A Computação Gráfica, área em franco desenvolvimento, têm caminhado em busca da geração, cada vez mais rápida, de imagens mais realísticas. Os algoritmos que permitem a síntese de imagens realísticas demandam alto poder computacional, fazendo com que a geração deste tipo de imagem, de forma rápida, requeira o uso de computadores paralelos. Hoje, a técnica que permite gerar as imagens mais realísticas é o "ray tracing" . Os multicomputadores, por sua vez, são a arquitetura de computadores paralelos mais promissora na busca do desempenho computacional necessário às aplicações modernas. Esta dissertação aborda o problema da implementação do algoritmo de "ray tracing" em multicomputadores. A paralelização desta técnica para uso em computadores paralelos de memória distribuída pode ser feita de muitas formas diferentes, sempre envolvendo um compromisso entre a velocidade de processamento e a memória utilizada. Neste trabalho conceitua-se este problema e introduz-se ferramentas para a avaliação de soluções que levam em consideração a eficiência de processamento e a redundância no uso de memória. Também é apresentada uma nova taxonomia que, além de permitir a classificação de propostas para implementações de "ray tracing" paralelo, orienta a procura de novas soluções para este problema. O desempenho das soluções em cada classe desta taxonomia é avaliado qualitativamente. Por fim, são sugeridas novas alternativas de paralelização do algoritmo de "ray tracing" em multicomputadores. / Computer Graphics is headed today towards the synthesis of more realistic images, in less time. The algorithms used for realistic image synthesis demand high computer power, so that the synthesis of this kind of image, in short periods of time, requires the use of parallel computers. Nowadays, the technique that yields the most realistic images is ray tracing. On its turn, multicomputers are the most promising parallel architecture for reaching the performance needed in modern applications. This dissertation is on the problem of implementing the ray tracing algorithm on multicomputers. The parallelization of this technique on distributed memory parallel computers can take several forms, always involving a compromise between speed and memory. In this work, this problem is conceptualized and tools for evaluation of solutions that account for efficiency and redundancy, are introduced. It is also presented a new taxonomy that can be used for both the classification of parallel ray tracing proposals and for driving the search of new solutions to this problem. The performances of entries in each class of the taxonomy are qualitatively assessed. New alternatives for parallelizing the ray tracing algorithm on multicomputers, are suggested.

Optical components made of anisotropic materials, such as crystal polarizers and crystal waveplates, are widely used in many complex optical system, such as display systems, microlithography, biomedical imaging and many other optical systems, and induce more complex aberrations than optical components made of isotropic materials. The goal of this dissertation is to accurately simulate the performance of optical systems with anisotropic materials using polarization ray trace. This work extends the polarization ray tracing calculus to incorporate ray tracing through anisotropic materials, including uniaxial, biaxial and optically active materials. The 3D polarization ray tracing calculus is an invaluable tool for analyzing polarization properties of an optical system. The 3×3 polarization ray tracing P matrix developed for anisotropic ray trace assists tracking the 3D polarization transformations along a ray path with series of surfaces in an optical system. To better represent the anisotropic light-matter interactions, the definition of the P matrix is generalized to incorporate not only the polarization change at a refraction/reflection interface, but also the induced optical phase accumulation as light propagates through the anisotropic medium. This enables realistic modeling of crystalline polarization elements, such as crystal waveplates and crystal polarizers. The wavefront and polarization aberrations of these anisotropic components are more complex than those of isotropic optical components and can be evaluated from the resultant P matrix for each eigen-wavefront as well as for the overall image. One incident ray refracting or reflecting into an anisotropic medium produces two eigenpolarizations or eigenmodes propagating in different directions. The associated ray parameters of these modes necessary for the anisotropic ray trace are described in Chapter 2. The algorithms to calculate the P matrix from these ray parameters are described in Chapter 3 for anisotropic ray tracing. This P matrix has the following characteristics: (1) Multiple P matrices are calculated to describe the polarization of the multiple eigenmodes at an anisotropic intercept. (2) Each P matrix maps the orthogonal incident basis vectors (Ê_m, Ê_n, Ŝ) before the optical interface into three orthogonal exiting vectors (a_m Ê'_m, a_n Ê'_n, Ŝ') after the interface, where a_m and a_n are the complex amplitude coefficients induced at the intercept. The ray tracing algorithms described in this dissertation handle three types of uncoated anisotropic interfaces isotropic/anisotropic, anisotropic/isotropic and anisotropic/anisotropic interfaces. (3) The cumulative P matrix associated with multiple surface interactions is calculated by multiplying individual P matrices in the order along the ray path. Many optical components utilize anisotropic materials to induce desired retardance. This important mechanism is modeled as the optical phase associated with propagation. (4) The optical path length OPL of an eigenpolarization along an anisotropic ray path is incorporated into the calculation of each P matrix. Chapter 4 presents the data reduction of the P matrix of a crystal waveplate. The diattenuation is embedded in the singular values of P. The retardance is divided into two parts: (A) The physical retardance induced by OPLs and surface interactions, and (B) the geometrical transformation induced by geometry of a ray path, which is calculated by the geometrical transform Q matrix. The Q matrix of an anisotropic intercept is derived from the generalization of s- and p-bases at the anisotropic intercept; the p basis is not confined to the plane of incidence due to the anisotropic refraction or reflection. Chapter 5 shows how the multiple P matrices associated with the eigenmodes resulting from propagation through multiple anisotropic surfaces can be combined into one P matrix when the multiple modes interfere in their overlapping regions. The resultant P matrix contains diattenuation induced at each surface interaction as well as the retardance due to ray propagation and total internal reflections. The polarization aberrations of crystal waveplates and crystal polarizers are studied in Chapter 6 and Chapter 7. A wavefront simulated by a grid of rays is traced through the anisotropic system and the resultant grid of rays is analyzed. The analysis is complicated by the ray doubling effects and the partially overlapping eigen-wavefronts propagating in various directions. The wavefront and polarization aberrations of each eigenmode can be evaluated from the electric field distributions. The overall polarization at the plane of interest or the image quality at the image plane are affected by each of these eigen-wavefronts. Isotropic materials become anisotropic due to stress, strain, or applied electric or magnetic fields. In Chapter 8, the P matrix for anisotropic materials is extended to ray tracing in stress birefringent materials which are treated as spatially varying anisotropic materials. Such simulations can predict the spatial retardance variation throughout the stressed optical component and its effects on the point spread function and modulation transfer function for different incident polarizations. The anisotropic extension of the P matrix also applies to other anisotropic optical components, such as anisotropic diffractive optical elements and anisotropic thin films. It systematically keeps track of polarization transformation in 3D global Cartesian coordinates of a ray propagating through series of anisotropic and isotropic optical components with arbitrary orientations. The polarization ray tracing calculus with this generalized P matrix provides a powerful tool for optical ray trace and allows comprehensive analysis of complex optical system.

En metod för att simulera exteriört bussljud med hjälp utav Ray Tracing har testats och utvärderats. En modell av en buss har byggts upp i ett CAD program. Dominerande ljudkällor i bussen samt materialkoefficienter har tagits fram för de material som ingår i bussen. Bussen har sedan förts in i simuleringsprogrammet Odeon, där ett antal simuleringar har utförts. Olika pass-by simulering har utförts och jämförts med mätningar. Olika grader inkapsling av motorrummet har simulerats. Ett grid response har tagits fram för att se vart det lönar sig att placera absorbenter. Ett beräkningsfel har hittats i den använda programvaran Odeon 10.13 vilket ledde till att en jämförelse mellan Odeon 10.13 och demoversionen av Odeon 12. Resultatet visar att simuleringsmetoden i dagsläget fungerar bäst då ingen ljudtransmission tas hänsyn till, detta kräver dock att det finns öppningar i bussen eftersom detta annars leder till ett antal problem ifall bussen simuleras med alltför hög grad av inkapsling. Inga strålar skulle i detta fall kunna nå någon mottagare. Anledningen till att transmissionen inte kan tas i hänsyn beror på de fel som hittats i Odeon 10.13. Programmet räknar fel och överskattar transmissionen samt transmitterar strålar även i de fall där en yta är definierad att inte transmittera några strålar alls, något som Odeon 12 räknar rätt på. Metoden kan tills detta är löst med fördel användas för att se energifördelning mellan frekvensbanden, optimal placering av absorbenter samt i viss mån även den totala ljudnivån för bussen. / A method to simulate exterior bus sound with the help of ray tracing has been tested and evaluated. To do this a model of a bus has been built up using CAD software. Dominant noise sources in the bus and material coefficients for the materials included in the bus have been researched. The bus has been imported into the simulation program Odeon where a number of simulations have been performed. Different pass-by simulations have been performed and compared with physical measurements. Different degrees of encapsulation of the engine compartment have been simulated. A grid response has been formulated to optimize the positioning of the absorbers. A calculation error has been found in release 10.13 of the Odeon Software which led to a comparison between Odeon 10.13 and a demonstration version of Odeon 12. The results show that the simulation method in its current state performs best when no sound transmission is taken into account. This requires that there are openings in the bus as problems will arise if the bus is simulated with too high a level of encapsulation. Theoretically, no rays would in this case be able to reach any receiver outside the engine compartment. The reason that the transmission loss cannot be taken into account depends on the errors found in Odeon 10.13. The software incorrectly overestimates the sound transmission and transmits rays even in cases where an area is defined to not transmit any rays at all, something that Odeon 12 calculates correctly. Until this is resolved, the simulation method can be used to estimate the energy distribution between the octave bands, the optimal placement of absorbers and to some extent the overall sound level of the bus.

Este trabalho apresenta uma proposta de aplicação da técnica de ray-tracing bidirecional em ambientes esféricos, contendo fontes luminosas puntiformes. Trata-se de um trabalho que discorre no contexto da área de Síntese de Imagens Realísticas dentro da Computação Gráfica. O trabalho tem como principal contribuição a definição e o desenvolvimento de uma técnica para simular o fenômeno físico de refração da luz proveniente das fontes luminosas puntiformes da cena. A Síntese de Imagens Realísticas é uma das principais áreas de aplicação e pesquisa da Computação Gráfica. Uma imagem realística é uma imagem que incorpora os efeitos da luz que interage com objetos fisicamente reais. A dificuldade fundamental para a síntese de imagens realísticas se encontra na complexidade do mundo real, que apresenta uma infinidade de graduações de cores, texturas, reflexões, sombras, etc. Para a criação destas imagens realísticas, percorre-se um grande número de estágios, englobando métodos de modelagem, definição da posição de visualização, remoção de elementos ocultos, efeitos de reflexão e refração, e assim por diante. O trabalho está organizado da seguinte forma. Inicialmente, faz-se um estudo aprofundado da Óptica, área da Física que estuda o comportamento da luz no mundo real. A seguir, são apresentados algoritmos que simulam este comportamento da luz, enfatizando-se o algoritmo de rastreamento de raios (ray-tracing). Discute-se a seguir os principais problemas relacionados a simulação de objetos transparentes na Computação Gráfica. Então, uma proposta para a simulação em ambientes esféricos da refração da luz que provem diretamente das fontes luminosas puntiformes da cena a apresentada. Esta proposta baseia-se na utilização do algoritmo de rastreamento bidirecional de raios. O algoritmo apresentado é composto de duas fases. Na primeira etapa, são geradas as fontes secundarias de luz. Na segunda etapa, utiliza-se a informação obtida na primeira etapa para simular a refração da luz que provem diretamente das fontes luminosas da cena. As fontes secundarias de luz tem sua origem na utilização dos objetos esféricos transparentes como lentes esféricas convergentes. A fonte luminosa secundaria localiza-se no ponto imagem da lente, considerando-se como ponto objeto a fonte luminosa puntiforme original. A localização da fonte luminosa secundaria é obtida através da equação dos pontos conjugados. Também armazena-se uma informação relacionada com a área de atuação da fonte luminosa secundaria (angulo de espalhamento). 0 angulo de espalhamento é essencial para que, na segunda fase do algoritmo, seja possível identificar se o ponto atual é iluminado ou não pela fonte secundaria em questão. Finalizando, são geradas imagens tanto no protótipo implementado quanto em um algoritmo de ray-tracing convencional. Os resultados obtidos são comparados em nível de realismo e tempo de execução. / This work presents a proposal of using the bidirectional ray tracing method in spherical modeling environments containing punctual light sources. This project was developed within the field of Computer Graphics, more precisely in the area of synthesis of realistic images. The main contribution of this work is the definition and the development of a method that simulates the light refraction proceeding from localized light sources in the scene. The synthesis of realistic images is one of the main areas of application and research in Computer Graphics. A realistic image is an image that contains light effects interacting with physically real objects. The major difficulty for rendering realistic images is the complexity of the real world, with several color graduations, textures, reflections, shadows, etc. For this rendering, many steps like modeling methods, definition of visualization position, hidden-surface algorithms, reflection and refraction effects, and so forth, are developed. At first, this work presents a study about Optics, the area of Physics that studies the behaviour of light in the real world. In sequence, algorithms that simulate that behaviour are presented, with special attention to ray tracing method. After that, the principal problems of the simulation of transparency in Computer Graphics are discussed. So, a proposal for simulation of the light refraction proceeding from light source in spherical modeling environment, is presented. This proposal is based on use of the bidirectional ray tracing algorithm. This algorithm is divided in two main stages. In the first stage, the secondary light sources are generated. In the second stage, the information about the secondary light sources is utilized to simulate the light refraction directly proceeding from light sources of the scene. The secondary light sources are originated from transparent spherical objects like convergent spherical lenses. The position of the secondary light source is the image point of the lens, corresponding to punctual light source like object point. The position of the secondary light source is calculated by the equation of the conjugated points. Also the information about the scattering angle of the secondary light source is stored. The scattering angle is essential, in first stage of algorithm, to establish if the current point is illuminated by any secondary light source. Finally, images are generated both in the implemented prototype as in conventional ray tracing. The final results of this work are evaluated based on realism and runtime.

Este trabalho apresenta uma proposta de aplicação da técnica de ray-tracing bidirecional em ambientes esféricos, contendo fontes luminosas puntiformes. Trata-se de um trabalho que discorre no contexto da área de Síntese de Imagens Realísticas dentro da Computação Gráfica. O trabalho tem como principal contribuição a definição e o desenvolvimento de uma técnica para simular o fenômeno físico de refração da luz proveniente das fontes luminosas puntiformes da cena. A Síntese de Imagens Realísticas é uma das principais áreas de aplicação e pesquisa da Computação Gráfica. Uma imagem realística é uma imagem que incorpora os efeitos da luz que interage com objetos fisicamente reais. A dificuldade fundamental para a síntese de imagens realísticas se encontra na complexidade do mundo real, que apresenta uma infinidade de graduações de cores, texturas, reflexões, sombras, etc. Para a criação destas imagens realísticas, percorre-se um grande número de estágios, englobando métodos de modelagem, definição da posição de visualização, remoção de elementos ocultos, efeitos de reflexão e refração, e assim por diante. O trabalho está organizado da seguinte forma. Inicialmente, faz-se um estudo aprofundado da Óptica, área da Física que estuda o comportamento da luz no mundo real. A seguir, são apresentados algoritmos que simulam este comportamento da luz, enfatizando-se o algoritmo de rastreamento de raios (ray-tracing). Discute-se a seguir os principais problemas relacionados a simulação de objetos transparentes na Computação Gráfica. Então, uma proposta para a simulação em ambientes esféricos da refração da luz que provem diretamente das fontes luminosas puntiformes da cena a apresentada. Esta proposta baseia-se na utilização do algoritmo de rastreamento bidirecional de raios. O algoritmo apresentado é composto de duas fases. Na primeira etapa, são geradas as fontes secundarias de luz. Na segunda etapa, utiliza-se a informação obtida na primeira etapa para simular a refração da luz que provem diretamente das fontes luminosas da cena. As fontes secundarias de luz tem sua origem na utilização dos objetos esféricos transparentes como lentes esféricas convergentes. A fonte luminosa secundaria localiza-se no ponto imagem da lente, considerando-se como ponto objeto a fonte luminosa puntiforme original. A localização da fonte luminosa secundaria é obtida através da equação dos pontos conjugados. Também armazena-se uma informação relacionada com a área de atuação da fonte luminosa secundaria (angulo de espalhamento). 0 angulo de espalhamento é essencial para que, na segunda fase do algoritmo, seja possível identificar se o ponto atual é iluminado ou não pela fonte secundaria em questão. Finalizando, são geradas imagens tanto no protótipo implementado quanto em um algoritmo de ray-tracing convencional. Os resultados obtidos são comparados em nível de realismo e tempo de execução. / This work presents a proposal of using the bidirectional ray tracing method in spherical modeling environments containing punctual light sources. This project was developed within the field of Computer Graphics, more precisely in the area of synthesis of realistic images. The main contribution of this work is the definition and the development of a method that simulates the light refraction proceeding from localized light sources in the scene. The synthesis of realistic images is one of the main areas of application and research in Computer Graphics. A realistic image is an image that contains light effects interacting with physically real objects. The major difficulty for rendering realistic images is the complexity of the real world, with several color graduations, textures, reflections, shadows, etc. For this rendering, many steps like modeling methods, definition of visualization position, hidden-surface algorithms, reflection and refraction effects, and so forth, are developed. At first, this work presents a study about Optics, the area of Physics that studies the behaviour of light in the real world. In sequence, algorithms that simulate that behaviour are presented, with special attention to ray tracing method. After that, the principal problems of the simulation of transparency in Computer Graphics are discussed. So, a proposal for simulation of the light refraction proceeding from light source in spherical modeling environment, is presented. This proposal is based on use of the bidirectional ray tracing algorithm. This algorithm is divided in two main stages. In the first stage, the secondary light sources are generated. In the second stage, the information about the secondary light sources is utilized to simulate the light refraction directly proceeding from light sources of the scene. The secondary light sources are originated from transparent spherical objects like convergent spherical lenses. The position of the secondary light source is the image point of the lens, corresponding to punctual light source like object point. The position of the secondary light source is calculated by the equation of the conjugated points. Also the information about the scattering angle of the secondary light source is stored. The scattering angle is essential, in first stage of algorithm, to establish if the current point is illuminated by any secondary light source. Finally, images are generated both in the implemented prototype as in conventional ray tracing. The final results of this work are evaluated based on realism and runtime.

Este trabalho apresenta uma proposta de aplicação da técnica de ray-tracing bidirecional em ambientes esféricos, contendo fontes luminosas puntiformes. Trata-se de um trabalho que discorre no contexto da área de Síntese de Imagens Realísticas dentro da Computação Gráfica. O trabalho tem como principal contribuição a definição e o desenvolvimento de uma técnica para simular o fenômeno físico de refração da luz proveniente das fontes luminosas puntiformes da cena. A Síntese de Imagens Realísticas é uma das principais áreas de aplicação e pesquisa da Computação Gráfica. Uma imagem realística é uma imagem que incorpora os efeitos da luz que interage com objetos fisicamente reais. A dificuldade fundamental para a síntese de imagens realísticas se encontra na complexidade do mundo real, que apresenta uma infinidade de graduações de cores, texturas, reflexões, sombras, etc. Para a criação destas imagens realísticas, percorre-se um grande número de estágios, englobando métodos de modelagem, definição da posição de visualização, remoção de elementos ocultos, efeitos de reflexão e refração, e assim por diante. O trabalho está organizado da seguinte forma. Inicialmente, faz-se um estudo aprofundado da Óptica, área da Física que estuda o comportamento da luz no mundo real. A seguir, são apresentados algoritmos que simulam este comportamento da luz, enfatizando-se o algoritmo de rastreamento de raios (ray-tracing). Discute-se a seguir os principais problemas relacionados a simulação de objetos transparentes na Computação Gráfica. Então, uma proposta para a simulação em ambientes esféricos da refração da luz que provem diretamente das fontes luminosas puntiformes da cena a apresentada. Esta proposta baseia-se na utilização do algoritmo de rastreamento bidirecional de raios. O algoritmo apresentado é composto de duas fases. Na primeira etapa, são geradas as fontes secundarias de luz. Na segunda etapa, utiliza-se a informação obtida na primeira etapa para simular a refração da luz que provem diretamente das fontes luminosas da cena. As fontes secundarias de luz tem sua origem na utilização dos objetos esféricos transparentes como lentes esféricas convergentes. A fonte luminosa secundaria localiza-se no ponto imagem da lente, considerando-se como ponto objeto a fonte luminosa puntiforme original. A localização da fonte luminosa secundaria é obtida através da equação dos pontos conjugados. Também armazena-se uma informação relacionada com a área de atuação da fonte luminosa secundaria (angulo de espalhamento). 0 angulo de espalhamento é essencial para que, na segunda fase do algoritmo, seja possível identificar se o ponto atual é iluminado ou não pela fonte secundaria em questão. Finalizando, são geradas imagens tanto no protótipo implementado quanto em um algoritmo de ray-tracing convencional. Os resultados obtidos são comparados em nível de realismo e tempo de execução. / This work presents a proposal of using the bidirectional ray tracing method in spherical modeling environments containing punctual light sources. This project was developed within the field of Computer Graphics, more precisely in the area of synthesis of realistic images. The main contribution of this work is the definition and the development of a method that simulates the light refraction proceeding from localized light sources in the scene. The synthesis of realistic images is one of the main areas of application and research in Computer Graphics. A realistic image is an image that contains light effects interacting with physically real objects. The major difficulty for rendering realistic images is the complexity of the real world, with several color graduations, textures, reflections, shadows, etc. For this rendering, many steps like modeling methods, definition of visualization position, hidden-surface algorithms, reflection and refraction effects, and so forth, are developed. At first, this work presents a study about Optics, the area of Physics that studies the behaviour of light in the real world. In sequence, algorithms that simulate that behaviour are presented, with special attention to ray tracing method. After that, the principal problems of the simulation of transparency in Computer Graphics are discussed. So, a proposal for simulation of the light refraction proceeding from light source in spherical modeling environment, is presented. This proposal is based on use of the bidirectional ray tracing algorithm. This algorithm is divided in two main stages. In the first stage, the secondary light sources are generated. In the second stage, the information about the secondary light sources is utilized to simulate the light refraction directly proceeding from light sources of the scene. The secondary light sources are originated from transparent spherical objects like convergent spherical lenses. The position of the secondary light source is the image point of the lens, corresponding to punctual light source like object point. The position of the secondary light source is calculated by the equation of the conjugated points. Also the information about the scattering angle of the secondary light source is stored. The scattering angle is essential, in first stage of algorithm, to establish if the current point is illuminated by any secondary light source. Finally, images are generated both in the implemented prototype as in conventional ray tracing. The final results of this work are evaluated based on realism and runtime.

This master thesis focuses on application of tracking and tracing technologies in the tobacco industry. As per Directive 2014/40/EU, overall trackability and traceability will be an obligation for all unit packs of tobacco products. The reason for this is the fight against the black market. The thesis analyses the current track and trace technologies, evaluates the important points of the Directive and describes tobacco market specifications. The core is to propose a specific technology for this objective and to summarise essential features of the system. In addition, a technology called Codentify is described in detail, as it has the potential to fulfil the legislative demands.

A Monte Carlo light transport simulation is used in scattering-aware color 3D printing pipeline (Elek et al. [2017], Sumin et al. [2019]) to drive an iterative optimization loop. Its purpose is to find a material arrangement that yields the closest match in terms of surface appearance towards a target. As the light transport prediction takes up about 90% of the time it poses a significant bottleneck towards a practical application of this technology. The dense volumetric textures also require a lot of memory. Explicitly simulating every light interaction is particularly challenging in the setting of 3D printouts due to the heterogeneity, high density and high albedo of the media. In this thesis, we explore existing volumetric rendering techniques (Křivánek et al. [2014], Herholz et al. [2019]) and finally engineer a customized estimator for our setting, improving the performance considerably. Additionally, we investigate various storage solutions for the volumetric data and successfully reduce the memory footprint. All the algorithms are available in the form of Mitsuba renderer plugins.

Traditionally, when debugging a software system, developers rely on having access to the input data that caused the error. However, with data privacy concerns on the rise, it is becoming increasingly challenging to rely on input data as it might be sensitive or even classified. Telemetry is a method of collecting information about a system that can offer assistance. This thesis proposes a telemetry solution for debugging systems where input data is sensitive. The telemetry solution was implemented in a geographical 3D visualization system and evaluated based on two aspects: its effectiveness in assisting the developers working on the system to locate if and where a problem has occurred, and its ability to deduce the input data that generated the output. The results indicate that the telemetry solution is successful in helping developers identify system errors. Additionally, the system's privacy is maintained, as it is not feasible to directly ascertain the input data responsible from the output. However, no proof is presented and as such, no guarantee can be made. We conclude that telemetry can be a useful tool for developers, making the debugging process more effective while protecting sensitive input data. However, this might not be the case for different customers or systems. The thesis demonstrates the potential of using telemetry for debugging privacy-sensitive systems, with a proof-of-concept solution that can be improved upon in the future.

Das Glioblastom (GBM) repräsentiert den am schwierigsten zu behandelnden primären soliden Tumor des Zentralnervensystems dar, trotz der intensiv wachsenden Zahl von Studien zu seinen molekularen und zellulären Eigenschaften. Obwohl die GBM-Therapie aggressiv ist und chirurgische Resektion, Strahlentherapie und Chemotherapie umfasst, ist ein Wiederauftreten des Tumors unvermeidlich. Die GBM-Behandlungsresistenz ist mit genetischer und zellulärer Heterogenität sowie phänotypischer Plastizität verbunden. Um das Verständnis der Heterogenität des Glioblastoms zu vertiefen, haben wir maßgeschneiderte genetische Tracing-Strategien für subtypspezifische Transkriptionszustände aus Glioblastom-Patientensignaturen entwickelt. In GBM-Zellen ermöglichte uns unsere neuartige Technologie, intrinsische und nicht-zellautonome Bestimmungsfaktoren von Zellzuständen zu identifizieren. In vitro und in vivo konnten wir zeigen, dass sich der mesenchymale GBM-Subtyp als adaptive Identität in Gegenwart von Mikroumgebungssignalen ausbildet und durch Entzündungs- und Differenzierungsprogramme reguliert wird. Wir haben gezeigt, dass die Ausbildung eines mesenchymalen Zellzustand adaptiv und reversibel ist und durch verschiedene Auslöser wie externer Signaltransduktion und ionisierende Strahlung mit teilweise überlappenden transkriptionellen Signaturen eingenommen werden kann. Insbesondere konnten wir mithilfe synthetischer Locus-Kontrollregionen (sLCRs) eine Interaktion zwischen Zellen des angeborenen Immunsystems und Glioma-Zellen aufdecken, wodurch die Tumorzellen in einen mesenchymalen Zustand versetzt wurden, der mit einer erhöhten Resistenz gegen Chemotherapie verbunden ist. Hier bauen wir auf diesem innovativen Ansatz auf, um Übergänge von Zellzuständen in komplexen biologischen Umgebungen zu verfolgen, mit einem Schwerpunkt auf der zellulären Wechselwirkung zwischen gesunden und Tumorzellen im Zusammenhang mit phänotypischer Plastizität und therapeutischer Resistenz. Darüber hinaus bietet diese Methode ein breites translationales Potenzial für die Anwendung auf andere Forschungsgebiete, einschließlich der Entwicklungsbiologie oder der regenerativen Medizin. / Glioblastoma (GBM) remains the most difficult primary solid tumor of the central nervous system despite the intensively growing body of research on its molecular and cellular characteristics. Whereas GBM treatment is aggressive and involves surgical resection, radiotherapy, and chemotherapy, tumor recurrence is unavoidable. GBM treatment resistance is associated with genetic and cellular heterogeneity, as well as phenotypic plasticity. To improve understanding of Glioblastoma heterogeneity, we developed custom genetic tracing strategies for subtype-specific transcriptional states from Glioblastoma patient signatures. In GBM cells, our novel technology enabled us to identify intrinsic and non-cell autonomous determinants of cell fate commitment. In vitro and in vivo, we discovered that the mesenchymal GBM adapts in the presence of microenvironmental signaling and is regulated by inflammatory and differentiation programs. We demonstrated that cell fate commitment towards a mesenchymal state is adaptive and reversible and occurs through partially overlapping transcriptional responses, including external signaling and ionizing radiation. Importantly, using synthetic locus control regions (sLCRs), we were able to uncover crosstalk between innate immune cells and glioma-initiating cells, directing the tumor cells into a mesenchymal state linked to increased resistance to chemotherapy. Here, we build on this innovative approach to trace cell fate transitions in complex biological settings, with a focus on the cellular crosstalk between malignant and non-tumor cells in the context of phenotypic plasticity and therapeutic resistance. Beyond that, this method offers the broad translational potential to be applied to other fields of research, including developmental biology or regenerative medicine.