Cellular Mechanism of Arglabin-Dimethylaminohydrochloride Cytotoxicity

Cancer is the second leading killer in the United States. Anticancer drug development is always based on the understanding of molecular and cellular mechanisms of carcinogenesis, as well as comprehensive knowledge of potential anticancer drugs. Arglabin-dimethylaminohydrochloride (arglabin-DMA) represents one of the new classes of anti-cancer agents that have shown promise in suppressing the growth of various tumor cells. However, the cellular mechanism of arglabin-DMA cytotoxic effects on tumor cells is still unclear. The current study was to determine the farnesyltransferase (FTase) inhibitory activity of arglabin-DMA and to investigate the effects of arglabin-DMA on three proteins: Ras, Rho and cyclin kinase inhibitor p21/WAF1/CIP1. In vitro FTase assays were used to study the effect of arglabin-DMA on FTase activity. The FTase assay using expressed FTase showed that the 50% inhibition concentration of arglabin-DMA was 2.9 mM. The FTase assay using lysates of Ras/3T3 cells that had been incubated with arglabin-DMA showed that the highest FTase inhibition was 59% as compared to the no treatment control, and this inhibition plateaued when the arglabin-DMA concentration was 100 nM or higher. These results suggested that arglabin-DMA was transformed in cells and that the transformed arglabin-DMA inhibited FTase activity in Ras/3T3 cells. However, this inhibition was limited by the substrate availability in cells that may transform arglabin-DMA to an FTase inhibitor. The study of the effects of arglabin-DMA on Ras protein, Rho protein, and cyclin kinase inhibitor p21/WAF1/CIP1 was performed using Ras/3T3 cells incubated with arglabin-DMA or FTI-277 (positive control) for 24 or 72 hours. Western blots and densitometry showed a decreased ratio of processed to unprocessed H-Ras protein in cell lysates incubated with 100 μM of arglabin-DMA. Western blotting of active H-Ras protein from GTPase pull-down assays showed significant reduction of active H-Ras after incubation with 50 μM of arglabin-DMA for 24 hours, or 1 μM of arglabin-DMA for 72 hours. Only unprocessed RhoA was detected by Western blot after incubation with 10 μM (or higher) arglabin-DMA or FTI-277. Western blots showed a trend of increased p21/WAF1/CIP1 production after 72 hours of incubation with arglabin-DMA and this increase was not found in the FTI-277 control

One-sample aggregate data meta-analysis of medians

An aggregate data meta-analysis is a statistical method that pools the summary statistics of several selected studies to estimate the outcome of interest. When considering a continuous outcome, typically each study must report the same measure of the outcome variable and its spread (e.g., the sample mean and its standard error). However, some studies may instead report the median along with various measures of spread. Recently, the task of incorporating medians in meta-analysis has been achieved by estimating the sample mean and its standard error from each study that reports a median in order to meta-analyze the means. In this paper, we propose two alternative approaches to meta-analyze data that instead rely on medians. We systematically compare these approaches via simulation study to each other and to methods that transform the study-specific medians and spread into sample means and their standard errors. We demonstrate that the proposed median-based approaches perform better than the transformation-based approaches, especially when applied to skewed data and data with high inter-study variance. In addition, when meta-analyzing data that consists of medians, we show that the median-based approaches perform considerably better than or comparably to the best-case scenario for a transformation approach: conducting a meta-analysis using the actual sample mean and standard error of the mean of each study. Finally, we illustrate these approaches in a meta-analysis of patient delay in tuberculosis diagnosis

Latest lessons from the bankruptcy of state-owned enterprises (SOEs) in China : an interpretative structural model (ISM) approach

State-owned enterprises (SOEs) play an important role in China. During the transformation from a planned to a market economy, plenty of Chinese SOEs fell into trouble. Dalian machine tool group (DMTG) who was once a leading enterprise in the Chinese machine tool industry bankrupted in 2017. To explore the causes of its collapse, we employ the interpretative structural model (ISM) to investigate the reasons for its failures from multi-aspect and at different levels. The results indicate that the root cause of this bankruptcy is the top manager’s mismanagement; the lack of a reasonable strategic positioning and long-term product planning are also important factors of DMTG’s failure, and the problems of human resource management accelerated the bankruptcy. Findings provide lessons to be learned from the bankruptcy for SOEs and offer managerial insight into SOEs.Peer ReviewedPostprint (published version

Pore Characteristics of the Upper Carboniferous Taiyuan Shale in Liaohe Depression

High pressure mercury, nitrogen adsorption, nano-CT, and scanning electron microscope with energy spectrum analysis were conducted on core shale samples for studying the characteristics of Taiyuan formation in the eastern uplift of Liaohe depression. The research results show that the shale gas reservoir pores are mainly open pores such as the wedge-shape pores and parallel-plate pores. By a genetic type, pores mainly include organic pore, pyrite crystal particle pore, illite intragranular pore, illite-smectite mixed layer intragranular pore, and feldspar dissolved pore. The micropore and mesopore play an important role in shale gas reservoir, and their surface area and pore volume are 9.56 m2/g, 0.0414 mL/g, 97.3%, and 68.8% respectively. The pores diameter presents a bimodal distribution with two main peaks at 43 nm and 6.35 μm. Based on the nano-CT, the porosity is 4.36% and the permeability is 204 nD. The brittle minerals played a supportive and protective role for the pores and controlled their spatial distribution

Foreground-background salience effect in traffic risk communication

Pie charts are often used to communicate risk, such as the risk of driving. In the foreground-background salience effect (FBSE), foreground (probability of bad event) has greater salience than background (no bad event) in such a chart. Experiment 1 confirmed that the displays format of pie charts showed a typical FBSE. Experiment 2 showed that the FBSE resulted from a difference in cognitive efforts in processing the messages and that a foreground-emphasizing display was easier to process. Experiment 3 manipulated subjects’ information processing mindset and explored the interaction between displays format and information processing mindset. In the default mindset, careless subjects displayed a typical FBSE, while those who were instructed to be careful reported similar risk-avoidant behavior preference reading both charts. Suggestions for improving risk communication are discussed