MiR-494-3p mediates oxaliplatin resistance of colorectal cancer cells via PTEN/AKT pathway

Purpose: To unravel the influence of miR-494-3p on the insensitivity of colorectal cancer (CRC) cells to oxaliplatin.Methods: The mRNA level of miR-494-3p in oxaliplatin-resistant HT-29 cells was evaluated with reverse transcript-polymerase chain reaction (RT-PCR). The cells were treated with miR-494-3p suppressor or mimic, and then apoptotic changes were determined flow cytometrically. Resistancerelated gene expressions were measured using RT-PCR and western blotting. In addition, in vivo mouse experiments were conducted.Results: MiR-494-3p expression in oxaliplatin-resistant HT-29 cells was much higher than that in parental HT-29 cells, accompanied by increased levels of MRP, P-gp, and AKT phosphorylation (p-AKT), and decreased phosphatase and tensin homolog (PTEN) (p < 0.001). The miR-494-3p mimic suppressed oxaliplatin-induced parental HT-29 cell apoptosis, while miR-494-3p inhibitor promoted oxaliplatin-resistant HT-29 cell apoptosis and decreased the levels of p-AKT, MRP and P-gp, while upregulating PTEN (p < 0.001). Furthermore, AKT inhibitor had similar effects as miR-494-3p inhibitor (p < 0.001). Experiments using nude mice demonstrated that inhibition of miR-494-3p accentuated the sensitivity of oxaliplatin-resistant HT-29 cells to oxaliplatin (p < 0.05).Conclusion: Suppression of miR-494-3p attenuates oxaliplatin insensitivity to CRC cells via a mechanism which may involve PTEN/AKT pathway. Therefore, miR-494-3p may be an effective target for overcoming drug resistance of CRC

Angle dependent field-driven reorientation transitions in uniaxial antiferromagnet MnBi2_2Te4_4 single crystal

MnBi$_2$Te$_4$, a two-dimensional magnetic topological insulator with a uniaxial antiferromagnetic structure, is an ideal platform to realize quantum anomalous Hall effect. However, the strength of magnetic interactions is not clear yet. We performed systematic studies on the magnetization and angle dependent magnetotransport of MnBi$_2$Te$_4$ single crystal. The results show that the direction of the magnetic field has significant effects on the critical field values and magnetic structure of this compound, which leads to different magnetotransport behaviors. The field-driven reorientation transitions can be utilized to estimate the AFM interlayer exchange interaction coupling and uniaxial magnetic anisotropy D. The obtained Hamiltonian can well explain the experimental data by Monte Carlo simulations. Our comprehensive studies on the field-driven magnetic transitions phenomenon in MnBi$_2$Te$_4$ provide a general approach for other topological systems with antiferromagnetism.Comment: 6 figure

Transcriptional Profiling of the Dose Response: A More Powerful Approach for Characterizing Drug Activities

The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmacological parameters such as the EC50, and enable an in-depth analysis of coordinated dose-dependent treatment effects. The approach was applied to a transcriptional profiling study that evaluated four kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901) across a six-logarithm dose range, using 12 arrays per compound. The transcript responses proved a powerful means to characterize and compare the compounds: the distribution of EC50 values for the transcriptome was linked to specific targets, dose-dependent effects on cellular processes were identified using automated pathway analysis, and a connection was seen between EC50s in standard cellular assays and transcriptional EC50s. Our approach greatly enriches the information that can be obtained from standard transcriptional profiling technology. Moreover, these methods are automated, robust to non-optimized assays, and could be applied to other sources of quantitative data

Grid Resource Management and Scheduling for Data Streaming Applications

Data streaming applications bring new challenges to resource management and scheduling for grid computing. Since real-time data streaming is required as data processing is going on, integrated grid resource management becomes essential among processing, storage and networking resources. Traditional scheduling approaches may not be sufficient for such applications, since usually only one aspect of grid resource scheduling is focused. In this work, an integrated resource scheduling approach is proposed and coordinated resource allocation of CPU cycles, storage capability and network bandwidth is implemented. Resource allocation is performed periodically with updated information on resources and applications and heuristic search for optimal solutions is used to assign various resources for running applications simultaneously. Performance metrics considered in this work include data throughput and utilization of processors, storage, and bandwidth, which are actually tightly coupled with each other when applied for grid data streaming applications. Experimental results show dramatic improvement of performance and scalability using our implementation