Uncertainty of the wind power output is the main influence factor for wind power utilization in the bulk power system. Because of the large capacity and the load characteristic, energy-intensive load ...holds great potentials to share the burden of wind power fluctuation smoothing. In this paper, a direct control scheme of the energy-intensive load power is proposed to smooth the wind power fluctuation. Based on the characteristic of the energy-intensive load production technology, the feasibility of energy-intensive load control and its influence on the production are discussed. A feedback control is designed to regulate the saturable reactor and transformer tap changer when the power support from the bulk power system is limited. Regulation capacity is analyzed quantitatively based on the energy-intensive load equivalent circuit model. A grid-connected energy-intensive enterprise driven by self-generation wind power plants and thermal power plants is studied as an example case. By the proposed energy-intensive load control scheme, power fluctuation of the wind farms can be smoothed with the minimum control cost. Besides, the regulation requirement of the bulk power system is eased correspondingly so that the utilization capacity of the power system can be improved significantly. Simulation is done on the real-time digital simulator to verify the effectiveness of the proposed control method.
Efficient and accurate prediction of molecular properties, such as lipophilicity and solubility, is highly desirable for rational compound design in chemical and pharmaceutical industries. To this ...end, we build and apply a graph-neural-network framework called self-attention-based message-passing neural network (SAMPN) to study the relationship between chemical properties and structures in an interpretable way. The main advantages of SAMPN are that it directly uses chemical graphs and breaks the black-box mold of many machine/deep learning methods. Specifically, its attention mechanism indicates the degree to which each atom of the molecule contributes to the property of interest, and these results are easily visualized. Further, SAMPN outperforms random forests and the deep learning framework MPN from Deepchem. In addition, another formulation of SAMPN (Multi-SAMPN) can simultaneously predict multiple chemical properties with higher accuracy and efficiency than other models that predict one specific chemical property. Moreover, SAMPN can generate chemically visible and interpretable results, which can help researchers discover new pharmaceuticals and materials. The source code of the SAMPN prediction pipeline is freely available at Github (
https://github.com/tbwxmu/SAMPN
).
Objective
We conducted a Mendelian randomization (MR) study to disentangle the comparative effects of lipids and apolipoproteins on ischemic stroke.
Methods
Single‐nucleotide polymorphisms associated ...with low‐ and high‐density lipoprotein (LDL and HDL) cholesterol, triglycerides, and apolipoprotein A‐I and B (apoA‐I and apoB) at the level of genomewide significance (p < 5 × 10−8) in the UK Biobank were used as instrumental variables. Summary‐level data for ischemic stroke and its subtypes were obtained from the MEGASTROKE consortium with 514,791 individuals (60,341 ischemic stroke cases, and 454,450 non‐cases).
Results
Increased levels of apoB, LDL cholesterol, and triglycerides were associated with higher risk of any ischemic stroke, large artery stroke, and small vessel stroke in the main and sensitivity univariable MR analyses. In multivariable MR analysis including apoB, LDL cholesterol, and triglycerides in the same model, apoB retained a robust effect (p < 0.05), whereas the estimate for LDL cholesterol was reversed, and that for triglycerides largely attenuated. Decreased levels of apoA‐I and HDL cholesterol were robustly associated with increased risk of any ischemic stroke, large artery stroke, and small vessel stroke in all univariable MR analyses, but the association for apoA‐I was attenuated to the null after mutual adjustment.
Interpretation
The present MR study reveals that apoB is the predominant trait that accounts for the etiological basis of apoB, LDL cholesterol, and triglycerides in relation to ischemic stroke, in particular large artery and small vessel stroke. Whether HDL cholesterol exerts a protective effect on ischemic stroke independent of apoA‐I needs further investigation. ANN NEUROL 2020;88:1229–1236
Battery Electric Vehicles (BEVs) are considered to have higher energy efficiency and advantages to better control CO2 emissions compared to Internal Combustion Engine Vehicles (ICEVs). However, in ...the context that a large amount of thermal power is still used in developing countries, the CO2 emission reduction effectiveness of BEVs can be weakened or even counterproductive. To reveal the impact of the electricity generation mix on carbon emissions from vehicles, this paper compares the life cycle carbon emissions of BEVs with ICEVs considering the regional disparity of electricity generation mix in China. According to Life Cycle Assessment (LCA) analysis and regional electricity carbon intensity, this study demonstrates that BEVs in the region with high penetration of thermal power produce more CO2 emissions, while BEVs in the region with higher penetration of renewable energy have better environmental performance in carbon emission reduction. For instance, in the region with over 50% penetration of renewable energy, a BEV can reduce more CO2 (18.32 t) compared to an ICEV. Therefore, the regions with high carbon emissions from vehicles need to increase the proportion of renewable generation as a priority rather than promoting BEVs.
In order to clarify the mechanism of how surface coatings affect surface withstand ability of insulator at dc voltage, the study of surface flashover on SiC/epoxy-coated insulator was conducted and a ...method that how to determine the approaching flashover moment (AFM) was proposed. Based on the plate-insulator and finger-shaped electrode arrangement, the flashover characters, as well as dynamic surface charge distribution during the applied voltage rising, were studied under two kinds of charging methods, i.e., compact and uncompact contact condition at electrode-insulator interface. It was found that the surface flashover voltage was increased with the increment of SiC contents in coatings. The dynamic surface charging evolution confirms that homocharge accumulation was the main charging phenomenon approaching the flashover occurrence, and the evolution mechanism of dynamic surface charge distribution was also explained. In addition, the surface electric field at the AFM was calculated; then, the effect of charge accumulation on flashover voltage was analyzed. At last, from the sight of charge accumulation, the influence of SiC contents on surface withstand ability at dc voltage was discussed.
Aims/hypothesis
Observational studies have shown a bidirectional association between major depressive disorder (MDD) and cardiometabolic diseases. We conducted a two-sample bidirectional Mendelian ...randomisation (MR) study to assess the causal associations of MDD with type 2 diabetes, coronary artery disease (CAD) and heart failure and vice versa.
Methods
We extracted summary-level data for MDD, type 2 diabetes, CAD and heart failure from corresponding published large genome-wide association studies of individuals mainly of European-descent. In total, 96 SNPs for MDD, 202 SNPs for type 2 diabetes, 44 SNPs for CAD and 12 SNPs for heart failure were proposed as instrumental variables at the genome-wide significance level (
p
< 5 × 10
−8
). The random-effects inverse-variance weighted method was used for the main analyses.
Results
Genetic liability to MDD was significantly associated with type 2 diabetes and CAD at the Bonferroni-corrected significance level. The ORs of type 2 diabetes and CAD were respectively 1.26 (95% CI 1.10, 1.43;
p
= 6 × 10
−4
) and 1.16 (95% CI 1.05, 1.29;
p
= 0.0047) per one-unit increase in log
e
odds of MDD. There was a suggestive association between MDD and heart failure (OR 1.11 95% CI 1.01, 1.21;
p
= 0.033). We found limited evidence supporting causal effects of cardiometabolic diseases on MDD risk in the reverse MR analyses.
Conclusions/interpretation
The present study strengthened the evidence that MDD is a potential risk factor for type 2 diabetes and CAD. Whether MDD is causally related to heart failure needs further study.
Data availability
All data included in this study were uploaded as supplements and are also publicly available through published GWASs and open GWAS datasets (UK Biobank, 23andMe and Psychiatric Genomics:
https://datashare.is.ed.ac.uk/handle/10283/3203;
DIAGRAM:
http://diagram-consortium.org/downloads.html;
CARDIoGRAMplusCD4:
www.cardiogramplusc4d.org/;
HERMES:
http://www.kp4cd.org/datasets/mi
).
Graphical abstract
IntroductionThe lung is recognized as a primary site in the induction of rheumatoid arthritis (RA). Our study aimed to assess the effect of common occupational inhalable exposures on risk of ...developing RA and their interactions with smoking and RA-risk genes.Material and MethodsFrom 1996 to 2017, 4,033 incident RA cases and 6,485 controls matched on age, sex, and residential area were recruited from central and southern Sweden, all answering a self-administered questionnaire. For each participant, occupational history was retrieved, which together with information from a Swedish national job-exposure matrix allowed us to estimate the cumulative exposure to 32 different inhalable agents, taking prevalence and concentration into account. Approximately 3,400 cases and 2,800 controls had concomitant genetic data (genome-wide genotypes). Two subtypes of RA were assessed based on the status of anti-citrullinated protein/peptide antibodies (ACPA), comprising 2,642 ACPA-positive cases and 1,391 ACPA-negative cases).Results and ConclusionsAn increased risk of developing ACPA-positive RA was found for individuals ever exposed to any of the 32 occupational inhalable agents (OR=1.25, 95%CI=1.12–1.38). The risk increased in a dose-response manner according to number of agents (Ptrend< 0.001) and duration of exposure (Ptrend< 0.001).Across 16 specific collections of agents, a very large risk of developing RA in the triple-exposed group (occupational exposure, smoking, and high genetic risk) was observed for the ACPA-positive subtype with odds ratios (ORs) ranging from 18.0 to 45.1, while the estimates for ACPA-negative subtype were much weaker with ORs ranging from 0.85 to 2.64.Occupational inhalable agents could act as important environmental triggers in RA development and interact with smoking and RA-risk genes leading to an excessive disease risk. These effects are specific to ACPA-positive RA. Preventive strategies aimed at reducing occupational hazards and smoking are warranted for reduction of the burden of RA, especially for those who are genetically vulnerable.
Scope
Polycystic ovary syndrome (PCOS) is closely related to non‐alcoholic fatty liver disease (NAFLD), and sex hormone‐binding globulin (SHBG) is a glycoprotein produced by the liver. Hepatic ...lipogenesis inhibits hepatic SHBG synthesis, which leads to hyperandrogenemia and ovarian dysfunction in PCOS. Therefore, this study aims to characterize the mechanism whereby liver lipogenesis inhibits SHBG synthesis.
Methods and results
This study establishes a rat model of PCOS complicated by NAFLD using a high‐fat diet in combination with letrozole and performs transcriptomic analysis of the liver. Transcriptomic analysis of the liver shows that the expression of neurite growth inhibitor‐B receptor (NgBR), hepatocyte nuclear factor 4α (HNF4α), and SHBG is low. Meantime, HepG2 cells are treated with palmitic acid (PA) to model NAFLD in vitro, which causes decreases in the expression of NgBR, HNF4α, and SHBG. However, the expression of HNF4α and SHBG is restored by treatment with the AMP‐activated protein kinase (AMPK) agonist AICAR.
Conclusions
NgBR regulates the expression of HNF4α by activating the AMPK signaling pathway, thereby affecting the synthesis of SHBG in the liver. Further mechanistic studies regarding the effect of liver fat on NGBR expression are warranted.
Hypothetical mechanism of NgBR regulating liver SHBG synthesis to mediate polycystic ovary syndrome. NgBR, neurite growth inhibitor‐B receptor; SHBG, human sex hormone‐binding globulin.
The drug repurposing of known approved drugs (e.g., lopinavir/ritonavir) has failed to treat SARS-CoV-2-infected patients. Therefore, it is important to generate new chemical entities against this ...virus. As a critical enzyme in the lifecycle of the coronavirus, the 3C-like main protease (3CLpro or Mpro) is the most attractive target for antiviral drug design. Based on a recently solved structure (PDB ID: 6LU7), we developed a novel advanced deep Q-learning network with a fragment-based drug design (ADQN–FBDD) for generating potential lead compounds targeting SARS-CoV-2 3CLpro. We obtained a series of derivatives from the lead compounds based on our structure-based optimization policy (SBOP). All of the 47 lead compounds obtained directly with our AI model and related derivatives based on the SBOP are accessible in our molecular library. These compounds can be used as potential candidates by researchers to develop drugs against SARS-CoV-2.
Objective
To investigate the association between obesity‐related traits and risk of rheumatoid arthritis (RA).
Methods
We conducted genetic correlation analysis and a 2‐sample Mendelian randomization ...(MR) study, using genome‐wide genetic data based on >850,000 individuals of European ancestry. Summary statistics were collected from the largest genome‐wide association study conducted to date for body mass index (BMI; n = 806,810), waist‐to‐hip ratio (WHR; n = 697,734), WHR adjusted for BMI (WHRadjBMI; n = 694,649), and RA (ncase = 14,361, ncontrol = 43,923). We conducted cross‐trait linkage disequilibrium score regression and ρ‐HESS analyses to quantify genetic correlation between pairs of traits (causal overlap). For each obesity‐related exposure, we utilized independent, genome‐wide significant single‐nucleotide polymorphisms (P < 5 × 10−9) as instruments to perform MR analysis (causal relationship). We interrogated the causal relationship both in the general population and in a sex‐specific manner and calculated odds ratios (ORs) and 95% confidence intervals (95% CIs). Sensitivity analyses were performed to validate MR model assumptions.
Results
Despite a negligible overall genetic correlation between the 3 obesity‐related traits and RA, we found significant local genetic correlations at several regions on chromosome 6 (positions 28–29M, 30–35M, and 50–52M), highlighting a shared genetic basis. We further observed an increased risk of RA per SD increment (4.8 kg/m2) in genetically predicted BMI (OR 1.22 95% CI 1.09–1.37). The effect was consistent across sensitivity analyses and comparable between sexes (OR 1.22 95% CI 1.04–1.44 in male subjects and 1.19 95% CI 1.04–1.36 in female subjects). However, we did not find evidence supporting a causal role of either WHR (OR 0.98 95% CI 0.84–1.14) or WHRadjBMI (OR 0.90 95% CI 0.79–1.04) in RA.
Conclusion
Genetically predicted BMI significantly increases RA risk. Future studies are needed to understand the biologic mechanisms underlying this link.
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