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Denton M.L.,TASC Inc | Noojin G.D.,TASC Inc | Foltz M.S.,TASC Inc | Clark III C.D.,TASC Inc | And 3 more authors.
Journal of Biomedical Optics | Year: 2011

We measured threshold temperatures for cell death resulting from short (0.1-1.0s) 514-nm laser exposures using an in vitro retinal model. Real-time thermal imaging at sub-cellular resolution provides temperature information that is spatially correlated with cells at the boundary of cell death, as indicate by post-exposure fluorescence images. Our measurements indicate markedly similar temperatures, not only around individual boundaries (single exposure), but among all exposures of the same duration in a laser irradiance-independent fashion. Two different methods yield similar threshold temperatures with low variance. Considering the experimental uncertainties associated with the thermal camera, an average peak temperature of 53 ± 2 °C is found for laser exposures of 0.1, 0.25, and 1.0 s. Additionally, we find a linear relationship between laser exposure duration and time-averaged integrated temperature. The mean thermal profiles for cells at the boundary of death were assessed using the Arrhenius rate law using parameter sets (frequency factor and energy of activation) found in three different articles. © 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). Source


Wilmink G.J.,National Academy of science | Wilmink G.J.,Air Force Research Lab | Roth C.L.,General Dynamics Corporation | Roth C.L.,Air Force Research Lab | And 5 more authors.
Cell Stress and Chaperones | Year: 2010

MicroRNAs (miRNAs) are a class of small RNAs that play a critical role in the coordination of fundamental cellular processes. Recent studies suggest that miRNAs participate in the cellular stress response (CSR), but their specific involvement remains unclear. In this study, we identify a group of thermally regulated miRNAs (TRMs) that are associated with the CSR. Using miRNA microarrays, we show that dermal fibroblasts differentially express 123 miRNAs when exposed to hyperthermia. Interestingly, only 27 of these miRNAs are annotated in the current Sanger registry. We validated the expression of the annotated miRNAs using qPCR techniques, and we found that the qPCR and microarray data was in well agreement. Computational target-prediction studies revealed that putative targets for the TRMs are heat shock proteins and Argonaute-2-the core functional unit of RNA silencing. These results indicate that cells express a specific group of miRNAs when exposed to hyperthermia, and these miRNAs may function in the regulation of the CSR. Future studies will be conducted to determine if other cells lines differentially express these miRNAs when exposed to hyperthermia. © 2010 Cell Stress Society International. Source


Schuster K.J.,TASC Inc | Estlack L.E.,Conceptual MindWorks Inc. | Wigle J.C.,Air Force Research Lab
Progress in Biomedical Optics and Imaging - Proceedings of SPIE | Year: 2013

The objective of this study was to elucidate cellular mechanisms of protection against laser-induced thermal killing utilizing an in vitro retina model. When exposed to a 1-sec pulse of 2-μm laser radiation 24 hr after illuminating hTERT-RPE cells with red light (preconditioning), the cells are more resistant to thermal challenge than unilluminated controls (adaptive response). Results of efforts to understand the physiology of this effect led us to two genes: Vascular Endothelial Growth Factor C (VEGF-C) and Micro RNA 146a (miR-146a). Transfecting wild type (WT) cells with siRNA for VEGF-C and miR-146a mRNA resulted in knockdown strains (VEGF-C(KD) and miR- 146a(-)) with 10% and 30% (respectively) of the constitutive levels expressed in the WT cells. To induce gene expression, WT or KD cells were preconditioned with 1.44 to 5.40 J/cm2, using irradiances between 0.40 and 1.60 mW/cm2 of either 671-nm (diode) or 637-nm (laser) radiation. Probit analysis was used to calculate threshold damage irradiance, expressed as ED50, between 10 and 100 W/cm2 for the 2-μm laser pulse. In the WT cells there is a significant increase in ED50 (p 0.05) with the maximum response occurring at 2.88 J/cm2 in the preconditioned cells. Neither KD cell strain showed a significant increase in the ED50, although some data suggest the response may just be decreased in the knockdown cells instead of absent. So far the response does not appear to be dependent upon either wavelength (637 vs. 671 nm) or coherence (laser vs. LED), but there is an irradiance dependence. © 2013 SPIE. Source


Denton M.L.,TASC Inc | Clark III C.D.,TASC Inc | Foltz M.S.,TASC Inc | Schuster K.J.,TASC Inc | And 3 more authors.
Journal of Biomedical Optics | Year: 2010

We use laser damage thresholds in an in-vitro retinal model, and computational simulations to examine the laser exposure durations at which damage transitions from photothermal to photochemical at 413 nm. Our results indicate a dramatic shift in 1-h damage thresholds between exposure durations of 60 and 100 s. The trend in our in-vitro results is similar to a trend found in a recent study where retinal lesions were assessed 1-h post laser exposure in the rhesus eye Our data suggest that nonthermal mechanisms did not significantly contribute to cell death, even for exposures of 60 s. Knowledge of the transition point, and lack of concurrent thermal and nonthermal damage processes, are significant for those wishing to devise a comprehensive computational damage model. © 2010 Society of Photo-Optical Instrumentation Engineers. Source


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Conceptual MindWorks Inc. | Date: 2010-09-21

Computer hardware and software, for use with medical patient monitoring equipment, for receiving, processing, transmitting and displaying data; Computer software for controlling and managing patient medical information.

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