Evaluating Model Mismatch Impacting CACC Controllers in Mixed Traffic using a Driving Simulator

International audienceAt early market penetration, automated vehicles will share the road with legacy vehicles. For a safe transportation system, automated vehicle controllers therefore need to estimate the behavior of the legacy vehicles. However, mismatches between the estimated and real human behaviors can lead to inefficient control inputs, and even collisions in the worst case. In this paper, we propose a framework for evaluating the impact of model mismatch by interfacing a controller under test with a driving simulator. As a proof-of-concept, an algorithm based on Model Predictive Control (MPC) is evaluated in a braking scenario. We show how model mismatch between estimated and real human behavior can lead to a decrease in avoided collisions by almost 46%, and an increase in discomfort by almost 91%. Model mismatch is therefore non-negligible and the proposed framework is a unique method to evaluate them

Buffer-Aided Model Predictive Controller to Mitigate Model Mismatches and Localization Errors

Any vehicle needs to be aware of its localization, destination, and neighboring vehicles\u27 state information for collision free navigation. A centralized controller computes controls for cooperative adaptive cruise control (CACC) vehicles based on the assumed behavior of manually driven vehicles (MDVs) in a mixed vehicle scenario. The assumed behavior of the MDVs may be different from the actual behavior, which gives rise to a model mismatch. The use of erroneous localization information can generate erroneous controls. The presence of a model mismatch and the use of erroneous controls could potentially result into collisions. A controller robust to issues such as localization errors and model mismatches is thus required. This paper proposes a robust model predictive controller, which accounts for localization errors and mitigates model mismatches. Future control values computed by the centralized controller are shared with CACC vehicles and are stored in a buffer. Due to large localization errors or model mismatches when control computations are infeasible, control values from the buffer are used. Simulation results show that the proposed robust controller with buffer can avoid almost the same number of collisions in a scenario impacted by localization errors as that in a scenario with no localization errors despite model mismatch

Modeling and understanding the implications of future truck technology scenarios for performance-based freight corridor planning

Autonomous highway vehicles are coming. The question regarding this technology has shifted from “if” to “when”. Many advocates predict that autonomous trucks, in particular, will be commercially available within the next decade, and perhaps even before autonomous passenger vehicles. This includes the emergence of autonomous and connected multi-vehicle truck platoons. Unfortunately, this technology is developing more rapidly than the public sector is preparing for it; the situation is exacerbated by the fact that the timeframe for which the technology is expected to make up a substantial portion of the motor vehicle fleet is within the current planning horizon of most transportation planning agencies. Thus, there is an immediate need to explore the implications of this technology for public agency planning purposes; exploring these implications will in turn require the development of tools to quantify the potential costs and benefits involved. With these needs in mind, the objectives of this dissertation were to (1) develop a simulation modeling and performance measurement tool that incorporates autonomous and connected truck platooning technology into the long-range planning process, (2) demonstrate how this tool can be applied to a selected interstate corridor in Georgia (I-85 and I-285), and (3) develop a scenario planning framework that uses the results from the tool to guide policy development. The model consists of an iteratively linked, supply-demand equilibrium based multi-commodity and multi-vehicle class truck trip distribution and a highway traffic assignment model, requiring changes be made to the typical travel demand modeling process to capture the characteristics of platooning technology. The results from an empirical application of this model were then used to assess the safety-, economic-, congestion-, and emissions-related impacts of platooning technology. The model developed is flexible enough to allow for a number of variations in platooning details, and was supported by a multi-variable sensitivity analysis of key input variables. This sensitivity analysis showed a range of costs and benefits of the technology, with the greatest benefits seen when labor costs were cut by allowing some of the trucks to be driverless (which would also help to alleviate a currently significant shortage of experienced truck drivers). Allowing the autonomous trucks to operate on a dedicated lane was found to tremendously reduce travel time and congestion for those trucks. However, the magnitude of cost savings depends on a variety of factors, including the deployment of platoons of different sizes, the potential for platoon-supported fuel savings, and the level of corridor traffic congestion. In some scenarios, these congestion benefits came at the expense of the convenience of other vehicles, while in other scenarios, these vehicles experienced modest congestion-reduction benefits. The emissions impacts varied; the benefits for fuel consumption and emissions for platoons were as much as 9.6% at optimal speeds. While these findings are insightful, it is important to note that they are based on a specific set of assumptions and do not consider infrastructure costs related to the implementation of the technology. Changing the assumptions in some cases could significantly change the results. This research is one of the first efforts to modify a traditional travel demand model to simulate autonomous truck platoons. One of the key components of this contribution is the use of an origin-user equilibrium (OUE) traffic assignment, a relatively new path-based assignment which allows the user to specify vehicle class and origin specific traffic flows, and assign them to the network simultaneously. The OUE assignment has yet to be explored in depth with respect to multiple truck class-based, notably platoon-inclusive freight movements. Additionally, the research presents a new application of the Freight Analysis Framework, which is a widely used freight database within the United States. Given the uncertainty associated with platooning technology, there are a number of limitations associated with this research, and the final chapter of this dissertation discusses such limitations and presents opportunities for future work. As the details of platooning technology become clearer, tools such as the one developed here can assist transportation planners with incorporating such technological advances into their planning processes.Ph.D

Male genital tract versus blood HIV-1 compartmentalization and selection: the first step of the transmission bottleneck?

Introduction Sexual transmission of HIV-1 accounts for more than 80% of all the transmissions globally. After transmission, approximately 80% of the newly disseminated infections can be traced to a single variant, which comes from the minor HIV-1 population within the transmitting donor. This has led to the widely accepted idea of an HIV-1 transmission bottleneck. The nature of this bottleneck is not fully understood. Many studies working on understanding the nature of the transmitted virus have reported discordant traits of transmitted/founder viruses compared to viral isolates from chronically infected individuals. Such studies therefore lacked analysis of the intermediate step between these two populations: HIV-1 from the genital tract of the donors: where viruses are on their way to transmission to a new recipient. Importantly, numerous prior studies have shown that there is compartmentalization of HIV-1 populations between the general circulation and the genital tract, raising the possibility that the genital tract is an important selective environment. Collectively, prior studies of genital tract compartmentalization in males detected compartmentalization in about half of the donors studied, although by using techniques with limited depth of sampling than that employed in our study. The virus that establishes disseminated infection in a new recipient is selected. However, the extent to which this selection occurs before, during or after crossing the mucosal surfaces of the recipient is less clear – the period during which transmission selection could extend far back to the donor, and the donor’s genital tract. In other words, it is not clear as to what extent the transmission bottleneck occurs during compartmentalization of viral populations in the genital tract tissues. The design of an effective vaccine and other intervention strategies will rely upon the understanding the nature of the transmitted virus as this is the virus that must be targeted. This thesis Compartmentalization of minor variants cannot be tracked by techniques previously used to describe compartmentalization between the genital tract and the blood circulation. We therefore used deep sequencing-based techniques to further understand compartmentalization of viral populations between blood and the male genital tract. In addition, we tested the sensitivity of variants to a range of entry and other inhibitors in order to explore possible changes in function that may arise when viral variants grow in the shifted selective milieu of the genital tract. We further hypothesized that this change of selective milieu as HIV-1 moves from blood into the genital tract may lead to viral variants in semen that are sensitive to autologous neutralization because such sensitive variants may be able to grow in the genital tract, which is presumably partially or completely shielded from antibodies. Because the viral populations in semen comes from a site that may be relatively protected from antibodies, they may be permitted to evolve differently in the relative absence of antibody pressure. It is possible that evolution of the virus within the genital tract is a significant part of the change the virus undergoes on its way to establishment of a new disseminated infection in the new recipient. We considered this possibility because even some small molecules like those of some antiretroviral drugs do not penetrate the genital tract effectively under some circumstances, raising the possibility that antibodies might not always penetrate in all areas of the genital tract. This thesis had three objectives: 1. To evaluate HIV-1 compartmentalization in blood and the male genital tract using next generation sequencing to understand the nature of viral populations in these anatomical sites in greater detail. 2. To identify the differences in sensitivity of blood and semen variants to entry inhibitors to obtain information about differences in function between HIV-1 populations in blood vs the male genital tract. 3. To compare neutralization sensitivities of viral variants compartmentalized in blood and semen by testing their sensitivity to neutralization by autologous antibodies. As a control, we measured sensitivity to a pool of clade-matched heterologous sera to determine if any observed difference was due to global changes in neutralization sensitivity. Methods Study participants Forty-four HIV-1 seropositive men were recruited and then requested to donate blood and semen samples at ANOVA Health’s Ivan Toms clinics at Woodstock and Green Point or through their mobile clinic in Khayelitsha, all in Cape Town, South Africa. Viral loads from blood and semen and CD4+ T cell counts from blood were measured. HIV-1 was enriched from semen using a Nycodenz gradient, and then concentrated using ultracentrifugation. Chapter 2: HIV-1 Compartmentalization in blood and semen Next generation sequencing on Illumina paired-end Miseq platform was performed. To our knowledge there is no published study that has used this technique to study male genital tract HIV-1 variants in chronically infected male donors, although there is one that does so for acutely infected donors. We argue here that this is a superior method of sampling populations in blood and the male genital tract. In particular, it allowed us to more accurately track minor populations within each compartment. Additionally, the use of PrimerID approach allowed us to more clearly identify clonal amplification events in the HIV-1 populations. Sequencing was performed on either the V3 or C3-V5 region of the HIV-1 envelope gene from paired blood and semen samples from 11 donors. To evaluate compartmentalization, populations from blood and semen were compared using three standard techniques, Slatkin Maddison Test (SMT), Wrights measure of population subdivision (FST) and nearest neighbour statistic (Snn). Clonal amplification and results of modelling a lower depth of sampling are also presented. Chapter 3: Sensitivity of blood and semen variants to entry inhibitors and changes in function From three subjects who exhibited the highest extent of compartmentalization, full-length envelope clones derived from semen and blood RNA were made using limiting dilution PCR (single genome amplification), which provided the advantage of minimizing PCR-based artificial recombination. A high fidelity Taq polymerase was also used to minimize base-substitution errors. An average of 10 clones were isolated per compartment. Pseudoviruses were then constructed from the full-length envelope clones from blood and semen. The sensitivities of these pseudoviruses were tested against HIV-1 entry inhibitors; Maraviroc, PSCRANTES, enfurvirtide (T-20) and JM2987. Maraviroc and PSC-RANTES are CCR5 inhibitors while JM2987 is a CXCR4 inhibitor. Enfurvirtide (T-20) is a fusion inhibitor blocking the virus from entering cells. The full-length clones used to make the pseudoviruses were also sequenced and genomic variations in variable loop characteristics (length and number of potential glycosylation sites) between blood and semen compared. Chapter 4: Sensitivity of blood and semen variants to autologous and heterologous antibodies To study the differences in sensitivity of blood and semen variants to antibodies, pseudoviruses cloned from semen RNA and blood RNA (above) were tested for their sensitivities to donor antibodies collected at the same time the samples were collected or to a pool of HIV-1 subtype C sera. Results Objective 1: Viral compartmentalization via next generation sequencing HIV-1 populations were compartmentalized in all the 11 donors studied but to varying extents. Donor SVB043 had the most compartmentalized viral populations between blood and the male genital compartment using all the three measures of compartmentalization. Further analysis of the phylogenetic trees revealed that some clusters contained either purely blood or semen sequences, even in trees generated from analysis of donors with weakest compartmentalization. This might explain the viral compartmentalization signal in these weakly compartmentalized donors. To mimic reduced sampling depth, subsampling of the Illumina Miseq data with a small number of sequences was done. This analysis revealed that viral compartmentalization between blood and male genital tract would likely (>50% estimated likelihood) have been detected in only 5/11 (45%) of the donors, a proportion which is very similar to the aggregate proportion from previous studies that had used single genome amplification (SGA) analysis. This means that the difference in detecting HIV-1 compartmentalization in this thesis vs previous studies can be explained by the depth of sequencing achieved here and that there is no evidence that the dynamics of the viral populations studied in this thesis were different from those previously studied. In addition, the most recent common ancestor of semen variants was mostly located in blood, indicating the male genital tract was seeded by incoming variants from blood. Clonal amplification was also observed in all the 11 study participants and it was a characteristic of variants from blood and the male genital tract and its frequency did not obviously correlate with the severity of compartmentalization. In sum, blood and male genital tract HIV-1 compartmentalization and clonal amplification is present in most or all HIV-1 infected males but was not detected in all individuals in previous studies when using techniques with lower depth of sampling. Objective 2: Sensitivities of blood and semen variants to entry inhibitors and variable loop characteristics Viral variants from the most compartmentalized donors had variations in sensitivities to entry inhibitors; although the direction of the difference was inconsistent. Donor SVB043 who had the most severely compartmentalized viral populations between blood and semen, had semen viruses that were 1.67 (95%CI 1.08 – 2.56) times more resistant to maraviroc (p=0.024) while SVB008 which was the second most compartmentalized donor, had semen isolates that were 4.8 (95%CI 2.76 – 8.28) times more sensitive to inhibition by maraviroc (p < 0.0001). The meaning of this discrepancy is not entirely clear. It could mean that trait(s) that are selected for in genital tract variants over blood circulation variants are linked to the CCR5 binding region, and that the linked CCR5 genotype was carried along with the selected trait(s). There were no differences in sensitivity to maraviroc between blood and semen clones for donor SVB049 (p=0.847); although this donor on further investigation was found to have functional levels of efavirenz in his blood (3µg/ml, which were within the therapeutic range of 1-4µg/ml) indicating that he was likely on antiretroviral therapy (ART). This was not known to the clinic staff at the clinic at which he was known to receive care and was recruited to this study. The direction of sensitivities to PSC_RANTES (another CCR5 inhibitor) was concordant to that observed for maraviroc for donors SVB008 and SVB049 but not for donor SVB043 where semen variants were 1.67 (95%CI 1.08 – 2.56) times less sensitive than blood variants to maraviroc, with no detected difference in sensitivity to PSC_RANTES (p = 0.783). This discrepancy for donor SVB043 probably reflects the difference in mode of action between Maraviroc and PSC_RANTES. The change in envelope conformation over movement from blood into the genital tract presumably affected the maraviroc binding site and not PSC_RANTES. All the clones from blood and semen for the three most viral compartmentalized donors were resistant to CXCR4 inhibitor suggesting that they were all R5 tropic viruses. There were no differences in sensitivities of blood and semen viruses to fusion inhibitor T-20. The findings here suggest a changed viral envelope conformation/structure for the viruses in the male genital tract. The discordance suggests that the selected trait over movement of virus from blood into genital tract is linked or close to CCR5 binding site but itself does not involve binding to CCR5 coreceptor. Differences in length and number of glycosylation sites were found between variants from blood and those from the genital tract but the direction of the difference was also inconsistent. Donor SVB043 who had the most compartmentalized blood and seminal variants had semen variants that had longer and more glycosylated envelopes. Donor SVB008 who had the second most compartmentalized blood and semen variants had no difference in variable loop length, but semen variants were less glycosylated. This therefore shows that selection for some of the previous reported traits of acute viral isolates may have started in the genital tract in a subset of the donors. Objective 3: Sensitivities of blood and semen variants to autologous and heterologous antibodies Viral populations compartmentalized in blood and the male genital compartment displayed a range of sensitivities to autologous and heterologous neutralization. Donor SVB043 who had the most compartmentalized viral populations between blood and the genital tract; had semen clones that were 1.75 (95%CI 1.11-2.78) times more sensitive to autologous neutralization compared to blood clones (p = 0.018). In contrast, donors SVB008 and SVB049 who exhibited substantial compartmentalization, but to a lesser extent than that found in donor SVB043, showed no differences in sensitivities of blood and semen variants to autologous serum. Neutralization sensitivity to a pool of heterologous subtypematched sera revealed no differences in sensitivities between clones from blood and semen for donors SVB043 and SVB008. Interpretation of results from donor SVB049 are clouded by the donor’s ART use. Overall, these results suggest that, in some individuals, a shift in selective milieu of the genital tract virus occurs. This is presumably due to partial or complete shielding of the genital tract tissue from circulating antibodies, and this shielding shape the populations of HIV-1 variants available for transmission from some but not all individuals. Overall conclusions Our data add to the existing knowledge of existence of distinct viral populations between blood and the male genital tract of chronically HIV-1 infected donors. Importantly, and for the first time, we present evidence that HIV-1 compartmentalization between blood and the male genital tract is present in most or all donors, and that some clones are severely compartmentalized even in donors who exhibit very mild compartmentalization. It appears that viral compartmentalization and clonal amplification in these anatomical sites may be present in most individuals but remained undetected in some individuals in previous studies due to the lower depth of sampling applied. We observed a discordance in entry inhibitor sensitivities and variable loop characteristics between blood vs semen variants among different donors. This may suggest a changed envelope conformation over importation of virus from blood into the genital tract. This change seems to be near or linked to the co-receptor binding site but does not appear to directly involve the co-receptor binding tested in this thesis. This interpretation also may explain the discordance in viral characteristics for the virus establishing infection reported in other studies. This thesis also shows that some of these traits of the transmitted/founder virus relating to neutralization sensitivity, sensitivity to entry inhibitors and variable loop characteristics may originate in and/or be enhanced by transition through the genital tract on the way to becoming a founder virus. These results are important in understanding how the populations in the genital compartment are selected, giving rise to the population of HIV-1 that is available for transmission to a new individual. An understanding of the dynamics of HIV-1 populations prior to and during transmission is important for vaccine design and other intervention strategies