skip to main content


Search for: All records

Creators/Authors contains: "Aaron, G."

Note: When clicking on a Digital Object Identifier (DOI) number, you will be taken to an external site maintained by the publisher. Some full text articles may not yet be available without a charge during the embargo (administrative interval).
What is a DOI Number?

Some links on this page may take you to non-federal websites. Their policies may differ from this site.

  1. Abstract

    Protein-based virus-like particles (P-VLPs) are commonly used to spatially organize antigens and enhance humoral immunity through multivalent antigen display. However, P-VLPs are thymus-dependent antigens that are themselves immunogenic and can induce B cell responses that may neutralize the platform. Here, we investigate thymus-independent DNA origami as an alternative material for multivalent antigen display using the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, the primary target of neutralizing antibody responses. Sequential immunization of mice with DNA-based VLPs (DNA-VLPs) elicits protective neutralizing antibodies to SARS-CoV-2 in a manner that depends on the valency of the antigen displayed and on T cell help. Importantly, the immune sera do not contain boosted, class-switched antibodies against the DNA scaffold, in contrast to P-VLPs that elicit strong B cell memory against both the target antigen and the scaffold. Thus, DNA-VLPs enhance target antigen immunogenicity without generating scaffold-directed immunity and thereby offer an important alternative material for particulate vaccine design.

     
    more » « less
  2. Free, publicly-accessible full text available May 1, 2024
  3. Broadly neutralizing antibodies (bnAbs) that neutralize diverse variants of a particular virus are of considerable therapeutic interest. Recent advances have enabled us to isolate and engineer these antibodies as therapeutics, but eliciting them through vaccination remains challenging, in part due to our limited understanding of how antibodies evolve breadth. Here, we analyze the landscape by which an anti-influenza receptor binding site (RBS) bnAb, CH65, evolved broad affinity to diverse H1 influenza strains. We do this by generating an antibody library of all possible evolutionary intermediates between the unmutated common ancestor (UCA) and the affinity-matured CH65 antibody and measure the affinity of each intermediate to three distinct H1 antigens. We find that affinity to each antigen requires a specific set of mutations – distributed across the variable light and heavy chains – that interact non-additively (i.e., epistatically). These sets of mutations form a hierarchical pattern across the antigens, with increasingly divergent antigens requiring additional epistatic mutations beyond those required to bind less divergent antigens. We investigate the underlying biochemical and structural basis for these hierarchical sets of epistatic mutations and find that epistasis between heavy chain mutations and a mutation in the light chain at the V H -V L interface is essential for binding a divergent H1. Collectively, this is the first work to comprehensively characterize epistasis between heavy and light chain mutations and shows that such interactions are both strong and widespread. Together with our previous study analyzing a different class of anti-influenza antibodies, our results implicate epistasis as a general feature of antibody sequence-affinity landscapes that can potentiate and constrain the evolution of breadth. 
    more » « less
  4. Free, publicly-accessible full text available May 24, 2024
  5. Mobile robots must navigate efficiently, reliably, and appropriately around people when acting in shared social environments. For robots to be accepted in such environments, we explore robot navigation for the social contexts of each setting. Navigating through dynamic environments solely considering a collision-free path has long been solved. In human-robot environments, the challenge is no longer about efficiently navigating from one point to another. Autonomously detecting the context and adapting to an appropriate social navigation strategy is vital for social robots’ long-term applicability in dense human environments. As complex social environments, museums are suitable for studying such behavior as they have many different navigation contexts in a small space.Our prior Socially-Aware Navigation model considered con-text classification, object detection, and pre-defined rules to define navigation behavior in more specific contexts, such as a hallway or queue. This work uses environmental context, object information, and more realistic interaction rules for complex social spaces. In the first part of the project, we convert real-world interactions into algorithmic rules for use in a robot’s navigation system. Moreover, we use context recognition, object detection, and scene data for context-appropriate rule selection. We introduce our methodology of studying social behaviors in complex contexts, different analyses of our text corpus for museums, and the presentation of extracted social norms. Finally, we demonstrate applying some of the rules in scenarios in the simulation environment. 
    more » « less
  6. Grounding lines exist where land-based glacial ice flows on to a body of water. Accurately modelling grounding-line migration at the ice–ocean interface is essential for estimating future ice-sheet mass change. On the interior of ice sheets, the shores of subglacial lakes are also grounding lines. Grounding-line positions are sensitive to water volume changes such as sea-level rise or subglacial-lake drainage. Here, we introduce numerical methods for simulating grounding-line dynamics in the marine ice sheet and subglacial-lake settings. Variational inequalities arise from contact conditions that relate normal stress, water pressure and velocity at the base. Existence and uniqueness of solutions to these problems are established using a minimisation argument. A penalty method is used to replace the variational inequalities with variational equations that are solved using a finite-element method. We illustrate the grounding-line response to tidal cycles in the marine ice-sheet problem and filling–draining cycles in the subglacial-lake problem. We introduce two computational benchmarks where the known lake volume change is used to measure the accuracy of the numerical method. 
    more » « less
  7. null (Ed.)
    Global declines in biodiversity have the potential to affect ecosystem function, and vice versa, in both terrestrial and aquatic ecological realms. While many studies have considered biodiversity-ecosystem function (BEF) relationships at local scales within single realms, there is a critical need for more studies examining BEF linkages among ecological realms, across scales, and across trophic levels. We present a framework linking abiotic attributes, productivity, and biodiversity across terrestrial and inland aquatic realms. We review examples of the major ways that BEF linkages form across realms–cross-system subsidies, ecosystem engineering, and hydrology. We then formulate testable hypotheses about the relative strength of these connections across spatial scales, realms, and trophic levels. While some studies have addressed these hypotheses individually, to holistically understand and predict the impact of biodiversity loss on ecosystem function, researchers need to move beyond local and simplified systems and explicitly investigate cross-realm and trophic interactions and large-scale patterns and processes. Recent advances in computational power, data synthesis, and geographic information science can facilitate studies spanning multiple ecological realms that will lead to a more comprehensive understanding of BEF connections. 
    more » « less