Mel-18 has been implicated in several processes in tumor progression, in which the Akt pathway is involved as an important key molecular event. However, the function of Mel-18 in human cancers has not been fully established yet. Here, we examined the effect of Mel-18 on tumor angiogenesis in human breast cancer, and found that Mel-18 was a novel regulator of HIF-1a. Mel-18 negatively regulated the HIF-1a expression and its target gene VEGF transcription during both normoxia and hypoxia. We demonstrated that Mel-18 regulated the HIF-1a expression and activity via the PI3K/Akt pathway. Loss of Mel-18 downregulated Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression, consequently activating the PI3K/Akt/MDM2 pathway, and leading to an increase of HIF-1a protein level. Mel-18 modulated the HIF-1a transcriptional activity via regulating the cytoplasmic retention of FOXO3a, a downstream effector of Akt, and recruitment of HIF-1a/CBP complex to the VEGF promoter. Furthermore, our data shows that Mel-18 blocked tumor angiogenesis both in vitro and in vivo. Mel-18 overexpression inhibited in vitro tube formation in human umbilical endothelial cells (HUVECs). Xenografts in NOD/SCID mice derived from stably Mel-18 knocked down MCF7 human breast cancer cells showed increased tumor volume, microvessel density, and phospho-Akt and HIF-1a expression levels. In conclusion, our findings provide that Mel-18 is a novel regulator of tumor angiogenesis through regulating HIF-1a and its target VEGF expressions mediated by the PTEN/PI3K/Akt pathway, suggesting a new tumor-suppressive role of Mel-18 in human breast cancer.

A monolayer of 20 nm sized Fe3C nanoparticles encapsulated by graphite was fabricated by heat treating a polyimide/Fe/polyimide thin-film stack. Transmission electron microscopy and Raman spectroscopy confirmed the graphitization of the polyimide film in the vicinity of the Fe3C particles when annealed above 600 °C. Carbon-encapsulated Fe3C nanoparticles with a narrow size distribution were produced by introducing two-step annealing to initially produce a monolayer of γ-Fe2O3 particles which was converted into carbon-encapsulated Fe3C nanoparticles during the second annealing stage. The thus-produced nanoparticles exhibited a saturation magnetization of 55.4 emu g−1 and coercivity of 360 Oe at room temperature.

In proton therapy, it is important to very accurately determine the range of the proton beam. Recently it was found that this range can be determined from the distribution of the prompt gammas generated along the beam's passage. The Compton imaging technique can be considered to be a promising candidate for accurate determination of prompt gamma distributions, in that it produces a better image for higher-energy gammas when compared with conventional mechanicalcollimation-type imagers. In the present study, the Compton imaging technique was evaluated by experimentally obtaining Compton images of relatively high-energy gamma sources positioned in an anthropomorphic phantom. Preparatory to that, two point-like gamma sources, 137 Cs (662 keV) and 22 Na (1275 keV), were placed in the brain region of the phantom at different depths and imaged using a double-scattering Compton camera. The Compton camera, recently developed as a prototype system, consists of two position-sensitive semiconductor detectors as scatterer detectors and a scintillation detector as an absorber detector. The evaluated imaging and angular resolutions for the source energies of 662 and 1275 keV were 13.7 mm and 5.9 ˚FWHM and 11.4 mm and 3.8 ˚FWHM, respectively.

This paper presents an observer-based controller for vehicle semi-active suspensions. Vehicle suspensions are disturbance-affected dynamic systems and semi-active suspensions can be represented as a bilinear model. A new methodology for designing observers for vehicle semi-active suspensions has been proposed. The proposed methodology simplifies the observer design process and is convenient for implementation. An observer is formulated such that the estimation error is independent of unknown road disturbances. The proposed observer uses easily accessible measurements, such as accelerations, and guarantees exponentially convergent state estimations for suspension deflections and velocities. The absolute sprung mass and unsprung mass velocities can be estimated using the proposed observer. Simulations and experimental rig tests show that all states of a semi-active suspension can be estimated only with acceleration measurements. The estimated states are used to improve ride quality in a semi-active suspension. It has been shown that the performance of the observer-based controller is comparable to that of a controller using measured states.

Purpose Patients with diabetes mellitus have an elevated risk of atrial fibrillation (AF). However, whether insulin resistance may elevate risk of AF incidence in non-diabetic is inconsistent. The aim of our study was to verify the association between insulin resistance and incidence of AF in non-diabetics. Methods We evaluated population-based cohorts embedded in the Korean Genome Epidemiology Study. Insulin resistance was expressed as Homeostasis Model Assessment for Insulin resistance (HOMA-IR). Baseline data including HOMA-IR and electrocardiography (ECG) were obtained at 2001. Subsequent biennial ECG was performed for identification of AF until 2016. Results Among the 8220 participants (46.8% male; median age 49 years), 25 participants had AF (0.3%) at baseline and 101 participants developed AF (1.2%) during follow up of 12 years. In multivariate Cox regression analysis, high HOMA-IR (≥1.4) was significantly associated with incident AF compared with low HOMA-IR (<1.40) (adjusted hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.3–3.0). In subgroup analysis, these association was consistent regardless of obesity (BMI<25; adjust HR 1.8, 95% CI 1.1–3.0, BMI≥25; adjust HR 2.3, 95% CI 1.3–4.0) Subgroup analysis Conclusion Based on prospective cohort study, insulin resistance (HOMA-IR) was associated with AF independently of obesity in non-diabetics.