Automatic Cage Construction for Retargeted Muscle Fitting

The animation of realistic characters necessitates the construction of complicated anatomical structures such as muscles, which allow subtle shape variation of the character's outer surface to be displayed believably. Unfortunately despite numerous efforts, the modelling of muscle structures is still left for an animator who has to painstakingly build up piece by piece, making it a very tedious process. What is even more frustrating is the animator has to build the same muscle structure for every new character. We propose a muscle retargeting technique to help an animator to automatically construct a muscle structure by reusing an already built and tested model (the template model). Our method defines a spatial transfer between the template model and a new model based on the skin surface and the rigging structure. To ensure that the retargeted muscle is tightly packed inside a new character, we define a novel spatial optimization based on spherical parameterization. Our method requires no manual input, meaning that an animator does not require anatomical knowledge to create realistic accurate musculature models

Skeleton based cage generation guided by harmonic fields

International audienceWe propose a novel user-assisted cage generation tool. We start from a digital character and its skeleton, and create a coarse control cage for its animation. Our method requires minimal interaction to select bending points on the skeleton, and computes the corresponding cage automatically. The key contribution is a volumetric field defined in the interior of the character and embedding the skeleton. The integral lines of such field are used to propagate cutting surfaces from the interior of the character to its skin, and allow us to robustly trace non-planar cross sections that adapt to the local shape of the character. Our method overcomes previous approaches that rely on the popular (but tedious and limiting) cutting planes. We validated our software on a variety of digital characters. Our final cages are coarse yet entirely compliant with the structure induced by the underlying skeleton, enriched with the semantics provided by the bending points selected by the user. Automatic placement of bending nodes for a fully automatic caging pipeline is also supported

A Framework for the Semantics-aware Modelling of Objects

The evolution of 3D visual content calls for innovative methods for modelling shapes based on their intended usage, function and role in a complex scenario. Even if different attempts have been done in this direction, shape modelling still mainly focuses on geometry. However, 3D models have a structure, given by the arrangement of salient parts, and shape and structure are deeply related to semantics and functionality. Changing geometry without semantic clues may invalidate such functionalities or the meaning of objects or their parts. We approach the problem by considering semantics as the formalised knowledge related to a category of objects; the geometry can vary provided that the semantics is preserved. We represent the semantics and the variable geometry of a class of shapes through the parametric template: an annotated 3D model whose geometry can be deformed provided that some semantic constraints remain satisfied. In this work, we design and develop a framework for the semantics-aware modelling of shapes, offering the user a single application environment where the whole workflow of defining the parametric template and applying semantics-aware deformations can take place. In particular, the system provides tools for the selection and annotation of geometry based on a formalised contextual knowledge; shape analysis methods to derive new knowledge implicitly encoded in the geometry, and possibly enrich the given semantics; a set of constraints that the user can apply to salient parts and a deformation operation that takes into account the semantic constraints and provides an optimal solution. The framework is modular so that new tools can be continuously added. While producing some innovative results in specific areas, the goal of this work is the development of a comprehensive framework combining state of the art techniques and new algorithms, thus enabling the user to conceptualise her/his knowledge and model geometric shapes. The original contributions regard the formalisation of the concept of annotation, with attached properties, and of the relations between significant parts of objects; a new technique for guaranteeing the persistence of annotations after significant changes in shape's resolution; the exploitation of shape descriptors for the extraction of quantitative information and the assessment of shape variability within a class; and the extension of the popular cage-based deformation techniques to include constraints on the allowed displacement of vertices. In this thesis, we report the design and development of the framework as well as results in two application scenarios, namely product design and archaeological reconstruction

Paracrine Adenoviral Delivery of Therapeutic Payloads for Cancer Therapy

Adenoviral vectors are the most commonly used delivery vectors for clinical gene therapy due to their favorable characteristics: (i) they do not integrate into the host cell genome and thus harbor a reduced risk of insertional mutagenesis, (ii) they efficiently transduce dividing and non-dividing cells, and (iii) they have a large packaging capacity allowing large and/or multiple cargo delivery. However, site-specific gene delivery in vivo is still compromised because of the endogenous adenoviral tropism and interactions with the host immune system. To overcome this limitation, our research group developed a generic adenoviral de-/retargeting system consisting of a designed ankyrin repeat protein (DARPin)-based adapter mediating cell-specific transduction and a single-chain variable fragment (scFv)-based vector shield. In an autocrine delivery approach, efficient cancer drug delivery to tumor cells could previously be demonstrated in vivo by applying tumor cell marker-specific DARPin adapters to the adenoviral vector. Building on this approach, we then aimed to expand our system and enable alternative targeting strategies to further improve the efficacy of targeted vector delivery. The aim of this thesis was to retarget a human adenovirus serotype 5 (HAdV5)-derived vector to stromal cells in the tumor microenvironment in order to deliver therapeutic biomolecules to the tumor microenvironment (TME). The therapeutic biomolecules, initially encoded by the adenoviral vector, would thus be produced by the transduced stromal cells and locally secreted into the TME, where they could exert their anti-tumorigenic effect. This should increase the therapeutic efficacy, reduce off-target effects, and prevent systemic toxicities. Since stromal cells are genetically more stable than tumor cells, in some cancers also more abundant than tumor cells, and theoretically not affected by the vector-encoded cancer drug, we anticipated this paracrine delivery approach to harbor several advantages over the existing, tumor cell- targeted autocrine delivery approach. In the main part of this thesis (presented in chapter three and Hartmann et al., 2023), the stromal cell-targeted paracrine adenoviral delivery of cancer therapeutics to the TME is presented. To realize the project, a suitable stromal target for adenoviral retargeting, namely fibroblast activation protein (FAP) on cancer-associated fibroblasts (CAFs), was first identified. Aiming to generate FAP-specific adenoviral retargeting adapters, ribosome display selections were performed to obtain FAP-specific DARPins, which were then utilized as targeting domain in the previously developed bispecific modular adapter. Biologically functional adapters capable to successfully mediate retargeting of HAdV5 to CAFs via FAP were subsequently selected in a cell-based screening approach. These adapters were characterized in great detail for several binding characteristics (including binding kinetics, potential binding epitopes, and cross-reactivity to human/mouse FAP), and tested in vitro for specificity and selectivity using various target and non-target cell lines. HAdV5-based vector retargeting to CAFs was furthermore investigated in vivo using a selected, human/mouse FAP cross-reactive adapter and a suitable mouse model of cancer which had been established before. In these in vivo studies, efficient vector retargeting to CAFs by the FAP-specific adapter was demonstrated. Using the same mouse model of cancer, adenoviral delivery of a therapeutic monoclonal antibody with anti-tumor activity to CAFs could subsequently be investigated in vivo, and showed to be successful as evidenced by reduced tumor growth. Importantly, the therapeutic effect of the monoclonal antibody was superior when encoded and delivered by the FAP- retargeted adenoviral vector than when administered directly as recombinant protein. Altogether, it was thus demonstrated that retargeting of HAdV5-based vectors via FAP-specific adapters enables an efficient, stromal cell-targeted paracrine delivery of anti-cancer therapeutics to the TME. In addition to developing the stromal cell-targeted adenoviral vector for a paracrine cancer drug delivery, it was also possible to contribute to other research projects dealing with the retargeting of HAdV5-based vectors for cancer therapeutic applications. In one collaboration project (presented in chapter four and Freitag et al., 2023), it was intended to retarget HAdV5 to T cells and achieve an efficient transduction of these immune cells, which are naturally not susceptible to an HAdV5 infection. This goal was achieved using the adapter- based retargeting strategy in combination with the experimental finding that T cells ought to be activated to be adenovirally transduced. As a result, novel scFv-based adapters targeting the T cell co-receptor CD3, the co-stimulatory receptor CD28, and the interleukin (IL)-2 receptor were developed and deployed concurrently to promote cell specificity for adenoviral retargeting while providing T cell activation stimuli. Cell-specific retargeting of HAdV5-based vectors to human T cells and efficient human T cell transduction was shown in vitro as well as in vivo in relevant humanized mouse models. This T cell-retargeted adenoviral vector could now be used to engineer T cells in vivo in order to improve chimeric antigen receptor (CAR)-T cell therapy for cancer treatment. In two other collaboration projects, the adenoviral delivery of cancer therapeutics to the TME via the previously established, tumor cell-targeted autocrine approach was investigated in vivo. In both these projects the HAdV5-based vector was retargeted to tumor cells via the human epidermal growth factor receptor 2 (HER2) using specific DARPin adapters. However, different therapeutic biomolecules, including the cytokine IL-12 or a bispecific T cell engager (BiTE) aiming to enhance anti-tumor NK cell (presented in chapter six and Kirchhammer et al., 2022) or T cell activity (presented in chapter five and Freitag and Kolibius et al., manuscript in preparation for publication), were encoded by the adenoviral vector. Targeted payload delivery as well as therapeutic effects were investigated in vivo in relevant tumor mouse models. In both projects, target-specific adenovirus-mediated payload delivery with great therapeutic efficacy could be successfully demonstrated

Physics-based Reconstruction and Animation of Humans

Creating digital representations of humans is of utmost importance for applications ranging from entertainment (video games, movies) to human-computer interaction and even psychiatrical treatments. What makes building credible digital doubles difficult is the fact that the human vision system is very sensitive to perceiving the complex expressivity and potential anomalies in body structures and motion. This thesis will present several projects that tackle these problems from two different perspectives: lightweight acquisition and physics-based simulation. It starts by describing a complete pipeline that allows users to reconstruct fully rigged 3D facial avatars using video data coming from a handheld device (e.g., smartphone). The avatars use a novel two-scale representation composed of blendshapes and dynamic detail maps. They are constructed through an optimization that integrates feature tracking, optical flow, and shape from shading. Continuing along the lines of accessible acquisition systems, we discuss a framework for simultaneous tracking and modeling of articulated human bodies from RGB-D data. We show how semantic information can be extracted from the scanned body shapes. In the second half of the thesis, we will deviate from using standard linear reconstruction and animation models, and rather focus on exploiting physics-based techniques that are able to incorporate complex phenomena such as dynamics, collision response and incompressibility of the materials. The first approach we propose assumes that each 3D scan of an actor records his body in a physical steady state and uses a process called inverse physics to extract a volumetric physics-ready anatomical model of him. By using biologically-inspired growth models for the bones, muscles and fat, our method can obtain realistic anatomical reconstructions that can be later on animated using external tracking data such as the one resulting from tracking motion capture markers. This is then extended to a novel physics-based approach for facial reconstruction and animation. We propose a facial animation model which simulates biomechanical muscle contractions in a volumetric head model in order to create the facial expressions seen in the input scans. We then show how this approach allows for new avenues of dynamic artistic control, simulation of corrective facial surgery, and interaction with external forces and objects

Learning from the Artist: Theory and Practice of Example-Based Character Deformation

Movie and game production is very laborious, frequently involving hundreds of person-years for a single project. At present this work is difficult to fully automate, since it involves subjective and artistic judgments. Broadly speaking, in this thesis we explore an approach that works with the artist, accelerating their work without attempting to replace them. More specifically, we describe an “example-based” approach, in which artists provide examples of the desired shapes of the character, and the results gradually improve as more examples are given. Since a character’s skin shape deforms as the pose or expression changes, or particular problem will be termed character deformation. The overall goal of this thesis is to contribute a complete investigation and development of an example-based approach to character deformation. A central observation guiding this research is that character animation can be formulated as a high-dimensional problem, rather than the two- or three-dimensional viewpoint that is commonly adopted in computer graphics. A second observation guiding our inquiry is that statistical learning concepts are relevant. We show that example-based character animation algorithms can be informed, developed, and improved using these observations. This thesis provides definitive surveys of example-based facial and body skin deformation. This thesis analyzes the two leading families of example-based character deformation algorithms from the point of view of statistical regression. In doing so we show that a wide variety of existing tools in machine learning are applicable to our problem. We also identify several techniques that are not suitable due to the nature of the training data, and the high-dimensional nature of this regression problem. We evaluate the design decisions underlying these example-based algorithms, thus providing the groundwork for a ”best practice” choice of specific algorithms. This thesis develops several new algorithms for accelerating example-based facial animation. The first algorithm allows unspecified degrees of freedom to be automatically determined based on the style of previous, completed animations. A second algorithm allows rapid editing and control of the process of transferring motion capture of a human actor to a computer graphics character. The thesis identifies and develops several unpublished relations between the underlying mathematical techniques. Lastly, the thesis provides novel tutorial derivations of several mathematical concepts, using only the linear algebra tools that are likely to be familiar to experts in computer graphics. Portions of the research in this thesis have been published in eight papers, with two appearing in premier forums in the field

CteG, a Chlamydia trachomatis protein involved in host cell lytic exit

The Phylum Chlamydiae comprises bacteria that only multiply inside eukaryotic host cells, within a membrane-bound vacuole. Among Chlamydiae, the Family Chlamydiaceae includes Chlamydia trachomatis, a major human pathogen causing ocular and genital infections. The characteristic infectious cycle of Chlamydiae involves chlamydial-mediated host cell invasion and egress. Throughout the cycle, Chlamydiae subvert host cell processes through effector proteins delivered into host cells by a type III secretion system. Previously, it was shown that the C. trachomatis CteG effector localizes at the Golgi and plasma membrane of infected cells. Moreover, the first 100 residues of CteG fused to EGFP (EGFP-CteG100) localize at the Golgi upon their ectopic expression in mammalian cells. In this work, we found that CteG mediates C. trachomatis host cell lytic exit. Cells infected by a CteG-deficient strain showed less chlamydiae in the culture supernatant and displayed lower levels of cytotoxicity comparing to cells infected by CteG-producing wild-type and complemented strains. We further showed that CteG and Pgp4, a global regulator of transcription encoded in the C. trachomatis virulence plasmid, act on the same pathway leading to chlamydial host cell lytic exit. We also found a predicted α-helix on the N-terminal region of CteG that is essential for the localization of ectopically expressed EGFP-CteG100 at the Golgi and plays a role in adequate targeting of CteG to the Golgi and plasma membrane in infected cells. Finally, we identified host cell proteins that may interact with CteG and provided insights into the evolutionary history of cteG by bioinformatics analysis of its homologs in Chlamydiaceae. In summary, this work revealed a role of CteG in C. trachomatis host cell exit, a crucial step of the chlamydial infectious cycle. Together with other findings, this expanded the knowledge on C. trachomatis-host cell interactions and opened avenues for future research.O Filo Chlamydiae abrange bactérias que se multiplicam exclusivamente em células de hospedeiros eucariontes, no interior de um vacúolo. Chlamydia trachomatis, da Família Chlamydiaceae, causa infeções genitais e oculares em humanos. O ciclo infecioso das Chlamydiae envolve processos de invasão e saída da célula hospedeira promovidos pela bactéria. Durante este ciclo, as Chlamydiae manipulam as células hospedeiras através de proteínas efetoras, transportadas para essas células hospedeiras por um sistema de secreção do tipo III. Previamente, observou-se que CteG, uma proteína efetora de C. trachomatis, se localiza no Golgi e na membrana plasmática de células infetadas. Adicionalmente, os primeiros 100 aminoácidos de CteG, fundidos a EGFP (EGFP-CteG100), localizam-se no Golgi após a sua expressão ectópica em células de mamífero. Neste trabalho, mostrou-se que CteG intervém na saída lítica de C. trachomatis da célula hospedeira. Verificou-se também que CteG e Pgp4, uma proteína codificada no plasmídeo de virulência de C. trachomatis, atuam na mesma via que resulta na saída lítica desta bactéria da célula hospedeira. Noutra parte do trabalho, descobriu-se que uma possível hélice-α na região N-terminal de CteG é essencial para a localização de EGFP-CteG100 no Golgi, após a sua expressão ectópica em células de mamífero. Também se mostrou que esta hélice-α é importante para um eficiente direcionamento de CteG para o Golgi e para a membrana plasmática de células infetadas. Finalmente, foram identificadas proteínas da célula hospedeira que podem interagir com CteG e foi investigada a história evolutiva de cteG através de uma análise bioinformática dos seus homólogos em Chlamydiaceae. Em resumo, este trabalho revelou uma função de CteG na saída lítica de C. trachomatis, um passo crucial no ciclo infecioso desta bactéria. Juntamente com outras descobertas, foi assim expandido o conhecimento sobre as interações entre C. trachomatis e a célula hospedeira e abriram-se várias novas linhas futuras de investigação

The Second Conference on Lunar Bases and Space Activities of the 21st Century, volume 1

These papers comprise a peer-review selection of presentations by authors from NASA, LPI industry, and academia at the Second Conference (April 1988) on Lunar Bases and Space Activities of the 21st Century, sponsored by the NASA Office of Exploration and the Lunar Planetary Institute. These papers go into more technical depth than did those published from the first NASA-sponsored symposium on the topic, held in 1984. Session topics covered by this volume include (1) design and operation of transportation systems to, in orbit around, and on the Moon, (2) lunar base site selection, (3) design, architecture, construction, and operation of lunar bases and human habitats, and (4) lunar-based scientific research and experimentation in astronomy, exobiology, and lunar geology