Exploring Customers’ Preferences for Online Games

Online content providers who use the Internet to distribute content experience an extremely competitive business environment. To survive in this environment, they have started charging a fee for the content that they provide. However, there have been very few success stories in commercializing online content. Although one of few success stories is the online game, it still has customers’ psychological resistance against paying a high fee for playing games. To pay back their high R&D or development costs quickly, many online game producers have a tendency to assign high prices to their online games. Without examining customers’ perceived prices for online games, many online game producers have tended to decide prices from their perspectives. Although many online game-related research works have focused on psychological and technical aspects, very few works have examined online gamers’ preferences carefully. This study aims at exploring online gamers’ preference by measuring their WTP (Willingness To Pay) for online games

Genome-wide analysis of hepatic LRH-1 reveals a promoter binding preference and suggests a role in regulating genes of lipid metabolism in concert with FXR

<p>Abstract</p> <p>Background</p> <p>In a previous genome-wide analysis of FXR binding to hepatic chromatin, we noticed that an extra nuclear receptor (NR) half-site was co-enriched close to the FXR binding IR-1 elements and we provided limited support that the monomeric LRH-1 receptor that binds to NR half-sites might function together with FXR to activate gene expression.</p> <p>Results</p> <p>To analyze the global pattern for LRH-1 binding and to determine whether it might associate with FXR on a whole genome-wide scale, we analyzed LRH-1 binding to the entire hepatic genome using a non-biased genome-wide ChIP-seq approach. We identified over 10,600 LRH-1 binding sites in hepatic chromatin and over 20% were located within 2 kb of the 5' end of a known mouse gene. Additionally, the results demonstrate that a significant fraction of the genome sites occupied by LRH-1 are located close to FXR binding sites revealed in our earlier study. A Gene ontology analysis revealed that genes preferentially enriched in the LRH-1/FXR overlapping gene set are related to lipid metabolism. These results demonstrate that LRH-1 recruits FXR to lipid metabolic genes. A significant fraction of FXR binding peaks also contain a nuclear receptor half-site that does not bind LRH-1 suggesting that additional monomeric nuclear receptors such as RORs and NR4As family members may also target FXR to other pathway selective genes related to other areas of metabolism such as glucose metabolism where FXR has also been shown to play an important role.</p> <p>Conclusion</p> <p>These results document an important role for LRH-1 in hepatic metabolism through acting predominantly at proximal promoter sites and working in concert with additional nuclear receptors that bind to neighboring sites</p

REGNET: Mining context-specific human transcription networks using composite genomic information

Background: Genome-wide expression profiles reflect the transcriptional networks specific to the given cell context. However, most statistical models try to estimate the average connectivity of the networks from a collection of gene expression data, and are unable to characterize the context-specific transcriptional regulations. We propose an approach for mining context-specific transcription networks from a large collection of gene expression fold-change profiles and composite gene-set information.Results: Using a composite gene-set analysis method, we combine the information of transcription factor binding sites, Gene Ontology or pathway gene sets and gene expression fold-change profiles for a variety of cell conditions. We then collected all the significant patterns and constructed a database of context-specific transcription networks for human (REGNET). As a result, context-specific roles of transcription factors as well as their functional targets are readily explored. To validate the approach, nine predicted targets of E2F1 in HeLa cells were tested using chromatin immunoprecipitation assay. Among them, five (Gadd45b, Dusp6, Mll5, Bmp2 and E2f3) were successfully bound by E2F1. c-JUN and the EMT transcription networks were also validated from literature.Conclusions: REGNET is a useful tool for exploring the ternary relationships among the transcription factors, their functional targets and the corresponding cell conditions. It is able to provide useful clues for novel cell-specific transcriptional regulations. The REGNET database is available at http://mgrc.kribb.re.kr/regnet.open0

Characterization of Carbonyl Compounds in the Ambient Air of an Industrial City in Korea

The purpose of this study was to characterize spatial and temporal variations of carbonyl compounds in Gumi city, where a number of large electronic-industrial complexes are located. Carbonyl samples were collected at five sites in the Gumi area: three industrial, one commercial, and one residential area. Sampling was carried out throughout a year from December 2003 to November 2004. At one industrial site, samples were taken every six days, while those of the other sites were for seven consecutive days in every season. Each sample was collected for 150 minutes and at intervals of three times a day (morning, afternoon, and evening). A total of 476 samples were analyzed to determine 15 carbonyl compounds by the USEPA TO-11A (DNPH-cartridge/HPLC) method. In general, acetaldehyde appeared to be the most abundant compound, followed by formaldehyde, and acetone+acrolein. Mean concentrations of acetaldehyde were two to three times higher in the industrial sites than in the other sites, with its maximum of 77.7 ppb. In contrast, ambient levels of formaldehyde did not show any significant difference between the industrial and non-industrial groups. Its concentrations peaked in summer probably due to the enhanced volatilization and photochemical reactivity. These results indicate significant emission sources of acetaldehyde in the Gumi industrial complexes. Mean concentrations of organic solvents (such as acetone+acrolein and methyl ethyl ketone) were also significantly high in industrial areas. In conclusion, major sources of carbonyl compounds, including acetaldehyde, are strongly associated with industrial activities in the Gumi city area

G-protein-coupled receptor 81 promotes a malignant phenotype in breast cancer through angiogenic factor secretion

G-protein-coupled receptor 81 (GPR81) functions as a receptor for lactate and plays an important role in the regulation of anti-lipolytic effects in adipocytes. However, to data, a role for GPR81 in the tumor microenvironment has not been clearly defined. Here, GPR81 expression in breast cancer patients and several breast cancer cell lines was significantly increased compared with normal mammary tissues and cells. GPR81 knockdown resulted in impaired breast cancer growth and led to apoptosis both in vitro and in vivo. Furthermore, the inhibition of GPR81 signaling suppressed angiogenesis through a phosphoinositide 3-OH kinase (PI3K)/Akt-cAMP response element binding protein (CREB) pathway, which led to decreased production of the pro-angiogenic mediator amphiregulin (AREG). Overall, these findings identify GPR81 as a tumor-promoting receptor in breast cancer progression and suggest a novel mechanism that regulates GPR81-dependent activation of the PI3K/Akt signaling axis in tumor microenvironment.open

Tidal Effects on Intermediate Waters: A Case Study in the East/Japan Sea

Although tides are believed to be the most important source for diapycnal mixing in the ocean, few studies have directly simulated open-ocean circulation including tides. Because the East/Japan Sea (EJS) has been considered to be a “miniature ocean,” tidal effects on the intermediate water of the EJS are investigated by using an eddy-resolving ocean general circulation model that can take account of M2 and K1 tides as well as oceanic flows. The simulated temperature and salinity in the intermediate layer are significantly improved by including tides. The improvement results from the combined effect of two internal tides. The M2 internal tide, propagating into the interior of the EJS, enhances vertical mixing and brings watermass characteristics closer to those observed. The K1 internal tide, trapped along the coast, induces southwestward flow along the Russian coast in the upper layer and thereby enhances the so-called Liman Current, which transports fresh waters with density conducive to the ventilation of intermediate waters in the EJS

Inhibition of autophagy promotes salinomycin-induced apoptosis via reactive oxygen species-mediated PI3K/AKT/mTOR and ERK/p38 MAPK-dependent signaling in human prostate cancer cells

Recently, the interplay between autophagy and apoptosis has become an important factor in chemotherapy for cancer treatment. Inhibition of autophagy may be an effective strategy to improve the treatment of chemo-resistant cancer by consistent exposure to chemotherapeutic drugs. However, no reports have clearly elucidated the underlying mechanisms. Therefore, in this study, we assessed whether salinomycin, a promising anticancer drug, induces apoptosis and elucidated potential antitumor mechanisms in chemo-resistant prostate cancer cells. Cell viability assay, Western blot, annexin V/propidium iodide assay, acridine orange (AO) staining, caspase-3 activity assay, reactive oxygen species (ROS) production, and mitochondrial membrane potential were assayed. Our data showed that salinomycin alters the sensitivity of prostate cancer cells to autophagy. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, enhanced the salinomycin-induced apoptosis. Notably, salinomycin decreased phosphorylated of AKT and phosphorylated mammalian target of rapamycin (mTOR) in prostate cancer cells. Pretreatment with LY294002, an autophagy and PI3K inhibitor, enhanced the salinomycin-induced apoptosis by decreasing the AKT and mTOR activities and suppressing autophagy. However, pretreatment with PD98059 and SB203580, an extracellular signal-regulated kinases (ERK), and p38 inhibitors, suppressed the salinomycin-induced autophagy by reversing the upregulation of ERK and p38. In addition, pretreatment with N-acetyl-L-cysteine (NAC), an antioxidant, inhibited salinomycin-induced autophagy by suppressing ROS production. Our results suggested that salinomycin induces apoptosis, which was related to ROS-mediated autophagy through regulation of the PI3K/AKT/mTOR and ERK/p38 MAPK signaling pathways

Salinomycin enhances doxorubicin-induced cytotoxicity in multidrug resistant MCF-7/MDR human breast cancer cells via decreased efflux of doxorubicin

Salinomycin is a monocarboxylic polyether antibiotic, which is widely used as an anticoccidial agent. The anticancer property of salinomycin has been recognized and is based on its ability to induce apoptosis in human multidrug resistance (MDR). The present study investigated whether salinomycin reverses MDR towards chemotherapeutic agents in doxorubicin-resistant MCF-7/MDR human breast cancer cells. The results demonstrated that doxorubicin-mediated cytotoxicity was significantly enhanced by salinomycin in the MCF-7/MDR cells, and this occurred in a dose-dependent manner. This finding was consistent with subsequent observations made under a confocal microscope, in which the doxorubicin fluorescence signals of the salinomycin-treated cells were higher compared with the cells treated with doxorubicin alone. In addition, flow cytometric analysis revealed that salinomycin significantly increased the net cellular uptake and decreased the efflux of doxorubicin. The expression levels of MDR-1 and MRP-1 were not altered at either the mRNA or protein levels in the cells treated with salinomycin. These results indicated that salinomycin was mediated by its ability to increase the uptake and decrease the efflux of doxorubicin in MCF-7/MDR cells. Salinomycin reversed the resistance of doxorubicin, suggesting that chemotherapy in combination with salinomycin may benefit MDR cancer therapyopen

Effect of analgesia nociception index monitor-based nociception control on perioperative stress responses during laparoscopic surgery in Trendelenburg position: a randomized controlled trial

IntroductionThe analgesia nociception index (ANI) monitor is a nociception monitoring device based on heart rate variability. We aimed to determine the effect of ANI monitor-based intraoperative nociception control on the perioperative stress response during laparoscopic surgery in the Trendelenburg position.MethodsAltogether, 72 female patients who underwent total laparoscopic hysterectomy were randomized to either the control or ANI group. Intraoperative nociception was controlled by remifentanil administration in a conventional manner (based on blood pressure and heart rate) in the control group and by ANI monitoring in the ANI group. Perioperative stress responses were estimated by measuring the levels of serum catecholamines and catabolic stress hormones at three timepoints: after loss of consciousness, at the end of surgery, and 1 h after the end of surgery.ResultsThe serum cortisol level at the end of surgery was significantly higher in the ANI group than in the control group (p &lt; 0.001), although more remifentanil was administered in the ANI group than in the control group (p &lt; 0.001). Changes in the other estimators’ levels were comparable between groups during the perioperative period. The hemodynamic profiles during surgery were also significantly different between the two groups. Phenylephrine use to treat hypotension was more common in the ANI group than in the control group (p = 0.005). However, postoperative clinical outcomes such as pain and nausea/vomiting did not differ between groups.ConclusionANI monitor-based nociception control in laparoscopic surgery in the Trendelenburg position did not improve perioperative stress responses, intraoperative opioid consumption, or postoperative clinical outcomes.Clinical trial registration:ClinicalTrials.gov (NCT04343638)