Prion Infectivity and PrPBSE in the Peripheral and Central Nervous System of Cattle 8 Months Post Oral BSE Challenge

After oral exposure of cattle with classical bovine spongiform encephalopathy (C-BSE), the infectious agent ascends from the gut to the central nervous system (CNS) primarily via the autonomic nervous system. However, the timeline of this progression has thus far remained widely undetermined. Previous studies were focused on later time points after oral exposure of animals that were already 4 to 6 months old when challenged. In contrast, in this present study, we have orally inoculated 4 to 6 weeks old unweaned calves with high doses of BSE to identify any possible BSE infectivity and/or PrPBSE in peripheral nervous tissues during the first eight months postinoculation (mpi). For the detection of BSE infectivity, we used a bovine PrP transgenic mouse bioassay, while PrPBSE depositions were analyzed by immunohistochemistry (IHC) and by protein misfolding cyclic amplification (PMCA). We were able to show that as early as 8 mpi the thoracic spinal cord as well as the parasympathetic nodal ganglion of these animals contained PrPBSE and BSE infectivity. This shows that the centripetal prion spread starts early after challenge at least in this age group, which represents an essential piece of information for the risk assessments for food, feed, and pharmaceutical products produced from young calves

High, in Contrast to Low Levels of Acute Stress Induce Depressive-like Behavior by Involving Astrocytic, in Addition to Microglial P2X7 Receptors in the Rodent Hippocampus

Extracellular adenosine 50-triphosphate (ATP) in the brain is suggested to be an etiological factor of major depressive disorder (MDD). It has been assumed that stress-released ATP stimulates P2X7 receptors (Rs) at the microglia, thereby causing neuroinflammation; however, other central nervous system (CNS) cell types such as astrocytes also possess P2X7Rs. In order to elucidate the possible involvement of the MDD-relevant hippocampal astrocytes in the development of a depressive-like state, we used various behavioral tests (tail suspension test [TST], forced swim test [FST], restraint stress, inescapable foot shock, unpredictable chronic mild stress [UCMS]), as well as fluorescence immunohistochemistry, and patch-clamp electrophysiology in wild-type (WT) and genetically manipulated rodents. The TST and FST resulted in learned helplessness manifested as a prolongation of the immobility time, while inescapable foot shock caused lower sucrose consumption as a sign of anhedonia. We confirmed the participation of P2X7Rs in the development of the depressive-like behaviors in all forms of acute (TST, FST, foot shock) and chronic stress (UCMS) in the rodent models used. Further, pharmacological agonists and antagonists acted in a different manner in rats and mice due to their diverse potencies at the respective receptor orthologs. In hippocampal slices of mice and rats, only foot shock increased the current responses to locally applied dibenzoyl-ATP (Bz-ATP) in CA1 astrocytes; in contrast, TST and restraint depressed these responses. Following stressful stimuli, immunohistochemistry demonstrated an increased co-localization of P2X7Rs with a microglial marker, but no change in co-localization with an astroglial marker. Pharmacological damage to the microglia and astroglia has proven the significance of the microglia for mediating all types of depression-like behavioral reactions, while the astroglia participated only in reactions induced by strong stressors, such as foot shock. Because, in addition to acute stressors, their chronic counterparts induce a depressive-like state in rodents via P2X7R activation, we suggest that our data may have relevance for the etiology of MDD in humans

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Characterizing the performance of low impact development under changes in climate and urbanization

Over the past decades, climate change and urbanization have altered the regional hydro-environments, causing a series of stormwater management problems including urban flood and non-point pollution. Low impact development (LID) has been identified as a sustainable strategy for stormwater management. However, given the complex impacts of climate change and urbanization on hydro-environments, the performance of LID strategy under future changes remains largely unexplored. Accordingly, this research characterized the LID performance under changes in climate and urbanization. To provide an additional reference to sustainable stormwater management, the following specific topics were addressed: (1) Through hydraulic and water quality modeling, the LID performances of flood mitigation and pollution removal were systematically evaluated at the city scale. (2) Through uncertainty analysis, the impact of model parameter uncertainty on the LID performance was taken into account. (3) Through sensitivity analysis, the impact of LID technical parameters (e.g., surface features, soil textures) on the LID performance was quantified. (4) Through scenario analysis, the LID performances under different hydrological patterns were compared. (5) Through spatial analysis, the distribution of LID performance on different land-cover types was determined. (6) Through adopting general circulation model (GCM) projections, the LID performance under future climate scenarios with different representative concentration pathways (RCPs) was investigated. (7) Through adopting integrated assessment model (IAM) projections, the LID performance under future urbanization scenarios with different shared socioeconomic pathways (SSPs) was explored. (8) By coupling climate and urbanization projections with land-cover distribution, the spatiotemporal trends of LID performance in the future were characterized.:Table of Contents List of Abbreviations VII List of Peer-Reviewed Publications on the Ph.D. Topic IX List of Co-authored Peer-Reviewed Publications on the Ph.D. Topic X 1 General Introduction 1 1.1 Background 1 1.2 Objectives 3 1.3 Innovation and Contribution to the Knowledge 3 1.4 Outline of the Dissertation 4 1.5 References 5 2 Literature Review 9 2.1 Hydraulic and Water Quality Modeling 9 2.1.1 Hydraulic Model 9 2.1.2 Water Quality Model 10 2.2 Low Impact Development (LID) 10 2.2.1 LID Practice 10 2.2.2 LID Performance 11 2.3 Performance Evaluation 13 2.3.1 Scenario Analysis 13 2.3.2 Spatial Analysis 13 2.3.3 Uncertainty Analysis 14 2.3.4 Sensitivity Analysis 14 2.4 Future Changes in Climate and Urbanization 15 2.4.1 Climate Change 15 2.4.2 Future Urbanization 16 2.5 References 17 3 Impact of Technical Factors on LID Performance 27 3.1 Introduction 28 3.2 Methods 30 3.2.1 Study Area 30 3.2.2 Model Description 31 3.2.2.1 Model Theory 31 3.2.2.2 Model Construction 31 3.2.2.3 Model Calibration and Validation 32 3.2.2.4 Model Uncertainty Analysis by GLUE Method 34 3.2.3 Hydrological Pattern Design 35 3.2.4 LID Strategy Design 35 3.2.4.1 Implementation of LID Practices 35 3.2.4.2 Sensitivity Analysis by Sobol’s Method 36 3.2.5 Correlation Analysis Using a Self-Organizing Map 37 3.2.6 Description of the RDS Load Components 37 3.3 Results 38 3.3.1 RDS Migration and Distribution in Baseline Strategy 38 3.3.1.1 RDS Migration under Hydrological Scenarios 38 3.3.1.2 RDS Distribution on Land-Cover Types 39 3.3.2 RDS Removal in LID Strategies 40 3.3.2.1 RDS Removal by LID Strategies 40 3.3.2.2 Spatial Distribution of the RDS Removal 42 3.3.2.3 LID Parameter Sensitivity Analysis Result 43 3.4 Discussion 45 3.4.1 Factors Influencing RDS Migration in the Baseline Strategy 45 3.4.2 RDS Removal Performance by LID Strategy 46 3.5 Conclusions 47 3.6 References 47 4 Impact of Hydro-Environmental Factors on LID Performance 53 4.1 Introduction 54 4.2 Methods 56 4.2.1 Study Area 56 4.2.2 Modeling Approach 56 4.2.2.1 Model Theory 56 4.2.2.2 Model Construction 56 4.2.2.3 Model Calibration and Validation 57 4.2.2.4 Model Uncertainty Analysis 57 4.2.3 LID Performance Analysis 58 4.2.3.1 LID Practice Implementation 58 4.2.3.2 LID Performance Evaluation 58 4.2.4 Hydrological Pattern Analysis 59 4.2.4.1 Scenario of ADP Length 59 4.2.4.2 Scenario of Rainfall Magnitude 59 4.2.4.3 Scenario of Long-Term pre-Simulation 60 4.2.5 Sensitivity Analysis of Hydrological Scenarios 60 4.3 Results 61 4.3.1 LID Performance under Different ADP Lengths 61 4.3.2 LID Performance under Different Rainfall Magnitudes 62 4.3.3 Spatial Distribution of LID Performance 63 4.3.4 Sensitivities of LID Performance to ADP Length and Rainfall Magnitude 66 4.4 Discussion 68 4.4.1 Impact of ADP Length and Rainfall Magnitude on LID Performance 68 4.4.2 Spatial Heterogeneity of LID Performance 68 4.4.3 Research Implications 69 4.5 Conclusions 70 4.6 References 71 5 Impact of Future Climate Patterns on LID Performance 77 5.1 Introduction 78 5.2 Methods 80 5.2.1 Study Area 80 5.2.2 Hydraulic and Water Quality Model 80 5.2.2.1 Model Development 80 5.2.2.2 Model Calibration and Validation 81 5.2.3 Climate Change Scenario Analysis 81 5.2.3.1 GCM Evaluation 81 5.2.3.2 Greenhouse Gas (GHG) Concentration Scenario 82 5.2.3.3 GCM Downscaling 83 5.2.4 LID Performance Analysis 83 5.2.4.1 Implementation of LID Practices 83 5.2.4.2 Evaluation of LID Performance 84 5.2.4.3 Sensitivity Analysis on LID Performance 86 5.3 Results 86 5.3.1 Hydrological Characteristics under Future Climate Scenarios 86 5.3.2 LID Performance under Future Climate Scenarios 87 5.3.2.1 LID Short-Term Performance 87 5.3.2.2 LID Long-Term Performance 90 5.3.3 Impact of ADP Length and Rainfall Magnitude on LID Performance 92 5.3.3.1 LID Performance Uncertainty 92 5.3.3.2 Spatial Distribution of LID Performance 93 5.3.3.3 Sensitivity of LID Performance to Climate Change 95 5.4 Discussion 97 5.4.1 LID Performance in Short-Term Extremes and Long-Term Events 97 5.4.2 Impact of Climate Change on LID Performance 97 5.4.3 Research Implications 99 5.5 Conclusions 100 5.6 References 100 6 Impact of Climate and Urbanization Changes on LID Perfor-mance 109 6.1 Introduction 110 6.2 Methods 112 6.2.1 Study Area 112 6.2.2 Modeling Approach 112 6.2.2.1 Model Development 112 6.2.2.2 Model Calibration and Validation 113 6.2.3 Future Scenario Derivation 113 6.2.3.1 Climate Change Scenario 113 6.2.3.2 Urbanization Scenario 115 6.2.4 Flood Exposure Assessment 115 6.2.5 Implementation and Evaluation of LID Strategy 117 6.2.5.1 Implementation Scheme of LID Strategy 117 6.2.5.2 Performance Evaluation of LID Strategy 117 6.3 Results 118 6.3.1 Flood Exposure in Baseline and Future Scenarios 118 6.3.1.1 Hydrological Change in Future Climate Scenarios 118 6.3.1.2 Catchment Change in Future Urbanization Scenarios 118 6.3.1.3 Population and GDP Exposures to Flood in Future 121 6.3.2 Flood Exposure with Consideration of LID Strategy 123 6.3.2.1 Runoff Mitigation Performance of LID Strategy 123 6.3.2.2 Peak Mitigation Performance of LID Strategy 124 6.3.2.3 Population and GDP Exposures to Flood under LID Strategy 125 6.4 Discussion 126 6.4.1 Climate Change and Urbanization Exacerbated Flood Exposure Risk 126 6.4.2 LID Strategy Mitigated Flood Exposure Risk 126 6.5 Conclusions 127 6.6 References 127 7 Discussion and General Conclusions 133 7.1 Stormwater Management Performance of LID Strategy 133 7.2 Impact of Influencing Factors on LID Performance 134 7.3 LID Performance under Future Changes 135 7.4 Research Implications 136 7.5 References 137 8 Outlook of Future Research 139 8.1 Optimization of LID Performance 139 8.2 Cross-regional Study on Future Changes 139 8.3 Macro-scale Flood Risk Management 140 8.4 References 141 9 Appendices 143 9.1 Appendix for Chapter 3 143 9.1.1 The Determination of the GLUE Criteria 143 9.1.2 Model Uncertainty Analysis 143 9.1.3 The LID Installation Location 144 9.1.4 Figures 145 9.1.5 Tables 147 9.2 Appendix for Chapter 4 153 9.2.1 Scenario of Long-term pre-Simulation 153 9.2.2 Figures 153 9.2.3 Tables 158 9.3 Appendix for Chapter 5 164 9.3.1 Tables 164 9.4 Appendix for Chapter 6 169 9.4.1 Figures 169 9.4.2 Tables 170 9.5 Data Source 177 9.6 References 17

Design of a Self-Powered Energy Management Circuit for Piezoelectric Energy Harvesting based on Synchronized Switching Technology

Vibration converters based on piezoelectric materials are currently becoming increasingly important for powering low-power wireless sensor nodes and wearable electronic devices. Piezoelectric materials generate variable electrical charges under mechanical stress, requiring an energy management interface to meet load requirements. Resonant interfaces like Parallel Synchronized Switch Harvesting on Inductor (P-SSHI) are highly efficient and robust to energy sources and loads variations. Nevertheless, SSHI circuits require synchronous switch control for efficient energy transfer. At irregular excitation, SSHI circuits may not perform optimally because the resonant frequency of the circuit is typically tuned to match the frequency of the energy source, which in the case of footsteps can be irregular and unpredictable. In addition, the circuit may also be susceptible to noise and interference from irregular excitations, which can further affect its performance. The aim is to design a self-powered energy management solution that can operate autonomously even at low frequencies and for irregular chock excitations, while at the same time allowing higher energy flow to the energy storage device and maintaining high levels of energy efficiency. To evaluate the performance of the proposed circuit, a piezoelectric shoe insole is designed and used for testing with different storage capacitance values and loads as a proof of the circuit’s adaptability to various loading conditions.:1 Introduction 2 Theoretical background 3 State of the art of piezoelectric energy harvesting interfaces 4 Novel approach of SP-PSSHI piezoelectric energy harvesting interface 5 Experimental investigations 6 Conclusions and Outloo