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Yu Wang,1,* Hanning Zha,1,* Xiang Fang,2 Tianjiao Shen,1 Kunyun Pan,1 Jianping Zhang,1 Keqiang He,1 Sheng Wang,1 Liguo Hu1 1Department of Anesthesiology, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2Department of Anesthesiology, Hefei BOE Hospital, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Sheng Wang; Liguo Hu, Email iamsheng2020@ustc.edu.cn; hulg@163.comObjective: The dose selection of ropivacaine for spinal anesthesia in clinical work mainly depends on the experience of the anesthesiologist. In this study, a prospective and modified up-down sequential allocation design was used to provide the optimal dose selection of ropivacaine for spinal anesthesia.Patients and methods: This study was divided into two stages, and a total of 164 elderly patients with elective hip fractures were included. In stage I, the dose of ropivacaine was selected using the up-down sequential method of height correction, and the 50% effective dose (ED50) and 95% effective dose (ED95) were obtained. A nomogram for predicting satisfactory anesthesia and a formula for predicting the optimal dose was also given in this stage. In stage II, the dose of ropivacaine was calculated by using the optimal dose prediction formula, so as to evaluate the efficacy and safety of the model.Results: The ED50 and ED95 of the stage I were 7.036 mg (95%CI 6.549– 7.585 mg) and 8.709 mg (95%CI 7.902– 14.275 mg), respectively. And provided a nomogram predicting satisfactory anesthesia with a C-index of 0.847 (95%CI 0.774– 0.92). The optimal dose prediction formula of ropivacaine was calculated, including variables for age, gender, height, and weight. This formula was found to be 90% efficient. It is worth mentioning that the incidence of direct transfer to the ward in the

This paper presents a systematic methodology to optimise the geometry of a three-body hinge-barge wave energy converter, to maximise the energy extraction of the device in given sea states and in site specific wave climates. To that end, a 5-degree-of-freedom mathematical model is proposed to describe the system dynamics in two-dimensional space and a two-layer optimisation is designed to find the optimal design and control variables. The inner-layer optimisation is used to find the optimal control parameters of the power take-off system and the outer-layer optimisation, which uses a genetic algorithm, is employed to find the optimal design parameters of barge lengths and of optimal ballast positioning. In the case study, this methodology is applied to a 1:20 scale prototype of the McCabe Wave Pump device. Numerical results indicate that the optimal dimensions of the device, under given sea states, can be found efficiently and accurately, and that there appears to be no obvious benefit in the use of three barges, over a two-barge system.

This paper presents a systematic methodology to optimise the geometry of a three-body hinge-barge wave energy converter, to maximise the energy extraction of the device in given sea states and in site specific wave climates. To that end, a 5-degree-of-freedom mathematical model is proposed to describe the system dynamics in two-dimensional space and a two-layer optimisation is designed to find the optimal design and control variables. The inner-layer optimisation is used to find the optimal control parameters of the power take-off system and the outer-layer optimisation, which uses a genetic algorithm, is employed to find the optimal design parameters of barge lengths and of optimal ballast positioning. In the case study, this methodology is applied to a 1:20 scale prototype of the McCabe Wave Pump device. Numerical results indicate that the optimal dimensions of the device, under given sea states, can be found efficiently and accurately, and that there appears to be no obvious benefit in the use of three barges, over a two-barge system.

Based on a small prototype of the McCabe wave pump device, this paper studies the optimal size of an interconnected pontoon system, where the power take-off systems attached to each barge are equipped with optimal linear passive dampers. To this end, an optimization procedure is developed, where the objective is to maximize the extracted energy of the device under given sea states. A multi-DOF mathematical model is presented to describe the device motion, and associated hydrodynamic parameters are computed using a boundary element model tool, based on linear potential flow theory. Numerical results, under regular and irregular waves, are presented. Simulation results show that the optimal dimension of the device, under given sea states, can be found using the developed methodology. In addition, it is found that the three-body hinge-barge device tends to perform like a two-body system under optimal control conditions. This indicates that a two-barge control system may be a better design solution in those situations, considering the high cost of power take-off systems.

Based on a small prototype of the McCabe wave pump device, this paper studies the optimal size of an interconnected pontoon system, where the power take-off systems attached to each barge are equipped with optimal linear passive dampers. To this end, an optimization procedure is developed, where the objective is to maximize the extracted energy of the device under given sea states. A multi-DOF mathematical model is presented to describe the device motion, and associated hydrodynamic parameters are computed using a boundary element model tool, based on linear potential flow theory. Numerical results, under regular and irregular waves, are presented. Simulation results show that the optimal dimension of the device, under given sea states, can be found using the developed methodology. In addition, it is found that the three-body hinge-barge device tends to perform like a two-body system under optimal control conditions. This indicates that a two-barge control system may be a better design solution in those situations, considering the high cost of power take-off systems.

Establishing causal links between inherited polymorphisms and cancer risk is challenging. Here, we focus on the single-nucleotide polymorphism rs55705857, which confers a sixfold greater risk of isocitrate dehydrogenase (IDH)-mutant low-grade glioma (LGG). We reveal that rs55705857 itself is the causal variant and is associated with molecular pathways that drive LGG. Mechanistically, we show that rs55705857 resides within a brain-specific enhancer, where the risk allele disrupts OCT2/4 binding, allowing increased interaction with the Myc promoter and increased Myc expression. Mutating the orthologous mouse rs55705857 locus accelerated tumor development in an Idh1R132H-driven LGG mouse model from 472 to 172 days and increased penetrance from 30% to 75%. Our work reveals mechanisms of the heritable predisposition to lethal glioma in ~40% of LGG patients.

Establishing causal links between inherited polymorphisms and cancer risk is challenging. Here, we focus on the single nucleotide polymorphism rs55705857 (A>G), which confers a 6-fold increased risk of IDH-mutant low-grade glioma (LGG) and is amongst the highest genetic associations with cancer. By fine-mapping the locus, we reveal that rs55705857 itself is the causal variant and is associated with molecular pathways that drive LGG. Mechanistically, we show that rs55705857 resides within a brain-specific enhancer, where the risk allele disrupts OCT2/4 binding, allowing increased interaction with the Myc promoter and increased Myc expression. To functionally test rs55705857, we generated an IDH1 R132H -driven LGG mouse model and show that mutating the highly conserved, orthologous mouse rs55705857 locus dramatically accelerated tumor development from 463 to 172 days and increased penetrance from 30% to 75%. Overall, our work generates new LGG models and reveals mechanisms of the heritable predisposition to lethal glioma in ∼40% of LGG-patients.

Deep learning methods, especially convolutional neural network (CNN)-based methods, have shown promising performance for hyperspectral image (HSI) change detection (CD). It is acknowledged widely that different spectral channels and spatial locations in input image patches may contribute differently to CD. However, they are treated equally in existing CNN-based approaches. To increase the accuracy of HSI CD, we propose an end-to-end Siamese CNN (SiamNet) with a spectral-spatial-wise attention (SSA-SiamNet) mechanism. The proposed SSA-SiamNet method can emphasize informative channels and locations and suppress less informative ones to refine the spectral-spatial features adaptively. Moreover, in the network training phase, the weighted contrastive loss function is used for more reliable separation of changed and unchanged pixels and to accelerate the convergence of the network. SSA-SiamNet was validated using four groups of bitemporal HSIs. The accuracy of CD using the SSA-SiamNet was found to be consistently greater than for ten benchmark methods.

In this study, nanosheet g–C3N4–H2 was prepared by thermal exfoliation of bulk g-C3N4 under hydrogen. A series of Ru/g–C3N4–H2 catalysts with Ru species supported on the nanosheet g–C3N4–H2 were synthesized via ultrasonic assisted impregnation-deposition method. Ultrafine Ru nanoparticles (<2 nm) were highly dispersed on nanosheet g–C3N4–H2. Strong interaction due to Ru-Nx coordination facilitated the uniform distribution of Ru species. Meanwhile, the involvement of surface basicity derived from abundant nitrogen sites was favourable for enhancing the selective hydrogenation performance of bi-benzene ring, i.e. almost complete 4,4′-diaminodiphenylmethane (MDA) conversion and >99% 4,4′-diaminodicyclohexylmethane selectivity, corresponding to a reaction activity of 35.7 molMDA molRu−1h−1. Moreover, the reaction activity of catalyst in the fifth run was 36.5 molMDA molRu−1h−1, which was comparable with that of the fresh one. The computational results showed that g-C3N4 as support was favorable for adsorption and dissociation of H2 molecules. Moreover, the substrate scope can be successfully expanded to a variety of other aromatic diamines. Therefore, this work provides an efficient and green catalyst system for selective hydrogenation of aromatic diamines.

Retarders have an important regulation effect on the hydration speed and setting time of cement. However, retarders are not conducive to the early strength development of concrete, so use early strength agents to improve their early performance. In this paper, the effects of different amounts of triethanolamine (TEA) and citric acid (CA) on the hydration dynamics and mechanical properties of silicate cement were investigated. The results showed that, as the CA content increases, the setting time of the cement slurry can be effectively prolonged. And the right amount of TEA can not only make the cement reach the early strength, but also increase the compressive strength in the later stage, and control the setting time of the cement paste. TEA shortens the induction period of CA-incorporated cement and increases the heat release rate during cement hydration induction period.

In this paper, four kinds of ecological fine aggregates (manufactured sand, recycled sand, aeolian sand and river sand) were used to prepared UHPC, the effects of the fine aggregates on the workability, rheological properties and mechanical properties of UHPC were studied. The results reveal that the type and content of fine aggregate have an effect on the rheological properties and mechanical strength of UHPC. Under the same mix proportion, the yield stress and plastic viscosity of recycled sand UHPC are higher than those of river sand UHPC, manufactured sand UHPC and aeolian sand UHPC, mainly due to its high water absorption. The high intergranular porosity, high surface area and low fineness modulus of aeolian sand contributes to an increase in yield stress, and high rate into thin and irregular shapes of manufactured sand are the major ingredients which affect the workability of UHPC. The yield stress and plastic viscosity of UHPC decrease with the increase of water-binder ratio, and the gap between the four fine aggregate systems is gradually narrowed. The effects of different fine aggregates on the mechanical properties of UHPC are arranged according to the improvement effect: recycled sand > manufactured sand > river sand > aeolian sand.

This paper reports on a study to determine the possibility of using ultra-fine fly ash (UFA) for partial or total replacement of normal fly ash (NFA) in ultra-high performance concrete (UHPC). Workability, microstructure, porosity, drying shrinkage as well as mechanical properties were comprehensively studied to investigate the influence of UFA on UHPC. The fly ash, which was a compound of NFA and UFA with various mass fractions, had a total content of 30 wt%. The results demonstrated that compressive strength is enhanced if NFA is partially or totally replaced with UFA. Compared to the reference mixture containing 100 wt% NFA, incorporating UFA into UHPC has been shown to improve its workability. Contrarily, adverse effects on drying shrinkage were discovered when NFA is substituted with UFA.

This paper describes outcomes of the 2019 Cryo-EM Model Challenge. The goals were to (1) assess the quality of models that can be produced from cryogenic electron microscopy (cryo-EM) maps using current modeling software, (2) evaluate reproducibility of modeling results from different software developers and users and (3) compare performance of current metrics used for model evaluation, particularly Fit-to-Map metrics, with focus on near-atomic resolution. Our findings demonstrate the relatively high accuracy and reproducibility of cryo-EM models derived by 13 participating teams from four benchmark maps, including three forming a resolution series (1.8 to 3.1 Å). The results permit specific recommendations to be made about validating near-atomic cryo-EM structures both in the context of individual experiments and structure data archives such as the Protein Data Bank. We recommend the adoption of multiple scoring parameters to provide full and objective annotation and assessment of the model, reflective of the observed cryo-EM map density.

Background: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silica models built using existing data facilitate rapid acute tox- icity predictions without using animals. Objkctivks: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organ- ized an international collaboration to develop in silica models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50 ≤ 50 mg/kg)], and nontoxic chemicals (LD50 > 2,000 mg/kg). Mkthods: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. Results: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in viva results. Discussion: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in viva rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemica

Retarders have an important regulation effect on the hydration speed and setting time of cement. However, retarders are not conducive to the early strength development of concrete, so use early strength agents to improve their early performance. In this paper, the effects of different amounts of triethanolamine (TEA) and citric acid (CA) on the hydration dynamics and mechanical properties of silicate cement were investigated. The results showed that, as the CA content increases, the setting time of the cement slurry can be effectively prolonged. And the right amount of TEA can not only make the cement reach the early strength, but also increase the compressive strength in the later stage, and control the setting time of the cement paste. TEA shortens the induction period of CA-incorporated cement and increases the heat release rate during cement hydration induction period.

In this paper, four kinds of ecological fine aggregates (manufactured sand, recycled sand, aeolian sand and river sand) were used to prepared UHPC, the effects of the fine aggregates on the workability, rheological properties and mechanical properties of UHPC were studied. The results reveal that the type and content of fine aggregate have an effect on the rheological properties and mechanical strength of UHPC. Under the same mix proportion, the yield stress and plastic viscosity of recycled sand UHPC are higher than those of river sand UHPC, manufactured sand UHPC and aeolian sand UHPC, mainly due to its high water absorption. The high intergranular porosity, high surface area and low fineness modulus of aeolian sand contributes to an increase in yield stress, and high rate into thin and irregular shapes of manufactured sand are the major ingredients which affect the workability of UHPC. The yield stress and plastic viscosity of UHPC decrease with the increase of water-binder ratio, and the gap between the four fine aggregate systems is gradually narrowed. The effects of different fine aggregates on the mechanical properties of UHPC are arranged according to the improvement effect: recycled sand > manufactured sand > river sand > aeolian sand.

This paper reports on a study to determine the possibility of using ultra-fine fly ash (UFA) for partial or total replacement of normal fly ash (NFA) in ultra-high performance concrete (UHPC). Workability, microstructure, porosity, drying shrinkage as well as mechanical properties were comprehensively studied to investigate the influence of UFA on UHPC. The fly ash, which was a compound of NFA and UFA with various mass fractions, had a total content of 30 wt%. The results demonstrated that compressive strength is enhanced if NFA is partially or totally replaced with UFA. Compared to the reference mixture containing 100 wt% NFA, incorporating UFA into UHPC has been shown to improve its workability. Contrarily, adverse effects on drying shrinkage were discovered when NFA is substituted with UFA.

This paper describes outcomes of the 2019 Cryo-EM Model Challenge. The goals were to (1) assess the quality of models that can be produced from cryogenic electron microscopy (cryo-EM) maps using current modeling software, (2) evaluate reproducibility of modeling results from different software developers and users and (3) compare performance of current metrics used for model evaluation, particularly Fit-to-Map metrics, with focus on near-atomic resolution. Our findings demonstrate the relatively high accuracy and reproducibility of cryo-EM models derived by 13 participating teams from four benchmark maps, including three forming a resolution series (1.8 to 3.1 Å). The results permit specific recommendations to be made about validating near-atomic cryo-EM structures both in the context of individual experiments and structure data archives such as the Protein Data Bank. We recommend the adoption of multiple scoring parameters to provide full and objective annotation and assessment of the model, reflective of the observed cryo-EM map density.

This paper aims to investigate electric dynamics and improve electric power generation of an isolated wave energy converter that uses a linear permanent magnet generator as the power take-off system, excited by regular or irregular waves. This is of significant concern when considering actual operating conditions of an offshore wave energy converter, where the device will encounter different sea states and its electric load needs to be tuned on a sea-state-to-sea-state basis. To that end, a fully coupled fluid-mechanical-electric-magnetic-electronic mathematical model and an optimization routine are developed. This proposed time-domain wave-to-wire model is used to simulate the hydrodynamic and electric response of a wave energy converter connected to specific electric loads and also used in an optimization routine that searches optimal resistive load value for a wave energy converter under specific sea states. Sample results are presented for a point-absorber type wave energy converter, showing that the electric power generation of a device under irregular waves can be significantly improved. Keywords: wave energy converter, wave power system, wave-to-wire model, linear permanent magnet generator, electric load optimization., Comment: Accepted by Energy

This paper aims to investigate electric dynamics and improve electric power generation of an isolated wave energy converter that uses a linear permanent magnet generator as the power take-off system, excited by regular or irregular waves. This is of significant concern when considering actual operating conditions of an offshore wave energy converter, where the device will encounter different sea states and its electric load needs to be tuned on a sea-state-to-sea-state basis. To that end, a fully coupled fluid-mechanical-electric-magnetic-electronic mathematical model and an optimization routine are developed. This proposed time-domain wave-to-wire model is used to simulate the hydrodynamic and electric response of a wave energy converter connected to specific electric loads and also used in an optimization routine that searches optimal resistive load value for a wave energy converter under specific sea states. Sample results are presented for a point-absorber type wave energy converter, showing that the electric power generation of a device under irregular waves can be significantly improved.

Methanol synthesized from carbonate hydrogenation is of great importance for CO2 utilization indirectly. Herein, a series of Cu/Zn/Al heterogeneous catalysts were prepared by co-precipitation with a synchronous aging step, and were applied for hydrogenation of diethyl carbonate (DEC) to produce methanol. Furthermore, the catalysts were characterized by physicochemical methods, such as N2 adsorption, ICP-OES, N2O titration, SEM, TEM, XRD, H2-TPR and XPS in detail. Higher copper concentration led to a higher ratio of bulk CuOx species in the calcined samples, which resulted in different copper species distribution after the reduction process. Structure activity relationship analysis indicated that the balance of surface Cu0 and Cu+ species influenced the formation rate of methanol. A higher proportion of Cu+ to (Cu+ + Cu0) was conductive to methanol formation, while excessive Cu0 site density played a negative influence on the methanol synthesized from DEC. Cu/Zn/Al with a 45.2% weight fraction of copper showed better performance with a total methanol formation rate of 131.0 mg gcat.-1 h-1. The reaction temperature and reaction time could obviously affect the reaction performance and the results suggested that 200 °C and 6 h were suitable. Furthermore, the long-term stability and activity of the catalyst was also studied on a fixed bed, and the yield of total methanol reached to 88.5% and the selectivity of total methanol gradually decreased to 74.0% within 200 h, which could be attributed to the detrimental influence derived from the increase of Cu0. The reaction pathways involved in the hydrogenation of DEC process were proposed. The substance scope was also extended to other carbonates and the catalyst exhibited superior catalytic performance toward linear carbonates. This work provided insights into carbonate hydrogenation over an effective Cu/Zn/Al catalyst, which could be utilized into upgrading CO2 indirectly to produce commodity methanol under relatively mild

BACKGROUND: Global disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men.OBJECTIVE: To systematically explore the genomic complexity and define disease-driven genetic alterations in PCa.DESIGN, SETTING, AND PARTICIPANTS: The study sequenced whole-genome and transcriptome of tumor-benign paired tissues from 65 treatment-naive Chinese PCa patients. Subsequent targeted deep sequencing of 293 PCa-relevant genes was performed in another cohort of 145 prostate tumors.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The genomic alteration landscape in PCa was analyzed using an integrated computational pipeline. Relationships with PCa progression and survival were analyzed using nonparametric test, log-rank, and multivariable Cox regression analyses.RESULTS AND LIMITATIONS: We demonstrated an association of high frequency of CHD1 deletion with a low rate of TMPRSS2-ERG fusion and relatively high percentage of mutations in androgen receptor upstream activator genes in Chinese patients. We identified five putative clustered deleted tumor suppressor genes and provided experimental and clinical evidence that PCDH9, deleted/loss in approximately 23% of tumors, functions as a novel tumor suppressor gene with prognostic potential in PCa. Furthermore, axon guidance pathway genes were frequently deregulated, including gain/amplification of PLXNA1 gene in approximately 17% of tumors. Functional and clinical data analyses showed that increased expression of PLXNA1 promoted prostate tumor growth and independently predicted prostate tumor biochemical recurrence, metastasis, and poor survival in multi-institutional cohorts of patients with PCa. A limitation of this study is that other genetic alterations were not experimentally investigated.CONCLUSIONS: There are shared and salient genetic characteristics of PCa in Chinese and Cau

Ocean waves are a promising source of renewable energy. In this paper, we briefly introduce the characteristics of ocean wave energy and summarize the principles of harvesting ocean energy by wave energy converters. We also review the prototypes or commercial devices deployed in real sea between 2005 and July 2016. In addition, we present the concept of a wave-to-wire model as a framework to systematically review and compare control strategies for wave energy conversion systems, with a focus on the numerical and experimental validation.

Liguo Wang,1,* Peng Chen,2,* Chao Zheng3 1Department of Infectious Diseases, First Affiliated Hospital of Xiamen University, Fujian Province, China; 2Department of Emergency, Xinglin Hospital, First Affiliated Hospital of Xiamen University, Fujian Province, China; 3Department of Respiratory, First Affiliated Hospital of Xiamen University, Fujian Province, China *These authors contributed equally to this work Objective: The objective of this study was to explore the risk factors of poor adherence of nucleoside analogs (NUC) treatment in chronic hepatitis B (CHB) patients and the virological changes in patients with poor adherence. Subjects and methods: A total of 205 CHB patients were enrolled. The patients’ demographic data and family history were collected. NUC adherence was calculated every 12 weeks as follows: number of NUC tablets taken by the patients was divided by the number of NUC tablets prescribed. NUC adherence > 90% was defined as good adherence of NUC treatment. Results: NUC adherence of male patients was significantly lower than that of female patients. Adherence among patients with previous NUC treatment was poorer than that of patients without previous NUC treatment. Multivariate analysis indicated that female gender (OR =0.367, P=0.013) was the protective factor for NUC adherence in CHB patients, while pretreatment with NUC was the risk factor for NUC adherence (OR =3.209, P=0.002). A total of six patients in the good adherence group experienced virological breakthroughs while 15 of 77 patients in the poor adherence group experienced virological breakthroughs (P=0.001). Similar trends were observed in NUC resistance. Four of the 128 patients with good adherence developed NUC resistance while nine of the 77 patients with poor adherence developed resistance (P=0.015). Multivariate analysis suggested that pretreatment with NUC (OR =3.133, P=0.031), NUC drugs (OR = 3.951, P=0.010), and adhere

The chemical utilization of CO2 is a crucial step for the recycling of carbon resource. In recent years, the study on the conversion of CO2 into a wide variety of C2 + important chemicals and fuels has received considerable attention as an emerging technology. Since CO2 is thermodynamically stable and kinetically inert, the effective activation of CO2 molecule for the selective transformation to target products still remains a challenge. The well-designed CO2 reduction route and efficient catalyst system has imposed the feasibility of CO2 conversion into C2 + chemicals and fuels. In this paper, we have reviewed the recent advances on chemical conversion of CO2 into C2 + chemicals and fuels with wide practical applications, including important alcohols, acetic acid, dimethyl ether, olefins and gasoline. In particular, the synthetic routes for C-C coupling and carbon chain growth, multifunctional catalyst design and reaction mechanisms are exclusively emphasized.

Ocean wave energy is a promising renewable source to contribute to supplying the world’s energy demand. The Division of Electricity at Uppsala University is developing a technology to capture energy from ocean waves with a wave energy converter (WEC) consisting of a linear permanent magnet generator and a point absorber. The linear generator is placed on sea bed and is driven directly by the floating absorber. Since March 2006, multiple wave energy converters have been deployed on the Swedish west coast outside the town of Lysekil. The technology is verified by long-term operation during at sea and satisfactory reliability of the electricity generation. This thesis focuses on developing advanced control strategies for fully coupled wave energy converters subject to constraints. A nonlinear control strategy is studied in detail for a single WEC subject to constraints under regular and irregular waves. Besides, two coordinated control strategies are developed to investigate the performance of a wave energy farm subject to constraints. The performance of the WECs using these control strategies are investigated in case studies, and optimal PTO damping coefficients are found to maximize the output power. The results show that these control strategies can significantly improve the performance of the WECs, in terms of mean power, compared to a conventional control. Besides these control strategies, a wave-to-wire simulation platform is built to study the power generation control of the WEC subject to constraints. The wave-to-wire simulation platform allows both nonlinear and linear control force. The results show that there is a good agreement between the desired value and the actual value after advanced control.

Ocean wave energy is a promising renewable source to contribute to supplying the world’s energy demand. The Division of Electricity at Uppsala University is developing a technology to capture energy from ocean waves with a wave energy converter (WEC) consisting of a linear permanent magnet generator and a point absorber. The linear generator is placed on sea bed and is driven directly by the floating absorber. Since March 2006, multiple wave energy converters have been deployed on the Swedish west coast outside the town of Lysekil. The technology is verified by long-term operation during at sea and satisfactory reliability of the electricity generation. This thesis focuses on developing advanced control strategies for fully coupled wave energy converters subject to constraints. A nonlinear control strategy is studied in detail for a single WEC subject to constraints under regular and irregular waves. Besides, two coordinated control strategies are developed to investigate the performance of a wave energy farm subject to constraints. The performance of the WECs using these control strategies are investigated in case studies, and optimal PTO damping coefficients are found to maximize the output power. The results show that these control strategies can significantly improve the performance of the WECs, in terms of mean power, compared to a conventional control. Besides these control strategies, a wave-to-wire simulation platform is built to study the power generation control of the WEC subject to constraints. The wave-to-wire simulation platform allows both nonlinear and linear control force. The results show that there is a good agreement between the desired value and the actual value after advanced control.

Ocean wave energy is a promising renewable source to contribute to supplying the world’s energy demand. The Division of Electricity at Uppsala University is developing a technology to capture energy from ocean waves with a wave energy converter (WEC) consisting of a linear permanent magnet generator and a point absorber. The linear generator is placed on sea bed and is driven directly by the floating absorber. Since March 2006, multiple wave energy converters have been deployed on the Swedish west coast outside the town of Lysekil. The technology is verified by long-term operation during at sea and satisfactory reliability of the electricity generation. This thesis focuses on developing advanced control strategies for fully coupled wave energy converters subject to constraints. A nonlinear control strategy is studied in detail for a single WEC subject to constraints under regular and irregular waves. Besides, two coordinated control strategies are developed to investigate the performance of a wave energy farm subject to constraints. The performance of the WECs using these control strategies are investigated in case studies, and optimal PTO damping coefficients are found to maximize the output power. The results show that these control strategies can significantly improve the performance of the WECs, in terms of mean power, compared to a conventional control. Besides these control strategies, a wave-to-wire simulation platform is built to study the power generation control of the WEC subject to constraints. The wave-to-wire simulation platform allows both nonlinear and linear control force. The results show that there is a good agreement between the desired value and the actual value after advanced control.

Ocean wave energy is a promising renewable source to contribute to supplying the world’s energy demand. The Division of Electricity at Uppsala University is developing a technology to capture energy from ocean waves with a wave energy converter (WEC) consisting of a linear permanent magnet generator and a point absorber. The linear generator is placed on sea bed and is driven directly by the floating absorber. Since March 2006, multiple wave energy converters have been deployed on the Swedish west coast outside the town of Lysekil. The technology is verified by long-term operation during at sea and satisfactory reliability of the electricity generation. This thesis focuses on developing advanced control strategies for fully coupled wave energy converters subject to constraints. A nonlinear control strategy is studied in detail for a single WEC subject to constraints under regular and irregular waves. Besides, two coordinated control strategies are developed to investigate the performance of a wave energy farm subject to constraints. The performance of the WECs using these control strategies are investigated in case studies, and optimal PTO damping coefficients are found to maximize the output power. The results show that these control strategies can significantly improve the performance of the WECs, in terms of mean power, compared to a conventional control. Besides these control strategies, a wave-to-wire simulation platform is built to study the power generation control of the WEC subject to constraints. The wave-to-wire simulation platform allows both nonlinear and linear control force. The results show that there is a good agreement between the desired value and the actual value after advanced control.

Ocean wave energy is a promising renewable source to contribute to supplying the world’s energy demand. The Division of Electricity at Uppsala University is developing a technology to capture energy from ocean waves with a wave energy converter (WEC) consisting of a linear permanent magnet generator and a point absorber. The linear generator is placed on sea bed and is driven directly by the floating absorber. Since March 2006, multiple wave energy converters have been deployed on the Swedish west coast outside the town of Lysekil. The technology is verified by long-term operation during at sea and satisfactory reliability of the electricity generation. This thesis focuses on developing advanced control strategies for fully coupled wave energy converters subject to constraints. A nonlinear control strategy is studied in detail for a single WEC subject to constraints under regular and irregular waves. Besides, two coordinated control strategies are developed to investigate the performance of a wave energy farm subject to constraints. The performance of the WECs using these control strategies are investigated in case studies, and optimal PTO damping coefficients are found to maximize the output power. The results show that these control strategies can significantly improve the performance of the WECs, in terms of mean power, compared to a conventional control. Besides these control strategies, a wave-to-wire simulation platform is built to study the power generation control of the WEC subject to constraints. The wave-to-wire simulation platform allows both nonlinear and linear control force. The results show that there is a good agreement between the desired value and the actual value after advanced control.

It is well known that the total power converted by a wave energy farm is influenced by the hydrodynamic interactions between wave energy converters, especially when they are close to each other. Therefore, to improve the performance of a wave energy farm, the hydrodynamic interaction between converters must be considered, which can be influenced by the power take-off damping of individual converters. In this paper, the performance of arrays of wave energy converters under optimal hydrodynamic interaction and power take-off damping is investigated. This is achieved by coordinating the power take-off damping of individual converters, resulting in optimal hydrodynamic interaction as well as higher production of time-averaged power converted by the farm. Physical constraints on motion amplitudes are considered in the solution, which is required for the practical implementation of wave energy converters. Results indicate that the natural frequency of a wave energy converter under optimal damping will not vary with sea states, but the production performance of a wave energy farm can be improved significantly while satisfying the motion constraints., Performance and Survivability of Wave power Farm

In this paper, a generic coordinated control method for wave energy converters is proposed, and the constraints on motion amplitudes and the hydrodynamic interaction between converters are considered. The objective of the control problem is to maximize the energy converted from ocean waves, and this is achieved by coordinating the power take-off (PTO) damping of each wave energy converter in the frequency domain in each sea state. In a case study, a wave energy farm consisting of four converters based on the concept developed by Uppsala University is studied. In the solution, motion constraints, including constraints on the amplitudes of displacement and velocity, are included. Twelve months of sea states, based on measured wave data at the Lysekil test site on the Swedish west coast, are used in the simulation to evaluate the performance of the wave energy farm using the new method. Results from the new coordinated control method and traditional control method are compared, indicating that the coordinated control of wave energy converters is an effective way to improve the energy production of wave energy farm in harmonic waves.

It is well known that the total power converted by a wave energy farm is influenced by the hydrodynamic interactions between wave energy converters, especially when they are close to each other. Therefore, to improve the performance of a wave energy farm, the hydrodynamic interaction between converters must be considered, which can be influenced by the power take-off damping of individual converters. In this paper, the performance of arrays of wave energy converters under optimal hydrodynamic interaction and power take-off damping is investigated. This is achieved by coordinating the power take-off damping of individual converters, resulting in optimal hydrodynamic interaction as well as higher production of time-averaged power converted by the farm. Physical constraints on motion amplitudes are considered in the solution, which is required for the practical implementation of wave energy converters. Results indicate that the natural frequency of a wave energy converter under optimal damping will not vary with sea states, but the production performance of a wave energy farm can be improved significantly while satisfying the motion constraints., Performance and Survivability of Wave power Farm

In this paper, a generic coordinated control method for wave energy converters is proposed, and the constraints on motion amplitudes and the hydrodynamic interaction between converters are considered. The objective of the control problem is to maximize the energy converted from ocean waves, and this is achieved by coordinating the power take-off (PTO) damping of each wave energy converter in the frequency domain in each sea state. In a case study, a wave energy farm consisting of four converters based on the concept developed by Uppsala University is studied. In the solution, motion constraints, including constraints on the amplitudes of displacement and velocity, are included. Twelve months of sea states, based on measured wave data at the Lysekil test site on the Swedish west coast, are used in the simulation to evaluate the performance of the wave energy farm using the new method. Results from the new coordinated control method and traditional control method are compared, indicating that the coordinated control of wave energy converters is an effective way to improve the energy production of wave energy farm in harmonic waves.

It is well known that the total power converted by a wave energy farm is influenced by the hydrodynamic interactions between wave energy converters, especially when they are close to each other. Therefore, to improve the performance of a wave energy farm, the hydrodynamic interaction between converters must be considered, which can be influenced by the power take-off damping of individual converters. In this paper, the performance of arrays of wave energy converters under optimal hydrodynamic interaction and power take-off damping is investigated. This is achieved by coordinating the power take-off damping of individual converters, resulting in optimal hydrodynamic interaction as well as higher production of time-averaged power converted by the farm. Physical constraints on motion amplitudes are considered in the solution, which is required for the practical implementation of wave energy converters. Results indicate that the natural frequency of a wave energy converter under optimal damping will not vary with sea states, but the production performance of a wave energy farm can be improved significantly while satisfying the motion constraints., Performance and Survivability of Wave power Farm

In this paper, a generic coordinated control method for wave energy converters is proposed, and the constraints on motion amplitudes and the hydrodynamic interaction between converters are considered. The objective of the control problem is to maximize the energy converted from ocean waves, and this is achieved by coordinating the power take-off (PTO) damping of each wave energy converter in the frequency domain in each sea state. In a case study, a wave energy farm consisting of four converters based on the concept developed by Uppsala University is studied. In the solution, motion constraints, including constraints on the amplitudes of displacement and velocity, are included. Twelve months of sea states, based on measured wave data at the Lysekil test site on the Swedish west coast, are used in the simulation to evaluate the performance of the wave energy farm using the new method. Results from the new coordinated control method and traditional control method are compared, indicating that the coordinated control of wave energy converters is an effective way to improve the energy production of wave energy farm in harmonic waves.

It is well known that the total power converted by a wave energy farm is influenced by the hydrodynamic interactions between wave energy converters, especially when they are close to each other. Therefore, to improve the performance of a wave energy farm, the hydrodynamic interaction between converters must be considered, which can be influenced by the power take-off damping of individual converters. In this paper, the performance of arrays of wave energy converters under optimal hydrodynamic interaction and power take-off damping is investigated. This is achieved by coordinating the power take-off damping of individual converters, resulting in optimal hydrodynamic interaction as well as higher production of time-averaged power converted by the farm. Physical constraints on motion amplitudes are considered in the solution, which is required for the practical implementation of wave energy converters. Results indicate that the natural frequency of a wave energy converter under optimal damping will not vary with sea states, but the production performance of a wave energy farm can be improved significantly while satisfying the motion constraints., Performance and Survivability of Wave power Farm

In this paper, a generic coordinated control method for wave energy converters is proposed, and the constraints on motion amplitudes and the hydrodynamic interaction between converters are considered. The objective of the control problem is to maximize the energy converted from ocean waves, and this is achieved by coordinating the power take-off (PTO) damping of each wave energy converter in the frequency domain in each sea state. In a case study, a wave energy farm consisting of four converters based on the concept developed by Uppsala University is studied. In the solution, motion constraints, including constraints on the amplitudes of displacement and velocity, are included. Twelve months of sea states, based on measured wave data at the Lysekil test site on the Swedish west coast, are used in the simulation to evaluate the performance of the wave energy farm using the new method. Results from the new coordinated control method and traditional control method are compared, indicating that the coordinated control of wave energy converters is an effective way to improve the energy production of wave energy farm in harmonic waves.

It is well known that the total power converted by a wave energy farm is influenced by the hydrodynamic interactions between wave energy converters, especially when they are close to each other. Therefore, to improve the performance of a wave energy farm, the hydrodynamic interaction between converters must be considered, which can be influenced by the power take-off damping of individual converters. In this paper, the performance of arrays of wave energy converters under optimal hydrodynamic interaction and power take-off damping is investigated. This is achieved by coordinating the power take-off damping of individual converters, resulting in optimal hydrodynamic interaction as well as higher production of time-averaged power converted by the farm. Physical constraints on motion amplitudes are considered in the solution, which is required for the practical implementation of wave energy converters. Results indicate that the natural frequency of a wave energy converter under optimal damping will not vary with sea states, but the production performance of a wave energy farm can be improved significantly while satisfying the motion constraints., Performance and Survivability of Wave power Farm

In this paper, a generic coordinated control method for wave energy converters is proposed, and the constraints on motion amplitudes and the hydrodynamic interaction between converters are considered. The objective of the control problem is to maximize the energy converted from ocean waves, and this is achieved by coordinating the power take-off (PTO) damping of each wave energy converter in the frequency domain in each sea state. In a case study, a wave energy farm consisting of four converters based on the concept developed by Uppsala University is studied. In the solution, motion constraints, including constraints on the amplitudes of displacement and velocity, are included. Twelve months of sea states, based on measured wave data at the Lysekil test site on the Swedish west coast, are used in the simulation to evaluate the performance of the wave energy farm using the new method. Results from the new coordinated control method and traditional control method are compared, indicating that the coordinated control of wave energy converters is an effective way to improve the energy production of wave energy farm in harmonic waves.

Leiming Li,1,* Yan Li,2,* Jiansong Zhao,2 Shuli Fan,3 Liguo Wang,1 Xu Li1 1Department of Joint Surgery and Sports Medicine, The First Affiliated Hospital, 2Department of Spine and Joint Surgery, Sheng Jing Hospital, 3Department of Geriatrics, The First Affiliated Hospital, China Medical University, Shenyang, People’s Republic of China *These authors contributed equally to this work Abstract: Osteosarcoma (OS) is the most common primary bone tumor, but molecular mechanisms of the disease have not been well understood, and treatment of metastatic OS remains a challenge. Rapid ribosomal RNA synthesis in cancer is transcribed by RNA polymerase I, which results in unbridled cell growth. The recent discovery of CX-5461, a selective RNA polymerase I inhibitor, exerted its inhibitory effect of ribosomal RNA synthesis and antiproliferative potency. Here, we demonstrate that CX-5461 induces G2 arrest in the cell cycle and expression of microtubule-associated protein 1 light chain 3 II isoform in OS cell lines. Autophagic vacuoles could be observed in electron microscopy and 3-methyladenine prevented cell death mediated by CX-5461. Moreover, it significantly augmented phosphorylated AMP-Activated Protein Kinases α (p-AMPK α). (Thr172) expression in U2-OS cells and decreased p-Akt (Ser473) expression in MNNG cells, respectively, which repressed their downstream effector, mammalian target of rapamycin. On the other hand, CX-5461 increased p53 accumulation and messenger RNA level of its target genes, p21, MDM2, and Sestrin1/2 in U2-OS cells. Knockdown of p53 expression markedly impaired cell death as well as the expression of light chain 3-II and p21 induced by CX-5461. It also significantly enhanced doxorubicin-mediated cytotoxic effect in vitro and in vivo together with additive expression of p53, p21, and light chain 3-II in U2-OS cells. Our data indicate that CX-5461 might induce autophagy via mammalian target of rapamycin-associated sig

Shuli Fan,1,* Xu Li,2,* Leiming Li,2 Liguo Wang,2 Zhangzhen Du,2 Yan Yang,2 Jiansong Zhao,3 Yan Li3 1Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Sports Medicine and Joint Surgery, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 3Department of Orthopaedic Surgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China *These authors contributed equally to this work Abstract: Carboxypeptidase E (CPE), a prohormone processing enzyme, has been implicated in the progression of multiple malignancies. However, the biological role and molecular mechanisms of CPE in osteosarcoma remain elusive. In this study, we assessed the effects of CPE on cell proliferation, tumorigenicity, migration, and invasion in osteosarcoma. Our results showed that silencing of CPE significantly inhibited cell proliferation, caused cell cycle arrest at G0/G1 phase, decreased the expression levels of cell cycle protein, cyclin D1, and inhibited tumorigenicity in vivo. Additionally, CPE downregulation repressed the migratory and invasive capacities of osteosarcoma cells in vitro. Furthermore, overexpression of CPE-ΔN (a splice variant of CPE) enhanced the cell growth, migration, and invasion of osteosarcoma cells. It is possible that both CPE forms are involved in the tumorigenesis and development of osteosarcoma, and therefore CPE may provide a promising biological target for osteosarcoma therapy. Keywords: carboxypeptidase E, osteosarcoma, proliferation, tumorigenicity, migration, invasion

The paper presents an exploratory investigation to determine and prioritise the critical success measuring criteria, which can measure and guide the successful application and performance improvement of business to business (B2B) e-commerce system (BBECS) in a medical supply chain’s selling and buying functions, in the context of global business expansion. The research reveals that the buying and the selling functions have different prioritisations on majority of the determined critical success measuring criteria. These criteria are categorised into three Critical Success Measuring Criteria Groups (CSMCGs), for the selling and the buying functions respectively, guiding medical supply chain members in harnessing the full advantage of a BBECS.

This paper investigates a method for optimal control of a point absorbing wave energy converter by considering the constraints on motions and forces in the time domain. The problem is converted to an optimization problem with the cost function being convex quadratic and the constraints being nonlinear. The influence of the constraints on the converter is studied, and the results are compared with uncontrolled cases and established theoretical bounds. Since this method is based on the knowledge of the future sea state or the excitation force, the influence of the prediction horizon is indicated. The resulting performance of the wave energy converter under different regular waves shows that this method leads to a substantial increase in conversion efficiency.

The paper presents an exploratory investigation to determine and prioritise the critical success measuring criteria, which can measure and guide the successful application and performance improvement of business to business (B2B) e-commerce system (BBECS) in a medical supply chain’s selling and buying functions, in the context of global business expansion. The research reveals that the buying and the selling functions have different prioritisations on majority of the determined critical success measuring criteria. These criteria are categorised into three Critical Success Measuring Criteria Groups (CSMCGs), for the selling and the buying functions respectively, guiding medical supply chain members in harnessing the full advantage of a BBECS.

This paper investigates a method for optimal control of a point absorbing wave energy converter by considering the constraints on motions and forces in the time domain. The problem is converted to an optimization problem with the cost function being convex quadratic and the constraints being nonlinear. The influence of the constraints on the converter is studied, and the results are compared with uncontrolled cases and established theoretical bounds. Since this method is based on the knowledge of the future sea state or the excitation force, the influence of the prediction horizon is indicated. The resulting performance of the wave energy converter under different regular waves shows that this method leads to a substantial increase in conversion efficiency.