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At least 145 records · Page 8Linked to original sources
PubMed2006

Mitochondrial Ca2+ uptake during simulated ischemia does not affect permeability transition pore opening upon simulated reperfusion.

OBJECTIVE: Reenergization of ischemic cardiomyocytes may be associated with acute necrotic cell death due in part to cytosolic Ca2+ overload and opening of a permeability transition pore (PTP) in mitochondria. It has been suggested that Ca2+ overload during ischemia primes mitochondria for PTP opening during reperfusion. We investigated the ability of mitochondria to uptake Ca2+ during simulated ischemia (SI) and whether this uptake determines PTP opening and cell death upon simulated reperfusion (SR). METHODS: Rat heart mitochondria were submitted to either hypoxia (anoxic chamber) or to SI (respiratory inhibition, substrate depletion and acidosis) and subsequent SR. Mitochondrial Ca2+ uptake was monitored using Ca2+ microelectrodes after exposure to different [Ca2+] up to 25 microM during SI, and PTP opening was assessed by quantification of mitochondrial swelling (changes in absorbance rate at 540 nm) and calcein release. Mitochondrial Ca2+ uptake (Rhod-2 fluorescence) and cytosolic Ca2+ rise (Fura-2 ratio fluorescence) were further investigated in HL-1 cardiac myocytes submitted to SI/SR, and the effect of reducing mitochondrial Ca2+ load (with 25 microM ruthenium red) or blocking PTP opening (with 0.5 microM cyclosporin A) on the rate of cell death was investigated in adult cardiomyocytes exposed to SI/SR. RESULTS: SI induced a progressive dissipation of mitochondrial membrane potential (TMRE fluorescence); however, prior to the completion of depolarization, high levels of Ca2+ uptake were observed in mitochondria. SR induced PTP opening but this phenomenon was not influenced by the magnitude of mitochondrial Ca2+ uptake during previous SI. Blockade of the mitochondrial Ca2+ uniporter during SI in cardiomyocytes attenuated mitochondrial Ca2+ uptake but increased cytosolic Ca2+ overload and cell death upon subsequent SR. CONCLUSION: Mitochondrial Ca2+ uptake during SI buffers cytosolic Ca2+ overload but its magnitude appears not to be an important determinant of PTP opening upon subsequent SR.

Animals↗
PubMed1999

The effects of simulated cataract on reading with normal vision and simulated central scotoma.

Reading rates are slower for persons with low vision than for normally-sighted persons. This study investigated the change in reading performance and reading eye movements when we simulated the two most common causes of low vision--central field loss and cataract--and their combination (scotoma + cataract). Three subjects read sentences with each of these simulated impairments at five different letter sizes. They required larger letters to read with the cataract or scotoma than they did with normal vision, and larger still to read with scotoma + cataract; the change in eye movements relative to normal vision was similar across conditions. When reading large letters (1.61 degrees), the cataract had almost no effect, while the scotoma and scotoma + cataract reduced reading rate for two of the subjects. The cataract had a greater impact on performance relative to normal vision for these same two subjects, while for the third subject the cataract had a greater impact with the scotoma in place. Cataract extraction tends to be postponed in patients with central field loss because it is not perceived to be beneficial. The findings from this study, as well as others, suggest that patients with central field loss would benefit from cataract extraction.

Adult↗
PubMed2002

Digestibility of food allergens and nonallergenic proteins in simulated gastric fluid and simulated intestinal fluid-a comparative study.

Information on the comparative digestibility of food allergens and nonallergenic proteins is crucial when stability to digestion is to be used as a criterion to assess the allergenic potential of novel proteins. In this work, we compared the digestive stability of a number of food allergens and proteins of unproven allergenicity and examined whether allergens possess a higher stability than nonallergenic proteins of similar cellular functions, and whether there is a correlation between protein digestibility and allergenicity. The stability of groups of storage proteins, plant lectins, contractile proteins, and enzymes, both allergens and proteins with unproven allergenicity, in a standard simulated gastric fluid and a standard simulated intestinal fluid was measured. Food allergens were not necessarily more resistant to digestion than nonallergenic proteins. There was not a clear relationship between digestibility measured in vitro and protein allergenicity.

Allergens↗
PubMed1996

Lip adaptation to simulated dental arch expansion. Part 2: One week of simulated expansion.

An increase in resting lip pressure and the resulting disruption of the intraoral pressure equilibrium may be responsible for the poor stability found with orthodontically expanded dentitions. Passive expansion strategies seek improved stability by altering lip pressure, thus creating a new equilibrium. One of these strategies has been shown to alter pressure favorably. However, pressure changes associated with conventional expansion need to be studied before conclusions regarding the superiority of passive expansion can be drawn. The purpose of this study was to examine lip pressure changes after 1 week of simulated conventional expansion. Twenty-two subjects agreed to wear a mandibular expansion-simulating stent full-time for 1 week. Resting pressure was measured in the midline and right canine areas. Midline lip pressure decreased significantly after 1 week. Resting pressure was measured in the midline and right canine areas. Midline lip pressure decreased significantly after 1 week while pressure in the canine area did not change significantly. This finding suggests an adaptive response that varies according to anatomic location.

Adaptation, Physiological↗
PubMed2006

Limitations of quantum simulation examined by simulating a pairing Hamiltonian using nuclear magnetic resonance.

Quantum simulation uses a well-known quantum system to predict the behavior of another quantum system. Certain limitations in this technique arise, however, when applied to specific problems, as we demonstrate with a theoretical and experimental study of an algorithm proposed by Wu, Byrd, and Lidar [Phys. Rev. Lett. 89, 057904 (2002).10.1103/PhysRevLett.89.057904] to find the low-lying spectrum of a pairing Hamiltonian. While the number of elementary quantum gates required scales polynomially with the size of the system, it increases inversely to the desired error bound E. Making such simulations robust to decoherence using fault tolerance requires an additional factor of approximately 1/E gates. These constraints, along with the effects of control errors, are illustrated using a three qubit NMR system.

Journal Article↗
PubMed1982

Kinematic analysis and simulation of vertebral motion under static load-part II: simulation study.

Based on the earlier work by the author on the development of a theoretical motion simulation model of an open-loop, kinematic chain, the present paper examines the motion characteristics of a human spine motion-segment. Based on the experimental data collected from the human spine cadaver specimens of lumbar spine, a static simulation model of a lumbar segment is proposed. The equivalent motion characteristic of the intervertebral joint is described by a spherical pair which is located for an intervertebral joint by fitting in a least-square sense a cone to a set of motion data describing the axode characteristics of the joint. The intervertebral disk and the ligaments are represented by an equivalent stiffness matrix whose elements are assumed to be constant over the entire range of mobility. The proposed model showed a good agreement with the observed motion data of an intervertebral joint.

Humans↗
PubMed2005

Simulations of a quasi-Taylor state geomagnetic field including polarity reversals on the Earth Simulator.

High-resolution, low-viscosity geodynamo simulations have been carried out on the Earth Simulator, one of the fastest supercomputers, in a dynamic regime similar to that of Earth's core, that is, in a quasi-Taylor state. Our dynamo models exhibit features of the geodynamo not only in spatial and temporal characteristics but also in dynamics. Polarity reversals occurred when magnetic flux patches at high latitudes moved poleward and disappeared; patches with reversed field at low and mid-latitudes then moved poleward.

Journal Article↗
PubMedDate not supplied

New equipment for a radiation therapy simulator: a device for simplifying irregular field shaping and integrating simulator and therapy machine.

Shaping of irregular treatment fields was facilitated by our newly developed Niwa-Fujikawa irregular field-shaping unit, which was mounted onto a standard radiation therapy simulator. The introduction of a "fieldgraph" led to the functional integration of the simulator and therapy machine. A fieldgraph is a radiograph of an irregular treatment field taken on the Niwa-Fujikawa unit at the same distance as the focus-to-shadow-tray distance of the corresponding therapy machine. The fieldgraph can be taken at the same time as the portal localization film. Through the fieldgraph, which is positioned on the shadow tray of the therapy machine, the irregular treatment field is directly projected onto the skin of the patient. Consequently, marking the irregular field on the skin of the patient is unnecessary. The authors believe that both the new unit and the fieldgraph contribute to greater efficiency and accuracy in daily application of radiation therapy.

Humans↗
PubMed1997

Model-free methods of analyzing domain motions in proteins from simulation: a comparison of normal mode analysis and molecular dynamics simulation of lysozyme.

Model-free methods are introduced to determine quantities pertaining to protein domain motions from normal mode analyses and molecular dynamics simulations. For the normal mode analysis, the methods are based on the assumption that in low frequency modes, domain motions can be well approximated by modes of motion external to the domains. To analyze the molecular dynamics trajectory, a principal component analysis tailored specifically to analyze interdomain motions is applied. A method based on the curl of the atomic displacements is described, which yields a sharp discrimination of domains, and which defines a unique interdomain screw-axis. Hinge axes are defined and classified as twist or closure axes depending on their direction. The methods have been tested on lysozyme. A remarkable correspondence was found between the first normal mode axis and the first principal mode axis, with both axes passing within 3 A of the alpha-carbon atoms of residues 2, 39, and 56 of human lysozyme, and near the interdomain helix. The axes of the first modes are overwhelmingly closure axes. A lesser degree of correspondence is found for the second modes, but in both cases they are more twist axes than closure axes. Both analyses reveal that the interdomain connections allow only these two degrees of freedom, one more than provided by a pure mechanical hinge.

Animals↗
PubMed1996

Incorporating Monte Carlo simulation into physiologically based pharmacokinetic models using advanced continuous simulation language (ACSL): a computational method.

Biologically based models with physiological parameters are becoming more popular as a tool to estimate target tissue doses from chemical exposures. However, the majority of current physiologically based pharmacokinetic (PBPK) models do not take into account the uncertainty and/or variability within the various model parameters. Consideration of uncertainty is important to evaluate the predictive ability and complexity of a model as well as identification of parameters which contribute disproportionately to variability in model output. In order to estimate the uncertainty in PBPK model output, a versatile and simple computational method is presented which can be readily incorporated into the majority of PBPK models without extensive additions to model computer code. In this paper, a separate computer program for Monte Carlo simulation is furnished that randomly samples values for model parameters and writes them into a run-time language (command file) format which can then be utilized to execute individual PBPK models. Modifications to the PBPK model allow the desired output to be written to a data file for statistical analysis. The method presented in this paper is applied to a simple PBPK model for benzene disposition.

Algorithms↗
PubMed1998

Deducing polymeric structure from aqueous molecular dynamics simulations of oligosaccharides: predictions from simulations of hyaluronan tetrasaccharides compared with hydrodynamic and X-ray fibre diffraction data.

Molecular dynamics simulations of the two hyaluronan tetrasaccharides in water predict that over a period of 500 ps, their central linkages populate a single primary minima. Over the same period the peripheral linkages explore this minima, but also a secondary minima. Structures constructed using the primary minima were found to be extended left-handed helices of axial rise per disaccharide (h) 0.8 to 1.0 nm and 2.8 to 4.5 disaccharides per turn (n), in good agreement with n=3 and n=4 helices found by X-ray fibre diffraction studies. We have used the predicted average conformation from molecular dynamics to calculate the translational diffusion coefficients of the oligosaccharide series up to decasaccharide, and compared these with experimental measurements obtained using the method of capillary dispersion. Our calculated values are found to be in good agreement with experiment beyond the size of a tetrasaccharide. A partial digest of hyaluronan in the molecular mass range 10 to 100 kDa was fractionated by gel chromatography. Molecular weights were determined by in-line laser light-scattering measurements, and the translational diffusion coefficients of selected fractions were determined by dynamic laser light-scattering. A similar experiment was performed on hyaluronan with a molecular mass greater than 1MDa. The data suggest a change from rod-like to stiff coil behaviour beyond a molecular weight of 10 kDa. We have also examined the conformations available using the secondary minima, found at the peripheral linkages. In contrast to the extended structures previously described we have found left and right-handed helices with high values of n (5-10) and low values of h. Although there is no experimental evidence for these structures, they are of interest as, over short stretches, they would introduce folds, loops, and turns into the hyaluronan molecule. Such shapes may play an important role in the hydrodynamics of hyaluronan and its interaction with lipids and proteins.

Carbohydrate Conformation↗
PubMed1991

Simulated bipolar cells in fovea of human retina. I. Computer simulation.

This static bipolar cell (BC) model of the human fovea is based on a number of reasonable assumptions. The human fovea is directly responsible for visual acuity and color vision. The fovea can be considered as having two parts; a central fovea with only red- and green-sensitive cones and a parafovea with blue-sensitive cones added to the other two. A cone mosaic can be precisely organized spatially into unit hexagons that specify inputs to horizontal cells (HC) and BCs. The retina up to and including BCs is piece-wise linear, i.e. at a given steady-state adapting light intensity BC outputs are linear functions of the physical image. BC centers receive inputs directly from weighted cones, while antagonistic surrounds receive inverted inputs from HCs. Appropriate optical and chromatic filtering due to the eye that are taken from human data are incorporated into the model. Chromatic aberrations are simulated by three separate point spread functions that also are taken from human data. Automatic gain control of cones is a function of intensity and wavelength of the steady adapting light.

Color Perception↗
PubMed2001

[Computer simulation and pharmacoeconomics. Computer simulation as an aid for the analysis of operating room efficiency: an example].

In this study we compared operating room (OR) efficiency of total intravenous anaesthesia (TIVA) with remifentanil and propofol and balanced anaesthesia (BAL) with fentanyl and isoflurane in cataract surgery using computersimulation. We simulated patient flow for one OR and for three ORs. Time intervals of patient flow were randomly generated from the results of a prospective, randomized trial. Both for one and for three ORs, the postanaesthesia care unit (PACU) finished earlier and one additional case per OR and per day could be performed when TIVA was used for the procedures. Overtime in the PACU was less after TIVA. With a workload of 13 or 15 operations per day in three ORs, monitoring equipment for an additional patient in the PACU was required when BAL was used. TIVA with remifentanil and propofol was associated with more OR efficiency than balanced anaesthesia with fentanyl and isoflurane when given for cataract surgery.

Anesthesia, Intravenous↗
PubMed1993

A hardware-independent data acquisition package incorporating a simulation driver and simulation description language.

Device drivers for commercial data acquisition boards (DASH-16, DT2801) and a device driver for a virtual data acquisition board have been developed and incorporated in a single package for a multiple station anesthesia research laboratory. The package provides a compiler for a simulation description language which is used to program the virtual board. The package, written in C for the IBM PC, was designed to be easily extended with additional drivers. Applications using the package can control all supported devices without the programmer having to learn the details of the hardware.

Computer Simulation↗
PubMed1990

CT simulator: a new 3-D planning and simulating system for radiotherapy: Part 2. Clinical application.

We have performed radiotherapy treatment planning (RTP) with a new system called CT simulator in 72 patients. With the system, RTP is performed with the patient lying on the CT couch within a short period of time. All the CT images scanned were immediately transported to the multi-image monitors and to the treatment planning device. Radiotherapy treatment planning could be performed not only at the beam center but also at any CT slice. Using a laser-beam field projector, field outlines were drawn over the patient's skin. In clinical use, the system was useful for cases in which a target lies adjacent to dose limiting organs, cases with a complicated target shape, cases with complicated dose distribution curves, and cases treated with tangential fields. This system enables us to make optimum use of CT information and to make accurate 3-dimensional treatment planning programs.

Computer Simulation↗
PubMed1995

A CT-based simulation for head and neck tumors in centers without CT-simulator and 3D-planning system.

We present a special CT-based simulation technique to optimize the radiotherapy treatments in head and neck tumors. On an immobilization device, some CT hyperdense markers are placed. Real-size CT slices are performed every 5 mm with the patient in the treatment position with the immobilization system. This study permits a more accurate knowledge of the gross tumoral volume and an optimization of the planning treatment.

Computer Simulation↗
PubMed2000

Accurate condensed history Monte Carlo simulation of electron transport. II. Application to ion chamber response simulations.

In this report the condensed history Monte Carlo simulation of electron transport and its application to the calculation of ion chamber response is discussed. It is shown that the strong step-size dependencies and lack of convergence to the correct answer previously observed are the combined effect of the following artifacts caused by the EGS4/PRESTA implementation of the condensed history technique: dose underprediction due to PRESTA'S pathlength correction and lateral correlation algorithm; dose overprediction due to the boundary crossing algorithm; dose overprediction due to the breakdown of the fictitious cross section method for sampling distances between discrete interaction and the inaccurate evaluation of energy-dependent quantities. These artifacts are now understood quantitatively and analytical expressions for their effect are given.

Algorithms↗