Demand response has become a key feature of the future smart grid. In addition to having advanced communication and computing infrastructures, a successful demand response program must respond to the ...needs of a power system. In other words, the efficiency and security of a power system dictate the locations, amounts and speeds of the load reductions of a demand response program. In this paper, we propose an event-driven emergency demand response scheme to prevent a power system from experiencing voltage collapse. A technique to design such a scheme is presented. This technique is able to provide key setting parameters such as the amount of demand reductions at various locations to arm the demand response infrastructure. The validity of the proposed technique has been verified by using several test power systems.
To adapt to habitat temperature, vertebrates have developed sophisticated physiological and ecological mechanisms through evolution. Transient receptor potential melastatin 8 (TRPM8) serves as the ...primary sensor for cold. However, how cold activates TRPM8 and how this sensor is tuned for thermal adaptation remain largely unknown. Here we established a molecular framework of how cold is sensed in TRPM8 with a combination of patch-clamp recording, unnatural amino acid imaging, and structural modeling. We first observed that the maximum cold activation of TRPM8 in eight different vertebrates (i.e., African elephant and emperor penguin) with distinct side-chain hydrophobicity (SCH) in the pore domain (PD) is tuned to match their habitat temperature. We further showed that altering SCH for residues in the PD with solventaccessibility changes leads to specific tuning of the cold response in TRPM8. We also observed that knockin mice expressing the penguin’s TRPM8 exhibited remarkable tolerance to cold. Together, our findings suggest a paradigm of thermal adaptation in vertebrates, where the evolutionary tuning of the cold activation in the TRPM8 ion channel through altering SCH and solvent accessibility in its PD largely contributes to the setting of the cold-sensitive/ tolerant phenotype.
The synthesis of alloys with long-range atomic-scale ordering (ordered intermetallics) is an emerging field of nanochemistry. Ordered intermetallic nanoparticles are useful for a wide variety of ...applications such as catalysis, superconductors, and magnetic devices. However, the preparation of nanostructured ordered intermetallics is challenging in comparison to disordered alloys, hindering progress in material development. Herein, we report a process for converting colloidally synthesized ordered intermetallic PdBi2 to ordered intermetallic Pd3Bi nanoparticles under ambient conditions by electrochemical dealloying. The low melting point of PdBi2 corresponds to low vacancy formation energies, which enables the facile removal of the Bi from the surface while simultaneously enabling interdiffusion of the constituent atoms via a vacancy diffusion mechanism under ambient conditions. The resulting phase-converted ordered intermetallic Pd3Bi exhibits 11 times and 3.5 times higher mass activity and high methanol tolerance for the oxygen reduction reaction compared with Pt/C and Pd/C, respectively, which is the highest reported for a Pd-based catalyst, to the best of our knowledge. These results establish a key development in the synthesis of noble-metal-rich ordered intermetallic phases with high catalytic activity and set forth guidelines for the design of ordered intermetallic compounds under ambient conditions.
Previous observational evidence has indicated the potential involvement of the gut microbiota (GM) in the development of endometriosis. However, the causal relationship of the association remains to ...be investigated.BACKGROUNDPrevious observational evidence has indicated the potential involvement of the gut microbiota (GM) in the development of endometriosis. However, the causal relationship of the association remains to be investigated.Genome-wide association study (GWAS) data of GM was obtained from the MiBioGen consortium, and GWAS for endometriosis data was from the FinnGen consortium. Initially, a two-sample Mendelian randomisation (MR) analysis was performed to identify specific bacteria associated with endometriosis. Inverse variance-weighted (IVW) was used as the main MR analysis to infer causal relationships. The other four popular MR methods including MR-Egger regression, weighted mode, weighted median, and simple mode were used for secondary confirmation. Subsequently, these selected bacteria were employed as exposure to investigate their causal effects on six sub-types of endometriosis. Furthermore, reverse MR analysis was implemented to evaluate the reverse causal effects. Cochran's Q statistics was used to test the heterogeneity of instrumental variables (IVs); MR-Egger regression was used to test horizontal pleiotropy; MR-PRESSO and leave-one-out sensitivity analysis were applied to find significant outliers.METHODGenome-wide association study (GWAS) data of GM was obtained from the MiBioGen consortium, and GWAS for endometriosis data was from the FinnGen consortium. Initially, a two-sample Mendelian randomisation (MR) analysis was performed to identify specific bacteria associated with endometriosis. Inverse variance-weighted (IVW) was used as the main MR analysis to infer causal relationships. The other four popular MR methods including MR-Egger regression, weighted mode, weighted median, and simple mode were used for secondary confirmation. Subsequently, these selected bacteria were employed as exposure to investigate their causal effects on six sub-types of endometriosis. Furthermore, reverse MR analysis was implemented to evaluate the reverse causal effects. Cochran's Q statistics was used to test the heterogeneity of instrumental variables (IVs); MR-Egger regression was used to test horizontal pleiotropy; MR-PRESSO and leave-one-out sensitivity analysis were applied to find significant outliers.A total of 1131 single nucleotide polymorphisms (SNPs) were collected as IVs for 196 GM taxa with endometriosis as the outcome. We identified 12 causal relationships between endometriosis and GM taxa including 1 phylum, 3 families, 2 orders, and 6 genera (Rikenellaceae RC9 gut group, Eubacterium ruminantium group, Faecalibacterium, Peptococcus, Clostridium sensu stricto 1, and Ruminococcaceae UCG005). Utilizing the Bonferroni method, we identified phylum Cyanobacteria as the strongest associated GM taxa. Subsequently, 6 significant causal effects were uncovered between the 12 selected specific GM and 6 sub-types of endometriosis. Meanwhile, no reverse causal relationship was found. Further, no horizontal pleiotropy and no significant outliers were detected in the sensitive analysis.RESULTA total of 1131 single nucleotide polymorphisms (SNPs) were collected as IVs for 196 GM taxa with endometriosis as the outcome. We identified 12 causal relationships between endometriosis and GM taxa including 1 phylum, 3 families, 2 orders, and 6 genera (Rikenellaceae RC9 gut group, Eubacterium ruminantium group, Faecalibacterium, Peptococcus, Clostridium sensu stricto 1, and Ruminococcaceae UCG005). Utilizing the Bonferroni method, we identified phylum Cyanobacteria as the strongest associated GM taxa. Subsequently, 6 significant causal effects were uncovered between the 12 selected specific GM and 6 sub-types of endometriosis. Meanwhile, no reverse causal relationship was found. Further, no horizontal pleiotropy and no significant outliers were detected in the sensitive analysis.This MR analysis revealed significant causal effects between GM and endometriosis and phylum Cyanobacteria had the strongest association.CONCLUSIONSThis MR analysis revealed significant causal effects between GM and endometriosis and phylum Cyanobacteria had the strongest association.
Autophagy of mitochondria, termed mitophagy, plays an important role in cerebral ischemia-reperfusion (IR) injury, but the mechanism is not yet clear. Tissue-type plasminogen activator (tPA) is the ...most important thrombolytic drug in the clinical treatment of ischemic stroke and has neuroprotective effects. Here, we explored the effects of tPA on neuronal apoptosis and mitophagy following IR. We found that knocking out the tPA gene significantly aggravated brain injury and increased neuronal apoptosis and mitochondrial damage. Exposure of neurons to tPA reduced injury severity and protected mitochondria. Further studies demonstrated that this protective effect of tPA was achieved via regulation of FUNDC1-mediated mitophagy. Furthermore, we found that tPA enhanced the expression level of FUNDC1 by activating the phosphorylation of AMPK. In summary, our results confirm that tPA exerts neuroprotective effects by increasing the phosphorylation of AMPK and the expression of FUNDC1, thereby inhibiting apoptosis and improving mitochondrial function.
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•After cerebral ischemia, tPA released by neurons has a neuroprotective effect.•tPA modulates mitophagy to decrease oxidative stress and inhibit apoptosis.•The mitochondrial membrane protein FUNDC1 and the AMPK signaling pathway are involved in the neuroprotective process of tPA.
The Tibetan Plateau, known as the “Water Tower of Asia”, is the source of many rivers in Asia, and its water conservation function is the basis for the optimization of the ecological barrier and the ...water security of Asian countries. Yet, the Tibetan Plateau is also an ecologically fragile area, facing numerous ecological issues and climate change risks, so the response of the water conservation function to the changing environment has received much attention.
This study systematically analyzed the variation trend of the water conservation function during 1961–2017, using the InVEST model simulations, linear regression analysis, and coefficients of variation.
The results show that the average annual water conservation of the Tibetan Plateau is about 256 billion m3, showing a decreasing trend from southeast to northwest, and the important areas scatter in the southeastern of the plateau, such as the lower Yarlung Zangbo watershed, the Nujiang watershed, and the Yalong watershed. The water conservation volume of the Tibetan Plateau was on the rise (P < 0.05), and there was spatial variability in the trends and coefficients of variation. The increase of precipitation and NDVI leads to the overall increase in the water conservation of the Tibetan Plateau. Our findings could be used to fill the spatiotemporal variation gaps in the water conservation function of the Tibetan Plateau.
Spatial distribution of average annual (a) water yield, (b) water conservation, (c) precipitation, and (d) actual evapotranspiration on the Tibetan Plateau from 1961 to 2017. Display omitted
•The water conservation has been analyzed in the Tibetan Plateau from 1961 to 2017.•The mean annual water conservation in the Tibetan Plateau is about 256 billion m3.•The interannual variation in water conservation shows an increasing trend.•The increase of precipitation and NDVI leads to the increase of water conservation.
Cisplatin is commonly used in ovarian cancer chemotherapy, however, chemoresistance to cisplatin remains a great clinical challenge. Oncogenic transcriptional factor FOXM1 has been reported to be ...overexpressed in ovarian cancer. In this study, we aimed to investigate the potential role of FOXM1 in ovarian cancers with chemoresistance to cisplatin. Our results indicate that FOXM1 is upregulated in chemoresistant ovarian cancer samples, and defends ovarian cancer cells against cytotoxicity of cisplatin. FOXM1 facilitates DNA repair through regulating direct transcriptional target EXO1 to protect ovarian cancer cells from cisplatin-mediated apoptosis. Attenuating FOXM1 and EXO1 expression by small interfering RNA, augments the chemotherapy efficacy against ovarian cancer. Our findings indicate that targeting FOXM1 and its target gene EXO1 could improve cisplatin effect in ovarian cancer, confirming their role in modulating cisplatin sensitivity.
Sustainability issues have gained growing awareness in recent years. Governments play an important role in environment and resources problems since they can affect enterprises’ production activities ...by enacting policies and regulations. To promote green production in the long term associated with the consideration of financial intervention of governments, we establish a three-population model of suppliers, manufacturers and governments based on evolutionary game theory, and analyze the evolutionary stable strategies (ESS) of their unilateral and joint behaviors. Further, system dynamics (SD) is applied to empirical analysis for exploring the dynamic interaction of the populations’ strategy, and the key factors affecting ESS are also discussed in detail. The results show that: (1) the proportion of green suppliers and manufacturers in their groups determines whether the government implements regulation; (2) any party of the supplier and manufacturer that adopts green strategy could promote green behavior of the other; (3) the government is advised to supervise and implement reward and punishment mechanism under the low proportion of green supply chain; (4) government regulation could promote the corporations to adopt green behavior and should preferentially implements the mechanism on manufacturers. The results provide insights into the policy-making of governments and enterprises management on sustainable development.
Deep soil water, defined here as the soil water below a certain depth and not recharged by precipitation in one growing season, plays a critical role in maintaining eco‐physiological functioning in ...thick‐vadose‐zone regions. However, science‐based evidence remains limited on how and the extent to which deep soil desiccation (DSD) affects the eco‐physiological features of apple trees. Here, we improve a process‐based model to disentangle trees' transpiration and photosynthesis responses to precipitation and DSD below 200 cm (DSD200) on the semiarid Loess Plateau. We defined four DSD200 scenarios: 60%–70% of field capacity (FC) as a control, 50%–60%, 40%–50%, and 30%–40% of FC representing mild (MID), moderate (MOD) and severe (SED) desiccation, respectively; and five precipitation scenarios: extremely dry (285.78 mm), dry (392 mm), normal (457.72 mm), wet (524.96 mm), and extremely wet years (630.44 mm). We found that the stomatal conductance, net photosynthetic rate and transpiration under MOD and SED decreased significantly (p < 0.05), independent of precipitation years, indicating clear stomatal limitation induced by DSD200. This phenomenon was greatly enhanced in extremely dry years, with these variables decreasing on average by 29%, 36%, and 37%, respectively. Furthermore, SED resulted in non‐stomatal limitation with a great decrease in electron transport rates (Jmax) and maximum carboxylation rates (VCmax). Jmax and VCmax decreased by 40% and 26%, respectively, on average, in extremely dry years. These findings indicate that the combination of severe meteorological drought and deep soil drought resulted in non‐stomatal limitation for the apple trees. Persistent non‐stomatal limitation may be an important mechanism causing tree mortality in semiarid loess regions.
Key Points
A process‐based model was improved to disentangle trees' eco‐physiological responses to precipitation and deep soil desiccation (DSD) below 2 m
Stomatal limitation occurs under moderate and severe DSD scenarios across precipitation years
Combination of severe meteorological drought and deep soil drought resulted in non‐stomatal limitation for trees
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