Research on Fatigue Damage and Affecting Factors of Defected Rock Mass Based on Ultrasonic Wave Velocity

In this paper the fatigue-loading test of defected rock-like specimen has been carried out by electro-hydraulic servo fatigue testing machine. At the same time, the ultrasonic data has been collected and analyzed by the digital ultrasonic instrument. The fatigue damage and influencing factors of the defective rock mass under dynamic load are studied. According to the experimental research and analysis, this paper chooses to define the damage variable by ultrasonic velocity, and the inverse function of the Logistic equation was used to describe the evolution curve of fatigue damage sample. The experimental data fitting results show that the damage model and the experimental data fit well. In addition, this paper analyzes the main influencing factors of fatigue damage in the test. The initial damage represents the damage state before the sample is cyclically loaded. Different initial damages have a significant effect on the fatigue life of the sample. In the case the initial damage is substantially the same, the upper limit stress is larger, the fatigue life of the sample is shorter, and conversely, the fatigue life is longer

A MicroRNA-1280/JAG2 Network Comprises a Novel Biological Target in High-Risk Medulloblastoma

Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRα and PDGFRβ signaling in MB biology remain poorly understood. Here, we report the subgroup specific expression of PDGFRα and PDGFRβ and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRβ but not PDGFRα, is involved in PDGFRβ signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRβ and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRβ and c-MYC reveals that increased expression of JAG2, a target of miR-1280, is associated with high metastatic dissemination at diagnosis and a poor outcome in MB patients. Our study may resolve the controversy on the role of PDGFRs in MB and unveils JAG2 as a key downstream effector of a PDGFRβ-driven signaling cascade and a potential therapeutic target

Improving alignment accuracy on homopolymer regions for semiconductor-based sequencing technologies

BACKGROUND: Ion Torrent and Ion Proton are semiconductor-based sequencing technologies that feature rapid sequencing speed and low upfront and operating costs, thanks to the avoidance of modified nucleotides and optical measurements. Despite of these advantages, however, Ion semiconductor sequencing technologies suffer much reduced sequencing accuracy at the genomic loci with homopolymer repeats of the same nucleotide. Such limitation significantly reduces its efficiency for the biological applications aiming at accurately identifying various genetic variants. RESULTS: In this study, we propose a Bayesian inference-based method that takes the advantage of the signal distributions of the electrical voltages that are measured for all the homopolymers of a fixed length. By cross-referencing the length of homopolymers in the reference genome and the voltage signal distribution derived from the experiment, the proposed integrated model significantly improves the alignment accuracy around the homopolymer regions. CONCLUSIONS: Besides improving alignment accuracy on homopolymer regions for semiconductor-based sequencing technologies with the proposed model, similar strategies can also be used on other high-throughput sequencing technologies that share similar limitations

Suppression of growth, migration and invasion of highly-metastatic human breast cancer cells by berbamine and its molecular mechanisms of action

<p>Abstract</p> <p>Background</p> <p>Breast cancer is the second leading cause of cancer related deaths among females worldwide. Berbamine (BER), a kind of bis-benzylisoquinoline alkaloid, has been used to treat clinical patients with inflammation and cancer for many years in China. The purpose of this study is to investigate the activity of BER against highly-metastatic human breast cancer and its molecular mechanisms of action.</p> <p>Results</p> <p>In our study, we found that BER inhibits growth of highly-metastatic human breast cancer cell lines MDA-MB-231 and MDA-MB-435S cells dose-dependently and time-dependently. The sera from BER-treated rats suppress the growth of MDA-MB-231 cells. BER shows synergistic effects with some existing anticancer agents such as trichostatin A (TSA, the histone deacetylase inhibitor), celecoxib (the inhibitor of COX-2), and carmofur against the growth of MDA-MB-231 cells. BER also displays the strong activity of inducing apoptosis in both estrogen receptor-negative MDA-MB-231 cells and estrogen receptor-alpha-positive MCF-7 breast cancer cells, but not in normal human mammary epithelial cell line MCF10A. BER down-regulates anti-apoptotic protein Bcl-2 levels and up-regulates pro-apoptotic protein Bax expressions in MDA-MB-231 and MDA-MB-435S cells. BER also has synergistic effects with anticancer agents trichostatin A, celecoxib and/or carmofur on reducing Bcl-2/Bax ratios and VEGF secretions in MDA-MB-231 cells. In addition, BER significantly suppresses cell migration and invasion, as well as decreases pro-MMP-9/pro-MMP-2 activation in breast cancer cells. Furthermore, BER suppresses Akt and nuclear factor <it>κ</it>B signaling by reducing the phosphorylation of c-Met and Akt, and inhibiting their downstream targets such as nuclear factor <it>κ</it>B p-65, Bcl-2/Bax, osteopontin, VEGF, MMP-9 and MMP-2 on protein and/or mRNA levels in breast cancer cells.</p> <p>Conclusion</p> <p>Our findings have showed that BER suppresses the growth, migration and invasion in highly-metastatic human breast cancer cells by possibly inhibiting Akt and NF-<it>κ</it>B signaling with their upstream target c-Met and downstream targets Bcl-2/Bax, osteopontin, VEGF, MMP-9 and MMP-2. BER has synergistic effects with anticancer agents trichostatin A, celecoxib and carmofur on inhibiting the growth of MDA-MB-231 cells and reducing the ratio of Bcl-2/Bax and/or VEGF expressions in the cancer cells. These findings suggest that BER may have the wide therapeutic and/or adjuvant therapeutic application in the treatment of human breast cancer and other cancers.</p

Mapping forests in monsoon Asia with ALOS PALSAR 50-m mosaic images and MODIS imagery in 2010.

Extensive forest changes have occurred in monsoon Asia, substantially affecting climate, carbon cycle and biodiversity. Accurate forest cover maps at fine spatial resolutions are required to qualify and quantify these effects. In this study, an algorithm was developed to map forests in 2010, with the use of structure and biomass information from the Advanced Land Observation System (ALOS) Phased Array L-band Synthetic Aperture Radar (PALSAR) mosaic dataset and the phenological information from MODerate Resolution Imaging Spectroradiometer (MOD13Q1 and MOD09A1) products. Our forest map (PALSARMOD50 m F/NF) was assessed through randomly selected ground truth samples from high spatial resolution images and had an overall accuracy of 95%. Total area of forests in monsoon Asia in 2010 was estimated to be ~6.3 × 10(6 )km(2). The distribution of evergreen and deciduous forests agreed reasonably well with the median Normalized Difference Vegetation Index (NDVI) in winter. PALSARMOD50 m F/NF map showed good spatial and areal agreements with selected forest maps generated by the Japan Aerospace Exploration Agency (JAXA F/NF), European Space Agency (ESA F/NF), Boston University (MCD12Q1 F/NF), Food and Agricultural Organization (FAO FRA), and University of Maryland (Landsat forests), but relatively large differences and uncertainties in tropical forests and evergreen and deciduous forests

Relationship between Neural Alteration and Perineural Invasion in Pancreatic Cancer Patients with Hyperglycemia

Background: Patients with higher levels of fasting serum glucose have higher death rates from pancreatic cancer compared to patients with lower levels of fasting serum glucose. However, the reasons have not been studied. The goal of the current study was to examine the neural alterations in pancreatic cancer patients with hyperglycemia and to identify the relationship between the neural alterations and perineural invasion. Methodology/Principal Findings: The clinical and pathological features of 61 formalin-fixed pancreatic cancer specimens and 10 normal pancreases as controls were analyzed. Furthermore, the expression of Protein Gene Product 9.5 (PGP9.5), Myelin P0 protein (MPP), NGF, TrkA, and p75 were examined by immunohistochemistry. The median number of nerves, the median area of neural tissue, and the median nerve diameter per 10 mm 2 were larger in the hyperglycemia group than those in the euglycemia group (p = 0.007, p = 0.009, and p = 0.004, respectively). The integrated optical density (IOD) of MPP staining was lower in the hyperglycemia group than those in the euglycemia group (p = 0.019), while the expression levels of NGF and p75 were higher in the hyperglycemia group than those in the euglycemia group (p = 0.002, and p = 0.026, respectively). The nerve bundle invasion of pancreatic cancer was more frequent in the hyperglycemia group than in the euglycemia group (p = 0.000). Conclusions/Significance: Nerve damage and regeneration occur simultaneously in the tumor microenvironment o

Cambogin Is Preferentially Cytotoxic to Cells Expressing PDGFR

Platelet-derived growth factor receptors (PDGFRs) have been implicated in a wide array of human malignancies, including medulloblastoma (MB), the most common brain tumor of childhood. Although significant progress in MB biology and therapeutics has been achieved during the past decades, MB remains a horrible challenge to the physicians and researchers. Therefore, novel inhibitors targeting PDGFR signaling pathway may offer great promise for the treatment of MB. In the present study, we investigated the cytotoxicity and mechanisms of cambogin in Daoy MB cells. Our results show that cambogin triggers significant S phase cell cycle arrest and apoptosis via down regulation of cyclin A and E, and activation of caspases. More importantly, further mechanistic studies demonstrated that cambogin inhibits PDGFR signaling in Daoy and genetically defined mouse embryo fibroblast (MEF) cell lines. These results suggest that cambogin is preferentially cytotoxic to cells expressing PDGFR. Our findings may provide a novel approach by targeting PDGFR signaling against MB

G protein-coupled receptor-mediated calcium signaling in astrocytes

Astrocytes express a large variety of G~protein-coupled receptors (GPCRs) which mediate the transduction of extracellular signals into intracellular calcium responses. This transduction is provided by a complex network of biochemical reactions which mobilizes a wealth of possible calcium-mobilizing second messenger molecules. Inositol 1,4,5-trisphosphate is probably the best known of these molecules whose enzymes for its production and degradation are nonetheless calcium-dependent. We present a biophysical modeling approach based on the assumption of Michaelis-Menten enzyme kinetics, to effectively describe GPCR-mediated astrocytic calcium signals. Our model is then used to study different mechanisms at play in stimulus encoding by shape and frequency of calcium oscillations in astrocytes.Comment: 35 pages, 6 figures, 1 table, 3 appendices (book chapter

Management control systems and relational performance in inter-organizational relationships : the role of justice and trust

This study investigates the relationships among organization justice, inter-firm trust and management control systems (MCS) in Australian inter-organizational relationships (IORs).2 page(s