Structure-based Discovery of a Series of NSD2-PWWP1 Inhibitors

Overexpression, point mutations or translocations of protein lysine methyltransferase NSD2 was occurred in many types of cancer cells. Therefore, it was recognized as onco-protein and considered as a promising anticancer drug target. NSD2 consists of a SET catalytic domain and two PWWP domains binding to methylated histone proteins. Here, we reported our efforts to develop a series of NSD2-PWWP1 inhibitors, and further structure-based optimization resulted a potent inhibitor 38, which has the high selectivity towards NSD2-PWWP1 domain. The detailed biological evaluation revealed that compound 38 can bind to NSD2-PWWP1 and then affect the expression of genes regulated by NSD2. The current discovery will provide a useful chemical probe to the future research in understanding the specific regulation mode of NSD2 by PWWP1 recognition, and pave the way to develop potential drugs targeting NSD2 protein.

Structure-based Discovery of a Series of NSD2-PWWP1 Inhibitor

Overexpression, point mutations or translocations of protein lysine methyltransferase NSD2 was occurred in many types of cancer cells. Therefore, it was recognized as onco-protein and considered as a promising anticancer drug target. NSD2 consists of a SET catalytic domain and two PWWP domains binding to methylated histone proteins. Here, we reported our efforts to develop a series of NSD2 PWWP1 inhibitors, and further structure-based optimization resulted a potent inhibitor 38, which has the high selectivity towards NSD2 PWWP1 domain. The detailed biological evaluation revealed that compound 38 can bind to NSD2-PWWP1 and then affect the expression of genes regulated by NSD2. We believe that the current discovery will provide a useful chemical probe to the future research in understanding the specific regulation mode of NSD2 by PWWP1 recognition.

Hierarchical Power Allocation Control for Star-Connected Hybrid Energy Storage System Using Cascaded Multilevel Converters

Hybrid energy storage system (HESS) using cascaded multilevel converters (CMC) has received increasing attention due to its merits on smoothing power fluctuations for renewable energy systems (RESs). However, CMC-based HESS still faces tough challenges due to asymmetrical ac power distribution. In this paper, hierarchical power allocation control strategy is utilized in CMC-based star-connected HESS to coordinate power between batteries and supercapacitors (SCs). Using the proposed power allocation mechanism, energy management strategy (EMS) with two operation modes can be achieved, which includes SC voltage regulation mode and power compensation mode. In SC voltage regulation mode, SC voltages are regulated to achieve long-term stable operation. Power compensation mode aims to allocate the active power fluctuation and employs SCs to mitigate it. Meanwhile, the principle of the hierarchical power allocation strategy is analyzed to facilitate the accurate control and flexible switching of different operation modes. A series of simulation and experiment tests are executed to demonstrate the performance of the proposed control strategy.

Research of Emergency Modes of Wind Power Plants Using Computer Simulation

The aim of this study is to investigate changes in the wind power plant energy production parameters under the conditions of sudden wind changes and voltage drop. To achieve these goals, a simulation of operation of wind power plants was performed. Twelve wind turbines with variable rotational speed equipped with a Fuhrländer FL 2500/104 asynchronous double-fed induction generator (DFIG) were used, each with an installed capacity of 2.5 MW. A general scheme of a wind power plant has been developed using a modular-trunk power distribution scheme. The system consists of wind power modules and a central substation, which allows total power to be supplied to the power system at a voltage of 35 kV. The central substation uses two high voltage switchgears. Four modules were used, each of them consisting of three wind turbines, with a power of 7.5 MW. The simulation of the wind turbines was performed in the MATLAB® Simulink® software environment. The mode of response of the turbines to a change in wind speed, a voltage drop in the 35 kV voltage system, and a one-phase short circuit to the ground in the system of 10.5 kV voltage was explored. The results show that a sudden voltage drop and the appearance of short circuits influence the wind power plant (WPP) operation in a different way independent of regulation mode. The power generation from WPP will be limited when voltage drop occurred for both AC and Voltage regulation mode and during short circuits while WPP is set on AC regulation mode.

Modeling Interprovincial Cooperative Carbon Reduction in China: An Electricity Generation Perspective

As the world faces great challenges from climate change, carbon reduction has become China’s basic national policy. However, as the main model for carbon reduction in China, the non-cooperative carbon reduction model (NCCRM) is a simple regulation mode, which is not beneficial for optimization of electricity generation capacity structure and cannot effectively motivate carbon reduction at the provincial level. Therefore, we propose an interprovincial cooperative carbon reduction model (CCRM) from the perspective of electricity generation, which provides a mechanism integrating two fundamental principles of efficiency and fairness. The CCRM consists of two parts: (1) an optimal model of carbon reduction with the object of minimizing the carbon emission of the cooperation union to determine the optimal annual electricity generation for each participating province and (2) a model that distributes the economic benefits of the cooperation among the provinces in the cooperation based on the Shapley value method. We applied the CCRM to the case of an interprovincial union of Shanghai, Sichuan, Shanxi, and Gansu in China. The results, based on the data from 2014 to 2017, show that cooperation can significantly reduce the carbon emission of the union by 425.78 × 108 kg, 11.06%; meanwhile, Shanghai, Sichuan, Shanxi, and Gansu can, respectively, get 2.79 × 108, 11.11 × 108, 4.07 × 108, and 3.19 × 108 CNY of extra benefits from carbon reduction. To test the impact of different parameter values on the results of the CCRM, a sensitivity analysis was conducted. Some policy recommendations are proposed to promote the implementation of the CCRM.

Mycobacterial CarD defines a novel mechanism of response to starvation stress

Under starvation conditions, bacteria tend to slow down their translation rate by reducing rRNA synthesis, but the way they accomplish that may vary in different bacteria. In Mycobacterium species, transcription of rRNA is activated by the RNA polymerase (RNAP) accessory transcription factor CarD, which interacts directly with RNAP to stabilize the RNAP-promoter open complex formed on rRNA genes. The functions of CarD have been extensively studied, but the mechanisms that control its expression remain obscure. Here, we report that the level of CarD was tightly regulated when mycobacterial cells switched from nutrient-rich to nutrient-deprived conditions. At the translational level, an antisense RNA of carD (AscarD) was induced in a SigF-dependent manner to bind with carD mRNA and inhibit CarD translation, while at the post-translational level, the Clp protease was activated and quickly degrades the residual CarD. AscarD thus worked synergistically with Clp protease to maintain CarD at the minimal level to help mycobacterial cells cope with the nutritional stress. Altogether, our work elucidates the regulation mode of CarD and delineates a new mechanism for the mycobacterial starvation response, which is important for the adaptation and persistence of mycobacterial pathogens in the host environment.

Stability Analysis of Different Regulation Modes of Hydropower Units

The dynamic characteristics of hydropower unit governing systems considerably influence the stability of hydropower units and the connected power system. The dynamic performances of hydropower units with power regulation mode (PRM) and opening regulation mode (ORM) are different. This paper establishes a detailed linear model of a hydropower unit based on the Phillips–Heffron model. The damping characteristic and stability of two regulation modes with different water inertia time constants TW were analyzed. ORM tended to provide negative damping, while PRM often provided positive damping in the major parts of the frequency range within the normal frequency oscillations when TW was large. Eigenvalue analysis illustrated that PRM has better stability than ORM. To validate the analysis, a simulation under two typical faults WAS conducted based on a nonlinear model of a hydropower unit. The simulation results illustrated that the responses of units with PRM are more stable in terms of important operating parameters, such as output power, rotor speed, and power angles. For hydropower units facing challenges in stable operation, PRM is recommended to obtain good dynamic stability.

Lactic Acid Bacterial Production of Exopolysaccharides from Fruit and Vegetables and Associated Benefits

Microbial polysaccharides have interesting and attractive characteristics for the food industry, especially when produced by food grade bacteria. Polysaccharides produced by lactic acid bacteria (LAB) during fermentation are extracellular macromolecules of either homo or hetero polysaccharidic nature, and can be classified according to their chemical composition and structure. The most prominent exopolysaccharide (EPS) producing lactic acid bacteria are Lactobacillus, Leuconostoc, Weissella, Lactococcus, Streptococcus, Pediococcus and Bifidobacterium sp. The EPS biosynthesis and regulation pathways are under the dependence of numerous factors as producing-species or strain, nutrient availability, and environmental conditions, resulting in varied carbohydrate compositions and beneficial properties. The interest is growing for fruits and vegetables fermented products, as new functional foods, and the present review is focused on exploring the EPS that could derive from lactic fermented fruit and vegetables. The chemical composition, biosynthetic pathways of EPS and their regulation mode is reported. The consequences of EPS on food quality, especially texture, are explored in relation to producing species. Attention is given to the scientific investigations on health benefits attributed to EPS such as prebiotic, antioxidant, anti-inflammatory and cholesterol lowering activities.