8,987 research outputs found

    Pollution-induced community tolerance in freshwater biofilms – from molecular mechanisms to loss of community functions

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    Exposure to herbicides poses a threat to aquatic biofilms by affecting their community structure, physiology and function. These changes render biofilms to become more tolerant, but on the downside community tolerance has ecologic costs. A concept that addresses induced community tolerance to a pollutant (PICT) was introduced by Blanck and WĂ€ngberg (1988). The basic principle of the concept is that microbial communities undergo pollution-induced succession when exposed to a pollutant over a long period of time, which changes communities structurally and functionally and enhancing tolerance to the pollutant exposure. However, the mechanisms of tolerance and the ecologic consequences were hardly studied up to date. This thesis addresses the structural and functional changes in biofilm communities and applies modern molecular methods to unravel molecular tolerance mechanisms. Two different freshwater biofilm communities were cultivated for a period of five weeks, with one of the communities being contaminated with 4 ÎŒg L-1 diuron. Subsequently, the communities were characterized for structural and functional differences, especially focusing on their crucial role of photosynthesis. The community structure of the autotrophs was assessed using HPLC-based pigment analysis and their functional alterations were investigated using Imaging-PAM fluorometry to study photosynthesis and community oxygen profiling to determine net primary production. Then, the molecular fingerprints of the communities were measured with meta-transcriptomics (RNA-Seq) and GC-based community metabolomics approaches and analyzed with respect to changes in their molecular functions. The communities were acute exposed to diuron for one hour in a dose-response design, to reveal a potential PICT and uncover related adaptation to diuron exposure. The combination of apical and molecular methods in a dose-response design enabled the linkage of functional effects of diuron exposure and underlying molecular mechanisms based on a sensitivity analysis. Chronic exposure to diuron impaired freshwater biofilms in their biomass accrual. The contaminated communities particularly lost autotrophic biomass, reflected by the decrease in specific chlorophyll a content. This loss was associated with a change in the molecular fingerprint of the communities, which substantiates structural and physiological changes. The decline in autotrophic biomass could be due to a primary loss of sensitive autotrophic organisms caused by the selection of better adapted species in the course of chronic exposure. Related to this hypothesis, an increase in diuron tolerance has been detected in the contaminated communities and molecular mechanisms facilitating tolerance have been found. It was shown that genes of the photosystem, reductive-pentose phosphate cycle and arginine metabolism were differentially expressed among the communities and that an increased amount of potential antioxidant degradation products was found in the contaminated communities. This led to the hypothesis that contaminated communities may have adapted to oxidative stress, making them less sensitive to diuron exposure. Moreover, the photosynthetic light harvesting complex was altered and the photoprotective xanthophyll cycle was increased in the contaminated communities. Despite these adaptation strategies, the loss of autotrophic biomass has been shown to impair primary production. This impairment persisted even under repeated short-term exposure, so that the tolerance mechanisms cannot safeguard primary production as a key function in aquatic systems.:1. The effect of chemicals on organisms and their functions .............................. 1 1.1 Welcome to the anthropocene .......................................................................... 1 1.2 From cellular stress responses to ecosystem resilience ................................... 3 1.2.1 The individual pursuit for homeostasis ....................................................... 3 1.2.2 Stability from diversity ................................................................................. 5 1.3 Community ecotoxicology - a step forward in monitoring the effects of chemical pollution? ................................................................................................................. 6 1.4 Functional ecotoxicological assessment of microbial communities ................... 9 1.5 Molecular tools – the key to a mechanistic understanding of stressor effects from a functional perspective in microbial communities? ...................................... 12 2. Aims and Hypothesis ......................................................................................... 14 2.1 Research question .......................................................................................... 14 2.2 Hypothesis and outline .................................................................................... 15 2.3 Experimental approach & concept .................................................................. 16 2.3.1 Aquatic freshwater biofilms as model community ..................................... 16 2.3.2 Diuron as model herbicide ........................................................................ 17 2.3.3 Experimental design ................................................................................. 18 3. Structural and physiological changes in microbial communities after chronic exposure - PICT and altered functional capacity ................................................. 21 3.1 Introduction ..................................................................................................... 21 3.2 Methods .......................................................................................................... 23 3.2.1 Biofilm cultivation ...................................................................................... 23 3.2.2 Dry weight and autotrophic index ............................................................. 23 3.2.4 Pigment analysis of periphyton ................................................................. 23 3.2.4.1 In-vivo pigment analysis for community characterization ....................... 24 3.2.4.2 In-vivo pigment analysis based on Imaging-PAM fluorometry ............... 24 3.2.4.3 In-vivo pigment fluorescence for tolerance detection ............................. 26 3.2.4.4 Ex-vivo pigment analysis by high-pressure liquid-chromatography ....... 27 3.2.5 Community oxygen metabolism measurements ....................................... 28 3.3 Results and discussion ................................................................................... 29 3.3.1 Comparison of the structural community parameters ............................... 29 3.3.2 Photosynthetic activity and primary production of the communities after selection phase ................................................................................................. 33 3.3.3 Acquisition of photosynthetic tolerance .................................................... 34 3.3.4 Primary production at exposure conditions ............................................... 36 3.3.5 Tolerance detection in primary production ................................................ 37 3.4 Summary and Conclusion ........................................................................... 40 4. Community gene expression analysis by meta-transcriptomics ................... 41 4.1 Introduction to meta-transcriptomics ............................................................... 41 4.2. Methods ......................................................................................................... 43 4.2.1 Sampling and RNA extraction................................................................... 43 4.2.2 RNA sequencing analysis ......................................................................... 44 4.2.3 Data assembly and processing................................................................. 45 4.2.4 Prioritization of contigs and annotation ..................................................... 47 4.2.5 Sensitivity analysis of biological processes .............................................. 48 4.3 Results and discussion ................................................................................... 48 4.3.1 Characterization of the meta-transcriptomic fingerprints .......................... 49 4.3.2 Insights into community stress response mechanisms using trend analysis (DRomic’s) ......................................................................................................... 51 4.3.3 Response pattern in the isoform PS genes .............................................. 63 4.5 Summary and conclusion ................................................................................ 65 5. Community metabolome analysis ..................................................................... 66 5.1 Introduction to community metabolomics ........................................................ 66 5.2 Methods .......................................................................................................... 68 5.2.1 Sampling, metabolite extraction and derivatisation................................... 68 5.2.2 GC-TOF-MS analysis ............................................................................... 69 5.2.3 Data processing and statistical analysis ................................................... 69 5.3 Results and discussion ................................................................................... 70 5.3.1 Characterization of the metabolic fingerprints .......................................... 70 5.3.2 Difference in the metabolic fingerprints .................................................... 71 5.3.3 Differential metabolic responses of the communities to short-term exposure of diuron ............................................................................................................ 73 5.4 Summary and conclusion ................................................................................ 78 6. Synthesis ............................................................................................................. 79 6.1 Approaches and challenges for linking molecular data to functional measurements ...................................................................................................... 79 6.2 Methods .......................................................................................................... 83 6.2.1 Summary on the data ............................................................................... 83 6.2.2 Aggregation of molecular data to index values (TELI and MELI) .............. 83 6.2.3 Functional annotation of contigs and metabolites using KEGG ................ 83 6.3 Results and discussion ................................................................................... 85 6.3.1 Results of aggregation techniques ........................................................... 85 6.3.2 Sensitivity analysis of the different molecular approaches and endpoints 86 6.3.3 Mechanistic view of the molecular stress responses based on KEGG functions ............................................................................................................ 89 6.4 Consolidation of the results – holistic interpretation and discussion ............... 93 6.4.1 Adaptation to chronic diuron exposure - from molecular changes to community effects.............................................................................................. 93 6.4.2 Assessment of the ecological costs of Pollution-induced community tolerance based on primary production ............................................................. 94 6.5 Outlook ............................................................................................................ 9

    Computertomographie-basierte Bestimmung von Aortenklappenkalk und seine Assoziation mit Komplikationen nach interventioneller Aortenklappenimplantation (TAVI)

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    Background: Severe aortic valve calcification (AVC) has generally been recognized as a key factor in the occurrence of adverse events after transcatheter aortic valve implantation (TAVI). To date, however, a consensus on a standardized calcium detection threshold for aortic valve calcium quantification in contrast-enhanced computed tomography angiography (CTA) is still lacking. The present thesis aimed at comparing two different approaches for quantifying AVC in CTA scans based on their predictive power for adverse events and survival after a TAVI procedure.   Methods: The extensive dataset of this study included 198 characteristics for each of the 965 prospectively included patients who had undergone TAVI between November 2012 and December 2019 at the German Heart Center Berlin (DHZB). AVC quantification in CTA scans was performed at a fixed Hounsfield Unit (HU) threshold of 850 HU (HU 850 approach) and at a patient-specific threshold, where the HU threshold was set by multiplying the mean luminal attenuation of the ascending aorta by 2 (+100 % HUAorta approach). The primary endpoint of this study consisted of a combination of post-TAVI outcomes (paravalvular leak ≄ mild, implant-related conduction disturbances, 30-day mortality, post-procedural stroke, annulus rupture, and device migration). The Akaike information criterion was used to select variables for the multivariable regression model. Multivariable analysis was carried out to determine the predictive power of the investigated approaches.   Results: Multivariable analyses showed that a fixed threshold of 850 HU (calcium volume cut-off 146 mm3) was unable to predict the composite clinical endpoint post-TAVI (OR=1.13, 95 % CI 0.87 to 1.48, p=0.35). In contrast, the +100 % HUAorta approach (calcium volume cut-off 1421 mm3) enabled independent prediction of the composite clinical endpoint post-TAVI (OR=2, 95 % CI 1.52 to 2.64, p=9.2x10-7). No significant difference in the Kaplan-Meier survival analysis was observed for either of the approaches.   Conclusions: The patient-specific calcium detection threshold +100 % HUAorta is more predictive of post-TAVI adverse events included in the combined clinical endpoint than the fixed HU 850 approach. For the +100 % HUAorta approach, a calcium volume cut-off of 1421 mm3 of the aortic valve had the highest predictive value.Hintergrund: Ein wichtiger Auslöser von Komplikationen nach einer Transkatheter-Aortenklappen-Implantation (TAVI) sind ausgeprĂ€gte Kalkablagerung an der Aortenklappe. Dennoch erfolgte bisher keine Einigung auf ein standardisiertes Messverfahren zur Quantifizierung der Kalklast der Aortenklappe in einer kontrastverstĂ€rkten dynamischen computertomographischen Angiographie (CTA). Die vorliegende Dissertation untersucht, inwieweit die Wahl des Analyseverfahrens zur Quantifizierung von Kalkablagerungen in der Aortenklappe die Prognose von Komplikationen und der Überlebensdauer nach einer TAVI beeinflusst.   Methodik: Der Untersuchung liegt ein umfangreicher Datensatz von 965 Patienten mit 198 Merkmalen pro Patienten zugrunde, welche sich zwischen 2012 und 2019 am Deutschen Herzzentrum Berlin einer TAVI unterzogen haben. Die Quantifizierung der Kalkablagerung an der Aortenklappe mittels CTA wurde einerseits mit einem starren Grenzwert von 850 Hounsfield Einheiten (HU) (HU 850 Verfahren) und andererseits anhand eines individuellen Grenzwertes bemessen. Letzterer ergibt sich aus der HU-DĂ€mpfung in dem Lumen der Aorta ascendens multipliziert mit 2 (+100 % HUAorta Verfahren). Der primĂ€re klinische Endpunkt dieser Dissertation besteht aus einem aus sechs Variablen zusammengesetzten klinischen Endpunkt, welcher ungewĂŒnschte Ereignisse nach einer TAVI abbildet (paravalvulĂ€re Leckage ≄mild, Herzrhythmusstörungen nach einer TAVI, Tod innerhalb von 30 Tagen, post-TAVI Schlaganfall, Ruptur des Annulus und Prothesendislokation). Mögliche Störfaktoren, die auf das Eintreten der Komplikationen nach TAVI Einfluss haben, wurden durch den Einsatz des Akaike Informationskriterium ermittelt. Um die Vorhersagekraft von Komplikationen nach einer TAVI durch beide Verfahren zu ermitteln, wurde eine multivariate Regressionsanalyse durchgefĂŒhrt.   Ergebnisse: Die multivariaten logistischen Regressionen zeigen, dass die Messung der Kalkablagerungen anhand der HU 850 Messung (Kalklast Grenzwert von 146 mm3) die Komplikationen und die Überlebensdauer nicht vorhersagen konnten (OR=1.13, 95 % CI 0.87 bis 1.48, p=0.35). Die nach dem +100 % HUAorta Verfahren (Kalklast Grenzwert von 1421 mm3) individualisierte Kalkmessung erwies sich hingegen als sehr aussagekrĂ€ftig, da hiermit Komplikationen nach einer TAVI signifikant vorhergesagt werden konnten (OR=2, 95 % CI 1.52 bis 2.64, p=9.2x10-7). In Hinblick auf die postoperative Kaplan-Meier Überlebenszeitanalyse kann auch mit dem +100 % HUAorta Verfahren keine Vorhersage getroffen werden.   Fazit: Aus der Dissertation ergibt sich die Empfehlung, die Messung von Kalkablagerungen nach dem +100 % HUAorta Verfahren vorzunehmen, da Komplikationen wesentlich besser und zuverlĂ€ssiger als nach der gĂ€ngigen HU 850 Messmethode vorhergesagt werden können. FĂŒr das +100 % HUAorta Verfahren lag der optimale Kalklast Grenzwert bei 1421 mm3

    Review of Methodologies to Assess Bridge Safety During and After Floods

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    This report summarizes a review of technologies used to monitor bridge scour with an emphasis on techniques appropriate for testing during and immediately after design flood conditions. The goal of this study is to identify potential technologies and strategies for Illinois Department of Transportation that may be used to enhance the reliability of bridge safety monitoring during floods from local to state levels. The research team conducted a literature review of technologies that have been explored by state departments of transportation (DOTs) and national agencies as well as state-of-the-art technologies that have not been extensively employed by DOTs. This review included informational interviews with representatives from DOTs and relevant industry organizations. Recommendations include considering (1) acquisition of tethered kneeboard or surf ski-mounted single-beam sonars for rapid deployment by local agencies, (2) acquisition of remote-controlled vessels mounted with single-beam and side-scan sonars for statewide deployment, (3) development of large-scale particle image velocimetry systems using remote-controlled drones for stream velocity and direction measurement during floods, (4) physical modeling to develop Illinois-specific hydrodynamic loading coefficients for Illinois bridges during flood conditions, and (5) development of holistic risk-based bridge assessment tools that incorporate structural, geotechnical, hydraulic, and scour measurements to provide rapid feedback for bridge closure decisions.IDOT-R27-SP50Ope

    Improving the estimation of Cost-of-Illness in rheumatoid arthritis

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    Cost-of-illness (COI) studies measure the economic burden of a disease and estimate the maximum amount that could potentially be saved or gained if a disease were to be eradicated. Estimates of the COI can help appropriately target specific problems and policies on a disease in policy agenda setting. COI studies are particularly useful for chronic diseases that impact heavily on health expenditures and productivity loss for the whole society. It is essential for policymakers to know where costs are incurred. Consequently, appropriate interventions can be implemented and prioritised. Over the past two decades, the accumulation of coexisting long-term conditions within an individual has been confirmed as the best predictor of sustained high costs. It is now an established priority for both research and clinical practice owing to the high prevalence of coexisting diseases among patients, particularly with ageing populations. Because of this shift in how we approach chronic diseases in medical research, it is pertinent that we also think about how this impacts the way we look at COI. On the other hand, inconsistencies in the designs and methodologies that COI studies are conducted and a lack of transparency in reporting have made interpretation and comparison difficult and have limited the usefulness of results in health decision making. Variations include data sources, perspectives, cost components, and costing approaches. On the other hand, while standardisation of methodology through the implementation of guidelines is becoming increasingly important, some flexibility may be required for diseases or different contexts with unique characteristics to be adequately described. Rheumatoid arthritis (RA), as one of the most common chronic diseases, is a leading cause of work disability worldwide. Although numerous COI studies have attempted to quantify the economic burden of RA, the cost estimates vary substantially due to different methodological approaches, perspectives and settings. This thesis aims to improve the estimation of COI. To explore the differences in estimating COI, two case studies were developed in diverse contexts: Scotland and Tanzania. Both studies were complementary to each other in terms of different approaches and contexts to estimating COI. The former was in a high-income country, using secondary data analysis from a RA inception cohort linked to routinely collected health records to estimate the COI. In contrast, the latter was in a low- and middle-income country with limited treatment options. Due to the absence of routinely collected health data and the availability of screening tools for RA, a widening criterion of musculoskeletal (MSK) disorders was adopted. A context-specific questionnaire was developed to collect primary data to estimate the COI of MSK in Tanzania. This thesis confirms the need for improved estimation of COI studies. Good quality COI studies are not easy to do. Current evidence shows a lack of consistency in taking into account indirect costs, resulting in underestimating COI in RA. Moreover, indirect costs need more attention, with improvements in terms of data collection and costing approaches. Health conditions are complex and multi-dimensional, especially when the way we look at them have evolved over time. It is becoming clear that context is also an influencing factor in estimating COI. These complexities need to be considered in COI. While many systematic reviews for COI studies have urged the need to increase comparability, it is more crucial to be transparent in reporting contexts and methodological clarity, including identifying, measuring, and valuing COI

    Sensors and Methods for Railway Signalling Equipment Monitoring

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    Signalling upgrade projects that have been installed in equipment rooms in the recent past have limited capability to monitor performance of certain types of external circuits. To modify the equipment rooms on the commissioned railway would prove very expensive to implement and would be unacceptable in terms of delays caused to passenger services due to re-commissioning circuits after modification, to comply with rail signalling standards. The use of magnetoresistive sensors to provide performance data on point circuit operation and point operation is investigated. The sensors are bench tested on their ability to measure current in a circuit in a non-intrusive manner. The effect of shielding on the sensor performance is tested and found to be significant. The response of the sensors with various levels of amplification produces linear responses across a range of circuit gain. The output of the sensor circuit is demonstrated for various periods of interruption of conductor current. A three-axis accelerometer is mounted on a linear actuator to demonstrate the type of output expected from similar sensors mounted on a set of points. Measurements of current in point detection circuits and acceleration forces resulting from vibration of out of tolerance mechanical assemblies can provide valuable information on performance and possible threats to safe operation of equipment. The sensors seem capable of measuring the current in a conductor with a comparatively high degree of sensitivity. There is development work required on shielding the sensor from magnetic fields other than those being measured. The accelerometer work is at a demonstration level and requires development. The future testing work with accelerometers should be at a facility where multiple point moves can be made; with the capability to introduce faults to the point mechanisms. Methods can then be developed for analysis of the vibration signatures produced by the various faults

    Preliminary investigation of multi-hazard resilience analysis for urban transportation networks and data availability for hazard models and vulnerability of physical objects

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    HUB-Istanbul work package (WP) 2.6 aims to develop tools to analyse the multi-hazard resilience of urban transportation network in complex and evolving metropolitan environment, and propose a demonstrative application to a case study area: Fikirtepe in Istanbul, Turkey. Research outcomes will be conveyed by five deliverables. This document is the first deliverable, summarising the overall framework of analysis and required data for assessing physical vulnerability. Based on the framework, the second deliverable will deal specifically with another type of data required to evaluate traffic functionality of roadways and network performance. Based on the framework and datasets identified in the first two deliverables, the third deliverable will develop a probabilistic model to incorporate multi-layered analysis and data, which will be demonstrated by pilot examples. The fourth deliverable will present a thorough analysis of real-world transportation networks in the case study area, including mapping, network analysis and network performance evaluation. The evaluation results should be used to support decisions through mathematically formulated decision tasks, which will be illustrated in the fifth deliverable. This first deliverable summarises and proposes the research objectives, the framework of multi-hazard disaster resilience analysis of urban transportation networks and data requirement for assessing physical vulnerability, which are accompanied with thorough literature review. Based on the development, major hazard threats and distributions of bridges are identified for the case study area, Fikirtepe in Istanbul, Turkey

    Consolidation of Urban Freight Transport – Models and Algorithms

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    Urban freight transport is an indispensable component of economic and social life in cities. Compared to other types of transport, however, it contributes disproportionately to the negative impacts of traffic. As a result, urban freight transport is closely linked to social, environmental, and economic challenges. Managing urban freight transport and addressing these issues poses challenges not only for local city administrations but also for companies, such as logistics service providers (LSPs). Numerous policy measures and company-driven initiatives exist in the area of urban freight transport to overcome these challenges. One central approach is the consolidation of urban freight transport. This dissertation focuses on urban consolidation centers (UCCs) which are a widely studied and applied measure in urban freight transport. The fundamental idea of UCCs is to consolidate freight transport across companies in logistics facilities close to an urban area in order to increase the efficiency of vehicles delivering goods within the urban area. Although the concept has been researched and tested for several decades and it was shown that it can reduce the negative externalities of freight transport in cities, in practice many UCCs struggle with a lack of business participation and financial difficulties. This dissertation is primarily focused on the costs and savings associated with the use of UCCs from the perspective of LSPs. The cost-effectiveness of UCC use, which is also referred to as cost attractiveness, can be seen as a crucial condition for LSPs to be interested in using UCC systems. The overall objective of this dissertation is two-fold. First, it aims to develop models to provide decision support for evaluating the cost-effectiveness of using UCCs. Second, it aims to analyze the impacts of urban freight transport regulations and operational characteristics on the cost attractiveness of using UCCs from the perspective of LSPs. In this context, a distinction is made between UCCs that are jointly operated by a group of LSPs and UCCs that are operated by third parties who offer their urban transport service for a fee. The main body of this dissertation is based on three research papers. The first paper focuses on jointly-operated UCCs that are operated by a group of cooperating LSPs. It presents a simulation model to analyze the financial impacts on LSPs participating in such a scheme. In doing so, a particular focus is placed on urban freight transport regulations. A case study is used to analyze the operation of a jointly-operated UCC for scenarios involving three freight transport regulations. The second and third papers take on a different perspective on UCCs by focusing on third-party operated UCCs. In contrast to the first paper, the second and third papers present an evaluation approach in which the decision to use UCCs is integrated with the vehicle route planning of LSPs. In addition to addressing the basic version of this integrated routing problem, known as the vehicle routing problem with transshipment facilities (VRPTF), the second paper presents problem extensions that incorporate time windows, fleet size and mix decisions, and refined objective functions. To heuristically solve the basic problem and the new problem variants, an adaptive large neighborhood search (ALNS) heuristic with embedded local search heuristic and set partitioning problem (SPP) is presented. Furthermore, various factors influencing the cost attractiveness of UCCs, including time windows and usage fees, are analyzed using a real-world case study. The third paper extends the work of the second paper and incorporates daily and entrance-based city toll schemes and enables multi-trip routing. A mixed-integer linear programming (MILP) formulation of the resulting problem is proposed, as well as an ALNS solution heuristic. Moreover, a real-world case study with three European cities is used to analyze the impact of the two city toll systems in different operational contexts

    False textual information detection, a deep learning approach

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    Many approaches exist for analysing fact checking for fake news identification, which is the focus of this thesis. Current approaches still perform badly on a large scale due to a lack of authority, or insufficient evidence, or in certain cases reliance on a single piece of evidence. To address the lack of evidence and the inability of models to generalise across domains, we propose a style-aware model for detecting false information and improving existing performance. We discovered that our model was effective at detecting false information when we evaluated its generalisation ability using news articles and Twitter corpora. We then propose to improve fact checking performance by incorporating warrants. We developed a highly efficient prediction model based on the results and demonstrated that incorporating is beneficial for fact checking. Due to a lack of external warrant data, we develop a novel model for generating warrants that aid in determining the credibility of a claim. The results indicate that when a pre-trained language model is combined with a multi-agent model, high-quality, diverse warrants are generated that contribute to task performance improvement. To resolve a biased opinion and making rational judgments, we propose a model that can generate multiple perspectives on the claim. Experiments confirm that our Perspectives Generation model allows for the generation of diverse perspectives with a higher degree of quality and diversity than any other baseline model. Additionally, we propose to improve the model's detection capability by generating an explainable alternative factual claim assisting the reader in identifying subtle issues that result in factual errors. The examination demonstrates that it does indeed increase the veracity of the claim. Finally, current research has focused on stance detection and fact checking separately, we propose a unified model that integrates both tasks. Classification results demonstrate that our proposed model outperforms state-of-the-art methods
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