Analysis of Home Location Estimation with Iteration on Twitter Following Relationship

User's home locations are used by numerous social media applications, such as social media analysis. However, since the user's home location is not generally open to the public, many researchers have been attempting to develop a more accurate home location estimation. A social network that expresses relationships between users is used to estimate the users' home locations. The network-based home location estimation method with iteration, which propagates the estimated locations, is used to estimate more users' home locations. In this study, we analyze the function of network-based home location estimation with iteration while using the social network based on following relationships on Twitter. The results indicate that the function that selects the most frequent location among the friends' location has the best accuracy. Our analysis also shows that the 88% of users, who are in the social network based on following relationships, has at least one correct home location within one-hop (friends and friends of friends). According to this characteristic of the social network, we indicate that twice is sufficient for iteration.Comment: The 2016 International Conference on Advanced Informatics: Concepts, Theory and Application (ICAICTA2016

Metabolic Characterization of Antifolate Responsiveness and Non-responsiveness in Malignant Pleural Mesothelioma Cells

Antifolates are a class of drugs effective for treating malignant pleural mesothelioma (MPM). The majority of antifolates inhibit enzymes involved in purine and pyrimidine synthesis such as dihydrofolate reductase (DHFR), thymidylate synthase (TYMS), and glycinamide ribonucleotide formyltransferase (GART). In order to select the most suitable patients for effective therapy with drugs targeting specific metabolic pathways, there is a need for better predictive metabolic biomarkers. Antifolates can alter global metabolic pathways in MPM cells, yet the metabolic profile of treated cells has not yet been clearly elucidated. Here we found that MPM cell lines could be categorized into two groups according to their sensitivity or resistance to pemetrexed treatment. We show that pemetrexed susceptibility could be reversed and DNA synthesis rescued in drug-treated cells by the exogenous addition of the nucleotide precursors hypoxanthine and thymidine (HT). We observed that the expression of pemetrexed-targeted enzymes in resistant MPM cells was quantitatively lower than that seen in pemetrexed-sensitive cells. Metabolomic analysis revealed that glycine and choline, which are involved in one-carbon metabolism, were altered after drug treatment in pemetrexed-sensitive but not resistant MPM cells. The addition of HT upregulated the concentration of inosine monophosphate (IMP) in pemetrexed-sensitive MPM cells, indicating that the nucleic acid biosynthesis pathway is important for predicting the efficacy of pemetrexed in MPM cells. Our data provide evidence that may link therapeutic response to the regulation of metabolism, and points to potential biomarkers for informing clinical decisions regarding the most effective therapies for patients with MPM

Honokiol Prevents Non-Alcoholic Steatohepatitis-Induced Liver Cancer via EGFR Degradation through the Glucocorticoid Receptor-MIG6 Axis.

Non-alcoholic steatohepatitis (NASH) has become a serious public health problem associated with metabolic syndrome. The mechanisms by which NASH induces hepatocellular carcinoma (HCC) remain unknown. There are no approved drugs for treating NASH or preventing NASH-induced HCC. We used a genetic mouse model in which HCC was induced via high-fat diet feeding. This mouse model strongly resembles human NASH-induced HCC. The natural product honokiol (HNK) was tested for its preventative effects against NASH progression to HCC. Then, to clarify the mechanisms underlying HCC development, human HCC cells were treated with HNK. Human clinical specimens were also analyzed to explore this study's clinical relevance. We found that epidermal growth factor receptor (EGFR) signaling was hyperactivated in the livers of mice with NASH and human HCC specimens. Inhibition of EGFR signaling by HNK drastically attenuated HCC development in the mouse model. Mechanistically, HNK accelerated the nuclear translocation of glucocorticoid receptor (GR) and promoted mitogen-inducible gene 6 (MIG6)/ERBB receptor feedback inhibitor 1 (ERRFI1) expression, leading to EGFR degradation and thereby resulting in robust tumor suppression. In human samples, EGFR-positive HCC tissues and their corresponding non-tumor tissues exhibited decreased ERRFI1 mRNA expression. Additionally, GR-positive non-tumor liver tissues displayed lower EGFR expression. Livers from patients with advanced NASH exhibited decreased ERRFI1 expression. EGFR degradation or inactivation represents a novel approach for NASH-HCC treatment and prevention, and the GR-MIG6 axis is a newly defined target that can be activated by HNK and related compounds

Effects of the chelating agent DTPA on naturally accumulating metals in the body

Diethylenetriaminepentaacetate (DTPA) is the most widely used chelating agent for Pu and Am. Volunteers were assigned to receive intravenous injections or aerosol inhalations of 1 g of DTPA on days 1-4; volunteers received once daily injections of CaDTPA or ZnDTPA, CaDTPA inhalation as an aerosol, or CaDTPA injection on day 1 and ZnDTPA on days 2-4. CaDTPA injection or inhalation increased the excretion rates of Zn in urine with concomitantly reduced levels of serum Zn. Injection of CaDTPA reduced activities of serum alkaline phosphatase (AP) in parallel with the kinetics of Zn, whereas CaDTPA and ZnDTPA injection reduced activities of lactate dehydrogenase (LDH), and reduced activities of creatinine kinase (CK) were observed upon CaDTPA injection and its inhalation. Intravenous administration of CaDTPA and ZnDTPA enhanced excretion rates of Mn in urine, whereas transient reduction of Mn levels in serum was detected only via CaDTPA injection. Both CaDTPA and ZnDTPA transiently reduced levels of Mg in serum without affecting the excretion rates. On the other hand, both DTPAs increased excretion rates of toxic metals such as Pb and Cd, and CaDTPA also increased the rates of Hg. These results suggest that DTPA, and especially CaDTPA, removes essential metals and that the activities of these metalloenzymes are good indicators for the imbalance of essential metals during the DTPA administration. Our results also show that CaDTPA injection is more potent for removing these metals than ZnDTPA and inhalation of CaDTPA, and DTPA may be useful for the treatment of acute heavy metal poisoning with Pb, Cd, or Hg

p62, Upregulated during Preneoplasia, Induces Hepatocellular Carcinogenesis by Maintaining Survival of Stressed HCC-Initiating Cells.

p62 is a ubiquitin-binding autophagy receptor and signaling protein that accumulates in premalignant liver diseases and most hepatocellular carcinomas (HCCs). Although p62 was proposed to participate in the formation of benign adenomas in autophagy-deficient livers, its role in HCC initiation was not explored. Here we show that p62 is necessary and sufficient for HCC induction in mice and that its high expression in non-tumor human liver predicts rapid HCC recurrence after curative ablation. High p62 expression is needed for activation of NRF2 and mTORC1, induction of c-Myc, and protection of HCC-initiating cells from oxidative stress-induced death