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At least 1,135 records · Page 63

Traffic Control via Connected and Automated Vehicles (CAVs): An Open-Road Field Experiment with 100 CAVs

The CIRCLES project aims to reduce instabilities in traffic flow, which are naturally occurring phenomena due to human driving behavior. Also called “phantom jams” or “stop-and-go waves,” these instabilities are a significant source of wasted energy. Toward this goal, the CIRCLES project designed a control system, referred to as the MegaController by the CIRCLES team, that could be deployed in real traffic. Our field experiment, the MegaVanderTest (MVT), leveraged a heterogeneous fleet of 100 longitudinally controlled vehicles as Lagrangian traffic actuators, each of which ran a controller with the architecture described in this article. The MegaController is a hierarchical control architecture that consists of two main layers. The upper layer is called the Speed Planner and is a centralized optimal control algorithm. It assigns speed targets to the vehicles, conveyed through the LTE cellular network. The lower layer is a control layer, running on each vehicle. It performs local actuation by overriding the stock adaptive cruise controller, using the stock onboard sensors. The Speed Planner ingests live data feeds provided by third parties as well as data from our own control vehicles and uses both to perform the speed assignment. The architecture of the Speed Planner allows for the modular use of standard control techniques, such as optimal control, model predictive control (MPC), kernel methods, and others. The architecture of the local controller allows for the flexible implementation of local controllers. Corresponding techniques include deep reinforcement learning (RL), MPC, and explicit controllers. Depending on the vehicle architecture, all onboard sensing data can be accessed by the local controllers or only some. Likewise, control inputs vary across different automakers, with inputs ranging from torque or acceleration requests for some cars to electronic selection of adaptive cruise control (ACC) setpoints in others. The proposed architecture technically allows for the combination of all possible settings proposed previously, that is {Speed Planner algorithms} × {local Vehicle Controller algorithms} × {full or partial sensing} × {torque or speed control}. As a result, most configurations were tested throughout the ramp up to the MegaVandertest (MVT).

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Automated phase segmentation and quantification of high-resolution TEM image for alloy design

In the alloy design and development process, a wealth of atomically resolved structural high-resolution transmission electron microscopy (HRTEM) images are produced. Identifying the different nano-precipitate phases and tracking their evolution under various compositions and during manufacturing or post-processing requires hundreds of HRTEM images and thousands of precipitates. The nanoscopic phase information labeling and analysis purely relies on humans are prohibitively costly and time-consuming, sometimes not reliable because of the lack of authoritative knowledge. Here, in this work, we develop a novel unsupervised machine learning approach coupled with adaptive computer vision techniques with features in the Fourier space to automatically determine the number of phases and segment/quantify the phases with nanoscale resolution, allowing for quantitative correlation between nanostructure formation, processing and functional properties. To automate the phase extraction/quantification and ascertain its applicability, we have applied the developed framework to the HRTEM images from several alloy systems, processing conditions, image magnifications, and phase types and morphologies (precipitates, nano-twins, stacking faults, crystalline matrix, and amorphous structures) for verification. This study paves the road for compression, visualization, and translation of raw image structural data into physically relevant information in real-time with minimal human supervision. It shows the promise of enabling high-throughput materials characterization for the acceleration of alloy manufacturing and design.

36 MATERIALS SCIENCE↗

The Exoproteome and Surfaceome of Toxigenic Corynebacterium diphtheriae 1737 and Its Response to Iron Restriction and Growth on Human Hemoglobin

Toxin-producing Corynebacterium diphtheriae strains are the etiological agents of the severe upper respiratory disease, diphtheria. A global phylogenetic analysis revealed that biotype gravis is particularly lethal as it produces diphtheria toxin and a range of other virulence factors, particularly when it encounters low levels of iron at sites of infection. Here, to gain insight into how it colonizes its host, we have identified iron-dependent changes in the exoproteome and surfaceome of C. diphtheriae strain 1737 using a combination of whole-cell fractionation, intact cell surface proteolysis, and quantitative proteomics. In total, we identified 1414 of the predicted 2265 proteins (62%) encoded by its reference genome. For each protein, we quantified its degree of secretion and surface exposure, revealing that exoproteases and hydrolases predominate in the exoproteome, while the surfaceome is enriched with adhesins, particularly DIP2093. Our analysis provides insight into how components in the heme-acquisition system are positioned, showing pronounced surface exposure of the strain-specific ChtA/ChtC paralogues and high secretion of the species-conserved heme-binding HtaA protein, suggesting it functions as a hemophore. Profiling the response of the exoproteome and surfaceome after microbial exposure to human hemoglobin and iron limitation reveals potential virulence factors that may be expressed at sites of infection. Data are available via ProteomeXchange with identifier PXD051674.

cell envelope↗

Uptake of polystyrene nanospheres by wheat and Arabidopsis roots in agar, hydroponics, and soil

Plant uptake of micro- and nanoplastics can lead to contamination of food with plastic particles and subsequent human consumption of plastics. There is evidence that plant roots can take up micro and nanoplastics; however, most of this evidence stems from experiments conducted with plants grown in hydroponics or agar systems where uptake of nanoparticles by roots is more favorable than when plants were grown in soil. Here, we discern the root uptake and accumulation of polystyrene nanospheres in plants grown in different growth media: agar, hydroponics, and soil. In addition, we tested the impacts of nanospheres on plant biomass and plant stress. Wheat and Arabidopsis thaliana were grown in agar, hydroponics, and soil media and exposed to polystyrene nanospheres. Three different nanospheres were used (40 nm and 200 nm carboxylate-modified and 200 nm amino-modified polystyrene) and uniformly mixed into the growth media. Plants were grown for 7 to 10 days and the roots were then examined for the presence of nanospheres by confocal laser scanning microscopy and scanning electron microscopy. Plant stress was evaluated by measuring reactive oxygen species (ROS). We observed the 40 nm nanospheres inside the plant roots, but the 200 nm nanospheres only adhered to the root cap cells showing no uptake into the roots. Furthermore, confocal images indicated that root uptake of nanospheres was favored in hydroponic solutions as compared to agar and soil media. Plant biomass was generally not affected by the nanospheres, except for hydroponically grown Arabidopsis thaliana, where biomass was significantly reduced. Small sized (40 nm) and positively charged (200 nm amino-modified) nanospheres showed higher ROS accumulation in plants than negatively charged 200 nm carboxylate-modified nanospheres. In conclusion, this study provides evidence that polystyrene nanospheres can be taken up into the interior of plant roots and cause plant stress, but these impacts are less pronounced in media where the plastic particles are less mobile, like in agar and soil media as compared to hydroponic systems.

54 ENVIRONMENTAL SCIENCES↗

Synchrotron fluorescence imaging of individual mouse beta-cells reveals changes in zinc, calcium, and iron in a model of low-grade inflammation

Pancreatic beta-cells synthesize and secrete insulin maintaining an organism's energy homeostasis. In humans, beta-cell dysfunction and death contribute to the pathogenesis of type 2 diabetes (T2D). Although the causes of beta-cell dysfunction are complex, obesity-induced low-grade systemic inflammation plays a role. For example, obese individuals exhibiting increased levels of proinflammatory cytokines IL-6 and IL-1beta have a higher risk of beta-cell dysfunction and T2D. Interestingly, obesity-induced inflammation changes the expression of several cellular metal regulating genes, prompting this study to examine changes in the beta-cell metallome after exposure to proinflammatory-cytokines. Here, primary mouse beta-cells were exposed to a combination of IL-6 and IL-1beta for 48 hours, were chemically fixed and imaged by synchrotron X-ray fluorescent microscopy. Quantitative analysis showed a surprising 2.4-fold decrease in the mean total cellular content of zinc from 158 ± 57.7 femtograms (fg) to 65.7 ± 29.7 fg; calcium decreased from 216 ± 67.4 to 154.3 ± 68.7 fg (control vs. cytokines, respectively). The mean total cellular iron content slightly increased from 30.4 ± 12.2 to 47.2 ± 36.4 fg after cytokine treatment; a sub-population of cells (38%) exhibited larger increases of iron density. Changes in the subcellular distributions of zinc and calcium were observed after cytokine exposure. Beta-cells contained numerous iron puncta that accumulated still more iron after exposure to cytokines. These findings provide evidence that exposure to low levels of cytokines is sufficient to cause changes in the total cellular content and/or subcellular distribution of several metals known to be critical for normal beta-cell function.

59 BASIC BIOLOGICAL SCIENCES↗

Announcing the Biomedical Data Translator: Initial Public Release

ABSTRACT The growing availability of biomedical data offers vast potential to improve human health, but the complexity and lack of integration of these datasets often limit their utility. To address this, the Biomedical Data Translator Consortium has developed an open‐source knowledge graph–based system—Translator—designed to integrate, harmonize, and make inferences over diverse biomedical data sources. We announce here Translator's initial public release and provide an overview of its architecture, standards, user interface, and core features. Translator employs a scalable, federated, knowledge graph framework for the integration of clinical, genomic, pharmacological, and other biomedical knowledge sources, enabling query retrieval, inference, and hypothesis generation. Translator's user interface is designed to support the exploration of knowledge relationships and the generation of insights, without requiring deep technical expertise and gradually revealing more detailed evidence, provenance, and confidence information, as needed by a given user. To demonstrate Translator's application and impact, we highlight features of the user interface in the context of three real‐world use cases: suggesting potential therapeutics for patients with rare disease; explaining the mechanism of action of a pipeline drug; and screening and validating drug candidates in a model organism. We discuss strengths and limitations of reasoning within a largely federated system and the need for rich concept modeling and deep provenance tracking. Finally, we outline future directions for enhancing Translator's functionality and expanding its data sources. Translator represents a significant step forward in making complex biomedical knowledge more accessible and actionable, aiming to accelerate translational research and improve patient care.

Research & Experimental Medicine↗

Differentially Private Map Matching (DPMM) v1.0

Human mobility trajectories provide valuable information for developing mobility applications, as they contain diverse and rich information about the users. User mobility data is valuable for various applications such as intelligent transportation systems (ITS), commercial business models, and disease-spread models. However, such spatio-temporal traces may pose a threat to user privacy. GPS trajectories in their raw form are not suitable for transportation studies, as they require matching locations with nearest road links — a process called map-matching. This software implements a differential privacy (DP)-based map-matching algorithm, called DPMM, that generates link-level location trajectories in a privacy-preserving manner to protect users' origin destinations (OD) and travel paths. OD privacy is achieved by injecting Planar Laplace noise to the user OD GPS points. Travel-path privacy is provided with randomized travel path construction using exponential DP mechanism. The injected noise level is selected adaptively, by considering the link density of the location and the functional category of the localized links. For path privacy, our mechanism samples waypoints and selects candidate paths between waypoints. DPMM provides privacy effectively with respect to link density instead of other trajectory samples in the database compared to other privacy mechanisms. Compared to the different baseline models our DP-based privacy model offers closer query responses to the raw data in terms of individual and aggregate trajectory-level statistics with an average at absolute deviation from the baseline for individual statistics on ϵ = 1.0. Beyond individual trajectory statistics, the DPMM outperforms the other benchmark DP-based mechanisms on different aggregate statistics with up to 8x improvement in utility.

Peisert, Sean [Lawrence Berkeley National Laborato↗

Quantifying the Influence of Size, Shape, and Density of Microplastics on Their Transport Modes: A Modeling Approach

Microplastics (MPs) pose significant risks to marine ecosystems and human health, necessitating accurate predictions of their distributions in aquatic environments for effective risk mitigation. However, understanding MP transport dynamics is challenging because of the inadequate representation of MP characteristics such as size, shape, and density in numerical models. Further, the accuracy of the MP vertical profiles in existing models has not been thoroughly validated. Thus, we developed an MP transport model within the Finite Volume Community Ocean Model framework (FVCOM-MP) by integrating MP characteristics. We validated FVCOM-MP against experimental and analytical data, focusing on various MP transport modes and transitions. FVCOM-MP successfully replicates MP profiles in different transport modes, including the bedload, surface-load, suspended-load, and mixed-load modes. Additionally, we introduce phase diagrams for classifying MP transport modes based on particle characteristics, enhancing our understanding of MP dynamics in aquatic systems. The transport modes for a number of real-world MP particles, including fishing line, plastic bag/bottle fragments, synthetic fibers, tire wear particles, polyvinyl chloride and expanded polystyrene pellets, were analyzed with these phase diagrams.

Microplastic transport, Settling velocity, Rising ↗

Initialized Earth system prediction from subseasonal to decadal timescales

Initialized Earth system predictions are made by starting a numerical prediction model in a state as consistent as possible to observations, and running it forward in time for up to ten years. Skillful predictions at time slices from subseasonal to seasonal (S2S), seasonal to interannual (S2I) and seasonal to decadal (S2D) offer information useful for various stakeholders, from agriculture to water resource management, and human and infrastructure safety. In this Review, we examine the processes influencing predictability, and discuss estimates of skill across S2S, S2I and S2D timescales. There are encouraging signs that skillful predictions can be made: at S2S timescales, there has been some skill in predicting the Madden-Julian Oscillation and North Atlantic Oscillation; at S2I in predicting the El Niño-Southern Oscillation; and at S2D, in predicting variability in North Atlantic sea surface temperatures. However, challenges remain, and future work must prioritise reducing model error, more effectively communicating forecasts to users, and increasing process and mechanistic understanding that could increase predictive skill and, in turn, confidence. As numerical models progress towards Earth system models, initialized predictions are expanding to include prediction of sea-ice, air pollution, terrestrial and ocean biochemistry which can bring clear benefit to society and various stakeholders.

climate prediction↗

Structure of the divergent human astrovirus MLB capsid spike

Despite their worldwide prevalence and association with human disease, the molecular bases of human astrovirus (HAstV) infection and evolution remain poorly characterized. Here, we report the structure of the capsid protein spike of the divergent HAstV MLB clade (HAstV MLB). While the structure shares a similar folding topology with that of classical-clade HAstV spikes, it is otherwise strikingly different. We find no evidence of a conserved receptor-binding site between the MLB and classical HAstV spikes, suggesting that MLB and classical HAstVs utilize different receptors for host-cell attachment. We provide evidence for this hypothesis using a novel HAstV infection competition assay. Comparisons of the HAstV MLB spike structure with structures predicted from its sequence reveal poor matches, but template-based predictions were surprisingly accurate relative to machine-learning-based predictions. Our data provide a foundation for understanding the mechanisms of infection by diverse HAstVs and can support structure determination in similarly unstudied systems.

59 BASIC BIOLOGICAL SCIENCES↗

Chemodiversity of riverine dissolved organic matter: Effects of local environments and watershed characteristics

Riverine dissolved organic matter (DOM) is crucial to global carbon cycling and aquatic ecosystems. However, the geographical patterns and environmental correlates of DOM chemodiversity remain elusive especially in surface waters and sediments of global rivers. Here, we systematically analyzed DOM molecular diversity and composition in surface waters and sediments across 97 globally distributed rivers using data from the Worldwide Hydrobiogeochemistry Observation Network for Dynamic River Systems (WHONDRS) consortium. Here, we further examined the associations of molecular richness and composition with geographical, climatic, physicochemical variables, as well as the watershed characteristics. We found that molecular richness significantly decreased toward higher latitudes, but only in sediments (r = -0.24, P < 0.001). The environmental variables like precipitation and non-purgeable organic carbon showed strong associations with DOM molecular richness and composition. Interestingly, we identified that less-documented factors like watershed characteristics were also related to DOM molecular richness and composition, and were stronger in waters than sediments. Such associations were further supported by the fact that 11 out of 13 watershed characteristics (e.g., land cover variables) showed more positive than negative correlations with molecular abundance especially in waters. The molecules positively and negatively correlated with specific watershed characteristics had distinct traits, such as stoichiometric ratios and aromaticity. Land covers shifted from natural (e.g., forests) to human-modified (e.g., impervious area) were associated with systematic changes in DOM molecular chemistry. Our findings imply that it may be possible to use a small set of broadly available data types to predict DOM molecular richness and composition across diverse river systems. Elucidation of mechanisms underlying these relationships will provide further enhancements to such predictions, especially when extrapolating to unsampled systems.

54 ENVIRONMENTAL SCIENCES↗

Use of Unmanned Aerial Systems for Post-closure Waste Site Maintenance and Surveillance - 20143

The P- and R-Area Reactor buildings, located at SRS near Aiken, SC, were in-situ decommissioned by grouting below-grade portions of the buildings and demolishing some above-grade structures to grade level. Other reactor building structures were left above-grade and sealed to prevent human or animal access. Because the above grade-structures are expected to continue in their present state for hundreds of years, the condition of the building roofs is critical to mitigate rainwater intrusion. For this reason, building roof areas were strengthened with high strength concrete to ensure the long-term integrity of the roof structure. Periodic inspections of the roof structures are required to ensure that the roofs are functioning properly and to identify damage areas. The traditional method of inspecting closed reactor buildings requires the use of a helicopter and photographer to generate photographs and videos for review. This method proved sufficient but lacked the resolution and clarity that is required for a thorough inspection of the building structure. Fortunately, the Savannah River National Laboratory (SRNL) has established a Small Unmanned Aircraft System (sUAS) program using commercially available and custom-built remote-controlled aircraft. EC and ACP contacted the SRNL program to evaluate whether the sUAS technology could be employed for periodic reactor building inspections. The sUAS can fly within a few meters of the reactor buildings and hover, allowing for a more thorough aerial inspection. The initial sUAS inspection of the P-Area Reactor building was completed in February 2018 and at the R-Area Reactor building in August 2018 and were successful in providing higher resolution photos and videos. The sUAS inspections also revealed that vegetation had begun to grow on the roofs that could potentially damage the structure integrity. SRNL partnered with Virginia Polytechnic Institute and State University to build a custom heavy lift sUAS that could be equipped with herbicides to remotely treat the vegetative growth. Herbicides were successfully applied to the R-Area Reactor building roof using the custom sUAS in September 2018. The use of unmanned aircraft systems at SRS to perform aerial inspections and herbicide treatment in otherwise inaccessible areas has proven to be an efficient and cost-effective technology that provides high value, increases knowledge of facility conditions, and provides for early detection of damage. Periodic inspections of the reactor building roofs using sUAS technology are performed safely, efficiently, and at a significant cost and schedule savings while reducing emissions, noise, and fossil fuel use. The use of sUAS equipment for building inspections and herbicide application at SRS is unique within the DOE complex. The goal of SRS is to apply this remote technology to other waste unit operations and maintenance activities in the future. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

CRISPR-prime editing, a versatile genetic tool to create specific mutations with a single nucleotide resolution in Leptospira

ABSTRACT Leptospirosis, caused by pathogenic bacteria from the genusLeptospira, is a global zoonosis responsible for more than one million human cases and 60,000 deaths annually. The disease also affects many domestic animal species. Historically, genetic manipulation ofLeptospirahas been difficult to perform, resulting in limited knowledge on pathogenic mechanisms of disease and the identification of virulence factors. The application of CRISPR/Cas9 and its variations have helped fill these gaps but the generation of knockout mutants remains challenging because double-strand breaks (DSBs) inflicted by Cas9 nuclease are lethal toLeptospiracells. The novel CRISPR prime editing (PE) strategy is the first precise genome-editing technology that allows deletions, insertions, and base substitutions without introducing DSBs. This revolutionary technique utilizes a nickase Cas9 that cleaves a single strand of DNA, coupled with an engineered reverse transcriptase and a modified single-guide RNA (termed prime editing guide RNA) containing an extended 3′ end with the desired edits. We demonstrate the application of CRISPR-PE in both saprophytic and pathogenicLeptospirafrom multiple species and serovars by introducing deletions or insertions into target DNA with a remarkable precision of just one nucleotide. Additionally, we demonstrate the ability to genetically manipulateLeptospira borgpetersenii, a prevalent pathogenic species of humans, domestic cattle, and wildlife animals. Rapid plasmid loss by mutated strains in liquid culture allows for the generation of knockout strains without selective markers, which can be readily used to elucidate virulence factors and develop optimized bacterin and/or live vaccines against leptospirosis. IMPORTANCE Leptospirosis is a geographically widespread bacterial zoonosis. Genetic manipulation of pathogenicLeptospiraspp. has been laborious and difficult to perform, limiting our ability to understand how leptospires cause disease. The application of the CRISPR/Cas9 system toLeptospiraenhanced our ability to generate knockdown and knockout mutants; however, the latter remains challenging. Here, we demonstrate the application of the CRISPR prime editing technique inLeptospira, allowing the generation of knockout mutants in several pathogenic species, with mutations comprising just a single nucleotide resolution. Notably, we generated a mutant in theLeptospira borgpeterseniibackground, a prevalent pathogenic species of humans and cattle. Our application of this method opens new avenues for studying pathogenic mechanisms ofLeptospiraand the identification of virulence factors across multiple species. These methods can also be used to facilitate the generation of marker-less knockout strains for updated and improved bacterin and/or live vaccines.

Microbiology↗

High-Fidelity Accelerated Design of High-performance Electrochemical Systems

Large-scale electrification is vital to addressing the climate crisis, but several scientific and technological challenges remain to fully electrify both the chemical industry and transportation. In both of these areas, new electrochemical materials will be critical, but their development currently relies heavily on human-time-intensive experimental trial and error and computationally expensive first-principles, meso-scale and continuum simulations. To accelerate this process, our team has developed the AutoMat platform. AutoMat can accelerate development of new electrochemical materials along two avenues: first, automated input generation and management of simulations at multiple lengthscales as well as “handoff” of outputs from one lengthscale as inputs to the next; and second, replacement of the most computationally intensive simulation processes with machine-learned surrogate models. The crux of our team’s effort was not “reinventing the wheel” by developing entirely new techniques, but rather building a “superhighway” that allows existing state-of-the-art techniques to run faster and more smoothly than before. AutoMat can utilize tools spanning from first-principles quantum chemistry computations to automated robotic experimentation, and is driven by design space search techniques to reduce the number of iterations through the full simulation loop by rapidly targeting promising regions of design spaces such as single-atom alloy catalysts or blends of liquid electrolytes.

25 ENERGY STORAGE↗

Power System Resilience Metrics Augmentation for Critical Load Prioritization

One of the major goals of new grid operation regimes, such as transactive energy systems (TESs), is to make the power grid more resilient to withstand natural or man-made disasters and potential reliability events, and to continue to serve the maximum number of its customers. But it is a well-known fact to system operators that not all customers are the same. This implies that any discussion of TESs’ impacts on the resilience of the power system should consider the needs of its critical customers (such as the power system operation centers, fire and police stations, and hospitals) over those of other customers. When evaluating the resilience of the system, bonus points must be awarded to any system that could maintain its power supply to critical customers during a disturbance that may cause an outage. This report discusses critical infrastructure (CI) as found in the literature and then categorizes it based on the field to which the operations belong (such as human life/safety-related, operations management, necessary city operation, industrial customers, etc.). Each of these CI categories is further divided into types of critical customers (e.g., the human life/safety-related category has different types of customers like hospitals, fire and police stations, etc.). The entire demand of each of the critical customer types is not categorized as critical load (CL); instead, only a portion of the total load of these critical customers is characterized as critical load. This is done based on the categories of equipment, the function of which is crucial in the operation of the overall facility. CL categorization is performed to provide the ratio of the critical load portion to the overall load , so that it can serve as a parameter in the resilience evaluation of the grid through a metrics-based approach. Such categorization is important as it helps to augment the existing quantifiable resilience metrics with CL categorization. The metrics for a power system need to not only consider how well a system performed during a disturbance event, but also how it reduced strain and supplied power to its CLs. The first step in this process is characterize CLs in the system. After CL characterization, the next step is the inclusion of these loads in the resilience metrics. To that end, in this report weight-based augmentation of resilience metrics is proposed, where certain customers (the ones that are categorized as critical) are assigned higher weights than others. Though an overview of assigning weights to customers is discussed, there is no one-size-fits-all approach for every power system. The decisions made about assigning such weights to customers vary greatly from one operator to another, based on their unique systems and the current and predicted states of critical customers. This decision-making can include the type of disturbance event, which might only affect certain parts of the system. In general, analyzing critical customers before an event helps understand system vulnerabilities. It also helps in planning and conducting operations during the event, evaluating system performance after the event, and supporting better planning for future events. An alternative to the current practices of managing the grid for outages is an innovative TES, which has the potential to provide a platform for including distributed energy resources for managing CLs. This report also describes how TES qualities can help (1) to maintain power supply to critical customers for uninterrupted operations and (2) to restore lost power supply to the critical customers rapidly.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Microsimulation of Energy and Flow Effects from Optimal Automated Driving in Mixed Traffic

In this paper we study the energy and traffic impact of a proposed Anticipative Cruise Controller in a PTV VISSIM microsimulation environment. We dissect our controller into two parts: 1. the unconnected mode, active when following a human-driven vehicle, and 2. the connected mode, active when following another automated vehicle equipped with connectivity. Probabilistic constraints balance safety considerations with inter-vehicle compactness, and vehicle constraints for acceleration capabilities are expressed through the use of powertrain maps. Emergent highway traffic scenarios are then modeled using time headway distributions from empirical traffic data. To study the impact of automation over a range of demands of free-flow to stop-and-go, we vary vehicle flux from low to high and vary automated vehicle penetration from low to high. When examining all-human driving scenarios, network capacity failed to meet demand in high-volume scenarios, such as rush-hour traffic. We further find that with connected automated vehicles introduced, network capacity was improved to support the high-volume scenarios. Finally, we examine energy efficiencies of the fleet for conventional, electric, and hybrid vehicles. We find that automated vehicles perform at a 10%-20% higher energy efficiency over human drivers when considering conventional powertrains, and find that automated vehicles perform at a 3%-9% higher energy efficiency over human drivers when considering electric and hybrid powertrains. Due to secondary effects of smoothing traffic flow and reducing unnecessary braking, energy benefits also apply to human-driven vehicles that interact with automated ones. Such simulated humans were found to drive up to 10% more energy-efficiently than they did in the baseline all-human scenario.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Antineoplastic activity of Salmonella Typhimurium outer membrane nanovesicles

Highlights: • ST-OMVs is a promising antitumor monotherapy or as an adjuvant to chemotherapies. • ST-OMVs downregulated Ki-67 and upregulated CD49b immune-expression. • ST-OMVs downregulated angiogenesis by inhibiting VEGF gene expression. • ST-OMVs increased tumor cells apoptosis and autophagy (increased caspase-3and Beclin1). Nano-sized Gram-negative bacterial outer membrane vesicles possess unique structural and immunostimulatory effects that could be exploited to regress tumors by alerting the host immune system and reversing the immunosuppressive tumor microenvironment. The current study was conducted to investigate the antitumor activity of the outer membrane vesicles (ST-OMVs) of Salmonella Typhimurium ATCC 14028, in vitro in human colorectal carcinoma (HTC116), breast cancer (MCF-7), and hepatocellular carcinoma (HepG2) cell lines and in vivo in Ehrlich solid carcinoma-bearing mice model either as a mono-immunotherapy or as an adjuvant to a commonly used conventional chemotherapy. In addition, we investigated the safety of ST-OMVs. Adult Swiss albino female mice with transplanted Ehrlich solid carcinoma were treated with either ST-OMVs, paclitaxel or a combination of both. Tumor volume, growth inhibition rate, quantitative RT-PCR of Bax and VEGF genes expression, histopathology and immune-expression of caspase-3, Beclin-1, CD49b and Ki-67 were all analyzed. Our results showed that ST-OMVs significantly decreased tumor volume, significantly increased tumor growth inhibition rate, up-regulated the immunohistochemical expression of caspase-3, Beclin-1, and CD49b (enhanced recruitment of NK cells). Furthermore, ST-OMVs down-regulated the expression of Ki-67, increased Bax gene expression and decreased VEGF gene expression as detected by qRT-PCR analysis. Histologically, ST-OMVs promoted apoptosis, decreased tumor invasion and mitotic activities. Moreover, ST-OMVs showed a remarkable cytotoxic activity in various investigated in vitro cancer cell lines. Our findings demonstrate potential antitumor activity of ST-OMVs that might be used as a promising safe antitumor immunotherapy or an adjuvant to conventional chemotherapeutic drugs, resolving some of their problems.

60 APPLIED LIFE SCIENCES↗