The role of CXCL10 in the pathogenesis of experimental septic shock

Introduction: The chemokine CXCL10 is produced during infection and inflammation to activate the chemokine receptor CXCR3, an important regulator of lymphocyte trafficking and activation. The goal of this study was to assess the contributions of CXCL10 to the pathogenesis of experimental septic shock in mice. Methods: Septic shock was induced by cecal ligation and puncture (CLP) in mice resuscitated with lactated Ringer's solution and, in some cases, the broad spectrum antibiotic Primaxin. Studies were performed in CXCL10 knockout mice and mice treated with anti-CXCL10 immunoglobulin G (IgG). Endpoints included leukocyte trafficking and activation, core body temperature, plasma cytokine concentrations, bacterial clearance and survival. Results: CXCL10 was present at high concentrations in plasma and peritoneal cavity during CLP-induced septic shock. Survival was significantly improved in CXCL10 knockout (CXCL10KO) mice and mice treated with anti-CXCL10 IgG compared to controls. CXCL10KO mice and mice treated with anti-CXCL10 IgG showed attenuated hypothermia, lower concentrations of interleukin-6 (IL-6) and macrophage inhibitory protein-2 (MIP-2) in plasma and lessened natural killer (NK) cell activation compared to control mice. Compared to control mice, bacterial burden in blood and lungs was lower in CXCL10-deficient mice but not in mice treated with anti-CXCL10 IgG. Treatment of mice with anti-CXCL10 IgG plus fluids and Primaxin at 2 or 6 hours after CLP significantly improved survival compared to mice treated with non-specific IgG under the same conditions. Conclusions: CXCL10 plays a role in the pathogenesis of CLP-induced septic shock and could serve as a therapeutic target during the acute phase of septic shock

Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses

Investigating the complex systems dynamics of the aging process requires integration of a broad range of cellular processes describing damage and functional decline co-existing with adaptive and protective regulatory mechanisms. We evolve an integrated generic cell network to represent the connectivity of key cellular mechanisms structured into positive and negative feedback loop motifs centrally important for aging. The conceptual network is casted into a fuzzy-logic, hybrid-intelligent framework based on interaction rules assembled from a priori knowledge. Based upon a classical homeostatic representation of cellular energy metabolism, we first demonstrate how positive-feedback loops accelerate damage and decline consistent with a vicious cycle. This model is iteratively extended towards an adaptive response model by incorporating protective negative-feedback loop circuits. Time-lapse simulations of the adaptive response model uncover how transcriptional and translational changes, mediated by stress sensors NF-κB and mTOR, counteract accumulating damage and dysfunction by modulating mitochondrial respiration, metabolic fluxes, biosynthesis, and autophagy, crucial for cellular survival. The model allows consideration of lifespan optimization scenarios with respect to fitness criteria using a sensitivity analysis. Our work establishes a novel extendable and scalable computational approach capable to connect tractable molecular mechanisms with cellular network dynamics underlying the emerging aging phenotype

R. Menendez, et al., “ Code-Grouping of Spectrally Phase Encoded OCDMA Based on Walsh-Decomposition of Hadamard Codes, ” IEEE ICC 2006 Code-Grouping of Spectrally Phase Encoded OCDMA based on Walsh-Decomposition of Hadamard Codes

Abstract (1) –We propose a novel optical networking concept enabling the routing of groups of spectrally phase encoded (SPE) optical code division multiple access (OCDMA) signals. This code grouping is based on particular properties of the Hadamard sequences, i.e. the existence of a multiplicative basis based on Walsh sequences. We describe here how this code grouping concept permits groups of SPE codes to be passively "labeled " and routed as groups on the basis of those labels and provide simulation results demonstrating the process. The ability to deal with groups of codes has important implications for routing and for the overall signal obscurity provided by OCDMA. I

Novel Results on the Coexistence of Spectrally Phase-Encoded OCDMA and DWDM

Abstract (1) –We propose and experimentally validate a novel method for transmitting several OCDMA channels in the unused bandwidth of a single WDM channel, thus allowing the OCDMA and SONET signals to share the same WDM channel. The theoretical justification of this new modulation scheme is based on a powerful property of spectrally phase-encoded OCDMA signals which is reported and proved for the first time: the operation of spectral phase encoding allows us to convey broadband signals over a disjoint (non-contiguous) frequency support. Remarkably, this property does not impair signal orthogonality so that it can be exploited both in synchronous and asynchronous OCDMA. I

Toliver at al., "Optical Network Compatibility Demontsration of O-CDMA Based on Hyperfine Spectral Phase Coding", IEEE LEOS'04 Optical Network Compatibility Demonstration of O-CDMA Based on Hyperfine Spectral Phase Coding

Abstract (1) : We demonstrate compatibility of Optical-CDMA with conventional DWDM networking by simultaneously transmitting two hyperfine spectral-phase-coded 2.5 Gb/s O-CDMA signals with six DWDM channels through a transparent reconfigurable network having 25 km node spacing. 1. Introduction: Recently, there has been a renewed interest in optical CDMA (O-CDMA) [1] due to its potential for offering increased levels of security at ultra-high data rates as well as simplifying critical networking functions such as code assignment and code conversion. However, much of the research done in this area has focused on homogeneous O-CDMA networking, where fiber bandwidth is used strictly for O-CDMA. On the other hand, emerging optically transparent networks could allow for a variety of signal types, modulation formats, and bit rate

S. Galli et al., “DWDM-Compatible Spectrally Phase Encoded Optical CDMA”, Globecom 2004 DWDM-Compatible Spectrally Phase Encoded Optical CDMA

Abstract (1) – We present initial results on a WDM compatibl

Network Applications of Cascaded Passive Code Translation For WDM-Compatible Spectrally Phase-Encoded Optical CDMA

Recently, there has been a renewed interest in optical code-division multiple access (OCDMA) due to its potential for offering increased levels of security at ultrahigh data rates as well as for simplifying key networking functions, such as replacing (active) wavelength translation with cascaded passive all-optical code translation (CT). Much of the research done in this area has focused on homogeneous OCDMA networking, where it is assumed that the fiber bandwidth is used only for OCDMA signals. In contrast to other proposed OCDMA systems, we have developed a novel narrowband (NB) spectrally phaseencoded (SPE) OCDMA that is compatible with existing transparent reconfigurable dense-WDM (DWDM) networks and has high spectral efficiency. In this paper, we experimentally demonstrate, for the first time, the feasibility of multistage CT in the proposed WDM-compatible SPE OCDMA system, and we also describe how cascaded CTs can play a central role in ring- and starnetwork architectures. Specifically, we describe a star-network architecture in which both unicast and multicast interconnections among ends are passively "routed" by means of such cascaded CTs, a ring-network architecture in which CT and fast optical switching enable a code-based equivalent to add/drop wavelength multiplexing, and a shared code-scrambling application for increased signal obscurity