Role of Rip2 in development of tumor-infiltrating MDSCs and bladder cancer metastasis.

Tumor invasion and metastases represent a complex series of molecular events that portends a poor prognosis. The contribution of inflammatory pathways mediating this process is not well understood. Nod-like receptors (NLRs) of innate immunity function as intracellular sensors of pathogen motifs and danger molecules. We propose a role of NLRs in tumor surveillance and in programming tumor-infiltrating lymphocytes (TILs). In this study, we examined the downstream serine/threonine and tyrosine kinase Rip2 in a murine model of bladder cancer. In Rip2-deficient C57Bl6 mice, larger orthotopic MB49 tumors developed with more numerous and higher incidence of metastases compared to wild-type controls. As such, increased tumor infiltration of CD11b+ Gr1hi myeloid-derived suppressor cells (MDSCs) with concomitant decrease in T cells and NK cells were observed in Rip2-deficient tumor bearing animals using orthotopic and subcutaneous tumor models. Rip2-deficient tumors showed enhanced epithelial-to-mesenchymal transition, with elevated expression of zeb1, zeb2, twist, and snail in the tumor microenvironment. We found that the absence of Rip2 plays an intrinsic role in fostering the development of granulocytic MDSCs by an autocrine and paracrine effect of granulocytic colony stimulating factor (G-CSF) expression. Our findings suggest that NLR pathways may be a novel modality to program TILs and influence tumor metastases

Classification of extremal elliptic K3 surfaces and fundamental groups of open K3 surfaces

We present a complete list of extremal elliptic K3 surfaces. There are altogether 325 of them. The first 112 coincides with Miranda-Persson's list for semi-stable ones. The data include the transcendental lattice which determines uniquely the K3 surface by a result of Shioda and Inose, the singular fibre type and the Mordell Weil group. As an application, we give a sufficient condition for the topological fundamental group of complement to an ADE-configuration of smooth rational curves on a K3 surface to be trivial.Comment: 25 pages, Nagoya Math. J. to appea

A Conservative Discontinuous Galerkin Scheme With O(N-2) Operations In Computing Boltzmann Collision Weight Matrix

In the present work, we propose a deterministic numerical solver for the homogeneous Boltzmann equation based on Discontinuous Galerkin (DG) methods. The weak form of the collision operator is approximated by a quadratic form in linear algebra setting. We employ the property of >shifting symmetry> in the weight matrix to reduce the computing complexity from theoretical O(N-3) down to O(N-2), with N the total number of freedom for d-dimensional velocity space. In addition, the sparsity is also explored to further reduce the storage complexity. To apply lower order polynomials and resolve loss of conserved quantities, we invoke the conservation routine at every time step to enforce the conservation of desired moments (mass, momentum and/or energy), with only linear complexity. Due to the locality of the DG schemes, the whole computing process is well parallelized using hybrid OpetiMP and MPI. The current work only considers integrable angular cross-sections under elastic and/or inelastic interaction laws. Numerical results on 2-D and 3-D problems are shown.Mathematic