6,245 research outputs found

    A Design Science Research Approach to Smart and Collaborative Urban Supply Networks

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    Urban supply networks are facing increasing demands and challenges and thus constitute a relevant field for research and practical development. Supply chain management holds enormous potential and relevance for society and everyday life as the flow of goods and information are important economic functions. Being a heterogeneous field, the literature base of supply chain management research is difficult to manage and navigate. Disruptive digital technologies and the implementation of cross-network information analysis and sharing drive the need for new organisational and technological approaches. Practical issues are manifold and include mega trends such as digital transformation, urbanisation, and environmental awareness. A promising approach to solving these problems is the realisation of smart and collaborative supply networks. The growth of artificial intelligence applications in recent years has led to a wide range of applications in a variety of domains. However, the potential of artificial intelligence utilisation in supply chain management has not yet been fully exploited. Similarly, value creation increasingly takes place in networked value creation cycles that have become continuously more collaborative, complex, and dynamic as interactions in business processes involving information technologies have become more intense. Following a design science research approach this cumulative thesis comprises the development and discussion of four artefacts for the analysis and advancement of smart and collaborative urban supply networks. This thesis aims to highlight the potential of artificial intelligence-based supply networks, to advance data-driven inter-organisational collaboration, and to improve last mile supply network sustainability. Based on thorough machine learning and systematic literature reviews, reference and system dynamics modelling, simulation, and qualitative empirical research, the artefacts provide a valuable contribution to research and practice

    Deep Transfer Learning Applications in Intrusion Detection Systems: A Comprehensive Review

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    Globally, the external Internet is increasingly being connected to the contemporary industrial control system. As a result, there is an immediate need to protect the network from several threats. The key infrastructure of industrial activity may be protected from harm by using an intrusion detection system (IDS), a preventive measure mechanism, to recognize new kinds of dangerous threats and hostile activities. The most recent artificial intelligence (AI) techniques used to create IDS in many kinds of industrial control networks are examined in this study, with a particular emphasis on IDS-based deep transfer learning (DTL). This latter can be seen as a type of information fusion that merge, and/or adapt knowledge from multiple domains to enhance the performance of the target task, particularly when the labeled data in the target domain is scarce. Publications issued after 2015 were taken into account. These selected publications were divided into three categories: DTL-only and IDS-only are involved in the introduction and background, and DTL-based IDS papers are involved in the core papers of this review. Researchers will be able to have a better grasp of the current state of DTL approaches used in IDS in many different types of networks by reading this review paper. Other useful information, such as the datasets used, the sort of DTL employed, the pre-trained network, IDS techniques, the evaluation metrics including accuracy/F-score and false alarm rate (FAR), and the improvement gained, were also covered. The algorithms, and methods used in several studies, or illustrate deeply and clearly the principle in any DTL-based IDS subcategory are presented to the reader

    A Decision Support System for Economic Viability and Environmental Impact Assessment of Vertical Farms

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    Vertical farming (VF) is the practice of growing crops or animals using the vertical dimension via multi-tier racks or vertically inclined surfaces. In this thesis, I focus on the emerging industry of plant-specific VF. Vertical plant farming (VPF) is a promising and relatively novel practice that can be conducted in buildings with environmental control and artificial lighting. However, the nascent sector has experienced challenges in economic viability, standardisation, and environmental sustainability. Practitioners and academics call for a comprehensive financial analysis of VPF, but efforts are stifled by a lack of valid and available data. A review of economic estimation and horticultural software identifies a need for a decision support system (DSS) that facilitates risk-empowered business planning for vertical farmers. This thesis proposes an open-source DSS framework to evaluate business sustainability through financial risk and environmental impact assessments. Data from the literature, alongside lessons learned from industry practitioners, would be centralised in the proposed DSS using imprecise data techniques. These techniques have been applied in engineering but are seldom used in financial forecasting. This could benefit complex sectors which only have scarce data to predict business viability. To begin the execution of the DSS framework, VPF practitioners were interviewed using a mixed-methods approach. Learnings from over 19 shuttered and operational VPF projects provide insights into the barriers inhibiting scalability and identifying risks to form a risk taxonomy. Labour was the most commonly reported top challenge. Therefore, research was conducted to explore lean principles to improve productivity. A probabilistic model representing a spectrum of variables and their associated uncertainty was built according to the DSS framework to evaluate the financial risk for VF projects. This enabled flexible computation without precise production or financial data to improve economic estimation accuracy. The model assessed two VPF cases (one in the UK and another in Japan), demonstrating the first risk and uncertainty quantification of VPF business models in the literature. The results highlighted measures to improve economic viability and the viability of the UK and Japan case. The environmental impact assessment model was developed, allowing VPF operators to evaluate their carbon footprint compared to traditional agriculture using life-cycle assessment. I explore strategies for net-zero carbon production through sensitivity analysis. Renewable energies, especially solar, geothermal, and tidal power, show promise for reducing the carbon emissions of indoor VPF. Results show that renewably-powered VPF can reduce carbon emissions compared to field-based agriculture when considering the land-use change. The drivers for DSS adoption have been researched, showing a pathway of compliance and design thinking to overcome the ‘problem of implementation’ and enable commercialisation. Further work is suggested to standardise VF equipment, collect benchmarking data, and characterise risks. This work will reduce risk and uncertainty and accelerate the sector’s emergence

    Statistical Learning for Gene Expression Biomarker Detection in Neurodegenerative Diseases

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    In this work, statistical learning approaches are used to detect biomarkers for neurodegenerative diseases (NDs). NDs are becoming increasingly prevalent as populations age, making understanding of disease and identification of biomarkers progressively important for facilitating early diagnosis and the screening of individuals for clinical trials. Advancements in gene expression profiling has enabled the exploration of disease biomarkers at an unprecedented scale. The work presented here demonstrates the value of gene expression data in understanding the underlying processes and detection of biomarkers of NDs. The value of novel approaches to previously collected -omics data is shown and it is demonstrated that new therapeutic targets can be identified. Additionally, the importance of meta-analysis to improve power of multiple small studies is demonstrated. The value of blood transcriptomics data is shown in applications to researching NDs to understand underlying processes using network analysis and a novel hub detection method. Finally, after demonstrating the value of blood gene expression data for investigating NDs, a combination of feature selection and classification algorithms were used to identify novel accurate biomarker signatures for the diagnosis and prognosis of Parkinson’s disease (PD) and Alzheimer’s disease (AD). Additionally, the use of feature pools based on previous knowledge of disease and the viability of neural networks in dimensionality reduction and biomarker detection is demonstrated and discussed. In summary, gene expression data is shown to be valuable for the investigation of ND and novel gene biomarker signatures for the diagnosis and prognosis of PD and AD

    Machine learning for managing structured and semi-structured data

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    As the digitalization of private, commercial, and public sectors advances rapidly, an increasing amount of data is becoming available. In order to gain insights or knowledge from these enormous amounts of raw data, a deep analysis is essential. The immense volume requires highly automated processes with minimal manual interaction. In recent years, machine learning methods have taken on a central role in this task. In addition to the individual data points, their interrelationships often play a decisive role, e.g. whether two patients are related to each other or whether they are treated by the same physician. Hence, relational learning is an important branch of research, which studies how to harness this explicitly available structural information between different data points. Recently, graph neural networks have gained importance. These can be considered an extension of convolutional neural networks from regular grids to general (irregular) graphs. Knowledge graphs play an essential role in representing facts about entities in a machine-readable way. While great efforts are made to store as many facts as possible in these graphs, they often remain incomplete, i.e., true facts are missing. Manual verification and expansion of the graphs is becoming increasingly difficult due to the large volume of data and must therefore be assisted or substituted by automated procedures which predict missing facts. The field of knowledge graph completion can be roughly divided into two categories: Link Prediction and Entity Alignment. In Link Prediction, machine learning models are trained to predict unknown facts between entities based on the known facts. Entity Alignment aims at identifying shared entities between graphs in order to link several such knowledge graphs based on some provided seed alignment pairs. In this thesis, we present important advances in the field of knowledge graph completion. For Entity Alignment, we show how to reduce the number of required seed alignments while maintaining performance by novel active learning techniques. We also discuss the power of textual features and show that graph-neural-network-based methods have difficulties with noisy alignment data. For Link Prediction, we demonstrate how to improve the prediction for unknown entities at training time by exploiting additional metadata on individual statements, often available in modern graphs. Supported with results from a large-scale experimental study, we present an analysis of the effect of individual components of machine learning models, e.g., the interaction function or loss criterion, on the task of link prediction. We also introduce a software library that simplifies the implementation and study of such components and makes them accessible to a wide research community, ranging from relational learning researchers to applied fields, such as life sciences. Finally, we propose a novel metric for evaluating ranking results, as used for both completion tasks. It allows for easier interpretation and comparison, especially in cases with different numbers of ranking candidates, as encountered in the de-facto standard evaluation protocols for both tasks.Mit der rasant fortschreitenden Digitalisierung des privaten, kommerziellen und öffentlichen Sektors werden immer grĂ¶ĂŸere Datenmengen verfĂŒgbar. Um aus diesen enormen Mengen an Rohdaten Erkenntnisse oder Wissen zu gewinnen, ist eine tiefgehende Analyse unerlĂ€sslich. Das immense Volumen erfordert hochautomatisierte Prozesse mit minimaler manueller Interaktion. In den letzten Jahren haben Methoden des maschinellen Lernens eine zentrale Rolle bei dieser Aufgabe eingenommen. Neben den einzelnen Datenpunkten spielen oft auch deren ZusammenhĂ€nge eine entscheidende Rolle, z.B. ob zwei Patienten miteinander verwandt sind oder ob sie vom selben Arzt behandelt werden. Daher ist das relationale Lernen ein wichtiger Forschungszweig, der untersucht, wie diese explizit verfĂŒgbaren strukturellen Informationen zwischen verschiedenen Datenpunkten nutzbar gemacht werden können. In letzter Zeit haben Graph Neural Networks an Bedeutung gewonnen. Diese können als eine Erweiterung von CNNs von regelmĂ€ĂŸigen Gittern auf allgemeine (unregelmĂ€ĂŸige) Graphen betrachtet werden. Wissensgraphen spielen eine wesentliche Rolle bei der Darstellung von Fakten ĂŒber EntitĂ€ten in maschinenlesbaren Form. Obwohl große Anstrengungen unternommen werden, so viele Fakten wie möglich in diesen Graphen zu speichern, bleiben sie oft unvollstĂ€ndig, d. h. es fehlen Fakten. Die manuelle ÜberprĂŒfung und Erweiterung der Graphen wird aufgrund der großen Datenmengen immer schwieriger und muss daher durch automatisierte Verfahren unterstĂŒtzt oder ersetzt werden, die fehlende Fakten vorhersagen. Das Gebiet der WissensgraphenvervollstĂ€ndigung lĂ€sst sich grob in zwei Kategorien einteilen: Link Prediction und Entity Alignment. Bei der Link Prediction werden maschinelle Lernmodelle trainiert, um unbekannte Fakten zwischen EntitĂ€ten auf der Grundlage der bekannten Fakten vorherzusagen. Entity Alignment zielt darauf ab, gemeinsame EntitĂ€ten zwischen Graphen zu identifizieren, um mehrere solcher Wissensgraphen auf der Grundlage einiger vorgegebener Paare zu verknĂŒpfen. In dieser Arbeit stellen wir wichtige Fortschritte auf dem Gebiet der VervollstĂ€ndigung von Wissensgraphen vor. FĂŒr das Entity Alignment zeigen wir, wie die Anzahl der benötigten Paare reduziert werden kann, wĂ€hrend die Leistung durch neuartige aktive Lerntechniken erhalten bleibt. Wir erörtern auch die LeistungsfĂ€higkeit von Textmerkmalen und zeigen, dass auf Graph-Neural-Networks basierende Methoden Schwierigkeiten mit verrauschten Paar-Daten haben. FĂŒr die Link Prediction demonstrieren wir, wie die Vorhersage fĂŒr unbekannte EntitĂ€ten zur Trainingszeit verbessert werden kann, indem zusĂ€tzliche Metadaten zu einzelnen Aussagen genutzt werden, die oft in modernen Graphen verfĂŒgbar sind. GestĂŒtzt auf Ergebnisse einer groß angelegten experimentellen Studie prĂ€sentieren wir eine Analyse der Auswirkungen einzelner Komponenten von Modellen des maschinellen Lernens, z. B. der Interaktionsfunktion oder des Verlustkriteriums, auf die Aufgabe der Link Prediction. Außerdem stellen wir eine Softwarebibliothek vor, die die Implementierung und Untersuchung solcher Komponenten vereinfacht und sie einer breiten Forschungsgemeinschaft zugĂ€nglich macht, die von Forschern im Bereich des relationalen Lernens bis hin zu angewandten Bereichen wie den Biowissenschaften reicht. Schließlich schlagen wir eine neuartige Metrik fĂŒr die Bewertung von Ranking-Ergebnissen vor, wie sie fĂŒr beide Aufgaben verwendet wird. Sie ermöglicht eine einfachere Interpretation und einen leichteren Vergleich, insbesondere in FĂ€llen mit einer unterschiedlichen Anzahl von Kandidaten, wie sie in den de-facto Standardbewertungsprotokollen fĂŒr beide Aufgaben vorkommen

    Antibody Targeting of HIV-1 Env: A Structural Perspective

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    A key component of contemporary efforts toward a human immunodeficiency virus 1 (HIV-1) vaccine is the use of structural biology to understand the structural characteristics of antibodies elicited both from human patients and animals immunized with engineered 'immunogens,' or early vaccine candidates. This thesis will report on projects characterizing both types of antibodies against HIV-1. Chapter 1 will introduce relevant topics, including the reasons HIV-1 is particularly capable of evading the immune system in natural infection and after vaccination, the 20+ year history of unsuccessful HIV-1 vaccine large-scale efficacy trials, an introduction to broadly neutralizing antibodies (bNAbs), and a review of common strategies utilized in HIV-1 immunogen design today. Chapter 2 describes the isolation, high-resolution structural characterization, and in vitro resistance profile of a new bNAb, 1-18, that is both very broad and potent, as well as able to restrict HIV-1 escape in vivo. Chapter 3 reports the results of an epitope-focusing immunogen design and immunization experiment carried out in wild type mice, rabbits, and non-human primates where it was shown that B cells targeting the desired epitope were expanded after a single prime immunization with immunogen RC1 or a variant, RC1-4fill. Chapter 4 describes Ab1245, an off-target non-neutralizing monoclonal antibody isolated in a macaque that had been immunized with a series of sequential immunogens after the prime immunization reported in Chapter 3. The antibody structure describes a specific type of distracting response as it binds in a way that causes a large structural change in Env, resulting in the destruction of the neutralizing fusion peptide epitope. Chapter 5 is adapted from a review about how antibodies differentially recognize the viruses HIV-1, SARS-CoV-2, and Zika virus. This review serves as an introduction to the virus SARS-CoV-2, which is the topic of the final chapter, Chapter 6. In this chapter, structures of many neutralizing antibodies isolated from SARS-CoV-2 patients were used to define potentially therapeutic classes of neutralizing receptor-binding domain (RBD) antibodies based on their epitopes and binding profiles

    Elasto-plastic deformations within a material point framework on modern GPU architectures

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    Plastic strain localization is an important process on Earth. It strongly influ- ences the mechanical behaviour of natural processes, such as fault mechanics, earthquakes or orogeny. At a smaller scale, a landslide is a fantastic example of elasto-plastic deformations. Such behaviour spans from pre-failure mech- anisms to post-failure propagation of the unstable material. To fully resolve the landslide mechanics, the selected numerical methods should be able to efficiently address a wide range of deformation magnitudes. Accurate and performant numerical modelling requires important compu- tational resources. Mesh-free numerical methods such as the material point method (MPM) or the smoothed-particle hydrodynamics (SPH) are particu- larly computationally expensive, when compared with mesh-based methods, such as the finite element method (FEM) or the finite difference method (FDM). Still, mesh-free methods are particularly well-suited to numerical problems involving large elasto-plastic deformations. But, the computational efficiency of these methods should be first improved in order to tackle complex three-dimensional problems, i.e., landslides. As such, this research work attempts to alleviate the computational cost of the material point method by using the most recent graphics processing unit (GPU) architectures available. GPUs are many-core processors originally designed to refresh screen pixels (e.g., for computer games) independently. This allows GPUs to delivers a massive parallelism when compared to central processing units (CPUs). To do so, this research work first investigates code prototyping in a high- level language, e.g., MATLAB. This allows to implement vectorized algorithms and benchmark numerical results of two-dimensional analysis with analytical solutions and/or experimental results in an affordable amount of time. After- wards, low-level language such as CUDA C is used to efficiently implement a GPU-based solver, i.e., ep2-3De v1.0, can resolve three-dimensional prob- lems in a decent amount of time. This part takes advantages of the massive parallelism of modern GPU architectures. In addition, a first attempt of GPU parallel computing, i.e., multi-GPU codes, is performed to increase even more the performance and to address the on-chip memory limitation. Finally, this GPU-based solver is used to investigate three-dimensional granular collapses and is compared with experimental evidences obtained in the laboratory. This research work demonstrates that the material point method is well suited to resolve small to large elasto-plastic deformations. Moreover, the computational efficiency of the method can be dramatically increased using modern GPU architectures. These allow fast, performant and accurate three- dimensional modelling of landslides, provided that the on-chip memory limi- tation is alleviated with an appropriate parallel strategy

    Developing automated meta-research approaches in the preclinical Alzheimer's disease literature

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    Alzheimer’s disease is a devastating neurodegenerative disorder for which there is no cure. A crucial part of the drug development pipeline involves testing therapeutic interventions in animal disease models. However, promising findings in preclinical experiments have not translated into clinical trial success. Reproducibility has often been cited as a major issue affecting biomedical research, where experimental results in one laboratory cannot be replicated in another. By using meta-research (research on research) approaches such as systematic reviews, researchers aim to identify and summarise all available evidence relating to a specific research question. By conducting a meta-analysis, researchers can also combine the results from different experiments statistically to understand the overall effect of an intervention and to explore reasons for variations seen across different publications. Systematic reviews of the preclinical Alzheimer’s disease literature could inform decision making, encourage research improvement, and identify gaps in the literature to guide future research. However, due to the vast amount of potentially useful evidence from animal models of Alzheimer’s disease, it remains difficult to make sense of and utilise this data effectively. Systematic reviews are common practice within evidence based medicine, yet their application to preclinical research is often limited by the time and resources required. In this thesis, I develop, build-upon, and implement automated meta-research approaches to collect, curate, and evaluate the preclinical Alzheimer’s literature. I searched several biomedical databases to obtain all research relevant to Alzheimer’s disease. I developed a novel deduplication tool to automatically identify and remove duplicate publications identified across different databases with minimal human effort. I trained a crowd of reviewers to annotate a subset of the publications identified and used this data to train a machine learning algorithm to screen through the remaining publications for relevance. I developed text-mining tools to extract model, intervention, and treatment information from publications and I improved existing automated tools to extract reported measures to reduce the risk of bias. Using these tools, I created a categorised database of research in transgenic Alzheimer’s disease animal models and created a visual summary of this dataset on an interactive, openly accessible online platform. Using the techniques described, I also identified relevant publications within the categorised dataset to perform systematic reviews of two key outcomes of interest in transgenic Alzheimer’s disease models: (1) synaptic plasticity and transmission in hippocampal slices and (2) motor activity in the open field test. Over 400,000 publications were identified across biomedical research databases, with 230,203 unique publications. In a performance evaluation across different preclinical datasets, the automated deduplication tool I developed could identify over 97% of duplicate citations and a had an error rate similar to that of human performance. When evaluated on a test set of publications, the machine learning classifier trained to identify relevant research in transgenic models performed was highly sensitive (captured 96.5% of relevant publications) and excluded 87.8% of irrelevant publications. Tools to identify the model(s) and outcome measure(s) within the full-text of publications may reduce the burden on reviewers and were found to be more sensitive than searching only the title and abstract of citations. Automated tools to assess risk of bias reporting were highly sensitive and could have the potential to monitor research improvement over time. The final dataset of categorised Alzheimer’s disease research contained 22,375 publications which were then visualised in the interactive web application. Within the application, users can see how many publications report measures to reduce the risk of bias and how many have been classified as using each transgenic model, testing each intervention, and measuring each outcome. Users can also filter to obtain curated lists of relevant research, allowing them to perform systematic reviews at an accelerated pace with reduced effort required to search across databases, and a reduced number of publications to screen for relevance. Both systematic reviews and meta-analyses highlighted failures to report key methodological information within publications. Poor transparency of reporting limited the statistical power I had to understand the sources of between-study variation. However, some variables were found to explain a significant proportion of the heterogeneity. Transgenic animal model had a significant impact on results in both reviews. For certain open field test outcomes, wall colour of the open field arena and the reporting of measures to reduce the risk of bias were found to impact results. For in vitro electrophysiology experiments measuring synaptic plasticity, several electrophysiology parameters, including magnesium concentration of the recording solution, were found to explain a significant proportion of the heterogeneity. Automated meta-research approaches and curated web platforms summarising preclinical research could have the potential to accelerate the conduct of systematic reviews and maximise the potential of existing evidence to inform translation

    Principles of Massively Parallel Sequencing for Engineering and Characterizing Gene Delivery

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    The advent of massively parallel sequencing and synthesis technologies have ushered in a new paradigm of biology, where high throughput screening of billions of nucleid acid molecules and production of libraries of millions of genetic mutants are now routine in labs and clinics. During my Ph.D., I worked to develop data analysis and experimental methods that take advantage of the scale of this data, while making the minimal assumptions necessary for deriving value from their application. My Ph.D. work began with the development of software and principles for analyzing deep mutational scanning data of libraries of engineered AAV capsids. By looking at not only the top variant in a round of directed evolution, but instead a broad distribution of the variants and their phenotypes, we were able to identify AAV variants with enhanced ability to transduce specific cells in the brain after intravenous injection. I then shifted to better understand the phenotypic profile of these engineered variants. To that end, I turned to single-cell RNA sequencing to seek to identify, with high resolution, the delivery profile of these variants in all cell types present in the cortex of a mouse brain. I began by developing infrastructure and tools for dealing with the data analysis demands of these experiments. Then, by delivering an engineered variant to the animal, I was able to use the single-cell RNA sequencing profile, coupled with a sequencing readout of the delivered genetic cargo present in each cell type, to define the variant’s tropism across the full spectrum of cell types in a single step. To increase the throughput of this experimental paradigm, I then worked to develop a multiplexing strategy for delivering up to 7 engineered variants in a single animal, and obtain the same high resolution readout for each variant in a single experiment. Finally, to take a step towards translation to human diagnostics, I leveraged the tools I built for scaling single-cell RNA sequencing studies and worked to develop a protocol for obtaining single-cell immune profiles of low volumes of self-collected blood. This study enabled repeat sampling in a short period of time, and revealed an incredible richness in individual variability and time-of-day dependence of human immune gene expression. Together, my Ph.D. work provides strategies for employing massively parallel sequencing and synthesis for new biological applications, and builds towards a future paradigm where personalized, high-resolution sequencing might be coupled with modular, customized gene therapy delivery.</p
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