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  1. Mapping of spatial hotspots, i.e., regions with significantly higher rates of generating cases of certain events (e.g., disease or crime cases), is an important task in diverse societal domains, including public health, public safety, transportation, agriculture, environmental science, and so on. Clustering techniques required by these domains differ from traditional clustering methods due to the high economic and social costs of spurious results (e.g., false alarms of crime clusters). As a result, statistical rigor is needed explicitly to control the rate of spurious detections. To address this challenge, techniques for statistically-robust clustering (e.g., scan statistics) have been extensively studied by the data mining and statistics communities. In this survey, we present an up-to-date and detailed review of the models and algorithms developed by this field. We first present a general taxonomy for statistically-robust clustering, covering key steps of data and statistical modeling, region enumeration and maximization, and significance testing. We further discuss different paradigms and methods within each of the key steps. Finally, we highlight research gaps and potential future directions, which may serve as a stepping stone in generating new ideas and thoughts in this growing field and beyond.
    Free, publicly-accessible full text available March 31, 2024
  2. Polymer-derived ceramics (PDCs) which are fabricated through pyrolysis of preceramic polymers have attracted increasing attention due to their versatility in structure architecture design and property tailoring. Shaping at the polymer state using 3D printing allows the final ceramic products to exhibit arbitrary shapes and complex architectures that are otherwise impossible to achieve through traditional processing routes. The polymer-to-ceramic phase transition also provides additional space for mechanical property tailoring. A multiscale computational model is developed to explore the phase transition mechanisms and their correlations with processing parameters and failure response. Calculations in this work concern PMHS/DVB preceramic polymers. Molecular dynamics (MD) simulations are carried out first to track the atomic structure evolution at different temperatures. Continuum-scale ceramic phase formation is calculated on the basis of the competition between gas generation and gas diffusion. The effect of processing parameters on mechanical properties of pyrolyzed PMHS/DVB is systematically studied. Conclusions from this study can provide direct guidance for fabricating PDC composites with tailored mechanical properties.
    Free, publicly-accessible full text available March 1, 2024
  3. Free, publicly-accessible full text available December 1, 2023
  4. Free, publicly-accessible full text available January 1, 2024
  5. The significant roles of extracellular vesicles (EVs) as intracellular mediators, disease biomarkers, and therapeutic agents, make them a scientific hotspot. In particular, EVs secreted by human stem cells show significance in treating neurological disorders, such as Alzheimer’s disease and ischemic stroke. However, the clinical applications of EVs are limited due to their poor targeting capabilities and low therapeutic efficacies after intravenous administration. Superparamagnetic iron oxide (SPIO) nanoparticles are biocompatible and have been shown to improve the targeting ability of EVs. In particular, ultrasmall SPIO (USPIO, <50 nm) are more suitable for labeling nanoscale EVs due to their small size. In this study, induced forebrain neural progenitor cortical organoids (iNPCo) were differentiated from human induced pluripotent stem cells (iPSCs), and the iNPCo expressed FOXG1, Nkx2.1, α-catenin, as well as β-tubulin III. EVs were isolated from iNPCo media, then loaded with USPIOs by sonication. Size and concentration of EV particles were measured by nanoparticle tracking analysis, and no significant changes were observed in size distribution before and after sonication, but the concentration decreased after labeling. miR-21 and miR-133b decreased after sonication. Magnetic resonance imaging (MRI) demonstrated contrast visualized for the USPIO labeled EVs embedded in agarose gel phantoms. Upon calculation, USPIO labeledmore »EVs exhibited considerably shorter relaxation times, quantified as T2 and T2* values, reducing the signal intensity and generating higher MRI contrast compared to unlabeled EVs and gel only. Our study demonstrated that USPIO labeling was a feasible approach for in vitro tracking of brain organoid-derived EVs, which paves the way for further in vivo examination.« less
    Free, publicly-accessible full text available December 1, 2023
  6. Retinal organoids are three-dimensional (3D) structures derived from human pluripotent stem cells (hPSCs) that mimic the retina’s spatial and temporal differentiation, making them useful as in vitro retinal development models. Retinal organoids can be assembled with brain organoids, the 3D self-assembled aggregates derived from hPSCs containing different cell types and cytoarchitectures that resemble the human embryonic brain. Recent studies have shown the development of optic cups in brain organoids. The cellular components of a developing optic vesicle-containing organoids include primitive corneal epithelial and lens-like cells, retinal pigment epithelia, retinal progenitor cells, axon-like projections, and electrically active neuronal networks. The importance of retinal organoids in ocular diseases such as age-related macular degeneration, Stargardt disease, retinitis pigmentosa, and diabetic retinopathy are described in this review. This review highlights current developments in retinal organoid techniques, and their applications in ocular conditions such as disease modeling, gene therapy, drug screening and development. In addition, recent advancements in utilizing extracellular vesicles secreted by retinal organoids for ocular disease treatments are summarized.
    Free, publicly-accessible full text available November 1, 2023
  7. In this paper, we propose a model for parallel magnetic resonance imaging (pMRI) reconstruction, regularized by a carefully designed tight framelet system, that can lead to reconstructed images with much less artifacts in comparison to those from existing models. Our model is motivated from the observations that each receiver coil in a pMRI system is more sensitive to the specific object nearest to the coil, and all coil images are correlated. To exploit these observations, we first stack all coil images together as a 3-dimensional (3D) data matrix, and then design a 3D directional Haar tight framelet (3DHTF) to represent it. After analyzing sparse information of the coil images provided by the high-pass filters of the 3DHTF, we separate the high-pass filters into effective ones and ineffective ones, and we then devise a 3D directional Haar semi-tight framelet (3DHSTF) from the 3DHTF by replacing its ineffective filters with only one filter. This 3DHSTF is tailor-made for coil images, meanwhile, giving a significant saving in computation comparing to the 3DHTF. With the 3DHSTF, we propose an l1-3DHSTF model for pMRI reconstruction. Numerical experiments for MRI phantom and in-vivo data sets are provided to demonstrate the superiority of our l1-3DHSTF model inmore »terms of the efficiency of reducing aliasing artifacts in the reconstructed images.« less
    Free, publicly-accessible full text available September 1, 2023
  8. Free, publicly-accessible full text available August 1, 2023
  9. Arabidopsis RESISTANCE TO POWDERY MILDEW 8.2 (RPW8.2) is specifically induced by the powdery mildew (PM) fungus (Golovinomyces cichoracearum) in the infected epidermal cells to activate immunity. However, the mechanism of RPW8.2-induction is not well understood. Here, we identify a G. cichoracearum effector that interacts with RPW8.2, named Gc-RPW8.2 interacting protein 1 (GcR8IP1), by a yeast two-hybrid screen of an Arabidopsis cDNA library. GcR8IP1 physically associated with RPW8.2 with its RING finger domain that is essential and sufficient for the association. GcR8IP1 was secreted and translocated into the nucleus of host cell infected with PM. Association of GcR8IP1 with RPW8.2 led to an increase of RPW8.2 in the nucleus. In turn, the nucleus-localised RPW8.2 promoted the activity of the RPW8.2 promoter, resulting in transcriptional self-amplification of RPW8.2 to boost immunity at infection sites. Additionally, ectopic expression or host-induced gene silencing of GcR8IP1 supported its role as a virulence factor in PM. Altogether, our results reveal a mechanism of RPW8.2-dependent defense strengthening via altered partitioning of RPW8.2 and transcriptional self-amplification triggered by a PM fungal effector, which exemplifies an atypical form of effector-triggered immunity.
    Free, publicly-accessible full text available December 15, 2023
  10. Free, publicly-accessible full text available August 14, 2023