Dynamics and Function of Langerhans Cells In Vivo: Dermal Dendritic Cells Colonize Lymph Node Areas Distinct from Slower Migrating Langerhans Cells

Langerhans cells (LCs) are prominent dendritic cells (DCs) in epithelia, but their role in immunity is poorly defined. To track and discriminate LCs from dermal DCs in vivo, we developed knockin mice expressing enhanced green fluorescent protein (EGFP) under the control of the langerin (CD207) gene. By using vital imaging, we showed that most EGFP(+) LCs were sessile under steady-state conditions, whereas skin inflammation induced LC motility and emigration to lymph nodes (LNs). After skin immunization, dermal DCs arrived in LNs first and colonized areas distinct from slower migrating LCs. LCs reaching LNs under steady-state or inflammatory conditions expressed similar levels of costimulatory molecules. Langerin and EGFP were also expressed on thymic DCs and on blood-derived, CD8alpha(+) DCs from all secondary lymphoid organs. By using a similar knockin strategy involving a diphtheria toxin receptor (DTR) fused to EGFP, we demonstrated that LCs were dispensable for triggering hapten-specific T cell effectors through skin immunization.

Parameter sensitivity for optimal design of 65 nm node SOI transistors

Mixed-mode simulation, where device simulation is embedded directly within a circuit simulator, is used for the first time to provide scaling guidelines to achieve optimal digital circuit performance for double gate SOI MOSFETs. This significant advance overcomes the lack of availability of SPICE model parameters. The sensitivity of the gate delay and on-off current ratio to each of the key geometric and technological parameters of the transistor is quantified. The impact of the source-drain doping profile on circuit performance is comprehensively investigated.

Fixed-node diffusion Monte Carlo computations for closed-shell jellium spheres

Fixed-node diffusion Monte Carlo computations are used to determine the ground state energy and electron density for jellium spheres with up to N = 106 electrons and background densities corresponding to the electron gas parameter 1 less than or equal to r(s)less than or equal to5.62. We analyze the density and size dependence of the surface energy, and we extrapolate our data to the thermodynamic limit. The results agree well with the predictions of density functional computations using the local density approximation. In the case of N = 20, we extend our computation to higher densities and identify a transition between atomic- and jelliumlike nodal structures occurring at the background density corresponding to r(s)=0.13. In this case the local density approximation is unable to reproduce the changes in the correlation energy due to the discontinuous transition in the ground state nodal structure. We discuss the relevance of our results for nonlocal approximations to density functional theory.

Cutting edge: Langerin+ dendritic cells in the mesenteric lymph node set the stage for skin and gut immune system cross-talk.

Topical transcutaneous immunization (TCI) presents many clinical advantages, but its underlying mechanism remains unknown. TCI induced Ag-specific IgA Ab-secreting cells expressing CCR9 and CCR10 in the small intestine in a retinoic acid-dependent manner. These intestinal IgA Abs were maintained in Peyer\'s patch-null mice but abolished in the Peyer\'s patch- and lymph node-null mice. The mesenteric lymph node (MLN) was shown to be the site of IgA isotype class switching after TCI. Unexpectedly, langerin(+)CD8alpha(-) dendritic cells emerged in the MLN after TCI; they did not migrate from the skin but rather differentiated rapidly from bone marrow precursors. Depletion of langerin(+) cells impaired intestinal IgA Ab responses after TCI. Taken together, these findings suggest that MLN is indispensable for the induction of intestinal IgA Abs following skin immunization and that cross-talk between the skin and gut immune systems might be mediated by langerin(+) dendritic cells in the MLN.

Effect of Selfish Node Behavior on Efficient Topology Design

The problem of topology control is to assign per-node transmission power such that the resulting topology is energy efficient and satisfies certain global properties such as connectivity. The conventional approach to achieve these objectives is based on the fundamental assumption that nodes are socially responsible. We examine the following question: if nodes behave in a selfish manner, how does it impact the overall connectivity and energy consumption in the resulting topologies? We pose the above problem as a noncooperative game and use game-theoretic analysis to address it. We study Nash equilibrium properties of the topology control game and evaluate the efficiency of the induced topology when nodes employ a greedy best response algorithm. We show that even when the nodes have complete information about the network, the steady-state topologies are suboptimal. We propose a modified algorithm based on a better response dynamic and show that this algorithm is guaranteed to converge to energy-efficient and connected topologies. Moreover, the node transmit power levels are more evenly distributed, and the network performance is comparable to that obtained from centralized algorithms.