2 = 3, 5, 7 and 9 sccm) films having (111) preferred orientations. The lattice parameters were found to be a = 2.950 Ǻ, c = 4.681Ǻ for the Ti (N2 = 0 sccm) film and a = 4.250A for the TiN films. The presence of different phases such as TiN and TiO2 were confirmed by XPS analysis. The FESEM images showed a smooth morphology of the film with columnar grain structures. The grain size of the TiN films was found to decrease from 22 to 15 nm as the nitrogen flow rate is increased from 0 to 9 sccm. The electrical resistivity measurement showed that the resistivity of the film increased from 11 × 10−6 to 17 × 10−6 Ohm cm on increasing nitrogen flow rate from 3 to 9 sccm, having the lowest resistivity of 11 × 10−6 Ohm cm for the film deposited at 3 sccm nitrogen flow.

Polyphenols have antioxidant effects. In view of the diverse biological activities of prenylated natural products, this study investigated whether polyphenols with prenyl residues have improved antioxidant and cytoprotective activity against oxidative stress, and explored the underlying basis for this effect. A set of structurally related polyphenols exhibited varying degrees of antioxidant effect in HepG2 cells, as evidenced by increases in cell viability against oxidative injury; kazinol E and C with three prenyls had greater potency than other kazinols having fewer prenyl chains. Polyphenols without prenyl (tupichinol C and resveratrol) showed weaker potency. Treatment with kazinol E diminished H(2)O(2) production and enabled cells to protect the mitochondria, as indicated by the inhibition of mitochondrial fragmentation, mitochondrial permeability transition, and cytochrome c release. Moreover, kazinol E activated LKB1 by its phosphorylation and cytoplasmic translocation, contributing to the protection of mitochondria via AMPK. In vitro or in a cell-based assay, tyrosine phosphorylation of Fyn was prohibited by kazinol E, which led to LKB1 activation, as shown by the experiments using Fyn over-expression construct or siRNA. SU6656, a known Fyn inhibitor, had a similar effect. Moreover, oxidative stress facilitated Fyn phosphorylation with repression of AMPKα and GSK3β phosphorylation, which was abolished by kazinol E treatment. The role of Fyn inhibition by kazinol E in AMPK-mediated protection of the cell viability and mitochondrial function was strengthened by ectopically expressed Fyn's reversal of these effects. In conclusion, kazinols as multi-prenylated polyphenols possess increased antioxidant and cytoprotective activity, which depends on the activation of LKB1-AMPK pathway downstream of Fyn inhibition.

Herein, we report the deposition of titanium nitride (TiN) film on silicon (100) substrate using DC magnetron sputtering technique. The effect of argon flow rate (5, 10, 15 and 20 sccm (Standard cubic centimeter per minute)) on the structural and morphological properties was studied using X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM), respectively. The XRD patterns revealed the FCC symmetry of the films with an increase in grain size with increasing argon flow. There is no peak of TiN for the film deposited at lower argon flow (5 sccm), however, with the increase in argon flow (10 and 15 sccm), mixed {(111)–(200)} orientations appeared. This mixed {(111)–(200)} orientation transformed to (111) orientation upon further increase in argon flow to 20 sccm. FESEM micrographs showed a smooth morphology of the film with columnar grain structure. The electrical resistivity measurement showed a higher resistivity value (30 μΩcm) for TiN film having (111) preferred orientation and lower resistivity value (18μΩcm) for the films having mixed {(111)–(200)} orientations. The lower value of resistivity is due to the formation of stoichiometric TiN for the mixed {(111)–(200)} orientation.

We demonstrate that a magnetic tunnel structure irradiated by microwaves can generate a significant voltage signal due to the rectification effect. The measurements were carried out using current-in-plane geometry with a current flowing parallel to the interfaces in the structure. A value of the microwave-induced voltage strongly depends on a bias current and can be driven by a magnetic field. The rectification effect is discussed both in classical terms of nonlinearity of the current-voltage characteristic and using a mechanism that involves the interplay between the spin-polarized current and magnetization dynamics in the magnetic tunnel structure.

Fyn kinase has emerged as a regulator of diverse pathological processes. However, therapeutic Fyn inhibitors are not available. This study investigated the potential of a series of cycloalkane-fused dithiolethiones (CDTs) or other congeners to increase antioxidant capacity in association with Fyn inhibition, as well as the molecular basis for this effect. Treatment of HepG2 cells with each agent protected the mitochondria from oxidative injury elicited by arachidonic acid and iron, which increased cell viability; 4,5,6,7-tetrahydrobenzo-1,2-dithiole-3-thione (SNU1A) and 5,6-dihydro-4H-cyclopenta-1,2-dithiole-3-thione (SNU2A) were the most effective, whereas 5-methyl-1,2-dithiole-3-thione (SNU3A) was less active. 5-(Quinolin-2-yl)-1,2-dithiole-3-thione (SNU3E) had a minimal effect. SNU1A treatment decreased mitochondrial superoxide production and enabled cells to restore mitochondrial membrane permeability. Oxidative injury caused by arachidonic acid and iron enhanced Fyn phosphorylation at a tyrosine residue, which was decreased by SNU1A treatment. 2,3-Dihydro-N,N-dimethyl-2-oxo-3-[(4,5,6,7-tetrahydro-1H-indol-2-yl)methylene]-1H-indole-5-sulfonamide (SU6656), a known Fyn inhibitor, had a similar effect. Fyn inhibition contributed to protecting mitochondria from injury through AMP-activated protein kinase (AMPK), as supported by reversal of this effect with Fyn overexpression. Consistently, Fyn overexpression attenuated AMPK activation by SNU1A, which strengthens the inhibitory role of Fyn in AMPK activity. CDTs had antioxidant effects, as shown by increases in GSH contents and inhibition of H(2)O(2) production. They also had the ability to activate nuclear factor E2-related factor 2 (Nrf2), a key antioxidant transcription factor. Fyn overexpression decreased the Nrf2 activation induced by SNU1A. Our results demonstrate that CDTs exert cytoprotective effects by protecting mitochondria and increasing the cellular antioxidant capacity, which may result not only from Fyn inhibition leading to AMPK activation but also from Nrf2 activation.

The Multiple-Marker (M-M) method is useful because it enables the determination of the intrinsic diffusion coefficients not only at the Kirkendall marker position but also at places where the M-M are located. However, the analysis is not applicable to the alloys with variable molar volume. In this work, a new graphical method that is applicable to the alloys with variable molar volume is proposed.

The microstructural evolutions of precipitates formed in a Cu75-Fe5-Ni20 alloy on isothermal annealing at 873 K and 1073 K have been investigated by means of transmission electron microscopy (TEM). Nano-scale magnetic particles were formed randomly in the Cu-rich matrix after receiving a short annealing due to phase decomposition in the alloy. With increasing the isothermal annealing time, however, the striking features that two or more nano-scale particles with a cubic shape and a rod shape were aligned linearly along (100) directions were observed on isothermal annealing at 873 K and 1073 K, respectively. To investigate electro-magnetic properties of precipitates in a Cu-Fe-Ni alloy, the superconducting quantum interference device (SQUID) magnetometer and physical property measurement system (PPMS) were also complemented. The present study revealed significant influences that the magnetic properties of the specimens were closely related to the microstructures in the Cu-Fe-Ni alloy, which microstructures significantly depend on the isothermal annealing temperature.

During the sputtering process in Ar gas, the sputtered target atoms and the reflected Ar neutrals from the target have much higher energy than the background gas. In this study, the Thompson distribution and an updated Meyer model based on the elastic energy transfer between two colliding particles were used to obtain energy distributions and average energies for the sputtered metal atoms and the reflected Ar neutrals. An energy dependent elastic collision cross section was incorporated into Meyer’s model and a thermalization criterion based on power balance was used. Under typical sputtering conditions (0.5 mTorr and 1000 K Ar, 400 eV incident Ar ion), the model predictions indicate that for Cu, Ti and Ta targets, the sputtered metal atoms have initial average energies from 15 to 22 eV and thermalize with the background Ar gas between 10 and 20 collisions. The reflected Ar neutrals thermalize after about 10 collisions. Depending on the number of collisions, the energy dependent mean free path values of the sputtered metal atoms range from 300 to 100 cm while the mean free path values for the reflected Ar neutrals range from 200 to 100 cm.

We have successfully synthesized large-scale aggregative flowerlike Zn1-xCo(x)O (0.0 < or = x < or = 0.07) nanostructures, consisting of many branches of nanorods at different orientations with diameter within 100-150 nm (tip diameter approximately 50 nm) and length of approximately 1 microm. The rods were prepared using Zinc nitrate, cobalt nitrate and KOH in 180 Watt microwave radiation for short time interval. The synthesized nanorods were characterized using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), field emission transmission electron microscopy (FETEM) and DC magnetization measurements. XRD and TEM results indicate that the novel flowerlike nanostructures are hexagonal with wurtzite structure and Co ions were successfully incorporated into the lattice position of Zn ions in ZnO matrix. The selected area electron diffraction (SAED) pattern reveals that the nanorods are single crystal in nature and preferentially grow along [0 0 1] direction. Magnetic studies show that Zn1-xCo(x)O nanorods exhibit room temperature ferromagnetism. This novel nanostructure could be a promising candidate for a variety of future spintronic applications.

Sphere-like rutile TiO2 nanocrystals have been synthesized by sol-gel method followed by hydrolysis of titanium tetrachloride in deionized water in the presence of ammonium hydroxide as hydrolysis catalyst. The as-prepared TiO2 nanoparticles have single rutile phase with average diameter approximately 26.4 nm. The results show that the temperature has a great influence on the particle size distribution and also crystalline phase (rutile) of TiO2 nanoparticles is consistent with the temperature. Characterization of the as-prepared nanocrystalline powder was carried out by different techniques such as powder X-ray diffraction (XRD), field emission transmission electron microscopy (FE-TEM) and Raman spectroscopy.

HVOF thermal spray coating of 80%WC-CoFe powder is one of the most promising candidate for the replacement of the traditional hard chrome plating and hard ceramics coating because of the environmental prob- lem of the very toxic Cr known as carcinogen by chrome plating and the brittleness of ceramics coatings. 80%WC-CoFe powder was coated by HVOF thermal spraying for the study of durability improvement of the high speed spindle such as air bearing spindle. The coating procedure was designed by the Taguchi program, includ- ing 4 parameters of hydrogen and oxygen flow rates, powder feed rate and spray distance. The surface proper- ties of the 80%WC-CoFe powder coating were investigated roughness, hardness and porosity. The optimal condition for thermal spray has been ensured by the relationship between the spary parameters and the hard- ness of the coatings. The optimal coating process obtained by Taguchi program is the process of oxygen flow rate 34 FRM, hydrogen flow rate 57 FRM, powder feed rate 35 g/min and spray distance 8 inch. The coating cross-sectional structure was observed scanning electron microscope before chemical etching. Estimation of coating porosity was performed using metallugical image analysis. The Friction and wear behaviors of HVOF WC-CoFe coating prepared by OCP are investigated by reciprocating sliding wear test at 25 C and 450 C. Fric- tion coefficients (FC) of coating decreases as sliding surface temperature increases from 25 C to 450 C. (Received October 31, 2011; Revised November 15, 2011; Accepted December 16, 2011)

Abstruct An influence of the addition of copper (0.5, 1.0 and 1.5 mass% Cu) on the microstructure andmechanical properties of high purity iron (99.998 mass%) was characterized. The microstructure and microhard-ness of high-purity iron based samples, which were rolled at room temperature and subsequently annealed,were investigated in this work. The microstructure of the samples has been observed by electron back scatter-ing diffraction (EBSD) and the mechanical properties have been studied by using micro-Vickers hardness test.The results of microstructural observation showed that deformation band was formed in high purity iron by roll-ing at room temperature, and it was recovered by annealing up to about 900 K. The microhardness resultsshowed that the softening of high-purity iron occurred by annealing up to about 900 K, while the hardness ofiron added with about 0.5-1.5 mass% copper was kept over 100 Hv and at the early time of annealing reached amaximum. The hardness of iron added with a small amount of copper may be attributed to precipitation harden-ing as well as solution hardening. The orientation of crystal in recrystallized grain was almost same as that ofdeformed grain. (Received November 21, 2011; Revised December 28, 2011; Accepted January 19, 2012)Key words: high purity iron, iron-copper alloy, recrystallization, EBSD, Vickers hardness, annealing, precipitation

In this paper, we report the synthesis of Zn 1− x Co x O (0.0 ⩽ x ⩽ 0.10) nanoparticles by an auto-combustion method using glycine as a fuel. The prepared nanoparticles were characterized by using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy and DC magnetization measurements. XRD results showed that Co doped ZnO have a single phase nature with wurtzite structure and Co 2+ ions were successfully incorporated into the lattice position of Zn 2+ ions in ZnO matrix. FTIR spectra demonstrated that the values of absorption bands were blue shifted with the increase of Co content. From the Raman spectra, all the peaks observed in undoped and Co-doped samples can be assigned to the Raman active modes of ZnO crystal. However, in case of Co doped ZnO sample, additional modes were observed that can be related to the substitution of Co into the Zn site. Magnetic studies showed that Co doped ZnO nanoparticles exhibit room temperature ferromagnetism.

The composites of 0.99La 0.7 (Ca x Sr 1− x ) 0.3 MnO 3 /0.01CuZnFe 4 O 4 (LCSMO/CZF) ( x = 0, 0.1, 0.2, 0.3, 0.5, 0.7 and 1) were fabricated by conventional solid state reaction method, and their electrical transport and magnetoresistance (MR) properties were investigated by physical property measurement system (PPMS). The result of X-ray diffraction (XRD) and scanning electronic microscopy (SEM) indicated that no new phase appeared in the composites except LCSMO and CZF phases. CZF is mainly distributed at the grain boundaries and surfaces of the matrix. The resistivity of all the composites was measured in the range 100–350 K at 0 T, 0.5 T and 1 T magnetic field. Room temperature MR peak appears for the composites x = 0.03. The observed variation of MR with varying Ca and Sr concentration has been qualitatively.

Epitaxial La 0.7 Ca 0.3 Mn 0.95 Co 0.05 O 3 (LCMCO) thin films were prepared on (1 0 0) LaAlO 3 single-crystal substrates by pulsed laser deposition (PLD). We have been studied using X-ray diffraction (XRD), electrical transport magneto-transport and dc magnetization. XRD pattern reflects that all films have c-axis epitaxial growth on LaAlO 3 substrates. The decrease in out-of-plane cell parameter specifies a progressive relaxation of in the plane compressive strain as the thickness film is increases. From the dc magnetization measurements, it is observed that ferromagnetic to paramagnetic transition temperature increases with increase in the film thickness. Magneto-resistance and temperature coefficient of resistance increases with thickness of film and have maximum value near its metal to insulator transition temperature.