Cruiser and PhoTable: Exploring Tabletop User Interface Software for Digital Photograph Sharing and Story Capture

Digital photography has not only changed the nature of photography and the photographic process, but also the manner in which we share photographs and tell stories about them. Some traditional methods, such as the family photo album or passing around piles of recently developed snapshots, are lost to us without requiring the digital photos to be printed. The current, purely digital, methods of sharing do not provide the same experience as printed photographs, and they do not provide effective face-to-face social interaction around photographs, as experienced during storytelling. Research has found that people are often dissatisfied with sharing photographs in digital form. The recent emergence of the tabletop interface as a viable multi-user direct-touch interactive large horizontal display has provided the hardware that has the potential to improve our collocated activities such as digital photograph sharing. However, while some software to communicate with various tabletop hardware technologies exists, software aspects of tabletop user interfaces are still at an early stage and require careful consideration in order to provide an effective, multi-user immersive interface that arbitrates the social interaction between users, without the necessary computer-human interaction interfering with the social dialogue. This thesis presents PhoTable, a social interface allowing people to effectively share, and tell stories about, recently taken, unsorted digital photographs around an interactive tabletop. In addition, the computer-arbitrated digital interaction allows PhoTable to capture the stories told, and associate them as audio metadata to the appropriate photographs. By leveraging the tabletop interface and providing a highly usable and natural interaction we can enable users to become immersed in their social interaction, telling stories about their photographs, and allow the computer interaction to occur as a side-effect of the social interaction. Correlating the computer interaction with the corresponding audio allows PhoTable to annotate an automatically created digital photo album with audible stories, which may then be archived. These stories remain useful for future sharing -- both collocated sharing and remote (e.g. via the Internet) -- and also provide a personal memento both of the event depicted in the photograph (e.g. as a reminder) and of the enjoyable photo sharing experience at the tabletop. To provide the necessary software to realise an interface such as PhoTable, this thesis explored the development of Cruiser: an efficient, extensible and reusable software framework for developing tabletop applications. Cruiser contributes a set of programming libraries and the necessary application framework to facilitate the rapid and highly flexible development of new tabletop applications. It uses a plugin architecture that encourages code reuse, stability and easy experimentation, and leverages the dedicated computer graphics hardware and multi-core processors of modern consumer-level systems to provide a responsive and immersive interactive tabletop user interface that is agnostic to the tabletop hardware and operating platform, using efficient, native cross-platform code. Cruiser's flexibility has allowed a variety of novel interactive tabletop applications to be explored by other researchers using the framework, in addition to PhoTable. To evaluate Cruiser and PhoTable, this thesis follows recommended practices for systems evaluation. The design rationale is framed within the above scenario and vision which we explore further, and the resulting design is critically analysed based on user studies, heuristic evaluation and a reflection on how it evolved over time. The effectiveness of Cruiser was evaluated in terms of its ability to realise PhoTable, use of it by others to explore many new tabletop applications, and an analysis of performance and resource usage. Usability, learnability and effectiveness of PhoTable was assessed on three levels: careful usability evaluations of elements of the interface; informal observations of usability when Cruiser was available to the public in several exhibitions and demonstrations; and a final evaluation of PhoTable in use for storytelling, where this had the side effect of creating a digital photo album, consisting of the photographs users interacted with on the table and associated audio annotations which PhoTable automatically extracted from the interaction. We conclude that our approach to design has resulted in an effective framework for creating new tabletop interfaces. The parallel goal of exploring the potential for tabletop interaction as a new way to share digital photographs was realised in PhoTable. It is able to support the envisaged goal of an effective interface for telling stories about one's photos. As a serendipitous side-effect, PhoTable was effective in the automatic capture of the stories about individual photographs for future reminiscence and sharing. This work provides foundations for future work in creating new ways to interact at a tabletop and to the ways to capture personal stories around digital photographs for sharing and long-term preservation

In vivo biomolecular imaging of zebrafish embryos using confocal Raman spectroscopy

Zebrafish embryos provide a unique opportunity to visualize complex biological processes, yet conventional imaging modalities are unable to access intricate biomolecular information without compromising the integrity of the embryos. Here, we report the use of confocal Raman spectroscopic imaging for the visualization and multivariate analysis of biomolecular information extracted from unlabeled zebrafish embryos. We outline broad applications of this method in: (i) visualizing the biomolecular distribution of whole embryos in three dimensions, (ii) resolving anatomical features at subcellular spatial resolution, (iii) biomolecular profiling and discrimination of wild type and ΔRD1 mutant Mycobacterium marinum strains in a zebrafish embryo model of tuberculosis and (iv) in vivo temporal monitoring of the wound response in living zebrafish embryos. Overall, this study demonstrates the application of confocal Raman spectroscopic imaging for the comparative bimolecular analysis of fully intact and living zebrafish embryos

Cytotoxic T cell function in solid tumors: principles and implications for immunotherapy

Activation of the immune system, the body’s own anti-cancer defense, is a promising approach for a range of cancer types with the potential to raise a specific, adaptive and long-lasting anti-cancer protection. In this thesis novel in vitro models which mimic the 3D tissue organization and in vivo imaging approaches were developed to visualize immune effector cells (cytotoxic T cells, CTL) within live melanoma lesions. As novel imaging modality in cancer research, third harmonic generation (THG) microscopy was established for label-free visualization of tissue structures. Monitoring CTL function at single-cell level shows how CTL cooperate to kill tumor cells and how an immune-modulatory antibody (a-CD137) enhances CTL efficiency. In summary, in this thesis kinetic imaging and intravital microscopy were applied to deepen the mechanistic understanding of immune cell function within complex tissues which forms the basis for improved, rationale design of immunotherapies

Cytotoxic T cell function in solid tumors: principles and implications for immunotherapy

Contains fulltext : 145309.pdf (publisher's version ) (Open Access)Activation of the immune system, the body’s own anti-cancer defense, is a promising approach for a range of cancer types with the potential to raise a specific, adaptive and long-lasting anti-cancer protection. In this thesis novel in vitro models which mimic the 3D tissue organization and in vivo imaging approaches were developed to visualize immune effector cells (cytotoxic T cells, CTL) within live melanoma lesions. As novel imaging modality in cancer research, third harmonic generation (THG) microscopy was established for label-free visualization of tissue structures. Monitoring CTL function at single-cell level shows how CTL cooperate to kill tumor cells and how an immune-modulatory antibody (a-CD137) enhances CTL efficiency. In summary, in this thesis kinetic imaging and intravital microscopy were applied to deepen the mechanistic understanding of immune cell function within complex tissues which forms the basis for improved, rationale design of immunotherapies.Radboud Universiteit Nijmegen, 24 november 2015Promotor : Friedl, P.H.A. Co-promotor : Zegers, M.M.P

Cancer cells: Stemness shaped by curvature

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T cell-mediated additive cytotoxicity - death by multiple bullets.

Immune effector cells, including cytotoxic T cells (CTLs), induce apoptosis and eliminate target cells by direct cell-cell contacts. In vivo, CTLs fail to efficiently kill solid tumor cells by individual contacts but rely upon multihit interactions by many CTLs (swarming). Recent evidence has indicated that multihit interactions by CTLs induce a series of sublethal damage events in target cells, including perforin-mediated membrane damage, induction of reactive oxygen species (ROS), nuclear envelope rupture, and DNA damage. Individual damage can be repaired, but when induced in rapid sequence, sublethal damage can accumulate and induce target cell death. Here, we summarize the sublethal damage and additive cytotoxicity concepts for CTL-induced and other cell stresses and discuss the implications for improving immunotherapy and multitargeted anticancer therapies

Cytotoxic T lymphocyte migration and effector function in the tumor microenvironment

Item does not contain fulltextImmunological control of cancer lesions requires local uptake of tumor-specific antigen followed by the activation and expansion of tumor specific cytotoxic T-lymphocytes (CTL). An efficient effector phase further depends upon the entry of activated CTL into the tumor microenvironment and scanning of tumor tissue, which leads to direct interaction of the CTL with target cells followed by apoptosis induction and shrinkage of the tumor lesion. Whereas the antigens and pathways that lead to efficient activation of tumor-specific CTL are well established, the local mechanisms that enable efficient - or deficient - CTL function in the tumor tissue are poorly understood. Firstly, effector T lymphocytes need to be mobile to reach the tumor lesion. Next, they must physically interact with and scan tumor cells for antigenic MHC/peptide complexes. Lastly, CTLs must undergo activation and functional conjugation with target cells to induce apoptosis either by the release of perforins or the engagement of Fas/FasL. All these steps of effector function are interdependent and require the amoeboid migration of CTL through tissue to reach, engage with and leave encountered cells

Mathematical Modelling Based on In Vivo Imaging Suggests CD137-Stimulated Cytotoxic T Lymphocytes Exert Superior Tumour Control Due to an Enhanced Antimitotic Effect on Tumour Cells

Simple SummaryCytotoxic T lymphocytes (CTLs) play an important role in controlling tumours, and an improved understanding of how they accomplish this will benefit immunotherapeutic cancer treatment strategies. Stimulation of CTLs by targeting their CD137 receptor is a strategy currently under investigation for enhancing responses against tumours, yet so far only limited quantitative knowledge regarding the effects of such stimulation upon CTLs has been obtained. Here, we develop mathematical models to describe dynamic in vivo two-photon imaging of tumour infiltrating CTLs, to characterise differences in their function either in the presence or absence of a CD137 agonist antibody. We showed that an increased antiproliferative effect and a more sustained presence of CTLs within the tumour were the most important effects associated with anti-CD137 treatment.Several immunotherapeutic strategies for the treatment of cancer are under development. Two prominent strategies are adoptive cell transfer (ACT) of CTLs and modulation of CTL function with immune checkpoint inhibitors or with costimulatory antibodies. Despite some success with these approaches, there remains a lack of detailed and quantitative descriptions of the events following CTL transfer and the impact of immunomodulation. Here, we have applied ordinary differential equation models to two photon imaging data derived from a B16F10 murine melanoma. Models were parameterised with data from two different treatment conditions: either ACT-only, or ACT with intratumoural costimulation using a CD137 targeted antibody. Model dynamics and best fitting parameters were compared, in order to assess the mode of action of the CTLs and examine how the CD137 antibody influenced their activities. We found that the cytolytic activity of the transferred CTLs was minimal without CD137 costimulation, and that the CD137 targeted antibody did not enhance the per-capita killing ability of the transferred CTLs. Instead, the results of our modelling study suggest that an antiproliferative effect of CTLs exerted upon the tumour likely accounted for the majority of the reduction in tumour growth after CTL transfer. Moreover, we found that CD137 most likely improved tumour control via enhancement of this antiproliferative effect, as well as prolonging the period in which CTLs were inside the tumour, leading to a sustained duration of their antitumour effects following CD137 stimulation.Cervix cance

Third harmonic generation microscopy of cells and tissue organization

The interaction of cells within their microenvironmental niche is fundamental to cell migration, positioning, growth and differentiation in order to form and maintain complex tissue organization and function. Third harmonic generation (THG) microscopy is a label-free scatter process that is elicited by water-lipid and water-protein interfaces, including intra- and extracellular membranes, and extracellular matrix structures. In applied life sciences, THG delivers a versatile contrast modality to complement multi-parameter fluorescence, second harmonic generation and fluorescence lifetime microscopy, which allows detection of cellular and molecular cell functions in three-dimensional tissue culture and small animals. In this Commentary, we review the physical and technical basis of THG, and provide considerations for optimal excitation, detection and interpretation of THG signals. We further provide an overview on how THG has versatile applications in cell and tissue research, with a particular focus on analyzing tissue morphogenesis and homeostasis, immune cell function and cancer research, as well as the emerging applicability of THG in clinical practice