TRA-950: A DYNAMIC PROGRAMMING APPROACH FOR ARTERIAL SIGNAL OPTIMIZATION IN A CONNECTED VEHICLE ENVIRONMENT

Within the Connected Vehicle (CV) environment, vehicles are able to communicate with each other and with infrastructure via wireless communication technology. The collected data from CVs provide a much more complete picture of the arterial traffic states and can be utilized for signal control. Based on the real-time traffic information from CVs, this paper enhances an arterial traffic flow model for arterial signal optimization. Then a dynamic programming optimization model is created to solve the signal optimization application. A real-world arterial corridor is modeled in VISSIM to validate the algorithms. This approach is shown to generate good results and may be superior to well-tuned fixed-time control

TRA-956: IMPROVING INTERSECTION THROUGHPUT USING CONNECTED VEHICLES

This paper proposes a connected vehicle based approach to improve the throughput at signalized intersections and ultimately increase the mobility of a transportation system. Connected vehicle technology demonstrates tremendous potential for improving safety and mobility, as it enables the real-time sharing of vehicle data, including position, speed, acceleration, etc., not only among vehicles but also between vehicles and infrastructure. The proposed approach takes advantage of such real-time data to develop a strategy that maximizes throughput of an isolated intersection locally. Accordingly, the problem is formulated as a two-step centralized optimization. There are two main processes in this method: optimization for vehicles in motion, and optimization for stopped vehicles. The first step maximizes the intersection throughput of vehicles in motion using advisory acceleration. The second one minimizes the total delay of the stopped vehicles by adjusting the positions at which vehicles stop. A case study is also presented to show the efficiency of the proposed approach, which improves the traffic flow throughput of an isolated signalized intersection and reduces the total delay of all vehicles

TRA-910: CONNECTED VEHICLE V2I COMMUNICATION APPLICATION TO ENHANCE DRIVER AWARENESS AT SIGNALIZED INTERSECTIONS

This study introduces a Vehicle-To-Infrastructure (V2I) architecture to enhance driver awareness at signalized intersections. The main objectives are to (i) provide a proof-of-concept field experiment on the use of V2I communication architecture at a signalized intersection and (ii) evaluate the impact of V2I communication on improving driver performance while crossing the intersection. The proposed V2I communication application will relay an advisory auditory message to the driver regarding the status of the traffic signal. It is expected that driver behaviour is going to change as a result of the in-vehicle audible message. Consequently, the proposed application will collect additional driver performance indicators which include information on average speed, maximum speed, and the acceleration\deceleration profiles. To understand the impact of the advisory message on changing driver behaviour, a comparison was performed between the indicators with and without the in-vehicle message. Driver behavior was investigated under two scenarios, namely; as the driver heads towards a green signal and as the driver heads towards a red signal. For both scenarios, the results show that the average speed of the driver have changed significantly after turning “on” the in-vehicle messages. In addition, the maximum speed distribution shifted towards a lower value indicating decreases in maximum speeds. Moreover, the difference between the acceleration\deceleration profiles near the intersection when driving with and without the message, while heading towards a red signal, was found to be significant. These preliminary results show that the proposed V2I communication application can have promising impacts on improving driver awareness at signalized intersections

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Trade-Offs Between Bus and Private Vehicle Delays at Signalized Intersections: Case Study of a Multiobjective Model

Mixed road users on most urban arterials are controlled by the same set of signals and must compete for shared road space. Transit signal priority (TSP) systems have been established to improve transit service operations in mixed traffic. To balance the benefits of priority control with the negative effects, most existing adaptive TSP strategies normally use an integrated performance index, a weighted sum of all types of delays, for evaluation and optimization. In a previous study, the authors formulated the TSP optimization into a quadratic programming problem with an enhanced delay-based performance index to obtain global optimization. In this study, the problem was formulated into a multiobjective optimization model, which was solved with a nondominated sorting genetic algorithm. Pareto-optimal front results were presented to evaluate the trade-offs between two objectives: minimization of private vehicle delay and of bus delay. Then the most appropriate solution was chosen with high-level information. A simulation study was conducted along 7.4 km of a bus corridor, with an adaptive TSP simulation platform, by using a full-scale signal simulator, ASC/3, in Vissim. The results show that the Pareto-optimal solutions provided more interesting practical options for decision makers