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State abstraction is a widely used technique in reinforcement learning (RL) that compresses the state space to accelerate learning algorithms. However, designing an effective abstraction function in large-scale or high-dimensional state space problems remains a significant challenge. In this brief, we present a novel state abstraction method based on deep supervised hash learning (DSH) and provide a theoretical analysis of its near-optimal property. Furthermore, by leveraging the DSH-based representation as the optimization objective, we propose a direct and concise optimization method based on the target value. In addition, we construct an auxiliary learning task for state abstraction that can be combined with various RL algorithms. In particular, we apply the DSH-based state abstraction to both deep Q -learning (DQN) and soft actor-critic (SAC). Extensive experiments are conducted on Atari and several classic control benchmarks to evaluate the effectiveness of the DSH-based state abstraction method, showing that our method surpasses existing state abstraction algorithms in performance.
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Neonicotinoids (NEOs) are commonly used pesticides in agriculture. Urban parks containing numerous green plants and flowers also require NEOs for pest control. However, information on the distribution patterns and environmental risks of NEOs and their metabolites in urban park soils has yet to be discovered, which seriously limits the comprehensive evaluation of the potential hazards of NEOs. Our study explored the occurrence and distribution patterns of ten NEOs and five major metabolites in park soils from Guangzhou, Shijiazhuang, and Urumqi of China. At least three NEOs were detected in 95 % of soil samples, with the sum of all NEOs (∑10NEOs) ranging from 2.21 to 204 ng/g. Guangzhou has the highest levels of ∑10NEOs (median: 52.1 ng/g), followed by Urumqi (49.3 ng/g) and Shijiazhuang (21.7 ng/g). The top three most common NEOs in all three cities are imidacloprid, acetamiprid, and thiacloprid, which together account for 67 % to 70 % of ∑10NEOs. The levels of the metabolites of NEOs show a significant positive correlation with their corresponding parent NEOs. These NEOs pose detrimental effects to non-targeted invertebrates in the soil. Our findings raise concern about the environmental risks posed by NEO exposure to humans and other organisms in urban parks.
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Cell cycle regulatory enzyme Pin1 both catalyzes pSer/Thr-cis/trans-Pro isomerization and binds the same motif separately in its WW domain. To better understand the function of Pin1, a way to separate these activities is needed. An unnatural peptide library, R1CO-pSer-Pro-NHR2, was designed to identify ligands specific for the Pin1 WW domain. A new solid-phase phosphorylating reagent (SPPR) containing a phosphoramidite functional group was synthesized in one step from Wang resin. The SPPR was used in the preparation of the library by parallel synthesis. The final 315-member library was screened with our WW-domain-specific, enzyme-linked enzyme-binding assay (ELEBA). Four of the best hits were resynthesized, and the competitive dissociation constants were measured by ELEBA. NMR chemical-shift perturbations (CSP) of ligands with 15N-labeled Pin1 were used to measure Kd for the best four ligands directly, demonstrating that they were specific Pin1 WW domain ligands. Models of the ligands bound to the Pin1 WW domain were used to visualize the mode of binding in the WW domain.
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As a novel class of chiral stationary phase (CPS) material, chiral covalent organic frameworks (CCOFs) have already shown great promise in open-tubular capillary electrochromatography (OT-CEC) for chiral separation. The synthesis methods of CCOFs used in OT-CEC mainly include bottom-up, post modification and chiral induction. The CCOFs synthesized by bottom-up and post modification strategies already have lots of applications in capillary electrochromatography, however, the chiral-induced synthesized via an asymmetric catalytic strategy has not yet been reported for using as the chiral stationary phase (CPS) in OT-CEC or even in chromatographic separation. Herein, the chiral-induced COF (Λ)-TpPa-1 was synthesized by asymmetric catalytic synthesis and coated on the inner surface of a capillary by an in-situ growth strategy as the CPS for chiral drug separation. The baseline separation of six enantiomers was achieved within 14 min, with a high-resolution (Rs) range from 1.85 to 6.75. Moreover, the resolution and migration time of the capillary keep stable within 160 runs, showing its superior stability and repeatability. This research provides a new idea for the development and application of novel CPS materials in the field of capillary electrochromatography separation, also shows the new application of chiral induced COFs. Furthermore, the chiral-induced CCOFs can be easily applied to other chromatographic separation fields, exhibiting its extensive application value in chiral analysis separation.
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Eletrocromatografia Capilar , Eletrocromatografia Capilar/métodos , Eletrocromatografia Capilar/instrumentação , Estereoisomerismo , Estruturas Metalorgânicas/química , Reprodutibilidade dos TestesRESUMO
Since 1999, The Arabidopsis Information Resource (www.arabidopsis.org) has been curating data about the Arabidopsis thaliana genome. Its primary focus is integrating experimental gene function information from the peer-reviewed literature and codifying it as controlled vocabulary annotations. Our goal is to produce a "gold standard" functional annotation set that reflects the current state of knowledge about the Arabidopsis genome. At the same time, the resource serves as a nexus for community-based collaborations aimed at improving data quality, access, and reuse. For the past decade, our work has been made possible by subscriptions from our global user base. This update covers our ongoing biocuration work, some of our modernization efforts that contribute to the first major infrastructure overhaul since 2011, the introduction of JBrowse2, and the resource's role in community activities such as organizing the structural reannotation of the genome. For gene function assessment, we used gene ontology annotations as a metric to evaluate: (1) what is currently known about Arabidopsis gene function and (2) the set of "unknown" genes. Currently, 74% of the proteome has been annotated to at least one gene ontology term. Of those loci, half have experimental support for at least one of the following aspects: molecular function, biological process, or cellular component. Our work sheds light on the genes for which we have not yet identified any published experimental data and have no functional annotation. Drawing attention to these unknown genes highlights knowledge gaps and potential sources of novel discoveries.
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Arabidopsis , Bases de Dados Genéticas , Anotação de Sequência Molecular , Arabidopsis/genética , Genoma de Planta , Ontologia Genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismoRESUMO
Due to their high flexibility, low cost, and ease of handling, Unmanned Aerial Vehicles (UAVs) are often used to perform difficult tasks in complex environments. Stable and reliable path planning capability is the fundamental demand for UAVs to accomplish their flight tasks. Most researches on UAV path planning are carried out under the premise of known environmental information, and it is difficult to safely reach the target position in the face of unknown environment. Thus, an autonomous collision-free path planning algorithm for UAVs in unknown complex environments (APPA-3D) is proposed. An anti-collision control strategy is designed using the UAV collision safety envelope, which relies on the UAV's environmental awareness capability to continuously interact with external environmental information. A dynamic reward function of reinforcement learning combined with the actual flight environment is designed and an optimized reinforcement learning action exploration strategy based on the action selection probability is proposed. Then, an improved RL algorithm is used to simulate the UAV flight process in unknown environment, and the algorithm is trained by interacting with the environment, which finally realizes autonomous collision-free path planning for UAVs. The comparative experimental results in the same environment show that APPA-3D can effectively guide the UAV to plan a safe and collision-free path from the starting point to the target point in an unknown complex 3D environment.
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As a novel class of stationary phase materials, covalent organic frameworks (COFs) have shown great promise in open-tubular capillary electrochromatography. However, the current preparation of COFs coating capillaries heavily relies on tedious and time-consuming covalent bond methods. In this work, a novel, simple and rapid adsorption method was developed for fabrication of TPB-DMTP COF (fabricated from 1,3,5-tris(4-aminophenyl)benzene (TPB) and 2,5-dimethoxyterephthalaldehyde (DMTP)) coated capillary. Due to the crystallization process of the COF is greatly shortened because pre-modification capillary does not require silane coupling agent, this method enables the rapid preparation of COFs-coated capillaries. The organic molecular building units only need 25 min to form a stable COFs coating on the inner wall of a capillary by this method. To our knowledge, this is the shortest method for preparing COFs coated capillary up to now. The performance of the TPB-DMTP COF coated capillary was evaluated by using phthalate esters as model analytes. The results demonstrated that the TPB-DMTP COF coated capillary has excellent repeatability and stability. The relative standard deviations (RSDs) of the analyte's retention time of intra-day, inter-day and column-to-column were in the range of 0.05 %-0.27 %, 0.31 %-0.63 % and 0.31 %-0.88 %, respectively. And, no significant changes were observed in separation efficiency and retention time after over 200 runs. Finally, the TPB-DMTP COF coated capillary was applied for the determination of phthalates in marketed plastic bag and the recovery ranged from 88.0 % to 114.0 %.
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Capillary electrochromatography (CEC) has received increased attention from the academic community because it combines the excellent selectivity of high performance liquid chromatography (HPLC) and the high efficiency of capillary electrophoresis (CE). Selecting the most appropriate stationary phase material is crucial to achieve better separation effects in CEC. In recent years, a considerable number of materials, such as graphene oxide, proteins, metal organic frameworks, and covalent organic frameworks (COFs), have been widely used as stationary phases in CEC to further improve its separation performance and extend its scope of potential applications. Among these materials, COFs have shown great application prospects in CEC owing to their unique properties, which include high porosity, large surface area, excellent stability, tunable pore size, and high designability of the framework structure. This review systematically summarizes published papers on the development and application of COFs in CEC from 2016 to 2023. First, two COF-based capillary columns (i. e., open-tube CEC columns and monolithic CEC columns) and their preparation methods are introduced. Second, the applications of CEC based on COF stationary phases in the separation of environmental endocrine disruptors, pesticides, aromatic compounds, amino acids, and drugs, particularly chiral drugs, are systematically summarized. The separation mechanism of CEC based on COF stationary phases is also introduced. At present, the good separation ability of COF-based CEC is mainly attributed to two factors: 1) The size exclusion effect of the pores of the COF stationary phase. Because of differences in the sizes of their organic molecular building units and side chains, COFs have varying pore sizes and topological structures. Thus, target analytes smaller than the pores of the COFs can enter the frameworks and interact with them during separation. On the other hand, target analytes larger than the pores of the COFs cannot enter the frameworks and interact with them during separation; thus, they can be separated. 2) The interactions between the target analytes and side chains (e. g., hydrophobic interactions, hydrogen bonding, π-π interactions, etc.) of the COFs. Since COFs usually contain alkyl side chains, aromatic structures, and oxygen and/or nitrogen atoms with high electronegativity, various interactions could occur between the COFs and target analytes. Finally, directions for the future development and strategic application of CEC based on COF stationary phases are proposed. We believe that future research in CEC based on COF stationary phases should focus on the following aspects: 1) The use of cheminformatics to design and construct COFs to improve the efficiency of COF capillary column preparation; 2) the development of milder methods to synthesize COFs that can meet the requirements of high performance COF capillary columns; and 3) in-depth research to explore the separation mechanism of CEC based on COF stationary phases to provide theoretical guidance for developing CEC methods suitable for the separation and analysis of complex samples.
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Metal-organic framework materials are a class of novel crystalline porous materials with regular pore structures formed by covalent bonding between metal centers and organic functional groups. Metal-organic framework materials have attracted great interest in analytical chemistry due to their unique properties such as good stability and permanent porosity. In this work, D-histidine was used to carry out chiral modification of zeolitic imidazolate framework-90 under mild conditions, and the D-histidine modified zeolitic imidazolate framework-90 coated capillary column was prepared. This chiral capillary column was used to separate epinephrine, norepinephrine, terbutaline, and tryptophan enantiomers. Under optimum conditions, baseline separations were achieved. The intra-day, inter-day, and inter-column relative standard deviations (n = 3) of the four pairs of enantiomeric migration times were 0.15%-0.56%, 0.74%-2.40%, and 1.93%-3.18%, respectively. Moreover, the D-histidine modified zeolitic imidazolate framework-90 coated capillary could be reused for at least 150 runs without significant changes in the separation efficiency and migration time.
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A series of lanthanide-containing water-resistant nitrates, namely RE(OH)2NO3 (RE = Tb(1), Dy(2), Ho(3), and Er(4)), was obtained through the hydrothermal process. As possible nonlinear optical materials, they feature a layered isomorph composed of an [REO3(OH)6] polyhedron and an [NO3] triangle, and the synergistic arrangement of the [REO3(OH)6] and [NO3] groups in their structures leads to their obvious second-order nonlinear optical effect. Nevertheless, the unique optical absorption caused by the electronic transitions on 4f-4f orbitals of lanthanides results in their second harmonic generation responses of different strengths, with 1 exhibiting 5.07 times that of KDP, but 2-4 showing less than half of KDP. In addition, 1 possesses an outstanding water-resistant capacity and a transparent cut-off edge around 300 nm, foreshadowing its potential value as a nonlinear optical crystal. Moreover, 1 is found to emit characteristic green fluorescence due to the typical 5D4 â 7F5 transitions of the excited Tb3+ ions.
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Covalent organic frameworks (COFs) are divided into two-dimensional (2D) and three-dimensional (3D) structures according to the connection dimension of covalent bonds. 3D COFs have smaller pore size and larger surface area, which would facilitate the separation of small organic molecules with similar structures and properties in capillary electrochromatographic (CEC) separation. However, the application of 3D COFs in CEC is still in its early stages. Thus, 3D COFs (3D-IL-COF-1 and 3D-IL-COF-2) were synthesis by a new synthesis method in this work. The related characterization results confirmed that spherical 3D-IL-COFs formed by the accumulation of small polyhedral particles were successfully synthesized. Then, 3D-IL-COFs were introduced into the inner wall of capillary by in-situ growth method to prepare the 3D COFs coated capillaries for the first time. The electrochromatographic separation performance of the 3D-IL-COFs coated capillaries was investigated using the 3D-IL-COF-1 coated capillary as the model. The results indicate that the 3D-IL-COF-1 coated capillary with uniform coating exhibits a broad-spectrum separation capacity not only for acidic, basic and neutral analytes but also for neutral isomers, which shows that 3D-IL-COFs becomes an attractive potential stationary phase for electrochromatographic separation.
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Uracil DNA glycosylase (UDG) and human alkyladenine DNA glycosylase (hAAG) are the important DNA glycosylases for initiating the repair of DNA damage, and the aberrant expression of DNA glycosylases is closely associated with various diseases, such as Parkinson's disease, several cancers, and human immunodeficiency. The simultaneous detection of UDG and hAAG is helpful for the study of early clinical diagnosis. However, the reported methods for multiple DNA glycosylase assay suffer from the application of an expensive single-molecule instrument, labor-tedious magnetic separation, and complicated design. Herein, we develop a simple fluorescence method with only three necessary DNA strands for the selective and sensitive detection of multiple DNA glycosylase activity based on the generation of 3'-OH terminal-triggered encoding of multicolor fluorescence. The method can achieve the detection limits of 5.5 × 10-5 U/mL for UDG and 3.3 × 10-3 U/mL for hAAG, which are lower than those of the reported fluorescence methods. Moreover, it can be further used to detect multiple DNA glycosylases in the human cervical carcinoma cell line (HeLa cells), normal human renal epithelial cells (293 T cells), and biological fluid and measure the enzyme kinetic parameters of UDG and hAAG.
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DNA , Uracila-DNA Glicosidase , Fluorescência , Células HeLa , HumanosRESUMO
Covalent organic frameworks (COFs) have great potential applications in chromatographic separation. So it is crucial to understand the relationship between the separation ability of COFs and their structures. Here we report a strategy to evaluate the separation ability of three 2D COFs and explore the relationship between separation ability and their molecular structures. The three 2D COFs (COF-LZU1, COF-42 and COF-LZU8) have one same building unit 1,3,5-triformylbenzene, while varied from the conjugated linking units and functional side-chains. They were used to construct coated capillary column for capillary electrochromatographic separation of same groups of phthalates. They exhibited different separation efficiencies. COF-42 and COF-LZU8 coated capillary columns provided good signal resolutions and high column efficiencies with high theoretical plate numbers. It is demonstrated that COFs with hydrazone unit and longer side-chains provided higher selectivity and resolutions for the phthalates separation. Molecular simulations and DFT calculations were further proceeded to explore the deep reason why the three COFs coated CEC displayed different separation ability based on the host-guest interactions on molecular level. This work highlights a new opportunity to select or design functional COFs and improve their efficiency in chromatographic separation based on host-guest chemistry.
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Background: Type 2 diabetes mellitus (T2DM) is a multifaceted disorder affecting epidemic proportion at global scope. Defective insulin secretion by pancreatic ß-cells and the inability of insulin-sensitive tissues to respond effectively to insulin are the underlying biology of T2DM. However, circulating biomarkers indicative of early diabetic onset at the asymptomatic stage have not been well described. We hypothesized that global and targeted mass spectrometry (MS) based metabolomic discovery can identify novel serological metabolic biomarkers specifically associated with T2DM. We further hypothesized that these markers can have a unique pattern associated with latent or early asymptomatic stage, promising an effective liquid biopsy approach for population T2DM risk stratification and screening. Methods: Four independent cohorts were assembled for the study. The T2DM cohort included sera from 25 patients with T2DM and 25 healthy individuals for the biomarker discovery and sera from 15 patients with T2DM and 15 healthy controls for the testing. The Pre-T2DM cohort included sera from 76 with prediabetes and 62 healthy controls for the model training and sera from 35 patients with prediabetes and 27 healthy controls for the model testing. Both global and targeted (amino acid, acylcarnitine, and fatty acid) approaches were used to deep phenotype the serological metabolome by high performance liquid chromatography-high resolution mass spectrometry. Different machine learning approaches (Random Forest, XGBoost, and ElasticNet) were applied to model the unique T2DM/Pre-T2DM metabolic patterns and contrasted with their effectiness to differentiate T2DM/Pre-T2DM from controls. Results: The univariate analysis identified unique panel of metabolites (n = 22) significantly associated with T2DM. Global metabolomics and subsequent structure determination led to the identification of 8 T2DM biomarkers while targeted LCMS profiling discovered 14 T2DM biomarkers. Our panel can effectively differentiate T2DM (ROC AUC = 1.00) or Pre-T2DM (ROC AUC = 0.84) from the controls in the respective testing cohort. Conclusion: Our serological metabolite panel can be utilized to identifiy asymptomatic population at risk of T2DM, which may provide utility in identifying population at risk at an early stage of diabetic development to allow for clinical intervention. This early detection would guide ehanced levels of care and accelerate development of clinical strategies to prevent T2DM.
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Chiral covalent organic frameworks (CCOFs) have recently exhibited particularly promising potential as effective chiral stationary phases (CSPs) for open tubular capillary electrochromatography (OT-CEC) enantioseparation. However, it remains difficult to synthesis of CCOFs and preparation of CCOFs coated capillary under mild reaction conditions. In this work, we designed and fabricated a CCOF (CB-DA-COF) with high chemical stability and high specific surface area at room temperature. Then, through one-step in situ growth method, the chiral CB-DA-COF coated capillary was fabricated at room temperature for the first time. This method requires neither pre-modification to the capillary by organic molecular building units nor harsh reaction conditions, and the preparation time of the CCOF coating was significantly shortened (within 2 h). This chiral CB-DA-COF coated capillary showed excellent enantioseparation ability and stability. Under optimal conditions, rapid enantioseparation (within 5 min) could be achieved for six enantiomers including terbutaline, propranolol, phenylephrine, verapamil, norepinephrine and isoprenaline. And, no significant change was observed in enantioseparation efficiency after over 200 runs. The relative standard deviations (RSDs) of the analyte's migration time for intra-day, inter-day and column-to-column were within the range of 0.8-3.5% (n = 5), 1.5-4.7% (n = 3) and 4.3-8.3% (n = 3), respectively. In addition, the enantioseparation mechanism was studied, which indicated that binding energy between of enantiomers and chiral site were the main factors for enantioseparation.
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Eletrocromatografia Capilar , Estruturas Metalorgânicas , Eletrocromatografia Capilar/métodos , Estruturas Metalorgânicas/química , Estereoisomerismo , TerbutalinaRESUMO
Molecular structural modifications are utilized to improve the short-circuit current (JSC ) of high-voltage organic photovoltaics (OPVs). Herein, the classic non-fullerene acceptor (NFA), BTA3, is chosen as a benchmark, with BTA3b containing the linear alkyl chains on the middle core and JC14 fusing thiophene on the benzotriazole (BTA) unit as a contrast. The photovoltaic devices based on J52-F: BTA3b and J52-F: JC14 achieve wider external quantum efficiency responses with band edges of 730 and 800 nm, respectively than that of the device based on J52-F: BTA3 (715 nm). The corresponding JSC increases to 14.08 and 15.78 mA cm-2 , respectively, compared to BTA3 (11.56 mA cm-2 ). The smaller Urbach energy and higher electroluminescence efficiency guarantee J52-F: JC14 a decreased energy loss (0.528 eV) and a high open-circuit voltage (VOC ) of 1.07 V. Finally, J52-F: JC14 combination achieves an increased power conversion efficiency (PCE) of 10.33% than that of J52-F: BTA3b (PCE = 9.81%) and J52-F: BTA3 (PCE = 9.04%). Overall, the research results indicate that subtle structure modification of NFAs, especially introducing fused rings, is a simple and effective strategy to extend the photoelectric response, boosting the JSC and ensuring a high VOC beyond 1.0 V.
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Herein, a novel chiral covalent organic framework, DA-TD COF, with good chemical/thermal stability was synthesized and used as a chiral stationary phase for open-tubular capillary electrochromatography enantioseparation. The DA-TD COF coated capillary exhibited excellent enantioseparation efficiency and its separation efficiency did not show an obvious decrease over 200 runs. Furthermore, the enantioseparation mechanism was studied.
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Recently, covalent organic frameworks (COFs), owning to their excellent and unique properties, are attracting the attention of numerous researchers in some areas, especially the domain of chromatographic separation. However, the application of hydrazine linkages COFs in open-tubular capillary electrochromatography (OT-CEC) lies in the early stage at present. Herein, a well-crystallized hydrazine-linked COF (Tf-DHzOH) was synthesized successfully from 2,5-dihydroxyterephtalohydrazide and 1,3,5-triformyl-benzene. Tf-DHzOH was firstly regarded as a stationary phase material to prepare the Tf-DHzOH coated capillaries with different coating thickness by covalent bonding in this work. The characterization results showed that Tf-DHzOH was successfully synthesized. The separation performance and stability of the Tf-DHzOH coated capillary were evaluated by considering amino acids, sulfonamides, tetracyclines and benzene compounds as analytes. The relative standard deviations (RSDs) of separation time in the intra-day (n = 9), inter-day (n = 6), column-to-column (n = 3) and batch-to-batch (n = 3) were 0.76-4.97%, 1.59-5.94%1.78-8.72% and 1.66%-8.23%, respectively, the RSDs of peak areas were 1.90-5.16%, 1.73-5.24%, 1.26-7.33% and 3.77%-11.24%, respectively. It was confirmed that there was no visible change of separation efficiency after the Tf-DHzOH-coated capillary was used more than 200 runs. The results make clear that 2D hydrazine-linked COF (Tf-DHzOH) has superior potential as the stationary phase in OT-CEC for chromatographic separation.
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Eletrocromatografia Capilar , Estruturas Metalorgânicas , Aminoácidos , HidrazinasRESUMO
Environmental quality data sets are typically imbalanced, because environmental pollution events are rarely observed in daily life. Prediction of imbalanced data sets is a major challenge in machine learning. Our recent work has shown deep cascade forest (DCF), as a base learning model, is promising to be recommended for environmental quality prediction. Although some traditional models were improved by introducing the cost matrix, little is known about whether cost matrix could enhance the prediction performance of DCF. Additionally, feature extraction is also an important way to potentially improve the model's ability to predict the imbalanced data. Here, we developed two novelty learning models based on DCF: cost-sensitive DCF (CS-DCF) and DCF that combines unsupervised learning models and greedy methods (USM-DCF-G). Subsequently, CS-DCF and USM-DCF-G were successfully verified by an imbalanced drinking water quality data set. Our data presented both CS-DCF and USM-DCF-G show better prediction performance than that of DCF alone did. In particular, USM-DCF-G shows the best performance with the highest F1-score (95.12 ± 2.56%), after feature extraction and selection by using unsupervised learning models and greedy methods. Thus, the two learning models, especially USM-DCF-G, were promising learning models to address environmental imbalanced issues and accurately predict environmental quality.
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Água Potável , Florestas , Aprendizado de Máquina , Qualidade da ÁguaRESUMO
A new 3D noncentrosymmetric mixed-metal sulfate iodate, AgBi(SO4)(IO3)2, has been designed based on a 2D iodate of AgBi(IO3)4via the aliovalent substitution of [IO3]- groups by [SO4]2- groups. Enhancement of the second harmonic generation response (3.0 × KDP to 3.9 × KDP) has been achieved while retaining a favorable NLO framework. This is a novel strategy to upgrade structural dimensions.