695 research outputs found

    Basin scale sources of siltation in a contaminated hydropower reservoir

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    Siltation and the loss of hydropower reservoir capacity is a global challenge with a predicted 26 % loss of storage at the global scale by 2050. Like in many other Latin American contexts, soil erosion constitutes one of the most significant water pollution problems in Chile with serious siltation consequences downstream. Identifying the sources and drivers affecting hydropower siltation and water pollution is a critical need to inform adaptation and mitigation strategies especially in the context of changing climate regimes e.g. rainfall patterns. We investigated, at basin scale, the main sources of sediments delivered to one of the largest hydropower reservoirs in South America using a spatio-temporal geochemical fingerprinting approach. Mining activities contributed equivalent to 9 % of total recent sediment deposited in the hydropower lake with notable concentrations of sediment-associated pollutants e.g. Cu and Mo in bed sediment between the mine tributary and the reservoir sediment column. Agricultural sources represented ca. 60 % of sediment input wherein livestock production and agriculture promoted the input of phosphorus to the lake. Evaluation of the lake sediment column against the tributary network showed that the tributary associated with both dominant anthropogenic activities (mining and agriculture) contributed substantially more sediment, but sources varied through time: mining activities have reduced in proportional contribution since dam construction and proportional inputs from agriculture have increased in recent years, mainly promoted by recent conversion of steep lands from native vegetation to agriculture. Siltation of major hydropower basins presents a global challenge exemplified by the Rapel basin. The specific challenges faced here highlight the urgent need for co-design of evidence-led, context-specific solutions that address the interplay of drivers both within and without the basin and its communities, enhancing the social acceptability of sediment management strategies to support the sustainability of clean, hydropower energy production

    Sensor-independent LAI/FPAR CDR: reconstructing a global sensor-independent climate data record of MODIS and VIIRS LAI/FPAR from 2000 to 2022

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    Leaf area index (LAI) and fraction of photosynthetically active radiation (FPAR) are critical biophysical parameters for the characterization of terrestrial ecosystems. Long-term global LAI/FPAR products, such as the moderate resolution imaging spectroradiometer (MODIS) and the Visible Infrared Imaging Radiometer Suite (VIIRS), provide the fundamental dataset for accessing vegetation dynamics and studying climate change. However, existing global LAI/FPAR products suffer from several limitations, including spatial–temporal inconsistencies and accuracy issues. Considering these limitations, this study develops a sensor-independent (SI) LAI/FPAR climate data record (CDR) based on Terra-MODIS/Aqua-MODIS/VIIRS LAI/FPAR standard products. The SI LAI/FPAR CDR covers the period from 2000 to 2022, at spatial resolutions of 500 m/5 km/0.05∘, 8 d/bimonthly temporal frequencies and available in sinusoidal and WGS1984 projections. The methodology includes (i) comprehensive analyses of sensor-specific quality assessment variables to select high-quality retrievals, (ii) application of the spatial–temporal tensor (ST-tensor) completion model to extrapolate LAI and FPAR beyond areas with high-quality retrievals, (iii) generation of SI LAI/FPAR CDR in various projections and various spatial and temporal resolutions, and (iv) evaluation of the CDR by direct comparisons with ground data and indirectly through reproducing results of LAI/FPAR trends documented in the literature. This paper provides a comprehensive analysis of each step involved in the generation of the SI LAI/FPAR CDR, as well as evaluation of the ST-tensor completion model. Comparisons of SI LAI (FPAR) CDR with ground truth data suggest an RMSE of 0.84 LAI (0.15 FPAR) units with R2 of 0.72 (0.79), which outperform the standard Terra/Aqua/VIIRS LAI (FPAR) products. The SI LAI/FPAR CDR is characterized by a low time series stability (TSS) value, suggesting a more stable and less noisy dataset than sensor-dependent counterparts. Furthermore, the mean absolute error (MAE) of the CDR is also lower, suggesting that SI LAI/FPAR CDR is comparable in accuracy to high-quality retrievals. LAI/FPAR trend analyses based on the SI LAI/FPAR CDR agree with previous studies, which indirectly provides enhanced capabilities to utilize this CDR for studying vegetation dynamics and climate change. Overall, the integration of multiple satellite data sources and the use of advanced gap filling modeling techniques improve the accuracy of the SI LAI/FPAR CDR, ensuring the reliability of long-term vegetation studies, global carbon cycle modeling, and land policy development for informed decision-making and sustainable environmental management. The SI LAI/FPAR CDR is open access and available under a Creative Commons Attribution 4.0 License at https://doi.org/10.5281/zenodo.8076540 (Pu et al., 2023a).</p

    Association between spatial distribution of leukocyte subsets and clinical presentation of head and neck squamous cell carcinoma

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    BackgroundInteractions between tumor cells and cells in the microenvironment contribute to tumor development and metastasis. The spatial arrangement of individual cells in relation to each other influences the likelihood of whether and how these cells interact with each other.MethodsThis study investigated the effect of spatial distribution on the function of leukocyte subsets in the microenvironment of human head and neck squamous cell carcinoma (HNSCC) using multiplex immunohistochemistry (IHC). Leukocyte subsets were further classified based on analysis of two previously published HNSCC single-cell RNA datasets and flow cytometry (FC).ResultsIHC revealed distinct distribution patterns of leukocytes differentiated by CD68 and CD163. While CD68hiCD163lo and CD68hiCD163hi cells accumulated near tumor sites, CD68loCD163hi cells were more evenly distributed in the tumor stroma. PD-L1hi and PD-1hi cells accumulated predominantly around tumor sites. High cell density of PD-L1hi CD68hiCD163hi cells or PD-1hi T cells near the tumor site correlated with improved survival. FC and single cell RNA revealed high variability within the CD68/CD163 subsets. CD68hiCD163lo and CD68hiCD163hi cells were predominantly macrophages (MΦ), whereas CD68loCD163hi cells appeared to be predominantly dendritic cells (DCs). Differentiation based on CD64, CD80, CD163, and CD206 revealed that TAM in HNSCC occupy a broad spectrum within the classical M1/M2 polarization. Notably, the MΦ subsets expressed predominantly CD206 and little CD80. The opposite was observed in the DC subsets.ConclusionThe distribution patterns and their distinct interactions via the PD-L1/PD-1 pathway suggest divergent roles of CD68/CD163 subsets in the HNSCC microenvironment. PD-L1/PD-1 interactions appear to occur primarily between specific cell types close to the tumor site. Whether PD-L1/PD-1 interactions have a positive or negative impact on patient survival appears to depend on both the spatial localization and the entity of the interacting cells. Co-expression of other markers, particularly CD80 and CD206, supports the hypothesis that CD68/CD163 IHC subsets have distinct functions. These results highlight the association between spatial leukocyte distribution patterns and the clinical presentation of HNSCC

    Improved overall survival in patients with high-grade serous ovarian cancer is associated with CD16a+ immunologic neighborhoods containing NK cells, T cells and macrophages

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    BackgroundFor patients with high grade serous carcinoma of the ovary (HGSC), survival rates have remained static for the last half century. Despite the presence of tumor mutations and infiltration of immune cells, existing immunotherapies have achieved little success against HGSC. These observations highlight a gap in the understanding of how the immune system functions and interacts within HGSC tumors.MethodsWe analyzed duplicate core samples from 939 patients with HGSC to understand patterns of immune cell infiltration, localization, and associations with clinical features. We used high-parameter immunohistochemical/Opal multiplex, digital pathology, computational biology, and multivariate analysis to identify immune cell subsets and their associations with HGSC tumors.ResultsWe defined six patterns of cellular infiltration by spatially restricted unsupervised clustering of cell subsets. Each pattern was represented to some extent in most patient samples, but their specific distributions differed. Overall (OS) and progression-free survival (PFS) corresponded with higher infiltration of CD16a+ cells, and their co-localization with macrophages, T cells, NK cells, in one of six cellular neighborhoods that we defined with our spatial assessment.ConclusionsImmune cell neighborhoods containing CD16a+ cells are associated with improved OS and PFS for patients with HGSC. Patterns of immunologic neighborhoods differentiate patient outcomes, and could inform future, more precise approaches to treatment

    Surface-Enhanced Coherent Raman scattering (SE-CRS) with Noble Metal Nanoparticles

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    Early cancer detection remains challenging due to numerous complex tempo-spatial metabolic changes in cell physiology. Based on their ability to recognise molecular structures and pathological changes at molecular levels, spectroscopic have recently emerged as promising non-invasive, non-ionising, and cost-efficient tools to help detect cancer, and other human pathologies. Raman spectroscopy is a valuable technique that provides information regarding the chemical properties of materials. Nevertheless, it has limitations due to the limited amount of Raman light scattered. Strategies for cancer diagnostics and therapies are based on the hypothesis that nanoparticles (NPs) can be precisely tailored to target cancer cells. However, the tools required to image NPs at cellular levels remain scarce in the literature. The work outlined in this thesis, for the first time, utilises noble metal NPs and Raman reporters, with the mechanisms of surface enhanced Raman scattering (SERS) and coherent anti-Stokes Raman scattering (CARS), in cancer cells and tumour spheroids to address the demerits of low spatial resolution, signal-to-noise ratio, and chemical specificity. SERS and CARS have broadly been explored in this regard. To increase the effectiveness of Raman scattering, a variety of techniques have been devised to boost its intensity. Primarily, I studied four techniques to increase Raman scattering intensity with the ultimate objective of improving sensitivity and assessing limits of various Raman methods: SERS, surface-enhanced coherent anti-Stokes Raman scattering (SE-CARS), surface-enhanced stimulated Raman scattering (SE-SRS), and broadband coherent anti-Stokes Raman scattering (BCARS). Coherent Raman scattering (CRS) is utilised to enhance weak Raman bands. The signal is enhanced by nonlinear interaction of the excitation lasers within the sample. Despite the advantages offered over Raman, CRS has been relatively unexploited for image Raman tagged NPs. This challenge has recently been addressed using surface plasmon enhancement, which gives significantly enhanced inelastic scattering signals as well as reduced signal-to-noise ratio. Surface-enhanced coherent Raman scattering (SE-CRS) has been characterised by using a variety of techniques such as SERS, CARS, and SE-CARS. This work provides a step forward to develop plasmon enhanced SRS and CARS in addressing critical biological questions using nonlinear bio-photonics. In the first part of this thesis, I developed a reproducible substrate that mimics gold nanoparticles (AuNPs) and allows forward detection which is critical for CRS. I investigated the effects of annealing on gold films deposited on glass substrates with thicknesses from 3 nm to 15 nm as described in depth in chapter 5. In addition to this, it provides an explanation of the work that was performed to explore the interaction between Raman tags BPT (biphenyl-4-thiol), BPE trans-1,2-bis(4-pyridyl) ethylene, and IR 820 (new indocyanine green) on gold films substrates using 785 nm laser excitation. In the second part of this thesis, I investigated the interactions between Raman tags of BPT on gold films substrates using CRS and broadband CARS techniques. These experiments also offer the SE-CRS enhancement signal. The research done to examine gold thin film substrates and to offer SE-SRS and SE-CARS enhancement signals in the fingerprint region as described in chapter 6. Using CRS microscopy, the investigations in this chapter study these interactions. In the third part of this thesis, I developed a novel imaging methodology for the visualisation of AuNPs inside cellular structures and spheroids, with the intention of acquiring distinct spectroscopic fingerprints. Consequently, I undertook the task of devising protocols for visualising AuNPs and Raman reporter molecules within cancer cell models, spheroids, and animal tissues as described in chapter 7. The aim was to attain distinctive spectroscopic profiles by employing the SE-CRS technique, achieved by illuminating AuNPs along with Raman reporter molecules (BPT, BPE, IR 820) using low intensity infrared light, with both the pump and Stokes beams operating at intensities below 0.2 mW. In summary, this thesis sheds light on the development of surface plasmon resonance phenomena based on metallic nanostructures for use in nonlinear inelastic scattering systems, including surface-enhanced Raman scattering (SERS), coherent Raman scattering (CRS), and surface-enhanced coherent Raman scattering (SE- CRS). The primary focus is to use this system for disease diagnostics, rooted in SERS, reflects a commitment to advancing cancer diagnostics, based on SERS thereby enhancing the precision and discrimination of molecular signals, making a significant stride towards more effective and nuanced cancer diagnostics

    Neuromotor and electrocortical activity characteristics of dynamic postural control

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    Subconcussive impacts to the head have become a growing area of research and concern in the athletic setting. While knowledge on the short- and long-term consequences of concussions has been identified, there is relatively less research on the effects of repetitive subconcussive impacts. Research has shown that neuromotor deficits (i.e., dynamic balance) can be detected acutely after repeatedly heading a soccer ball (a laboratory-based way to induce subconcussive head impacts), but this has typically been done with expensive and non-portable laboratory equipment. However, the AccWalker smartphone application may allow for an objective cost-effective test to examine the effective of repetitive subconcussive exposure. Nonetheless, while cost-effective and portable (e.g., a smartphone app), there is a need for examination of its reliability. Moreover, the extent to which cortical activity is related to dynamic balance control is not well understood. If an association between cortical activity is observed, an increase or decrease in the strength of the association after repeated subconcussive head impacts could be used as an indicator of nervous system impact. These gaps in the literature will be addressed through three specific aims in this dissertation 1) to investigate the reliability of the AccWalker app as a test for neuromotor performance before and after light athletic activity (e.g., kicking a soccer ball); 2) compare EEG spectral power characteristics of dynamic balance across three different AccWalker conditions, and 3) to examine correlations between EEG spectral power characteristics and temporal and spatial kinematic data during a stepping in place task (mTBI Assessment of Readiness Gait Evaluation Test (TARGET)). It was hypothesized that, 1) temporal and spatial characteristics of dynamic balance will not significantly change between pre- and post-soccer kicking activity, 2) EEG power spectral density (PSD) within the delta and theta frequency bands will increase across the three AccWalker conditions, and 3) EEG PSD within the delta and theta frequency bands will correlate with the temporal and spatial kinematic variables measured using the AccWalker TARGET protocol. Twenty-four participants were enrolled in this study. Aim 1 used a pre-test/post-test design. Both pre- and post-testing included using the TARGET protocol before and after kicking ten soccer balls. The findings for aim 1 indicated that that the AccWalker TARGET protocol displayed good test-retest reliability with similar data characteristics to previous work. Aim 2 results revealed that EEG PSD measures increased compared to the resting condition. Finally, for aim 3, several significant correlations between the AccWalker spatial metrics within the Delta and Theta frequencies were found. These findings suggest that postural control assessment can be measured reliably in a pre- to post-test design. This may be important as the AccWalker TARGET protocol may offer a reliable test for changes in neuromotor performance and the body’s ability to adapt to “real-life” (or more dynamic) situations. Additionally, this study has expanded on previous literature indicating increased involvement of the frontal-central and central regions of the brain during perturbed balance. Further, this study expands upon the simultaneous use of EEG and balance assessment; specifically, as it is the first study to use a truly dynamic balance task along with a 32-electrode mobile EEG system. This may be important for continued study of not only unaffected balance, but that study of neural changes due to injury or pathological processes

    Multiplexed High-Resolution Imaging Approach to Decipher the Cellular Heterogeneity of the Kidney and its Alteration in Kidney Disease and Nephrolithiasis

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    Indiana University-Purdue University Indianapolis (IUPUI)Kidney disease and nephrolithiasis both present a major burden on the health care system in the US and worldwide. The cellular and molecular events governing the pathogenesis of these diseases are not fully understood. We propose that defining the cellular heterogeneity and niches in human and mouse kidney tissue specimens from controls and various models of renal disease could provide unique insights into the molecular pathogenesis. For that purpose, a multiplexed fluorescence imaging approach using co-detection by Indexing (CODEX) was used, using a panel of 33 and 38 markers for mouse and human kidney tissues, respectively. A customized computational analytical pipeline was developed and applied to the imaging data using unsupervised and/or semi-supervised machine learning and statistical approaches. The goal was to identify various cell populations present within the tissues, as well as identify unique cellular niches that may be altered with disease and/or injury. In mice, we examined disease models of acute kidney injury (AKI) and in human tissues we analyzed specimens from patients with AKI, IgA nephropathy, chronic kidney disease, systemic lupus erythematosus, and nephrolithiasis. In both mice and humans, the disease and reference samples show similar broad cell populations for the main segments of the nephron, endothelium, as well as similar groups of immune cells, such as resident macrophages and neutrophils. When comparing between health and disease, however, a change in the distribution of few sub-populations occurred. For example, in human kidney tissues, the abundance and distribution of a subpopulation of proximal tubules positive for THY1 (a marker of differentiation and repair), was markedly reduced with disease. Changes observed in mouse tissues included shifts in the immune cell population types and niches with disease. We propose that our analytical workflow and the observed changes in situ will play an important role in deciphering the pathogenesis of kidney disease

    Engineering of Second-Generation Acoustic Reporter Genes

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    A major outstanding challenge in the fields of biological research, synthetic biology, and cell-based medicine is visualizing the functions of natural and engineered cells noninvasively inside opaque organisms. Ultrasound imaging has the potential to address this challenge as a widely available technique with a tissue penetration of several centimeters and spatial resolution below 100 µm. Recently, the first genetically encoded acoustic reporters were developed based on bacterial gas vesicles (GVs) to link ultrasound signals to molecular and cellular function. However, the properties of these first-generation acoustic reporter genes (ARGs) resulted in limited sensitivity and specificity for imaging gene expression in vivo. The goal of my thesis work has been to engineer second-generation ARGs with improved acoustic and expression phenotypes compared to the existing first-generation constructs. I took two complementary engineering approaches to developing these constructs: homolog screening and directed evolution, sometimes referred to as the “nature and nurture” of protein engineering. The resulting constructs offer major qualitative and quantitative improvements, including much stronger ultrasound contrast, the ability to produce nonlinear signals distinguishable from background tissue in vivo, stable long-term expression, and compatibility with in vitro multiplexed imaging. In collaboration with others in the lab, we demonstrate the capabilities of these next-generation ARGs by imaging in situ gene expression in mouse models of breast cancer and tumor-homing therapeutic bacteria, noninvasively revealing the unique spatial distributions of tumor growth and colonization by therapeutic cells in living subjects and providing real-time guidance for interventions such as needle biopsies. This thesis is organized as follows: in the first two chapters, I introduce the key background needed to understand both the importance and properties of ARGS, and how they have been and could be engineered. In the next two chapters, I detail specific efforts to engineer them—one involving the construction of a high-throughput, semi-automated setup for acoustic phenotyping of cells and its application to ARG directed evolution, and another involving the screening of several GV cluster homologs to identify ones suitable for use as improved ARGs. Finally, I conclude with insights gleaned from these two ARG engineering projects and suggestions for future ones. The approaches, results, and ideas presented in this thesis represent the current state-of-the-art in ARG engineering and application. While recent technology development in this field has unlocked exciting new use cases for ARGs in noninvasive biological imaging, most of their potential for basic science and disease diagnosis and treatment has yet to be realized.</p

    Multi-annual grassland mowing dynamics in Germany: spatio-temporal patterns and the influence of climate, topographic and socio-political conditions

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    Introduction: Grasslands cover one third of the agricultural area in Germany and are mainly used for fodder production. However, grasslands fulfill many other ecosystem functions, like carbon storage, water filtration and the provision of habitats. In Germany, grasslands are mown and/or grazed multiple times during the year. The type and timing of management activities and the use intensity vary strongly, however co-determine grassland functions. Large-scale spatial information on grassland activities and use intensity in Germany is limited and not openly provided. In addition, the cause for patterns of varying mowing intensity are usually not known on a spatial scale as data on the incentives of farmers behind grassland management decisions is not available.Methods: We applied an algorithm based on a thresholding approach utilizing Sentinel-2 time series to detect grassland mowing events to investigate mowing dynamics in Germany in 2018–2021. The detected mowing events were validated with an independent dataset based on the examination of public webcam images. We analyzed spatial and temporal patterns of the mowing dynamics and relationships to climatic, topographic, soil or socio-political conditions.Results: We found that most intensively used grasslands can be found in southern/south-eastern Germany, followed by areas in northern Germany. This pattern stays the same among the investigated years, but we found variations on smaller scales. The mowing event detection shows higher accuracies in 2019 and 2020 (F1 = 0.64 and 0.63) compared to 2018 and 2021 (F1 = 0.52 and 0.50). We found a significant but weak (R2 of 0–0.13) relationship for a spatial correlation of mowing frequency and climate as well as topographic variables for the grassland areas in Germany. Further results indicate a clear value range of topographic and climatic conditions, characteristic for intensive grassland use. Extensive grassland use takes place everywhere in Germany and on the entire spectrum of topographic and climatic conditions in Germany. Natura 2000 grasslands are used less intensive but this pattern is not consistent among all sites.Discussion: Our findings on mowing dynamics and relationships to abiotic and socio-political conditions in Germany reveal important aspects of grassland management, including incentives of farmers
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