Shippers of freight face many choices and trade-offs. Two choices of particular interest are those of mode of choice and shipment size. These two choices are interdependent, and they also depend on other commodity and modal attributes. Unlike previous studies on the subject, this paper considers the dependence between unit freight charge and shipment size in deriving a shipper's economic order quantity (EOQ). It also examines the nature of this dependence, and studies the effect of market and commodity attributes on optimal shipment size. A numerical example is provided in which optimal shipment size is calculated for full truckload (TL) and less-than-truckload (LTL), and the results are compared with those of previous studies.
The Macrophage-Inducible C-type Lectin receptor (Mincle) plays a critical role in innate immune recognition and pathology, and therefore represents a promising target for vaccine adjuvants. Innovative trehalose-based Mincle agonists with improved pharmacology and potency may prove useful in the development of Th17-mediated adaptive immune responses. Herein, we report on in vitro and in silico investigations of specific Mincle ligand-receptor interactions required for the effective receptor engagement and activation of Th17-polarizing cytokines. Specifically, we employed a library of trehalose benzoate scaffolds, varying the degree of aryl lipidation and regiochemistry that produce inflammatory cytokines in a Mincle-dependent fashion. In vitro interleukin-6 (IL-6) cytokine production by human peripheral blood mononuclear cells (hPBMCs) indicated that the lipid regiochemistry is key to potency and maximum cytokine output, with the tri-substituted compounds inducing higher levels of IL-6 in hPBMCs than the di-substituted derivatives. Additionally, IL-6 production trended higher after stimulation with compounds that contained lipids ranging from five to eight carbons long, compared to shorter (below five) or longer (above eight) carbon chains, across all the substitution patterns. An analysis of the additional cytokines produced by hPBMCs revealed that compound
This paper proposes a methodology for identifying and evaluating horizontal alignment consistency based on the analysis of speed reduction on horizontal curves. The paper also investigates the effects of a number of geometric design elements on operating speeds. It was found that the reduction in the 85th percentile speed on curves with long approach tangents is strongly correlated with both degree of curvature and curve deflection angle. A speed reduction model is developed and applied to compare two alternative horizontal alignments of a proposed rural highway in Jordan. It is recommended that existing minimum radius requirements, such as those of AASHTO, be extended under certain circumstances, to achieve consistency in horizontal alignments. (a)
Co-delivery of antigens and adjuvants to the same antigen presenting cells (APCs) can significantly improve the efficacy and safety profiles of vaccines. Here, we report amine-grafted silica nanoparticles (A-SNPs) as a tunable vaccine co-delivery platform for TLR7/8 agonists along with the recombinant influenza antigen hemagglutinin H7 (H7) to APCs. A-SNPs of two different sizes (50 and 200 nm) were prepared and coated with INI-4001 at different coating densities, followed by co-adsorption of H7. Both INI-4001 and H7 showed > 90% adsorption to the tested A-SNP formulations. TNF-α and IFN-α cytokine release by human peripheral blood mononuclear cells as well as TNF-α, IL-6, and IL-12 release by mouse bone marrow-derived dendritic cells revealed that the potency of the INI-4001-adsorbed A-SNPs (INI-4001/A-SNP) formulations can be improved relative to aqueous formulation control. This improved potency was dependent on particle size and ligand coating density. In addition, slow-release profiles of INI-4001 were measured from INI-4001/A-SNP formulations in plasma with 30-50% INI-4001 released after 7 days. In vivo murine immunization studies demonstrated significantly improved H7-specific humoral and Th1/Th17-polarized T cell immune responses with no observed adverse reactions. Low-density 50 nm INI-4001/A-SNP elicited significantly higher IFN-γ and IL-17 induction over that of the H7 antigen only group and INI-4001 aqueous formulation controls. In summary, this work introduces an effective and biocompatible SNP-based co-delivery platform that enhances the immunogenicity of TLR7/8 agonist-adjuvanted subunit influenza vaccines.
Silica nanoparticles have been increasingly used in developing bioanalytical, biomedical and in many other applications. Silica nanoparticles can easily be synthesized and with the advent of wide availability of modified TEOS reactive analogues only the researcher imagination is the limit of preparing silica nanoparticles that contain different molecules that are either copolymerized inside of the silica nanoparticle or chemically attached (bonded) to the silica nanoparticle surface. Relatively non-porous silica nanoparticles can contain copolymerized dyes for the creation of bright fluorescence labels while the surface of these silica nanoparticles can be bonded with reactive moieties that are suitable for covalently labeling the molecule of interest. Also the surface bonded moieties can serve other purposes, e.g., molecular recognition either on a non-fluorescent or fluorescent silica nanoparticle. As far as the fluorescent nanoparticles development concerns near-infrared (NIR) absorbing carbocyanine dyes have been increasingly used as they can be useful for developing bioanalytical, biomedical methods and in many other applications. Carbocyanines are preferred as they are relatively easy to synthesize and can be designed to achieve particular spectroscopic properties. For example either copolymerized or surface bound dyes can contain appropriate functional moieties absorption and fluorescence properties change when it is complexed to metal ions, to detect pH changes, bind to biological molecules, etc. Fluorescence intensity of carbocyanines significantly increases by enclosing several dye molecules in a single silica nanoparticle due to shielding however self quenching may become a problem at high dye concentrations in confined spaces. Large Stokes' shift dyes can significantly decrease this problem. This can be achieved by substituting meso position halogens in the NIR fluorescent carbocyanines with a linker containing amino moiety which can also serve as linker to covalently attach the dye molecule during the nanoparticle synthesis. This presentation discusses facile synthesis and applications of silica nanoparticles containing copolymerized fluorophores and/or surface bound moieties. Applications include silica nanoparticles containing several dye molecules as bright labels in immunochemical uses, cell imaging and forensic applications for latent blood detection. This latter application was developed using leuco fluorescein copolymerized silica nanoparticles. This synthesis proved that copolymerized dyes can be further modified after the dye containing silica nanoparticle was formed. Surface bound moiety examples will be given for capillary electrochromatography using amino acid-bonded silica nanoparticles as pseudostationary phases as chiral selectors.
The XIIIth World Meeting of the International Road Federation was held in Toronto, Ontario from June 16 to 20, 1997. The papers are presented in one of the three official languages of the conference as submitted by the author (English, French or Spanish). The proceedings are available on CD-Rom. This work session contains the following papers: A comparison of fuzzy and neural classifiers for road accidents analysis (Sayed,T, de Leur,P, Abdelwahab,W) [English]; A new train-illuminated sign for highway-railroad grade crossings (Russell,ER, Rys,M, Kovvali,V) [English]; A study of long combination vehicles on two-lane highways (Barton,R, Morrall,J, Zutautas,B) [English]; An analysis of the influence of speed on traffic security with the instrumented vehicle CANE (Aparicio,F, Martinez,L) [Spanish]; An improved installation method for luminaires and cameras in congested areas (Watson,CP, Fearnley,E) [English]; Are urban vehicle speed related to street environmental factors? (Lee-Joe,T, Dunn,RCM) [English]; Computerized road safety auditing, data collection and analysis techniques (Waugh,JM) [English]; Computer supported information system for traffic safety analysis (Certanc,N, Strah,B and Breska,Z) [English]; Criterion for evaluating the effectiveness of winter road maintenance on traffic safety (Hanbali,RM) [English]; Data collection and analysis methods with respect to safety (Moreira,EA) [English]; Electrical installation and safety equipment in road tunnels (Koller,R) [English]. (Continued on IRRD abstract No. 490258).
This paper was presented at the 'Cost-Effective Designs for Trucks' session. Long steep downgrades along rural mountainous highways constitute a significant risk to the trucking industry. This paper addresses this risk and suggests practical engineering solutions. The main objective of the paper is to introduce a systematic approach to determine the need for and location of truck escape ramps (TERs). The approach utilizes variables concerning the design vehicle, the road and the driver. These variables are included in either a stochastic or deterministic form. A number of supplementary variables are also used, such as accident history and the presence of objects within the trajectory of a runaway vehicle. The approach also utilizes a number of existing vehicle-road performance models to generate relevant data concerning the descent speed, cornering stability and brake temperature. The application of the methodology is illustrated with examples from highways in mountainous terrain in Jordan and Western Canada. The examples selected are diverse and were chosen to illustrate the generalized nature of the methodology. For the covering abstract of this conference see IRRD number 872812. (A)
