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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.


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).


Wilmink G.J.,Air Force Research Lab | Wilmink G.J.,National Academy of science | Rivest B.D.,Air Force Research Lab | Roth C.C.,General Dynamics Corporation | And 7 more authors.
Lasers in Surgery and Medicine | Year: 2011

Background Terahertz (THz) radiation sources are increasingly being used in military, defense, and medical applications. However, the biological effects associated with this type of radiation are not well characterized. In this study, we evaluated the cellular and molecular response of human dermal fibroblasts exposed to THz radiation. Methods In vitro exposures were performed in a temperature-controlled chamber using a molecular gas THz laser (2.52 THz, 84.8 mW cm-2, durations: 5, 10, 20, 40, or 80 minutes). Both computational and empirical dosimetric techniques were conducted using finite-difference time-domain (FDTD) modeling approaches, infrared cameras, and thermocouples. Cellular viability was assessed using conventional MTT assays. In addition, the transcriptional activation of protein and DNA sensing genes were evaluated using qPCR. Comparable analyses were also conducted for hyperthermic and genotoxic positive controls. Results We found that cellular temperatures increased by 3°C during all THz exposures. We also found that for each exposure duration tested, the THz and hyperthermic exposure groups exhibited equivalent levels of cell survival ( ¥90%) and heat shock protein expression ( 3.5-fold increases). In addition, the expression of DNA sensing and repair genes was unchanged in both groups; however, appreciable increases were observed in the genotoxic controls. Conclusions Human dermal fibroblasts exhibit comparable cellular and molecular effects when exposed to THz radiation and hyperthermic stress. These findings suggest that radiation at 2.52 THz generates primarily thermal effects in mammalian cells. Therefore, we conclude that THz-induced bioeffects may be accurately predicted with conventional thermal damage models. © 2010 Wiley-Liss, Inc.


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.


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.


Patent
Conceptual MindWorks Inc. | Date: 2011-08-05

Disclosed are systems and methods to provide a patient care recommendation. The systems and methods receive patient information and a plurality of patient physiological signals that are related to a patient. The systems and methods are then operable to produce at least one derived patient signal from at least one of the plurality of patient physiological signals. The systems and methods use the patient information, at least one of the plurality of patient physiological signals, and the at least one derived patient signal to provide at least one patient care recommendation.


Patent
Conceptual MindWorks Inc. | Date: 2011-08-05

Disclosed are systems and methods to provide a patient care recommendation. The systems and methods receive patient information and a plurality of patient physiological signals that are related to a patient. The systems and methods are then operable to produce at least one derived patient signal from at least one of the plurality of patient physiological signals. The systems and methods use the patient information, at least one of the plurality of patient physiological signals, and the at least one derived patient signal to provide at least one patient care recommendation.


Patent
Conceptual MindWorks Inc. | Date: 2011-08-05

Disclosed are systems and methods to provide a patient care recommendation. The systems and methods receive patient information and a plurality of patient physiological signals that are related to a patient. The systems and methods are then operable to produce at least one derived patient signal from at least one of the plurality of patient physiological signals. The systems and methods use the patient information, at least one of the plurality of patient physiological signals, and the at least one derived patient signal to provide at least one patient care recommendation.


Pdx

Trademark
Conceptual MindWorks Inc. | Date: 2014-02-14

computer software program for database management in the medical field.


Trademark
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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