32 research outputs found

    Examining queue-jumping phenomenon in heterogeneous traffic stream at signalized intersection using UAV-based data

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    © 2020, Springer-Verlag London Ltd., part of Springer Nature. This research presents an in-depth microscopic analysis of heterogeneous and undisciplined traffic at the signalized intersection. Traffic data extracted from the video recorded using an unmanned aerial vehicle (UAV) at an approach of a signalized intersection is analyzed to study the within green time dynamics of traffic flow. Various parameters of Wiedemann 74, Wiedemann 99, and lateral behavior models used in microscopic traffic simulation package, Vissim, are calibrated for the local heterogeneous traffic. This research is aimed at exploring the queue-jumping phenomenon of motorbikes at signalized intersections and its impact on the saturation flow rate, travel time, and delay. The study of within green time flow dynamics shows that the flow of traffic within green time is not uniform. Surprisingly, the results indicate that the traffic flow for the first few seconds of the green time is significantly higher than the remaining period of green time, which shows a contradiction to the fact that traffic flow for the first few seconds is lower due to accelerating vehicles. Mode-wise traffic counted per second shows that this anomaly is attributed to the presence of motorbikes in front of the queue. Consequently, the outputs of simulation results obtained from calibrated Vissim show that the simulated travel time for motorbikes is significantly lower than the field-observed travel times even though the average simulated traffic flow matches accurately with the field-observed traffic flow. The findings of this research highlight the need to incorporate the queue-jumping behavior of motorbikes in the microsimulation packages to enhance their capability to model heterogeneous and undisciplined traffic

    Inhibition of glucose metabolism selectively targets autoreactive follicular helper T cells.

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    Follicular helper T (TFH) cells are expanded in systemic lupus erythematosus, where they are required to produce high affinity autoantibodies. Eliminating TFH cells would, however compromise the production of protective antibodies against viral and bacterial pathogens. Here we show that inhibiting glucose metabolism results in a drastic reduction of the frequency and number of TFH cells in lupus-prone mice. However, this inhibition has little effect on the production of T-cell-dependent antibodies following immunization with an exogenous antigen or on the frequency of virus-specific TFH cells induced by infection with influenza. In contrast, glutaminolysis inhibition reduces both immunization-induced and autoimmune TFH cells and humoral responses. Solute transporter gene signature suggests different glucose and amino acid fluxes between autoimmune TFH cells and exogenous antigen-specific TFH cells. Thus, blocking glucose metabolism may provide an effective therapeutic approach to treat systemic autoimmunity by eliminating autoreactive TFH cells while preserving protective immunity against pathogens

    The TYK2-P1104A Autoimmune Protective Variant Limits Coordinate Signals Required to Generate Specialized T Cell Subsets

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    TYK2 is a JAK family member that functions downstream of multiple cytokine receptors. Genome wide association studies have linked a SNP (rs34536443) within TYK2 encoding a Proline to Alanine substitution at amino acid 1104, to protection from multiple autoimmune diseases including systemic lupus erythematosus (SLE) and multiple sclerosis (MS). The protective role of this SNP in autoimmune pathogenesis, however, remains incompletely understood. Here we found that T follicular helper (Tfh) cells, switched memory B cells, and IFNAR signaling were decreased in healthy individuals that expressed the protective variant TYK2A1104 (TYK2P). To study this variant in vivo, we developed a knock-in murine model of this allele. Murine Tyk2P expressing T cells homozygous for the protective allele, but not cells heterozygous for this change, manifest decreased IL-12 receptor signaling, important for Tfh lineage commitment. Further, homozygous Tyk2P T cells exhibited diminished in vitro Th1 skewing. Surprisingly, despite these signaling changes, in vivo formation of Tfh and GC B cells was unaffected in two models of T cell dependent immune responses and in two alternative SLE models. TYK2 is also activated downstream of IL-23 receptor engagement. Here, we found that Tyk2P expressing T cells had reduced IL-23 dependent signaling as well as a diminished ability to skew toward Th17 in vitro. Consistent with these findings, homozygous, but not heterozygous, Tyk2P mice were fully protected in a murine model of MS. Homozygous Tyk2P mice had fewer infiltrating CD4+ T cells within the CNS. Most strikingly, homozygous mice had a decreased proportion of IL-17+/IFNγ+, double positive, pathogenic CD4+ T cells in both the draining lymph nodes (LN) and CNS. Thus, in an autoimmune model, such as EAE, impacted by both altered Th1 and Th17 signaling, the Tyk2P allele can effectively shield animals from disease. Taken together, our findings suggest that TYK2P diminishes IL-12, IL-23, and IFN I signaling and that its protective effect is most likely manifest in the setting of autoimmune triggers that concurrently dysregulate at least two of these important signaling cascades

    An Automated Method To Predict Mouse Gene and Protein Sequences Using Variant Data

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    With recent advances in sequencing technologies, the scientific community has begun to probe the potential genetic bases behind complex phenotypes in humans and model organisms. In many cases, the genomes of genetically distinct strains of model organisms, such as the mouse (Mus musculus), have not been fully sequenced. Here, we report on a tool designed to use single-nucleotide polymorphism (SNP) and insertion-deletion (indel) data to predict gene, mRNA, and protein sequences for up to 36 genetically distinct mouse strains. By automated querying of freely accessible databases through a graphical interface, the software requires no data and little computational experience. As a proof of concept, we predicted the gene and amino acid sequence of the aryl hydrocarbon receptor (Ahr) for all inbred mouse strains of which variant data were currently available through Mouse Genome Project. Predicted sequences were compared with fully sequenced genomes to show that the tool is effective in predicting gene and protein sequences

    Growth of Pseudomonas and Bacillus biofilms on pretreated polypropylene surface

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    Unpretreated and Aquaregia, Fenton, thermal and short UV pretreated polypropylene films of 0.05 mm thickness were subjected to biodegradation in vitro in minimal medium with four soil cultures, namely Pseudomonas azotoformans, Pseudomonas stutzeri, Bacillus subtilis and Bacillus flexus separately for 12 months. P. azotoformans and B. subtilis are relatively hydrophobic, produce biosurfactant and form biofilm on the polymer with comparatively higher carbohydrate and protein than the other two organisms. All the organisms make use of the polymer as their carbon source. Highest weight loss (2.5%) was observed in the case of short UV treated polymer exposed to B. flexus after one year. The carbonyl indices decreased in one year in the case of pretreated polymer and increased in the case of untreated polymer, indicating only abiotic oxidation in the absence of pretreatment. Increase in surface energy indicated that the polymer became more hydrophilic when compared to the original. P. stutzeri had marginal effect on the polymer
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