Identification of Key Processes that Control Tumor Necrosis Factor Availability in a Tuberculosis Granuloma

Tuberculosis (TB) granulomas are organized collections of immune cells comprised of macrophages, lymphocytes and other cells that form in the lung as a result of immune response to Mycobacterium tuberculosis (Mtb) infection. Formation and maintenance of granulomas are essential for control of Mtb infection and are regulated in part by a pro-inflammatory cytokine, tumor necrosis factor-α (TNF). To characterize mechanisms that control TNF availability within a TB granuloma, we developed a multi-scale two compartment partial differential equation model that describes a granuloma as a collection of immune cells forming concentric layers and includes TNF/TNF receptor binding and trafficking processes. We used the results of sensitivity analysis as a tool to identify experiments to measure critical model parameters in an artificial experimental model of a TB granuloma induced in the lungs of mice following injection of mycobacterial antigen-coated beads. Using our model, we then demonstrated that the organization of immune cells within a TB granuloma as well as TNF/TNF receptor binding and intracellular trafficking are two important factors that control TNF availability and may spatially coordinate TNF-induced immunological functions within a granuloma. Further, we showed that the neutralization power of TNF-neutralizing drugs depends on their TNF binding characteristics, including TNF binding kinetics, ability to bind to membrane-bound TNF and TNF binding stoichiometry. To further elucidate the role of TNF in the process of granuloma development, our modeling and experimental findings on TNF-associated molecular scale aspects of the granuloma can be incorporated into larger scale models describing the immune response to TB infection. Ultimately, these modeling and experimental results can help identify new strategies for TB disease control/therapy

Second-Order Efficient Test for Inhomogeneous Poisson Processes

62M05, inhomogeneous Poisson processes, hypotheses testing, first and second order efficiency, locally asymptotically uniformly most powerful test,

A multilingual background for telecollaboration Practices and policies in European higher education

The Trans-Atlantic and Pacific Project (TAPP) is a telecollaboration network linking European university classes with classes in the US and beyond for nearly 20 years. Such collaborations have enabled students to participate in realistic projects, fostering transversal and language skills – including English as a lingua franca – which are highlighted in university policies at European, country/region and institutional levels. In turn, telecollaboration can support Internationalisation at Home, along with virtual mobility objectives, increasingly prominent in European higher education. Considering the grassroots nature of TAPP, whose instructors design their own partnerships and assignments, this contribution examines TAPP projects in light of language policies from a dual bottom-up/top-down perspective. Thus, considering the importance of language policies of several European countries involved in TAPP (Belgium, France, Italy, Spain), this paper analyses how TAPP teaching-learning practices align with such policies in terms of multilingualism and interculturality. Attention is paid to students’ roles – subject-matter experts, linguists/translators, project managers, usability experts – and their native languages. Emphasis is placed on how students relate to English from their various perspectives as native speakers, second-language speakers, language experts or language learners. Lessons derived from the analysis of such practices can inform policy makers as they make provisions for Internationalisation at Home, mainly in Europe, while also introducing comparisons between European and US perspectives.Peer ReviewedPostprint (published version