Genetic and Metabolic Characterization of Insomnia

Insomnia is reported to chronically affect 10∼15% of the adult population. However, very little is known about the genetics and metabolism of insomnia. Here we surveyed 10,038 Korean subjects whose genotypes have been previously profiled on a genome-wide scale. About 16.5% reported insomnia and displayed distinct metabolic changes reflecting an increase in insulin secretion, a higher risk of diabetes, and disrupted calcium signaling. Insomnia-associated genotypic differences were highly concentrated within genes involved in neural function. The most significant SNPs resided in ROR1 and PLCB1, genes known to be involved in bipolar disorder and schizophrenia, respectively. Putative enhancers, as indicated by the histone mark H3K4me1, were discovered within both genes near the significant SNPs. In neuronal cells, the enhancers were bound by PAX6, a neural transcription factor that is essential for central nervous system development. Open chromatin signatures were found on the enhancers in human pancreas, a tissue where PAX6 is known to play a role in insulin secretion. In PLCB1, CTCF was found to bind downstream of the enhancer and interact with PAX6, suggesting that it can probably inhibit gene activation by PAX6. PLCB4, a circadian gene that is closely located downstream of PLCB1, was identified as a candidate target gene. Hence, dysregulation of ROR1, PLCB1, or PLCB4 by PAX6 and CTCF may be one mechanism that links neural and pancreatic dysfunction not only in insomnia but also in the relevant psychiatric disorders that are accompanied with circadian rhythm disruption and metabolic syndrome

Vascular Protective Role of Samul-Tang in HUVECs: Involvement of Nrf2/HO-1 and NO

Samul-Tang (Si-Wu-Tang, SMT), composed of four medicinal herbs, is a well-known herbal formula treating hematological disorder or gynecologic disease. However, vascular protective effects of SMT and its molecular mechanisms on the vascular endothelium, known as the central spot of vascular inflammatory process, are not reported. The aim of this study was to investigate vascular protective effects of SMT water extract in human umbilical vein endothelial cells (HUVECs). Water extract of SMT was prepared and identified by HPLC-PDA analysis. Expression of cell adhesion molecules (CAMs) and heme oxygenase-1 (HO-1) and translocation of nuclear factor-kappa B (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were determined by western blot. Nuclear localization of NF-κB and Nrf2 was visualized by immunofluorescence and DNA binding activity of NF-κB was measured. ROS production, HL-60 monocyte adhesion, and intracellular nitric oxide (NO) were also measured using a fluorescent indicator. SMT suppressed NF-κB translocation and activation as well as expression of CAMs, monocyte adhesion, and ROS production induced by TNF-α in HUVECs. SMT treated HUVECs showed upregulation of HO-1 and NO which are responsible for vascular protective action. Our study suggests that SMT, a traditionally used herbal formula, protects the vascular endothelium from inflammation and might be used as a promising vascular protective drug

A Study of Solids and Gas Mixing in a Partitioned Fluidized Bed

A partitioned fluidized bed gasifier has been developed for improving coal gasification performance. The basic concept is to divide a fluidized bed into two parts, a gasifier and a combustor, by a partition. Char is burnt in the combustor and generated heat is supplied to the gasifier by solid mixing. Therefore, solid mixing should be maximized whereas gas mixing between syngas and the combusted gas should be minimized. In this study, gas and solid mixing behaviors were verified in cold model acrylic beds. For monitoring solid mixing behavior, transient temperature trends in the beds were analyzed. A heat source and a heat sink were installed in each bed. Dozens of thermocouples were used to monitor temperature distribution

Gene expression profiling of cancer stem cell in human lung adenocarcinoma A549 cells

<p>Abstract</p> <p>Background</p> <p>The studies on cancer-stem-cells (CSCs) have attracted so much attention in recent years as possible therapeutic implications. This study was carried out to investigate the gene expression profile of CSCs in human lung adenocarcinoma A549 cells.</p> <p>Results</p> <p>We isolated CSCs from A549 cell line of which side population (SP) phenotype revealed several stem cell properties. After staining the cell line with Hoechst 33342 dye, the SP and non-side population (non-SP) cells were sorted using flow cytometric analysis. The mRNA expression profiles were measured using an Affymetrix GeneChip^®oligonucleotide array. Among the sixty one differentially expressed genes, the twelve genes inclusive three poor prognostic genes; Aldo-keto reductase family 1, member C1/C2 (AKR1C1/C2), Transmembrane 4 L six family member 1 nuclear receptor (TM4SF1), and Nuclear receptor subfamily 0, group B, member 1 (NR0B1) were significantly up-regulated in SP compared to non-SP cells.</p> <p>Conclusion</p> <p>This is the first report indicating the differences of gene expression pattern between SP and non-SP cells in A549 cells. We suggest that the up-regulations of the genes AKR1C1/C2, TM4SF1 and NR0B1 in SP of human adenocarcinoma A549 cells could be a target of poor prognosis in anti-cancer therapy.</p

Evaluation of effectiveness of fault-tolerant techniques in a digital instrumentation and control system with a fault injection experiment

Recently, instrumentation and control (I&amp;C) systems in nuclear power plants have undergone digitalization. Owing to the unique characteristics of digital I&amp;C systems, the reliability analysis of digital systems has become an important element of probabilistic safety assessment (PSA). In a reliability analysis of digital systems, fault-tolerant techniques and their effectiveness must be considered. A fault injection experiment was performed on a safety-critical digital I&amp;C system developed for nuclear power plants to evaluate the effectiveness of fault-tolerant techniques implemented in the target system. A software-implemented fault injection in which faults were injected into the memory area was used based on the assumption that all faults in the target system will be reflected in the faults in the memory. To reduce the number of required fault injection experiments, the memory assigned to the target software was analyzed. In addition, to observe the effect of the fault detection coverage of fault-tolerant techniques, a PSA model was developed. The analysis of the experimental result also can be used to identify weak points of fault-tolerant techniques for capability improvement of fault-tolerant techniques

Bare-metal stents versus drug-eluting stents in large (≥3.5mm) single coronary artery: Angiographic and clinical outcomes at 6 months

SummaryBackgroundAlthough drug-eluting stents (DES) have been shown to dramatically reduce restenosis and improve the rate of event-free survival in large randomized trials, the benefit of DES appears to be limited to restenosis. In large arteries, it is not clear which type of stent is more superior in angiographic and clinical outcomes between DES and bare-metal stents (BMS). We compared the angiographic and clinical outcomes of DES versus BMS in large arteries (≥3.5mm).MethodTwo hundred and forty patients from March 2002 to March 2007 received stents; 196 patients were treated with DES (44.9% sirolimus-eluting stents; 43.9% paclitaxel-eluting stents; 11.2% zotarolimus-eluting stents) and 44 with cobalt–chromium BMS for single de novo lesions in a large vessel. All subjects received aspirin, clopidogrel, and/or cilostazol as the standard antiplatelet regimen. The angiographic and clinical outcomes were evaluated at 6 months.ResultsFor the baseline characteristics, there were no significant differences between the DES and BMS groups. In addition, for the initially implanted stent there was no difference in the length, stent diameter, and lesion site between the two groups. After 6 months, the follow-up angiogram showed that in-stent diameter restenosis and late loss was more common with BMS than DES (39±21% vs. 19±17%, p=0.007; 1.44±0.83mm vs. 0.62±0.58mm, p=0.009, respectively). However, the target-lesion revascularization/target-vessel revascularization, and total major adverse cardiac events showed no significant differences between the groups (5.3% vs. 3.6%, p=0.62; 5.3% vs. 4.6%, p=0.86, respectively).ConclusionThe DES and cobalt–chromium BMS placed in large coronary arteries showed equally favorable 6-month clinical outcomes, although the 6-month angiographic results appeared more favorable in the DES group than in the BMS group

Bioavailability of the amino acid-attached prodrug as a new anti-HIV agent in rats

The primary objective of this study was to compare the pharmacokinetics of a new anti-human immunodeficiency virus agent 1-(2-amino-pyridin-4-ylmethyl)-6-(3,5-dimethyl-benzoyl)-5-isopropyl-1H-pyrimidine-2,4-dione (VP-0502) with its amino acid prodrug alanine amide of VP-0502 (VP-0502AL), following intravenous and oral administrations to rats. The plasma concentrations of both analytes were analyzed via high-performance liquid chromatography coupled with photodiode-array detection (HPLC-DAD). When VP-0502 was intravenously administered at 20 mg/kg, the analyte appeared in low levels with an AUC of 0.3 µg · h/ml, and C0 of 0.2 µg/ml in plasma. However, both the prodrug VP-0502AL and its metabolite VP-0502 appeared at comparatively higher levels following intravenous injection of VP-0502AL at the same dose. VP-0502AL's pharmacokinetic parameters were Vd: 4.6 l/kg; AUC: 3 µg · h/ml; t1/2: 0.5 h; C0: 6 µg/ml; CLtot: 7 l/h/kg; and MRT: 0.6 h. Following oral administration of VP-0502 (100 mg/kg), it was not detectable in plasma (<50 ng/ml), while after the oral administration of VP-0502AL, VP-0502 was quantitatively detected as an active metabolite for the first 7 h, with a maximum plasma concentration (Cmax) of 0.8 µg/ml, and an area under the concentration-time curve (AUC) of 2 µg · h/ml. The oral pharmaco-kinetic parameters of VP-0502AL were calculated to be: maximum concentration time (tmax) 2.7 h; Cmax 0.2 µg/ml; elimination half-life (t1/2): 0.8 h; and AUC 0.5 µg · h/ml. Overall the findings indicate that VP-0502AL has a favorable pharmacokinetic profile as a prodrug with rapid transformation into the active metabolite, and that the attachment of the amino acid alanine to VP-0502 is an effective approach to improve its oral bioavailability. VP-0502AL is predicted to become a new highly bioavailable anti-AIDS drug candidate and/or lead compound