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This paper investigates the optimization of the inner thermal layout in nanofluid-filled horizontal annular pipes under natural convection conditions. Two-dimensional models of annular pipes are established using a numerical simulation approach. Then, using this as the simulation tool, the layouts of single-, triple-, and quadruple-heat-source annular pipes are optimized. The coordinates of the inner cylinders are defined as the decision variables, and the average Nusselt number (Nu) on the cold wall surface as the objective function. For the single-cylinder model, both the Bayesian optimization algorithm (BOA) and the genetic algorithm (GA) derive the same results: an axisymmetric layout where the single heat source is positioned slightly above the axis of the annulus. However, the BOA takes much less computational time than the GA and, consequently, is chosen for cases with more complex geometry. The optimization layout of the three-cylinder model also shows an axisymmetric distribution, while the result for the four-cylinder model presents a centrally symmetric distribution. Compared to the original average Nu, the optimized ones are enhanced by 17.83%, 8.36%, and 6.18% for single-, triple-, and quadruple-heat-source annular pipes, respectively. The results of this study can be used for guiding the layout design and optimization of the nanofluid-filled exchangers with multi-inner heat sources. [ABSTRACT FROM AUTHOR]

Establishing a novel design and accurate analytical models for XY nanopositioning stages based on voice coil motor (VCM) actuators is critical to achieving an optimal working performance. To overcome the existing design challenges of 2-degree-of-freedom guiding mechanisms, a four-layer structure composed of L-shaped spatial double parallelogram flexure mechanisms was proposed for the magnetic stage, which exhibits light weight and inhibits parasitic and decoupled motions. The guiding mechanisms were modeled by the compliance matrix method. Thereafter, by combining an electromagnetic model for the VCMs with the equivalent magnetic network method, an electromagnetic–mechanical coupling optimization method with multiple constraints was proposed for the stage to achieve a millimeter-range motion with a maximized natural frequency. The mechanical and electromagnetic performances were then verified by finite element analysis software. The optimized prototype was tested with a stroke of ±3.41 and ±3.08 mm for X axis and Y axis, respectively, a closed-loop resolution of 100 nm for X axis and 150 nm for Y axis, and a resonant frequency of 11.75 Hz for both axes. The tracking of a 0.1 Hz spiral of Archimedes achieved a maximum tracking error of 2.9%. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel, potent and effective EZH2 degraders were developed. • Compound P4 can effectively induce EZH2 protein degradation and inhibit breast cancer cell growth. • Compound P4 can significantly decrease the degree of H3K27me3 in MDA-MB-231 cell line, induce apoptosis and G 0 /G 1 phase arrest in Pfeiffer and MDA-MB-231 cell lines. • Compound P4 significantly inhibited the migratory and invasive capacity of MDA-MB-231 cells at micromolar concentrations in a dose-dependent manner. • Adequate metabolic stability in vitro. EZH2 (enhancer of zeste homolog 2) is one of the most important histone methyltransferases (HMTs), and overexpression of EZH2 can lead to proliferation, migration and angiogenesis of tumor cells. But most of EZH2 inhibitors are only effective against some hematologic malignancies and have poor efficacy against solid tumors. Here, we report the design, synthesis, and evaluation of highly potent proteolysis targeting chimeric (PROTACs) small molecules targeting EZH2. We developed a potent and effective EZH2 degrader P4 , which effectively induced EZH2 protein degradation and inhibited breast cancer cell growth. Further studies showed that P4 can significantly decrease the degree of H3K27me3 in MDA-MB-231 cell line, induce apoptosis and G 0 /G 1 phase arrest in Pfeiffer and MDA-MB-231 cell lines. Therefore, P4 is a potential anticancer molecule for breast cancer treatment. [ABSTRACT FROM AUTHOR]

α‐Substituted peroxides have been found in natural products and are widely used as anti‐malarial agents. Zn(OTf)2‐catalyzed peroxidation of 1,3,5‐triazines has been developed, accessing diversely substituted α‐amino tertiary alkylperoxides with high efficiency. Mechanistic investigations and useful synthetic application of the products have also been presented. [ABSTRACT FROM AUTHOR]

A Y(OTf)3‐catalyzed [3+2] cycloaddition of 1,3,5‐triazinanes with donor‐acceptor aziridines has been developed, accessing diversely substituted imidazolidines high efficiency. Mechanistic investigations support the formation of imidazolidines through an SN1‐like pathway. Furthermore, these imidazolidines exhibit promising anti‐tumor activity against a series of human cancer cell lines. [ABSTRACT FROM AUTHOR]

To improve the overall energy utilisation efficiency, the research of combined cooling, heat, and power (CCHP)‐based microgrids has become prevalent recently. However, the increasing penetration of uncertain renewable generation such as wind power brings new challenges to CCHP‐based microgrids energy management. In this study, the authors propose a two‐stage multi‐period distributionally robust energy management model for CCHP‐based microgrids, and this model considers the non‐anticipativity of uncertainty in dispatch process. A second‐order conic representable ambiguity set is designed to capture the uncertainty of wind power. Based on linear decision rule approximation, the proposed problem is transformed into a tractable mixed‐integer second‐order conic programme problem. Case studies and comparison experiments are conducted in the Matlab environment with real‐world data to validate the performance of the proposed approach. Particularly, the proposed method achieves a less conservative solution and smaller cost compared with a robust optimisation method with the same reliability guarantee. In addition, it is more reliable than the deterministic method which does not consider uncertainty. [ABSTRACT FROM AUTHOR]

Renewable generation has been increasingly utilized recently, and multi-microgrid (MMG) system shows great potential in absorbing renewable energy. In this paper, a two-stage distributionally robust model is proposed for the optimal design and operation of islanded MMG which is seldom studied. Considering the uncertainty of renewable generation, the first-stage design strategy and second-stage operation decision are co-optimized by minimizing the investment cost and operation cost. To model the uncertainty of renewable power, a distance-based ambiguity set is employed to capture the unknown probability distribution. Then the two-stage problem is solved by a column and constraint generation (CCG) based method. Simulation experiments and results with an islanded MMG system demonstrate the effectiveness and performance of the proposed model. • A novel two-stage distributionally robust framework is developed for optimal design and operation of islanded multi-microgrid system. • A data-driven distance-based ambiguity set is employed to describe the uncertain distribution of renewable generation. • The optimal design results of the proposed model perform better than those of independent operation model and fully connected model. • The influence of the unit investment cost of electric cables and the data size of renewable power on the optimal result is analyzed. [ABSTRACT FROM AUTHOR]

Microgrids play an important role in modern power systems which can integrate different kinds of distributed energy resources (DERs). To deal with the uncertainty from various factors such as renewable generation, robust energy management for microgrids has become a significant problem. In this work, a novel multistage robust energy management model for grid‐connected microgrids is developed which considers the uncertainty of renewable generation and load demand. The multistage energy management problem is complex and computationally difficult. To solve this problem, a robust version of dual dynamic programming method is proposed which includes a forward pass and a backward pass procedure and has a similar framework with the common stochastic dual dynamic programming (SDDP) method. Based on real datasets, a case study is carried out to validate the effectiveness of the proposed model and solution methodology. Numerical results show that the proposed approach can effectively achieve the robust optimal solution, and the comparison with other methods also testifies the advantage of the proposed multistage robust model. [ABSTRACT FROM AUTHOR]

In this paper a 5 × 5 micromachined digital electromagnetic actuator array for microdisplacements is presented. Each elementary actuator is composed of a permanent magnet placed in a silicon square cavity. This magnet can be switched between four discrete positions and can be switched by applying current pulses through wires placed below the cavity. A semi-analytical model has been developed to design the actuator. Then, a prototype, composed of a silicon part, has been manufactured using deep reactive ion etching process. An elementary actuator was as firstly experimentally characterized. Then the array was used to realize a conveyance task. The maximum displacement quantum of the conveyed object is 115 µm. [ABSTRACT FROM AUTHOR]

As the increasing energy demand and rapid depletion of conventional fossil fuel resources, renewable energy has caused great attention of the public. The main drawback of the renewable resources is their unpredictable nature. A hybrid renewable energy system (HRES) that integrates different resources in proper combination is a promising solution to overcome this challenge. In this context, the preference-inspired coevolutionary algorithm (PICEA) has been applied for the first time to the design of multi-objective hybrid renewable energy system. We propose an enhanced fitness assignment method to improve the preference-inspired coevolutionary algorithm using goal vectors (PICEA-g) in the optimization process minimizing, simultaneously, the annualized cost of system (ACS), the loss of power supply probability (LPSP) and the fuel emissions. As an example of application, a stand-alone hybrid system including PV panels, wind turbines, batteries and diesel generators has been designed to find the best combination of components, achieving a set of non-dominated solutions from which the decision maker can select a most adequate one. [ABSTRACT FROM AUTHOR]

• TfOH-catalyzed cycloaddition of N -tosylaziridine dicarboxylates and nitriles gave tetrafunctionalized 2-imidazolines. • The method features mild conditions and wide scope of substrates. • First example of C–N bond cleavage of N -tosylaziridine dicarboxylates catalyzed by Brønsted acid. • A S N 2 process. We developed an efficient method for synthesis of tetrafunctionalized 2-imidazolines using TfOH-catalyzed formal [3+2] cycloaddition of N -tosylaziridine dicarboxylates and nitriles. This is the first report of C–N bond cleavage of N -tosylaziridine dicarboxylates catalyzed by Brønsted acid and the reaction worked well over wide scope of substrates in good to excellent yields under mild conditions. The method has the potential to be applied to pharmaceutical design and synthesis of tetrafunctionalized 2-imidazolines. [ABSTRACT FROM AUTHOR]

To perform fast and portable grain moisture measurements under field conditions, a novel moisture sensor was designed, which consisted of a coaxial waveguide, a circular waveguide, and an isolation layer. The electromagnetic characteristics of the sensor were simulated and measured. The analytical model, which represented the relationship between the reflection coefficient of the sensor and the complex permittivity of grain, was established by using the mode matching method. The reflection coefficient of the sensor was measured by using an ultra-wideband (UWB) radar module, and the moisture content of grains was calculated from the complex permittivity by using density-independent model. To verify the performance of the proposed method, wheat, rough rice, and barley were taken as examples. The measured results in the range from 1.0% to 26.0%, wet basis, agreed well with the reference values (R2 was more than 0.99), and the maximum absolute errors for wheat, rough rice, and barley were 1.1%, 1.0%, and 1.4%, respectively. In addition, the effect of isolation layer was discussed. Both the simulation results and the experimental results showed that the isolation layer improved the stability of sensor. [ABSTRACT FROM AUTHOR]

A first catalytic enantioselective intermolecular radical aminotrifluoromethylation of alkene with hydrazine and Togni's reagent by Cu(I)/CPA cooperative catalysis has been reported, accessing diversely substituted CF3‐containing enantioenriched diarylmethylamines bearing an α‐tertiary stereocenter with high enantioselectivity and excellent chemoselectivity. The highly asymmetric induction of C−N bond formation between hydrazine and the carbocation intermediate was achieved by using a CPA catalyst via hydrogen‐bonding and ion pair interaction. [ABSTRACT FROM AUTHOR]

Presents a methodology to determine the surface concentrations of both underpotentially deposited metal adatoms and coadsorbed anions. Use of total charge density measurements with the chronocoulometric technique; Determination of the composition of the mixed copper-anion overlayers.

Acquired resistance leads to the failure of EGFR TKIs in NSCLC treatment. A novel series of hydroxamic acid-containing 4-aminoquinazoline derivatives as irreversible ErbB/HDAC multitargeted inhibitors for NSCLC therapy had been designed and synthesized, which displayed weak anti-proliferative activity in several EGFR wild-type cancer cell lines (NCI–H838, SK-BR-3, A549, A431) yet retained moderate activity to EGFRT790M resistance mutation harboring NCI–H1975 cells. The mechanistic studies revealed that the representative compound 11e was able to inhibit the phosphorylation of EGFR, up-regulate hyperacetylation of histone H3 and even reduce the expression of EGFR and Akt in NCI–H1975 cells. In further assays, compound 11e also showed moderate anti-proliferative activity in other EGFRT790M harboring tumor cell lines (NCI–H820, Ba/F3_EGFR_Del19-T790M-C797S) and low toxicities in normal cell lines (HL-7702, FHC). This selectivity of designed multitargeted compounds could serve as a potential strategy to circumvent multiple mechanisms of acquired resistance to EGFR-targeted therapy without severe toxicities and side effects resulting from broad inhibition. Image 1 • A series of hydroxamic acid-containing 4-aminoquinazoline derivatives were developed. • Compounds were selective for several EGFRT790M mutant over wild type cell lines. • Compound 11e reduced the expression of EGFR and Akt in NCI–H1975 cells. • Compound 11e induced apoptosis in NCI–H1975 cells. • Compound 11e showed low toxicities in HL-7702 and FHC normal cell lines. [ABSTRACT FROM AUTHOR]

Cooperative microgrids (CMGs) can effectively solve the energy interaction between microgrids (MGs) while increasing the penetration rate of renewable energy systems (RESs) and reducing the interaction frequency with the grid. However, the uncertainty of RESs will bring new challenges to the energy management and economic dispatch of CMGs, especially in increasing the number of MGs connected to the grid. Taking into account this uncertainty, it is extremely unlikely that the forecast uncertainty information will be at the worst values in every period, and this forecast uncertainty information is near the expected values in most cases. Therefore, a two-stage robust optimal model under expected scenarios for CMGs is proposed in this study to improve the conservatism of traditional models and minimise the daily cost. In this model, the first-stage decision results (FDRs) are determined by minimising the daily cost of CMGs under the expected scenarios. The proposed model is transformed based on two-stage zero-sum game theory and dual theory, a column and constraint generation algorithm is first used to test the robust feasibility of the FDR, and the second-stage decision results can be obtained without changing the FDR. Case studies verify that the proposed model can effectively solve energy transactions between MGs while mitigating the uncertainty disturbances in the operation of CMGs. [ABSTRACT FROM AUTHOR]

• A least square-based polynomial is fitted to a partial charging voltage curve. • A DBN model based on polynomial parameters is constructed to estimate the battery capacity. • The influence of different partial charging data spans on the capacity estimation accuracy is thoroughly explored. Accurate capacity estimation of lithium-ion batteries is an important topic for electric vehicles. In real cases, electric vehicles are usually not charged from zero to full capacity; thus, the battery management systems (BMSs) of electric vehicles have insufficient data when evaluating battery capacity degradation. Considering the above conditions, we propose a flexible battery capacity estimation method based on partial charging voltage curves and polynomial fitting. First, the charge voltage curve is fitted with a polynomial function with respect to time. Then, the parameters of the polynomial functions are selected as health indicators (HIs) for the battery. Finally, these parameters are input into a deep learning model to estimate the battery capacity. Compared with existing data-driven methods, the proposed method requires less voltage data and is more flexible, allowing the battery charging capacity to be estimated in different phases. Batteries in different working scenarios were compared with advanced features proposed in the literature to validate the effectiveness and superiority of the proposed method. [ABSTRACT FROM AUTHOR]

Objective: The purpose was to explore the clinical effects and safety of gemcitabine plus nedaplatin in the treatment of advanced nasopharyngeal carcinoma.Materials and Methods: From March 2014 to August 2015, we recruited 63 advanced nasopharyngeal carcinoma patients in our hospital. Moreover, the 62 cases were randomly divided into control group (n = 31) and treatment group (n = 32). Patients in the control groups were treated with 5-fluorouracil 500 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1-5 plus cisplatin 20 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1-5 with 21 days per cycle for 3 cycles; Moreover, patients in the treatment group were given gemcitabine 1000 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1 and 8 plus nedaplatin 20 mg/m 2 + 500 ml 0.9% sodium chloride injection intervenous drop infusion in day 1 with 21 days per cycle for 3 cycles. The objective response rate (ORR) and chemotherapy-associated toxicities were compared between the two groups.Results: After 3 cycle chemotherapy, the ORR was 41.9% and 78.1% in the control and treatment group, respectively, with statistical difference (P < 0.05); The main chemotherapy-related toxicity were hematological toxicity and gastrointestinal reaction with no statistical difference between the two groups (P > 0.05).Conclusion: The ORR was relative high for gemcitabine plus nedaplatin in the treatment of advanced nasopharyngeal carcinoma with main toxicity of hematological toxicity and gastrointestinal reaction. [ABSTRACT FROM AUTHOR]

Chemokine receptor 2 (CXCR2) is the receptor of glutamic acid–leucine–arginine sequence-contained chemokines CXCs (ELR+ CXCs). In recent years, CXCR2-target treatment strategy has come a long way in cancer therapy. CXCR2 antagonists could block CXCLs/CXCR2 axis, and are widely used in regulating immune cell migration, tumor metastasis, apoptosis and angiogenesis. Herein, two series of new CXCR2 small-molecule inhibitors, including 1,2,4-triazol-3-one derivatives 1 – 11 and pyridazinone derivatives 12 – 22 were designed and synthesized based on the proof-to-concept. The pyridazinone derivative 18 exhibited good CXCR2 antagonistic activity (69.4 ± 10.5 %Inh at 10 μM) and demonstrated its significant anticancer metastasis activity in MDA-MB-231 cells and remarkable anti-angiogenesis activity in HUVECs. Furthermore, noteworthy was that 18 exhibited an obvious synergistic effect with Sorafenib in anti-proliferation assay in MDA-MB-231 cells. Moreover, 18 showed a distinct reduction of the phosphorylation levels of both PI3K and AKT proteins in MDA-MB-231 cells, and also affected the expression levels of other PI3K/AKT signaling pathway-associated proteins. The molecular docking studies of 18 with CXCR2 also verified the rationality of our design strategy. All of these results revealed pyridazinone derivative 18 as a promising CXCR2 antagonist for future cancer therapy. [Display omitted] • Novel CXCR2 antagonists 1,2,4-triazol-3-one and pyridazinone derivatives were developed. • 18 reduced the phosphorylation levels of both PI3K and AKT proteins in MDA-MB-231 cells. • 18 showed significant anticancer metastasis activity in MDA-MB-231 cells. • 18 showed remarkable anti-angiogenesis activity in HUVEC cells. • 18 caused a comforting synergistic effect with Sorafenib and enhanced the efficiency of Sorafenib in MDA-MB-231 cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • Two series of cyclic amine-containing benzimidazole carboxamide derivatives were designed and synthesized as potent anticancer agents. Most of them exhibited potent PARP1/2 inhibitory activity and in vitro antitumor activity. • 2-(1-(4,4-difluorocyclohexyl)piperidin-4-yl)-1H-benzo[ d ]imidazole-4-carboxamide (17d) could significantly inhibit PARP1/2 enzymes. • 17d also possessed obvious selective antineoplastic activity and noteworthy microsomal metabolic stability. • Further studies revealed that 17d was endowed with an excellent ADME profile. • The findings highlighted the potential of these derivatives as new anticancer agents and 17d as a candidate for the treatment of cancer. In this work, two series of cyclic amine-containing benzimidazole carboxamide derivatives were designed and synthesized as potent anticancer agents. PARP1/2 inhibitory activity assays indicated that most of the compounds showed significant activity. The in vitro antiproliferative activity of these compounds was investigated against four human cancer cell lines (MDA-MB-436, MDA-MB-231, MCF-7 and CAPAN-1), and several compounds exhibited strong cytotoxicity to tumor cells. Among them, 2-(1-(4,4-difluorocyclohexyl)piperidin-4-yl)-1H-benzo[ d ]imidazole-4-carboxamide (17d) was found to be effective PARP1/2 inhibitors (IC 50 = 4.30 and 1.58 nM, respectively). In addition, 17d possessed obvious selective antineoplastic activity and noteworthy microsomal metabolic stability. What's more, further studies revealed that 17d was endowed with an excellent ADME profile. These combined results indicated that 17d could be a promising candidate for the treatment of cancer. [ABSTRACT FROM AUTHOR]