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  1. Abstract

    Vascular‐targeted drug delivery remains an attractive platform for therapeutic and diagnostic interventions in human diseases. This work focuses on the development of a poly‐lactic‐co‐glycolic‐acid (PLGA)‐based multistage delivery system (MDS). MDS consists of two stages: a micron‐sized PLGA outer shell and encapsulated drug‐loaded PLGA nanoparticles. Nanoparticles with average diameters of 76, 119, and 193 nm are successfully encapsulated into 3–6 µm MDS. Sustained in vitro release of nanoparticles from MDS is observed for up to 7 days. Both MDS and nanoparticles arebiocompatible with human endothelial cells. Sialyl‐Lewis‐A (sLeA) is successfully immobilized on the MDS and nanoparticle surfaces to enable specific targeting of inflamed endothelium. Functionalized MDS demonstrates a 2.7‐fold improvement in endothelial binding compared to PLGA nanoparticles from human blood laminar flow. Overall, the presented results demonstrate successful development and characterization of MDS and suggest that MDS can serve as an effective drug carrier, which can enhance the margination of nanoparticles to the targeted vascular wall.

     
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  2. null (Ed.)
    Abstract We demonstrate that structured illumination microscopy has the potential to enhance fluorescence lifetime imaging microscopy (FLIM) as an early detection method for oral squamous cell carcinoma. FLIM can be used to monitor or detect changes in the fluorescence lifetime of metabolic cofactors (e.g. NADH and FAD) associated with the onset of carcinogenesis. However, out of focus fluorescence often interferes with this lifetime measurement. Structured illumination fluorescence lifetime imaging (SI-FLIM) addresses this by providing depth-resolved lifetime measurements, and applied to oral mucosa, can localize the collected signal to the epithelium. In this study, the hamster model of oral carcinogenesis was used to evaluate SI-FLIM in premalignant and malignant oral mucosa. Cheek pouches were imaged in vivo and correlated to histopathological diagnoses. The potential of NADH fluorescence signal and lifetime, as measured by widefield FLIM and SI-FLIM, to differentiate dysplasia (pre-malignancy) from normal tissue was evaluated. ROC analysis was carried out with the task of discriminating between normal tissue and mild dysplasia, when changes in fluorescence characteristics are localized to the epithelium only. The results demonstrate that SI-FLIM (AUC = 0.83) is a significantly better (p-value = 0.031) marker for mild dysplasia when compared to widefield FLIM (AUC = 0.63). 
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  3. The Texas A&M University System (TAMUS) received funding from the National Science Foundation (NSF) for a Louis Stokes Alliance for Minority Participation (LSAMP) project in 1991 as one of the six initial awardees. As part of these efforts and upon reaching eligibility, the TAMUS LSAMP applied for and received additional funding to support a Bridge to the Doctorate (BTD) program. BTD programming provides financial, educational, and social support to incoming STEM master’s degree and PhD students for the first two years of their graduate study. BTD cohorts consist of up to 12 fellows who participate in a program of academic and professional development seminars and workshops. In project evaluation, annual interviews were conducted with the TAMUS BTD participants, the vast majority of whom were underrepresented minorities (92%). During the interviews, the BTD students were asked to discuss ten topics some of which addressed concerns specific to the implementation of the BTD project. This report considers answers provided in the five topic areas which have broader applicability: 1) the learning achieved by participants through participation in BTD, 2) the personal impact of participation in BTD, 3) the influence of BTD on informants’ educational goals, 4) the influence of BTD on informants’ career goals, and 5) barriers the BTD participants perceived to pursuing a PhD. Eighty project participants responded to the questions between 2009 and 2018. They were from eight distinct cohorts of BTD students and represented 32 different areas of STEM specialization. Qualitative analysis of their responses confirmed that students perceived the elements of the TAMUS BTD project to be efficacious and that there was a set of nine seminars from which participants consistently reported benefit. Additional findings were eight key areas in which learning was reported by participants, four areas in which the programming  had personal impact, five influences on educational goals,  nine impacts on career goals, and a detailed list of barriers graduate students who are underrepresented minorities (URM) perceive to pursuing a doctoral degree. The proven and easily replicated pattern of support programming, the demonstrated results of this programming, and insight into barriers URMs perceive to pursuing a STEM doctorate are immediately applicable to URM graduate student support at many institutions of higher education. 
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  4. With the view of developing electrophilic late-transition-metal catalysts, we have now synthesized [(o-(Ph2P)C6H4)2Sb(OTf)2]Pt(OTf) (2) and [(o-(iPr2P)C6H4)2Sb(OTf)2]Pt(OTf) (4) by treatment of the corresponding trichlorides ([(o-(R2P)C6H4)2SbCl2]PtCl (R = Ph, iPr)) with 3 equiv of AgOTf. The crystal structures of 2 and 4 confirmed that the chloride ligands have been fully substituted by more labile triflate ligands. Despite structural similarities in the dinuclear cores of 2 and 4, only 2 acts as a potent carbophilic catalyst in enyne cyclization reactions. The high activity of 2 is also reflected by its ability to promote the addition of pyrrole and thiophene derivatives to alkynes. Structural and computational analyses suggest that the superior reactivity of 2 results from both favorable steric and electronic effects. Finally, a comparison of 2 with the previously reported self-activating catalyst [(o-(Ph2P)C6H4)2Sb(OTf)2]PtCl underscores the benefits of triflate for chloride substitution. 
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  5. The optical activity of Raman scattering provides insight into the absolute configuration and conformation of chiral molecules. Applications of Raman optical activity (ROA) are limited by long integration times due to a relatively low sensitivity of the scattered light to chirality (typically 10^-3 to 10^-5). We apply ROA techniques to hyper-Raman scattering using incident circularly polarized light and a right-angle scattering geometry. We explore the sensitivity of hyper- Raman scattering to chirality as compared to spontaneous Raman optical activity. Using the excitation wavelength at around 532 nm, the photobleaching is minimized, while the hyper-Raman scattering benefits from the electronic resonant enhancement. For S/R-2-butanol and L/D-tartaric acid, we were unable to detect the hyper-Raman optical activity at the sensitivity level of 1%. We also explored parasitic thermal effects which can be mitigating by varying the repetition rate of the laser source used for excitation of hyper-Raman scattering. 
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  6. Monte Carlo Simulations (MCSs) allow for the estimation of photon propagation through media given knowledge of the geometry and optical properties. Previous research has demonstrated that the inverse of this problem may be solved as well, where neural networks trained on photon distributions can be used to estimate refractive index, scattering and absorption coefficients. To extend this work, time-dependent MCSs are used to generate data sets of photon propagation through various media. These simulations were treated as stacks of 2D images in time and used to train convolutional networks to estimate tissue parameters. To find potential features that drive network performance on this task, networks were randomly generated. Generated networks were then trained. The networks were validated using 4-fold cross validation. The consistently performing top 10 networks typically had an emphasis on convolutional chains and convolutional chains ending in max pooling. 
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  7. Scanning confocal Raman spectroscopy was applied for detecting and identifying topically applied ocular pharmaceuticals on rabbit corneal tissue. Raman spectra for Cyclosporin A, Difluprednate, and Dorzolamide were acquired together with Raman spectra from rabbit corneas with an unknown amount of applied drug. Kernel principle component analysis (KPCA) was then used to explore a transform that can describe the acquired set of Raman spectra. Using this transform, we observe some spectral similarity between cornea spectra and Cyclosporin A, with little similarity to Dorzolamide and Difluprednate. Further investigation is needed to identify why these differences occur. 
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