Effects of different tumors on the steady-state heat distribution in the human eye using the 3D finite element method

In this paper, a three-dimensional finite element method is developed to simulate the heat distribution in the human eye with different types of tumors to understand the effect of tumors on heat distribution in the human eye. The human eye is modeled as a composition of several homogeneous regions and the physical and thermal properties of each region used in this study are more accurate than the models used in previous studies. By considering the exact and complicated geometry of all parts, the finite element method is a proper solution for solving the heat equation inside the human eye. There are two kinds of boundary conditions called the radiation condition and the Robin condition. The radiation boundary condition is modeled as a Robin boundary condition. For modeling eye tumors and their effect on heat distribution, we need information about eye tumor properties such as heat conductivity, density, specific heat, and so on. Thanks to no accurate reported information about eye tumor properties, the properties of other types of tumors such as skin, and bowel tumors are used. Simulation results with different parameters of eye tumors show the effect of eye tumors on heat distribution in the human eye.Comment: 15 pages, 6 Figures, 5 Table

Mathematical Model: Comparative Study of Thermal Effects of Laser in Corneal Refractive Surgeries

Lasers have been widely used in ophthalmology. Refractive errors are some of the most common ophthalmic abnormalities worldwide. Laser refractive surgery was developed to correct refractive errors myopia, hyperopia and astigmatism. Two types of laser surgical techniques: lamellar and thermal are available to reshape the corneal curvature. Ultraviolet (UV) emitting argon fluoride (ArF) excimer laser is used to sculpt cornea in lamellar procedures, whereas, infrared (IR) emitting holmium yttrium aluminum garnet (Ho: YAG) laser is used to shrink cornea in thermal procedure. Tissue heating is common in all types of laser surgical techniques. Hence, in this paper, a finite element model is developed to investigate the temperature distribution of cornea in different laser refractive surgeries. Characteristics of optical and thermal processes and influence of the parameters of radiation and tissues on the results of laser action are investigated. The results of mathematical modeling in different surgical techniques are discussed, compared, and validated with experimental results

Microgravity: A Teacher's Guide With Activities in Science, Mathematics, and Technology

The purpose of this curriculum supplement guide is to define and explain microgravity and show how microgravity can help us learn about the phenomena of our world. The front section of the guide is designed to provide teachers of science, mathematics, and technology at many levels with a foundation in microgravity science and applications. It begins with background information for the teacher on what microgravity is and how it is created. This is followed with information on the domains of microgravity science research; biotechnology, combustion science, fluid physics, fundamental physics, materials science, and microgravity research geared toward exploration. The background section concludes with a history of microgravity research and the expectations microgravity scientists have for research on the International Space Station. Finally, the guide concludes with a suggested reading list, NASA educational resources including electronic resources, and an evaluation questionnaire

Validation of Transcranial Electrical Stimulation (TES) Finite Element Modeling Against MREIT Current Density Imaging in Human Subjects

abstract: Transcranial electrical stimulation (tES) is a non-invasive brain stimulation therapy that has shown potential in improving motor, physiological and cognitive functions in healthy and diseased population. Typical tES procedures involve application of weak current (< 2 mA) to the brain via a pair of large electrodes placed on the scalp. While the therapeutic benefits of tES are promising, the efficacy of tES treatments is limited by the knowledge of how current travels in the brain. It has been assumed that the current density and electric fields are the largest, and thus have the most effect, in brain structures nearby the electrodes. Recent studies using finite element modeling (FEM) have suggested that current patterns in the brain are diffuse and not concentrated in any particular brain structure. Although current flow modeling is useful means of informing tES target optimization, few studies have validated tES FEM models against experimental measurements. MREIT-CDI can be used to recover magnetic flux density caused by current flow in a conducting object. This dissertation reports the first comparisons between experimental data from in-vivo human MREIT-CDI during tES and results from tES FEM using head models derived from the same subjects. First, tES FEM pipelines were verified by confirming FEM predictions agreed with analytic results at the mesh sizes used and that a sufficiently large head extent was modeled to approximate results on human subjects. Second, models were used to predict magnetic flux density, and predicted and MREIT-CDI results were compared to validate and refine modeling outcomes. Finally, models were used to investigate inter-subject variability and biological side effects reported by tES subjects. The study demonstrated good agreements in patterns between magnetic flux distributions from experimental and simulation data. However, the discrepancy in scales between simulation and experimental data suggested that tissue conductivities typically used in tES FEM might be incorrect, and thus performing in-vivo conductivity measurements in humans is desirable. Overall, in-vivo MREIT-CDI in human heads has been established as a validation tool for tES predictions and to study the underlying mechanisms of tES therapies.Dissertation/ThesisDoctoral Dissertation Biomedical Engineering 201

Antenna Arrangement in UWB Helmet Brain Applicators for Deep Microwave Hyperthermia

Deep microwave hyperthermia applicators are typically designed as narrow-band conformal antenna arrays with equally spaced elements, arranged in one or more rings. This solution, while adequate for most body regions, might be sub-optimal for brain treatments. The introduction of ultra-wide-band semi-spherical applicators, with elements arranged around the head and not necessarily aligned, has the potential to enhance the selective thermal dose delivery in this challenging anatomical region. However, the additional degrees of freedom in this design make the problem non-trivial. We address this by treating the antenna arrangement as a global SAR-based optimization process aiming at maximizing target coverage and hot-spot suppression in a given patient. To enable the quick evaluation of a certain arrangement, we propose a novel E-field interpolation technique which calculates the field generated by an antenna at any location around the scalp from a limited number of initial simulations. We evaluate the approximation error against full array simulations. We demonstrate the design technique in the optimization of a helmet applicator for the treatment of a medulloblastoma in a paediatric patient. The optimized applicator achieves 0.3\ua0 (Formula presented.) C higher T90 than a conventional ring applicator with the same number of elements

Chmp1 negatively regulates Epidermal Growth Factor signaling in the Drosophila wing

A critical step in cellular signaling through transmembrane receptors is the down-regulation of activated receptors through the multivesicular body (MVB) pathway to the lysosome. MVB generation is mediated by the highly conserved ESCRT (0, I, II, and III) protein complexes. Though the ESCRT-III complex provides the core function of the ESCRT machinery, it is the least characterized of the ESCRT complexes. The Chmp1 protein is an ESCRT-III component and a putative tumor suppressor that has been linked to pancreatic and renal cancers in humans. However, published data on Chmp1 activity are conflicting and its role during tissue development is not well defined. Drosophila melanogaster (the common fruit fly) provides a powerful model system for investigating the function of genes involved in human development and disease. In this study, knockdown and over-expression techniques were used to investigate the function of Chmp1 in Drosophila. RNAi was used to reduce Chmp1 expression, and transgenic fly lines that allow for expression of either wild-type or epitope tagged Chmp1 were used to investigate over-expression, as well as the subcellular localization of Chmp1. Knockdown of Chmp1 expression using RNAi was lethal in the fly, suggesting that Chmp1 is an essential gene for Drosophila development. In the wing, loss of Chmp1 activity caused a cell fate change from intervein to vein, which was likely a result of de-regulation of the Drosophila Epidermal Growth Factor Receptor (DER) pathway. Genetic interactions between Chmp1 and regulators of DER signaling suggest that Chmp1 negatively regulates DER signaling. Furthermore, Chmp1 knockdown also decreased Blistered expression, which is repressed by DER signaling. Over-expression of Chmp1 had mild phenotypic effects, suggesting that dosage of Chmp1 is not critical for cellular function. Some of the epitope tagged Chmp1 protein was detected at the late endosome in Drosophila embryonic epithelial cells. This is consistent with Chmp1 functioning as an ESCRT-III component during MVB formation. Therefore, Drosophila Chmp1 may negatively regulate DER signaling through its role in MVB formation as an ESCRT-III component

A study on the change in plasma membrane potential during sonoporation

Posters: no. 4Control ID: 1680329OBJECTIVES: There has been validated that the correlation of sonoporation with calcium transients is generated by ultrasound-mediated microbubbles activity. Besides calcium, other ionic flows are likely involved in sonoporation. Our hypothesis is the cell electrophysiological properties are related to the intracellular delivery by ultrasound and microbubbles. In this study, a real-time live cell imaging platform is used to determine whether plasma membrane potential change is related to the sonoporation process at the cellular level. METHODS: Hela cells were cultured in DMEM supplemented with 10% FBS in Opticell Chamber at 37 °C and 5% CO2, and reached 80% confluency before experiments. The Calcein Blue-AM, DiBAC4(3) loaded cells in the Opticell chamber filled with PI solution and Sonovue microbubbles were immerged in a water tank on a inverted fluorescence microscope. Pulsed ultrasound (1MHz freq., 20 cycles, 20Hz PRF, 0.2-0.5MPa PNP) was irradiated at the angle of 45° to the region of interest for 1s.The real-time fluorescence imaging for different probes was acquired by a cooled CCD camera every 20s for 10min. The time-lapse fluorescence images were quantitatively analyzed to evaluate the correlation of cell viability, intracellular delivery with plasma membrane potential change. RESULTS: Our preliminary data showed that the PI fluorescence, which indicated intracellular delivery, was immediately accumulated in cells adjacent to microbubbles after exposure, suggesting that their membranes were damaged by ultrasound-activated microbubbles. However, the fluorescence reached its highest level within 4 to 6 minutes and was unchanged thereafter, indicating the membrane was gradually repaired within this period. Furthermore, using DIBAC4(3), which detected the change in the cell membrane potential, we found that the loss of membrane potential might be associated with intracellular delivery, because the PI fluorescence accumulation was usually accompanied with the change in DIBAC4 (3) fluorescence. CONCLUSIONS: Our study suggests that there may be a linkage between the cell membrane potential change and intracellular delivery mediated by ultrasound and microbubbles. We also suggest that other ionic flows or ion channels may be involved in the cell membrane potential change in sonoporation. Further efforts to explore the cellular mechanism of this phenomenon will improve our understanding of sonoporation.postprin

Developmental delays and subcellular stress as downstream effects of sonoporation

Posters: no. 2Control ID: 1672434OBJECTIVES: The biological impact of sonoporation has often been overlooked. Here we seek to obtain insight into the cytotoxic impact of sonoporation by gaining new perspectives on anti-proliferative characteristics that may emerge within sonoporated cells. We particularly focused on investigating the cell-cycle progression kinetics of sonoporated cells and identifying organelles that may be stressed in the recovery process. METHODS: In line with recommendations on exposure hardware design, an immersion-based ultrasound platform has been developed. It delivers 1 MHz ultrasound pulses (100 cycles; 1 kHz PRF; 60 s total duration) with 0.45 MPa peak negative pressure to a cell chamber that housed HL-60 leukemia cells and lipid-shelled microbubbles at a 10:1 cell-tobubble ratio (for 1e6/ml cell density). Calcein was used to facilitate tracking of sonoporated cells with enhanced uptake of exogenous molecules. The developmental trend of sonoporated cells was quantitatively analyzed using BrdU/DNA flow cytometry that monitors the cell population’s DNA synthesis kinetics. This allowed us to measure the temporal progression of DNA synthesis of sonoporated cells. To investigate whether sonoporation would upset subcellular homeostasis, post-exposure cell samples were also assayed for various proteins using Western blot analysis. Analysis focus was placed on the endoplasmic reticulum (ER): an important organelle with multi-faceted role in cellular functioning. The post-exposure observation time spanned between 0-24 h. RESULTS: Despite maintaining viability, sonoporated cells were found to exhibit delays in cell-cycle progression. Specifically, their DNA synthesis time was lengthened substantially (for HL-60 cells: 8.7 h for control vs 13.4 h for the sonoporated group). This indicates that sonoporated cells were under stress: a phenomenon that is supported by our Western blot assays showing upregulation of ER-resident enzymes (PDI, Ero1), ER stress sensors (PERK, IRE1), and ER-triggered pro-apoptotic signals (CHOP, JNK). CONCLUSIONS: Sonoporation, whilst being able to facilitate internalization of exogenous molecules, may inadvertently elicit a cellular stress response. These findings seem to echo recent calls for reconsideration of efficiency issues in sonoporation-mediated drug delivery. Further efforts would be necessary to improve the efficiency of sonoporation-based biomedical applications where cell death is not desirable.postprin

How sonoporation disrupts cellular structural integrity: morphological and cytoskeletal observations

Posters: no. 1Control ID: 1672429OBJECTIVES: In considering sonoporation for drug delivery applications, it is essential to understand how living cells respond to this puncturing force. Here we seek to investigate the effects of sonoporation on cellular structural integrity. We hypothesize that the membrane morphology and cytoskeletal behavior of sonoporated cells under recovery would inherently differ from that of normal viable cells. METHODS: A customized and calibrated exposure platform was developed for this work, and the ZR-75-30 breast carcinoma cells were used as the cell model. The cells were exposed to either single or multiple pulses of 1 MHz ultrasound (pulse length: 30 or 100 cycles; PRF: 1kHz; duration: up to 60s) with 0.45 MPa spatial-averaged peak negative pressure and in the presence of lipid-shelled microbubbles. Confocal microscopy was used to examine insitu the structural integrity of sonoporated cells (identified as ones with exogenous fluorescent marker internalization). For investigations on membrane morphology, FM 4-64 was used as the membrane dye (red), and calcein was used as the sonoporation marker (green); for studies on cytoskeletal behavior, CellLight (green) and propidium iodide (red) were used to respectively label actin filaments and sonoporated cells. Observation started from before exposure to up to 2 h after exposure, and confocal images were acquired at real-time frame rates. Cellular structural features and their temporal kinetics were quantitatively analyzed to assess the consistency of trends amongst a group of cells. RESULTS: Sonoporated cells exhibited membrane shrinkage (decreased by 61% in a cell’s cross-sectional area) and intracellular lipid accumulation (381% increase compared to control) over a 2 h period. The morphological repression of sonoporated cells was also found to correspond with post-sonoporation cytoskeletal processes: actin depolymerization was observed as soon as pores were induced on the membrane. These results show that cellular structural integrity is indeed disrupted over the course of sonoporation. CONCLUSIONS: Our investigation shows that the biophysical impact of sonoporation is by no means limited to the induction of membrane pores: e.g. structural integrity is concomitantly affected in the process. This prompts the need for further fundamental studies to unravel the complex sequence of biological events involved in sonoporation.postprin