A Model-based Approach towards Human-Machine-Interfaces

International audienceSpecification and development of Human-Machine-Interfaces (HMI) for infotainment systems pose a difficult challenge for those automotive OEMs who claim this topic as one of their core competences. Experience shows that a major problem arises from the non optimal communication of all involved parties during the HMI development. This article describes a model-based approach towards HMI-development which combines conceptual design, specification and implementation based on a single complete HMI-model which serves as an improved means of communication between designers, ergonomists and software developers

T-cell co-stimulatory pathways in autoimmunity

T-cell activation and differentiation depend on the signal strength received by the T-cell receptor and on signals provided by co-stimulatory molecules. The most prominent co-stimulatory molecule is CD28, which controls the activation of naïve and memory T cells by antigen presented on professional antigen-presenting cells. Blocking of the CD28-CD80/86 pathway has been an appealing strategy for inducing tolerance in autoimmune diseases where the disease-inducing autoantigens are not known. Although CD28 has maintained its unique position, the past decade has witnessed the recognition that a large number of regulatory molecules on T cells must be stimulated to generate a fully protective immune response. These regulatory receptors differ in their preferential expression on T-cell subsets, in the ligands that they recognize, and in the signaling pathways that they trigger. They have in common the fact that they provide information on the cellular environment in which the T-cell response occurs. By intercepting these signals, we may be able to influence disease-relevant T-cell responses in autoimmune diseases while potentially minimizing broad immunosuppression

Developments in the scientific understanding of rheumatoid arthritis

Rheumatoid arthritis (RA) is recognized to be an autoimmune disease that causes preclinical systemic abnormalities and eventually leads to synovial inflammation and destruction of the joint architecture. Recently identified genetic risk factors and novel insights from animal models of spontaneous arthritis have lent support to the concept that thymic selection of an autoreactive T-cell repertoire is an important risk factor for this disease. With advancing age, defects in the homeostatic control of the T-cell pool and in the setting of signaling thresholds lead to the accumulation of pro-inflammatory T-effector cell populations and loss of tolerance to neo-antigens, such as citrullinated peptides. As the breakdown of tolerance to modified self-antigens can precede synovitis by decades, repair of homeostatic defects may open a unique window of opportunity for preventive interventions in RA. The end result of RA, destruction of cartilage and bone, appears to be driven by cytokine- and cell contact-induced activation of synoviocytes and monocytic cells, some of which differentiate into tissue-destructive osteoclasts. Targeting mediators involved in this process has greatly improved the management of this chronic inflammatory syndrome

Fully exploiting the potential of speech dialog in automotive applications

International audienceToday users are faced with infotainment devices and applications of increasing complexity. The design of easy-to-use and intuitive interfaces becomes a more and more challenging task. Users are usually not aware of the underlying applications and their restrictions when they want to use certain functionalities. Therefore, hierarchical menu structures are difficult to handle especially in situations where eyes and hands are occupied with other tasks, such as driving. For quite a while speech-enabled interfaces have been used to solve this problem since they allow users to control various applications without occupying hands and eyes. However, state-of-the-art multimodal applications often do not exploit the full potential that speech dialog offers simply because this modality is not well integrated with the "traditional" modalities such as graphics and haptics. The resulting speech interfaces do not run smoothly, exhibit plenty of inconsistencies concerning the GUI and are thus more or less tedious to use. Such kind of interfaces result in low acceptance because users do not see the immediate benefit. In this paper we present an approach that develops multimodal interfaces in an integrated way, thus ensuring highly consistent interfaces that closely couple the involved modalities and are thus easier to use

B cells in rheumatoid synovitis

In rheumatoid arthritis, T cells, B cells, macrophages, and dendritic cells invade the synovial membranes, establishing complex microstructures that promote inflammatory/tissue destructive lesions. B cell involvement has been considered to be limited to autoantibody production. However, recent studies suggest that B cells support rheumatoid disease through other mechanisms. A critical element of rheumatoid synovitis is the process of ectopic lymphoid neogenesis, with highly efficient lymphoid architectures established in a nonlymphoid tissue site. Rheumatoid synovitis recapitulates the pathways of lymph node formation, and B cells play a key role in this process. Furthermore, studies of rheumatoid lesions implanted in immunodeficient mice suggest that T cell activation in synovitis is B cell dependent, indicating the role played by B cells in presenting antigens and providing survival signals

Heterogeneity of memory T cells in aging

Immune memory is a requisite and remarkable property of the immune system and is the biological foundation of the success of vaccinations in reducing morbidity from infectious diseases. Some vaccines and infections induce long-lasting protection, but immunity to other vaccines and particularly in older adults rarely persists over long time periods. Failed induction of an immune response and accelerated waning of immune memory both contribute to the immuno-compromised state of the older population. Here we review how T cell memory is influenced by age. T cell memory is maintained by a dynamic population of T cells that are heterogeneous in their kinetic parameters under homeostatic condition and their function. Durability of T cell memory can be influenced not only by the loss of a clonal progeny, but also by broader changes in the composition of functional states and transition of T cells to a dysfunctional state. Genome-wide single cell studies on total T cells have started to provide insights on the influence of age on cell heterogeneity over time. The most striking findings were a trend to progressive effector differentiation and the activation of pro-inflammatory pathways, including the emergence of CD4+ and CD8+ cytotoxic subsets. Genome-wide data on antigen-specific memory T cells are currently limited but can be expected to provide insights on how changes in T cell subset heterogeneity and transcriptome relate to durability of immune protection