Search for: All records

Small-molecule sensing in plants is dominated by chemical-induced dimerization modules. In the abscisic acid (ABA) system, allosteric receptors recruit phosphatase effectors and achieve nM in vivo responses from µM receptor–ligand interactions. This sensitivity amplification could enable ABA receptors to serve as generic scaffolds for designing small-molecule sensors. To test this, we screened collections of mutant ABA-receptors against 2,726 drugs and other ligands and identified 553 sensors for 6.6% of these ligands. The mutational patterns indicate strong selection for ligand-specific binding pockets. We used these data to develop a sensor design pipeline and isolated sensors for multiple plant natural products, 2,4,6-trinitrotoluene (TNT), and “forever” per- and polyfluoroalkyl substances (PFAS). Thus, the ABA sensor system enables design and isolation of small-molecule sensors with broad chemical scope and antibody-like simplicity. 

Abstract The HIV reservoir consists of infected cells in which the HIV-1 genome persists as provirus despite effective antiretroviral therapy (ART). Studies exploring HIV cure therapies often measure intact proviral DNA levels, time to rebound after ART interruption, or ex vivo stimulation assays of latently infected cells. This study utilizes barcoded HIV to analyze the reservoir in humanized mice. Using bulk PCR and deep sequencing methodologies, we retrieve 890 viral RNA barcodes and 504 proviral barcodes linked to 15,305 integration sites at the single RNA or DNA molecule in vivo. We track viral genetic diversity throughout early infection, ART, and rebound. The proviral reservoir retains genetic diversity despite cellular clonal proliferation and viral seeding by rebounding virus. Non-proliferated cell clones are likely the result of elimination of proviruses associated with transcriptional activation and viremia. Elimination of proviruses associated with viremia is less prominent among proliferated cell clones. Proliferated, but not massively expanded, cell clones contribute to proviral expansion and viremia, suggesting they fuel viral persistence. This approach enables comprehensive assessment of viral levels, lineages, integration sites, clonal proliferation and proviral epigenetic patterns in vivo. These findings highlight complex reservoir dynamics and the role of proliferated cell clones in viral persistence. 

The spectral properties of traditional (dyadic) graphs, where an edge connects exactly two vertices, are widely studied in different applications. These spectral properties are closely connected to the structural properties of dyadic graphs. We generalize such connections and characterize higher-order networks by their spectral information. We first split the higher-order graphs by their “edge orders” into several uniform hypergraphs. For each uniform hypergraph, we extract the corresponding spectral information from the transition matrices of carefully designed random walks. From each spectrum, we compute the first few spectral moments and use all such spectral moments across different “edge orders” as the higher-order graph representation. We show that these moments not only clearly indicate the return probabilities of random walks but are also closely related to various higher-order network properties such as degree distribution and clustering coefficient. Extensive experiments show the utility of this new representation in various settings. For instance, graph classification on higher-order graphs shows that this representation significantly outperforms other techniques. 

Abstract Nonlocal models have demonstrated their indispensability in numerical simulations across a spectrum of critical domains, ranging from analyzing crack and fracture behavior in structural engineering to modeling anomalous diffusion phenomena in materials science and simulating convection processes in heterogeneous environments. In this study, we present a novel framework for constructing nonlocal convection–diffusion models using Gaussian‐type kernels. Our framework uniquely formulates the diffusion term by correlating the constant diffusion coefficient with the variance of the Gaussian kernel. Simultaneously, the convection term is defined by integrating the variable velocity field into the kernel as the expectation of a multivariate Gaussian distribution, facilitating a comprehensive representation of convective transport phenomena. We rigorously establish the well‐posedness of the proposed nonlocal model and derive a maximum principle to ensure its stability and reliability in numerical simulations. Furthermore, we develop a meshfree discretization scheme tailored for numerically simulating our model, designed to uphold both the discrete maximum principle and asymptotic compatibility. Through extensive numerical experiments, we validate the efficacy and versatility of our framework, demonstrating its superior performance compared to existing approaches. 

Network data has become widespread, larger, and more complex over the years. Traditional network data is dyadic, capturing the relations among pairs of entities. With the need to model interactions among more than two entities, significant research has focused on higher-order networks and ways to represent, analyze, and learn from them. There are two main directions to studying higher-order networks. One direction has focused on capturing higher-order patterns in traditional (dyadic) graphs by changing the basic unit of study from nodes to small frequently observed subgraphs, called motifs. As most existing network data comes in the form of pairwise dyadic relationships, studying higher-order structures within such graphs may uncover new insights. The second direction aims to directly model higher-order interactions using new and more complex representations such as simplicial complexes or hypergraphs. Some of these models have long been proposed, but improvements in computational power and the advent of new computational techniques have increased their popularity. Our goal in this paper is to provide a succinct yet comprehensive summary of the advanced higher-order network analysis techniques. We provide a systematic review of the foundations and algorithms, along with use cases and applications of higher-order networks in various scientific domains.