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Local, nonlinear effects of cGMP and Ca2+ reduce single photon response variability in retinal rods.
Caruso G, Gurevich VV, Klaus C, Hamm H, Makino CL, DiBenedetto E
(2019) PLoS One 14: e0225948
MeSH Terms: Algorithms, Animals, Biomarkers, Calcium, Cyclic GMP, Mice, Models, Biological, Photons, Retinal Rod Photoreceptor Cells, Rod Cell Outer Segment, Signal Transduction
Show Abstract · Added March 18, 2020
The single photon response (SPR) in vertebrate photoreceptors is inherently variable due to several stochastic events in the phototransduction cascade, the main one being the shutoff of photoactivated rhodopsin. Deactivation is driven by a random number of steps, each of random duration with final quenching occurring after a random delay. Nevertheless, variability of the SPR is relatively low, making the signal highly reliable. Several biophysical and mathematical mechanisms contributing to variability suppression have been examined by the authors. Here we investigate the contribution of local depletion of cGMP by PDE*, the non linear dependence of the photocurrent on cGMP, Ca2+ feedback by making use of a fully space resolved (FSR) mathematical model, applied to two species (mouse and salamander), by varying the cGMP diffusion rate severalfold and rod outer segment diameter by an order of magnitude, and by introducing new, more refined, and time dependent variability functionals. Globally well stirred (GWS) models, and to a lesser extent transversally well stirred models (TWS), underestimate the role of nonlinearities and local cGMP depletion in quenching the variability of the circulating current with respect to fully space resolved models (FSR). These distortions minimize the true extent to which SPR is stabilized by locality in cGMP depletion, nonlinear effects linking cGMP to current, and Ca2+ feedback arising from the physical separation of E* from the ion channels located on the outer shell, and the diffusion of these second messengers in the cytoplasm.
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11 MeSH Terms
Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies.
Kaiser A, Eley JG, Onyeuku NE, Rice SR, Wright CC, McGovern NE, Sank M, Zhu M, Vujaskovic Z, Simone CB, Hussain A
(2019) J Vis Exp :
MeSH Terms: Humans, Male, Photons, Prostatic Neoplasms, Proton Therapy, Radiometry, Radiotherapy Planning, Computer-Assisted
Show Abstract · Added March 30, 2020
Radiation therapy is a frequently used modality for the treatment of solid cancers. Although the mechanisms of cell kill are similar for all forms of radiation, the in vivo properties of photon and proton beams differ greatly and maybe exploited to optimize clinical outcomes. In particular, proton particles lose energy in a predictable manner as they pass through the body. This property is used clinically to control the depth at which the proton beam is terminated, and to limit radiation dose beyond the target region. This strategy can allow for substantial reductions in radiation dose to normal tissues located just beyond a tumor target. However, the degradation of proton energy in the body remains highly sensitive to tissue density. As a consequence, any changes in tissue density during the course of treatment may significantly alter proton dosimetry. Such changes may occur through alterations in body weight, respiration, or bowel filling/gas, and may result in unfavorable dose deposition. In this manuscript, we provide a detailed method for the delivery of proton therapy using both passive scatter and pencil beam scanning techniques for prostate cancer. Although the described procedure directly pertains to prostate cancer patients, the method may be adapted and applied for the treatment of virtually all solid tumors. Our aim is to equip readers with a better understanding of proton therapy delivery and outcomes in order to facilitate the appropriate integration of this modality during cancer therapy.
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MeSH Terms
Photonic crystal microring resonator for label-free biosensing.
Lo SM, Hu S, Gaur G, Kostoulas Y, Weiss SM, Fauchet PM
(2017) Opt Express 25: 7046-7054
MeSH Terms: Biosensing Techniques, Light, Optics and Photonics, Photons
Show Abstract · Added May 5, 2017
A label-free optical biosensor based on a one-dimensional photonic crystal microring resonator with enhanced light-matter interaction is demonstrated. More than a 2-fold improvement in volumetric and surface sensing sensitivity is achieved compared to conventional microring sensors. The experimental bulk detection sensitivity is ~248nm/RIU and label-free detection of DNA and proteins is reported at the nanomolar scale. With a minimum feature size greater than 100nm, the photonic crystal microring resonator biosensor can be fabricated with the same standard lithographic techniques used to mass fabricate conventional microring resonators.
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4 MeSH Terms
Development and validation of a GEANT4 radiation transport code for CT dosimetry.
Carver DE, Kost SD, Fernald MJ, Lewis KG, Fraser ND, Pickens DR, Price RR, Stabin MG
(2015) Health Phys 108: 419-28
MeSH Terms: Child, Computer Simulation, Humans, Monte Carlo Method, Phantoms, Imaging, Photons, Polymethyl Methacrylate, Radiation Dosage, Radiation Monitoring, Spectrometry, Gamma, Tomography, X-Ray Computed
Show Abstract · Added October 18, 2016
The authors have created a radiation transport code using the GEANT4 Monte Carlo toolkit to simulate pediatric patients undergoing CT examinations. The focus of this paper is to validate their simulation with real-world physical dosimetry measurements using two independent techniques. Exposure measurements were made with a standard 100-mm CT pencil ionization chamber, and absorbed doses were also measured using optically stimulated luminescent (OSL) dosimeters. Measurements were made in air with a standard 16-cm acrylic head phantom and with a standard 32-cm acrylic body phantom. Physical dose measurements determined from the ionization chamber in air for 100 and 120 kVp beam energies were used to derive photon-fluence calibration factors. Both ion chamber and OSL measurement results provide useful comparisons in the validation of the Monte Carlo simulations. It was found that simulated and measured CTDI values were within an overall average of 6% of each other.
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11 MeSH Terms
Simulation study comparing high-purity germanium and cadmium zinc telluride detectors for breast imaging.
Campbell DL, Peterson TE
(2014) Phys Med Biol 59: 7059-79
MeSH Terms: Breast, Cadmium, Computer Simulation, Female, Germanium, Humans, Image Processing, Computer-Assisted, Monte Carlo Method, Phantoms, Imaging, Photons, Positron-Emission Tomography, Radionuclide Imaging, Signal-To-Noise Ratio, Tellurium, Zinc
Show Abstract · Added February 16, 2015
We conducted simulations to compare the potential imaging performance for breast cancer detection with High-Purity Germanium (HPGe) and Cadmium Zinc Telluride (CZT) systems with 1% and 3.8% energy resolution at 140 keV, respectively. Using the Monte Carlo N-Particle (MCNP5) simulation package, we modelled both 5 mm-thick CZT and 10 mm-thick HPGe detectors with the same parallel-hole collimator for the imaging of a breast/torso phantom. Simulated energy spectra were generated, and planar images were created for various energy windows around the 140 keV photopeak. Relative sensitivity and scatter and the torso fractions were calculated along with tumour contrast and signal-to-noise ratios (SNR). Simulations showed that utilizing a ±1.25% energy window with an HPGe system better suppressed torso background and small-angle scattered photons than a comparable CZT system using a -5%/+10% energy window. Both systems provided statistically similar contrast and SNR, with HPGe providing higher relative sensitivity. Lowering the counts of HPGe images to match CZT count density still yielded equivalent contrast between HPGe and CZT. Thus, an HPGe system may provide equivalent breast imaging capability at lower injected radioactivity levels when acquiring for equal imaging time.
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15 MeSH Terms
Multidimensional mapping of spin-exchange optical pumping in clinical-scale batch-mode 129Xe hyperpolarizers.
Nikolaou P, Coffey AM, Ranta K, Walkup LL, Gust BM, Barlow MJ, Rosen MS, Goodson BM, Chekmenev EY
(2014) J Phys Chem B 118: 4809-16
MeSH Terms: Equipment Design, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Optics and Photonics, Photons, Pressure, Spectrophotometry, Infrared, Xenon Isotopes
Show Abstract · Added June 10, 2014
We present a systematic, multiparameter study of Rb/(129)Xe spin-exchange optical pumping (SEOP) in the regimes of high xenon pressure and photon flux using a 3D-printed, clinical-scale stopped-flow hyperpolarizer. In situ NMR detection was used to study the dynamics of (129)Xe polarization as a function of SEOP-cell operating temperature, photon flux, and xenon partial pressure to maximize (129)Xe polarization (PXe). PXe values of 95 ± 9%, 73 ± 4%, 60 ± 2%, 41 ± 1%, and 31 ± 1% at 275, 515, 1000, 1500, and 2000 Torr Xe partial pressure were achieved. These PXe polarization values were separately validated by ejecting the hyperpolarized (129)Xe gas and performing low-field MRI at 47.5 mT. It is shown that PXe in this high-pressure regime can be increased beyond already record levels with higher photon flux and better SEOP thermal management, as well as optimization of the polarization dynamics, pointing the way to further improvements in hyperpolarized (129)Xe production efficiency.
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8 MeSH Terms
Uncertainties in estimating health risks associated with exposure to ionising radiation.
Preston RJ, Boice JD, Brill AB, Chakraborty R, Conolly R, Hoffman FO, Hornung RW, Kocher DC, Land CE, Shore RE, Woloschak GE
(2013) J Radiol Prot 33: 573-88
MeSH Terms: Animals, Animals, Laboratory, Dose-Response Relationship, Radiation, Environmental Exposure, Humans, Occupational Exposure, Photons, Radiation Dosage, Radiation Injuries, Radiation Protection, Radiation, Ionizing, Radiologic Health, Radon, Risk Assessment, Uncertainty, United States, United States National Aeronautics and Space Administration
Show Abstract · Added March 7, 2014
The information for the present discussion on the uncertainties associated with estimation of radiation risks and probability of disease causation was assembled for the recently published NCRP Report No. 171 on this topic. This memorandum provides a timely overview of the topic, given that quantitative uncertainty analysis is the state of the art in health risk assessment and given its potential importance to developments in radiation protection. Over the past decade the increasing volume of epidemiology data and the supporting radiobiology findings have aided in the reduction of uncertainty in the risk estimates derived. However, it is equally apparent that there remain significant uncertainties related to dose assessment, low dose and low dose-rate extrapolation approaches (e.g. the selection of an appropriate dose and dose-rate effectiveness factor), the biological effectiveness where considerations of the health effects of high-LET and lower-energy low-LET radiations are required and the transfer of risks from a population for which health effects data are available to one for which such data are not available. The impact of radiation on human health has focused in recent years on cancer, although there has been a decided increase in the data for noncancer effects together with more reliable estimates of the risk following radiation exposure, even at relatively low doses (notably for cataracts and cardiovascular disease). New approaches for the estimation of hereditary risk have been developed with the use of human data whenever feasible, although the current estimates of heritable radiation effects still are based on mouse data because of an absence of effects in human studies. Uncertainties associated with estimation of these different types of health effects are discussed in a qualitative and semi-quantitative manner as appropriate. The way forward would seem to require additional epidemiological studies, especially studies of low dose and low dose-rate occupational and perhaps environmental exposures and for exposures to x rays and high-LET radiations used in medicine. The development of models for more reliably combining the epidemiology data with experimental laboratory animal and cellular data can enhance the overall risk assessment approach by providing biologically refined data to strengthen the estimation of effects at low doses as opposed to the sole use of mathematical models of epidemiological data that are primarily driven by medium/high doses. NASA's approach to radiation protection for astronauts, although a unique occupational group, indicates the possible applicability of estimates of risk and their uncertainty in a broader context for developing recommendations on: (1) dose limits for occupational exposure and exposure of members of the public; (2) criteria to limit exposures of workers and members of the public to radon and its short-lived decay products; and (3) the dosimetric quantity (effective dose) used in radiation protection.
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17 MeSH Terms
Ultra-compact silicon photonic devices reconfigured by an optically induced semiconductor-to-metal transition.
Ryckman JD, Hallman KA, Marvel RE, Haglund RF, Weiss SM
(2013) Opt Express 21: 10753-63
MeSH Terms: Equipment Design, Equipment Failure Analysis, Miniaturization, Photons, Semiconductors, Silicon, Surface Plasmon Resonance
Show Abstract · Added April 27, 2017
Vanadium dioxide (VO(2)) is a promising reconfigurable optical material and has long been a focus of condensed matter research owing to its distinctive semiconductor-to-metal phase transition (SMT), a feature that has stimulated recent development of thermally reconfigurable photonic, plasmonic, and metamaterial structures. Here, we integrate VO(2) onto silicon photonic devices and demonstrate all-optical switching and reconfiguration of ultra-compact broadband Si-VO(2) absorption modulators (L < 1 μm) and ring-resonators (R ~ λ(0)). Optically inducing the SMT in a small, ~0.275 μm(2), active area of polycrystalline VO(2) enables Si-VO(2) structures to achieve record values of absorption modulation, ~4 dB μm(-1), and intracavity phase modulation, ~π/5 rad μm(-1). This in turn yields large, tunable changes to resonant wavelength,
Δλ(SMT)
~ 3 nm, approximately 60 times larger than Si-only control devices, and enables reconfigurable filtering and optical modulation in excess of 7 dB from modest Q-factor (~10(3)), high-bandwidth ring resonators (>100 GHz). All-optical integrated Si-VO(2) devices thus constitute platforms for reconfigurable photonics, bringing new opportunities to realize dynamic on-chip networks and ultrafast optical shutters and modulators.
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7 MeSH Terms
Identification of key factors that reduce the variability of the single photon response.
Caruso G, Bisegna P, Andreucci D, Lenoci L, Gurevich VV, Hamm HE, DiBenedetto E
(2011) Proc Natl Acad Sci U S A 108: 7804-7
MeSH Terms: Animals, Calcium, Cyclic GMP, Light, Light Signal Transduction, Mice, Models, Biological, Photons, Retinal Rod Photoreceptor Cells, Rhodopsin, Rod Cell Outer Segment, Second Messenger Systems, Stochastic Processes
Show Abstract · Added December 10, 2013
Rod photoreceptors mediate vision in dim light. Their biological function is to discriminate between distinct, very low levels of illumination, i.e., they serve as reliable photon counters. This role requires high reproducibility of the response to a particular number of photons. Indeed, single photon responses demonstrate unexpected low variability, despite the stochastic nature of the individual steps in the transduction cascade. We analyzed individual system mechanisms to identify their contribution to variability suppression. These include: (i) cooperativity of the regulation of the second messengers; (ii) diffusion of cGMP and Ca(2+) in the cytoplasm; and (iii) the effect of highly localized cGMP hydrolysis by activated phosphodiesterase resulting in local saturation. We find that (i) the nonlinear relationships between second messengers and current at the plasma membrane, and the cGMP hydrolysis saturation effects, play a major role in stabilizing the system; (ii) the presence of a physical space where the second messengers move by Brownian motion contributes to stabilization of the photoresponse; and (iii) keeping Ca(2+) at its dark level has only a minor effect on the variability of the system. The effects of diffusion, nonlinearity, and saturation synergize in reducing variability, supporting the notion that the observed high fidelity of the photoresponse is the result of global system function of phototransduction.
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13 MeSH Terms
Kinetics of rhodopsin deactivation and its role in regulating recovery and reproducibility of rod photoresponse.
Caruso G, Bisegna P, Lenoci L, Andreucci D, Gurevich VV, Hamm HE, DiBenedetto E
(2010) PLoS Comput Biol 6: e1001031
MeSH Terms: Animals, Arrestin, Computational Biology, G-Protein-Coupled Receptor Kinase 1, Kinetics, Markov Chains, Mice, Mice, Transgenic, Models, Neurological, Phosphorylation, Photons, Reproducibility of Results, Retinal Rod Photoreceptor Cells, Rhodopsin
Show Abstract · Added December 10, 2013
The single photon response (SPR) in vertebrate phototransduction is regulated by the dynamics of R* during its lifetime, including the random number of phosphorylations, the catalytic activity and the random sojourn time at each phosphorylation level. Because of this randomness the electrical responses are expected to be inherently variable. However the SPR is highly reproducible. The mechanisms that confer to the SPR such a low variability are not completely understood. The kinetics of rhodopsin deactivation is investigated by a Continuous Time Markov Chain (CTMC) based on the biochemistry of rhodopsin activation and deactivation, interfaced with a spatio-temporal model of phototransduction. The model parameters are extracted from the photoresponse data of both wild type and mutant mice, having variable numbers of phosphorylation sites and, with the same set of parameters, the model reproduces both WT and mutant responses. The sources of variability are dissected into its components, by asking whether a random number of turnoff steps, a random sojourn time between steps, or both, give rise to the known variability. The model shows that only the randomness of the sojourn times in each of the phosphorylated states contributes to the Coefficient of Variation (CV) of the response, whereas the randomness of the number of R* turnoff steps has a negligible effect. These results counter the view that the larger the number of decay steps of R*, the more stable the photoresponse is. Our results indicate that R* shutoff is responsible for the variability of the photoresponse, while the diffusion of the second messengers acts as a variability suppressor.
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14 MeSH Terms