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BackgroundMild cognitive impairment (MCI), a syndrome defined as decline of cognitive function greater than expected for an individual’s age and education level, occurs in up to 22.7% of elderly patients in United States, causing the heavy psychological and economic burdens to families and society. Cellular senescence (CS) is a stress response that accompanies permanent cell-cycle arrest, which has been reported to be a fundamental pathological mechanism of many age-related diseases. This study aims to explore biomarkers and potential therapeutic targets in MCI based on CS.MethodsThe mRNA expression profiles of peripheral blood samples from patients in MCI and non-MCI group were download from gene expression omnibus (GEO) database (GSE63060 for training and GSE18309 for external validation), CS-related genes were obtained from CellAge database. Weighted gene co-expression network analysis (WGCNA) was conducted to discover the key relationships behind the co-expression modules. The differentially expressed CS-related genes would be obtained through overlapping among the above datasets. Then, pathway and GO enrichment analyses were performed to further elucidate the mechanism of MCI. The protein–protein interaction network was used to extract hub genes and the logistic regression was performed to distinguish the MCI patients from controls. The hub gene-drug network, hub gene-miRNA network as well as transcription factor-gene regulatory network were used to analyze potential therapeutic targets for MCI.ResultsEight CS-related genes were identified as key gene signatures in MCI group, which were mainly enriched in the regulation of response to DNA damage stimulus, Sin3 complex and transcription corepressor activity. The receiver operating characteristic curves of logistic regression diagnostic model were constructed and presented great diagnostic value in both training and validation set.ConclusionEight CS-related hub genes – SMARCA4, GAPDH, SMARCB1, RUNX1, SRC, TRIM28, TXN, and PRPF19 – serve as candidate biomarkers for MCI and display the excellent diagnostic value. Furthermore, we also provide a theoretical basis for targeted therapy against MCI through the above hub genes.

The incidence of pancreatic duct stones (PDS) is less than 1%. After the formation of stones, the lumen of the pancreatic duct is blocked, and the pancreatic juice cannot be discharged smoothly, resulting in the impairment of the internal and external secretions of the pancreas. Several national guidelines now recommend endoscopic retrograde cholangiopancreatography (ERCP) as the treatment for PDS. The emergence of SpyGlass makes it possible to visualize the ERCP blind area of the pancreatic system directly. Electrohydraulic lithotripsy (EHL) under SpyGlass can crush large and pressure-resistant stones into smaller fragments, significantly improving the success of the endoscopic treatment of large stones. Here, we report a patient presented with acute alcohol-associated pancreatitis, found to have PDS on imaging, who underwent ERCP combined with SpyGlass (EHL), avoiding surgery, reducing trauma, and being discharged from the hospital with a rapid recovery. Therefore, endoscopic therapy is effective and safe for PDS patients. The combination therapy of this patient is the first use of SpyGlass for PDS in our centre, which marks a new stage in the application of endoscopic therapy for pancreatic diseases.

Additional file 1: The details of the real datasets, implementation of baseline methods and additional tables and plots.

Cholangiocarcinoma is a malignant tumor originating from the bile duct epithelium, with the increasing incidence year by year. Its early symptoms are atypical and the diagnosis rate is low. Most of the patients are already in advanced stage when they are diagnosed, losing the best surgery period. Currently, the conservative treatments for unresectable extrahepatic cholangiocarcinoma include stent placement, radiofrequency ablation, radiotherapy and chemotherapy, targeted and immunotherapy and other systemic treatments. But due to the high malignancy of biliary tract tumors, the tendency to develop drug resistance and the limited population benefited from the emerging treatment modalities, we urgently need to explore new treatment strategies to break this bottleneck. As a new treatment for cholangiocarcinoma, photodynamic therapy has attracted much attention for its clinical application and therapeutic effects. In this paper, we summarize the principles of photodynamic therapy, the combination of photodynamic and other therapeutic modalities, especially the combination of photodynamic with emerging immune and targeted therapies, and describe the current hotspot directions of photodynamic therapy research at home and abroad to provide reference for clinical treatment and research.

The doubly-fed induction generator (DFIG) with virtual inertia control and reactive damping control gives a renewable energy generation system inertia and damping characteristics similar to those of a thermal power plant, and the parameters of the control strategy have a direct impact on the small-signal stability of the system. This paper firstly introduces the operating characteristics and control strategies of DFIG-based damping control and virtual inertia control, establishes a small-signal model of the control-based DFIG integrated interconnected system, and investigates the effects of virtual inertia and reactive damping values on the small-signal stability of the system; then, the maximum damping ratio of the interval oscillation mode in small disturbance analysis is taken as the optimization objective, and the control parameters are the optimization variables. An optimization method of inertia and damping parameters is established for improving the small disturbance stability of the system. The results show that the optimization procedure could improve the damping ratio of the interval oscillation mode while ensuring the system frequency. The effects of virtual inertia and reactive damping values on the small signal stability of the system are investigated, and an optimal allocation model and method for virtual inertia used to improve the small disturbance stability of the system is proposed.

В работе представлены результаты исследований по получению композитов при обработке алюминиевого расплава на основе высокопрочного сплава В95 активированными дисперсными частицами нитридов (AlN, Si3N4, TiN), карбидов (SiC, TiC), наноструктурированного углерода (фуллереновой сажи), азотсодержащими компонентами (глицин C2H5NO2, карбамид CH4N2O). Приведена оценка прочностных свойств получаемых композитов от режимов активации шихты с дисперсными частицами и режимов термообработки материала. Показана возможность повышения прочностных характеристик литейного композита на 15–20 % за счет дополнительной механоактивации шихты и достижения после термической обработки предела прочности при сжатии 900–1050 МПа, твердости 150–160 НВ, модуля упругости 20–25 ГПа.

Background Eliglustat, a new oral substrate-reduction therapy, was recently approved as a first-line therapy for Gaucher's disease type 1 (GD1) patients. Purpose The purpose of the present study was to develop and validate a simple UPLC-MS/MS method for the measurement of plasma-eliglustat concentration and to investigate the effects of amiodarone and quinidine on eliglustat metabolism in rats. Methods Eighteen rats were randomly divided into three groups (n=6): control (0.5% CMC-Na, group A), amiodarone (60 mg/kg, group B), and quinidine (100 mg/kg, group C). Thirty minutes later, 10 mg/kg eliglustat was orally administered to each rat and concentrations of eliglustat in the rats determined by our UPLC-MS/MS method. Results Amiodarone and quinidine increased the main pharmacokinetic parameters (AUC0→t, AUC0→∞, and Cmax) of eliglustat significantly and decreased clearance obviously. Conclusion Amiodarone and quinidine can elevate eliglustat exposure and have an inhibitory effect on eliglustat metabolism. Clearly, appropriate pharmacological studies of eliglustat in patients treated with amiodarone or quinidine should be done in future.

KRAS mutant lung adenocarcinomas remain intractable for targeted therapies. Genetic interrogation of KRAS downstream effectors, including the MAPK pathway and the interphase CDKs, identified CDK4 and RAF1 as the only targets whose genetic inactivation induces therapeutic responses without causing unacceptable toxicities. Concomitant CDK4 inactivation and RAF1 ablation prevented tumor progression and induced complete regression in 25% of KRAS/p53-driven advanced lung tumors, yet a significant percentage of those tumors that underwent partial regression retained a population of CDK4/RAF1-resistant cells. Characterization of these cells revealed two independent resistance mechanisms implicating hypermethylation of several tumor suppressors and increased PI3K activity. Importantly, these CDK4/RAF1-resistant cells can be pharmacologically controlled. These studies open the door to new therapeutic strategies to treat KRAS mutant lung cancer, including resistant tumors. We thank S. Ortega for the generation of the Cdk4FxKD mouse model; and M. San Roman, R. Villar, M. C. Gonzalez, A. Lopez, N. Cabrera, P. Villanueva, J. Condo, J. Klett, A. Cebria, A. Otero, O. Dominguez, G. Luengo, G. Garaulet, F. Mulero, and D. Megias for excellent technical support. This work was supported by European Research Council Grant ERC-2015-AdG/695566, THERACAN, Spanish Ministry of Science, Innovation, and Universities Grant RTC-2017-6576-1, and the Autonomous Community of Madrid Grant B2017/BMD-3884 iLUNG-CM (to M.B.); Spanish Ministry of Science, Innovation, and Universities Grant RTI2018-094664B-I00 (to M.B. and M.M.); and National Natural Science Foundation of China Grant 31771469 (to H.W.). M.B. is a recipient of an Endowed Chair from the AXA Research Fund. L.E.-B. is the recipient of an FPI fellowship from the Spanish Ministry of Economy and Competitiveness. F.F.-G., M.S., and P.N. were supported by an FPU fellowships from the Spanish Ministry of Education. Sí

Qiong Wang,1 Haiyun Wang,1 Youyan Zhong,1 Qiang Zhang2 1Department of Pharmacy, Wenzhou People’s Hospital, Wenzhou, Zhejiang 325000, People’s Republic of China; 2Department of Clinical Laboratory, The People’s Hospital of Lishui, Lishui, Zhejiang 323000, People’s Republic of ChinaCorrespondence: Qiang ZhangDepartment of Clinical Laboratory, The People’s Hospital of Lishui, Lishui, Zhejiang 323000, People’s Republic of ChinaEmail zhangqianglsrmyy@sina.comBackground: Eliglustat, a new oral substrate-reduction therapy, was recently approved as a first-line therapy for Gaucher’s disease type 1 (GD1) patients.Purpose: The purpose of the present study was to develop and validate a simple UPLC-MS/MS method for the measurement of plasma-eliglustat concentration and to investigate the effects of amiodarone and quinidine on eliglustat metabolism in rats.Methods: Eighteen rats were randomly divided into three groups (n=6): control (0.5% CMC-Na, group A), amiodarone (60 mg/kg, group B), and quinidine (100 mg/kg, group C). Thirty minutes later, 10 mg/kg eliglustat was orally administered to each rat and concentrations of eliglustat in the rats determined by our UPLC-MS/MS method.Results: Amiodarone and quinidine increased the main pharmacokinetic parameters (AUC0→t, AUC0→∞, and Cmax) of eliglustat significantly and decreased clearance obviously.Conclusion: Amiodarone and quinidine can elevate eliglustat exposure and have an inhibitory effect on eliglustat metabolism. Clearly, appropriate pharmacological studies of eliglustat in patients treated with amiodarone or quinidine should be done in future.Keywords: eliglustat, drug–drug interaction, UPLC-MS/MS, amiodarone, quinidine

The Fourier amplitude spectrum of acceleration will drop rapidly in the high frequency range. Anderson and Hough quantitatively studied the attenuation law of the acceleration Fourier spectrum above the corner frequency, and proposed the high-frequency attenuation parameter Kappa ( ) to describe this phenomenon. It has important applications in the field of engineering earthquakes, and is widely used by seismologists and engineers in the work of ground motion simulation and attenuation relations. Based on the Anderson method, this paper proposed a method of first smoothing the Fourier acceleration spectrum with a 0.4 Hz Parzen window and then fitting the solution value. The Fukushima earthquake data from Japan’s KiK-net seismic network on February 13, 2021 was used to verify the reliability of the method. The results showed that when the width of the Parzen window was set to 0.4 Hz, the calculation accuracy of the value was effectively improved.

The Whitney (2018) linear baseline correction method is used to analyze the near-fault strong motion data of the 1999 Chi-Chi earthquake and quickly calculate the co-seismic displacement. The feasibility of this method is verified by comparison with the coseismic displacement data of adjacent GPS stations. The results show that the coseismic displacement of the hanging wall is significantly larger than that of the foot wall, and largest displacements reached 707.0cm north and 369.7cm up respectively, and occurred at the hanging wall station TCU052. The results in this paper can provide references for the rapid identification of coseismic displacements using strong motion data.

This paper evaluates application feasibility of a Hybrid Multi-terminal HVDC system and wind-thermal-bundled plants simulated in DIgSLIENT PowerFactory environment. The proposed hybrid MTDC system consists of two line-communicated converters (LCC), which are connected to both wind farms and thermal power plants, and one voltage source converter (VSC) at the grid side. Control strategies for each converter are designed to handle this system under different disturbance conditions. Simulation results show that the wind power fluctuation can be compensated by the thermal-generated power. Results demonstrate the effectiveness of the proposed control strategies of the hybrid MTDC system compared to a conventional MTDC system. The proposed scheme combines advantages of both LCC and VSC HVDC systems and provides a new way to transmit wind power over long distances to the main grid.

High-altitude and cold regions (HACR) have extremely low temperatures accompanied by frequent cold currents in winter, causing significant thermal stress and cracking in concrete structures. Based on previous studies, by using ABAQUS as the development platform and FORTRAN as the development tool, a calculation program for temperature fields during concrete dam construction and operation processes was established to test the accuracy of the program. Jinqiao Rock-filled Concrete (RFC) Gravity Dam, located in HACR of Tibet, China, is as an example to simulate the thermal stress under three working conditions. The results show that: (1) the hydration temperature rise of RFC is lower than that of normal concrete; the use of RFC can reduce the temperature and thermal stress of the concrete dam. (2) In HACR, installing an insulation layer on the surface of the dam body can significantly increase the surface temperature and reduce its difference and tensile stress, meeting the requirements of temperature control and crack prevention.

This study presents an optimal design of a combined cooling, heating and power generation system consists of a heat recovery system, a 5 kW proton exchange membrane stack, a small absorption chiller, a humidifier, and a gas compressor based on multi-criteria assessment for apartment simultaneously. The system is analyzed in terms of economics, environment, and thermodynamics. An improved version of butterfly optimization algorithm is employed for optimizing the system performance. The system efficiency is analyzed based on annual cost, exergy and energy efficiencies, and pollutant emission reduction. Final results illustrated that high relative humidity, pressure of inlet gases, and low operating temperature develop GHG emission reduction and system exergy performance. The optimized values of annual GHG reduction and exergy efficiency are 2.67e7 g and 47.1%, respectively, meanwhile, annual cost can be decreased to 3.139e3 $.

The local site effect of vibration propagation during earthquakes is usually considered by one-dimensional site response analysis, while the ground motion of the site is the result of the combined effect of the source, the propagation path and the local site conditions. In the study, the influence of ground motion input, soil layer properties and analysis methods need to be considered. Based on a large number of related literatures, this paper briefly summarizes the research status of seismic response of one-dimensional soil layer sites through the determination of bedrock ground motions, soil dynamic constitutive models, and analysis methods. In the future, the development of seismic response of soil sites is prospected and summarized.

Several anti-angiogenic cancer drugs that inhibit VEGF receptor (VEGFR) signalling for efficacy are associated with a 15-60% incidence of hypertension. Tyrosine kinase inhibitors (TKIs) that have off-target activity at VEGFR-2 may also cause blood pressure elevation as an undesirable side effect. Therefore, the ability to translate VEGFR-2 off-target potency into blood pressure elevation would be useful in development of novel TKIs. Here, we have sought to quantify the relationship between VEGFR-2 inhibition and blood pressure elevation for a range of kinase inhibitors.Porcine aortic endothelial cells overexpressing VEGFR-2 (PAE) were used to determine ICAll-grade hypertension was predominantly observed when the CTaken together, these data show that the risk of blood pressure elevation is proportional to the amount of VEGFR-2 inhibition, and a margin of10-fold between VEGFR-2 IC

For the Sr2-xIrO4 system, recent work pointed out the abnormal electronic and magnetic properties around the critical point. Here, to understand Sr-vacancy effect on spin-orbit coupled Mott insulator Sr2IrO4, the electronic structure and local structure distortion for Sr2-xIrO4 system have been investigated by x-ray absorption spectroscopy (XAS). By comparing the intensity of white-line features at the IrL2,3-edge x-ray absorption near-edge spectroscopy (XANES), we observe a sudden rise of the branching ratio in the vicinity of the critical point.Further analysis on theIrL3 -edge extended x-ray absorption fine structure (EXAFS) and calculated data demonstrated that the abrupt enhancement of the branching ratio is intimately related to the less distorted IrO6 octahedra induced by deep Sr-vacancies, which in turn alters the relatively strength of the spin-orbit coupling (SOC) and crystal electric field (CEF)that would dictate the abnormal behavior of electronic and magnetic structure near the critical point., 18 pages, 5 figures. arXiv admin note: text overlap with arXiv:1610.09839

Sr2IrO4 exhibits a novel insulating state assisted by spin-orbit interactions. A series of polycrystalline samples of Sr2-xIrO4 have been synthesized. It is found that deep Sr-vacancies of Sr2-xIrO4 greatly reduce the rotation of IrO6 octahedral, and more importantly, a significant structural change occurs around x = 0.48 in both the lattice constants and the Ir-O2 bond length. An insulator-metal transition (IMT) appears and a non-Fermi-liquid metallic electronic state has been proved at x>0.48 in Sr2-xIrO4. Furthermore, a sudden drop emerges of the localization temperature T0 and the antiferromagnetic (AFM) transition temperature TN in Sr1.5IrO4, together with the Curie-Weiss temperature reversing its sign. These abrupt changes are closely related with the reduction of the rotation crystal structure., 31 pages, 13 figures

The power battery of electric vehicle may be limited by battery safety issues and power problems. The key points of this paper are firstly it combines discrete Frechet distance method with discharge curve identification method, and then it proposes a kind of new state of health diagnose method base on line testing platform. Through the CAN communication module, the system could control the power battery to finish on line full charge and discharge test. And also the system could get the actual operational status data to build life cycle databases of electric vehicle, which can predict the state of health diagnose. The results of the SOH could guide power battery safety assessment and balance maintain. Through analyzing simulation results between the SOH diagnose results with returned test data results, qualitative indicates the decline of EV battery.

The paraconductivity of both electron- and hole-doped LaOFeAs superconductors is studied within the existed fluctuation mechanisms. It is found that the FC data at the temperature close to T c can be explained with the three-dimensional (3D) Aslamazov–Larkin (AL) theory. The Gaussian–Ginzburg–Landau (GGL) approach under various cutoff conditions can only account for the fluctuation conductivity (FC) data in the 3D AL regime. While the approach taking into account the pseudogap effect can describe the paraconductivity very well in the whole temperature region. This result suggests that the pseudogap state of doped LaOFeAs system is probably due to the formation of paired fermions in the form of strongly bound bosons (local pairs) at T c T T ∗ .

The dimensional characteristic is studied through magnetoresistance of an F-doped SmFeAsO superconductor reported in literature. The fluctuation conductivity is scaled within both three-dimensional (3D) and two-dimensional (2D) Lowest Landau Level (LLL) approaches. It is found that the 3D LLL scaling can be clearly seen but in a relatively small temperature interval below T c(H), while 2D LLL scaling is observed in all other temperature regions. Moreover, the lower part of the magnetoresistance can be scaled within the modified Kosterlitz–Thouless (KT) transition proposed in our previous work.

The fluctuation conductivity under magnetic fields is studied in RFeAsO ( R = Nd , Pr , Sm ) superconductors reported in literatures within the lowest Landau level (LLL) scaling approach. The mean filed critical temperature T c ( H ) is determined by the crossing point technique. With the determined values of T c ( H ) , the fluctuation conductivity is scaled within both three-dimensional (3D) and two-dimensional (2D) LLL approach. For all the samples studied, the 3D-LLL scaling is found but in a relatively small temperature interval around T c ( H ) , while 2D-LLL scaling is observed in all other temperature region. These results suggest a 3D–2D crossover of the fluctuation conductivity in RFeAsO superconductors.

The scaling relation of single parameter scaling hypothesis is applied to the study of the scaling behavior of high temperature superconductors under pressure. The data of resistance and magnetization under various pressures are scaled onto a universal curve according to this scaling relation. The scaling parameters are pressure dependent while temperature independent. It is found that the controlling parameter B i equals the relative critical temperature t cP , which indicates that the superconducting energy gap at the zero temperature 2Δ s0 is the controlling parameter in this scaling.

The scaling relation of single parameter scaling hypothesis is applied to the study of the scaling behavior of high temperature superconductors under pressure. The data of resistance and specific heat coefficient under various pressures are scaled onto a universal curve according to this scaling relation. The scaling parameters are pressure dependent while temperature independent. It is found that the controlling parameter B i equals to the relative critical temperature t cP , which indicates that the superconducting energy gap at the zero temperature 2 Δ s 0 is the controlling parameter in this scaling.

Multiple-Graphics Processing Units (Multi-GPUs) means using two or more display adapters in the same PC to speed up the graphics animation for gamers. In this paper, we provide a way of using multi-GPUs in image processing acceleration based on NVIDIA CUDA technique that makes the processing progress more flexible and controllable. For demonstration we deal with canny edge detection using GTX295, which with the power of two GeForce GTX 200 GPUs on a single card, we show how to use multi-GPUs when accelerating image processing. Also, we did some optimization work. We found out that in image processing which contains mass data and complex algorithm, by using multi-GPUs the processing time almost can be reduced to half; however in the case have less data and simple algorithm, the advantage of multi-GPUs is not obvious even takes more time.

The conduct of the town sewage treatment plant process commissioning CAST experimental study and the actual control results show that bio-stable phase, a significant treatment effect, the effluent compliance indicators control of temperature, dissolved oxygen, sedimentation ratio, sludge index, biological phase changes, run the cycle of 4.5 h, compared with 35% of the settlement, sludge age 15d, biota DO 31mg / L, to achieve biological bacteria the best kind of training and acclimation conditions, the sludge concentration is up to 2000mg / L.

The temperature dependence of the resistivity ρ(T) of 122-Fe-pnictides is studied. The normal state resistivity ρn(T) is analyzed with the scaling method. It is found that the ρn(T) data can be scaled onto the universal curves for optimal, overdoped and underdoped samples, by using the energy scale Δ, the resistivity ρΔ and the residual resistivity ρ0 as the scaling parameters, where the universal curves can be described by an exponential function. The overall resistivity can be described by a uniform formula by taking the three-dimensional (3D) Aslamazov–Larkin (AL) fluctuation contribution into account, which is consistent with the two-channel scenario proposed for the cuprate superconductors.

Background Development of robust and efficient methods for analyzing and interpreting high dimension gene expression profiles continues to be a focus in computational biology. The accumulated experiment evidence supports the assumption that genes express and perform their functions in modular fashions in cells. Therefore, there is an open space for development of the timely and relevant computational algorithms that use robust functional expression profiles towards precise classification of complex human diseases at the modular level. Results Inspired by the insight that genes act as a module to carry out a highly integrated cellular function, we thus define a low dimension functional expression profile for data reduction. After annotating each individual gene to functional categories defined in a proper gene function classification system such as Gene Ontology applied in this study, we identify those functional categories enriched with differentially expressed genes. For each functional category or functional module, we compute a summary measure (s) for the raw expression values of the annotated genes to capture the overall activity level of the module. In this way, we can treat the gene expressions within a functional module as an integrative data point to replace the multiple values of individual genes. We compare the classification performance of decision trees based on functional expression profiles with the conventional gene expression profiles using four publicly available datasets, which indicates that precise classification of tumour types and improved interpretation can be achieved with the reduced functional expression profiles. Conclusion This modular approach is demonstrated to be a powerful alternative approach to analyzing high dimension microarray data and is robust to high measurement noise and intrinsic biological variance inherent in microarray data. Furthermore, efficient integration with current biological knowledge has facilitated the interpretation of the underlying molecular mechanisms for complex human diseases at the modular level.

The Circular Electron Positron Collider (CEPC) is a large international scientific facility proposed by the Chinese particle physics community to explore the Higgs boson and provide critical tests of the underlying fundamental physics principles of the Standard Model that might reveal new physics. The CEPC, to be hosted in China in a circular underground tunnel of approximately 100 km in circumference, is designed to operate as a Higgs factory producing electron-positron collisions with a center-of-mass energy of 240 GeV. The collider will also operate at around 91.2 GeV, as a Z factory, and at the WW production threshold (around 160 GeV). The CEPC will produce close to one trillion Z bosons, 100 million W bosons and over one million Higgs bosons. The vast amount of bottom quarks, charm quarks and tau-leptons produced in the decays of the Z bosons also makes the CEPC an effective B-factory and tau-charm factory. The CEPC will have two interaction points where two large detectors will be located. This document is the second volume of the CEPC Conceptual Design Report (CDR). It presents the physics case for the CEPC, describes conceptual designs of possible detectors and their technological options, highlights the expected detector and physics performance, and discusses future plans for detector R&D and physics investigations. The final CEPC detectors will be proposed and built by international collaborations but they are likely to be composed of the detector technologies included in the conceptual designs described in this document. A separate volume, Volume I, recently released, describes the design of the CEPC accelerator complex, its associated civil engineering, and strategic alternative scenarios., 424 pages