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This study aimed to identify the mediating effects of depression amid the influence of fear and social distancing arising from Coronavirus disease 2019 (COVID-19) in Korean women's suicidal ideation.A descriptive correlation study was conducted. Study participants, recruited by Hankook Research from March 2 to March 5, 2021, included 300 women aged 19 to 49 living in South Korea, and 100 people were randomly allocated and enlisted for each age group out of 700,000 Hankook Research Panels recruited in advance from 17 cities and provinces nationwide. Data were collected through a self-reported questionnaire and analyzed using Pearson's correlation coefficient and Hayes' Process Macro Model 4 with 95% bias-corrected bootstrap confidence interval via SPSS statistics 27.0.Suicidal ideation was significantly correlated with fear of COVID-19 (r = .16,It is necessary to develop and apply interventions to prevent depression and suicidal behaviors by continuously observing and reducing the negative psychological responses caused by COVID-19.

Not only is fabrication important for research in materials science, but also materials characterization and analysis. Special microscopes capable of ultra-high magnification are more essential for observing and analyzing nanoparticles than for macro-size particles. Recently, electron microscopy (EM) and scanning probe microscopy (SPM) are commonly used for observing and analyzing nanoparticles. In this chapter, the basic principles of various techniques in optical and electron microscopy are described and classified. In particular, techniques such as transmission electron microscopy (TEM) and scanning electron microscopy (SEM) are explained.

Atomic layer deposition (ALD) of SnO and SnO 2 thin films was successfully demonstrated over a wide temperature range of 70–300 °C using a divalent Sn-precursor, bis( N- ethoxy-2,2-dimethyl propanamido)tin (Sn(edpa) 2 ). The regulated growth of the SnO 2 and SnO films was realized by employing O 2 -plasma and H 2 O, respectively. Pure SnO 2 and SnO films were deposited with negligible C and N contents at all the growth temperatures, and the films exhibited polycrystalline and amorphous structures, respectively. The SnO 2 films presented a high transmittance of > 85% in the wavelength range of 400–700 nm and an indirect band gap of 3.6–4.0 eV; meanwhile, the SnO films exhibited a lower transmittance of > 60% and an indirect band gap of 2.9–3.0 eV. The SnO 2 films exhibited n-type semiconducting characteristics with carrier concentrations of 8.5 × 10 16 –1.2 × 10 20 cm −3 and Hall mobilities of 2–26 cm 2 /V s. By employing an alternate ALD growth of SnO and SnO 2 films, SnO 2 /SnO multilayer structures were successfully fabricated at 120 °C. The in-situ quadrupole mass spectrometry analysis performed during ALD revealed that the oxidation of chemisorbed Sn-precursor occurs dominantly during the Sn(edpa) 2 /O 2 -plasma ALD process, resulting in the production of combustion by-products, whereas the Sn(edpa) 2 /H 2 O ALD process was governed by a ligand exchange reaction with the maintenance of the original oxidation state of Sn 2+ .

Background Surgery is the most important treatment modality for papillary thyroid cancer (PTC). However, the relationship between surgeon volume and long-term oncological outcomes has not been explored. Methods Patients diagnosed with N1b PTC after initial thyroid surgery between 1 July 1994 and 31 December 2011 were eligible for inclusion in the study. Surgeons were categorized into high (at least 100 operations per year) and low (fewer than 100 operations per year) volume groups. Kaplan–Meier survival analysis according to surgeon volume was performed, and Cox proportional hazard modelling was used to estimate hazard ratios (HRs) with 95 per cent confidence intervals according to patient, tumour and surgeon factors. Results A total of 1103 patients with a median follow-up of 81 (i.q.r. 62–108) months were included in the study. During follow-up, 200 patients (18·1 per cent) developed structural recurrence. A high surgeon volume was associated with low structural recurrence (P = 0·006). After adjustment for age, sex and conventional risk factors for recurrence (histology, tumour size, gross extrathyroidal extension, margin status, more than 5 positive lymph nodes, radioactive iodine therapy), the adjusted HR for structural recurrence for low-volume surgeons was 1·46 (95 per cent c.i. 1·08 to 1·96), compared with high-volume surgeons. Distant metastasis (P = 0·242) and disease-specific mortality (P = 0·288) were not affected by surgeon volume. Conclusion Surgeon volume is associated with structural recurrence, but not distant metastasis or cancer-specific death in patients with N1b PTC. Surgeon volume is important in initial surgery for advanced PTC with extensive nodal metastasis in order to ensure curative outcome and reduce treatment-related morbidity.

Aluminum oxide (AlO x ) thin films were synthesized by mist-chemical vapor deposition (mist-CVD) using aluminum acetylacetonate (Al(acac) 3 ) dissolved in an aqueous solvent mixture of acetone and water. Nitrogen gas was used to purge the precursor solution and growth rates between 7.5–13.3 nm/min were achieved at substrate temperatures of 250–350 °C. The AlO x layers deposited at temperatures below 350 °C exhibit 3–5 at% residual carbon levels, however those grown at 350 °C exhibit only 1–2 at% carbon impurity. Reasonable dielectric properties were obtained in the latter, with a dielectric constant (κ) of ~ 7.0, breakdown field of ~ 9 MV/cm and relatively low leakage current density of ~ 8.3×10 −10 A/cm 2 .

In 2 O 3 thin films were grown from a newly developed, liquid, homoleptic, In-based complex, tris(1-dimethylamino-2-methyl-2-propoxy)indium [In(dmamp) 3 ], and O 3 by atomic layer deposition (ALD) at growth temperatures of 150–200 °C. In(dmamp) 3 exhibited single-step evaporation with negligible residue and excellent thermal stability between 30 and 250 °C. The self-limiting surface reaction of In 2 O 3 during ALD was demonstrated by varying the In(dmamp) 3 and O 3 pulse lengths, with a growth rate of 0.027 nm/cycle achieved at 200 °C. The In 2 O 3 films grown at temperatures over 175 °C exhibited negligible concentrations of impurities, whereas that grown below 175 °C had concentrations of residual C of 6–8 at.%. Glancing angle X-ray diffraction revealed that the In 2 O 3 films were polycrystalline in nature when the deposition temperature was greater than 200 °C. The In 2 O 3 films grown at 150–200 °C exhibited carrier concentrations of 1.5 × 10 18 –6.6 × 10 19 cm −3 , resistivities of 15.1–2 × 10 −3 Ω cm, and Hall mobilities of 0.8–42 cm 2 /(V s).

Low-temperature growth of In2O3 films was demonstrated at 70–250 °C by plasma-enhanced atomic layer deposition (PEALD) using a newly synthesized liquid indium precursor, dimethyl(N-ethoxy-2,2-dimethylcarboxylicpropanamide)indium (Me2In(EDPA)), and O2 plasma for application to high-mobility thin film transistors. Self-limiting In2O3 PEALD growth was observed with a saturated growth rate of approximately 0.053 nm/cycle in an ALD temperature window of 90–180 °C. As-deposited In2O3 films showed negligible residual impurity, film densities as high as 6.64–7.16 g/cm3, smooth surface morphology with a root-mean-square (RMS) roughness of approximately 0.2 nm, and semiconducting level carrier concentrations of 1017–1018 cm–3. Ultrathin In2O3 channel-based thin film transistors (TFTs) were fabricated in a coplanar bottom gate structure, and their electrical performances were evaluated. Because of the excellent quality of In2O3 films, superior electronic switching performances were achieved with high field effect mo...

A new bis((2-(dimethylamino)ethyl)(methyl)amido)methyl(tert-butylimido)tantalum complex was synthesized for plasma-enhanced atomic layer deposition (PEALD) of tantalum nitride (TaN) film. Using the synthesized Ta compound, PEALD of TaN was conducted at growth temperatures of 150–250 °C in combination with NH 3 plasma. The TaN PEALD showed a saturated growth rate of 0.062 nm/cycle and a high film density of 9.1–10.3 g/cm 3 at 200–250 °C. Auger depth profiling revealed that the deposited TaN film contained low carbon and oxygen impurity levels of approximately 3–4%. N-rich amorphous TaN films were grown at all growth temperatures and showed highly resistive characteristic. The Cu barrier performance of the TaN film was evaluated by annealing of Cu/TaN (0–6 nm)/Si stacks at 400–800 °C, and excellent Cu diffusion barrier properties were observed even with ultrathin 2 nm-thick TaN film.

Background In the eighth edition of the AJCC staging system for differentiated thyroid carcinoma (DTC), minimal extrathyroidal extension (ETE) is no longer a determinant of T3 category. Instead, gross ETE invading only strap muscles has been designated as a new T3b category. The long-term prognosis of patients with DTC and gross ETE invading only strap muscles was investigated. Methods This was a retrospective analysis of patients who underwent thyroidectomy between 1996 and 2005. Differences in cancer-specific and recurrence-free survival according to extent of ETE were assessed. Results A total of 3174 patients with DTC were included. No significant differences were observed in 10-year cancer-specific survival among patients with no ETE (98·6 per cent), microscopic ETE (98·3 per cent) and gross ETE invading only strap muscles (98·9 per cent) (P = 0·375). The 10-year recurrence-free survival rate for patients with gross ETE invading only strap muscles (89·2 per cent) was shorter than that for patients with no ETE (93·7 per cent; P = 0·016), but similar to that of patients with microscopic ETE (90·3 per cent). In univariable analysis, patients with gross ETE invading only strap muscles had a significantly higher risk of recurrence than those with no ETE (hazard ratio (HR) 1·67, 95 per cent c.i. 1·10 to 2·55; P = 0·017). In multivariable analysis, gross ETE invading only strap muscles was not an independent predictor of recurrence (HR 1·09, 0·71 to 1·69; P = 0·685). Conclusion Although gross ETE invading only strap muscles may provide prognostic information about long-term recurrence, it does not affect mortality. The actual impact of gross ETE invading only strap muscles will be important in revising the staging system in the future.

The emergence and spread of antibiotic-resistant Aeromonas spp. is a serious public and animal health concern. Wild animals serve as reservoirs, vectors, and sentinels of these bacteria and can facilitate their transmission to humans and livestock. The nutria (Myocastor coypus), a semi-aquatic rodent, currently is globally considered an invasive alien species that has harmful impacts on natural ecosystems and carries various zoonotic aquatic pathogens. This study aimed to determine the prevalence of antibiotic-resistant zoonotic Aeromonas spp. in wild invasive nutrias captured in Korea during governmental eradication program. Three potential zoonotic Aeromonas spp. (A. hydrophila, A. caviae, and A. dhakensis) were identified among isolates from nutria. Some strains showed unexpected resistance to fluoroquinolones, third-generation cephalosporins, and carbapenems. In carbapenem-resistant isolates, the cphA gene, which is related to intrinsic resistance of Aeromonas to carbapenems, was identified, and phylogenetic analysis based on this gene revealed the presence of two major groups represented by A. hydrophila (including A. dhakensis) and other Aeromonas spp. These results indicate that wild nutrias in Korea are a potential reservoir of zoonotic and antibiotic-resistant Aeromonas spp. that can cause infection and treatment failure in humans. Thus, measures to prevent contact of wild nutrias with livestock and humans are needed.

Background To determine the frequency and predictive impact of ROS1 rearrangements on treatment outcomes in never-smoking patients with lung adenocarcinoma. Patients and methods We concurrently analyzed ROS1 and ALK rearrangements and mutations in the epidermal growth factor receptor (EGFR), and KRAS in 208 never smokers with lung adenocarcinoma. ROS1 and ALK rearrangements were identified by fluorescent in situ hybridization. Results Of 208 tumors screened, 7 (3.4%) were ROS1 rearranged, and 15 (7.2%) were ALK-rearranged. CD74-ROS1 fusions were identified in two patients using reverse transcriptase–polymerase chain reaction. The frequency of ROS1 rearrangement was 5.7% (6 of 105) among EGFR/KRAS/ALK-negative patients. Patients with ROS1 rearrangement had a higher objective response rate (ORR; 60.0% versus 8.5%; P = 0.01) and a longer median progression-free survival (PFS; not reached versus 3.3 months; P = 0.008) to pemetrexed than those without ROS1/ALK rearrangement. The PFS to EGFR-tyrosine kinase inhibitors in patients harboring ROS1 rearrangement was shorter than those without ROS1/ALK rearrangement (2.5 versus 7.8 months; P = 0.01). Conclusions The frequency of ROS1 rearrangements in clinically selected patients is higher than that reported for unselected patients, suggesting that ROS1 rearrangement is a druggable target in East-Asian never smokers with lung adenocarcinoma. Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1 rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.

This study examined the hepatoprotective effect of the HV-P411 complex, an herbal extract mixture from the seeds of Vitis vinifera, Schisandra chinensis and Taraxacum officinale, against D-galactosamine (D-GalN)-induced hepatitis. Hepatotoxicity was induced by D-GalN (700 mg/kg, i.p.), and the HV-P411 complex was administered orally 48, 24, and 2 h before and 6 h after D-GalN injection. Increases in serum aminotransferase activity and lipid peroxidation and a decrease in hepatic glutathione content were attenuated by the HV-P411 complex 24 h after D-GalN treatment. The HV-P411 complex attenuated the increases in serum tumor necrosis factor-α, interleukin (IL)-6 level and cyclooxygenase-2 protein production and their mRNA expressions, while increases in serum IL-10 level and heme oxygenase-1 protein production and their mRNA expressions were augmented by the HV-P411 complex. The increased translocation of nuclear factor-κB and c-Jun phosphorylation were attenuated by treatment with the HV-P411 complex. Our results suggest that the HV-P411 complex prevents D-GalN-induced hepatotoxicity via antioxidative and anti-inflammatory activities.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine that stimulates the differentiation and function of hematopoietic cells. GM-CSF has been implicated in nervous system function. The goal of the present study was to understand the effects of hypoxia-induced GM-CSF on neural stem cells (NSCs) in a model of spinal cord injury (SCI). GM-CSF-overexpressing NSCs were engineered utilizing a hypoxia-inducible gene expression plasmid, including an Epo enhancer ahead of an SV promoter (EpoSV-GM-CSF). Cells were then subjected to hypoxia (pO(2), 1%) or a hypoxia-mimicking reagent (CoCl(2)) in vitro. The progression of time of GM-CSF expression was tracked in EpoSV-GM-CSF-transfected NSCs. Overexpression of GM-CSF in undifferentiated and differentiated NSCs created resistance to H(2)O(2)-induced apoptosis in hypoxia. NSCs transfected with EpoSV-GM-CSF or SV-GM-CSF were transplanted into rats after SCI to assess the effect of GM-CSF on NSC survival and restoration of function. Moreover, a significantly higher amount of surviving NSCs and neuronal differentiation was observed in the EpoSV-GM-CSF-treated group. Significant improvement in locomotor function was also found in this group. Thus, GM-CSF overexpression by the Epo enhancer in hypoxia was beneficial to transplanted NSC survival and to behavioral improvement, pointing toward a possible role for GM-CSF in the treatment of SCI.

This study investigated the effect of human placenta extract (HPE) on cartilage degradation in vitro MG-63 cells, articular cartilage explants, and in vivo monoiodoacetate (MIA)-induced osteoarthritis (OA). Matrix metalloproteinase (MMP)-2 activity was measured in HPE-treated osteoblastic MG-63 cells. Articular cartilage explants in rabbit were cultured, and the degree of proteoglycan (PG) degradation was assessed by measuring the amount of glycosaminoglycan (GAG) released into the culture medium. Experimental osteoarthritis was induced by intra-articular injection of 3 mg MIA in rats. Beginning 14 d post-MIA injection, HPE was administered intra-articularly once a day for 14 d. The knee joints were assessed by roentgenography, histology, and gelatinase activity. HPE inhibited PG degradation in articular cartilage explants. HPE significantly reduced deformity of knee joints and suppressed the histological change in MIA-induced OA. HPE inhibited MMP-2 activity in MG-63 cells. MMP-2 and -9 activities were also reduced in the cartilages of HPE-treated knee joints. Our results indicate that HPE has therapeutic effects on OA by protecting cartilage.

Forsythiae Fructus is known to have diuretic, anti-bacterial, and anti-inflammatory activities. This study examined the hepatoprotective effects of pinoresinol, a lignan isolated from Forsythiae Fructus, against carbon tetrachloride (CCl4 )–induced liver injury. Mice were treated intraperitoneally with vehicle or pinoresinol (25, 50, 100, and 200 mg/kg) 30 min before and 2 h after CCl4 (20μl/kg) injection. In the vehicle-treated CCl4 group, serum aminotransferase activities were significantly increased 24 h after CCl4 injection, and these increases were attenuated by pinoresinol at all doses. Hepatic glutathione contents were significantly decreased and lipid peroxidation was increased after CCl4 treatment. These changes were attenuated by 50 and 100 mg/kg of pinoresinol. The levels of protein and mRNA expression of inflammatory mediators, including tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2, were significantly increased after CCl4 injection; and these increases were attenuated by pinoresinol. Nuclear translocation of nuclear factor-κB (NF-κB) and phosphorylation of c-Jun, one of the components of activating protein 1 (AP-1), were inhibited by pinoresinol. Our results suggest that pinoresinol ameliorates CCl4-induced acute liver injury, and this protection is likely due to antioxidative activity and down-regulation of inflammatory mediators through inhibition of NF-κB and AP-1. Keywords:: carbon tetrachloride, hepatoprotective activity, inflammation, oxidative stress, pinoresinol

The immunomodulatory effects of Korean mistletoe lectin (KML), one of the major active components in Viscum album L. var. coloratum, were investigated in vitro in immune cell proliferation and natural killer (NK) cell- and macrophage-mediated cytotoxicity, and in vivo in the forced swim test and cold stress. In mitogen-induced lymphocyte proliferation of murine splenocytes, concanavalin A and lipopolysaccharide significantly increased the proliferation of T cell and B cell lymphocytes, respectively. KML exposure increased lymphocyte proliferation in response to mitogen. KML also increased the splenic NK cell and macrophage activities in vitro. Exposure to KML increased production of cytokines such as interleukin-1 and interleukin-6 by macrophages. Two-week treatment with KML (30, 100, 300 and 600 microg/kg) increased the recruitment of lymphocytes, monocytes and macrophages. In the forced swim test, the immobility time was significantly attenuated by treatment with KML (300 and 600 microg/kg). In a cold stress experiment, spleen and thymus weight increased in KML-treated mice, while the weight of adrenal gland was lower than that in vehicle-treated mice. The levels of serum aminotransferases, lactate dehydrogenase and alkaline phosphatase were decreased by KML treatment. KML treatment also induced increases in the percentages of CD4(+) and CD8(+) cells in thymus. Our results suggest that KML enhances the immune system through modulation of lymphocytes, NK cells, and macrophages.

The pressing challenge for contemporary gene therapy is to deliver enough therapeutic genes to enough cancer cells in vivo. With the aim of improving viral distribution and tumor penetration, we explored the use of decorin to enhance viral spreading and tumor tissue penetration. We generated decorin-expressing replication-incompetent (dl-LacZ-DCNG, dl-LacZ-DCNQ and dl-LacZ-DCNK) and replication-competent (Ad-DeltaE1B-DCNG, Ad-DeltaE1B-DCNQ and Ad-DeltaE1B-DCNK) adenoviruses (Ads). Point mutants of decorin gene (DCNG), DCNK and DCNQ, have a negative and moderate binding affinity to type-I collagen fibril, respectively. In both tumor spheroids and established solid tumors in vivo, tissue penetration potency of dl-LacZ-DCNG was greatly enhanced than those of dl-LacZ, dl-LacZ-DCNQ and dl-LacZ-DCNK, and this enhanced tissue penetration effect derived from decorin-expressing Ad was dependent on the binding affinity of decorin to collagen fibril. Expression of DCNG enhanced viral spread of replicating Ad, leading to improved tumor reduction and survival benefit. Moreover, the tumoricidal effects of Ad-DeltaE1B-DCNQ and Ad-DeltaE1B-DCNK were lessened, as the binding affinity to collagen was decreased, showing that the increased cancer cell cytotoxicity was driven by the action of decorin on extracellular matrix (ECM). Furthermore, Ad-DeltaE1B-DCNG substantially decreased ECM components within the tumor tissue. Finally, intratumoral injection of Ad-DeltaE1B-DCNG in primary tumor site greatly reduced the formation of B16BL6 melanoma cell pulmonary metastases in mice. Taken together, these data show the utility of decorin as a dispersion agent and highlight its utility and potential in improving the efficacy of replicating Ad-mediated cancer gene therapy.

RNA interference, due to its target specificity, may be highly effective as a novel therapeutic modality, but direct delivery of synthetic small interfering RNA still remains a major obstacle for this approach. To induce long-term expression and specific gene silencing, novel delivery vector system is also required. In this study, we have generated an efficient oncolytic adenovirus (Ad)-based short hairpin (shRNA) expression system (Ad-DeltaB7-U6shIL8) against IL-8, a potent proangiogenic factor. To demonstrate IL-8-specificity of this newly engineered Ad-based shRNA, we also manufactured replication-incompetent Ads (Ad-DeltaE1-CMVshIL8 and Ad-DeltaE1-U6shIL8) under the control of the cytomegalovirus (CMV) and U6 promoters, respectively. Ad-DeltaE1-U6shIL8 was highly effective in reducing IL-8 expression, and was much more effective in driving IL-8-specific shRNA than the CMV promoter-driven vector. The reduced IL-8 expression then translated into decreased angiogenesis in vitro as measured by migration, tube formation and rat aortic ring sprouting assays. In addition to its effect on endothelial cells, Ad-DeltaE1-U6shIL8 also effectively suppressed the migration and invasion of cancer cells. In vivo, intratumoral injection of Ad-DeltaB7-U6shIL8 significantly inhibited the growth of Hep3B and A549 human tumor xenografts. Histopathological analysis of Ad-DeltaB7-U6shIL8-treated tumors revealed an increase in apoptotic cells and a reduction in vessel density. Finally, Ad-DeltaB7-U6shIL8 was also shown to inhibit the growth of disseminated MDA-MB-231 breast cancer metastases. Taken together, these findings demonstrate the utility and antitumor effectiveness of oncolytic Ad expressing shRNA against IL-8.

Inflammasome activation by danger signals in ischemia/reperfusion (I/R) injury is responsible for the sterile inflammatory response. Signals triggering formation and activation of the inflammasome involve the generation of oxidative stress. The aim of this study was to examine the molecular mechanisms of inflammasome activation and the involvement of reactive oxygen species in hepatic I/R. I/R induced the formation of nucleotide-binding domain leucine-rich repeat containing family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes and the subsequent serum release of interleukin 1β. Pannexin-1 inhibitor and anti-cathepsin B antibody attenuated I/R-induced inflammasome activation and hepatic injury. The expression of the thioredoxin-interacting protein gene and the interaction between NLRP3 and the thioredoxin-interacting protein increased after I/R. Treatment with the antioxidant N-acetylcysteine significantly attenuated protein conversion of interleukin 1β after hepatic I/R. Moreover, pannexin-1 protein expression and cathepsin B release were strongly attenuated by N-acetylcysteine. The depletion of Kupffer cells with gadolinium chloride markedly decreased NLRP3 and AIM2 inflammasome expression and activation of their signaling pathways, and also reduced the level of caspase-1 protein in F4/80-positive cells. Our findings suggest that reactive-oxygen-species-mediated activation of NLRP3 and AIM2 inflammasomes leads to I/R-induced inflammatory responses in which Kupffer cells play a crucial role.

Geniposide is an active product extracted from the gardenia fruit, and is one of the most widely used herbal preparations for liver disorders. This study examined the cytoprotective properties of geniposide and its metabolite, genipin, against hepatic ischemia/reperfusion (I/R) injury. C57BL/6 mice were subjected to 60 min of ischemia followed by 6 h of reperfusion. Geniposide (100 mg/kg) and genipin (50 mg/kg) were administered orally 30 min before ischemia. In the I/R mice, the levels of serum alanine aminotransferase and hepatic lipid peroxidation were elevated, whereas hepatic glutathione/glutathione disulfide ratio was decreased. These changes were attenuated by geniposide and genipin administration. On the other hand, increased hepatic heme oxygenase-1 protein expression was potentiated by geniposide and genipin administration. The increased levels of tBid, cytochrome c protein expression and caspase-3 activity were attenuated by geniposide and genipin. Increased apoptotic cells in the I/R mice were also significantly reduced by geniposide and genipin treatment. Our results suggest that geniposide and genipin offer significant hepatoprotection against I/R injury by reducing oxidative stress and apoptosis.

9055Background: T790M mediates acquired resistance to 1st/2nd generation EGFR-TKIs. BI 1482694 is a 3rd generation TKI active against mutant EGFR, including T790M. This Phase I/II trial is evaluati...

Spin cleaning tools have advantages in cross contamination compared to bath cleaning tools. Although spin speed is one of key parameters to increase the cleaning efficiency of the spin cleaning tools, its optimization has been limited due to the generation of ESD (Electrostatic discharge) damage to optical masks. EUV masks, however, consist of more "stable" materials in terms of ESD damage so that it is allowed to increase spin speed to improve cleaning performance for EUV mask. In this paper, we showed particle removal efficiencies dependent on mask spin speed for megasonic, nano-binary, or the combination module of those two cleaning mechanisms. We also demonstrated that different characteristics of particle removal efficiency as a function of spin speed for megasonic and nano-binary cleanings can be predicted from simulation of particle trajectory in liquid medium and liquid hitting rates on mask spinning at various spin speeds. This work clearly signifies that it is possible to improve cleaning performance through optimization of known parameters.

Ferulic acid (FA), a phenolic compound found in various medicinal plants, has hepatoprotective effects against oxidative stress and inflammation. Here, we investigated the protective effects and the specific mechanisms of FA against hepatocyte apoptosis caused by ischemia/reperfusion (I/R). Mice were treated intraperitoneally with vehicle or FA 30 min prior to 60 min of ischemia. After 5h of reperfusion, serum aminotransferase activities and hepatic lipid peroxidation were elevated and hepatic glutathione content was depleted. These alterations were attenuated by FA. I/R increased caspase-3 activity and release of cytochrome c, and these were suppressed by FA. FA also attenuated the increases in the serum tumor necrosis factor (TNF)-α levels and TNF receptor type 1-associated DEATH domain protein and TNF receptor-associated factor 2 protein expressions. The cytosolic levels of Bcl-2-associated X protein (Bax), truncated BH3 interacting domain death agonist (tBid), and Bcl-2-like protein 11 were upregulated after reperfusion. The increases in Bax and tBid protein expression were attenuated by FA. Moreover, I/R induced c-Jun N-terminal kinase 1 (JNK1) and JNK2 phosphorylation, and FA attenuated the JNK activation. FA protects against I/R-induced hepatocyte apoptosis by attenuating oxidative stress and JNK activation.

This study evaluated the potential beneficial effect of Moutan Cortex Radicis (MCR) in a murine model of carbon tetrachloride (CCl(4))-, D-galactosamine (GalN)- and α-naphthylisothiocyanate (ANIT)-induced liver injury. Acute hepatotoxicity was induced by intraperitoneal injection of CCl(4) (10 µL/kg), GalN (700 mg/kg), and ANIT (40 mg/kg). Animals received MCR (30, 100, and 300 mg/kg ) orally at 48, 24, and 2 h before and 6 h after administration of CCl(4), GalN, and ANIT. Serum activities of aminotransferase were significantly higher at 24 h after CCl(4) or GalN treatment. These changes were attenuated by MCR. Histopathological analysis revealed multiple and extensive areas of portal inflammation, hepatocellular necrosis, and an increase in inflammatory cell infiltration. These changes were inhibited by MCR. Serum total bilirubin concentration increased and bile flow decreased significantly 48 h after ANIT treatment, which was attenuated by MCR. Our results suggest that MCR has a protective effect on acute liver injury.

This study evaluated the influence of tobacco Possession-Use-Purchase (PUP) law enforcement and illicit drug use and offers. Twenty-four towns were randomly assigned into two conditions. Both conditions focused on reducing minors’ access to commercial sources of tobacco. The communities assigned to the experimental condition also increased their PUP law enforcement, whereas among communities in the control condition, PUP law enforcement remained at low levels. A Hierarchical Linear Modeling analytical approach was selected due to the multilevel data and nested design. The likelihood of a child currently using drugs, ever having used drugs, or illicit drug offers was lower in the experimental versus control conditions. These outcomes suggest that police efforts to reduce specific substance use behaviors (i.e., underage tobacco use) may have a positive spillover effect and help reduce teen drug use and illicit drug offers.

Homeodomain only protein X (HOPX), an unusual homeodomain protein, was originally identified as a key regulator of cardiac development. We first demonstrated that the expression of HOPX was dependent on the differentiation of human keratinocytes and has an effect on the expression of differentiation markers. HOPX was suppressed in proliferating human keratinocytes and was gradually induced by calcium-triggered differentiation of human keratinocytes. In the epidermis, HOPX is highly expressed in the terminally differentiated suprabasal layers. Among the transcript variants of HOPX, the variant 3 driven by promoter A was the main transcript and it was regulated by cell differentiation in human keratinocytes. The expression of HOPX was induced through the phorbol-12-myristate-13-acetate (PMA)-dependent protein kinase C (PKC) signaling pathway, and not by the demethylating agent, 5-aza-dC (5-aza-2'-deoxycitidine) suggesting the suppression of HOPX is not associated with DNA methylation in human keratinocytes. The RNA interference (RNAi) silencing experiment showed that the knockdown of HOPX expression resulted in the increase of such differentiation markers as involucrin and loricrin. Exogenous expression of HOPX down-regulated the expression of differentiation marker genes in immortalized human keratinocytes (HaCaT). Collectively, HOPX is modulated by cell differentiation in human keratinocytes and this might contribute to homeostasis of keratinocytes by controlling differentiation-dependent genes.

8084 Background: HM61713 is an orally available EGFR mutation-specific inhibitor with sparing EGFR WT tumors that previously showed promising efficacy in T790M positive tumors at the dose of 300 mg...

Using the pretransplant bone mineral density (BMD) data records of renal recipients, we retrospectively examined risk factors affecting posttransplant changes in BMD and the effect of antiosteoporosis management. For 294 kidney transplant recipients from January 1996 to September 2003, BMD values were expressed as spine and femur T-scores. Gender, age, pretransplant diabetes, blood type compatibility, mode and duration of dialysis, and previous transplantation were considered to be variables affecting BMD changes. T-test or ANOVA was used to compare risk factors. At the time of transplantation, mean spine T-scores were significantly lower among the retransplant group. Mean femur T-scores were significantly lower among the retransplant group, older patients (older than 45 years), and female recipients. Prolonged hemodialysis (>12 months) and retransplant were risk factors for BMD loss during the first year posttransplant. Early application of antiosteoporosis management was effective to ameliorate posttransplant BMD loss. However, antiosteoporosis management after 1 year posttransplant was relatively ineffective. Pretransplant evaluation of BMD and the possibility of significant BMD loss during the first posttransplant year should not be overlooked. Prophylaxis against bone loss and treatment should be started as soon as possible after transplantation for recipients with either normal or abnormal pretransplant BMD.

Oncolytic adenoviral vectors are currently being developed as biologic anticancer agents. Coupling the lytic function of an oncolytic adenovirus (Ad) with its ability as a transgene delivery system represents a powerful extension of this methodology. A clear advantage is the amplification of a therapeutic gene, as replicating vectors would be able to infect and deliver the gene of interest to neighboring cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of the most potent stimulators of a specific and long-lasting antitumor immunity and its important role in the maturation of antigen-presenting cells to induce T-cell activation has been well documented. Similarly, the B7 family has also been shown to play an integral role in mediating an antitumor response. Most tumor cells, however, lack the expression of these costimulatory molecules on their surface, thus escaping immune system recognition. To increase the antitumor effect of an oncolytic Ad, we have generated an E1B 55 kDa-deleted oncolytic adenoviral vector, YKL-GB, that expresses both GM-CSF and B7-1. The therapeutic efficacy of YKL-GB Ad was evaluated in immunocompetent mice bearing murine melanoma B16-F10 tumors. Significant inhibition of tumor growth was seen in mice treated with YKL-GB compared to those treated with the analogous vector, YKL-1. Moreover, YKL-GB oncolytic Ad demonstrated enhanced antitumor activity and higher incidences of tumor regression compared to a replication-incompetent Ad, dl-GB, which coexpresses GM-CSF and B7-1. Localized GM-CSF and B7-1 gene transfer also conferred long-lasting immunity against a tumor re-challenge. To establish that the observed antitumor effect is associated with the generation of a tumor-specific immune response, we carried out interferon-gamma enzyme-linked immune spot assay. We observed that YKL-GB induced significantly higher immune cell activation than YKL-1. Furthermore, immunohistochemical studies demonstrated robust dendritic cells and CD4(+)/CD8(+) T-cell infiltration in these mice compared to the YKL-1-treated groups. In agreement with these results, splenocytes from tumor-bearing mice treated with YKL-GB expressed high levels of the costimulatory and activation molecules. These findings demonstrate the effectiveness of enhancing the immune response against tumors with an oncolytic Ad expressing both GM-CSF and B7-1 and provide a potential therapeutic strategy for the management of neoplasia.

8011 Background: HM61713 is a novel, oral, selective inhibitor for EGFR mutations including both activating mutations and T790M, but not EGFR wild-type. This phase 1 trial was conducted to evaluate...

It has been challenging to find suitable chemistries for cleaning of EUV mask consisting of various materials including multilayer (multiple stacking layer of silicon/ molybdenum), absorber, and capping layers. Recent investigation reveals that tantalum-based absorber layer has limited resistance against SPM chemicals while ruthenium-based capping layer is still robust. Active oxygen or hydroxyl radical cleaning which is more effective than SPM in removal of organic contaminant including carbon contamination on EUV mask surface turns out to cause serious damages on ruthenium capping layer. It is hypothesized that diffusion of oxygen radicals into capping layer oxidizes metallic ruthenium into more unstable ruthenium oxide compounds and the oxidized compounds are further damaged by following alkali cleaning combined with physical forces. Such diffusion of oxygen through ruthenium might oxidize layers beneath it to weaken the adhesion between ruthenium and beneath layers, which can further accelerate damage propagation on ruthenium capping. In this work, we try to understand root-causes of ruthenium damage by using of qualitative analysis of TOF-SIMS, TEM, EDX, and XPS. Based on the analysis, we propose innovative and powerful technologies of ruthenium passivation to mitigate diffusion of oxygen radicals into ruthenium layer, thereby reducing oxidation and damage of ruthenium capping layer. Fig.1 Scanning electron microscope image of ruthenium layer damaged by cleaning of active ozone or hydroxyl radicals.