Novel Liquid Crystal Monomers for Stereolithography: Reaction Rates and Photopolymerization Conversion

Liquid crystal (LC) monomers are a novel type ofresin for stereolithography that result in polymers having unique physical and mechanical properties. These monomers consist ofrigid central cores connected to acrylate functional groups by short aliphatic chains. Because ofthe rigid-rod structure ofthe monomer the cross-linked polymer networks formed have high glass transition temperatures (Tg). The high TglS result in particularly high upper-use temperatures for stereolithography parts. This paper reports on photopolymerization reaction rates and monomer conversion for two acrylate monomers measured using reflectance real-time infra-red spectroscopy (RRTIR). The RRTIR method measures the disappearance ofreactive acrylate groups in the monomer as a function oftime while the monomers are being exposed to UV light. For the two new resins, UV irradiation using an argon ion laser gives rapid photopolymerization with acrylate conversion as high as 95 %. Conversion and polymerization rates in these monomers are dependent upon photo-initiator selection and concentration. In addition, the results indicate that conversion increases with increased laser intensity and elevated temperatures.Mechanical Engineerin

EUS-guided verteporfin photodynamic therapy for pancreatic cancer

BACKGROUND AND AIMS: Locally advanced pancreatic cancer (LAPC) often causes obstruction. Verteporfin photodynamic therapy (PDT) can feasibly "debulk" tumor more safely than noncurative surgery and has multiple advantages over older PDT agents. We aimed to assess the feasibility of EUS-guided verteporfin PDT in ablating nonresectable LAPC. METHODS: Adults with LAPC with adequate biliary drainage were prospectively enrolled. Exclusion criteria included significant metastatic disease burden, disease involving >50% duodenal or major artery circumference, and recent treatment with curative intent. CT was obtained between day -28 to 0. On day 0, verteporfin 0.4 mg/kg was infused 60 to 90 minutes before EUS, during which a diffuser was positioned in the tumor and delivered light at 50 J/cm for 333 seconds. CT was obtained on day 2, with adverse event monitoring occurring on days 1, 2, and 14. Primary outcome was presence of necrosis. RESULTS: Of 8 patients (62.5% male, mean age 65±7.9 y) included in the study, 5 were staged at T3, 2 at T2, and 1 at T1. Most (4) had primary lesions in the pancreatic head. Mean pretrial tumor diameter was 33.3±13.4 mm. On day 2 CT, 5 lesions demonstrated a zone of necrosis measuring a mean diameter of 15.7±5.5 mm; 3 cases did not develop necrosis. No adverse events were noted during the procedure or postprocedure observation period (day 1-3), and no changes in patient reported outcomes were noted. CONCLUSIONS: In this pilot study, EUS-guided verteporfin PDT is feasible and shows promise as a minimally invasive ablative therapy for LAPC in select patients. Tumor necrosis is visible within 48 hours after treatment. Patient enrollment and data collection are ongoing

Microdose Fluorescence Imaging of ABY-029 on an Operating Microscope Adapted by Custom Illumination and Imaging Modules

Fluorescence guided surgery has the potential to positively impact surgical oncology; current operating microscopes and stand-alone imaging systems are too insensitive or too cumbersome to maximally take advantage of new tumor-specific agents developed through the microdose pathway. To this end, a custom-built illumination and imaging module enabling picomolar-sensitive near-infrared fluorescence imaging on a commercial operating microscope is described. The limits of detection and system specifications are characterized, and in vivo efficacy of the system in detecting ABY-029 is evaluated in a rat orthotopic glioma model following microdose injections, showing the suitability of the device for microdose phase 0 clinical trials

Criteria for the design of tissue-mimicking phantoms for the standardization of biophotonic instrumentation

A lack of accepted standards and standardized phantoms suitable for the technical validation of biophotonic instrumentation hinders the reliability and reproducibility of its experimental outputs. In this Perspective, we discuss general criteria for the design of tissue-mimicking biophotonic phantoms, and use these criteria and state-of-the-art developments to critically review the literature on phantom materials and on the fabrication of phantoms. By focusing on representative examples of standardization in diffuse optical imaging and spectroscopy, fluorescence-guided surgery and photoacoustic imaging, we identify unmet needs in the development of phantoms and a set of criteria (leveraging characterization, collaboration, communication and commitment) for the standardization of biophotonic instrumentation

In Vitro Identification and In Vivo Confirmation of Inhibitors for Sweet Potato Chlorotic Stunt Virus RNA Silencing Suppressor, a Viral RNase III

Sweet potato virus disease (SPVD), caused by synergistic infection of Sweet potato chlorotic stunt virus (SPCSV) and Sweet potato feathery mottle virus (SPFMV), is responsible for substantial yield losses all over the world. However, there are currently no approved treatments for this severe disease. The crucial role played by RNase III of SPCSV (CSR3) as an RNA silencing suppressor during the viruses' synergistic interaction in sweetpotato makes it an ideal drug target for developing antiviral treatment. In this study, high-throughput screening (HTS) of small molecular libraries targeting CSR3 was initiated by a virtual screen using Glide docking, allowing the selection of 6,400 compounds out of 136,353. We subsequently developed and carried out kinetic-based HTS using fluorescence resonance energy transfer technology, which isolated 112 compounds. These compounds were validated with dose-response assays including kinetic-based HTS and binding affinity assays using surface plasmon resonance and microscale thermophoresis. Finally, the interference of the selected compounds with viral accumulation was verified in planta. In summary, we identified five compounds belonging to two structural classes that inhibited CSR3 activity and reduced viral accumulation in plants. These results provide the foundation for developing antiviral agents targeting CSR3 to provide new strategies for controlling sweetpotato virus diseases. IMPORTANCE We report here a high-throughput inhibitor identification method that targets a severe sweetpotato virus disease caused by coinfection with two viruses (SPCSV and SPFMV). The disease is responsible for up to 90% yield losses. Specifically, we targeted the RNase III enzyme encoded by SPCSV, which plays an important role in suppressing the RNA silencing defense system of sweetpotato plants. Based on virtual screening, laboratory assays, and confirmation in planta, we identified five compounds that could be used to develop antiviral drugs to combat the most severe sweetpotato virus disease.Peer reviewe

Decomposition Analyses Applied to a Complex Ultradian Biorhythm: The Oscillating NADH Oxidase Activity of Plasma Membranes Having a Potential Time-Keeping (Clock) Function

Seasonal decomposition analyses were applied to the statistical evaluation of an oscillating activity for a plasma membrane NADH oxidase activity with a temperature compensated period of 24 min. The decomposition fits were used to validate the cyclic oscillatory pattern. Three measured values, average percentage error (MAPE), a measure of the periodic oscillation, mean average deviation (MAD), a measure of the absolute average deviations from the fitted values, and mean standard deviation (MSD), the measure of standard deviation from the fitted values plus R-squared and the Henriksson-Merton p value were used to evaluate accuracy. Decomposition was carried out by fitting a trend line to the data, then detrending the data if necessary, by subtracting the trend component. The data, with or without detrending, were then smoothed by subtracting a centered moving average of length equal to the period length determined by Fourier analysis. Finally, the time series were decomposed into cyclic and error components. The findings not only validate the periodic nature of the major oscillations but suggest, as well, that the minor intervening fluctuations also recur within each period with a reproducible pattern of recurrence. biological clockdecomposition analysesultradian rhythmtemperature compensationcircadian rhythmcultured cells

Sub-Diffusive Scattering Parameter Maps Recovered Using Wide-Field High-Frequency Structured Light Imaging

This study investigates the hypothesis that structured light reflectance imaging with high spatial frequency patterns (fx) can be used to quantitatively map the anisotropic scattering phase function distribution (P(θs)) in turbid media. Monte Carlo simulations were used in part to establish a semi-empirical model of demodulated reflectance (Rd) in terms of dimensionless scattering (μ′sf−1x) and γ, a metric of the first two moments of the P(θs) distribution. Experiments completed in tissue-simulating phantoms showed that simultaneous analysis of Rd spectra sampled at multiple fx in the frequency range [0.05-0.5] mm−1 allowed accurate estimation of both μ′s(λ) in the relevant tissue range [0.4-1.8] mm−1, and γ(λ) in the range [1.4-1.75]. Pilot measurements of a healthy volunteer exhibited γ-based contrast between scar tissue and surrounding normal skin, which was not as apparent in wide field diffuse imaging. These results represent the first wide-field maps to quantify sub-diffuse scattering parameters, which are sensitive to sub-microscopic tissue structures and composition, and therefore, offer potential for fast diagnostic imaging of ultrastructure on a size scale that is relevant to surgical applications

Review of Fluorescence Guided Surgery Visualization and Overlay Techniques

In fluorescence guided surgery, data visualization represents a critical step between signal capture and display needed for clinical decisions informed by that signal. The diversity of methods for displaying surgical images are reviewed, and a particular focus is placed on electronically detected and visualized signals, as required for near-infrared or low concentration tracers. Factors driving the choices such as human perception, the need for rapid decision making in a surgical environment, and biases induced by display choices are outlined. Five practical suggestions are outlined for optimal display orientation, color map, transparency/alpha function, dynamic range compression, and color perception check