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This paper intends to explore the bidirectional DC/DC converter concept and super capacitor which are used in conversion of the kinetic energy in moving vehicles during braking into electrical energy and can be used again during the acceleration of a car. Three modes of Electrical Vehicle (EV) are examined. Power balance is guaranteed under fluctuations or ups and downs in load values. Implementation is carried out by MATLAB /Simulink software to show the feasibility of the presented control strategy. The simulation results indicate the amalgamation of the of bi-directional converters and assortment super capacitor show that the imposed cost of electrical energy generation can be decreased significantly by the proposed method, at the same time satisfaction of the EV user is also taken into account.

Stealthy false data injection attack can evade the detection of state estimation and so put the smart grid in danger because the wrong states will affect the decision making in dispatch center. Therefore, it is crucial to study the impacts of cyber-attacks on smart grid and thus improve its security. Uased on the characteristic of false data injection attack, a power flow scenario based bi-level sparse cyber-attack model of AC grid with incomplete information is proposed in this paper. The proposed model is able to find the most vulnerable scenarios of the power grid. In this scenario, attackers are more likely to launch cyber-attacks, thereby this is crucial to the study of defense mechanisms against cyberattacks. Finally, the effectiveness of the proposed method is verified on standard IEEE 30-bus system.

Power inverter is an important part of a grid-connected system. Compared with the traditional L or LC filter, LCL filter is widely used in the grid-connected inverter due to its harmonic attenuation performance and system stability. The resonance frequency of LCL filter is determined by the parameters ofits components. However, the inductance of inductor may change in accordance with the current flowing through it that would have an impact on the harmonic attenuation. This paper presents a nonlinear inductor model to determine the components of LCL filter on a three-phase grid-connected inverter system. The control method of the proposed system is a double current closed-loop control method. The current harmonic distortion and total harmonic distortion are analyzed and compared with the traditional linear inductor model. The experimental results show that the LCL filter can be designed more efficiently when the nonlinear characteristics of the inductor is considered.

Background/Aims: Cancer stem cells (CSCs) are largely responsible for tumor relapse and metastatic behavior. Doublecortin-like kinase 1 (DCLK1) was recently reported to be a biomarker for gastrointestinal CSCs and involved in the epithelial-mesenchymal transition (EMT) and tumor progression. B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) is a crucial regulator of CSC self-renewal, malignant transformation and EMT, and a previous study from our group showed that Bmi-1 is upregulated in pancreatic cancer progression and participates in EMT. However, it remains unclear whether DCLK1 is involved in pancreatic cancer or whether DCLK1 is associated with the altered level of Bmi-1 expression. Methods: The correlation of DCLK1 expression and clinical features of pancreatic cancer was analyzed in 210 paraffin-embedded archived pancreatic cancer specimens by immunohistochemical analysis. The biological effects of DCLK1 siRNA on cells were investigated by examining cell proliferation using a cell counting kit and cell colony assays, cell migration by wound healing assay and cell invasion by Transwell invasion assay. We further investigated the effect of therapeutic siRNA targeting DCLK1 on pancreatic cancer cell growth in vivo. Moreover, the molecular mechanism by which DCLK1 upregulates Bmi-1 expression was explored using real-time PCR, western blotting and Co-immunoprecipitation assay. Results: DCLK1 is overexpressed in pancreatic cancer and is related to metastasis and prognosis. Knockdown of DCLK1 markedly suppressed cell growth in vitro and in vivo and also inhibited the migration and invasion of pancreatic cancer cells. Furthermore, we found that DCLK1 silencing could inhibit EMT in cancer cells via downregulation of Bmi-1 and the mesenchymal markers Snail and Vimentin and upregulation of the epithelial marker E-cadherin. Moreover, high DCLK1 expression in human pancreatic cancer samples was associated with a mesenchymal phenotype and increased cell proliferation. Further co-immunoprecipitation indicated that DCLK1 did not interact with Bmi-1 directly. Conclusion: Our data suggest that upregulation of DCLK1 may contribute to pancreatic cancer metastasis and poor prognosis by increasing Bmi-1 expression indirectly. The findings indicate that inhibiting DCLK1 expression might be a novel strategy for pancreatic cancer therapy.

The promotion of tumor development by Dickkopf 4 (DKK4) is receiving increased attention. However, the association between DKK4 and pancreatic cancer remains unclear. DKK4 expression was measured in pancreatic ductal adenocarcinoma tissues using qRT-PCR and immunohistochemistry. A DKK4-overexpressing pancreatic cancer cell line was established, and the differentially expressed genes (DEGs) that were induced by DKK4 were identified using transcriptome sequencing. The association between the identified DEGs and pancreatic cancer was assessed using gene ontology (GO), pathway analysis, pathway interaction networks, differentially expressed gene interaction network analysis, and co-expression gene networks. Finally, the accuracy of the analyses was validated using serial paraffin and frozen sections of clinical samples. DKK4 is highly expressed in pancreatic cancer tissues. DEGs of overexpression DKK4 of PANC-1 are mostly upregulated. GO and pathway analysis showed that DKK4 are associated with tumor and organ development and immune inflammation. The mitogen-activated protein kinase (MAPK) signaling pathway was the main signal transduction pathway that showed significant enrichment in overexpression DKK4 of PANC-1. The results of GO, pathway analyses, and differentially expressed gene interaction network identified genes that are closely associated with tumor development, including MAPK3, PIK3R3, VAV3, JAG1, and Notch3. The immunohistochemistry and immunofluorescence results suggested that DKK4 is co-expressed with MAPK3 and VAV3 in pancreatic cancer tissues. The results presented here show for the first time that DKK4 is highly expressed in pancreatic cancer tissues. Bioinformatics analysis of a DKK4-overexpressing of PANC-1 identified several oncogenes that are closely associated with tumors, and the MAPK signaling pathway is the core signal transduction pathway. DKK4 can be co-expressed with MAPK3 and VAV3 in pancreatic ductal adenocarcinoma tissues. Thus, DKK4 may have function on the development and progression of pancreatic cancer.

Background & Aims Multidrug resistance-associated protein 2 (MRP2) excretes conjugated organic anions including bilirubin and bile acids. Malfunction of MRP2 leads to jaundice in patients. Studies in rodents indicate that Radixin plays a critical role in determining Mrp2 canalicular membrane expression. However, it is not known how human hepatic MRP2 expression is regulated in cholestasis. Methods We assessed liver MRP2 expression in patients with obstructive cholestasis caused by gallstone blockage of bile ducts, and investigated the regulatory mechanism in HepG2 cells. Results Western blot detected that liver MRP2 protein expression in obstructive cholestatic patients (n=30) was significantly reduced to 25% of the non-cholestatic controls (n=23). Immunoprecipitation identified Ezrin but not Radixin associating with MRP2 in human livers, and the increased amount of phospho-Ezrin Thr567 was positively correlated with the amount of co-precipitated MRP2 in cholestatic livers, whereas Ezrin and Radixin total protein levels were unchanged in cholestasis. Further detailed studies indicate that Ezrin Thr567 phosphorylation plays an important role in MRP2 internalization in HepG2 cells. Since increased expression of PKCα, δ and e were detected in these cholestatic livers, we further confirmed that these PKCs stimulated Ezrin phosphorylation and reduced MRP2 membrane expression in HepG2 cells. Finally, we identified GP78 as the key ubiquitin ligase E3 involved in MRP2 proteasome degradation. Conclusions Activation of liver PKCs during cholestasis leads to Ezrin Thr567 phosphorylation resulting in MRP2 internalization and degradation where ubiquitin ligase E3 GP78 is involved. This process provides a mechanistic explanation for jaundice seen in patients with obstructive cholestasis.

Hydrogen has been demonstrated to function as a novel antioxidant and exert therapeutic antioxidant activity in a number of diseases. The present study was designed to investigate the effect of hydrogen inhalation on liver ischemia/reperfusion (I/R) injury in rats. The portal triad to the left lobe and the left middle lobe of the liver were completely occluded for 90 min. This was followed by reperfusion for 180 min. The rats subsequently underwent syngeneic orthotopic liver transplantation. Inhalation of various concentrations (1, 2 and 3%) of hydrogen gas and its administration for different durations (1, 3 and 6 h) immediately prior to the I/R injury allowed the optimal dose and duration of administration to be determined. Liver injury was evaluated through biochemical and histopathological examinations. The expression levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-6, were measured by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction (qPCR). Liver nuclear factor κB (NF-κB) was detected by qPCR and western blot analysis. Inhalation of hydrogen gas at 2% concentration for 1 h significantly reduced the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, the expression of cytokines, including IL-6, TNF-α, early growth response protein 1 (Egr-1) and IL-1β, and morphological damage. In addition, the mRNA and protein expression levels of NF-κB, heme oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl-2) and zinc finger protein A20 (A20) in rats where only the donors received hydrogen were significantly increased compared with those in rats where both the donor and recipient, or only the recipient received hydrogen. The results indicate that hydrogen inhalation at 2% concentration for 1 h prior to liver transplantation protected the rats from ischemia/reperfusion injury by activation of the NF-κB signaling pathway.

In order to reduce the pressure caused by the precipitous depletion of natural resources and realize the sustainable development, renewable energy resource is playing a more and more significant role with an exponential growth speed in the smart grid, especially for solar energy. Given the stochastic characteristics of the Photovoltaic (PV) generation and to maintain the security and reliability of the power grid operation, finding a forecasting method with higher accuracy is a pressing need. Facing with this challenge, a novel prediction model that combines Convolutional Neural Network with Wavelet Decomposition (CNN+WD) is presented in this paper. WD technique is aimed to decompose the historical photovoltaic power data into several wavelets with different frequencies. CNN is used to train the decomposed wavelets separately and predict the future output PV power. Three other kinds of models are investigated to compare with the presented approach. The performance is respectively assessed for 15mins, 30mins, 45mins, 60mins, 90mins and 120mins ahead power forecasting in deterministic prediction. Numerical results presented in simulations show that the proposed model has good reliability and high accuracy in comparison with other models selected for this study.

Circular RNAs (CircRNAs) are a novel type of endogenous noncoding RNAs that regulate target gene expression by interacting with microRNA (miRNA). Emerging evidence shows that dysregulation of circRNAs plays important roles in biological and pathological processes, including cancer development and progression. The functional role of circRNA in PDAC (pancreatic ductal adenocarcinoma) remains to be investigated. In this study, high throughput microarray assay revealed that hsa_circ_0000977 was aberrantly up-regulated in pancreatic cancer tissues; this was also validated by qRT-PCR. Silencing hsa_circ_0000977 suppressed pancreatic cancer cell proliferation and induced cell cycle arrest, which was simulated by hsa-miR-874-3p mimics and blocked by hsa-miR-874-3p inhibitor. Bioinformatics analysis predicted that there is an hsa_circ_0000977/hsa-miR-874-3p/PLK1 (Polo like kinase 1) axis in pancreatic cancer progression. Dual-luciferase reporter system and FISH assay validated the direct interaction of hsa_circ_0000977, hsa-miR-874-3p, and PLK1. Western blot verified that inhibition of hsa_circ_0000977 decreased PLK1 expression. Furthermore, silencing hsa_circ_0000977 suppressed pancreatic cancer growth in vivo. Altogether, silencing hsa_circ_0000977 suppresses progression of pancreatic cancer by interacting with hsa-miR-874-3p and decreasing inhibiting PLK1 expression. Our results may provide a promising strategy for future diagnosis and treatment of pancreatic cancer.

Background & Aims Bile acid transporters maintain bile acid homeostasis. Little is known about the functions of some transporters in cholestasis or their regulatory mechanism. We investigated the hepatic expression of solute carrier organic anion transporter family member 3A1 (SLCO3A1, also called OATP3A1) and assessed its functions during development of cholestasis. Methods We measured levels of OATP3A1 protein and messenger RNA and localized the protein in liver tissues from 22 patients with cholestasis and 21 patients without cholestasis, using real-time quantitative polymerase chain reaction, immunoblot, and immunofluorescence analyses. We performed experiments with Slco3a1-knockout and C57BL/6J (control) mice. Mice and Sprague-Dawley rats underwent bile duct ligation (BDL) or a sham operation. Some mice were placed on a 1% cholic acid (CA) diet to induce cholestasis or on a control diet. Serum and liver tissues were collected and analyzed; hepatic levels of bile acids and 7-α-C4 were measured using liquid chromatography/mass spectrometry. Human primary hepatocytes and hepatoma (PLC/PRF/5) cell lines were used to study mechanisms that regulate OATP3A1 expression and transport. Results Hepatic levels of OATP3A1 messenger RNA and protein were significantly increased in liver tissues from patients with cholestasis and from rodents with BDL or 1% CA diet–induced cholestasis. Levels of fibroblast growth factor 19 (FGF19, FGF15 in rodents) were also increased in liver tissues from patients and rodents with cholestasis. FGF19 signaling activated the Sp1 transcription factor and nuclear factor κB to increase expression of OATP3A1 in hepatocytes; we found binding sites for these factors in the SLCO3A1 promoter. Slco3a1-knockout mice had shorter survival times and increased hepatic levels of bile acid, and they developed more liver injury after the 1% CA diet or BDL than control mice. In hepatoma cell lines, we found OATP3A1 to take prostaglandin E2 and thyroxine into cells and efflux bile acids. Conclusions We found levels of OATP3A1 to be increased in cholestatic liver tissues from patients and rodents compared with healthy liver tissues. We show that OATP3A1 functions as a bile acid efflux transporter that is up-regulated as an adaptive response to cholestasis.

A new approach to determine the operating point of multiterminal dc (MTDC) network for improving transition smooth, based on an optimal power flow OPF model. Aim of the method is to reduce transition distance of MTDC network. Therefore, in the proposed method, distance between the BOPs of a system at different load level ratios is deployed as an objective function. Operating points are being determined by the output of the OPF model we proposed in this paper. The proposed method is programmed in MATLAB and implemented on an eight-bus test power system. Compared to previous works, results show the validity of proposed approach and ability to improve the transition smooth in a MTDC network.

State estimation is critical for the normal operation of power system. In conventional state estimator, bad data detector (BDD) is used to prevent power systems from being misled by erroneous measurements. However, many studies have pointed out that hackers can exploit security vulnerabilities of BDD to launch cyber-attack on power systems. In order to detect cyber-attack effectively, a novel defense mechanism based on interval state estimation is proposed. In the defense mechanism, the lower- and upper bounds of state variables are modeled as a dual bi-level optimization problem, whose objective is to maximize and minimize the boundary values of the state variables. In addition, the uncertainty of load forecasting is modeled as a parametric Gaussian distribution. Finally, the effectiveness of the proposed method is verified on standard IEEE 30-bus system.

Grid-connected inverter is an important part of the grid-connected system. Compared with the traditional L or LC filter, LCL filter has a better high-frequency harmonic attenuation performance. However, LCL filter has resonant peak, which has a great influence on the stability of the system. This paper first analyzes the effect of passive damping method on the resonance peak; then a double closed-loop control strategy with the inner loop of capacitor current and the outer loop of grid current is introduced; finally, the LCL three-phase grid-connected inverter with double-loop current control significantly reduces the Total Harmonic Distortion (THD), which verifies the feasibility of parameters design scheme of control strategy.

Power switch devices which base on wide band-gap (WBG) semiconductor, such as silicon carbide metal-oxide-semiconductor-field-effect-transistor (SiC MOSFET) and gallium nitride high-electron-mobility transistor (GaN-HEMT) perform superior performance as compared with silicon (Si) MOSFET in high switching frequency, high blocking voltage, and high temperature operation. In this paper, a series of characteristic test and comparative evaluation of power loss and efficiency which based on Si MOSFET (IPW65R080CFDA), SiC MOSFET (C2M0080120D), and GaN HEMT (TPH3212PS) with similar current rating are conducted in the single-ended flyback converter. It shows that the WBG switch devices can reduce more power loss, improve efficiency, and enhance more power density instead of Si MOSFET.

False data injection attack can bypass the bad data defense process in the power systems and affect the results of state estimation, so that the system security is in danger because of the wrong states obtained in the dispatch center. The traditional false data injection attack is based on the DC power flow model and has many limitations. In this paper, a global attack model and local attack model are proposed separately. The models are not only nonlinear but also sparse. The proposed sparse attack models take the smart grid as the attack object and minimize the change of the tampering meter as the objective function and take the line overload and the node power balance as the constraints. The attack vector obtained by the proposed attack model not only satisfies the node power balance constraints, but also can avoid traditional bad data detection process in power systems. Because the line overload will drive the grid into a dangerous running state that may cause the protection malfunction, a large blackout may be resulted. The proposed nonlinear sparse attack model is comprehensively validated on IEEE standard models.

Methyltranscriptome is an exciting new area that studies the mechanisms and functions of methylation in transcripts. A knowledge base with the systematic collection and curation of context specific transcriptome-wide methylations is critical for elucidating their biological functions as well as for developing bioinformatics tools. Since its inception in 2014, the Met-DB (Liu, H., Flores, M.A., Meng, J., Zhang, L., Zhao, X., Rao, M.K., Chen, Y. and Huang, Y. (2015) MeT-DB: a database of transcriptome methylation in mammalian cells. Nucleic Acids Res., 43, D197–D203), has become an important resource for methyltranscriptome, especially in the N6-methyl-adenosine (m6A) research community. Here, we report Met-DB v2.0, the significantly improved second version of Met-DB, which is entirely redesigned to focus more on elucidating context-specific m6A functions. Met-DB v2.0 has a major increase in context-specific m6A peaks and single-base sites predicted from 185 samples for 7 species from 26 independent studies. Moreover, it is also integrated with a new database for targets of m6A readers, erasers and writers and expanded with more collections of functional data. The redesigned Met-DB v2.0 web interface and genome browser provide more friendly, powerful, and informative ways to query and visualize the data. More importantly, MeT-DB v2.0 offers for the first time a series of tools specifically designed for understanding m6A functions. Met-DB V2.0 will be a valuable resource for m6A methyltranscriptome research. The Met-DB V2.0 database is available at http://compgenomics.utsa.edu/MeTDB/ and http://www.xjtlu.edu.cn/metdb2.

Magnetic components are very important part in the power electronics system. Given weight and constrain space in the power converter, high power density converter is increasely required. In the whole system, half of the weight are the magnetic components. For the grid-connected system, the LCL filter is a necessary part to suppress the noise due to the high switching frequency transistor appeared. This paper introduce the procedure to choose the approximate magnetic components for the LCL filter of grid-connected system. Finally, the design procedure is carried out and verified in a grid connected power converter.

The urban agglomeration polders type of flood control pattern is a general flood control pattern in the eastern plain area and some of the secondary river basins in China. A HEC-HMS model of Qinhuai River basin based on the flood control pattern was established for simulating basin runoff, examining the impact of urban agglomeration polders on flood events, and estimating the effects of urbanization on hydrological processes of the urban agglomeration polders in Qinhuai River basin. The results indicate that the urban agglomeration polders could increase the peak flow and flood volume. The smaller the scale of the flood, the more significant the influence of the polder was to the flood volume. The distribution of the city circle polder has no obvious impact on the flood volume, but has effect on the peak flow. The closer the polder is to basin output, the smaller the influence it has on peak flows. As the level of urbanization gradually improving of city circle polder, flood volumes and peak flows gradually increase compared to those with the current level of urbanization (the impervious rate was 20%). The potential change in flood volume and peak flow with increasing impervious rate shows a linear relationship.

Background Our main aim was to evaluate the value of medical image three-dimensional visualization system (MI-3DVS) in pancreaticoduodenctomy patients with hepatic artery variance. Methods 114 patients who had undergone pancreatoduodenectomy were retrospectively summarized and analyzed. Clinical data of 64-slice multidetector CT angiography (64-MDCTA) scanning was introduced into MI-3DVS for procedural segmentation, registration and 3-dimensional (3D) reconstruction. The findings were compared with those found during the operation and by postoperative digital subtraction angiography (DSA) of coeliac artery. Results The 3D model demonstrated the origination and bifurcations of blood vessels, and the relationships among neoplasms, organs and blood vessels efficiently. About (14/114 cases, 12.3%) had variant. The sensitivity, specificity and accuracy of MI-3DVS in variant hepatic artery diagnosis were 100%. It assisted in preoperative procedural planning that was consistent with intraoperative findings. Conclusions MI-3DVS can be applied for accurate diagnosis of hepatic artery variance. It also provides detailed preoperative guidance for individualized procedural planning. Copyright © 2014 John Wiley & Sons, Ltd.

Information and communication technologies (ICTs) introduce many Internet-based entry points that pose potential risks to cyber physical energy system (CPES). Therefore, it is significant to enhance the cybersecurity of CPES from cyber-attacks. In this paper, a new dynamic attack model that takes into account the dynamic characteristics of energy systems is developed based on traditional false data injection attack. The proposed attack model can be used to describe the attack behaviors of a malicious attacker over time. Then, we propose a new generalized interval state estimator to quantify the normal fluctuations of all CPES state variables. In this state estimator, the Unscented Kalman Filter (UKF) is used to predict the real-time operating level of the state variables. Copula theory is introduced to model the prediction uncertainty of sustainable energy and load as a set of conditional quantiles. We then model the normal fluctuation range of each CPES state as a bilevel nonlinear programming problem based on the worst case analysis. Consequently, an anomaly detection method is developed to detect whether there is an attack or not in the CPES. In this method, any state variable that falls outside its estimated interval is considered an abnormal point. Finally, the feasibility of the dynamic attack model and the effectiveness of the anomaly detection method have been extensively validated on test systems in power and energy society of the Institute of Electrical and Electronics Engineers (IEEE).

Accurate and reliable wind power forecasting is of great significance for the economic and safe operation of electric power and energy systems. However, due to the negative factors such as inaccurate numerical weather prediction and frequent ramping events, previous wind power prediction methods are difficult to meet actual needs for practical applications. To this end, this paper originally proposes a new wind power prediction method with high accuracy based on echo state network. This method is a hybrid of wavelet transform, echo state network and ensemble technique. Wavelet transform is used to decompose raw wind power time series data into different frequencies with better outliers and behaviors. Then, we adopt the echo state network to automatically learn the nonlinear mapping relationship between input and output in each frequency. Later, ensemble technique is applied to deal with the model misspecification and data noise problems, which are common in wind power prediction, thereby reducing the uncertainty of wind power forecasting and improving prediction accuracy. Finally, we use wind power data from real wind farms in Belgium and China to verify the feasibility and effectiveness of the proposed method. The simulation results show that the proposed method is superior to other benchmark algorithms in prediction accuracy, which indicates that the method has high potentials for practical application in real electric power and energy systems.

As renewable energy becomes increasingly popular in the global electric energy grid, improving the accuracy of renewable energy forecasting is critical to power system planning, management, and operations. However, this is a challenging task due to the intermittent and chaotic nature of renewable energy data. To date, various methods have been developed, including physical models, statistical methods, artificial intelligence techniques, and their hybrids to improve the forecasting accuracy of renewable energy. Among them, deep learning, as a promising type of machine learning capable for discovering the inherent nonlinear features and high-level invariant structures in data, has been frequently reported in the literature. This paper provides a comprehensive and extensive review of renewable energy forecasting methods based on deep learning to explore its effectiveness, efficiency and application potential. We divide the existing deterministic and probabilistic forecasting methods based on deep learning into four groups, namely deep belief network, stack auto-encoder, deep recurrent neural network and others. We also dissect the feasible data preprocessing techniques and error post-correction methods to improve the forecasting accuracy. Extensive analysis and discussion of various deep learning based forecasting methods are given. Finally, we explore the current research activities, challenges and potential future research directions in this topic.

Treatment of pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge associated with resistance and early recurrence. There is an urgent need to discover and develop new strategies to enhance treatment efficacy and improve prognosis for pancreatic cancer patients. microRNAs (miRNAs) play critical roles as oncogenes or tumor suppressors in the regulation of cancer development and progression. Our previous study identified miR-15a as a tumor suppressor miRNA and potential therapeutic candidate in PDAC. The expression of miR-15a is significantly down-regulated in PDAC compared to normal pancreas and is associated with proliferation and epithelial mesenchymal transition (EMT) through targeting genes such as BMI-1. In addition to BMI-1, we have identified Wee1, Chk1, and Yap-1 as direct targets of miR-15a in PDAC. We also analyzed the correlation between expression of miR-15a and its downstream target Cdc2 in PDAC clinical samples by real-time PCR and immunochemistry (IHC). Our results show that miR-15a expression is inversely correlated with Cdc2 expression in PDAC tissues and miR-15a expression is significantly associated with prognosis. To further explore the therapeutic potential of miR-15a in PDAC, we have designed a modified version of miR-15a, by replacing uracil residues in the guide strand of miR-15a with 5-Fluorouracil (5-FU). This modified miR-15a mimic combines the therapeutic powers of 5-FU and miR-15a. The miR-15a mimic has improved stability and efficacy compared to the native miR-15a. miR-15a mimic also retains target specificity for Wee1, Chk1, BMI-1 and Yap-1, and regulates the Wee1/Chk1-Cdc25c-Cdc2 signaling pathway. Another unique feature of this miR-15a mimic is that it can be delivered to cancer cells without the aid of a delivery vehicle. The miR-15a mimic has enhanced ability to inhibit the proliferation of a panel of pancreatic cancer cell lines compared to native miR-15a, with IC50 values of 18.713 nM and 37.541 nM respectively. miR-15a induces significant cell cycle arrest at the G1/S checkpoint and miR-15a mimic induces S phase arrest. In addition, we demonstrated that there is a synergistic effect by combining miR-15a mimic and gemcitabine in reducing pancreatic cancer cell proliferation, with reduced IC50 for both drugs. The therapeutic potential of miR-15a mimic was also demonstrated in vivo using a metastatic mouse pancreatic cancer model. miR-15a mimic (3.2 mg/kg) inhibits metastatic tumor growth at a dose that is 15-fold less than that of gemcitabine (50 mg/kg) and the inhibitory effect is enhanced in combination with gemcitabine. While mice treated with gemcitabine alone developed resistance, we did not observe any resistance in mice treated with miR-15a mimic. This study demonstrates that miR-15a mimic has great potential to be further developed as a novel therapeutic drug for treatment of PDAC. Citation Format: Shixiang Guo, Andrew Fesler, Wenjie Huang, Yunchao Wang, Jiali Yang, Xianxing Wang, Ga-Ram Hwang, Matthew Godwin, Huaizhi Wang, Jingfang Ju. Development of a novel modified miR-15a mimic with enhanced therapeutic potential for treatment of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2592.

12 sets of AC-13 asphalt mixture were designed and tested for high temperature stability. According to fractal theory and dynamic stability test results, the correlation equations of fractal dimension and dynamic stability index were established. Using this equation to predict high temperature stability of AC-13 asphalt mixture, it is expected reducing the amount of test, it can provide a reference for engineering design.

This paper proposes a novel method to calculate the best installed capacity of pumped storage power station. First, we choose the day with maximum load as the typical day for every month and simulate the system running in two cases of whether the pumped storage power station is put into operation. The difference of the total coal consumption between the two cases is the peak load shifting benefit. Furthermore, we build load model and power generation model to calculate the benefit of emergency use and frequency modulation, which are the major projects of dynamic benefits. At last, on the premise of ensuring the system requirements, the developed method employs the maximum benefit of the unit capacity as the objective function to get the best installed capacity of pumped storage power station by simulations. Tests on a provincial power grid have shown that the developed method which combines of load characteristics, electric structure and other factors can get the best installed capacity of pumped storage power station easily and has a certain guiding significance for the planning and construction of the pumped storage power station.

Power quality and electromagnetic interference (EMI) control are mandatory for any grid-connected power converter. This paper describes a procedure for LCL filter design in a grid-connected high power density converter (HPDC) with the objective to meet both power quality and EMI requirements. The performance of the LCL filter is simulated and then validated experimentally.

Multidrug resistance-associated protein 3 (MRP3, ABC subfamily C [ABCC]3) plays an important role in protecting hepatocytes and other tissues by excreting an array of toxic organic anion conjugates, including bile salts. MRP3/ABCC3 expression is increased in the liver of some cholestatic patients, but the molecular mechanism of this up-regulation remains elusive. In this report, we assessed liver MRP3/ABCC3 expression in patients (n = 22) with obstructive cholestasis caused by gallstone blockage of bile ducts and noncholestatic patient controls (n = 22). MRP3/ABCC3 messenger RNA (mRNA) and protein expression were significantly increased by 3.4- and 4.6-fold, respectively, in these cholestatic patients where elevated plasma tumor necrosis factor alpha (TNFα) (4.7-fold; P < 0.01) and hepatic specificity protein 1 transcription factor (SP1) and liver receptor homolog 1 expression (3.1- and 2.1-fold at mRNA level, 3.5- and 2.5-fold at protein level, respectively) were also observed. The induction of hepatic MRP3/ABCC3 mRNA expression is significantly positively correlated with the level of plasma TNFα in these patients. In HepG2 cells, TNFα treatment induced SP1 and MRP3/ABCC3 expression in a dose- and time-dependent manner, where increased phosphorylation of c-Jun NH2-terminal kinase/stress-activated protein kinase (JNK/SAPK) was also detected. These inductions were significantly reduced in the presence of the JNK inhibitor, SP600125. TNFα treatment enhanced HepG2 cell nuclear extract-binding activity to the MRP3/ABCC3 promoter, but was abolished by SP600125, as demonstrated by electrophoretic mobility shift assay (EMSA). An increase in nuclear protein-binding activity to the MRP3/ABCC3 promoter, consisting primarily of SP1, was also observed in liver samples from cholestatic patients, as assessed by supershift EMSA assays. Conclusions: Our findings indicate that up-regulation of hepatic MRP3/ABCC3 expression in human obstructive cholestasis is likely triggered by TNFα, mediated by activation of JNK/SAPK and SP1. (HEPATOLOGY 2012)

Pokemon gene has crucial but versatile functions in cell differentiation, proliferation and tumorigenesis. It is a master regulator of the ARF-HDM2-p53 and Rb-E2F pathways. The facts that the expression of Pokemon is essential for tumor formation and many kinds of tumors over-express the Pokemon gene make it an attractive target for therapeutic intervention for cancer treatment. In this study, we used an RNAi strategy to silence the Pokemon gene in a cervical cancer model. To address the issues involving tumor specific delivery and durable expression of siRNA, we applied the Arg-Gly-Asp (RGD) peptide ligand and polylysine (K(18)) fusion peptide to encapsulate a recombinant retrovirus plasmid expressing a siRNA targeting the Pokemon gene and produced the 'mimoretrovirus'. At charge ratio 2.0 of fusion peptide/plasmid, the mimoretrovirus formed stable and homogenous nanoparticles, and provided complete DNase I protection and complete gel retardation. This nanoparticle inhibited SiHa cell proliferation and invasion, while it promoted SiHa cell apoptosis. The binding of the nanoparticle to SiHa cells was mediated via the RGD-integrin α(v)β(3) interaction, as evidenced by the finding that unconjugated RGD peptide inhibited this binding significantly. This tumor-targeting mimoretrovirus exhibited excellent anti-tumor capacity in vivo in a nude mouse model. Moreover, the mimoretrovirus inhibited tumor growth with a much higher efficiency than recombinant retrovirus expressing siRNA or the K(18)/P4 nanoparticle lacking the RGD peptide. Results suggest that the RNAi/RGD-based mimoretrovirus developed in this study represents a novel anti-tumor strategy that may be applicable to most research involving cancer therapy and, thus, has promising potential as a cervical cancer treatment.

The plasma generated by 1064 nm Nd:YAG laser irradiation of aluminum alloy in air at atmospheric pressure was studied spectroscopically. The electron density inferred by measuring the Stark-broadened line profile of Si(I) 288.16 nm decreases with increasing distance from the target surface. The electron temperature was determined using the Boltzmann plot method with nine strong neutral aluminum lines. Due to the thermal conduction towards the solid target and radiative cooling of the plasma as well as conversion of thermal energy into kinetic energy, the electron temperature decreases both at the plasma edge and close to the target surface. Electron density and electron temperature were also studied as functions of laser power density. At the same time, the validity of the assumption of local thermodynamic equilibrium and the effect of selfabsorption were discussed in light of the results obtained.

Background & Aims Levels of bile acid metabolic enzymes and membrane transporters have been reported to change in cholestasis. These alterations (e.g. CYP7A1 repression and MRP4 induction) are thought to be adaptive responses that attenuate cholestatic liver injury. However, the molecular mechanisms of these adaptive responses in human obstructive cholestasis due to gallstone biliary obstruction remain unclear. Methods We collected liver samples from cholestatic patients with biliary obstruction due to gallstones and from control patients without liver disease (n = 22 per group). The expression levels of bile acid synthetic and detoxification enzymes, membrane transporters, and the related nuclear receptors and transcriptional factors were measured. Results The levels of bile acid synthetic enzymes, CYP7B1 and CYP8B1, and the detoxification enzyme CYP2B6 were increased in cholestatic livers by 2.4-fold, 2.8-fold, and 1.9-fold, respectively (p

To explore the application value of the MI-3DVS in patients with hepatic artery variation receiving duodenopancreatectomy.A total of 114 patients who had undergone pancreatoduodenectomy were retrospectively summarized and analyzed during January 2010 to July 2012. The clinical data of 64-slice multidetector CT angiography (64-MDCTA) scanning was introduced into MI-3DVS for procedural segmentation, registration and 3-dimensional reconstruction. Based on the reconstructed 3-dimensional model, the origination and bifurcations of variant hepatic artery was observed. And its anatomical relationships with abdominal organs and vessels were also observed. Thereafter, preoperative procedures planning was formulated. The findings were compared to those found during the operation and by postoperative digital subtraction angiography (DSA) of coeliac artery.The abdominal 3D models can clearly display the size and shape of tumor, the origin and course of the blood vessels, as well as the 3D anatomic relationship between tumors and organs, blood vessels. A total of 14 cases (12.3%, 14/114) were found with variant, including 9 cases (7.9%) with replaced right hepatic artery arising from superior mesenteric artery, 3 cases (2.6%) with replaced common hepatic artery arising from superior mesenteric artery, 2 cases (1.8%) with replaced left hepatic artery arising from left gastric artery. The 14 patients all received standard procedures of duodenopancreatectomy. Compared to the intraoperative findings and postoperative DSA examination, the sensitivity, specificity and accuracy of MI-3DVS to variant hepatic artery is 100%. The preoperative planning guided by MI-3DVS is in line with the intraoperative findings.No postoperative complications occurred in all 14 patients, including hepatic abscesses, biliary fistula and liver failure.MI-3DVS can accurately diagnose hepatic artery variation before duodenopancreatectomy. Therefore, it contributes to the formulation of preoperative surgical plans.It also increases the success rate of the surgical operations and decreases the occurrence of postoperative complications.

The objective of this study was to investigate the expression and clinical relevance of interleukin 22 (IL-22) and IL-22-producing CD4 T cells (IL-22CD4 T cells) in pancreatic cancer (PC) tissues.Interleukin 22 protein levels in PC tissues were measured by Western blot analysis and immunohistochemistry. The frequencies of IL-22CD4 T cells in tumors and peripheral blood from PC patients and control subjects were analyzed by flow cytometry. The association between IL-22 and phosphorylation of STAT-3 was investigated in in vitro model.Interleukin 22 protein was more highly expressed in PC tissues than in peritumoral and normal pancreatic tissues. The frequencies of all IL-22CD4 T cells and T helper 22 (TH22) cells (IL-22IFN-γIL-17CD4) were significantly higher in PC tissues than in the peripheral blood of PC patients and control subjects. It was observed that up-regulation pSTAT-3 and its downstream genes such as Bcl-2 and cyclin D1 in vitro. Finally, we found that increased intratumoral IL-22 expression and frequencies of TH22 and IL-22CD4 T cells were positively correlated with PC tumor-node-metastasis staging.Increased intratumoral IL-22 levels, IL-22CD4 T cells, and TH22 cells are correlated with PC tumor-node-metastasis staging, suggesting that IL-22 and IL-22CD4 T cells may be related to tumor progression and are potential therapeutic targets in patients with PC.

This study aimed to investigate the clinical significance of 3-dimensional (3D) reconstruction of peripancreatic vessels for patients with suspected pancreatic cancer (PC).A total of 89 patients with PC were included; 60 patients randomly underwent computed tomographic angiography. Based on the findings of 3D reconstruction of peripancreatic vessels, the appropriate method for individualized tumor resection was determined. These patients were compared with 29 conventionally treated patients with PC.The rate of visualization was 100% for great vessels around the pancreas. The detection rates for anterior superior pancreaticoduodenal artery, posterior superior pancreaticoduodenal artery, anterior inferior pancreaticoduodenal artery, posterior inferior pancreaticoduodenal artery, dorsal pancreatic artery, superior marginal arterial branch of the pancreatic head, anterior superior pancreaticoduodenal vein, posterior superior pancreaticoduodenal vein, anterior inferior pancreaticoduodenal vein, and posterior inferior pancreaticoduodenal vein were 86.6%, 85.0%, 76.6%, 71.6%, 91.6%, 53.3%, 61.6%, 55.0%, 43.3%, and 51.6%, respectively. Forty-three patients who had undergone 3D reconstruction underwent surgery. Of the 29 conventionally treated patients, 19 underwent surgery. The operative time, blood loss, length of hospital stay, and complication incidence of the 43 patients were superior to that of the 19 patients.A peripancreatic vascular reconstruction can reveal the vascular anatomy, variations of peripancreatic vascular, and tumor-induced vascular changes; the application of the simulation surgery platform could reduce surgical trauma and decrease operative time.

The use of prosthetic grafts for superior mesenteric-portal vein reconstruction (SMPVR) after pancreaticoduodenectomy (PD) with venous resection remains controversial. We evaluated the effectiveness and safety of using polytetrafluoroethylene (PTFE) interposition grafts for SMPVR after PD. We identified 76 patients who underwent PD with segmental vein resection for pancreatic head and periampullary neoplasms at three centers between January 2007 and June 2012. The venous reconstruction technique depended on the length of venous involvement. Forty-two and 34 patients underwent SMPVR with primary anastomosis and SMPVR with PTFE interposition grafts, respectively. The postoperative morbidity, mortality, and patency were compared. For the patients with pancreatic ductal adenocarcinoma (n = 65), survival was compared between the SMPVR with primary anastomosis (n = 36) and SMPVR with PTFE interposition graft groups (n = 29). Patients undergoing SMPVR with PTFE grafts had larger tumor sizes (3.4 ± 0.9 cm, 2.9 ± 0.9 cm, P = 0.016), longer operative durations (492.9 ± 107.5 min, 408.8 ± 78.8 min, P

Purposes To investigate whether miR-15a inhibits cell proliferation and epithelial–mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) via the down-regulation of B cell-specific moloney murine leukemia virus insertion site 1 (Bmi-1) expression. Methods and Results miR-15a and Bmi-1 expressions in normal pancreatic tissue and PDAC tissue were measured. The relationship between miR-15a and Bmi-1 expression was analyzed. We found that miR-15a suppressed the expression of Bmi-1 and PDAC cell proliferation; E-cadherin expression was visibly up-regulated after silencing Bmi-1 by transfecting miR-15a into PDAC cell line. Conclusion miR-15a inhibits cell proliferation and EMT in PDAC via the down-regulation of Bmi-1 expression.

Apigenin is a potential chemopreventive agent for cancer prevention. Because of the central role of transcription factor nuclear factor-κB (NF-κB) in pancreatic cancer, we investigated the roles of NF-κB in apigenin-induced growth inhibition in pancreatic cancer cells. It showed that apigenin reduced cell growth and induced apoptosis in the cells. Apigenin treatment down-regulated not only basal but also TNF-α-induced NF-κB DNA binding activity, NF-κB transcription activity, inhibitor of κB (IκB)-α phosphorylation together with translocation of p65 and p50, and it accompanied with the blockade of IκB kinase (IKK)-β activity. Moreover, IKK blockage potentiated the anticancer efficacy of apigenin and IKK-β overexpression attenuated the apigenin-induced cell growth inhibition. Additionally, apigenin (30 mg/kg) administration suppressed pancreatic cancer growth and IKK-β activation in nude mice xenograft. These results indicated that apigenin had a potential to inhibit IKK-β-mediated NF-κB activation, and was a valuable agent for the pancreatic cancer treatment.

Double common bile duct (DCBD) is a rare congenital anomaly of the biliary system, often associated with biliary lithiasis, choledochal cyst, pancreaticobiliary maljunction (PBM), and upper gastrointestinal tract malignancies. We report a case of type I DCBD with choledochal cyst and cholelithiasis in a 52-year-old Chinese man. We also reviewed 24 cases of DCBD reported in the Chinese literature between 1965 and 2012. Most (58.3%) of these cases were classified as type I DCBD, with accompanying choledocholithiasis in 79.2%, cholecystolithiasis in 37.5%, choledochal cyst in 33.3%, and PBM in 8.3%. There was no case of concomitant cancer. The type and coexistence of PBM with DCBD are clinically important because of its close implications with concomitant pathology. Most Chinese people with DCBD have type I. Moreover, the high incidences of choledochal cyst and biliary lithiasis and the extremely low incidences of PBM and biliary cancer are the major clinical characteristics of DCBD in China.

Objective To establish a new standard for assessing the resectability of pancreatic and periampullary tumors by the Medical Image Three-Dimensional Visualization System (MI-3DVS). Methods Eighty cases of pancreatic and periampullary tumors were examined. The 64-slice multidetector CT (64-MDCT) images and patient data were processed by MI-3DVS. The main elements examined by MI-3DVS included tumor shape, size, and location; distribution of related vessels; luminal morphology of large vessels; distribution and morphology of the small peripancreatic veins; morphology, degree of dilation, and obstructive sites of bile and pancreatic ducts. Based on vascular characteristics of MI-3DVS findings, the cases were classified into five types. Type I and II were resectable, type III were potentially resectable or resectable with combined vascular resection and reconstruction, and type IV and V were unresectable. The outcome was then compared with corresponding CT angiography (CTA) analysis and actual surgical observations. Results Among the 80 cases, MI-3DVS indicated that 60 were resectable and the remaining 20 were not. In contrast, CTA indicated 50 resectable cases and 30 unresectable cases. For 57 cases of pancreatic ductal carcinomas and all 80 cases periampullary tumors, MI-3DVS assessment yielded a positive predictive value of 100%, negative predictive value of 100%, a sensitivity of 100%, a specificity of 100%, and an accuracy of 100%. While CTA generated corresponding values of 96%, 60%, 80%, 90%, 82.5%. The overall differences between the two methods were significant ( P Conclusion The new classification system is able to reliably assess the resectability of pancreatic and periampullary tumors.

The main cause of gastroesophageal variceal bleeding (GEVB) is portal hypertension (PH) due to liver cirrhosis. Here, we report a case of regional PH and refractory GEVB secondary to neuroendocrine carcinoma (NC) in the pancreatic tail. This condition was treated using a pancreatic tail resection, splenectomy, and portal azygous devascularization. Regional PH caused by a pancreatic NC is rare and is usually presented as isolated gastric varices. This case report of regional PH details simultaneous esophageal and gastric varices that were caused by a pancreatic NC, which is a rare occurrence. Therefore, after excluding liver cirrhosis, unusual causes should be considered in cases of refractory GEVB with PH. and IAP.

Hepatic multidrug resistance-associated protein 4 (Mrp4) levels are low, but increase markedly in rodent cholestatic liver. Nuclear receptors (NRs) are essential for regulating Mrp4 expression in cholestasis models. However, information about MRP4 and related NRs, including constitutive androstane receptor (CAR), pregnane X receptor (PXR), and retinoic X receptor-α (RXRα), is relatively lacking in human obstructive cholestasis. We collected liver samples from patients with obstructive cholestasis or without liver disease and investigated the expression of MRP4 and NRs CAR, PXR, and RXRα by semi-quantitative RT-PCR, Western blot and immunostaining assays.MRP4 mRNA/protein levels were markedly increased in obstructive cholestasis. Concentration of serum total bile acids (TBA) was significantly correlated with MRP4 protein in cholestasis samples (P 0.01). PXR and RXRα mRNA/protein levels were significantly increased in obstructive cholestasis. CAR mRNA levels were unchanged while protein levels were markedly induced in obstructive cholestasis. There was a statistically positive correlation between MRP4 mRNA and CAR protein (P 0.05), suggesting that CAR may activate transcription of MRP4 genes by its nuclear translocation.Hepatic MRP4 levels were dramatically induced in human obstructive cholestasis, which may reduce liver injury by increasing efflux of toxic bile acids from hepatocytes into blood.