Th. 3e cycle--Géogr. et aménage. urbain--Paris 1, 1986.

The growing number of trucks traveling on freeways has caused more traffic congestion and increased the likelihood of truck-related crashes. Many transportation agencies are considering a new concept of truck-only toll (TOT) lanes to provide a more efficient and safer freight transportation system. This research develops a methodology for identifying candidate TOT lanes in the freeway system. The modeling of TOT lanes in different geographic applications includes individual TOT corridors, a regional TOT network, and a statewide TOT network. The criteria employed in a geographic information system (GIS)-based screening process to determine feasible TOT corridors and their boundaries/extents include: freeway level of service, truck volumes, truck percentage of total freeway flow, truck-related crashes, and truckers willingness to pay. The research also presents the process for determining optimum toll rates for TOT lanes. Furthermore, this research addresses issues of assessing the engineering design of TOT lane placement and the performance measures of using either mandatory or voluntary TOT lanes. This research also examines freeway performance under two scenarios -- adding general purpose lanes or building TOT lanes with both mandatory and voluntary use. Finally, this research addresses the strategies for critical issues associated with the planning, design, and operation of TOT lanes and presents TOT planning guidance.

Thesis (M.A.)--Virginia Polytechnic Institute and State University, 1994. / Vita. Abstract. Includes bibliographical references (leaves 165-190). Also available via the Internet.

Thesis (M.P.A.)--University of Hong Kong, 1997. / Includes bibliographical references (leaf i-viii).

Thesis (M.P.A.)--University of Hong Kong, 1997. / Includes bibliographical references (leaves i-viii). Also available in print.

Submitted to the faculty of Indiana University in partial fulfillment of the requirements for the degree Master of Science in the department of Bioinformatics in School of Informatics of Indiana University 29 January, 2004 / Background: Toll and Toll-related proteins play an important role in antibacterial innate immunity and are widespread in insects, plants, and mammals. The completion of new genomes such as Anopheles gambiae has provided an avenue for a deeper understanding of Toll evolution. While most evolutionary analyses are performed on protein sequences, here, we present a unique phylogenetic analysis of Toll genes from the perspective of upstream regulatory regions so as to study the importance of evolutionary information inherited in such sequences. Results: In a comparative study, phylogeny on the protein products of Toll like genes showed consistency with earlier literature except for the single point of divergence between insects and mammals. On the other hand, the phylogeny based on upstream regulatory sequences (-3000 to +10) showed a broader distinction between the plants and the rest, though the tree was not well resolved probably due to poor alignment of these sequences. The phylogeny based on TFBs necessitated the development of a supervised statistical approach to determine their “evolutionary informativeness”. Employing the frequency of evolutionarily informative TFBs, a phylogeny was derived using pair-wise distances. It suggested a closer relationship between Anopheles and plants than to Drosophila and a significant homology among mammalian TLRs. Conclusions: A unique approach of using TFBs in studying evolution of Toll genes has been developed. Broadly, this approach showed results similar to the protein phylogeny. The inclusion of the evolutionary information from TFBs may be relevant to such analyses due to the selective pressure of conservation in upstream sequences.

The effectiveness of modifying a conventional toll plaza for implementation of an open road tolling concept with express ETC lanes was evaluated in this thesis. Speed controlled dedicated ETC lanes were replaced with express ETC lanes at the Orlando-Orange County Expressway Authority (OOCEA) University Mainline Toll Plaza. This evaluation was accomplished by utilizing collected field data and simulated scenarios using Toll Plaza SIMulation (TPSIM) software developed by the University of Central Florida. The speed controlled dedicated ETC lanes were located within toll lanes (contained within a toll plaza canopy) with widths ranging between 10 to 14 ft. These types of lanes required all vehicles to reduce their speed from the highway speed to 35 mph. Express ETC lanes (sometimes referenced as open road tolling or non-stop tolling) allow vehicles to pass through the plaza at high speeds. Open road tolling is a concept that employs high speed toll lanes. A before and after study of the University toll plaza was conducted. Benefits in the form of reduced delays and increased capacities were observed when making the comparison between the before and after studies. Since we expect the capacity of an express ETC lane to be greater than the dedicated ETC lanes (due to an increase in free-flow speed), further analysis using equations and car-following theory proved that if the ETC speed was increased, then the capacity would increase as well. Using equations derived from the Highway Capacity Manual (HCM) and car-following theory, the capacity was increased from 2016 to 2314 vph when the ETC speed increased from 31 mph to 65 mph. This indicated an increase in capacity of 14.8 percent (based on the conversion from dedicated to express ETC lanes). The field data was also used as input for TPSIM (a computer simulation model) in order to perform a sensitivity analysis of the express ETC lanes by varying the type of ETC lane, number of approach lanes, and plaza configurations (the addition of an ACM lane) between scenarios. Results that were observed during the after study were verified using the TPSIM scenarios. Reductions in delays for the entire plaza were observed using the TPSIM model when making similar improvements to the plaza as in the after study. The changes made to the University Mainline Toll Plaza after construction was completed resulted in benefits by reducing delays and increasing the capacity of the toll plaza (by converting dedicated ETC lanes to express ETC lanes and adding an additional A/ETC lane per direction). These benefits were measured using field data and confirmed when performing the TPSIM scenarios. A customer's travel time along the toll facility will be reduced by using the express ETC lanes (since they are not required to decelerate at the toll plaza). In addition, weaving maneuvers downstream of the plaza are no longer required by customers using the express ETC lanes due to the location of the downstream travel lanes in relation to the express ETC lanes. These benefits may have led to changes in the number and percentage of ETC users in each of the toll lanes. Changes in ETC usage in the conventional mixed-use lanes directly impacted the throughput and delays for each of these lanes, since ETC equipped vehicles have a service time of zero seconds. In addition to the operational benefits, other possible benefits for express ETC lanes were identified and recommended for further evaluation and research. The re-distribution of customers at the plaza due to the implementation of open road tolling, in the form of express ETC lanes, was a great benefit to the overall traffic operations for the University Mainline Toll Plaza in Orlando, Florida.

The molecular mechanism(s) by which Toll-like receptors become activated are not well understood. For the majority of TLR receptors, dimerization is a prerequisite to facilitate MyD88-TLR complex formation and subsequent cellular signaling to activate NF-κB. However, the parameters controlling interactions between the receptors and their ligands still remain poorly defined. Previous reports have identified that neuraminidase-1 (NEU1) is an important intermediate in the initial process of TLR ligand induced receptor activation and subsequent cell function. What we do not yet understand is how NEU1 is activated following TLR ligand binding. In this thesis, the findings disclose a receptor signaling paradigm involving a process of receptor ligand-induced GPCR-signaling via neuromedin-B (NMBR) Gα-proteins, matrix metalloproteinase-9 (MMP-9) activation, and the induction of Neu1 activation. Central to this process is that NEU1–MMP-9-NMBR complex is associated with TLR-4 receptors on the cell surface of naive primary macrophages and TLR-expressing cell lines. Ligand binding to the receptor initiate GPCR-signaling via GPCR Gα subunit proteins and MMP-9 activation to induce NEU1. Activated NEU1 targets and hydrolyzes sialyl α-2-3-linked to β-galactosyl residues at the ectodomain of TLRs, enabling the removal of steric hindrance to receptor association, activation of receptors and cellular signaling. Furthermore, a novel glycosylation model is uncovered for the activation of nucleic acid sensing intracellular TLR-7 and TLR-9 receptors. It discloses an identical signaling paradigm as described for the cell-surface TLRs. NEU1 and MMP9 cross-talk in alliance with neuromedin-B receptors tethered to TLR-7 and -9 receptors at the ectodomain is essential for ligand activation of the TLRs and pro-inflammatory responses. However, the mechanism(s) behind this GPCR and TLR cross-talk has not been fully defined. Here, GPCR agonists mediate GPCR-signaling via membrane Gα subunit proteins to induce NEU1 and MMP-9 cross-talk at the TLR ectodomain on the cell surface. This molecular organizational GPCR signaling platform is proposed to be an initial processing stage for GPCR agonist-induced transactivation of TLRs and subsequent cellular signaling. Collectively, these novel findings radically redefine the current dogma(s) governing the mechanism(s) of the interaction of TLRs and their ligands, which may provide important pioneering approaches to disease intervention strategies. / Thesis (Ph.D, Microbiology & Immunology) -- Queen's University, 2013-04-30 12:23:42.429

Une compréhension fine et détaillée ciblant les mécanismes d’action de nouvelles molécules adjuvantes sur notre système immunitaire vise de manière directe à l’élaboration de nouveaux vaccins plus ciblés et plus efficaces, mais aussi à élargir nos connaissances quant à l’induction d’une réponse immune protectrice. Au cours de cette thèse nous avons voulu comprendre les modes d’action de deux molécules lipidiques distinctes. La première est le lipide cationique diC14-amidine dont il avait été démontré une action sur les cellules dendritiques en culture par une voie qui restait à élucider. Ce lipide cationique s'organise sous forme de liposomes en milieu aqueux et peut s'associer à de nombreux antigènes. La seconde est un analogue synthétique de l'adjuvant monophosphoryl lipide A (MPL), un dérivé du LPS, nommé CRX-527. À l'instar de sa molécule parente, le CRX-527 active le récepteur TLR4 et est considéré comme un adjuvant potentiel de vaccin ou comme immunostimulant isolé. Au cours de notre travail, nous avons démontré que la diC14-amidine active les cellules cibles via le récepteur TLR4. En effet, l'absence de ce récepteur abolit les réponses induites par le lipide cationique diC14-amidine et la transfection du gène codant pour TLR4 rend répondeuses des cellules qui n'exprimaient pas ce récepteur. De plus, la diC14-amidine active et mature des cellules dendritiques, aussi bien de provenance murine qu'humaine, suggérant qu'elle puisse être utilisée en tant qu’adjuvant. Il avait d’ailleurs été précédemment décrit que l'injection d'un complexe diC14-amidine / allergène chez la souris induisait une réponse immune suffisante pour conférer une protection contre cet allergène. Dans ce contexte, nous avons caractérisé au niveau cellulaire la réponse induite suite à l'injection du complexe diC14-amidine / ovalbumine chez la souris. Cette réponse se manifeste par une production d'IFNγ lors d'une re-stimulation ex vivo par l'antigène OVA. En ce qui concerne la molécule CRX-527, nous nous sommes particulièrement focalisés sur le rôle du co-récepteur du TLR4, le CD14, dans les réponses innées induites par le CRX-527. Nous avons établi que, de manière inattendue et contrairement à la plupart des ligands TLR4, le CRX-527 induit la production de nombreuses cytokines et chimiokines en complète absence de CD14, même à faible dose. De plus, l'ajout de CD14 sous sa forme soluble ne modifie pas le niveau des réponses associées à la voie de signalisation MyD88 / NF-κB. Cependant, il semblerait que la stimulation de cellules par du CRX-527 en présence de CD14 soluble recombinant, favorise plutôt la voie TRIF / IRF3, comme le suggère l'augmentation du taux de production d'IFNβ et d'activation d'IRF3. La molécule CD14 (membranaire et/ou soluble) ne serait donc pas qu'un simple transporteur de ligands, comme il l'a été décrit par le passé, mais bien une protéine impliquée dans la modulation des réponses induites lors de l'activation du TLR4. Le CD14 jouerait donc un rôle, aussi bien au niveau de la discrimination des ligands, que celle des voies de signalisation activées.

Thesis (doctoral)--University of Oulu, 2007. / Title from PDF title screen. Includes bibliographical references (p. 226-238). Also available on the World Wide Web.