Down-regulation of Survivin enhances sensitivity to BPR0L075 in human cancer cells via caspase-independent mechanisms

Background: BPR0L075 [6-methoxy-3-(3',4',5'-trimethoxy-benzoyl)-1H-indole] is a novel anti-cancer compound. It inhibits tubulin polymerization and induces mitochondrial-dependent apoptosis in various human cancer cells with different multi-drug resistance (MDR) status. Over-expression of an anti-apoptotic molecule, survivin, causes drug-resistance in various cancers. Survivin inhibits apoptosis by interfering caspase-3 and promotes cell growth by stabilizing microtubule networks. Here, we determined the effects of down-regulation of survivin in BPR0L075 (L075) treatment. Methods: Western blot analysis was used to determine the expression level of survivin in L075-untreated/-treated human oral carcinoma KB and nasopharyngeal carcinoma HONE-1 cancer cells. siRNA was used to down-regulate endogenous survivin. MTT cell viability assay, real-time caspase-3 activity assay and immuno-fluorescence microscopy were used to analyze downstream effects. Results: Survivin expression was up-regulated in both KB and HONE-1 cells in response to L075 treatment. Down-regulation of survivin induced hyper-sensitivity to L075 in KB and re-stored sensitivity to L075 in KB-derived L075-resistant KB-L30 cancer cells. At the molecular level, down-regulation of survivin induced changes in microtubule dynamics in both KB and KB-L30 cells. Surprisingly, down-regulation of survivin did not enhance the activity of caspase-3 in L075 therapy. Instead, down-regulation of survivin induced translocation of the apoptosis-inducing factor (AIF) from cytoplasm to nucleus. Conclusion: Down-regulation of survivin improved drug sensitivity to L075 in both KB and L075-resistant KB-L30 cancer cells, possibly through a tubulin-dependent and caspase-independent mechanism. We suggest that combining BPR0L075 and survivin inhibitor may give better clinical outcome than the use of BPR0L075 monotherapy in future clinical trials

Understorey plant community and light availability in conifer plantations and natural hardwood forests in Taiwan

Questions: What are the effects of replacing mixed species natural forests with Cryptomeria japonica plantations on understorey plant functional and species diversity? What is the role of the understorey light environment in determining understorey diversity and community in the two types of forest? Location: Subtropical northeast Taiwan. Methods: We examined light environments using hemispherical photography, and diversity and composition of understorey plants of a 35‐yr C. japonica plantation and an adjacent natural hardwood forest. Results: Understorey plant species richness was similar in the two forests, but the communities were different; only 18 of the 91 recorded understorey plant species occurred in both forests. Relative abundance of plants among different functional groups differed between the two forests. Relative numbers of shade‐tolerant and shade‐intolerant seedling individuals were also different between the two forest types with only one shade‐intolerant seedling in the plantation compared to 23 seedlings belonging to two species in the natural forest. In the natural forest 11 species of tree seedling were found, while in the plantation only five were found, and the seedling density was only one third of that in the natural forest. Across plots in both forests, understorey plant richness and diversity were negatively correlated with direct sunlight but not indirect sunlight, possibly because direct light plays a more important role in understorey plant growth. Conclusions: We report lower species and functional diversity and higher light availability in a natural hardwood forest than an adjacent 30‐yr C. japonica plantation, possibly due to the increased dominance of shade‐intolerant species associated with higher light availability. To maintain plant diversity, management efforts must be made to prevent localized losses of shade‐adapted understorey plants

Application of Non-dominated Sorting Genetic Algorithm in Calibration of HBV Rainfall-runoff Model: a Case Study of Tsengwen Reservoir Catchment in Southern Taiwan

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchive

Western North Pacific Typhoons with Concentric Eyewalls

Mon. Wea. Rev. 137, 3758-3770.This study examines the intensity change and moat dynamics of typhoons with concentric eyewalls using passive microwave data and best track data in the western North Pacific between 1997 and 2006. Of the 225 typhoons examined, we have indentified 55 typhoons and 62 cases with concentric eyewalls. The data indicate that approximately 50% of Category 4 and 75% of Category 5 typhoons possessed concentric eyewalls at some point during their life time. While major typhoons are most likely to form the concentric eyewalls, the formation of concentric structure may not be necessarily at the lifetime maximum intensity. Approximately one-third of concentric eyewall cases are formed at the time of maximum intensity A theoretical parameter called filamentation moat width is devised. The filamentation moat width can be computed from the best track typhoon intensity and the passive microwave satellite-estimated inner eyewall radius for each typhoon with concentric eyewalls. The filamentation moat width explains 40% of the variance of the satellite observed moat width in the group with concentric eyewall formation intensity greater than 130 kts. The moat is generally recognized to be heavily influenced by the subsidence forced by the two eyewalls. Our results suggest that the rapid filamentation dynamics may also be contributing to the organizational aspect of the moat in very intense typhoons. The intensity time series in both the concentric and non-concentric composites are studied. Intensity of the concentric typhoons tends to peak at the time of secondary eyewall formation; but the standard model of intensification followed by weakening is valid for only half of the cases. Approximately 74% of the cases intensify 24 h before secondary eyewall formation and approximately 72% of the cases weaken 24 h after formation. The concentric composites have a much slower

Optimal replenishment decisions under two-level trade credit with partial upstream trade credit linked to order quantity and limited storage capacity

[[abstract]]This paper extends the previous economic order quantity (EOQ) models under two-level trade credit such as Goyal (1985), Teng (2002), Huang (2003, 2007), Kreng and Tan (2010), Ouyang et al. (2013), and Teng et al. (2007) to reflect the real-life situations by incorporating the following concepts: (1) the storage capacity is limited, (2) the supplier offers the retailer a partially upstream trade credit linked to order quantity, and (3) both the dispensable assumptions that the upstream trade credit is longer than the downstream trade credit N<M and the interest charged per dollar per year is larger than or equal to the interest earned per dollar per year Ic<Ie are relaxed. We then study the necessary and sufficient conditions for finding the optimal solution for various cases and establish a useful algorithm to obtain the solution. Finally, numerical examples are given to illustrate the theoretical results and provide the managerial insights.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]紙本[[booktype]]電子

Acute hepatitis with nontyphoidal salmonella and hepatitis E virus coinfection

SummaryA 65-year-old Taiwanese man presented with dark urine for 5 days before admission to hospital and with fever on the 2nd day of admission to hospital. Laboratory studies showed acute hepatitis with hyperbilirubinemia. Acute hepatitis with nontyphoidal salmonella and hepatitis E virus coinfection was diagnosed. The fever subsided after treatment with ceftriaxone and cefepime. His serum bilirubin reached its peak value on the 3rd week after admission to hospital and then gradually returned to the normal range. To the best of our knowledge, acute hepatitis E coinfection with nontyphoidal salmonella has not been reported previously

Antcin K, a Triterpenoid Compound from Antrodia camphorata

The purpose of this study was to screen firstly the potential effects of antcin K (AnK), the main constituent of the fruiting body of Antrodia camphorata, in vitro and further evaluate the activities and mechanisms in high-fat-diet- (HFD-) induced mice. Following 8-week HFD-induction, mice were treated with AnK, fenofibrate (Feno), metformin (Metf), or vehicle for 4 weeks afterward. In C2C12 myotube cells, the membrane GLUT4 and phospho-Akt expressions were higher in insulin and AnK-treated groups than in the control group. It was observed that AnK-treated mice significantly lowered blood glucose, triglyceride, total cholesterol, and leptin levels in AnK-treated groups. Of interest, AnK at 40 mg/kg/day dosage displayed both antihyperglycemic effect comparable to Metf (300 mg/kg/day) and antihypertriglyceridemic effect comparable to Feno (250 mg/kg/day). The combination of significantly increased skeletal muscular membrane expression levels of glucose transporter 4 (GLUT4) but decreased hepatic glucose-6-phosphatase (G6 Pase) mRNA levels by AnK thus contributed to a decrease in blood glucose levels. Furthermore, AnK enhanced phosphorylation of AMP-activated protein kinase (phospho-AMPK) expressions in the muscle and liver. Moreover, AnK treatment exhibited inhibition of hepatic fatty acid synthase (FAS) but enhancement of fatty acid oxidation peroxisome proliferator-activated receptor α (PPARα) expression coincident with reduced sterol response element binding protein-1c (SREBP-1c) mRNA levels in the liver may contribute to decreased plasma triglycerides, hepatic steatosis, and total cholesterol levels. The present findings indicate that AnK displays an advantageous therapeutic potential for the management of type 2 diabetes and hyperlipidemia

Decision Support System For Safety Warning Of Bridge – A Case Study In Central Taiwan

This study aims at developing the decision support system (DSS) for safety warning of bridge. In the DSS, real-time and forecasted radar rainfalls are used to predict flood stage, velocity and scouring depth around bridge piers for one to three hours ahead. The techniques adopted in the DSS include (1) measurement and correction models of radar rainfall, (2) a grid-based distributed rainfall-runoff model for simulating reservoir inflows, (3) models for predicting flood stages, velocities and scouring depths around bridge piers, and (4) ultimate analysis approaches for evaluating safety of pier foundation. The DSS can support the management department to decide whether they should close bridges or not during floods. The proposed DSS gave a test-run during Typhoon Morakot in 2009 in Dajia River Basin, central Taiwan. The results show the DSS has reasonable performances during floods