Monte Carlo modeling of polarized light propagation: Stokes vs Jones - Part I

This bipartite comparative study aims at inspecting the similarities and differences between the Jones and Stokes–Mueller formalisms when modeling polarized light propagation with numerical simulations of the Monte Carlo type. In this first part, we review the theoretical concepts that concern light propagation and detection with both pure and partially/totally unpolarized states. The latter case involving fluctuations, or “depolarizing effects,” is of special interest here: Jones and Stokes–Mueller are equally apt to model such effects and are expected to yield identical results. In a second, ensuing paper, empirical evidence is provided by means of numerical experiments, using both formalisms

Monte Carlo modeling of polarized light propagation: Stokes vs Jones - Part II

In this second part of our comparative study inspecting the (dis)similarities between “Stokes” and “Jones,” we present simulation results yielded by two independent Monte Carlo programs: (i) one developed in Bern with the Jones formalism and (ii) the other implemented in Ulm with the Stokes notation. The simulated polarimetric experiments involve suspensions of polystyrene spheres with varying size. Reflection and refraction at the sample/air interfaces are also considered. Both programs yield identical results when propagating pure polarization states, yet, with unpolarized illumination, second order statistical differences appear, thereby highlighting the pre-averaged nature of the Stokes parameters. This study serves as a validation for both programs and clarifies the misleading belief according to which “Jones cannot treat depolarizing effects.

Binding of CD40L to Mac-1's i-domain involves the EQLKKSKTL motif and mediates leukocyte recruitment and atherosclerosis-but does not affect immunity and thrombosis in mice

Rationale: CD40L figures prominently in chronic inflammatory diseases such as atherosclerosis. However, since CD40L potently regulates immune function and hemostasis by interaction with CD40 receptor and the platelet integrin GPIIb/IIIa, its global inhibition compromises host defense and generated thromboembolic complications in clinical trials. We recently reported that CD40L mediates atherogenesis independently of CD40 and proposed Mac-1 as an alternate receptor. Objective: Here, we molecularly characterized the CD40L-Mac-1 interaction and tested whether its selective inhibition by a small peptide modulates inflammation and atherogenesis in vivo. Methods and Results: CD40L concentration-dependently bound to Mac-1 I-domain in solid phase binding assays, and a high-affinity interaction was revealed by surface-plasmon-resonance analysis. We identified the motif EQLKKSKTL, an exposed loop between the α1 helix and the β-sheet B, on Mac-1 as binding site for CD40L. A linear peptide mimicking this sequence, M7, specifically inhibited the interaction of CD40L and Mac-1. A cyclisized version optimized for in vivo use, cM7, decreased peritoneal inflammation and inflammatory cell recruitment in vivo. Finally, LDLr -/- mice treated with intraperitoneal injections of cM7 developed smaller, less inflamed atherosclerotic lesions featuring characteristics of stability. However, cM7 did not interfere with CD40L-CD40 binding in vitro and CD40L-GPIIb/IIIa-mediated thrombus formation in vivo. Conclusions: We present the novel finding that CD40L binds to the EQLKKSKTL motif on Mac-1 mediating leukocyte recruitment and atherogenesis. Specific inhibition of CD40L-Mac-1 binding may represent an attractive anti-inflammatory treatment strategy for atherosclerosis and other inflammatory conditions, potentially avoiding the unwanted immunologic and thrombotic effects of global inhibition of CD40L.Fil: Wolf, Dennis. Albert-Ludwigs-Universität Freiburg; Alemania. Baker IDI Heart and Diabetes Institute; AustraliaFil: Hohmann, Jan David. Baker IDI Heart and Diabetes Institute; AustraliaFil: Wiedemann, Ansgar. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Bledzka, Kamila. Cleveland Clinic. Department of Molecular Cardiology; Estados UnidosFil: Blankenbach, Hermann. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Gutte, Katharina. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Zeschky, Katharina. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Bassler, Nicole. Baker IDI Heart and Diabetes Institute; AustraliaFil: Hoppe, Natalie. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Rodriguez, Alexandra Ortiz. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Herr, Nadine. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Hilgendorf, Ingo. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Stachon, Peter. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Willecke, Florian. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Duerschmied, Daniel. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: von zur Muhlen, Constantin. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Soloviev, Dmitry A.. Cleveland Clinic. Department of Molecular Cardiology; Estados UnidosFil: Zhang, Li. University of Maryland; Estados UnidosFil: Bode, Christoph. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Plow, Edward F.. Cleveland Clinic. Department of Molecular Cardiology; Estados UnidosFil: Libby, Peter. Harvard Medical School; Estados UnidosFil: Peter, Karlheinz. Baker IDI Heart and Diabetes Institute; AustraliaFil: Zirlik, Andreas. Albert-Ludwigs-Universität Freiburg; Alemani

A ligand-specific blockade of the integrin Mac-1 selectively targets pathologic inflammation while maintaining protective host-defense

Integrin-based therapeutics could block inflammatory processes but they also impair host defence, limiting their usefulness. Here the authors report an anti-Mac1 antibody that blocks its interaction with pro-inflammatory ligand CD40L but not other ligands, and show that it can protect against sepsis in mice