Air pollution has become an extremely serious problem, with particulate matter having a significantly greater impact on human health than other contaminants. The small diameter of fine particulate ...matter (PM2.5) allows it to penetrate deep into the alveoli as far as the bronchioles, interfering with a gas exchange within the lungs. Long-term exposure to particulate matter has been shown to cause the cardiovascular disease, respiratory disease, and increase the risk of lung cancers. Therefore, forecasting air quality has also become important to help guide individual actions. This paper aims to forecast air quality for up to 48 h using a combination of multiple neural networks, including an artificial neural network, a convolutional neural network, and a long-short-term memory to extract spatial-temporal relations. The proposed predictive model considers various meteorology data from the previous few hours as well as information related to the elevation space to extract terrain impact on air quality. The model includes trends from multiple locations, extracted from correlations between adjacent locations, and among similar locations in the temporal domain. Experiments employing Taiwan and Beijing data sets show that the proposed model achieves excellent performance and outperforms current state-of-the-art methods.
With the deployment of advanced metering infrastructure (AMI), an avalanche of new energy-use information became available. Better understanding of the actual power consumption patterns of customers ...is critical for improving load forecasting and efficient deployment of smart grid technologies to enhance operation, energy management, and planning of electric power systems. Unlike traditional aggregated system-level load forecasting, the AMI data introduces a fresh perspective to the way load forecasting is performed, ranging from very short-term load forecasting to long-term load forecasting at the system level, regional level, feeder level, or even down to the consumer level. This paper addresses the efforts involved in improving the system level intraday load forecasting by applying clustering to identify groups of customers with similar load consumption patterns from smart meters prior to performing load forecasting.
Nutrient inputs from the Mississippi/Atchafalaya River system into the northern Gulf of Mexico promote high phytoplankton production and lead to high respiration rates. Respiration coupled with water ...column stratification results in seasonal summer hypoxia in bottom waters on the shelf. In addition to consuming oxygen, respiration produces carbon dioxide (CO2), thus lowering the pH and acidifying bottom waters. Here we present a high‐resolution biogeochemical model simulating this eutrophication‐driven acidification and investigate the dominant underlying processes. The model shows the recurring development of an extended area of acidified bottom waters in summer on the northern Gulf of Mexico shelf that coincides with hypoxic waters. Not reported before, acidified waters are confined to a thin bottom boundary layer where the production of CO2 by benthic metabolic processes is dominant. Despite a reduced saturation state, acidified waters remain supersaturated with respect to aragonite.
Key Points
A biogeochemical model realistically simulates eutrophication‐induced acidification in the northern Gulf of Mexico
The sediments, which are a major source of dissolved inorganic carbon (DIC), cause low pH that is restricted to the bottom boundary layer
The contribution of river‐derived organic matter to DIC production and acidification is small in the river outflow region
Nowadays, with the highly penetrated wind generations, the accurate wind farm (WF) model is required for power system stability analysis. Due to the complexity on detailed WF model, the aggregated ...model, with a reasonable reduction of the detailed model meanwhile retaining the required level of accuracy is essential to be developed. In this paper, an improved WF aggregated modeling method for large-scale power system stability studies is proposed. To overcome the limitations of the traditional methods, a geometric template matching based time series wind turbines clustering method is developed. Moreover, a multiobjective optimization algorithm, which fully considered the wind speed disturbance and system fault together, is designed to identify both the generator and control parameters. Additionally, to shrink the size of the identified parameters and increase the modeling accuracy, a sensitivity and correlation analysis based key parameters selection scheme is also adopted. To verify the effectiveness of the proposed method, dynamic responses of the proposed aggregated model are compared against the responses of the traditional equivalent model for various wind scenarios through an actual case.
To ensure the completion of DNA replication and maintenance of genome integrity, DNA repair factors protect stalled replication forks upon replication stress. Previous studies have identified a ...critical role for the tumor suppressors BRCA1 and BRCA2 in preventing the degradation of nascent DNA by the MRE11 nuclease after replication stress. Here we show that depletion of SMARCAL1, a SNF2-family DNA translocase that remodels stalled forks, restores replication fork stability and reduces the formation of replication stress-induced DNA breaks and chromosomal aberrations in BRCA1/2-deficient cells. In addition to SMARCAL1, other SNF2-family fork remodelers, including ZRANB3 and HLTF, cause nascent DNA degradation and genomic instability in BRCA1/2-deficient cells upon replication stress. Our observations indicate that nascent DNA degradation in BRCA1/2-deficient cells occurs as a consequence of MRE11-dependent nucleolytic processing of reversed forks generated by fork remodelers. These studies provide mechanistic insights into the processes that cause genome instability in BRCA1/2-deficient cells.
Display omitted
•SNF2 fork remodelers promote nascent DNA degradation in BRCA1/2-deficient cells•Fork remodelers favor MRE11 binding to stalled forks in BRCA1-deficient cells•Forks regressed by fork remodelers are degraded by MRE11 in BRCA1-deficient cells•Depletion of fork remodelers reduces genomic instability in BRCA1/2-deficient cells
Taglialatela et al. report that the replication fork remodelers SMARCAL1, ZRANB3, and HLTF promote the degradation of nascent DNA catalyzed by the MRE11 nuclease in BRCA1/2-deficient mammary epithelial cells treated with replication stress-inducing agents. Depletion of fork remodelers restores fork integrity and reduces genome instability in BRCA1/2-deficient cells.
Precise editing of genomic DNA can be achieved upon repair of CRISPR-induced DNA double-stranded breaks (DSBs) by homology-directed repair (HDR). However, the efficiency of this process is limited by ...DSB repair pathways competing with HDR, such as non-homologous end joining (NHEJ). Here we individually express in human cells 204 open reading frames involved in the DNA damage response (DDR) and determine their impact on CRISPR-mediated HDR. From these studies, we identify RAD18 as a stimulator of CRISPR-mediated HDR. By defining the RAD18 domains required to promote HDR, we derive an enhanced RAD18 variant (e18) that stimulates CRISPR-mediated HDR in multiple human cell types, including embryonic stem cells. Mechanistically, e18 induces HDR by suppressing the localization of the NHEJ-promoting factor 53BP1 to DSBs. Altogether, this study identifies e18 as an enhancer of CRISPR-mediated HDR and highlights the promise of engineering DDR factors to augment the efficiency of precision genome editing.
With more distributed energy resources penetrated into the residential community, nanogrid based peer-to-peer (P2P) energy market has rapidly emerged over recent years. Due to the complexities on the ...decision-making process of each market participant, an efficient, fair and beneficial oriented bidding strategy is thus necessary. In this article, a two-stage bidding strategy for P2P trading of nanogrid is proposed. To overcome the limitations of traditional methods, in the first stage, a supply-demand relationship considered two-step price predictor, which aims to promote the usage of local renewable energy, is formulated to provide the guidance on transaction adjustment. In the second stage, trading preference based simultaneous game-theoretic approach is fully introduced, which can optimize the market equilibrium and then increase the social welfare of the P2P market. Additionally, to mitigate the possible failure of price matching, value-at-risk is implemented through the trading process as a risk hedging tool. To verify the effectiveness of the proposed strategy, usages of local renewable energy, economic benefits and success rates of transaction is compared against the traditional method for various cases.
BRCA1/2 mutant tumor cells display an elevated mutation burden, the etiology of which remains unclear. Here, we report that these cells accumulate ssDNA gaps and spontaneous mutations during ...unperturbed DNA replication due to repriming by the DNA primase-polymerase PRIMPOL. Gap accumulation requires the DNA glycosylase SMUG1 and is exacerbated by depletion of the translesion synthesis (TLS) factor RAD18 or inhibition of the error-prone TLS polymerase complex REV1-Polζ by the small molecule JH-RE-06. JH-RE-06 treatment of BRCA1/2-deficient cells results in reduced mutation rates and PRIMPOL- and SMUG1-dependent loss of viability. Through cellular and animal studies, we demonstrate that JH-RE-06 is preferentially toxic toward HR-deficient cancer cells. Furthermore, JH-RE-06 remains effective toward PARP inhibitor (PARPi)-resistant BRCA1 mutant cells and displays additive toxicity with crosslinking agents or PARPi. Collectively, these studies identify a protective and mutagenic role for REV1-Polζ in BRCA1/2 mutant cells and provide the rationale for using REV1-Polζ inhibitors to treat BRCA1/2 mutant tumors.
Display omitted
•ssDNA gaps arise in BRCA1 mutant cancer cells due to PRIMPOL-mediated repriming•BRCA1/2 deficiency leads to mutagenic ssDNA gap repair by REV1-Polζ-dependent TLS•Targeted REV1-Polζ inhibition shows enhanced toxicity in HR-deficient cancer cells•ssDNA gaps formed by SMUG1 and PRIMPOL mediate the toxicity of REV1-Polζ inhibition
Taglialatela et al. report that homologous recombination (HR)-deficient cancer cells, such as BRCA1/2 mutant cells, display increased reliance on error-prone translesion synthesis (TLS) for the repair of ssDNA gaps arising spontaneously during DNA replication. TLS inhibition shows exquisite toxicity in BRCA1/2-deficient cancer cells, providing the basis for alternative therapies against BRCA1/2 mutant tumors.
With the emerging of prosumers in residential level, peer-to-peer (P2P) energy trading provides a novel way to prompt the localized management of distributed energy resources (DERs). However, the ...work of designing an appropriate market framework, with the fair and flexible pricing strategy for each participant, is still very challenging. This article proposes a two-settlement P2P energy market framework for the joint scheduling and trading of prosumers in community microgrid. To provide price certainty and increase the localized transaction volume of DERs, a risk-implemented simultaneous game approach is adopted into the hour-ahead market. For mitigating the supply uncertainties in local, meanwhile optimizing the overall financial benefits for the entire microgrid, a BRP-based reserve services mechanism, with an auction-based pricing strategy, is implemented to a real-time market. The various case-based simulation results are presented to verify the effectiveness of the proposed two-settlement trading scheme for financial benefits enhancing and DERs consumption increasing in the P2P energy market.
DNA damage tolerance during eukaryotic replication is orchestrated by PCNA ubiquitination. While monoubiquitination activates mutagenic translesion synthesis, polyubiquitination activates an ...error-free pathway, elusive in mammals, enabling damage bypass by template switching. Fork reversal is driven in vitro by multiple enzymes, including the DNA translocase ZRANB3, shown to bind polyubiquitinated PCNA. However, whether this interaction promotes fork remodeling and template switching in vivo was unknown. Here we show that damage-induced fork reversal in mammalian cells requires PCNA ubiquitination, UBC13, and K63-linked polyubiquitin chains, previously involved in error-free damage tolerance. Fork reversal in vivo also requires ZRANB3 translocase activity and its interaction with polyubiquitinated PCNA, pinpointing ZRANB3 as a key effector of error-free DNA damage tolerance. Mutations affecting fork reversal also induced unrestrained fork progression and chromosomal breakage, suggesting fork remodeling as a global fork slowing and protection mechanism. Targeting these fork protection systems represents a promising strategy to potentiate cancer chemotherapy.
Display omitted
•Fork slowing and reversal upon damage require K63-linked PCNA polyubiquitination•ZRANB3 mediates fork slowing/reversal in vivo via binding to polyubiquitinated PCNA•ZRANB3 DNA translocase—not nuclease—activity mediates fork slowing and reversal•Mammalian error-free postreplication repair entails global fork slowing and reversal
Vujanovic et al. show that UBC13-mediated, K63-linked PCNA polyubiquitination mediates DNA damage-induced replication fork slowing and reversal, via recruitment to forks of ZRANB3 DNA translocase. These data link the postreplication repair pathway, yet elusive in mammals, to the regulation of fork progression and remodeling.
PDF
