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1. A framework combined stacking ensemble algorithm to classify crop in complex agricultural landscape of high altitude regions with Gaofen-6 imagery and elevation data

Author: Zhiyuan Ma, Wei Li, Timothy A. Warner, Can He, Xue Wang, Yu Zhang, Caili Guo, Tao Cheng, Yan Zhu, Weixing Cao, and Xia Yao
Subjects: High altitude regions, Gaofen-6, Crop classification, Stacking algorithm, Physical geography, GB3-5030, Environmental sciences, GE1-350
Abstract: Mapping crop distribution using satellite technology is an effective approach for gaining information about food production over broad, regional scales. However, crop classification in high altitude regions from satellite platforms remains challenging, due to the spatial heterogeneity caused by the complex planting patterns. Moreover, the frequent cloud cover makes it difficult to collect time-series imagery for these regions. Thus, this study used a mosaic of single images of Gaofen-6 data to map the crop distribution in high altitude regions of Xining City and Haidong City prefectures of Qinghai Province, China. To improve the accuracy of the crop classification, random forest-recursive feature elimination (RF-RFE) was used to determine an optimal feature subset from existing spectral, texture and topographic features. Then, a two-layer stacking generalization ensemble model, incorporating Random Forest, XGBoost and AdaBoost, was trained. The results reveal that the stacking algorithm outperformed the other single classifiers, with overall accuracy higher than 85% (87.89% for the optimal feature subset and 85.38% for the original spectral band subset). In addition, the user’s and producer’s accuracies for wheat, rape and maize field all exceeded 90%. Elevation was the variable with the highest importance score, illustrating its importance in crop classification of high altitude regions. Overall, the framework, combining RF-RFE and a stacking algorithm, can improve the accuracy of the crop classification in high altitude regions.
Published: 2023
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2. Reduction of Subsidence and Large-Scale Rebound in the Beijing Plain after Anthropogenic Water Transfer and Ecological Recharge of Groundwater: Evidence from Long Time-Series Satellites InSAR

Author: Chaodong Zhou, Qiuhong Tang, Yanhui Zhao, Timothy A. Warner, Hongjiang Liu, and John J. Clague
Subjects: Beijing, rebound, subsidence, InSAR, groundwater, SNWDP, Science
Abstract: Beijing, China’s capital city, has experienced decades of severe land subsidence due to the long-term overexploitation of groundwater. The implementation of the South-to-North Water Diversion Project (SNWDP) and artificial ecological restoration have significantly changed Beijing’s hydro-ecological and geological environment in recent years, leading to a widespread rise in groundwater levels. However, whether the related land subsidence has slowed down or reversed under these measures has not yet been effectively monitored and quantitatively analyzed in terms of time and space. Accordingly, in this study, we proposed using an improved time-series deformation method, which combines persistent scatterers and distributed scatterers, to process Sentinel-1 images from 2015 to 2022 in the Beijing Plain region. We performed a geospatial analysis to gain a better understanding of how the new hydrological conditions changed the pattern of deformation on the Beijing Plain. The results indicated that our combined PS and DS method provided more measurements both in total quantity and spatial density than conventional PSI methods. The land subsidence in the Beijing Plain area has been effectively alleviated from a subsidence region of approximately 1377 km2 in 2015 to only approximately 78 km2 in 2022. Ecological restoration areas in the northeastern part of the Plain have even rebounded over this period, at a maximum of approximately 40 mm in 2022. The overall pattern of ground deformation (subsidence and uplift) is negatively correlated with changes in the groundwater table (decline and rise). Local deformation is controlled by the thickness of the compressible layer and an active fault. The year 2015, when anthropogenic water transfers were eliminated and ecological measures to recharge groundwater were implemented, was the crucial turning point of the change in the deformation trend in the subsidence history of Beijing. Our findings carry significance, not only for China, but also for other areas where large-scale groundwater extractions are causing severe ground subsidence or rebound.
Published: 2024
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3. Selecting and Interpreting Multiclass Loss and Accuracy Assessment Metrics for Classifications with Class Imbalance: Guidance and Best Practices

Author: Sarah Farhadpour, Timothy A. Warner, and Aaron E. Maxwell
Subjects: deep learning, accuracy assessment, loss metrics, data imbalance, class-based statistics, Science
Abstract: Evaluating classification accuracy is a key component of the training and validation stages of thematic map production, and the choice of metric has profound implications for both the success of the training process and the reliability of the final accuracy assessment. We explore key considerations in selecting and interpreting loss and assessment metrics in the context of data imbalance, which arises when the classes have unequal proportions within the dataset or landscape being mapped. The challenges involved in calculating single, integrated measures that summarize classification success, especially for datasets with considerable data imbalance, have led to much confusion in the literature. This confusion arises from a range of issues, including a lack of clarity over the redundancy of some accuracy measures, the importance of calculating final accuracy from population-based statistics, the effects of class imbalance on accuracy statistics, and the differing roles of accuracy measures when used for training and final evaluation. In order to characterize classification success at the class level, users typically generate averages from the class-based measures. These averages are sometimes generated at the macro-level, by taking averages of the individual-class statistics, or at the micro-level, by aggregating values within a confusion matrix, and then, calculating the statistic. We show that the micro-averaged producer’s accuracy (recall), user’s accuracy (precision), and F1-score, as well as weighted macro-averaged statistics where the class prevalences are used as weights, are all equivalent to each other and to the overall accuracy, and thus, are redundant and should be avoided. Our experiment, using a variety of loss metrics for training, suggests that the choice of loss metric is not as complex as it might appear to be, despite the range of choices available, which include cross-entropy (CE), weighted CE, and micro- and macro-Dice. The highest, or close to highest, accuracies in our experiments were obtained by using CE loss for models trained with balanced data, and for models trained with imbalanced data, the highest accuracies were obtained by using weighted CE loss. We recommend that, since weighted CE loss used with balanced training is equivalent to CE, weighted CE loss is a good all-round choice. Although Dice loss is commonly suggested as an alternative to CE loss when classes are imbalanced, micro-averaged Dice is similar to overall accuracy, and thus, is particularly poor for training with imbalanced data. Furthermore, although macro-Dice resulted in models with high accuracy when the training used balanced data, when the training used imbalanced data, the accuracies were lower than for weighted CE. In summary, the significance of this paper lies in its provision of readers with an overview of accuracy and loss metric terminology, insight regarding the redundancy of some measures, and guidance regarding best practices.
Published: 2024
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4. Regional Spatiotemporal Patterns of Fire in the Eurasian Subarctic Based on Satellite Imagery

Author: Yikang Zhou, Shunping Ji, and Timothy A. Warner
Subjects: fire pattern, Eurasian Subarctic, wildfire, remote sensing, land cover, Science
Abstract: The fire risks in the vast Eurasian Subarctic are increasing, raising concerns for both local and global climate systems. Although some studies have addressed this problem, their conclusions only draw from relatively lower resolution data, and the sub-regional analysis of fire patterns in this area is lacking. In this paper, using a huge amount of multi-temporal and multi-resolution remotely sensed data, derived products, and weather data between the period 2001 and 2021, we reveal several novel and recent findings concerning regional and overall fire patterns in the Eurasian Subarctic. First, we discovered that fire occurrence over the period 2001 and 2021 varied by sub-region within the Eurasian Subarctic, with perennial low fire incidence in the East European and West Siberian Plain, increasing fire incidence in the Central Siberian Plateau, and marked periodicity of fire in the East Siberian Highlands. Second, we reveal the larger scale of individual fires in the Eurasian Subarctic compared to the adjacent region to the south, with fires of longer duration (13 vs. 8 days), larger daily expansion area (7.5 vs. 3.0 km2/d), and faster propagation (442 vs. 280 m/d). Third, the northern limit of fire has extended poleward approximately 1.5° during the study period. Fourth, the start dates of fire seasons in Eurasian Subarctic, dominated by the Central Siberian Plateau, has advanced at a rate of 1.4 days per year. We also analyzed the factors resulting in the regional patterns of fire incidence including weather, human activity, land cover, and landscape structure. Our findings not only increase the knowledge of regional fire patterns and trends in Eurasian Subarctic but also will benefit the design of special fire management policies.
Published: 2022
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5. Creating high-resolution bare-earth digital elevation models (DEMs) from stereo imagery in an area of densely vegetated deciduous forest using combinations of procedures designed for lidar point cloud filtering

Author: Jessica D. DeWitt, Timothy A. Warner, Peter G. Chirico, and Sarah E. Bergstresser
Subjects: digital elevation model (dem), digital surface model (dsm), high-spatial resolution photogrammetric dsm, filtering, vegetation artifact, Mathematical geography. Cartography, GA1-1776, Environmental sciences, GE1-350
Abstract: For areas of the world that do not have access to lidar, fine-scale digital elevation models (DEMs) can be photogrammetrically created using globally available high-spatial resolution stereo satellite imagery. The resultant DEM is best termed a digital surface model (DSM) because it includes heights of surface features. In densely vegetated conditions, this inclusion can limit its usefulness in applications requiring a bare-earth DEM. This study explores the use of techniques designed for filtering lidar point clouds to mitigate the elevation artifacts caused by above ground features, within the context of a case study of Prince William Forest Park, Virginia, USA. The influences of land cover and leaf-on vs. leaf-off conditions are investigated, and the accuracy of the raw photogrammetric DSM extracted from leaf-on imagery was between that of a lidar bare-earth DEM and the Shuttle Radar Topography Mission DEM. Although the filtered leaf-on photogrammetric DEM retains some artifacts of the vegetation canopy and may not be useful for some applications, filtering procedures significantly improved the accuracy of the modeled terrain. The accuracy of the DSM extracted in leaf-off conditions was comparable in most areas to the lidar bare-earth DEM and filtering procedures resulted in accuracy comparable of that to the lidar DEM.
Published: 2017
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6. Accuracy Assessment in Convolutional Neural Network-Based Deep Learning Remote Sensing Studies—Part 2: Recommendations and Best Practices

Author: Aaron E. Maxwell, Timothy A. Warner, and Luis Andrés Guillén
Subjects: accuracy assessment, thematic mapping, feature extraction, object detection, semantic segmentation, instance segmentation, Science
Abstract: Convolutional neural network (CNN)-based deep learning (DL) has a wide variety of applications in the geospatial and remote sensing (RS) sciences, and consequently has been a focus of many recent studies. However, a review of accuracy assessment methods used in recently published RS DL studies, focusing on scene classification, object detection, semantic segmentation, and instance segmentation, indicates that RS DL papers appear to follow an accuracy assessment approach that diverges from that of traditional RS studies. Papers reporting on RS DL studies have largely abandoned traditional RS accuracy assessment terminology; they rarely reported a complete confusion matrix; and sampling designs and analysis protocols generally did not provide a population-based confusion matrix, in which the table entries are estimates of the probabilities of occurrence of the mapped landscape. These issues indicate the need for the RS community to develop guidance on best practices for accuracy assessment for CNN-based DL thematic mapping and object detection. As a first step in that process, we explore key issues, including the observation that accuracy assessments should not be biased by the CNN-based training and inference processes that rely on image chips. Furthermore, accuracy assessments should be consistent with prior recommendations and standards in the field, should support the estimation of a population confusion matrix, and should allow for assessment of model generalization. This paper draws from our review of the RS DL literature and the rich record of traditional remote sensing accuracy assessment research while considering the unique nature of CNN-based deep learning to propose accuracy assessment best practices that use appropriate sampling methods, training and validation data partitioning, assessment metrics, and reporting standards.
Published: 2021
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7. Accuracy Assessment in Convolutional Neural Network-Based Deep Learning Remote Sensing Studies—Part 1: Literature Review

Author: Aaron E. Maxwell, Timothy A. Warner, and Luis Andrés Guillén
Subjects: accuracy assessment, thematic mapping, feature extraction, object detection, semantic segmentation, instance segmentation, Science
Abstract: Convolutional neural network (CNN)-based deep learning (DL) is a powerful, recently developed image classification approach. With origins in the computer vision and image processing communities, the accuracy assessment methods developed for CNN-based DL use a wide range of metrics that may be unfamiliar to the remote sensing (RS) community. To explore the differences between traditional RS and DL RS methods, we surveyed a random selection of 100 papers from the RS DL literature. The results show that RS DL studies have largely abandoned traditional RS accuracy assessment terminology, though some of the accuracy measures typically used in DL papers, most notably precision and recall, have direct equivalents in traditional RS terminology. Some of the DL accuracy terms have multiple names, or are equivalent to another measure. In our sample, DL studies only rarely reported a complete confusion matrix, and when they did so, it was even more rare that the confusion matrix estimated population properties. On the other hand, some DL studies are increasingly paying attention to the role of class prevalence in designing accuracy assessment approaches. DL studies that evaluate the decision boundary threshold over a range of values tend to use the precision-recall (P-R) curve, the associated area under the curve (AUC) measures of average precision (AP) and mean average precision (mAP), rather than the traditional receiver operating characteristic (ROC) curve and its AUC. DL studies are also notable for testing the generalization of their models on entirely new datasets, including data from new areas, new acquisition times, or even new sensors.
Published: 2021
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8. Effects of Training Set Size on Supervised Machine-Learning Land-Cover Classification of Large-Area High-Resolution Remotely Sensed Data

Author: Christopher A. Ramezan, Timothy A. Warner, Aaron E. Maxwell, and Bradley S. Price
Subjects: training sample size, supervised machine learning, high-resolution imagery, large area, GEOBIA, Science
Abstract: The size of the training data set is a major determinant of classification accuracy. Nevertheless, the collection of a large training data set for supervised classifiers can be a challenge, especially for studies covering a large area, which may be typical of many real-world applied projects. This work investigates how variations in training set size, ranging from a large sample size (n = 10,000) to a very small sample size (n = 40), affect the performance of six supervised machine-learning algorithms applied to classify large-area high-spatial-resolution (HR) (1–5 m) remotely sensed data within the context of a geographic object-based image analysis (GEOBIA) approach. GEOBIA, in which adjacent similar pixels are grouped into image-objects that form the unit of the classification, offers the potential benefit of allowing multiple additional variables, such as measures of object geometry and texture, thus increasing the dimensionality of the classification input data. The six supervised machine-learning algorithms are support vector machines (SVM), random forests (RF), k-nearest neighbors (k-NN), single-layer perceptron neural networks (NEU), learning vector quantization (LVQ), and gradient-boosted trees (GBM). RF, the algorithm with the highest overall accuracy, was notable for its negligible decrease in overall accuracy, 1.0%, when training sample size decreased from 10,000 to 315 samples. GBM provided similar overall accuracy to RF; however, the algorithm was very expensive in terms of training time and computational resources, especially with large training sets. In contrast to RF and GBM, NEU, and SVM were particularly sensitive to decreasing sample size, with NEU classifications generally producing overall accuracies that were on average slightly higher than SVM classifications for larger sample sizes, but lower than SVM for the smallest sample sizes. NEU however required a longer processing time. The k-NN classifier saw less of a drop in overall accuracy than NEU and SVM as training set size decreased; however, the overall accuracies of k-NN were typically less than RF, NEU, and SVM classifiers. LVQ generally had the lowest overall accuracy of all six methods, but was relatively insensitive to sample size, down to the smallest sample sizes. Overall, due to its relatively high accuracy with small training sample sets, and minimal variations in overall accuracy between very large and small sample sets, as well as relatively short processing time, RF was a good classifier for large-area land-cover classifications of HR remotely sensed data, especially when training data are scarce. However, as performance of different supervised classifiers varies in response to training set size, investigating multiple classification algorithms is recommended to achieve optimal accuracy for a project.
Published: 2021
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9. Thematic Classification Accuracy Assessment with Inherently Uncertain Boundaries: An Argument for Center-Weighted Accuracy Assessment Metrics

Author: Aaron E. Maxwell and Timothy A. Warner
Subjects: thematic image classification, thematic accuracy assessment, error matrix, error, uncertainty, Science
Abstract: Accuracy assessment is one of the most important components of both applied and research-oriented remote sensing projects. For mapped classes that have sharp and easily identified boundaries, a broad array of accuracy assessment methods has been developed. However, accuracy assessment is in many cases complicated by classes that have fuzzy, indeterminate, or gradational boundaries, a condition which is common in real landscapes; for example, the boundaries of wetlands, many soil map units, and tree crowns. In such circumstances, the conventional approach of treating all reference pixels as equally important, whether located on the map close to the boundary of a class, or in the class center, can lead to misleading results. We therefore propose an accuracy assessment approach that relies on center-weighting map segment area to calculate a variety of common classification metrics including overall accuracy, class user’s and producer’s accuracy, precision, recall, specificity, and the F1 score. This method offers an augmentation of traditional assessment methods, can be used for both binary and multiclass assessment, allows for the calculation of count- and area-based measures, and permits the user to define the impact of distance from map segment edges based on a distance weighting exponent and a saturation threshold distance, after which the weighting ceases to grow. The method is demonstrated using synthetic and real examples, highlighting its use when the accuracy of maps with inherently uncertain class boundaries is evaluated.
Published: 2020
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10. Decomposing the Interactions between Fire Severity and Canopy Fuel Structure Using Multi-Temporal, Active, and Passive Remote Sensing Approaches

Author: Nicholas S. Skowronski, Michael R. Gallagher, and Timothy A. Warner
Subjects: light detection and ranging, fire severity, canopy fuel loading, Physics, QC1-999
Abstract: Within the realms of both wildland and prescribed fire, an understanding of how fire severity and forest structure interact is critical for improving fuels treatment effectiveness, quantifying the ramifications of wildfires, and improving fire behavior modeling. We integrated high resolution estimates of fire severity with multi-temporal airborne laser scanning data to examine the role that various fuel loading, canopy shape, and other variables had on predicting fire severity for a complex of prescribed fires and one wildfire and how three-dimensional fuels changed as a result of these fires. Fuel loading characteristics were widely variable, and fires were ignited using a several techniques (heading, flanking, and backing), leading to a large amount of variability in fire behavior and subsequent fire effects. Through our analysis, we found that fire severity was linked explicitly to pre-fire fuel loading and structure, particularly in the three-dimensional distribution of fuels. Fire severity was also correlated with post-fire fuel loading, forest structural heterogeneity, and shifted the diversity and abundance of canopy classes within the landscape. This work demonstrates that the vertical distribution of fuel is an important factor and that subtle difference has defined effects on fire behavior and severity.
Published: 2020
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11. Large-Area, High Spatial Resolution Land Cover Mapping Using Random Forests, GEOBIA, and NAIP Orthophotography: Findings and Recommendations

Author: Aaron E. Maxwell, Michael P. Strager, Timothy A. Warner, Christopher A. Ramezan, Alice N. Morgan, and Cameron E. Pauley
Subjects: land cover, land cover mapping, object-based image analysis, GEOBIA, machine learning, random forests, National Agriculture Imagery Program, NAIP, Science
Abstract: Despite the need for quality land cover information, large-area, high spatial resolution land cover mapping has proven to be a difficult task for a variety of reasons including large data volumes, complexity of developing training and validation datasets, data availability, and heterogeneity in data and landscape conditions. We investigate the use of geographic object-based image analysis (GEOBIA), random forest (RF) machine learning, and National Agriculture Imagery Program (NAIP) orthophotography for mapping general land cover across the entire state of West Virginia, USA, an area of roughly 62,000 km2. We obtained an overall accuracy of 96.7% and a Kappa statistic of 0.886 using a combination of NAIP orthophotography and ancillary data. Despite the high overall classification accuracy, some classes were difficult to differentiate, as highlight by the low user’s and producer’s accuracies for the barren, impervious, and mixed developed classes. In contrast, forest, low vegetation, and water were generally mapped with accuracy. The inclusion of ancillary data and first- and second-order textural measures generally improved classification accuracy whereas band indices and object geometric measures were less valuable. Including super-object attributes improved the classification slightly; however, this increased the computational time and complexity. From the findings of this research and previous studies, recommendations are provided for mapping large spatial extents.
Published: 2019
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12. Evaluation of Sampling and Cross-Validation Tuning Strategies for Regional-Scale Machine Learning Classification

Author: Christopher A. Ramezan, Timothy A. Warner, and Aaron E. Maxwell
Subjects: training sample selection, cross-validation, high resolution imagery, NAIP, Lidar, regional-scale, Science
Abstract: High spatial resolution (1–5 m) remotely sensed datasets are increasingly being used to map land covers over large geographic areas using supervised machine learning algorithms. Although many studies have compared machine learning classification methods, sample selection methods for acquiring training and validation data for machine learning, and cross-validation techniques for tuning classifier parameters are rarely investigated, particularly on large, high spatial resolution datasets. This work, therefore, examines four sample selection methods—simple random, proportional stratified random, disproportional stratified random, and deliberative sampling—as well as three cross-validation tuning approaches—k-fold, leave-one-out, and Monte Carlo methods. In addition, the effect on the accuracy of localizing sample selections to a small geographic subset of the entire area, an approach that is sometimes used to reduce costs associated with training data collection, is investigated. These methods are investigated in the context of support vector machines (SVM) classification and geographic object-based image analysis (GEOBIA), using high spatial resolution National Agricultural Imagery Program (NAIP) orthoimagery and LIDAR-derived rasters, covering a 2,609 km2 regional-scale area in northeastern West Virginia, USA. Stratified-statistical-based sampling methods were found to generate the highest classification accuracy. Using a small number of training samples collected from only a subset of the study area provided a similar level of overall accuracy to a sample of equivalent size collected in a dispersed manner across the entire regional-scale dataset. There were minimal differences in accuracy for the different cross-validation tuning methods. The processing time for Monte Carlo and leave-one-out cross-validation were high, especially with large training sets. For this reason, k-fold cross-validation appears to be a good choice. Classifications trained with samples collected deliberately (i.e., not randomly) were less accurate than classifiers trained from statistical-based samples. This may be due to the high positive spatial autocorrelation in the deliberative training set. Thus, if possible, samples for training should be selected randomly; deliberative samples should be avoided.
Published: 2019
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13. Change Detection Accuracy and Image Properties: A Study Using Simulated Data

Author: Abdullah Almutairi and Timothy A. Warner
Subjects: change detection, post-classification comparison, change classification, image differencing, principal component analysis, change vector analysis, simulated data, Science
Abstract: Simulated data were used to investigate the relationships between image properties and change detection accuracy in a systematic manner. The image properties examined were class separability, radiometric normalization and image spectral band-to-band correlation. The change detection methods evaluated were post-classification comparison, direct classification of multidate imagery, image differencing, principal component analysis, and change vector analysis. The simulated data experiments showed that the relative accuracy of the change detection methods varied with changes in image properties, thus confirming the hypothesis that caution should be used in generalizing from studies that use only a single image pair. In most cases, direct classification and post-classification comparison were the least sensitive to changes in the image properties of class separability, radiometric normalization error and band correlation. Furthermore, these methods generally produced the highest accuracy, or were amongst those with a high accuracy. PCA accuracy was highly variable; the use of four principal components consistently resulted in substantial decreased classification accuracy relative to using six components, or classification using the original six bands. The accuracy of image differencing also varied greatly in the experiments. Of the three methods that require radiometric normalization, image differencing was the method most affected by radiometric error, relative to change vector and classification methods, for classes that have moderate and low separability. For classes that are highly separable, image differencing was relatively unaffected by radiometric normalization error. CVA was found to be the most accurate method for classes with low separability and all but the largest radiometric errors. CVA accuracy tended to be the least affected by changes in the degree of band correlation in situations where the class means were moderately dispersed, or clustered near the diagonal. For all change detection methods, the classification accuracy increased as simulated band correlation increased, and direct classification methods consistently had the highest accuracy, while PCA generally had the lowest accuracy.
Published: 2010
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14. Spatiotemporal Evolution of Land Subsidence in the Beijing Plain 2003–2015 Using Persistent Scatterer Interferometry (PSI) with Multi-Source SAR Data

Author: Chaodong Zhou, Huili Gong, Youquan Zhang, Timothy A. Warner, and Cong Wang
Subjects: land subsidence, InSAR, PSI, spatiotemporal evolution, Beijing Plain, Science
Abstract: Land subsidence is one of the most important geological hazards in Beijing, China, and its scope and magnitude have been growing rapidly over the past few decades, mainly due to long-term groundwater withdrawal. Interferometric Synthetic Aperture Radar (InSAR) has been used to monitor the deformation in Beijing, but there is a lack of analysis of the long-term spatiotemporal evolution of land subsidence. This study focused on detecting and characterizing spatiotemporal changes in subsidence in the Beijing Plain by using Persistent Scatterer Interferometry (PSI) and geographic spatial analysis. Land subsidence during 2003–2015 was monitored by using ENVISAT ASAR (2003–2010), RADARSAT-2 (2011–2015) and TerraSAR-X (2010–2015) images, with results that are consistent with independent leveling measurements. The radar-based deformation velocity ranged from −136.9 to +15.2 mm/year during 2003–2010, and −149.4 to +8.9 mm/year during 2011–2015 relative to the reference point. The main subsidence areas include Chaoyang, Tongzhou, Shunyi and Changping districts, where seven subsidence bowls were observed between 2003 and 2015. Equal Fan Analysis Method (EFAM) shows that the maximum extensive direction was eastward, with a growing speed of 11.30 km2/year. Areas of differential subsidence were mostly located at the boundaries of the seven subsidence bowls, as indicated by the subsidence rate slope. Notably, the area of greatest subsidence was generally consistent with the patterns of groundwater decline in the Beijing Plain.
Published: 2018
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15. Quantify Wheat Canopy Leaf Angle Distribution Using Terrestrial Laser Scanning Data.

Author: Yongqing Wang, Yangyang Gu, Jinxin Tang, Binbin Guo, Timothy A. Warner, Caili Guo, Hengbiao Zheng, Fumiki Hosoi, Tao Cheng 0003, Yan Zhu 0005, Weixing Cao, and Xia Yao
Published: 2024
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16. RSARE: A physically-based vegetation index for estimating wheat green LAI to mitigate the impact of leaf chlorophyll content and residue-soil background

Author: Wei Li, Dong Li, Shouyang Liu, Frédéric Baret, Zhiyuan Ma, Can He, Timothy A. Warner, Caili Guo, Tao Cheng, Yan Zhu, Weixing Cao, and Xia Yao
Subjects: Computers in Earth Sciences, Engineering (miscellaneous), Atomic and Molecular Physics, and Optics, Computer Science Applications
Published: 2023
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17. A Multitemporal Remote Sensing Image Registration Method Based on Water Bodies for the Lake-Rich Region.

Author: Zhanfeng Shen, Junli Li, Yongwei Sheng, Timothy A. Warner, and Lifang Zhao
Published: 2019
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18. CompTIA A+ Certification All-in-One For Dummies

Author: Glen E. Clarke, Edward Tetz, Timothy L. Warner
Published: 2019

19. A pilot study assessing the implementation of 96-well plate-based aggregometry (Optimul) in Australia

Author: Hannah Hsu, Melissa V. Chan, Paul C. Armstrong, Marilena Crescente, Dea Donikian, Mayuko Kondo, Timothy Brighton, Vivien Chen, Qiang Chen, David Connor, Joanne Joseph, Marie-Christine Morel-Kopp, William S. Stevenson, Christopher Ward, Timothy D. Warner, and David J. Rabbolini
Subjects: Aspirin, Platelet Aggregation, Platelet Function Tests, Anti-Inflammatory Agents, Non-Steroidal, Humans, Pilot Projects, Blood Platelet Disorders, Clopidogrel, Pathology and Forensic Medicine
Abstract: Identification of disordered platelet function is important to guide peri-operative bleeding management as well as long term treatment and prognostic strategies in individuals with platelet bleeding disorders. Light transmission aggregometry (LTA), the current gold standard diagnostic test of platelet function is a time consuming technique almost exclusively performed in specialised laboratories and almost universally unavailable in regional centres in Australia, where there is an unmet need for access to specialised platelet function diagnostic services. 96-well plate-based aggregometry (Optimul, UK), has been utilised in research laboratories as a novel platform to investigate platelet function. We evaluated the Optimul assay at two centres in Australia, one regional and one tertiary metropolitan, to assess its feasibility as a screening test applicable to remote regional centres. Concentration-response curves were established from 45 healthy volunteers at the participating regional hospital and from 31 healthy volunteers at the tertiary institution. Optimul successfully detected anti-platelet effects in individuals taking aspirin (n=4), NSAID (n=2), clopidogrel (n=2) and dual therapy with aspirin and clopidogrel (n=1). When tested in parallel to LTA in individuals referred for the evaluation of abnormal bleeding symptoms there was overall a very good level of agreement between Optimul and LTA [Cohen's kappa (k
Published: 2022
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20. Characterizing seasonal and long-term dynamics of a lacustrine wetland in Xinjiang, China, using dense time-series remote sensing imagery

Author: Jiudan Zhang, Junli Li, Anming Bao, Timothy a Warner, Longhui Li, Cun Chang, Jie Bai, and Tie Liu
Subjects: General Earth and Planetary Sciences
Published: 2022
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21. Continuous annual land use and land cover mapping using AVHRR GIMMS NDVI3g and MODIS MCD12Q1 datasets over China from 1982 to 2012.

Author: Yaqian He, Eungul Lee, and Timothy A. Warner
Published: 2016
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22. Exploring golden eagle habitat preference using lidar-based canopy bulk density

Author: Timothy A. Warner, Tricia A. Miller, Inga P. La Puma, Lee Ann Nolan, Nicholas S. Skowronski, and Aaron E. Maxwell
Subjects: Earth and Planetary Sciences (miscellaneous), Electrical and Electronic Engineering
Published: 2022
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23. What can we learn from senescent platelets, their transcriptomes and proteomes?

Author: Harriet E. Allan, Ami Vadgama, Paul C. Armstrong, and Timothy D. Warner
Subjects: Hematology, General Medicine
Published: 2023
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24. Data from The Farnesoid X Receptor Is Expressed in Breast Cancer and Regulates Apoptosis and Aromatase Expression

Author: David Bishop-Bailey, Timothy D. Warner, Desmond T. Walsh, Robert Carpenter, Márta Korbonits, and Karen E. Swales
Abstract: Bile acids are present at high concentrations in breast cysts and in the plasma of postmenopausal women with breast cancer. The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that regulates bile acid homeostasis. FXR was detected in normal and tumor breast tissue, with a high level of expression in ductal epithelial cells of normal breast and infiltrating ductal carcinoma cells. FXR was also present in the human breast carcinoma cells, MCF-7 and MDA-MB-468. Activation of FXR by high concentrations of ligands induced MCF-7 and MDA-MB-468 apoptosis. At lower concentrations that had no direct effect on viability, the FXR agonist GW4064 induced expression of mRNA for the FXR target genes, small heterodimer partner (SHP), intestinal bile acid binding protein, and multidrug resistance–associated protein 2 (MRP-2), and repressed the expression of the SHP target gene aromatase. In contrast to MRP-2, mRNA for the breast cancer target genes MDR-3, MRP-1, and solute carrier transporter 7A5 were decreased. Although multidrug resistance transporters were regulated and are known FXR target genes, GW4064 had no effect on the cell death induced by the anticancer drug paclitaxel. Our findings show for the first time that FXR is expressed in breast cancer tissue and has multiple properties that could be used for the treatment of breast cancer. (Cancer Res 2006; 66(20): 10120-6)
Published: 2023
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25. Supplementary Figures 1-4 from The Farnesoid X Receptor Is Expressed in Breast Cancer and Regulates Apoptosis and Aromatase Expression

Author: David Bishop-Bailey, Timothy D. Warner, Desmond T. Walsh, Robert Carpenter, Márta Korbonits, and Karen E. Swales
Abstract: Supplementary Figures 1-4 from The Farnesoid X Receptor Is Expressed in Breast Cancer and Regulates Apoptosis and Aromatase Expression
Published: 2023
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26. Renal Function Underpins the Cyclooxygenase-2: Asymmetric Dimethylarginine Axis in Mouse and Man

Author: Plinio Ferreira, Ricky Vaja, Maria Lopes-Pires, Marilena Crescente, He Yu, Rolf Nüsing, Bin Liu, Yingbi Zhou, Magdi Yaqoob, Anran Zhang, Matthew Rickman, Hilary Longhurst, William E. White, Rebecca B. Knowles, Melissa V. Chan, Timothy D. Warner, Elizabeth Want, Nicholas S. Kirkby, and Jane A. Mitchell
Subjects: Nephrology
Published: 2023
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27. SARS-CoV-2 Spike protein activates TMEM16F-mediated platelet procoagulant activity

Author: Ambra Cappelletto, Harriet E. Allan, Marilena Crescente, Edoardo Schneider, Rossana Bussani, Hashim Ali, Ilaria Secco, Simone Vodret, Roberto Simeone, Luca Mascaretti, Serena Zacchigna, Timothy D. Warner, Mauro Giacca, Ali, Hashim [0000-0002-5056-845X], and Apollo - University of Cambridge Repository
Subjects: SARS-CoV-2, TMEM16F, platelets, COVID-19, Niclosamide, Spike, coagulation, Cardiology and Cardiovascular Medicine, Clofazimine
Abstract: Thrombosis of the lung microvasculature is a characteristic of COVID-19 disease, which is observed in large excess compared to other forms of acute respiratory distress syndrome and thus suggests a trigger for thrombosis that is endogenous to the lung. Our recent work has shown that the SARS-CoV-2 Spike protein activates the cellular TMEM16F chloride channel and scramblase. Through a screening on >3,000 FDA/EMA approved drugs, we identified Niclosamide and Clofazimine as the most effective molecules at inhibiting Spike-induced TMEM16 activation. As TMEM16F plays an important role in stimulating the procoagulant activity of platelets, we investigated whether Spike directly affects platelet activation and pro-thrombotic function and tested the effect of Niclosamide and Clofazimine on these processes. Here we show that Spike, present either on the virion envelope or on the cell plasma membrane, promotes platelet activation, adhesion and spreading. Spike was active as a sole agonist or, even more effectively, by enhancing the function of known platelet activators. In particular, Spike-induced a marked procoagulant phenotype in platelets, by enhancing Ca2+ flux, phosphatidylserine externalization on the platelet outer cell membrane, and thrombin generation. Eventually, this increased thrombin-induced clot formation and retraction. Both Niclosamide and Clofazimine blocked this Spike-induced procoagulant response. These findings provide a pathogenic mechanism to explain lung thrombosis-associated with severe COVID-19 infection. We propose that Spike, present in SARS-CoV-2 virions or exposed on the surface of infected cells in the lungs, enhances the effects of inflammation and leads to local platelet stimulation and subsequent activation of the coagulation cascade. As platelet TMEM16F is central in this process, these findings reinforce the rationale of repurposing Niclosamide for COVID-19 therapy.
Published: 2023
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28. Proteome and functional decline as platelets age in the circulation

Author: Laura Menke, Timothy D. Warner, Manuel Mayr, Melissa V. Chan, Marilena Crescente, Tania Maffucci, Melissa A. Hayman, Harriet E. Allan, Abhishek Joshi, Matthew L. Edin, Paul C Armstrong, Darryl C. Zeldin, and Simone Marcone
Subjects: Blood Platelets, Proteomics, Senescence, Hemostasis, Messenger RNA, medicine.medical_specialty, medicine.diagnostic_test, Proteome, Hematology, Mitochondrion, Biology, Immunofluorescence, Thrombocytopenia, Article, Endocrinology, Ageing, Apoptosis, Internal medicine, medicine, Humans, Secretion, Platelet
Abstract: Background Platelets circulate in the blood of healthy individuals for approximately 7-10 days regulated by finely balanced processes of production and destruction. As platelets are anucleate we reasoned that their protein composition would change as they age and that this change would be linked to alterations in structure and function. Objective To isolate platelets of different ages from healthy individuals to test the hypothesis that changes in protein content cause alterations in platelet structure and function. Methods Platelets were separated according to thiazole orange fluorescence intensity as a surrogate indicator of mRNA content and so a marker of platelet age and then subjected to proteomics, imaging, and functional assays to produce an in-depth analysis of platelet composition and function. Results Total protein content was 45±5% lower in old platelets compared to young platelets. Predictive proteomic pathway analysis identified associations with 28 biological processes, notably higher hemostasis in young platelets whilst apoptosis and senescence were higher in old platelets. Further studies confirmed platelet ageing was linked to a decrease in cytoskeletal protein and associated capability to spread and adhere, a reduction in mitochondria number, and lower calcium dynamics and granule secretion. Conclusions Our findings demonstrate changes in protein content are linked to alterations in function as platelets age. This work delineates physical and functional changes in platelets as they age and serves as a base to examine differences associated with altered mean age of platelet populations in conditions such as immune thrombocytopenia and diabetes.
Published: 2021
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29. Fully Automated Mapping of Disaster-Related Coastal Land Cover Changes with Google Earth Engine and R: The Chile 2010 Earthquake and Tsunami

Author: matias ivan volke, Rodrigo Abarca-del-Rio, and Timothy A. Warner
Published: 2023
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30. Assessment of Platelet Function by High-Throughput Screening Light Transmission Aggregometry: Optimul Assay

Author: Melissa V. Chan, Marie Lordkipanidzé, and Timothy D. Warner
Published: 2023
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31. Platelet ageing: A review

Author: Harriet E, Allan, Ami, Vadgama, Paul C, Armstrong, and Timothy D, Warner
Subjects: Hematology
Abstract: Platelet ageing is an area of research which has gained much interest in recent years. Newly formed platelets, often referred to as reticulated platelets, young platelets or immature platelets, are defined as RNA-enriched and have long been thought to be hyper-reactive. This latter view is largely rooted in associations and observations in patient groups with shortened platelet half-lives who often present with increased proportions of newly formed platelets. Evidence from such groups suggests that an increased proportion of newly formed platelets is associated with an increased risk of thrombotic events and a reduced effectiveness of standard anti-platelet therapies. Whilst research has highlighted the existence of platelet subpopulations based on function, size and age within patient groups, the common intrinsic changes which occur as platelets age within the circulation are only just being explored. By understanding the changes that occur during the natural ageing processes of platelets, we may be able to identify the triggers for alterations in platelet life span and platelet reactivity. Here we review research on platelet ageing in the context of health and disease, paying particular attention to the experimental approaches taken and the robustness of conclusions that can be drawn.
Published: 2022
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32. The information milieu of remote sensing: an overview

Author: Linda Blake and Timothy A. Warner
Published: 2014
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33. Platelet inhibition by P2Y 12 antagonists is potentiated by adenosine signalling activators

Author: Nicholas S. Kirkby, Ivana Vojnovic, Chih-Chin Shih, Paul C Armstrong, Timothy D. Warner, Jane A. Mitchell, and Melissa V. Chan
Subjects: Pharmacology, Prasugrel, Adenosine, Cyclic nucleotide, chemistry.chemical_compound, P2Y12, Thrombin, chemistry, medicine, Platelet, Platelet activation, Ticagrelor, medicine.drug
Abstract: Background and purpose P2Y12 receptor antagonists reduce platelet aggregation and the incidence of arterial thrombosis. Adenosine signalling in platelets directly affects cyclic nucleotide tone, which we have shown to have a synergistic relationship with P2Y12 inhibition. Several studies suggest that ticagrelor inhibits erythrocyte uptake of adenosine and that this could also contribute to its antiplatelet effects. We therefore examined the effects on platelet activation of adenosine signalling activators in combination with the P2Y12 receptor antagonists ticagrelor and prasugrel. Experimental approach Human washed platelets, platelet-rich plasma and whole blood were used to test the interactions between ticagrelor or prasugrel and adenosine or 5'-N-ethylcarboxamidoadenosine (NECA). Platelet reactivity to thrombin, protease-activated receptor 1 (PAR-1) activation or collagen was assessed by a combination of 96-well plate aggregometry, light transmission aggregometry, whole blood aggregometry, ATP release assay and levels of cAMP. Key results The inhibitory effects of ticagrelor and prasugrel on platelet aggregation and ATP release were enhanced in the presence of adenosine or NECA. Isobolographic analysis indicated a powerful synergy between P2Y12 receptor inhibition and adenosine signalling activators. Increased levels of cAMP in platelets were also observed. In all cases, ticagrelor showed similar synergistic effects on platelet inhibition as prasugrel in the presence of adenosine or NECA. Conclusion and implications These results indicate that P2Y12 antagonists have a synergistic relationship with adenosine signalling and that their efficacy may depend partly upon the presence of endogenous adenosine. This effect was common for prasugrel and ticagrelor despite reports of differences in their effects upon adenosine reuptake.
Published: 2021
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34. Oral Presentation No. 093 Assessing different noncoding RNAs as markers of platelet reactivity

Author: Clemens Gutmann, Temo Barwari, Christian Schulte, Bhawana Singh, Konstantinos Theofilatos, Abhishek Joshi, Anna Zampetaki, Melissa V Chan, Paul C Armstrong, Stefan Kiechl, Johann Willeit, Timothy D Warner, and Manuel Mayr
Subjects: Physiology, Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract: Background Antiplatelet therapy (APT) has improved cardiovascular outcomes, but some patients develop thrombosis despite APT. Adjusting APT to platelet reactivity with conventional platelet reactivity tests has proven unsuccessful. Many circulating noncoding RNAs (ncRNAs) are derived from platelets and could serve as novel platelet function markers. Material and methods Platelet reactivity was assessed using light transmission aggregometry (LTA) in the Bruneck 2015 study (N = 338), using the agonists arachidonic acid, adenosine diphosphate, collagen, TRAP-6 amide and U46619. LTA platelet releasates were then used for RT-qPCR of five platelet-enriched microRNAs, three circular RNAs and two long non-coding RNAs. Platelet-poor plasma (PPP) was used as negative control. Results and conclusions Platelet agonists induced aggregation and ncRNA release, with aspirin takers (N = 155) showing lower ncRNA release than individuals not on aspirin (N = 183). Agonist responsiveness differed among ncRNAs, with miR-150 being hyperresponsive to adenosine diphosphate and miR-21 being hyperresponsive to arachidonic acid, whereas other ncRNAs were most strongly released to collagen, suggesting a selective release mechanism. In individuals not on aspirin, the inflammation markers C-reactive protein and granulocyte counts correlated positively with platelet-derived ncRNAs in PPP, while they correlated inversely with platelet-derived ncRNAs in releasates. These correlations were not present in aspirin takers. Higher PPP levels and lower releasate levels of platelet-derived ncRNAs in inflammation suggest platelet exhaustion ex vivo due to platelet pre-activation in vivo. Funding sources British Heart Foundation, VASCage (Centre for Promoting Vascular Health in the Ageing Community) of the Austrian Research Promotion Agency FFG (COMET program - Competence Centers for Excellent Technologies).
Published: 2022
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35. Temporal in vivo platelet labeling in mice reveals age-dependent receptor expression and conservation of specific mRNAs

Author: Paul C. Armstrong, Harriet E. Allan, Nicholas S. Kirkby, Clemens Gutmann, Abhishek Joshi, Marilena Crescente, Jane A. Mitchell, Manuel Mayr, and Timothy D. Warner
Subjects: Blood Platelets, Mice, Receptor for Advanced Glycation End Products, Animals, Gene Expression, Thrombosis, Hematology, RNA, Messenger, Cytoplasmic Granules
Abstract: The proportion of young platelets, also known as newly formed or reticulated, within the overall platelet population has been clinically correlated with adverse cardiovascular outcomes. However, our understanding of this is incomplete because of limitations in the technical approaches available to study platelets of different ages. In this study, we have developed and validated an in vivo temporal labeling approach using injectable fluorescent antiplatelet antibodies to subdivide platelets by age and assess differences in functional and molecular characteristics. With this approach, we found that young platelets (
Published: 2022

36. Identification of a homozygous recessive variant in PTGS1 resulting in a congenital aspirin-like defect in platelet function

Author: Michael G. Malkowski, Michael Laffan, Nihr BioResource, Melissa A. Hayman, Darryl C. Zeldin, Liang Dong, Valerie B. O'Donnell, Melissa V. Chan, Daniel Greene, Kathleen Freson, Harriet E. Allan, Ginger L. Milne, Daniel P. Hart, Timothy D. Warner, Moghees Hanif, Suthesh Sivapalaratnam, Claire Lentaigne, Ernest Turro, Kate Downes, Marilena Crescente, Matthew L. Edin, Jonathan Stephens, Willem H. Ouwehand, Matthew Stubbs, and Katherine Wedderburn
Subjects: 0301 basic medicine, Proband, medicine.medical_specialty, Aspirin, Eicosanoid metabolism, business.industry, PTGS1, Hematology, 030204 cardiovascular system & hematology, 03 medical and health sciences, Thromboxane A2, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Endocrinology, chemistry, Internal medicine, Medicine, Missense mutation, Platelet, business, Eicosanoid Production, medicine.drug
Abstract: We have identified a rare missense variant on chromosome 9, position 125145990 (GRCh37), in exon 8 in PTGS1 (the gene encoding cyclo-oxygenase 1, COX-1, the target of anti-thrombotic aspirin therapy). We report that in the homozygous state within a large consanguineous family this variant is associated with a bleeding phenotype and alterations in platelet reactivity and eicosanoid production. Western blotting and confocal imaging demonstrated that COX-1 was absent in the platelets of three family members homozygous for the PTGS1 variant but present in their leukocytes. Platelet reactivity, as assessed by aggregometry, lumi-aggregometry and flow cytometry, was impaired in homozygous family members, as were platelet adhesion and spreading. The productions of COX-derived eicosanoids by stimulated platelets were greatly reduced but there were no changes in the levels of urinary metabolites of COX-derived eicosanoids. The proband exhibited additional defects in platelet aggregation and spreading which may explain why her bleeding phenotype was slightly more severe than those of other homozygous affected relatives. This is the first demonstration in humans of the specific loss of platelet COX-1 activity and provides insight into its consequences for platelet function and eicosanoid metabolism. Notably despite the absence of thromboxane A2 (TXA2) formation by platelets, urinary TXA2 metabolites were in the normal range indicating these cannot be assumed as markers of in vivo platelet function. Results from this study are important benchmarks for the effects of aspirin upon platelet COX-1, platelet function and eicosanoid production as they define selective platelet COX-1 ablation within humans.
Published: 2020
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37. Geointelligence for assessing natural resource project risks.

Author: J. V. Gardner, J.-M. Monget, R. Sinding-Larsen, and Timothy A. Warner
Published: 2003
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38. Temporal in vivo platelet labelling in mice reveals age-dependent receptor expression and conservation of specific mRNAs

Author: Paul C Armstrong, Harriet E Allan, Nicholas S Kirkby, Abhishek Joshi, Clemens Gutmann, Marilena Crescente, Jane A Mitchell, Manuel Mayr, and Timothy D Warner
Abstract: The proportion of young platelets, also known as newly formed or reticulated, within the overall platelet population has been clinically correlated with adverse cardiovascular outcomes. Our understanding of this is incomplete, however, because of limitations in the technical approaches available to study platelets of different ages. In this study we have developed and validated an in vivo ‘temporal labelling’ approach using injectable fluorescent anti-platelet antibodies to sub-divide platelets by age and assess differences in functional and molecular characteristics. With this approach we found that young platelets (in vitro and in vivo. Sequential sampling confirmed this altered functionality to be independent of platelet size with no size differences or changes relative to the global population seen at any age. The age associated decrease in thrombotic function was accompanied by significant decreases in the surface expression of GPVI and CD31 (PECAM-1) and an increase in CD9. Platelet mRNA content also decreased with age but at different rates for individual mRNAs indicating apparent conservation of those encoding granule proteins. Our pulse-chase type approach to define circulating platelet age has allowed timely re-examination of commonly held beliefs regarding size and reactivity of young platelets whilst providing novel insights into the temporal regulation of receptor and protein expression. Overall, future application of this validated tool will inform on age-based platelet heterogeneity in physiology and disease.
Published: 2021
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39. SARS-CoV-2 Spike protein activates TMEM16F-mediated platelet pro-coagulant activity

Author: Ambra Cappelletto, Harriet E. Allan, Marilena Crescente, Edoardo Schneider, Rossana Bussani, Hashim Ali, Ilaria Secco, Simone Vodret, Roberto Simeone, Luca Mascaretti, Serena Zacchigna, Timothy D. Warner, and Mauro Giacca
Subjects: Platelets, Coagulation, SARS-CoV-2, TMEM16F, Niclosamide, Clofazimine
Abstract: BackgroundThrombosis of the lung micro-vasculature is a characteristic of COVID-19 disease, which is observed in large excess compared to other forms of acute respiratory distress syndrome and thus suggests a trigger for thrombosis endogenous to the lung. Our recent work has shown that the SARS-CoV-2 Spike protein activates the cellular TMEM16F chloride channel and scramblase. Through a screening on >3,000 FDA/EMA approved drugs, we identified Niclosamide and Clofazimine as the most effective molecules at inhibiting this activity. As TMEM16F plays an important role in the stimulation of the pro-coagulant activity of platelets, and considering that platelet abnormalities are common in COVID-19 patients, we investigated whether Spike directly affects platelet activation and pro-thrombotic function and tested the effect of Niclosamide and Clofazimine on these processes.MethodsWe produced SARS-CoV-2 Spike or VSV-G protein-pseudotyped virions, or generated cells expressing Spike on their plasma membrane, and tested their effects on platelet adhesion (fluorescence), aggregation (absorbance), exposure of phosphatidylserine (flow cytometry for annexin V binding), calcium flux (flow cytometry for fluo-4 AM), and clot formation and retraction. These experiments were also conducted in the presence of the TMEM16F activity inhibitors Niclosamide and Clofazimine.ResultsHere we show that exposure to SARS-CoV-2 Spike promotes platelet activation, adhesion and spreading, both when present on the envelope of virions or upon expression on the plasma membrane of cells. Spike was effective both as a sole agonist or by enhancing the effect of known platelet activators, such as collagen and collagen-related peptide. In particular, Spike exerted a noticeable effect on the procoagulant phenotype of platelets, by enhancing calcium flux, phosphatidylserine externalisation, and thrombin generation. Eventually, this resulted in a striking increase in thrombin-induced clot formation and retraction. Both Niclosamide and Clofazimine almost abolished this Spike-induced pro-coagulant response.ConclusionsTogether, these findings provide a pathogenic mechanism to explain thrombosis associated to COVID-19 lung disease, by which Spike present in SARS-CoV-2 virions or exposed on the surface of infected cells, leads to local platelet stimulation and subsequent activation of the coagulation cascade. As platelet TMEM16F is central in this process, these findings reinforce the rationale of repurposing drugs targeting this protein, such as Niclosamide, for COVID-19 therapy.
Published: 2021
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40. Neutrophil-Derived Protein S100A8/A9 Alters the Platelet Proteome in Acute Myocardial Infarction and Is Associated With Changes in Platelet Reactivity

Author: Anthony Mathur, Ruifang Lu, Peter Willeit, Konstantinos Theofilatos, Timothy D. Warner, Sean A. Burnap, Peter Santer, Clemens Gutmann, Johann Willeit, Paul C Armstrong, Ferheen Baig, Abhishek Joshi, Lukas E Schmidt, Temo Barwari, Stefan Kiechl, Manuel Mayr, and Melissa V. Chan
Subjects: Blood Platelets, Male, Proteomics, medicine.medical_specialty, Time Factors, Proteome, Neutrophils, S100A9, Neutrophil Activation, S100A8, Coronary artery disease, Internal medicine, Cell Line, Tumor, medicine, Calgranulin B, Humans, Platelet, Calgranulin A, Myocardial infarction, Platelet activation, Prospective Studies, Aged, Aspirin, business.industry, Middle Aged, medicine.disease, Platelet Activation, Endocrinology, medicine.anatomical_structure, Case-Control Studies, ST Elevation Myocardial Infarction, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug, Artery
Abstract: Objective: Platelets are central to acute myocardial infarction (MI). How the platelet proteome is altered during MI is unknown. We sought to describe changes in the platelet proteome during MI and identify corresponding functional consequences. Approach and Results: Platelets from patients experiencing ST-segment–elevation MI (STEMI) before and 3 days after treatment (n=30) and matched patients with severe stable coronary artery disease before and 3 days after coronary artery bypass grafting (n=25) underwent quantitative proteomic analysis. Elevations in the proteins S100A8 and S100A9 were detected at the time of STEMI compared with stable coronary artery disease (S100A8: FC, 2.00; false discovery rate, 0.05; S100A9: FC, 2.28; false discovery rate, 0.005). During STEMI, only S100A8 mRNA and protein levels were correlated in platelets ( R =0.46, P =0.012). To determine whether de novo protein synthesis occurs, activated platelets were incubated with 13C-labeled amino acids for 24 hours and analyzed by mass spectrometry. No incorporation was confidently detected. Platelet S100A8 and S100A9 was strongly correlated with neutrophil abundance at the time of STEMI. When isolated platelets and neutrophils were coincubated under quiescent and activated conditions, release of S100A8 from neutrophils resulted in uptake of S100A8 by platelets. Neutrophils released S100A8/A9 as free heterodimer, rather than in vesicles or extracellular traps. In the community-based Bruneck study (n=338), plasma S100A8/A9 was inversely associated with platelet reactivity—an effect abrogated by aspirin. Conclusions: Leukocyte-to-platelet protein transfer may occur in a thromboinflammatory environment such as STEMI. Plasma S100A8/A9 was negatively associated with platelet reactivity. These findings highlight neutrophils as potential modifiers for thrombotic therapies in coronary artery disease.
Published: 2021

41. Image restoration based on multiscale relationships of image structures.

Author: Tomas Brandtberg, James B. McGraw, Timothy A. Warner, and Rick E. Landenberger
Published: 2003
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42. Reducing Uncertainties in Applying Remotely Sensed Land Use and Land Cover Maps in Land-Atmosphere Interaction: Identifying Change in Space and Time.

Author: Yaqian He, Timothy A. Warner, Brenden E. McNeil, and Eungul Lee
Published: 2018
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43. Serotonin-Affecting Antidepressant Use in Relation to Platelet Reactivity

Author: Joseph Grech, Melissa Victoria Chan, Chinedu Ochin, Amber Lachapelle, Florian Thibord, Zoe Schneider, Bongani Brian Nkambule, Paul Charles John Armstrong, Catherine Wallace de Melendez, Katherine L. Tucker, Mahdi Garelnabi, Timothy David Warner, Ming‐Huei Chen, and Andrew Danner Johnson
Subjects: Pharmacology, Adenosine Diphosphate, Blood Platelets, Serotonin, Aspirin, Platelet Aggregation, Platelet Function Tests, Humans, Pharmacology (medical), Antidepressive Agents, Platelet Aggregation Inhibitors
Abstract: Depression is an independent risk factor of cardiovascular disease morbidity. Serotonin is a key neurotransmitter in depressive pathology, contained within platelets, and is a weak activator of platelets. Our study assessed the link between platelet reactivity traits, depression, and antidepressant (AD) use in a large population sample. Our study was conducted in the Framingham Heart Study (n = 3,140), and AD use (n = 563) and aspirin use (n = 681) were noted. Depression was measured using the Center for Epidemiological Studies-Depression (CES-D) survey. Platelet reactivity traits were measured across multiple agonists using five distinct assays. We utilized a linear mixed effects model to test associations between platelet traits and depression, adjusting for age, sex, aspirin use, and AD use. Similarly, we analyzed trait associations with any AD use, serotonin-affecting ADs, and norepinephrine-affecting ADs, respectively. There were strong associations with reduced platelet function and AD use, particularly with serotonin-affecting medications. This included lower Optimul epinephrine maximal aggregation (P = 4.87E-13), higher U46619 half maximal effective concentration (P = 9.09E-11), lower light transmission aggregometry (LTA) adenosine diphosphate (ADP) final aggregation (P = 1.03E-05), and higher LTA ADP disaggregation (P = 2.28E-05). We found similar associations with serotonin-affecting ADs in an aspirin-taking subset of our sample. There were no significant associations between platelet traits and depression. In the largest study yet of AD use and platelet function we show that antidepressants, particularly serotonin-affecting ADs, inhibit platelets. We did not find evidence that depressive symptomatology in the absence of medication is associated with altered platelet function. Our results are consistent with AD use leading to platelet serotonin depletions, decreased stability of platelet aggregates, and overall decreased aggregation to multiple agonists, which may be a mechanism by which ADs increase risk of bleeding and decrease risk of thrombosis.
Published: 2021

44. Hypoxia Modulates Platelet Purinergic Signalling Pathways

Author: Eleanor W. Lee, Greig S. Torpey, Joseph A Willson, Timothy D. Warner, Sarah R. Walmsley, Melissa V. Chan, J K Baillie, Alfred Arthur Roger Thompson, Jason M. Young, Christopher J Graham, Gordon G. Paterson, and Rebecca C. Dru
Subjects: 0301 basic medicine, Adult, Blood Platelets, Male, P2Y receptor, Adolescent, Platelet Aggregation, Platelet Function Tests, 030204 cardiovascular system & hematology, Pharmacology, anti-platelet agents, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, P2Y12, Cangrelor, high altitude, Cellular Haemostasis and Platelets, ADP receptors, Humans, Platelet, Platelet activation, Phosphorylation, Hypoxia, Platelet-Rich Plasma, Altitude, platelet physiology, Microfilament Proteins, Receptors, Purinergic, Hematology, Purinergic signalling, Phosphoproteins, Platelet Activation, Adenosine Monophosphate, Adenosine Diphosphate, Oxygen, Adenosine diphosphate, 030104 developmental biology, chemistry, Female, Receptors, Thrombin, Cell Adhesion Molecules, Platelet Aggregation Inhibitors, Signal Transduction
Abstract: Background Hypoxia resulting from ascent to high-altitude or pathological states at sea level is known to increase platelet reactivity. Previous work from our group has suggested that this may be adenosine diphosphate (ADP)-specific. Given the clinical importance of drugs targeting ADP pathways, research into the impact of hypoxia on platelet ADP pathways is highly important. Methods Optimul aggregometry was performed on plasma from 29 lowland residents ascending to 4,700 m, allowing systematic assessment of platelet reactivity in response to several platelet agonists. Aggregometry was also performed in response to ADP in the presence of inhibitors of the two main ADP receptors, P2Y1 and P2Y12 (MRS2500 and cangrelor, respectively). Phosphorylation of vasodilator-stimulated phosphoprotein (VASP), a key determinant of platelet aggregation, was analysed using the VASPFix assay. Results Hypobaric hypoxia significantly reduced the ability of a fixed concentration of cangrelor to inhibit ADP-induced aggregation and increased basal VASP phosphorylation. However, in the absence of P2Y receptor inhibitors, we did not find evidence of increased platelet sensitivity to any of the agonists tested and found reduced sensitivity to thrombin receptor-activating peptide-6 amide. Conclusion Our results provide evidence of increased P2Y1 receptor activity at high altitude and suggest down-regulation of the P2Y12 pathway through increased VASP phosphorylation. These changes in ADP pathway activity are of potential therapeutic significance to high-altitude sojourners and hypoxic sea level patients prescribed platelet inhibitors and warrant further investigation.
Published: 2019
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45. A Multitemporal Remote Sensing Image Registration Method Based on Water Bodies for the Lake-Rich Region

Author: Timothy A. Warner, Zhanfeng Shen, Yongwei Sheng, Lifang Zhao, and Junli Li
Subjects: Atmospheric Science, 010504 meteorology & atmospheric sciences, Pixel, 0211 other engineering and technologies, Image registration, 02 engineering and technology, 01 natural sciences, Subpixel rendering, Multispectral Scanner, Medial axis, Polygon, Computers in Earth Sciences, Voronoi diagram, Change detection, Geology, 021101 geological & geomatics engineering, 0105 earth and related environmental sciences, Remote sensing
Abstract: Accurate multitemporal remotely sensed image registration is essential for water body change detection and analysis of lake dynamics. However, lake-rich regions, such as Siberia, are mostly dominated by rivers and lakes, with few stable geometry features such as those typically used as control points for image registration. Lakes in Arctic regions are generally not static; their shorelines tend to expand and shrink seasonally, and may change substantially between different years, making it difficult to find consistent features for image registration. Consequently, traditional image-to-image registration methods, and even many sophisticated registration algorithms, rarely achieve accurate geometric correction in Arctic regions due to a lack of sufficient control points. In this article, we proposed a summary lake spatial attribute, the inferred deepest point of the lake (DPL), as a feature that is relatively insensitive to lake area changes, and therefore useful for registration of multitemporal images. The central focus of the DPL estimation algorithm is the identification of the largest inner circle (LIC) of the lake polygon. First, the internal Voronoi diagram of a lake polygon is calculated by the ``divide-and-conquer” method. The medial axis (MA) is then calculated by Voronoi diagram simplification, and finally, the LIC center is obtained by computing the distance from the MA intersection to all polygon edges. The approach was used to register HJ-1 and Landsat multispectral scanner (MSS) images in Siberia, where water bodies dominate the landscape and change significantly over time. The proposed method found a large number of control points from the extracted water bodies. Subpixel registration accuracy of 0.62 pixels (18.5 m) and 0.33 pixels (19.6 m) root mean square error (RMSE) was obtained for the HJ-1 and MSS images, respectively. In comparison, the alternative method of using lake centroids, only achieved 0.75 pixels (22.4 m) and 0.49 pixels (29.3 m) RMSE. This registration accuracy improvement is potentially important for large-scale regional cartography and change detection applications.
Published: 2019
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46. Reduced rate of land subsidence since 2016 in Beijing, China: evidence from Tomo-PSInSAR using RadarSAT-2 and Sentinel-1 datasets

Author: John J. Clague, Huili Gong, Chaodong Zhou, Timothy A. Warner, Youquan Zhang, Hengxing Lan, and Yuming Wu
Subjects: 010504 meteorology & atmospheric sciences, 0211 other engineering and technologies, Subsidence, 02 engineering and technology, 01 natural sciences, Beijing, Remote sensing (archaeology), General Earth and Planetary Sciences, Environmental science, Extraction (military), Physical geography, China, Groundwater, 021101 geological & geomatics engineering, 0105 earth and related environmental sciences
Abstract: Land subsidence associated with groundwater extraction in the city of Beijing, China, has been a problem for decades. Remote sensing has been used extensively in prior studies to monitor su...
Published: 2019
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47. Preface for the Special Issue of IJRS Drones section in conjunction with the 6th UAS4Enviro conference

Author: Anita Simic Milas, Nicolas H. Younan, Matthew D. Larson, Timothy A. Warner, and Ivan Balenović
Subjects: Unmanned Aerial Systems (UAS), agriculture monitoring, monitoring urban areas, environmental and ecological applications, geoscience, vegetation and forest monitoring, Computer science, business.industry, Section (archaeology), Remote sensing (archaeology), Key (cryptography), General Earth and Planetary Sciences, Telecommunications, business, Drone, Conjunction (grammar)
Abstract: UAS4Enviro conference was held at the Faculty of Electrical Engineering, Mechanical Engineering and Naval Architecture (FESB), University of Split, Croatia from June 27–29, 2018. The conference sponsors were the Remote Sensing and Photogrammetry Society (RSPSoc), FESB, University of Split, the International Society for Photogrammetry and Remote Sensing (ISPRS), and SPatial LITeracy (SPLIT) Remote Sensing. The conference was attended by scholars and practitioners from across the global UAS community and featured presentations on the latest research into different data types, platforms, and methodologies. The conference highlighted the rapid development of Unmanned Aerial Systems (UAS) (aka drones), which are of worldwide interest, as this technology offers a low-cost alternative to high resolution satellite and airborne imagery. UAS technology is widely used across spatial science research …
Published: 2019
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48. Histone H4 induces platelet ballooning and microparticle release during trauma hemorrhage

Author: Paul C Armstrong, Timothy D. Warner, Paul Vulliamy, Harriet E. Allan, Karim Brohi, and Scarlett Gillespie
Subjects: Blood Platelets, 0301 basic medicine, Pathology, medicine.medical_specialty, Medical Sciences, Platelet Function Tests, Hemorrhage, 030204 cardiovascular system & hematology, Trauma hemorrhage, Ballooning, coagulopathy, Histones, Histone H4, 03 medical and health sciences, 0302 clinical medicine, Cell-Derived Microparticles, Leukocytes, Coagulopathy, medicine, Humans, Platelet, Blood Coagulation, Cause of death, Multidisciplinary, biology, business.industry, Thrombin, Biological Sciences, medicine.disease, Microparticle release, 3. Good health, trauma, 030104 developmental biology, Histone, platelets, biology.protein, Wounds and Injuries, Calcium, business
Abstract: Significance Membrane ballooning is a fundamental mechanism by which platelets contribute to thrombin generation. However, this process has not previously been described in human disease. In this study, we demonstrated the presence of ballooning procoagulant platelets free in the circulation of critically injured humans, a phenomenon which results in systemic generation of thrombin and contributes to an acute coagulopathy. The surfaces of ballooning platelets were decorated with the damage-associated molecular pattern histone H4, and exposure of healthy platelets to histone caused membrane disruption and recapitulated the phenotypic changes in injured patients. These findings provide a description of platelet ballooning contributing to human disease and identify histone release from injured tissues as a driver of the procoagulant ballooning process., Trauma hemorrhage is a leading cause of death and disability worldwide. Platelets are fundamental to primary hemostasis, but become profoundly dysfunctional in critically injured patients by an unknown mechanism, contributing to an acute coagulopathy which exacerbates bleeding and increases mortality. The objective of this study was to elucidate the mechanism of platelet dysfunction in critically injured patients. We found that circulating platelets are transformed into procoagulant balloons within minutes of injury, accompanied by the release of large numbers of activated microparticles which coat leukocytes. Ballooning platelets were decorated with histone H4, a damage-associated molecular pattern released in massive quantities after severe injury, and exposure of healthy platelets to histone H4 recapitulated the changes in platelet structure and function observed in trauma patients. This is a report of platelet ballooning in human disease and of a previously unrecognized mechanism by which platelets contribute to the innate response to tissue damage.
Published: 2019
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49. The therapeutic effect of stiripentol in Gabrg2 mice associated with epileptic encephalopathy

Author: Jing-Qiong Kang, Nicholas K. Smith, and Timothy A. Warner
Subjects: 0301 basic medicine, Agonist, Benzodiazepine, GABAA receptor, medicine.drug_class, business.industry, Pharmacology, medicine.disease, 03 medical and health sciences, Epilepsy, 030104 developmental biology, 0302 clinical medicine, Neurology, Dravet syndrome, medicine, Stiripentol, Neurology (clinical), Pentylenetetrazol, business, Diazepam, 030217 neurology & neurosurgery, medicine.drug
Abstract: Anti-seizure drugs (ASDs) are widely used and known to increase inhibitory tone on neuro-circuits and reduce aberrant synchronous firing in epilepsy. Some ASDs act as agonist at the GABAA receptor. Stiripentol, known to increase GABAA receptor activity as well as the metabolites of GABAA receptor agonists, is often used in the treatment of an epileptic encephalopathy, Dravet syndrome (DS), which is caused by mutations mainly in SCN1A and in other genes such as GABRG2. We have recently generated a Gabrg2+/Q390X knockin mouse model associated with DS in humans. The objective of the study was to explore the effects of stiripentol in DS with GABAA receptor functional deficiency because of the etiology heterogeneity in DS. Monotherapy (stiripentol or Diazepam) and polytherapy (stiripentol and diazepam) treatments were tested in Gabrg2+/Q390X mice challenged with pentylenetetrazol (PTZ) seizure induction in conjunction with video-monitoring synchronized electroencephalogram (EEG) recordings. A combination of stiripentol and diazepam greatly reduced seizure-related events in Gabrg2+/Q390X mice following PTZ administration and increased survival. However, the treatment of stiripentol alone was mostly ineffective in alleviating seizure-related events except that it reduced mortality in PTZ challenged Gabrg2+/Q390X mice. The study suggests that stiripentol could be only used as add-on therapy for DS with GABAA receptor functional deficiency, which is consistent with the most established clinical application of stiripentol. The study highlights the importance of mechanism-based precision treatment for DS considering the highly heterogeneous nature of etiology in DS and the fact that mutations in different genes give rise to the same clinical phenotype.
Published: 2019
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50. Climate, forest growing season, and evapotranspiration changes in the central Appalachian Mountains, USA

Author: B. A. Gaertner, Nicolas Zegre, Timothy A. Warner, Rodrigo Fernandez, Eric R. Merriam, and Yaqian He
Subjects: education.field_of_study, Environmental Engineering, 010504 meteorology & atmospheric sciences, Vapour Pressure Deficit, Phenology, Population, Climate change, Growing season, 010501 environmental sciences, Atmospheric sciences, 01 natural sciences, Pollution, Streamflow, Evapotranspiration, Environmental Chemistry, Environmental science, Water cycle, education, Waste Management and Disposal, 0105 earth and related environmental sciences
Abstract: We analyzed trends in climatologic, hydrologic, and growing season length variables, identified the important variables effecting growing season length changes, and evaluated the influence of a lengthened growing season on increasing evapotranspiration trends for the central Appalachian Mountains region of the United States. We generated three growing season length variables using remotely sensed GIMMS NDVI3g data, two variables from measured streamflow, and 13 climate parameters from gridded datasets. We included various climate, hydrology, and phenology explanatory variables in two applications of Principle Components Analysis to reduce dimensionality, then utilized the final variables in two Linear Mixed Effects models to evaluate the role of climate on growing season length and evapotranspiration. The results showed that growing season length has increased, on average, by ~22 days and evapotranspiration has increased up to ~12 mm throughout the region. The results also suggest that a suite of climatic variables including temperature, vapor pressure deficit, wind, and humidity are important in growing season length change. The climatic variables work synergistically to produce greater evaporative demand and atmospheric humidity, which is theoretically consistent with intensification of the water cycle and the Clausius-Clapeyron relation, which states that humidity increases nonlinearly by 7%/K. Optimization of the evapotranspiration model was increased by the inclusion of growing season length, suggesting that growing season length is partially responsible for variations in evapotranspiration over time. The results of this research imply that a longer growing season has the potential to increase forest water cycling and evaporative loss in temperate forests, which may lead to decreased freshwater provisioning from forests to downstream population centers. Additionally, results from this study provide important information for runoff and evapotranspiration modelling and forest water management under changing climate.
Published: 2019
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