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  1. Free, publicly-accessible full text available September 20, 2024
  2. Yang, Junyuan (Ed.)
    In this work, we develop a new set of Bayesian models to perform registration of real-valued functions. A Gaussian process prior is assigned to the parameter space of time warping functions, and a Markov chain Monte Carlo (MCMC) algorithm is utilized to explore the posterior distribution. While the proposed model can be defined on the infinite-dimensional function space in theory, dimension reduction is needed in practice because one cannot store an infinite-dimensional function on the computer. Existing Bayesian models often rely on some pre-specified, fixed truncation rule to achieve dimension reduction, either by fixing the grid size or the number of basis functions used to represent a functional object. In comparison, the new models in this paper randomize the truncation rule. Benefits of the new models include the ability to make inference on the smoothness of the functional parameters, a data-informative feature of the truncation rule, and the flexibility to control the amount of shape-alteration in the registration process. For instance, using both simulated and real data, we show that when the observed functions exhibit more local features, the posterior distribution on the warping functions automatically concentrates on a larger number of basis functions. Supporting materials including code and data to perform registration and reproduce some of the results presented herein are available online. 
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    Free, publicly-accessible full text available July 7, 2024
  3. Free, publicly-accessible full text available July 24, 2024
  4. Evaluation of Gastrointestinal Stromal Tumors (GIST) during initial clinical staging, surgical intervention, and postoperative management can be challenging. Current imaging modalities ( e.g. , PET and CT scans) lack sensitivity and specificity. Therefore, advanced clinical imaging modalities that can provide clinically relevant images with high resolution would improve diagnosis. KIT is a tyrosine kinase receptor overexpressed on GIST. Here, the application of a specific DNA aptamer targeting KIT, decorated onto a fluorescently labeled porous silicon nanoparticle (pSiNP), is used for the in vitro & in vivo imaging of GIST. This nanoparticle platform provides high-fidelity GIST imaging with minimal cellular toxicity. An in vitro analysis shows greater than 15-fold specific KIT protein targeting compared to the free KIT aptamer, while in vivo analyses of GIST-burdened mice that had been injected intravenously (IV) with aptamer-conjugated pSiNPs show extensive nanoparticle-to-tumor signal co-localization (>90% co-localization) compared to control particles. This provides an effective platform for which aptamer-conjugated pSiNP constructs can be used for the imaging of KIT-expressing cancers or for the targeted delivery of therapeutics. 
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  5. Abstract

    Fluorine magnetic resonance imaging (19F MRI) has emerged as an attractive alternative to conventional1H MRI due to enhanced specificity deriving from negligible background signal in this modality. We report a dual nanoparticle conjugate (DNC) platform as an aptamer‐based sensor for use in19F MRI.DNCconsists of core–shell nanoparticles with a liquid perfluorocarbon core and a mesoporous silica shell (19F‐MSNs), which give a robust19F MR signal, and superparamagnetic iron oxide nanoparticles (SPIONs) as magnetic quenchers. Due to the strong magnetic quenching effects of SPIONs, this platform is uniquely sensitive and functions with a low concentration of SPIONs (4 equivalents) relative to19F‐MSNs. The probe functions as a “turn‐on” sensor using target‐induced dissociation of DNA aptamers. The thrombin binding aptamer was incorporated as a proof‐of‐concept (DNCThr), and we demonstrate a significant increase in19F MR signal intensity whenDNCThris incubated with human α‐thrombin. This proof‐of‐concept probe is highly versatile and can be adapted to sense ATP and kanamycin as well. Importantly,DNCThrgenerates a robust19F MRI “hot‐spot” signal in response to thrombin in live mice, establishing this platform as a practical, versatile, and biologically relevant molecular imaging probe.

     
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  6. Abstract

    Fluorine magnetic resonance imaging (19F MRI) has emerged as an attractive alternative to conventional1H MRI due to enhanced specificity deriving from negligible background signal in this modality. We report a dual nanoparticle conjugate (DNC) platform as an aptamer‐based sensor for use in19F MRI.DNCconsists of core–shell nanoparticles with a liquid perfluorocarbon core and a mesoporous silica shell (19F‐MSNs), which give a robust19F MR signal, and superparamagnetic iron oxide nanoparticles (SPIONs) as magnetic quenchers. Due to the strong magnetic quenching effects of SPIONs, this platform is uniquely sensitive and functions with a low concentration of SPIONs (4 equivalents) relative to19F‐MSNs. The probe functions as a “turn‐on” sensor using target‐induced dissociation of DNA aptamers. The thrombin binding aptamer was incorporated as a proof‐of‐concept (DNCThr), and we demonstrate a significant increase in19F MR signal intensity whenDNCThris incubated with human α‐thrombin. This proof‐of‐concept probe is highly versatile and can be adapted to sense ATP and kanamycin as well. Importantly,DNCThrgenerates a robust19F MRI “hot‐spot” signal in response to thrombin in live mice, establishing this platform as a practical, versatile, and biologically relevant molecular imaging probe.

     
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