15,461 research outputs found

    Identifizierung prädiktiver und prognostischer Biomarker in unterschiedlichen Tumorkompartimenten des ösophagealen Adenokarzinoms

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    Das ösophageale Adenokarzinom zeigt eine global steigende Inzidenz und hat mit einer 5-Jahres-Überlebensrate von weniger als 25% eine schlechte Prognose. Personalisierte Therapieansätze sind selten und prognostische/prädiktive Biomarker des Tumormikromilieus sind unzureichend charakterisiert. Die kumulative Promotion nähert sich dieser Problematik in drei unterschiedlichen Schwerpunkten. 1. Zur Identifizierung Kompartiment-spezifischer Biomarker wurde eine Methode entwickelt, welche als kostengünstige Alternative zum sc-Seq Expressionsprofile individueller Zelltypen generiert. Dabei erfolgt die Extraktion der RNA nicht aus Einzelzellen, sondern aus flowzytometrisch-getrennten Zellkompartimenten. Die Separation der Proben in Epithelzellen, Immunzellen und Fibroblasten wurde durch verschiedene Verfahren validiert und eine suffiziente Ausbeute an RNA auch für kleine Gewebemengen gezeigt. 2. Biomarker des Immunzellkompartiments als therapeutische Angriffspunkte wurden in einem Patientenkollektiv von bis zu 551 Patienten auf ihre Bedeutung beim EAC überprüft. Es zeigte sich eine Expression der Immuncheckpoints LAG3, VISTA und IDO auf TILs durch IHC und RNA-Sonden basierte Verfahren in einem relevanten Anteil (LAG3: 11,4%, VISTA: 29%, IDO: 52,6%). Es konnte eine prognostisch günstige Bedeutung der VISTA, LAG3 und IDO Expression gezeigt werden. Durch den Vergleich von Genexpressionsprofilen aus therapienaiven und vorbehandelten Tumoren konnte zudem ein immunsuppressiver Effekt von neoadjuvanten Therapiekonzepten auf das Tumormikromilieu des EACs gezeigt werden. Dabei kam es zur verminderten Expression von Checkpoints und Anzahl TILs nach (Radio-) Chemotherapie. 3. Im Tumorzellkompartiment wurde die Rolle von Amplifikationen in ErbB-Rezeptor abhängigen Signalwegen durch FISH-Technik und Immunhistochemie evaluiert. Es fanden sich KRAS Amplifikationen in 17,1%, PIK3CA Amplifikationen in 5% sowie eine HER2/neu-Überexpression in 14,9% der untersuchten Tumore

    Countermeasures for the majority attack in blockchain distributed systems

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    La tecnología Blockchain es considerada como uno de los paradigmas informáticos más importantes posterior al Internet; en función a sus características únicas que la hacen ideal para registrar, verificar y administrar información de diferentes transacciones. A pesar de esto, Blockchain se enfrenta a diferentes problemas de seguridad, siendo el ataque del 51% o ataque mayoritario uno de los más importantes. Este consiste en que uno o más mineros tomen el control de al menos el 51% del Hash extraído o del cómputo en una red; de modo que un minero puede manipular y modificar arbitrariamente la información registrada en esta tecnología. Este trabajo se enfocó en diseñar e implementar estrategias de detección y mitigación de ataques mayoritarios (51% de ataque) en un sistema distribuido Blockchain, a partir de la caracterización del comportamiento de los mineros. Para lograr esto, se analizó y evaluó el Hash Rate / Share de los mineros de Bitcoin y Crypto Ethereum, seguido del diseño e implementación de un protocolo de consenso para controlar el poder de cómputo de los mineros. Posteriormente, se realizó la exploración y evaluación de modelos de Machine Learning para detectar software malicioso de tipo Cryptojacking.DoctoradoDoctor en Ingeniería de Sistemas y Computació

    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

    Implementing Health Impact Assessment as a Required Component of Government Policymaking: A Multi-Level Exploration of the Determinants of Healthy Public Policy

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    It is widely understood that the public policies of ‘non-health’ government sectors have greater impacts on population health than those of the traditional healthcare realm. Health Impact Assessment (HIA) is a decision support tool that identifies and promotes the health benefits of policies while also mitigating their unintended negative consequences. Despite numerous calls to do so, the Ontario government has yet to implement HIA as a required component of policy development. This dissertation therefore sought to identify the contexts and factors that may both enable and impede HIA use at the sub-national (i.e., provincial, territorial, or state) government level. The three integrated articles of this dissertation provide insights into specific aspects of the policy process as they relate to HIA. Chapter one details a case study of purposive information-seeking among public servants within Ontario’s Ministry of Education (MOE). Situated within Ontario’s Ministry of Health (MOH), chapter two presents a case study of policy collaboration between health and ‘non-health’ ministries. Finally, chapter three details a framework analysis of the political factors supporting health impact tool use in two sub-national jurisdictions – namely, Québec and South Australia. MOE respondents (N=9) identified four components of policymaking ‘due diligence’, including evidence retrieval, consultation and collaboration, referencing, and risk analysis. As prospective HIA users, they also confirmed that information is not routinely sought to mitigate the potential negative health impacts of education-based policies. MOH respondents (N=8) identified the bureaucratic hierarchy as the brokering mechanism for inter-ministerial policy development. As prospective HIA stewards, they also confirmed that the ministry does not proactively flag the potential negative health impacts of non-health sector policies. Finally, ‘lessons learned’ from case articles specific to Québec (n=12) and South Australia (n=17) identified the political factors supporting tool use at different stages of the policy cycle, including agenda setting (‘policy elites’ and ‘political culture’), implementation (‘jurisdiction’), and sustained implementation (‘institutional power’). This work provides important insights into ‘real life’ policymaking. By highlighting existing facilitators of and barriers to HIA use, the findings offer a useful starting point from which proponents may tailor context-specific strategies to sustainably implement HIA at the sub-national government level

    Learning disentangled speech representations

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    A variety of informational factors are contained within the speech signal and a single short recording of speech reveals much more than the spoken words. The best method to extract and represent informational factors from the speech signal ultimately depends on which informational factors are desired and how they will be used. In addition, sometimes methods will capture more than one informational factor at the same time such as speaker identity, spoken content, and speaker prosody. The goal of this dissertation is to explore different ways to deconstruct the speech signal into abstract representations that can be learned and later reused in various speech technology tasks. This task of deconstructing, also known as disentanglement, is a form of distributed representation learning. As a general approach to disentanglement, there are some guiding principles that elaborate what a learned representation should contain as well as how it should function. In particular, learned representations should contain all of the requisite information in a more compact manner, be interpretable, remove nuisance factors of irrelevant information, be useful in downstream tasks, and independent of the task at hand. The learned representations should also be able to answer counter-factual questions. In some cases, learned speech representations can be re-assembled in different ways according to the requirements of downstream applications. For example, in a voice conversion task, the speech content is retained while the speaker identity is changed. And in a content-privacy task, some targeted content may be concealed without affecting how surrounding words sound. While there is no single-best method to disentangle all types of factors, some end-to-end approaches demonstrate a promising degree of generalization to diverse speech tasks. This thesis explores a variety of use-cases for disentangled representations including phone recognition, speaker diarization, linguistic code-switching, voice conversion, and content-based privacy masking. Speech representations can also be utilised for automatically assessing the quality and authenticity of speech, such as automatic MOS ratings or detecting deep fakes. The meaning of the term "disentanglement" is not well defined in previous work, and it has acquired several meanings depending on the domain (e.g. image vs. speech). Sometimes the term "disentanglement" is used interchangeably with the term "factorization". This thesis proposes that disentanglement of speech is distinct, and offers a viewpoint of disentanglement that can be considered both theoretically and practically

    Statistical-dynamical analyses and modelling of multi-scale ocean variability

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    This thesis aims to provide a comprehensive analysis of multi-scale oceanic variabilities using various statistical and dynamical tools and explore the data-driven methods for correct statistical emulation of the oceans. We considered the classical, wind-driven, double-gyre ocean circulation model in quasi-geostrophic approximation and obtained its eddy-resolving solutions in terms of potential vorticity anomaly and geostrophic streamfunctions. The reference solutions possess two asymmetric gyres of opposite circulations and a strong meandering eastward jet separating them with rich eddy activities around it, such as the Gulf Stream in the North Atlantic and Kuroshio in the North Pacific. This thesis is divided into two parts. The first part discusses a novel scale-separation method based on the local spatial correlations, called correlation-based decomposition (CBD), and provides a comprehensive analysis of mesoscale eddy forcing. In particular, we analyse the instantaneous and time-lagged interactions between the diagnosed eddy forcing and the evolving large-scale PVA using the novel `product integral' characteristics. The product integral time series uncover robust causality between two drastically different yet interacting flow quantities, termed `eddy backscatter'. We also show data-driven augmentation of non-eddy-resolving ocean models by feeding them the eddy fields to restore the missing eddy-driven features, such as the merging western boundary currents, their eastward extension and low-frequency variabilities of gyres. In the second part, we present a systematic inter-comparison of Linear Regression (LR), stochastic and deep-learning methods to build low-cost reduced-order statistical emulators of the oceans. We obtain the forecasts on seasonal and centennial timescales and assess them for their skill, cost and complexity. We found that the multi-level linear stochastic model performs the best, followed by the ``hybrid stochastically-augmented deep learning models''. The superiority of these methods underscores the importance of incorporating core dynamics, memory effects and model errors for robust emulation of multi-scale dynamical systems, such as the oceans.Open Acces

    Detection of Hyperpartisan news articles using natural language processing techniques

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    Yellow journalism has increased the spread of hyperpartisan news on the internet. It is very difficult for online news article readers to distinguish hyperpartisan news articles from mainstream news articles. There is a need for an automated model that can detect hyperpartisan news on the internet and tag them as hyperpartisan so that it is very easy for readers to avoid that news. A hyperpartisan news detection article was developed by using three different natural language processing techniques named BERT, ELMo, and Word2vec. This research used the bi-article dataset published at SEMEVAL-2019. The ELMo word embeddings which are trained on a Random forest classifier has got an accuracy of 0.88, which is much better than other state of art models. The BERT and Word2vec models have got the same accuracy of 0.83. This research tried different sentence input lengths to BERT and proved that BERT can extract context from local words. Evidenced from the described ML models, this study will assist the governments, news’ readers, and other political stakeholders to detect any hyperpartisan news, and also helps policy to track, and regulate, misinformation about the political parties and their leaders

    TOWARDS AN UNDERSTANDING OF EFFORTFUL FUNDRAISING EXPERIENCES: USING INTERPRETATIVE PHENOMENOLOGICAL ANALYSIS IN FUNDRAISING RESEARCH

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    Physical-activity oriented community fundraising has experienced an exponential growth in popularity over the past 15 years. The aim of this study was to explore the value of effortful fundraising experiences, from the point of view of participants, and explore the impact that these experiences have on people’s lives. This study used an IPA approach to interview 23 individuals, recognising the role of participants as proxy (nonprofessional) fundraisers for charitable organisations, and the unique organisation donor dynamic that this creates. It also bought together relevant psychological theory related to physical activity fundraising experiences (through a narrative literature review) and used primary interview data to substantiate these. Effortful fundraising experiences are examined in detail to understand their significance to participants, and how such experiences influence their connection with a charity or cause. This was done with an idiographic focus at first, before examining convergences and divergences across the sample. This study found that effortful fundraising experiences can have a profound positive impact upon community fundraisers in both the short and the long term. Additionally, it found that these experiences can be opportunities for charitable organisations to create lasting meaningful relationships with participants, and foster mutually beneficial lifetime relationships with them. Further research is needed to test specific psychological theory in this context, including self-esteem theory, self determination theory, and the martyrdom effect (among others)
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