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Funding Acknowledgements Type of funding sources: None. Background/Introduction Anticoagulant therapy has been important for stroke prevention in patients with atrial fibrillation (AF). However, it was not recommended due to its relatively higher risk of bleeding than its lower risk of stroke in patients with a CHA2DS2-VASc score of 0. Purpose This study aimed to evaluate the predictors of stroke in AF patients with very low risk of stroke. Methods Between 1990 and 2020, 542 patients with non-valvular AF (NVAF) with a CHA2DS2-VASc score of 0 followed up for at least 6 months were enrolled. Patients whose only risk factor was female were included as a CHA2DS2-VASc score of 0 in this study. The primary outcome was stroke or systemic embolism. Results The mean age at AF diagnosis was 49.9 years, and 398 (73.4%) were men. During the mean follow-up of 4.7 years, the primary outcome rate was 0.78%/year (stroke, 0.70%/year; systemic embolism, 0.08%/year), and major bleeding and all-cause death occurred in 0.31%/year and 1.02%/year, respectively. The proportions of age ≥50 years at diagnosis, left ventricular end-diastolic dimension (LVEDD) of ≥46 mm, and non-paroxysmal AF in patients with stroke or systemic embolism were significantly higher than in those without. Cox proportional hazard model, age of ≥50 years at diagnosis (hazard ratio [HR] 6.710, 95% confidence interval [CI] 1.811–24.860, P-value=0.004), LVEDD of ≥46 mm (HR 4.513, 95% CI 1.038–19.626, P-value=0.045), and non-paroxysmal AF (HR 5.575, 95% CI 1.621–19.175, P-value=0.006) were identified as independent predictors of stroke or systemic embolism. Patients with all three independent predictors had a higher risk of stroke or systemic embolism (4.21%/year), whereas those without did not have stroke or systemic embolism. Conclusion The annual stroke or systemic embolism rate in NVAF patients with CHA2DS2-VASc score of 0 was 0.78%/year. Age at AF diagnosis, LVEDD, and non-paroxysmal AF were independent predictors of stroke or systemic embolism in patients considered to be at very low risk of stroke.

The objective of this study was to examine the effects of glutamine on heat-shock protein beta 1 (HSPB1) expression in bovine embryonic fibroblast cells during myogenesis. First, to elucidate the role of glutamine on HSPB1 expression during myogenesis, we treated with glutamine in myogenic lineage determinant (MyoD) over-expressed bovine embryonic fibroblast cells (BEFS-MyoD cells). Second, knockdown of HSPB1 using small interference RNA was performed to evaluate whether muscle development by glutamine is dependent on HSPB1 in BEFS-MyoD cells. As a result, glutamine promoted the mRNA level of HSPB1, Myogenin, Desmin, and mTOR as well as myotube formation, and protein synthesis (p

The objective of the present study was to determine the effect of vitamin A restriction on serum metabolites and carcass performance in Korean native steers during a fattening period. In Study 1, 61 steers were divided into three groups and supplied diets with concentrate and roughage containing 890 IU/kg of provitamin A and then supplemented with either 8000 IU (control), 3000 IU (T1) or 0 IU (T2) of premix vitamin A per kilogram of dry matter. In Study 2, 19 steers were divided into two groups and provided with the same basic diets then supplemented with 8000 IU (control) or 0 IU (T) of premix vitamin A per kilogram of dry matter. In Study 1, we found that serum vitamin A concentrations were significantly (P < 0.05) lower in the T2 group, along with significant (P < 0.05) increases in blood urea nitrogen, albumin, creatinine and non-esterified fatty acid concentrations. In Study 2, the T group had a higher (P < 0.05) skeletal muscle mRNA expression levels of myogenic factor 6 and a trend for the greater yield grade (P=0.095). However, marbling scores in the study showed no significant. Therefore, vitamin A restriction with vitamin premix during the fattening period was associated with a trend for a higher yield grade, but marbling scores that were not significantly higher. Metabolic parameters in this stage could be used as indicators in future metabolic studies and as early health status markers in Korean native steers.

The power train of mixer gearbox for concrete mixer truck includes differential planetary gears to get large reduction ratio for operating mixer a drum and simple structure. The planetary gears are very important part of a mixer gearbox where strength problems namely gear bending stress, gear compressive stress and scoring failure are the main concern. In the present study, calculating specifications of the differential planetary gears and analyzing the gear bending and compressive stresses as well as scoring factor of the differential planetary gears gearbox for an optimal design of the mixer gearbox in respect to cost and reliability are investigated. The analyses of actual gear bending and compressive stresses of the differential planetary gears using Lewes & Hertz equation and verifications of the calculated specifications of the differential planetary gears evaluate the results with the data of allowable bending and compressive stress from the Stress-No. of cycles curves of gears. In addition, we also analyze actual gear scoring factor as well as evaluate the possibility of scoring failure of the differential planetary gear.

Human cathepsin K, a cysteine proteinase of the papain family, has been recognized as a potential drug target for the treatment of osteoporosis. The predominant expression of cathepsin K in osteoclasts has rendered the enzyme into a major target for the development of novel antiresorptive drugs. Now, we report the pharmacological properties of OST-4077 [furan-2-carboxylic acid (1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl}-cyclohexyl)-amide] as a novel selective cathepsin K inhibitor. Human and rat cathepsin K were inhibited in vitro by OST-4077 with the IC50 values of 11 and 427 nM, respectively. OST-4077 suppressed bone resorption induced by rabbit osteoclasts (IC50, 37 nM) but did not affect bone mineralization or cellular alkaline phosphatase activity in MC3T3-E1 cells. Parathyroid hormone-induced bone resorption was inhibited in a dose-dependent manner in thyroparathyroidectomized rats gavaged with a single dose of OST-4077 (ED50, 69 mg/kg). When given orally twice daily for 4 weeks to 3-month-old ovariectomized (OVX) rats, OST-4077 dose-dependently prevented bone loss, as monitored by bone densitometry, ash content, and urinary excretion of deoxypyridinoline. No change in serum osteocalcin in the OVX rats by OST-4077 suggested that bone formation might not be affected by the agent. In summary, OST-4077 selectively inhibited bone resorbing activities of osteoclasts and prevented bone loss induced by estrogen deficiency but did not affect bone formation. OST-4077, an orally active selective human cathepsin K inhibitor, may have the therapeutic potential for the treatment of diseases characterized by excessive bone loss including osteoporosis.

High density (In)GaAs/GaAs/AIGaAs nanowires (NWs) consisting of n-type core and p-type shell have been vertically grown on (111) GaAs substrate using metal organic chemical vapor deposition (MOCVD) and fabricated into solar cells. Au colloidal nanoparticles (NPs) are employed as a catalyst. High density nanowires were obtained by uniform distribution of Au NPs. Fe-SEM, TEM and HRTEM images show that the morphology of shell is sensitive to p-doping concentration. Increase in the density of p-doping precursor results in "kinking" of NPs and rough shell surface. The origin of kinking has been explained by the GaAs twin phases due to Zn segregation on the surface of shell. It has been observed that the morphology of NPs can be controlled through optimizing various source purge technique of DEZn and deposition temperature. Electrical properties of core-shell doped NWs are carried out using I-V characterization. The core-shell NWs show characteristics of p-n junction as revealed by I-V studies.

InSb nanostructures embedded in InAs and InAsSb matrices were grown on InAs (001) and GaAs (001) substrates by molecular beam epitaxy. The diameter and height of InSb quantum dots (QDs) on InAs with 2ML-InSb coverage grown by Stranski-Krastanov (S-K) are ~36.8 nm and ~3.1 nm, respectively. The density of QDs is ~2.5×1010 cm-2. The size distribution of InSb QDs on InAs with 2ML-InSb coverage grown by migration enhanced epitaxy (MEE) was larger than that of its S-K counterpart. Unique InSb quantum dashes (Q-dashes) on InAsSb elongated along two directions were found on an AlSb-buffered GaAs substrate. InSb Q-dashes grown by migration enhanced epitaxy (MEE) were ~159 nm in length, ~63 nm in width, and ~11 nm in height. A large reduction of volume of InSb structures between those in the matrix and those on the surface was found. Threading disl°Cations resulting from the Q-dash structures were also observed. This may be attributed to As-Sb exchange.

We have previously reported that the exposure of human HepG2 cells to hypoxic conditions results in the overexpression of human insulin-like growth factor II (IGF-II) mRNA whose size is 6.0 kb. This particular size of IGF-II mRNA is transcribed under the control of the IGF-II P3 promoter. In the present study, to delineate the molecular mechanism for the activation of the IGF-II gene, we examined the induction of P3 promoter activity in HepG2 cells by hypoxia in the transient expression system. In this system, hypoxia induced a linear increase within 24 h in the expression of luciferase that was driven by the IGF-II P3 promoter. To further delineate which factors mediate this response, the expression pattern of regulators of the P3 promoter, Egr-1, Sp1, and WT1, were analyzed by reverse transcription-PCR and Northern blot analysis. We found that hypoxia increased the expression of Egr-1 but not of Sp1. In contrast, the level of WT1, a repressor of IGF-II expression, was markedly decreased during hypoxia. The mRNA stability assay revealed that the induction of transcription is the mechanism of underlying Egr-1 mRNA elevation. We then investigated the effects of hypoxia on the DNA binding activity of Egr-1. Both electrophoretic mobility shift assay and supershift assay demonstrated that the DNA binding activity of the Egr-1 protein was increased by hypoxia. In addition, the level of Egr-1 protein was also increased under the hypoxia as determined by Western blot analysis. Cotransfection of HepG2 cells with an Egr-1 expression vector and an IGF-II P3 promoter-luciferase reporter plasmid showed that the transcription of IGF-II was activated by Egr-1 in a dose-dependent manner. Moreover, the elevation of IGF-II P3 promoter activity was induced synergistically by the cotreatment of hypoxia with Egr-1 overexpression. Deletion of sequences in the IGF-II P3 promoter containing Egr-1 binding sites did not respond to hypoxic stress. Taken together, these data strongly indicate that hypoxia-induced IGF-II expression in HepG2 cells is due to the enhanced activity of Egr-1 on the IGF-II P3 promoter and that the Egr-1 binding site in the IGF-II P3 promoter is essential for the transcriptional regulation of IGF-II under hypoxic conditions.

Insulin-like growth factor II (IGF-II) is highly expressed during hepatocarcinogenesis (P. Schirmacher et al., Cancer Res., 52: 2549-2556, 1992; B. C. Park et al., J. Hepatol., 22: 286-294, 1995). However, the mechanism of its enhanced expression is largely unknown. In this study, we show that IGF-II mRNA levels are increased within six h of exposing human hepatoma cell cultures to hypoxia, suggesting that hypoxia may be a strong stimulus for the induction of IGF-II expression in the process of hepatocarcinogenesis. This finding and the fact that hepatocellular carcinoma (HCC) is a typical hypervascular tumor (M. Mise et al., Hepatology, 23: 455-464, 1996) imply that IGF-II may play an important role in the development of neovascularization of HCC. Here we demonstrate that IGF-II substantially increases vascular endothelial growth factor (VEGF) mRNA and protein levels in a time-dependent manner in human hepatoma cells. The induction of VEGF by IGF-II was additively increased by hypoxia. Moreover, the direct angiogenic activity of IGF-II was observed in the quantitative chick chorioallantoic membrane assay (M. Nguyen et al., Microvasc. Res., 47: 31-40, 1994). These data suggest that IGF-II may be a hypoxia-inducible angiogenic factor in HCC.

The mean frequency aliasing problem originating from the pulse repetition frequency is one of major limitations in ultrasound pulsed Doppler systems. A conventional approach to resolving this problem is to track the mean frequencies close to and beyond the Nyquist frequency along the temporal axis. In this paper, a new concept of tracking the mean frequencies along the spatial axis is proposed for the same problem. The technique is fault tolerable and more suitable for multigate and 2-D Doppler systems than conventional methods. Simulation and experimental results show that the proposed system has improved performance compared with that of the conventional systems.