EFFECTS OF POLYUNSATURATED FATTY ACIDS ON MULTIDRUG RESISTANCE AND DNA METHYLATION IN HUMAN CANCER CELL LINES

Accumulating evidences indicate that dietary intake of long-chain polyunsaturated fatty acids (PUFAs) can affect various cellular processes and improve response of cancer cells to chemotherapy. The mechanisms by which PUFAs affect this response are not well understood. P-glycoprotein (P-gp), encoded by the multidrug resistance gene MDR1, is a drug efflux transporter that plays an important role in the bioavailability of anti-cancer drugs. Effects of long-chain polyunsaturated fatty acids on MDR1 gene expression and functional activity in the human colon cancer cell line Caco-2 were studied in this research. Caco-2 cells were treated with different concentrations of three PUFAs: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA). All three PUFAs down-regulated the expression of the MDR1 gene (EPA, 34%, DHA, 32% and AA, 27%). The inhibition of gene expression by these PUFAs was accompanied by reduction in protein levels of P-gp. The calcein-AM efflux assay indicated that EPA, DHA, and AA can increase intracellular accumulation (hence decrease the efflux) of calcein-AM (a P-gp substrate) by 25% to 31%. In addition, incubation of cells with PUFAs greatly enhanced the cytotoxicity of the anti-cancer drug paclitaxel. All three PUFAs also induced apoptosis and enhanced paclitaxel-induced apoptosis in Caco-2 cells. Together, these results suggest that inhibition of the multidrug resistance MDR1/P-gp is one mechanism through which dietary polyunsaturated fatty acids exert a positive effect on the response of tumor cells to anti-cancer drugs. In addition, transcriptional promotion of the nuclear receptors CAR and PXR by PUFAs was also observed in this study. Moreover, to determine whether the eicosapentaenoic acid affects BRCA1 expression through promoter methylation, BRCA1 promoter methylation patterns and gene expression in U937 cells were examined. The methylation status of the BRCA1 promoter was evaluated by methylation-specific PCR (MSP) of bisulfite conversion products. The results indicate that methylation of BRCA1 promoter DNA is reduced in EPA-treated cells. The reduction of methylation in the BRCA1 promoter was accompanied by an increase in mRNA levels obtained by real-time quantitative PCR (qPCR), suggesting that DNA methylation is a possible mechanism by which the dietary polyunsaturated fatty acids mediate gene expression in human cells. Because of these characteristics, use of PUFAs as adjuvants presents a promising strategy in cancer prevention and therapeutics

協方差型隨機子空間識別法之應用

In this research the application of output-only system identification technique known as Stochastic Subspace Identification (SSI) algorithms in civil structures is carried out. With the aim of finding accurate modal parameters of the structure in off-line analysis, a stabilization diagram is constructed by plotting the identified poles of the system with increasing the size of data matrix. A sensitivity study of the implementation of SSI through stabilization diagram is firstly carried out, different scenarios such as noise effect, nonlinearity, time-varying systems and closely-spaced frequencies are considered. Comparison between different SSI approaches was also discussed. In the following, the identification task of a real large scale structure: Canton Tower, a benchmark problem for structural health monitoring of high-rise slender structures is carried out, for which the capacity of Covariance-driven SSI algorithm (SSI-COV) will be demonstrated. The introduction of a subspace preprocessing algorithm known as Singular Spectrum Analysis (SSA) can greatly enhance the identification capacity, which in conjunction with SSI-COV is called the SSA-SSI-COV method, it also allows the determination of the best system order. The objective of the second part of this research is to develop on-line system parameter estimation and damage detection technique through Recursive Covariance-driven Stochastic Subspace identification (RSSI-COV) approach. The Extended Instrumental Variable version of Projection Approximation Subspace Tracking algorithm (EIV-PAST) is taking charge of the system-related subspace updating task. To further reduce the noise corruption in field experiments, the data pre-processing technique called recursive Singular Spectrum Analysis technique (rSSA) is developed to remove the noise contaminant measurements, so as to enhance the stability of data analysis. Through simulation study as well as the experimental research, both RSSI-COV and rSSA-SSI-COV method are applied to identify the dynamic behavior of systems with time-varying characteristics, the reliable control parameters for the model are examined. Finally, these algorithms are applied to track the evolution of modal parameters for: (1) shaking table test of a 3-story steel frame with instantaneous stiffness reduction. (2) Shaking table test of a 1-story 2-bay reinforced concrete frame, both under earthquake excitation, and at last, (3) damage detection and early warning of an experimental steel bridge under continuous scour.UCR::Vicerrectoría de Docencia::Ingeniería::Facultad de Ingeniería::Escuela de Ingeniería Civi

Personalized Acoustic Modeling by Weakly Supervised Multi-Task Deep Learning using Acoustic Tokens Discovered from Unlabeled Data

It is well known that recognizers personalized to each user are much more effective than user-independent recognizers. With the popularity of smartphones today, although it is not difficult to collect a large set of audio data for each user, it is difficult to transcribe it. However, it is now possible to automatically discover acoustic tokens from unlabeled personal data in an unsupervised way. We therefore propose a multi-task deep learning framework called a phoneme-token deep neural network (PTDNN), jointly trained from unsupervised acoustic tokens discovered from unlabeled data and very limited transcribed data for personalized acoustic modeling. We term this scenario "weakly supervised". The underlying intuition is that the high degree of similarity between the HMM states of acoustic token models and phoneme models may help them learn from each other in this multi-task learning framework. Initial experiments performed over a personalized audio data set recorded from Facebook posts demonstrated that very good improvements can be achieved in both frame accuracy and word accuracy over popularly-considered baselines such as fDLR, speaker code and lightly supervised adaptation. This approach complements existing speaker adaptation approaches and can be used jointly with such techniques to yield improved results.Comment: 5 pages, 5 figures, published in IEEE ICASSP 201

ASA: Adaptive VNF Scaling Algorithm for 5G Mobile Networks

5G mobile networks introduce Virtualized Network Functions (VNFs) to provide flexible services for incoming huge mobile data traffic. Compared with fixed capacity legacy network equipment, VNFs can be scaled in/out to adjust system capacity. However, hardware-based legacy network equipment is designed dedicatedly for its purpose so that it is more efficient in terms of unit cost. One challenge is to best use VNF resources and to balance the traffic between legacy network equipment and VNFs. To address this challenge, we first formulate the problem as a cost-performance tradeoff, where both VNF resource cost and system performance are quantified. Then, we propose an adaptive VNF scaling algorithm to balance the tradeoff. We derive the suitable VNF instances to handle data traffic with minimizing cost. Through extensive simulations, the adaptive algorithm is proven to provide good performance

The Improvement of Reliability of High-k/Metal Gate pMOSFET Device with Various PMA Conditions

The oxygen and nitrogen were shown to diffuse through the TiN layer in the high-k/metal gate devices during PMA. Both the oxygen and nitrogen annealing will reduce the gate leakage current without increasing oxide thickness. The threshold voltages of the devices changed with various PMA conditions. The reliability of the devices, especially for the oxygen annealed devices, was improved after PMA treatments

Ginseng essence, a medicinal and edible herbal formulation, ameliorates carbon tetrachloride-induced oxidative stress and liver injury in rats

AbstractBackgroundGinseng essence (GE) is a formulation comprising four medicinal and edible herbs including ginseng (Panax ginseng), American ginseng (Panax quinquefolius), lotus seed (Nelumbo nucifera), and lily bulb (Lilium longiflorum). This study was aimed at investigating the hepatoprotective effect of GE against carbon tetrachloride (CCl4)-induced liver injury in rats.MethodsWe treated Wistar rats daily with low, medium, and high [0.625 g/kg body weight (bw), 1.25 g/kg bw, and 3.125 g/kg bw, respectively] doses of GE for 9 wk. After the 1st wk of treatment, rats were administered 20% CCl4 (1.5 mL/kg bw) two times a week to induce liver damage until the treatment ended.ResultsSerum biochemical analysis indicated that GE ameliorated the elevation of aspartate aminotransferase and alanine aminotransferase and albumin decline in CCl4-treated rats. Moreover, CCl4-induced accumulation of hepatic total cholesterol and triglyceride was inhibited. The hepatoprotective effects of GE involved enhancing the hepatic antioxidant defense system including glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase. In addition, histological analysis using hematoxylin and eosin and Masson's trichrome staining showed that GE inhibited CCl4-induced hepatic inflammation and fibrosis. Furthermore, immunohistochemical staining of alpha-smooth muscle actin indicated that CCl4-triggered activation of hepatic stellate cells was reduced.ConclusionThese findings demonstrate that GE improves CCl4-induced liver inflammation and fibrosis by attenuating oxidative stress. Therefore, GE could be a promising hepatoprotective herbal formulation for future development of phytotherapy

Modulating Microglia/Macrophage Activation by CDNF Promotes Transplantation of Fetal Ventral Mesencephalic Graft Survival and Function in a Hemiparkinsonian Rat Model

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra pars compacta, which leads to the motor control deficits. Recently, cell transplantation is a cutting-edge technique for the therapy of PD. Nevertheless, one key bottleneck to realizing such potential is allogenic immune reaction of tissue grafts by recipients. Cerebral dopamine neurotrophic factor (CDNF) was shown to possess immune-modulatory properties that benefit neurodegenerative diseases. We hypothesized that co-administration of CDNF with fetal ventral mesencephalic (VM) tissue can improve the success of VM replacement therapies by attenuating immune responses. Hemiparkinsonian rats were generated by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle of Sprague Dawley (SD) rats. The rats were then intrastriatally transplanted with VM tissue from rats, with/without CDNF administration. Recovery of dopaminergic function and survival of the grafts were evaluated using the apomorphine-induced rotation test and smallanimal positron emission tomography (PET) coupled with [F-18] DOPA or [F-18] FE-PE2I, respectively. In addition, transplantation-related inflammatory response was determined by uptake of [F-18] FEPPA in the grafted side of striatum. Immunohistochemistry (IHC) examination was used to determine the survival of the grated dopaminergic neurons in the striatum and to investigate immune-modulatory effects of CDNF. The modulation of inflammatory responses caused by CDNF might involve enhancing M2 subset polarization and increasing fractal dimensions of 6-OHDA-treated BV2 microglial cell line. Analysis of CDNF-induced changes to gene expressions of 6-OHDA-stimulated BV2 cells implies that these alternations of the biomarkers and microglial morphology are implicated in the upregulation of protein kinase B signaling as well as regulation of catalytic, transferase, and protein serine/threonine kinase activity. The effects of CDNF on 6-OHDA-induced alternation of the canonical pathway in BV2 microglial cells is highly associated with PI3K-mediated phagosome formation. Our results are the first to show that CDNF administration enhances the survival of the grafted dopaminergic neurons and improves functional recovery in PD animal model. Modulation of the polarization, morphological characteristics, and transcriptional profiles of 6-OHDA-stimualted microglia by CDNF may possess these properties in transplantation-based regenerative therapies.Peer reviewe

Modulating Microglia/Macrophage Activation by CDNF Promotes Transplantation of Fetal Ventral Mesencephalic Graft Survival and Function in a Hemiparkinsonian Rat Model

Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra pars compacta, which leads to the motor control deficits. Recently, cell transplantation is a cutting-edge technique for the therapy of PD. Nevertheless, one key bottleneck to realizing such potential is allogenic immune reaction of tissue grafts by recipients. Cerebral dopamine neurotrophic factor (CDNF) was shown to possess immune-modulatory properties that benefit neurodegenerative diseases. We hypothesized that co-administration of CDNF with fetal ventral mesencephalic (VM) tissue can improve the success of VM replacement therapies by attenuating immune responses. Hemiparkinsonian rats were generated by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle of Sprague Dawley (SD) rats. The rats were then intrastriatally transplanted with VM tissue from rats, with/without CDNF administration. Recovery of dopaminergic function and survival of the grafts were evaluated using the apomorphine-induced rotation test and small-animal positron emission tomography (PET) coupled with [18F] DOPA or [18F] FE-PE2I, respectively. In addition, transplantation-related inflammatory response was determined by uptake of [18F] FEPPA in the grafted side of striatum. Immunohistochemistry (IHC) examination was used to determine the survival of the grated dopaminergic neurons in the striatum and to investigate immune-modulatory effects of CDNF. The modulation of inflammatory responses caused by CDNF might involve enhancing M2 subset polarization and increasing fractal dimensions of 6-OHDA-treated BV2 microglial cell line. Analysis of CDNF-induced changes to gene expressions of 6-OHDA-stimulated BV2 cells implies that these alternations of the biomarkers and microglial morphology are implicated in the upregulation of protein kinase B signaling as well as regulation of catalytic, transferase, and protein serine/threonine kinase activity. The effects of CDNF on 6-OHDA-induced alternation of the canonical pathway in BV2 microglial cells is highly associated with PI3K-mediated phagosome formation. Our results are the first to show that CDNF administration enhances the survival of the grafted dopaminergic neurons and improves functional recovery in PD animal model. Modulation of the polarization, morphological characteristics, and transcriptional profiles of 6-OHDA-stimualted microglia by CDNF may possess these properties in transplantation-based regenerative therapies