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  1. Article ; Online: PTransIPs: Identification of Phosphorylation Sites Enhanced by Protein PLM Embeddings.

    Xu, Ziyang / Zhong, Haitian / He, Bingrui / Wang, Xueying / Lu, Tianchi

    IEEE journal of biomedical and health informatics

    2024  Volume PP

    Abstract: Phosphorylation is pivotal in numerous fundamental cellular processes and plays a significant role in the onset and progression of various diseases. The accurate identification of these phosphorylation sites is crucial for unraveling the molecular ... ...

    Abstract Phosphorylation is pivotal in numerous fundamental cellular processes and plays a significant role in the onset and progression of various diseases. The accurate identification of these phosphorylation sites is crucial for unraveling the molecular mechanisms within cells and during viral infections, potentially leading to the discovery of novel therapeutic targets. In this study, we develop PTransIPs, a new deep learning framework for the identification of phosphorylation sites. Independent testing results demonstrate that PTransIPs outperforms existing state-of-the-art (SOTA) methods, achieving AUCs of 0.9232 and 0.9660 for the identification of phosphorylated S/T and Y sites, respectively. PTransIPs contributes from three aspects. 1) PTransIPs is the first to apply protein pre-trained language model (PLM) embeddings to this task. It utilizes ProtTrans and EMBER2 to extract sequence and structure embeddings, respectively, as additional inputs into the model, effectively addressing issues of dataset size and overfitting, thus enhancing model performance; 2) PTransIPs is based on Transformer architecture, optimized through the integration of convolutional neural networks and TIM loss function, providing practical insights for model design and training; 3) The encoding of amino acids in PTransIPs enables it to serve as a universal framework for other peptide bioactivity tasks, with its excellent performance shown in extended experiments of this paper. Our code, data and models are publicly available at https://github.com/StatXzy7/PTransIPs.
    Language English
    Publishing date 2024-03-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2695320-1
    ISSN 2168-2208 ; 2168-2194
    ISSN (online) 2168-2208
    ISSN 2168-2194
    DOI 10.1109/JBHI.2024.3377362
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Synergistic effect of genistein and adiponectin reduces fat deposition in chicken hepatocytes by activating the ERβ-mediated SIRT1-AMPK signaling pathway.

    Jiang, Zhihao / Huang, Benzeng / Cui, Ziyi / Lu, Ze / Ma, Haitian

    Poultry science

    2024  Volume 103, Issue 6, Page(s) 103734

    Abstract: Dietary supplementation with bioactive substances that can regulate lipid metabolism is an effective approach for reducing excessive fat deposition in chickens. Genistein (GEN) has the potential to alleviate fat deposition; however, the underlying ... ...

    Abstract Dietary supplementation with bioactive substances that can regulate lipid metabolism is an effective approach for reducing excessive fat deposition in chickens. Genistein (GEN) has the potential to alleviate fat deposition; however, the underlying mechanism of GEN's fat-reduction action in chickens remains unclear. Therefore, the present study aimed to explore the underlying mechanism of GEN on the reduction of fat deposition from a novel perspective: intercellular transmission of adipokine between adipocytes and hepatocytes. The findings showed that GEN enhanced the secretion of adiponectin (APN) in chicken adipocytes, and the enhancement effect of GEN was completely blocked when the cells were pretreated with inhibitors targeting estrogen receptor β (ERβ) or proliferator-activated receptor γ (PPARγ) signals, respectively. Furthermore, the results demonstrated that both co-treatment with GEN and APN or treatment with the medium supernatant (Med SUP) derived from chicken adipocytes treated with GEN significantly decreased the content of triglyceride and increased the protein levels of ERβ, Sirtuin 1 (SIRT1) and phosphor-AMP-activated protein kinase (p-AMPK) in chicken hepatocytes compared to the cells treated with GEN or APN alone. Moreover, the increase in the protein levels of SIRT1 and p-AMPK induced by GEN and APN co-treatment or Med SUP treatment were blocked in chicken hepatocytes pretreated with the inhibitor of ERβ signals. Importantly, the up-regulatory effect of GEN and APN co-treatment or Med SUP treatment on the protein level of p-AMPK was also blocked in chicken hepatocytes pretreated with a SIRT1 inhibitor; however, the increase in the protein level of SIRT1 induced by GEN and APN co-treatment or Med SUP treatment was not reversed when the hepatocytes were pretreated with an AMPK inhibitor. In conclusion, the present study demonstrated that GEN enhanced APN secretion by activating the ERβ-Erk-PPARγ signaling pathway in chicken adipocytes. Subsequently, adipocyte-derived APN synergized with GEN to activate the ERβ-mediated SIRT1-AMPK signaling pathway in chicken hepatocytes, ultimately reducing fat deposition. These findings provide substantial evidence from a novel perspective, supporting the potential use of GEN as a dietary supplement to prevent excessive fat deposition in poultry.
    Language English
    Publishing date 2024-04-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 242586-5
    ISSN 1525-3171 ; 0032-5791
    ISSN (online) 1525-3171
    ISSN 0032-5791
    DOI 10.1016/j.psj.2024.103734
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Semantic Layout Manipulation With High-Resolution Sparse Attention.

    Zheng, Haitian / Lin, Zhe / Lu, Jingwan / Cohen, Scott / Zhang, Jianming / Xu, Ning / Luo, Jiebo

    IEEE transactions on pattern analysis and machine intelligence

    2023  Volume 45, Issue 3, Page(s) 3768–3782

    Abstract: We tackle the problem of semantic image layout manipulation, which aims to manipulate an input image by editing its semantic label map. A core problem of this task is how to transfer visual details from the input images to the new semantic layout while ... ...

    Abstract We tackle the problem of semantic image layout manipulation, which aims to manipulate an input image by editing its semantic label map. A core problem of this task is how to transfer visual details from the input images to the new semantic layout while making the resulting image visually realistic. Recent work on learning cross-domain correspondence has shown promising results for global layout transfer with dense attention-based warping. However, this method tends to lose texture details due to the resolution limitation and the lack of smoothness constraint on correspondence. To adapt this paradigm for the layout manipulation task, we propose a high-resolution sparse attention module that effectively transfers visual details to new layouts at a resolution up to 512x512. To further improve visual quality, we introduce a novel generator architecture consisting of a semantic encoder and a two-stage decoder for coarse-to-fine synthesis. Experiments on the ADE20k and Places365 datasets demonstrate that our proposed approach achieves substantial improvements over the existing inpainting and layout manipulation methods.
    Language English
    Publishing date 2023-02-03
    Publishing country United States
    Document type Journal Article
    ISSN 1939-3539
    ISSN (online) 1939-3539
    DOI 10.1109/TPAMI.2022.3181587
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Structural analysis and attenuates hyperuricemic nephropathy of dextran from the Imperata cylindrica Beauv. var. major (Nees) C. E. Hubb.

    Yu, Wenchen / Xiong, Yi / Liu, Mengnan / Zeng, Deyong / Zhao, Haitian / Liu, Jiaren / Lu, Weihong

    Carbohydrate polymers

    2023  Volume 317, Page(s) 121064

    Abstract: ICPC-a was from the Imperata cylindrica with a molecular weight of 45 kDa, which was composed of α-D-1,3-Glcp and α-D-1,6-Glcp. The ICPC-a showed thermal stability, maintaining its structural integrity up to 220°C. X-ray diffraction analysis confirmed ... ...

    Abstract ICPC-a was from the Imperata cylindrica with a molecular weight of 45 kDa, which was composed of α-D-1,3-Glcp and α-D-1,6-Glcp. The ICPC-a showed thermal stability, maintaining its structural integrity up to 220°C. X-ray diffraction analysis confirmed its amorphous nature, while scanning electron microscopy revealed a layered morphology. ICPC-a significantly ameliorated uric acid stimulation-induced HK-2 cell injury and apoptosis and reduced uric acid levels in mice with hyperuricemic nephropathy. ICPC-a protected against renal injury by inhibiting lipid peroxidation levels, increasing antioxidant damage and defense levels, inhibiting secretion of pro-inflammatory factors, regulating purine metabolism, PI3K-Akt signaling pathway, NF-κB signaling pathway, inflammatory bowel disease, mTOR signaling pathway, and MAPK signaling pathway. These findings indicate that ICPC-a is a promising natural substance with multiple targets, multiple pathways of action, and without toxicity, making it a valuable subject for further research and development.
    MeSH term(s) Mice ; Animals ; Uric Acid ; Dextrans/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Poaceae/metabolism ; Kidney/metabolism ; NF-kappa B/metabolism
    Chemical Substances Uric Acid (268B43MJ25) ; Dextrans ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; NF-kappa B
    Language English
    Publishing date 2023-05-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 1501516-6
    ISSN 1879-1344 ; 0144-8617
    ISSN (online) 1879-1344
    ISSN 0144-8617
    DOI 10.1016/j.carbpol.2023.121064
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Structural analysis and attenuates hyperuricemic nephropathy of dextran from the Imperata cylindrica Beauv. var. major (Nees) C. E. Hubb

    Yu, Wenchen / Xiong, Yi / Liu, Mengnan / Zeng, Deyong / Zhao, Haitian / Liu, Jiaren / Lu, Weihong

    Carbohydrate Polymers. 2023 May 29, p.121064-

    2023  , Page(s) 121064–

    Abstract: ICPC-a was from the Imperata cylindrica with a molecular weight of 45 kDa, which was composed of α-D-1,3-Glcp and α-D-1,6-Glcp. The ICPC-a showed thermal stability, maintaining its structural integrity up to 220 °C. X-ray diffraction analysis confirmed ... ...

    Abstract ICPC-a was from the Imperata cylindrica with a molecular weight of 45 kDa, which was composed of α-D-1,3-Glcp and α-D-1,6-Glcp. The ICPC-a showed thermal stability, maintaining its structural integrity up to 220 °C. X-ray diffraction analysis confirmed its amorphous nature, while scanning electron microscopy revealed a layered morphology. ICPC-a significantly ameliorated uric acid stimulation-induced HK-2 cell injury and apoptosis and reduced uric acid levels in mice with hyperuricemic nephropathy. ICPC-a protected against renal injury by inhibiting lipid peroxidation levels, increasing antioxidant damage and defense levels, inhibiting secretion of pro-inflammatory factors, regulating purine metabolism, PI3K-Akt signaling pathway, NF-κB signaling pathway, inflammatory bowel disease, mTOR signaling pathway, and MAPK signaling pathway. These findings indicate that ICPC-a is a promising natural substance with multiple targets, multiple pathways of action, and without toxicity, making it a valuable subject for further research and development.
    Keywords Imperata cylindrica ; X-ray diffraction ; antioxidants ; apoptosis ; dextran ; electron microscopy ; inflammatory bowel disease ; kidney diseases ; lipid peroxidation ; metabolism ; molecular weight ; research and development ; secretion ; thermal stability ; toxicity ; uric acid ; NMR spectrometry ; Hyperuricemic nephropathy
    Language English
    Dates of publication 2023-0529
    Publishing place Elsevier Ltd
    Document type Article ; Online
    Note Pre-press version
    ZDB-ID 1501516-6
    ISSN 1879-1344 ; 0144-8617
    ISSN (online) 1879-1344
    ISSN 0144-8617
    DOI 10.1016/j.carbpol.2023.121064
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Effects of assignments of dedicated automated vehicle lanes and inter-vehicle distances of automated vehicle platoons on car-following performance of nearby manual vehicle drivers.

    Chen, Facheng / Lu, Guangquan / Tan, Haitian / Liu, Miaomiao / Wan, Hongfei

    Accident; analysis and prevention

    2022  Volume 177, Page(s) 106826

    Abstract: Deploying dedicated lanes for automated vehicles (AVs) can effectively alleviate the coordination issues between AVs and manual vehicles (MVs). However, AV platoons running on dedicated AV lanes (DAVLs) have a prominent collective behavior characteristic ...

    Abstract Deploying dedicated lanes for automated vehicles (AVs) can effectively alleviate the coordination issues between AVs and manual vehicles (MVs). However, AV platoons running on dedicated AV lanes (DAVLs) have a prominent collective behavior characteristic of small inter-vehicle distance. The nearby MV drivers' imitation of this characteristic may reduce their car-following time headway (THW). The researchers conducted a simulation experiment to investigate the influence of DAVL assignments, inter-vehicle distances of AV platoons and AV platoon speed on the car-following performance of nearby MV drivers. The data of mean THW, standard deviation of THW, standard deviation of lateral position, standard deviation of velocity, standard deviation of horizontal gaze position and mean saccadic peak velocity were collected from 36 participants. Statistical analysis results show that the three factors considerably affected the MV drivers' car-following performance. In particular, the MV drivers showed a worse car-following safety but a better driving stability when the left lane was dedicated to AVs than when the right lane was dedicated to AVs (Note the experiments were done in a drive-on-the-left environment.). With respect to the inter-vehicle distances of AV platoons, the MV drivers' car-following safety was poorer under the 4 m condition than that under the 10 and 18 m conditions. In addition, the MV drivers showed a poorer car-following safety and bore a larger mental workload when driving next to the AV platoons running at 110 km/h. This study may provide some suggestions for DAVLs. Assigning the right lane of a three-lane motorway as the DAVL may have a slighter negative impact on the nearby MV drivers in China. In terms of traffic management in DAVLs, the inter-vehicle distance of AV platoons can be reduced to 10 m, and the speed of AVs should not be higher than the design speed of adjacent MV lanes.
    MeSH term(s) Accidents, Traffic ; Automobile Driving ; Automobiles ; Autonomous Vehicles ; Computer Simulation ; Humans
    Language English
    Publishing date 2022-09-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 210223-7
    ISSN 1879-2057 ; 0001-4575
    ISSN (online) 1879-2057
    ISSN 0001-4575
    DOI 10.1016/j.aap.2022.106826
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: A contrarian growth

    Haitian Lu / Ruifeng Zhao / Liu Zhao / Binyang Lyu / Jingfa Wang / Lihua Zhang

    Ecological Indicators, Vol 157, Iss , Pp 111249- (2023)

    The spatiotemporal dynamics of open-surface water bodies on the northern slope of Kunlun Mountains

    2023  

    Abstract: Identifying and monitoring open-surface water bodies are significant for understanding regional water resource distribution and evolving trends. This understanding carries profound value for comprehensively assessing the effects of climate change and ... ...

    Abstract Identifying and monitoring open-surface water bodies are significant for understanding regional water resource distribution and evolving trends. This understanding carries profound value for comprehensively assessing the effects of climate change and human social activities on water resources and maintaining water security. This study pioneers’ improvements in surface water detection rules with the central aim of constructing a Method with Enhanced Impurity Control, specifically tailored for complex environmental scenarios (OA = 98.97 % ± 0.06). This is achieved by incorporating intricate exponential constraints and targeted data masks. Our analysis is grounded in the examination of 21,709 preprocessed high-quality images, covering the period from 1990 to 2021 across the northern slope of the Kunlun Mountains. Through this comprehensive study, we have gleaned insightful results regarding the spatiotemporal dynamics of open-surface water bodies. In the past 32 years, the surface water body area on the northern slope of the Kunlun Mountains has exhibited a significantly increasing trend. Specifically, the size of permanent water bodies expanded by 71.03 % (with a 95 % confidence interval: ± 27.73 %), while the area of seasonal water bodies grew by a substantial 170.63 % (with a 95 % confidence interval: ± 17.50 %). Open-surface water bodies display discernible spatiotemporal differences. Stable and continuous permanent water bodies are predominantly in mountainous areas, whereas seasonal water bodies with pronounced fluctuations are chiefly found in desert-oasis areas. Climate change is the dominant factor that affects the changes of water bodies on the surface of mountain regions, while human social activities also have a significant impact on desert-oasis areas. The improved methodology adopted in this study offers a robust and scalable framework that can be tailored for studying changes in open-surface water bodies in intricate environments. We performed a comprehensive analysis of the changes and drivers of ...
    Keywords Open-surface water body detection method ; The northern slope of Kunlun Mountains ; Open-surface water body dynamics ; Google Earth Engine ; Times series Landsat images ; Ecology ; QH540-549.5
    Subject code 550
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: The Impact of Marketization on Sustainable Economic Growth—Evidence from West China

    Tingying Chen / Haitian Lu / Rong Chen / Lina Wu

    Sustainability, Vol 13, Iss 3745, p

    2021  Volume 3745

    Abstract: In this paper, we aim to study the relation between the marketization level in the western region of China and its economic development, and to provide policy guidance for the economic development of underdeveloped regions. Mixed methods data analysis ... ...

    Abstract In this paper, we aim to study the relation between the marketization level in the western region of China and its economic development, and to provide policy guidance for the economic development of underdeveloped regions. Mixed methods data analysis was conducted using panel data from 82 prefecture-level cities in west China from 2003 to 2017. The overall regression results show that the level of marketization has a significant role in promoting economic growth. At the same time, regional heterogeneity analyses show that the sub-indicators of marketization have different degrees of influence on economic growth in the southwest and northwest of China, whereas the overall level indicator plays a significant role in both regions. In addition, the threshold panel model was used to test whether the influence of marketization on economic growth in the western region had interval characteristics. Through the self-sampling method, it was found that there are double thresholds. In terms of the gradual progress of the marketization level range, it shows a trend of first increasing, then decreasing and then increasing again. The results show that the level of marketization in west China has significantly promoted the economic development of the western region. Additionally, the impact of marketization on economic development in relatively backward regions is gradually increasing and surpassing that of relatively developed regions. Underdeveloped areas in west China can stimulate their advantages by continuously promoting the construction of marketization and improving the level of economic organization, so as to gradually narrow the development gap between regions.
    Keywords marketization ; sustainable economic growth ; China ; heterogeneity ; Environmental effects of industries and plants ; TD194-195 ; Renewable energy sources ; TJ807-830 ; Environmental sciences ; GE1-350
    Subject code 950
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Genistein alleviates chronic heat stress-induced lipid metabolism disorder and mitochondrial energetic dysfunction by activating the GPR30-AMPK-PGC-1α signaling pathways in the livers of broiler chickens.

    Li, Longlong / Lu, Ze / Wang, Yulei / Yang, Ying / Wang, Huihui / Ma, Haitian

    Poultry science

    2023  Volume 103, Issue 1, Page(s) 103251

    Abstract: The objective of this study was to investigate the preventive effects and mechanisms of genistein (GEN) on production performance and metabolic disorders in broilers under chronic heat stress (HS). A total of 120 male 3-wk-old Ross broilers were randomly ...

    Abstract The objective of this study was to investigate the preventive effects and mechanisms of genistein (GEN) on production performance and metabolic disorders in broilers under chronic heat stress (HS). A total of 120 male 3-wk-old Ross broilers were randomly assigned to 5 groups: a thermoneutral zone (TN) group maintained at normal temperature (21°C ± 1°C daily), an HS group subjected to cyclic high temperature (32°C ± 1°C for 8 h daily), and 3 groups exposed to HS with varying doses of GEN (50, 100, or 150 mg/kg diet). The experimental period lasted for 3 wk. Here, HS led to a decline in growth performance parameters and hormone secretion disorders (P < 0.05), which were improved by 100 and 150 mg/kg GEN treatment (P < 0.05). Moreover, the HS-induced increases in the liver index (P < 0.01) and abdominal fat rate (P < 0.05) were attenuated by 150 mg/kg GEN (P < 0.05). The HS-induced excessive lipid accumulation in the liver and serum (P < 0.01) was ameliorated after 100 and 150 mg/kg GEN treatment (P < 0.05). Furthermore, the HS-induced decreases in lipolysis-related mRNA levels and increases in lipid synthesis-related mRNA levels in the liver (P < 0.01) were effectively blunted after 100 and 150 mg/kg GEN treatment (P < 0.05). Importantly, the HS-stimulated hepatic mitochondrial energetic dysfunction and decreases in the mRNA or protein levels of peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A in the liver were ameliorated by 150 mg/kg GEN (P < 0.05). Moreover, 50 to 150 mg/kg GEN treatment resulted in a significant increase in the mRNA or protein levels of G protein-coupled estrogen receptor (GPR30), AMP-activated protein kinase (AMPK) α1, phosphorylated AMPKα, and phosphorylated acetyl-CoA carboxylase α. Collectively, GEN alleviated metabolic disorders and hepatic mitochondrial energetic dysfunction under HS, possibly through the activation of GPR30-AMPM-PGC-1α pathways. These data provide a sufficient basis for GEN as an additive to alleviate HS in broilers.
    MeSH term(s) Animals ; Male ; Chickens/physiology ; AMP-Activated Protein Kinases/metabolism ; Genistein/pharmacology ; Genistein/metabolism ; Lipid Metabolism ; Liver/metabolism ; Heat-Shock Response ; Heat Stress Disorders/drug therapy ; Heat Stress Disorders/veterinary ; Signal Transduction ; Lipid Metabolism Disorders/metabolism ; Lipid Metabolism Disorders/veterinary ; RNA, Messenger/metabolism ; Lipids
    Chemical Substances AMP-Activated Protein Kinases (EC 2.7.11.31) ; Genistein (DH2M523P0H) ; RNA, Messenger ; Lipids
    Language English
    Publishing date 2023-10-30
    Publishing country England
    Document type Randomized Controlled Trial, Veterinary ; Journal Article
    ZDB-ID 242586-5
    ISSN 1525-3171 ; 0032-5791
    ISSN (online) 1525-3171
    ISSN 0032-5791
    DOI 10.1016/j.psj.2023.103251
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Structure-Guided Image Completion with Image-level and Object-level Semantic Discriminators.

    Zheng, Haitian / Lin, Zhe / Lu, Jingwan / Cohen, Scott / Shechtman, Eli / Barnes, Connelly / Zhang, Jianming / Liu, Qing / Amirghodsi, Sohrab / Zhou, Yuqian / Luo, Jiebo

    IEEE transactions on pattern analysis and machine intelligence

    2024  Volume PP

    Abstract: Structure-guided image completion aims to inpaint a local region of an image according to an input guidance map from users. While such a task enables many practical applications for interactive editing, existing methods often struggle to hallucinate ... ...

    Abstract Structure-guided image completion aims to inpaint a local region of an image according to an input guidance map from users. While such a task enables many practical applications for interactive editing, existing methods often struggle to hallucinate realistic object instances in complex natural scenes. Such a limitation is partially due to the lack of semantic-level constraints inside the hole region as well as the lack of a mechanism to enforce realistic object generation. In this work, we propose a learning paradigm that consists of semantic discriminators and object-level discriminators for improving the generation of complex semantics and objects. Specifically, the semantic discriminators leverage pretrained visual features to improve the realism of the generated visual concepts. Moreover, the object-level discriminators take aligned instances as inputs to enforce the realism of individual objects. Our proposed scheme significantly improves the generation quality and achieves state-of-the-art results on various tasks, including segmentation-guided completion, edge-guided manipulation and panoptically-guided manipulation on Places2 datasets. Furthermore, our trained model is flexible and can support multiple editing use cases, such as object insertion, replacement, removal and standard inpainting. In particular, our trained model combined with a novel automatic image completion pipeline achieves state-of-the-art results on the standard inpainting task.
    Language English
    Publishing date 2024-04-26
    Publishing country United States
    Document type Journal Article
    ISSN 1939-3539
    ISSN (online) 1939-3539
    DOI 10.1109/TPAMI.2024.3393898
    Database MEDical Literature Analysis and Retrieval System OnLINE

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