276 research outputs found

    The Carcinogenicity of Aflatoxin B1

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    Aflatoxins are a class of carcinogenic mycotoxins, products of Aspergillus fungi, which are known contaminants in a large portion of the world’s food supply. Aflatoxin B1 (AFB1) is the most potent toxin, which has been strongly linked to the development of hepatocellular carcinoma (HCC), especially given coinfection with hepatitis B virus (HBV). AFB1 is catalyzed by cytochrome P450 (CYP450) into aflatoxin B1-8,9-exo-epoxide to form DNA adducts, which leads to carcinogenesis by disrupting DNA repair. AFB1-induced DNA damage is also caused by the production of excessive ROS, leading to the oxidation of DNA bases. The majority of AFB1-related to HCC carry G-to-T transversion of p53 gene. When the p53 gene is mutated, it shows a “gain of oncogenic function.” In addition, epigenetic alterations may potentially be beneficial for the treatment of HCC, because the epigenetic changes are reversible. This chapter will provide important information on the carcinogenicity of AFB1, including DNA damage checkpoint response and epigenetic alteration

    Flow Field in a Novel Short Residence Time Gas-solid Separator

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    The gas flow field in a short residence time separator was investigated. The tangential velocity in the separator housing increases with increasing angle to the positive x axis, and decreases with increasing radial position. A swirl of opposite direction to the main current in the separator housing occurs in the gas outlet

    Bubble Size and Mass Transfer in a Modified Airlift Loop Reactor with Continuous Slurry Phase

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    A modified internal airlift loop reactor with continuous slurry phases was explored to investigate the local bubble size and the local mass transfer properties. A mathematical model was derived to simulate the bubble size in every flow region. Also, a new method was developed to measure the dissolved oxygen concentration

    The impact of launching Stock Index Futures on the volatility of the Chinese stock market

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    In order to make forecast on the spot market volatility after the launching of stock index futures in China, this dissertation used data from the Hong Kong stock market and the Indian stock market to do empirical analysis. Econometrics models used are the ARCH family models, including GARCH model, EGARCH model and TARCH model. For each time series dataset, results from the most suitable model were adopted. Briefly speaking, the Hang Seng Index (HSI) volatility decreased both in the long run and short run after HSI futures were launched. The Indian stock market volatility decreased in the long run after NIFTY index futures were introduced, while in the short run, the spot market volatility did not show significant change. The forecast on the Chinese stock market I made is that the long term spot market volatility will decrease after index futures were launched and the short term volatility will not change significantly. In addition, the best time to launch the CSI 300futures should not be at present in the current bear condition, but at the beginning of the next bull condition. Besides the above work, discussion on the design of CSI 300 futures contracts forms the last part

    Intrinsic and Extrinsic Connections of Tet3 Dioxygenase with CXXC Zinc Finger Modules.

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    Tet proteins are emerging as major epigenetic modulators of cell fate and plasticity. However, little is known about how Tet proteins are targeted to selected genomic loci in distinct biological contexts. Previously, a CXXC-type zinc finger domain in Tet1 was shown to bind CpG-rich DNA sequences. Interestingly, in human and mouse the Tet2 and Tet3 genes are adjacent to Cxxc4 and Cxxc10-1, respectively. The CXXC domains encoded by these loci, together with those in Tet1 and Cxxc5, identify a distinct homology group within the CXXC domain family. Here we provide evidence for alternative mouse Tet3 transcripts including the Cxxc10-1 sequence (Tet3(CXXC)) and for an interaction between Tet3 and Cxxc4. In vitro Cxxc4 and the isolated CXXC domains of Tet1 and Tet3(CXXC) bind DNA substrates with similar preference towards the modification state of cytosine at a single CpG site. In vivo Tet1 and Tet3 isoforms with and without CXXC domain hydroxylate genomic 5-methylcytosine with similar activity. Relative transcript levels suggest that distinct ratios of Tet3(CXXC) isoforms and Tet3-Cxxc4 complex may be present in adult tissues. Our data suggest that variable association with CXXC modules may contribute to context specific functions of Tet proteins

    Copper-related genes predict prognosis and characteristics of breast cancer

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    BackgroundThe role of copper in cancer treatment is multifaceted, with copper homeostasis-related genes associated with both breast cancer prognosis and chemotherapy resistance. Interestingly, both elimination and overload of copper have been reported to have therapeutic potential in cancer treatment. Despite these findings, the exact relationship between copper homeostasis and cancer development remains unclear, and further investigation is needed to clarify this complexity.MethodsThe pan-cancer gene expression and immune infiltration analysis were performed using the Cancer Genome Atlas Program (TCGA) dataset. The R software packages were employed to analyze the expression and mutation status of breast cancer samples. After constructing a prognosis model to separate breast cancer samples by LASSO-Cox regression, we examined the immune statement, survival status, drug sensitivity and metabolic characteristics of the high- and low-copper related genes scoring groups. We also studied the expression of the constructed genes using the human protein atlas database and analyzed their related pathways. Finally, copper staining was performed with the clinical sample to investigate the distribution of copper in breast cancer tissue and paracancerous tissue.ResultsPan-cancer analysis showed that copper-related genes are associated with breast cancer, and the immune infiltration profile of breast cancer samples is significantly different from that of other cancers. The essential copper-related genes of LASSO-Cox regression were ATP7B (ATPase Copper Transporting Beta) and DLAT (Dihydrolipoamide S-Acetyltransferase), whose associated genes were enriched in the cell cycle pathway. The low-copper related genes scoring group presented higher levels of immune activation, better probabilities of survival, enrichment in pathways related to pyruvate metabolism and apoptosis, and higher sensitivity to chemotherapy drugs. Immunohistochemistry staining showed high protein expression of ATP7B and DLAT in breast cancer samples. The copper staining showed copper distribution in breast cancer tissue.ConclusionThis study displayed the potential impacts of copper-related genes on the overall survival, immune infiltration, drug sensitivity and metabolic profile of breast cancer, which could predict patients’ survival and tumor statement. These findings may serve to support future research efforts aiming at improving the management of breast cancer

    CFD simulation of hydrodynamic characteristics in a modified internally circulating fluidized bed mixer

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    A modified internally circulating fluidized bed (MICFB) was proposed as a particle mixer by coupling a pre-mixing section and a modified ICFB section[1]. Four slots were opened at the upside of the draft tube to improve further particle mixing. Hydrodynamics of MICFB was numerically investigated by multi-scale simulation based on a structure–dependent EMMS model[2]. Results showed that strong particle mixing mainly occurred in three regions, the bottom region, the draft tube region and the rectangular slots affected region. At the bottom region, due to the jet and the particles circulating from the annulus, bed density and particle velocity distributed unevenly. A cross-flow occurred in this region, with the circulating particles moving horizontally and the initial bubbles rising vertically. With increasing superficial gas velocity, particle rising velocity and particle circulating mass flow rate increased, leading to better particle mixing. In the slots affected region, radial distribution of bed density seems flat and the rising velocity decreased in the draft tube, while bed density significantly increased in the annulus. Nearly 62 wt. % particles entered the gas-solid separator region and then flowed into the annulus region, while the rest particles directly circulated into the annulus through the slots. A cross-flow of particles was also observed near the slots, with particles from the gas-solid separator region moving downwards and those circulating through slots flowing horizontally. Compared with ICFB with no slots, MICFB had a greater particle circulation mass flow rate with an increase of 20%, which consequently resulted in further particle mixing. Please click Additional Files below to see the full abstract

    The emerging roles of PHOSPHO1 and its regulated phospholipid homeostasis in metabolic disorders

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    Emerging evidence suggests that phosphoethanolamine/phosphocholine phosphatase 1 (PHOSPHO1), a specific phosphoethanolamine and phosphocholine phosphatase, is involved in energy metabolism. In this review, we describe the structure and regulation of PHOSPHO1, as well as current knowledge about the role of PHOSPHO1 and its related phospholipid metabolites in regulating energy metabolism. We also examine mechanistic evidence of PHOSPHO1- and phospholipid-mediated regulation of mitochondrial and lipid droplets functions in the context of metabolic homeostasis, which could be potentially targeted for treating metabolic disorders

    Shift invariant sparse coding ensemble and its application in rolling bearing fault diagnosis

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    This paper proposes an automatic diagnostic scheme without manual feature extraction or signal pre-processing. It directly handles the original data from sensors and determines the condition of the rolling bearing. With proper application of the new technique of shift invariant sparse coding (SISC), it is much easier to recognize the fault. Yet, this SISC, though being a powerful machine learning algorithm to train and test the original signals, is quite demanding computationally. Therefore, this paper proposes a highly efficient SISC which has been proved by experiments to be capable of representing signals better and making converges faster. For better performance, the AdaBoost algorithm is also combined with SISC classifier. Validated by the fault diagnosis of bearings and compared with other methods, this algorithm has higher accuracy rate and is more robust to load as well as to certain variation of speed
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