The landscape of combination therapies against glioblastoma:From promises to challenges

We demonstrate in this thesis how new targets can be identified and highlight the challenges that lie in front of us when trying to translate these steps toward the clinic. We conclude that the blood-brain barrier, PD/PK of drugs, and therapy resistance are still major challenges and explain the limited improvement in treatment options for patients with GBM. First, GBM is a diffuse glioma located in the brain where the blood-brain barrier prevents the crossing of drugs and thereby limits the efficacy of treatment. Second, inter- and intratumoral heterogeneity have been observed in GBM leading to different cellular subpopulations with distinctive genetic profiles. Hence, treating these subpopulations with targeted drugs allows until now still survival of certain subpopulations that are not sensitive to this treatment. Lastly, therapy resistance is often seen in GBM patients and is probably related to intratumoral heterogeneity, but the intrinsic molecular mechanism is still not fully understood. Together they lead to the inevitable recurrence of the tumor

Applied Mathematics to Mechanisms and Machines

This book brings together all 16 articles published in the Special Issue "Applied Mathematics to Mechanisms and Machines" of the MDPI Mathematics journal, in the section “Engineering Mathematics”. The subject matter covered by these works is varied, but they all have mechanisms as the object of study and mathematics as the basis of the methodology used. In fact, the synthesis, design and optimization of mechanisms, robotics, automotives, maintenance 4.0, machine vibrations, control, biomechanics and medical devices are among the topics covered in this book. This volume may be of interest to all who work in the field of mechanism and machine science and we hope that it will contribute to the development of both mechanical engineering and applied mathematics

Quantitative electron microscopy for microstructural characterisation

Development of materials for high-performance applications requires accurate and useful analysis tools. In parallel with advances in electron microscopy hardware, we require analysis approaches to better understand microstructural behaviour. Such improvements in characterisation capability permit informed alloy design. New approaches to the characterisation of metallic materials are presented, primarily using signals collected from electron microscopy experiments. Electron backscatter diffraction is regularly used to investigate crystallography in the scanning electron microscope, and combined with energy-dispersive X-ray spectroscopy to simultaneusly investigate chemistry. New algorithms and analysis pipelines are developed to permit accurate and routine microstructural evaluation, leveraging a variety of machine learning approaches. This thesis investigates the structure and behaviour of Co/Ni-base superalloys, derived from V208C. Use of the presently developed techniques permits informed development of a new generation of advanced gas turbine engine materials.Open Acces

On the use of context information for an improved application of data-based algorithms in condition monitoring

xi, 124 p.En el campo de la monitorización de la condición, los algoritmos basados en datos cuentan con un amplio recorrido. Desde el uso de los gráficos de control de calidad que se llevan empleando durante casi un siglo a técnicas de mayor complejidad como las redes neuronales o máquinas de soporte vectorial que se emplean para detección, diagnóstico y estimación de vida remanente de los equipos. Sin embargo, la puesta en producción de los algoritmos de monitorización requiere de un estudio exhaustivo de un factor que es a menudo obviado por otros trabajos de la literatura: el contexto. El contexto, que en este trabajo es considerado como el conjunto de factores que influencian la monitorización de un bien, tiene un gran impacto en la algoritmia de monitorización y su aplicación final. Por este motivo, es el objeto de estudio de esta tesis en la que se han analizado tres casos de uso. Se ha profundizado en sus respectivos contextos, tratando de generalizar a la problemática habitual en la monitorización de maquinaria industrial, y se ha abordado dicha problemática de monitorización de forma que solucionen el contexto en lugar de cada caso de uso. Así, el conocimiento adquirido durante el desarrollo de las soluciones puede ser transferido a otros casos de uso que cuenten con contextos similares

딥러닝 방법론을 이용한 높은 적용성을 가진 수경재배 파프리카 대상 절차 기반 모델 개발

학위논문(박사) -- 서울대학교대학원 : 농업생명과학대학 농림생물자원학부, 2022. 8. 손정익.Many agricultural challenges are entangled in a complex interaction between crops and the environment. As a simplifying tool, crop modeling is a process of abstracting and interpreting agricultural phenomena. Understanding based on this interpretation can play a role in supporting academic and social decisions in agriculture. Process-based crop models have solved the challenges for decades to enhance the productivity and quality of crop production; the remaining objectives have led to demand for crop models handling multidirectional analyses with multidimensional information. As a possible milestone to satisfy this goal, deep learning algorithms have been introduced to the complicated tasks in agriculture. However, the algorithms could not replace existing crop models because of the research fragmentation and low accessibility of the crop models. This study established a developmental protocol for a process-based crop model with deep learning methodology. Literature Review introduced deep learning and crop modeling, and it explained the reasons for the necessity of this protocol despite numerous deep learning applications for agriculture. Base studies were conducted with several greenhouse data in Chapters 1 and 2: transfer learning and U-Net structure were utilized to construct an infrastructure for the deep learning application; HyperOpt, a Bayesian optimization method, was tested to calibrate crop models to compare the existing crop models with the developed model. Finally, the process-based crop model with full deep neural networks, DeepCrop, was developed with an attention mechanism and multitask decoders for hydroponic sweet peppers (Capsicum annuum var. annuum) in Chapter 3. The methodology for data integrity showed adequate accuracy, so it was applied to the data in all chapters. HyperOpt was able to calibrate food and feed crop models for sweet peppers. Therefore, the compared models in the final chapter were optimized using HyperOpt. DeepCrop was trained to simulate several growth factors with environment data. The trained DeepCrop was evaluated with unseen data, and it showed the highest modeling efficiency (=0.76) and the lowest normalized root mean squared error (=0.18) than the compared models. With the high adaptability of DeepCrop, it can be used for studies on various scales and purposes. Since all methods adequately solved the given tasks and underlay the DeepCrop development, the established protocol can be a high throughput for enhancing accessibility of crop models, resulting in unifying crop modeling studies.농업 시스템에서 발생하는 문제들은 작물과 환경의 상호작용 하에 복잡하게 얽혀 있다. 작물 모델링은 대상을 단순화하는 방법으로써, 농업에서 일어나는 현상을 추상화하고 해석하는 과정이다. 모델링을 통해 대상을 이해하는 것은 농업 분야의 학술적 및 사회적 결정을 지원할 수 있다. 지난 수년 간 절차 기반 작물 모델은 농업의 문제들을 해결하여 작물 생산성 및 품질을 증진시켰으며, 현재 작물 모델링에 남아있는 과제들은 다차원 정보를 다방향에서 분석할 수 있는 작물 모델을 필요로 하게 되었다. 이를 만족시킬 수 있는 지침으로써, 복잡한 농업적 과제들을 목표로 딥러닝 알고리즘이 도입되었다. 그러나, 이 알고리즘들은 낮은 데이터 완결성 및 높은 연구 다양성 때문에 기존의 작물 모델들을 대체하지는 못했다. 본 연구에서는 딥러닝 방법론을 이용하여 절차 기반 작물 모델을 구축하는 개발 프로토콜을 확립하였다. Literature Review에서는 딥러닝과 작물 모델에 대해 소개하고, 농업으로의 딥러닝 적용 연구가 많음에도 이 프로토콜이 필요한 이유를 설명하였다. 제1장과 2장에서는 국내 여러 지역의 데이터를 이용하여 전이 학습 및 U-Net 구조를 활용하여 딥러닝 모델 적용을 위한 기반을 마련하고, 베이지안 최적화 방법인 HyperOpt를 사용하여 기존 모델과 딥러닝 기반 모델을 비교하기 위해 시험적으로 WOFOST 작물 모델을 보정하는 등 모델 개발을 위한 기반 연구를 수행하였다. 마지막으로, 제3장에서는 주의 메커니즘 및 다중 작업 디코더를 가진 완전 심층 신경망 절차 기반 작물 모델인 DeepCrop을 수경재배 파프리카(Capsicum annuum var. annuum) 대상으로 개발하였다. 데이터 완결성을 위한 기술들은 적합한 정확도를 보여주었으며, 전체 챕터 데이터에 적용하였다. HyperOpt는 식량 및 사료 작물 모델들을 파프리카 대상으로 보정할 수 있었다. 따라서, 제3장의 비교 대상 모델들에 대해 HyperOpt를 사용하였다. DeepCrop은 환경 데이터를 이용하고 여러 생육 지표를 예측하도록 학습되었다. 학습에 사용하지 않은 데이터를 이용하여 학습된 DeepCrop를 평가하였으며, 이 때 비교 모델들 중 가장 높은 모형 효율(EF=0.76)과 가장 낮은 표준화 평균 제곱근 오차(NRMSE=0.18)를 보여주었다. DeepCrop은 높은 적용성을 기반으로 다양한 범위와 목적을 가진 연구에 사용될 수 있을 것이다. 모든 방법들이 주어진 작업을 적절히 풀어냈고 DeepCrop 개발의 근거가 되었으므로, 본 논문에서 확립한 프로토콜은 작물 모델의 접근성을 향상시킬 수 있는 획기적인 방향을 제시하였고, 작물 모델 연구의 통합에 기여할 수 있을 것으로 기대한다.LITERATURE REVIEW 1 ABSTRACT 1 BACKGROUND 3 REMARKABLE APPLICABILITY AND ACCESSIBILITY OF DEEP LEARNING 12 DEEP LEARNING APPLICATIONS FOR CROP PRODUCTION 17 THRESHOLDS TO APPLY DEEP LEARNING TO CROP MODELS 18 NECESSITY TO PRIORITIZE DEEP-LEARNING-BASED CROP MODELS 20 REQUIREMENTS OF THE DEEP-LEARNING-BASED CROP MODELS 21 OPENING REMARKS AND THESIS OBJECTIVES 22 LITERATURE CITED 23 Chapter 1 34 Chapter 1-1 35 ABSTRACT 35 INTRODUCTION 37 MATERIALS AND METHODS 40 RESULTS 50 DISCUSSION 59 CONCLUSION 63 LITERATURE CITED 64 Chapter 1-2 71 ABSTRACT 71 INTRODUCTION 73 MATERIALS AND METHODS 75 RESULTS 84 DISCUSSION 92 CONCLUSION 101 LITERATURE CITED 102 Chapter 2 108 ABSTRACT 108 NOMENCLATURE 110 INTRODUCTION 112 MATERIALS AND METHODS 115 RESULTS 124 DISCUSSION 133 CONCLUSION 137 LITERATURE CITED 138 Chapter 3 144 ABSTRACT 144 INTRODUCTION 146 MATERIALS AND METHODS 149 RESULTS 169 DISCUSSION 182 CONCLUSION 187 LITERATURE CITED 188 GENERAL DISCUSSION 196 GENERAL CONCLUSION 201 ABSTRACT IN KOREAN 203 APPENDIX 204박

On the use of context information for an improved application of data-based algorithms in condition monitoring

xi, 124 p.En el campo de la monitorización de la condición, los algoritmos basados en datos cuentan con un amplio recorrido. Desde el uso de los gráficos de control de calidad que se llevan empleando durante casi un siglo a técnicas de mayor complejidad como las redes neuronales o máquinas de soporte vectorial que se emplean para detección, diagnóstico y estimación de vida remanente de los equipos. Sin embargo, la puesta en producción de los algoritmos de monitorización requiere de un estudio exhaustivo de un factor que es a menudo obviado por otros trabajos de la literatura: el contexto. El contexto, que en este trabajo es considerado como el conjunto de factores que influencian la monitorización de un bien, tiene un gran impacto en la algoritmia de monitorización y su aplicación final. Por este motivo, es el objeto de estudio de esta tesis en la que se han analizado tres casos de uso. Se ha profundizado en sus respectivos contextos, tratando de generalizar a la problemática habitual en la monitorización de maquinaria industrial, y se ha abordado dicha problemática de monitorización de forma que solucionen el contexto en lugar de cada caso de uso. Así, el conocimiento adquirido durante el desarrollo de las soluciones puede ser transferido a otros casos de uso que cuenten con contextos similares

A Defense of Pure Connectionism

Connectionism is an approach to neural-networks-based cognitive modeling that encompasses the recent deep learning movement in artificial intelligence. It came of age in the 1980s, with its roots in cybernetics and earlier attempts to model the brain as a system of simple parallel processors. Connectionist models center on statistical inference within neural networks with empirically learnable parameters, which can be represented as graphical models. More recent approaches focus on learning and inference within hierarchical generative models. Contra influential and ongoing critiques, I argue in this dissertation that the connectionist approach to cognitive science possesses in principle (and, as is becoming increasingly clear, in practice) the resources to model even the most rich and distinctly human cognitive capacities, such as abstract, conceptual thought and natural language comprehension and production. Consonant with much previous philosophical work on connectionism, I argue that a core principle—that proximal representations in a vector space have similar semantic values—is the key to a successful connectionist account of the systematicity and productivity of thought, language, and other core cognitive phenomena. My work here differs from preceding work in philosophy in several respects: (1) I compare a wide variety of connectionist responses to the systematicity challenge and isolate two main strands that are both historically important and reflected in ongoing work today: (a) vector symbolic architectures and (b) (compositional) vector space semantic models; (2) I consider very recent applications of these approaches, including their deployment on large-scale machine learning tasks such as machine translation; (3) I argue, again on the basis mostly of recent developments, for a continuity in representation and processing across natural language, image processing and other domains; (4) I explicitly link broad, abstract features of connectionist representation to recent proposals in cognitive science similar in spirit, such as hierarchical Bayesian and free energy minimization approaches, and offer a single rebuttal of criticisms of these related paradigms; (5) I critique recent alternative proposals that argue for a hybrid Classical (i.e. serial symbolic)/statistical model of mind; (6) I argue that defending the most plausible form of a connectionist cognitive architecture requires rethinking certain distinctions that have figured prominently in the history of the philosophy of mind and language, such as that between word- and phrase-level semantic content, and between inference and association

Machine learning for the sustainable energy transition: a data-driven perspective along the value chain from manufacturing to energy conversion

According to the special report Global Warming of 1.5 °C of the IPCC, climate action is not only necessary but more than ever urgent. The world is witnessing rising sea levels, heat waves, events of flooding, droughts, and desertification resulting in the loss of lives and damage to livelihoods, especially in countries of the Global South. To mitigate climate change and commit to the Paris agreement, it is of the uttermost importance to reduce greenhouse gas emissions coming from the most emitting sector, namely the energy sector. To this end, large-scale penetration of renewable energy systems into the energy market is crucial for the energy transition toward a sustainable future by replacing fossil fuels and improving access to energy with socio-economic benefits. With the advent of Industry 4.0, Internet of Things technologies have been increasingly applied to the energy sector introducing the concept of smart grid or, more in general, Internet of Energy. These paradigms are steering the energy sector towards more efficient, reliable, flexible, resilient, safe, and sustainable solutions with huge environmental and social potential benefits. To realize these concepts, new information technologies are required, and among the most promising possibilities are Artificial Intelligence and Machine Learning which in many countries have already revolutionized the energy industry. This thesis presents different Machine Learning algorithms and methods for the implementation of new strategies to make renewable energy systems more efficient and reliable. It presents various learning algorithms, highlighting their advantages and limits, and evaluating their application for different tasks in the energy context. In addition, different techniques are presented for the preprocessing and cleaning of time series, nowadays collected by sensor networks mounted on every renewable energy system. With the possibility to install large numbers of sensors that collect vast amounts of time series, it is vital to detect and remove irrelevant, redundant, or noisy features, and alleviate the curse of dimensionality, thus improving the interpretability of predictive models, speeding up their learning process, and enhancing their generalization properties. Therefore, this thesis discussed the importance of dimensionality reduction in sensor networks mounted on renewable energy systems and, to this end, presents two novel unsupervised algorithms. The first approach maps time series in the network domain through visibility graphs and uses a community detection algorithm to identify clusters of similar time series and select representative parameters. This method can group both homogeneous and heterogeneous physical parameters, even when related to different functional areas of a system. The second approach proposes the Combined Predictive Power Score, a method for feature selection with a multivariate formulation that explores multiple sub-sets of expanding variables and identifies the combination of features with the highest predictive power over specified target variables. This method proposes a selection algorithm for the optimal combination of variables that converges to the smallest set of predictors with the highest predictive power. Once the combination of variables is identified, the most relevant parameters in a sensor network can be selected to perform dimensionality reduction. Data-driven methods open the possibility to support strategic decision-making, resulting in a reduction of Operation & Maintenance costs, machine faults, repair stops, and spare parts inventory size. Therefore, this thesis presents two approaches in the context of predictive maintenance to improve the lifetime and efficiency of the equipment, based on anomaly detection algorithms. The first approach proposes an anomaly detection model based on Principal Component Analysis that is robust to false alarms, can isolate anomalous conditions, and can anticipate equipment failures. The second approach has at its core a neural architecture, namely a Graph Convolutional Autoencoder, which models the sensor network as a dynamical functional graph by simultaneously considering the information content of individual sensor measurements (graph node features) and the nonlinear correlations existing between all pairs of sensors (graph edges). The proposed neural architecture can capture hidden anomalies even when the turbine continues to deliver the power requested by the grid and can anticipate equipment failures. Since the model is unsupervised and completely data-driven, this approach can be applied to any wind turbine equipped with a SCADA system. When it comes to renewable energies, the unschedulable uncertainty due to their intermittent nature represents an obstacle to the reliability and stability of energy grids, especially when dealing with large-scale integration. Nevertheless, these challenges can be alleviated if the natural sources or the power output of renewable energy systems can be forecasted accurately, allowing power system operators to plan optimal power management strategies to balance the dispatch between intermittent power generations and the load demand. To this end, this thesis proposes a multi-modal spatio-temporal neural network for multi-horizon wind power forecasting. In particular, the model combines high-resolution Numerical Weather Prediction forecast maps with turbine-level SCADA data and explores how meteorological variables on different spatial scales together with the turbines' internal operating conditions impact wind power forecasts. The world is undergoing a third energy transition with the main goal to tackle global climate change through decarbonization of the energy supply and consumption patterns. This is not only possible thanks to global cooperation and agreements between parties, power generation systems advancements, and Internet of Things and Artificial Intelligence technologies but also necessary to prevent the severe and irreversible consequences of climate change that are threatening life on the planet as we know it. This thesis is intended as a reference for researchers that want to contribute to the sustainable energy transition and are approaching the field of Artificial Intelligence in the context of renewable energy systems

NON-VERBAL COMMUNICATION WITH PHYSIOLOGICAL SENSORS. THE AESTHETIC DOMAIN OF WEARABLES AND NEURAL NETWORKS

Historically, communication implies the transfer of information between bodies, yet this phenomenon is constantly adapting to new technological and cultural standards. In a digital context, it’s commonplace to envision systems that revolve around verbal modalities. However, behavioural analysis grounded in psychology research calls attention to the emotional information disclosed by non-verbal social cues, in particular, actions that are involuntary. This notion has circulated heavily into various interdisciplinary computing research fields, from which multiple studies have arisen, correlating non-verbal activity to socio-affective inferences. These are often derived from some form of motion capture and other wearable sensors, measuring the ‘invisible’ bioelectrical changes that occur from inside the body. This thesis proposes a motivation and methodology for using physiological sensory data as an expressive resource for technology-mediated interactions. Initialised from a thorough discussion on state-of-the-art technologies and established design principles regarding this topic, then applied to a novel approach alongside a selection of practice works to compliment this. We advocate for aesthetic experience, experimenting with abstract representations. Atypically from prevailing Affective Computing systems, the intention is not to infer or classify emotion but rather to create new opportunities for rich gestural exchange, unconfined to the verbal domain. Given the preliminary proposition of non-representation, we justify a correspondence with modern Machine Learning and multimedia interaction strategies, applying an iterative, human-centred approach to improve personalisation without the compromising emotional potential of bodily gesture. Where related studies in the past have successfully provoked strong design concepts through innovative fabrications, these are typically limited to simple linear, one-to-one mappings and often neglect multi-user environments; we foresee a vast potential. In our use cases, we adopt neural network architectures to generate highly granular biofeedback from low-dimensional input data. We present the following proof-of-concepts: Breathing Correspondence, a wearable biofeedback system inspired by Somaesthetic design principles; Latent Steps, a real-time auto-encoder to represent bodily experiences from sensor data, designed for dance performance; and Anti-Social Distancing Ensemble, an installation for public space interventions, analysing physical distance to generate a collective soundscape. Key findings are extracted from the individual reports to formulate an extensive technical and theoretical framework around this topic. The projects first aim to embrace some alternative perspectives already established within Affective Computing research. From here, these concepts evolve deeper, bridging theories from contemporary creative and technical practices with the advancement of biomedical technologies.Historicamente, os processos de comunicação implicam a transferência de informação entre organismos, mas este fenómeno está constantemente a adaptar-se a novos padrões tecnológicos e culturais. Num contexto digital, é comum encontrar sistemas que giram em torno de modalidades verbais. Contudo, a análise comportamental fundamentada na investigação psicológica chama a atenção para a informação emocional revelada por sinais sociais não verbais, em particular, acções que são involuntárias. Esta noção circulou fortemente em vários campos interdisciplinares de investigação na área das ciências da computação, dos quais surgiram múltiplos estudos, correlacionando a actividade nãoverbal com inferências sócio-afectivas. Estes são frequentemente derivados de alguma forma de captura de movimento e sensores “wearable”, medindo as alterações bioeléctricas “invisíveis” que ocorrem no interior do corpo. Nesta tese, propomos uma motivação e metodologia para a utilização de dados sensoriais fisiológicos como um recurso expressivo para interacções mediadas pela tecnologia. Iniciada a partir de uma discussão aprofundada sobre tecnologias de ponta e princípios de concepção estabelecidos relativamente a este tópico, depois aplicada a uma nova abordagem, juntamente com uma selecção de trabalhos práticos, para complementar esta. Defendemos a experiência estética, experimentando com representações abstractas. Contrariamente aos sistemas de Computação Afectiva predominantes, a intenção não é inferir ou classificar a emoção, mas sim criar novas oportunidades para uma rica troca gestual, não confinada ao domínio verbal. Dada a proposta preliminar de não representação, justificamos uma correspondência com estratégias modernas de Machine Learning e interacção multimédia, aplicando uma abordagem iterativa e centrada no ser humano para melhorar a personalização sem o potencial emocional comprometedor do gesto corporal. Nos casos em que estudos anteriores demonstraram com sucesso conceitos de design fortes através de fabricações inovadoras, estes limitam-se tipicamente a simples mapeamentos lineares, um-para-um, e muitas vezes negligenciam ambientes multi-utilizadores; com este trabalho, prevemos um potencial alargado. Nos nossos casos de utilização, adoptamos arquitecturas de redes neurais para gerar biofeedback altamente granular a partir de dados de entrada de baixa dimensão. Apresentamos as seguintes provas de conceitos: Breathing Correspondence, um sistema de biofeedback wearable inspirado nos princípios de design somaestético; Latent Steps, um modelo autoencoder em tempo real para representar experiências corporais a partir de dados de sensores, concebido para desempenho de dança; e Anti-Social Distancing Ensemble, uma instalação para intervenções no espaço público, analisando a distância física para gerar uma paisagem sonora colectiva. Os principais resultados são extraídos dos relatórios individuais, para formular um quadro técnico e teórico alargado para expandir sobre este tópico. Os projectos têm como primeiro objectivo abraçar algumas perspectivas alternativas às que já estão estabelecidas no âmbito da investigação da Computação Afectiva. A partir daqui, estes conceitos evoluem mais profundamente, fazendo a ponte entre as teorias das práticas criativas e técnicas contemporâneas com o avanço das tecnologias biomédicas