Dysregulation of of phospholipid-specific phagocytosis by B1 B cells in diet-induced obese mice

B1 B cells have received increasing attention recently due to their newly discovered phagocytic and microbicidal capabilities. Several studies have demonstrated that B1 cells can phagocytize polystyrene fluorescent particles, bacteria (Staphylococcus aureus, Escherichia coli), and even apoptotic cells. Nevertheless, little is known about the biological significance of this seemingly redundant function of B1 B cells as compared to that of conventional phagocytes. Here we investigate the unique phosphotidylcholine (PtC)-specific B1 B cell phagocytosis. PtC is a major phospholipid in the biological membrane and a classical antigen recognized by B1 B cell-derived natural antibodies. These antibodies play important roles in immune defense as well as tissue homeostasis. Here we report that B1 cells preferentially phagocytose PtC-coated beads, differing from that of conventional macrophages. We further attest that these beads were truly internalized and subsequently fused with hydrolytic lysosomes indicated by increasing fluorescent intensity of a pH-sensitive dye. Despite the differences in antigen specificity, phagocytosis of both B1 cells and macrophages can be inhibited by the microtubule-inhibitor, Colchicine, in a dose-dependent manner. Most intriguingly, upon chronic high-fat diet (HFD) consumption by the host, B1 cell phagocytosis starts to lose antigen-specificity for PtC. Morphologically, some of these B1 B cells in DIO mice show enlarged cytosol and engulfed more beads, indicating a transition to macrophage-like cells. Our study suggests for the first time that B1 B cells have unique phospholipid-specific phagocytosis capacity, which is affected by diet-induced obesity

SOFTWARE TESTABILITY MEASURE FOR SAE ARCHITECTURE ANALYSIS AND DESIGN LANGUAGE (AADL)SOFTWARE TESTABILITY MEASURE FOR SAE ARCHITECTURE ANALYSIS AND DESIGN LANGUAGE (AADL)

Testability is an important quality attribute of software, especially for critical systems such as avionics, medical, and automotive. Improvement in the early testability of software architecture, the first artifact of the software system, will help reduce issues and costs later in the development process. AADL, an architecture analysis description language suitable for critical embedded, real-time systems, can be used for design documentation, analysis and code generation. Because the capability of AADL can be extended, it is possible to add new analyses to its core language. Tools such as the Open Source AADL Tool Environment (OSATE) provide plugins for processing AADL models. Although adding new plugins in OSATE extends AADL, there currently exists no AADL extension for testability measurement. The purpose of this thesis is to propose such a method to measure the testability of AADL models as well as to develop a testability plugin in OSATE. Much research has been conducted on testability of hardware, software and embedded systems, resulting in several approaches for measuring this quality attribute. Among them, the approach measuring testability as a product of controllability and observability using information transfer graph (ITG) is the most applicable for measuring the testability of AADL models. This thesis proposes a method applying this approach to AADL models. A complete testability measure plugin for OSATE was developed based on this approach and detailed examples are given in this thesis to demonstrate its applicability

On the definition and the properties of the principal eigenvalue of some nonlocal operators

In this article we study some spectral properties of the linear operator $\mathcal{L}\_{\Omega}+a$ defined on the space $C(\bar\Omega)$ by :$$\mathcal{L}\_{\Omega}[\varphi] +a\varphi:=\int\_{\Omega}K(x,y)\varphi(y)\,dy+a(x)\varphi(x)$$ where $\Omega\subset \mathbb{R}^N$ is a domain, possibly unbounded, $a$ is a continuous bounded function and $K$ is a continuous, non negative kernel satisfying an integrability condition. We focus our analysis on the properties of the generalised principal eigenvalue $\lambda\_p(\mathcal{L}\_{\Omega}+a)$ defined by \lambda\_p(\mathcal{L}\_{\Omega}+a):= \sup\{\lambda \in \mathbb{R} \,|\, \exists \varphi \in C(\bar \Omega), \varphi\textgreater{}0, \textit{such that}\, \mathcal{L}\_{\Omega}[\varphi] +a\varphi +\lambda\varphi \le 0 \, \text{in}\;\Omega\}. We establish some new properties of this generalised principal eigenvalue $\lambda\_p$. Namely, we prove the equivalence of different definitions of the principal eigenvalue. We also study the behaviour of $\lambda\_p(\mathcal{L}\_{\Omega}+a)$ with respect to some scaling of $K$. For kernels $K$ of the type, $K(x,y)=J(x-y)$ with $J$ a compactly supported probability density, we also establish some asymptotic properties of $\lambda\_{p} \left(\mathcal{L}\_{\sigma,m,\Omega} -\frac{1}{\sigma^m}+a\right)$ where $\mathcal{L}\_{\sigma,m,\Omega}$ is defined by $\displaystyle{\mathcal{L}\_{\sigma,m,\Omega}[\varphi]:=\frac{1}{\sigma^{2+N}}\int\_{\Omega}J\left(\frac{x-y}{\sigma}\right)\varphi(y)\, dy}$. In particular, we prove that $$\lim\_{\sigma\to 0}\lambda\_p\left(\mathcal{L}\_{\sigma,2,\Omega}-\frac{1}{\sigma^{2}}+a\right)=\lambda\_1\left(\frac{D\_2(J)}{2N}\Delta +a\right),$$where $D\_2(J):=\int\_{\mathbb{R}^N}J(z)|z|^2\,dz$ and $\lambda\_1$ denotes the Dirichlet principal eigenvalue of the elliptic operator. In addition, we obtain some convergence results for the corresponding eigenfunction $\varphi\_{p,\sigma}$