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PubMed2001

Optimization of the step-and-shoot leaf sequence for delivery of intensity modulated radiation therapy using a variable division scheme.

To deliver an intensity modulated radiation therapy (IMRT) plan by multileaf collimator (MLC) it is necessary to convert beam profiles, generated from the inverse treatment planning algorithm, into a series of instructions that the MLC control system can execute. An idealized IMRT beam profile can be regarded as a continuously varying two-dimensional function and is usually represented by an intensity map, i.e., a discretized description in space and in intensity of the beam profile. It is common to assume that the intensity map be defined over a regular grid with N steps and equal increments of intensity levels. In reality, this may not be the optimal representation of the beam profile and may introduce unnecessary discrepancies between the intensity pattern delivered and that ideally required. We have implemented an algorithm capable of minimizing the difference between the two patterns on a beam specific basis. In other words, it can produce optimized intensity maps, individually produced to suit the (continuous function) intensity profile they are intended to approximate. This enhancement in conformation is achieved by allowing variable step size and unconstrained intensity levels in the final leaf sequence.

Algorithms↗
PubMed2006

Schwarz meets Schwann: design and fabrication of biomorphic and durataxic tissue engineering scaffolds.

Tissue engineering is a discipline at the leading edge of the field of computer assisted intervention. This multidisciplinary engineering science attempts to meet the reparative and regenerative needs of tissues and organs based on the notion of design and fabrication of scaffolds- porous, three-dimensional "trellis-like" biomimetic structures that, on implantation, provide a viable environment to recuperate and regenerate damaged cells. Existing scaffold fabrication strategies produce sub-optimal porous labyrinths with contra-naturam straight edges. The biomorphic geometry that mimics the secundam-naturam substrate would be one that is continuous through all space, partitioned into two not-necessarily-equal sub-spaces by a non-intersecting, two-sided surface. Minimal surface geometry is not only ideal to describe such a space but is also the preferentially assumed geometry in natural and pathological or manipulated cells. We present results on the premier attempt in computer-controlled fabrication, modulation, and mechanical characterization of tissue engineering scaffolds based on triply periodic minimal surfaces (TPMS). We also present novel strategies to realize coterminous seeding-feeding networks thereby guaranteeing blood/nutrient supply to the proliferating cells at close proximity. This initiative of linking Schwann's 1838 cell theory with Schwarz's 1865 discovery of TPMS is a significant step to fabricate the previously elusive optimal biomorphic tissue analogs.

Animals↗
PubMed1997

Microgravity tissue engineering.

Tissue engineering studies were done using isolated cells, three-dimensional polymer scaffolds, and rotating bioreactors operated under conditions of simulated microgravity. In particular, vessel rotation speed was adjusted such that 10 mm diameter x 2 mm thick cell-polymer constructs were cultivated in a state of continuous free-fall. Feasibility was demonstrated for two different cell types: cartilage and heart. Conditions of simulated microgravity promoted the formation of cartilaginous constructs consisting of round cells, collagen and glycosaminoglycan (GAG), and cardiac tissue constructs consisting of elongated cells that contracted spontaneously and synchronously. Potential advantages of using a simulated microgravity environment for tissue engineering were demonstrated by comparing the compositions of cartilaginous constructs grown under four different in vitro culture conditions: simulated microgravity in rotating bioreactors, solid body rotation in rotating bioreactors, turbulent mixing in spinner flasks, and orbital mixing in petri dishes. Constructs grown in simulated microgravity contained the highest fractions of total regenerated tissue (as a percent of construct dry weight) and of GAG, the component required for cartilage to withstand compressive force.

Animals↗
PubMed1985

Bacterial fouling in a model core system.

We have used a sintered glass bead core to simulate the spaces and surfaces of reservoir rock in studies of the bacterial plugging phenomenon that affects waterflood oil recovery operations. The passage of pure or mixed natural populations of bacteria through this solid matrix was initially seen to promote the formation of adherent bacterial microcolonies on available surfaces. Bacteria within these microcolonies produced huge amounts of exopolysaccharides and coalesced to form a confluent plugging biofilm that eventually caused a >99% decrease in core permeability. Aerobic bacteria developed a plugging biofilm on the inlet face of the core, facultative anaerobes plugged throughout the core, and dead bacteria did not effectively plug the narrow (33-mum) spaces of this solid matrix because they neither adhered extensively to surfaces nor produced the extensive exopolysaccharides characteristic of living cells. The presence of particles in the water used in these experiments rapidly decreased the core permeability because they became trapped in the developing biofilm and accelerated the plugging of pore spaces. Once established, cells within the bacterial biofilm could be killed by treatment with a biocide (isothiazalone), but their essentially inert carbohydrate biofilm matrix persisted and continued to plug the pore spaces, whereas treatment with 5% sodium hypochlorite killed the bacteria, dissolved the exopolysaccharide biofilm matrix, and restored permeability to these plugged glass bead cores.

Journal Article↗
PubMed2003

Blind estimation of reverberation time.

The reverberation time (RT) is an important parameter for characterizing the quality of an auditory space. Sounds in reverberant environments are subject to coloration. This affects speech intelligibility and sound localization. Many state-of-the-art audio signal processing algorithms, for example in hearing-aids and telephony, are expected to have the ability to characterize the listening environment, and turn on an appropriate processing strategy accordingly. Thus, a method for characterization of room RT based on passively received microphone signals represents an important enabling technology. Current RT estimators, such as Schroeder's method, depend on a controlled sound source, and thus cannot produce an online, blind RT estimate. Here, a method for estimating RT without prior knowledge of sound sources or room geometry is presented. The diffusive tail of reverberation was modeled as an exponentially damped Gaussian white noise process. The time-constant of the decay, which provided a measure of the RT, was estimated using a maximum-likelihood procedure. The estimates were obtained continuously, and an order-statistics filter was used to extract the most likely RT from the accumulated estimates. The procedure was illustrated for connected speech. Results obtained for simulated and real room data are in good agreement with the real RT values.

Acoustics↗
PubMed2003

Rhythmic oscillations in the performance of a sustained attention task.

Attempts to sustain a narrow focus of attention over a long period of time are effortful and are punctuated by lapses. Most studies of sustained attention performance obscure the presence and pattern oflapses by reporting measures that are summed across the entire period of an individual's performance, or that are average scores for blocks of trials across many participants. In the present study we attempted to explore fluctuation in the attention of individual participants over the course of a vigilance task and to quantify its periodicity, if any exists. Normal university students listened to letters of the alphabet, arranged randomly and presented at a rate of 2 per second for 20 min. They were instructed to press a hand-held button when they detected a target two consecutive identical letters). Continuous estimates of performance accuracy (correctly detected targets) at regularly spaced time intervals were created for each participant using a moving time window. The resulting functions were analyzed in order to detect and quantify periodicity using a Fast Fourier Transform (FF). The most often observed rhythms for those participants with adequate FFT power congregated at 1-2 min, 4-7 min and greater than 10 min. Performance functions from 36 of the 40 subjects displayed at least two of these frequencies. Other studies have identified cycles in performance during similar vigilance challenges, but without particular rhythms or with no particular shared frequencies amongst participants. The possible sources of these fluctuations and the differences in the findings of these studies and the present study are discussed.

Adolescent↗
PubMed1996

Discrete versus syncytial tissue behavior in a model of cardiac stimulation--I: Mathematical formulation.

This paper presents a model describing the steady-state response of a two-dimensional (2-D) slice of myocardium to extracellular current injection. The model incorporates a continuous representation of the multicellular, syncytial cardiac tissue based on the bidomain model. The classical bidomain model is modified by introducing periodic conductivities to better represent the electrical properties of the intracellular space. Thus, junctional discontinuity between abutting myocytes is reflected in the macroscopic representation of cardiac tissue behavior. Since a solution to the resulting coupled differential equations governing the intracellular and extracellular potentials in the tissue preparation is not computationally tractable when traditional numerical approaches, such as finite element or finite difference methods are used, spectral techniques are employed to reduce the problem to the solution of a set of algebraic equations for the transform of the bidomain potentials. Further, the solution to the "periodic" bidomain problem in the Fourier space is decomposed into two separate solutions: One for the classical-bidomain potentials where it is assumed that the intracellular conductivity values along and across cells incorporate the average contribution from cytoplasm and junction, and another for the junctional potential component. The decomposition of the total solution allows to approximately solve for the junctional component thus achieving high overall computational efficiency. The results of simulation are presented in an accompanying paper.

Anisotropy↗
PubMed2001

A comparison study of self-adaptation in evolution strategies and real-coded genetic algorithms.

This paper discusses the self-adaptive mechanisms of evolution strategies (ES) and real-coded genetic algorithms (RCGA) for optimization in continuous search spaces. For multi-membered evolution strategies, a self-adaptive mechanism of mutation parameters has been proposed by Schwefel. It introduces parameters such as standard deviations of the normal distribution for mutation into the genetic code and lets them evolve by selection as well as the decision variables. In the RCGA, crossover or recombination is used mainly for search. It utilizes information on several individuals to generate novel search points, and therefore, it can generate offspring adaptively according to the distribution of parents without any adaptive parameters. The present paper discusses characteristics of these two self-adaptive mechanisms through numerical experiments. The self-adaptive characteristics such as translation, enlargement, focusing, and directing of the distribution of children generated by the ES and the RCGA are examined through experiments.

Algorithms↗
PubMed2000

Critical transitions in colliding cascades

We consider here the interaction of direct and inverse cascades in a hierarchical nonlinear system that is continuously loaded by external forces. The load is applied to the largest element and is transferred down the hierarchy to consecutively smaller elements, thereby forming a direct cascade. The elements of the system fail (i. e., break down) under the load. The smallest elements fail first. The failures gradually expand up the hierarchy to the larger elements, thus forming an inverse cascade. Eventually the failures heal, ensuring that the system will function indefinitely. The direct and inverse cascades collide and interact. Loading triggers the failures, while failures release and redistribute the load. Notwithstanding its relative simplicity, this model reproduces the major dynamical features observed in seismicity, including the seismic cycle, intermittence of seismic regime, power-law energy distribution, clustering in space and time, long-range correlations, and a set of seismicity patterns premonitory to a strong earthquake. In this context, the hierarchical structure of the model crudely imitates a system of tectonic blocks spread by a network of faults (note that the behavior of such a network is different from that of a single fault). Loading mimics the impact of tectonic forces, and failures simulate earthquakes. The model exhibits three basic types of premonitory pattern reflecting seismic activity, clustering of earthquakes in space and time, and the range of correlation between the earthquakes. The colliding-cascade model seemingly exhibits regularities that are common in a wide class of complex hierarchical systems, not necessarily Earth specific.

Journal Article↗
PubMed1998

Efficient, robust, and unified method for mapping complex traits (I): two-point linkage analysis.

The completion of a preliminary human genome map and development of molecular methods have enabled researchers to assay a large number of polymorphic markers that are evenly spaced along the entire human genome. Among many applications, marker data are valuable for mapping complex traits through linkage or linkage-disequilibrium analysis, the former of which is the focus of this paper, the first in a series on this subject. Formalizing the concept and computation for linkage analysis, Elston and Stewart [1971; Human Heredity 21:523-542] introduced a likelihood function to capture relevant genetic information and a recursive algorithm for computing the likelihood function. However, the computing burden is prohibitive in processing complex pedigrees. Since that fundamental development, improving the computational algorithm and extending the method has been a dynamic area of research. The primary objective of this communication is to introduce a semiparametric method for linkage analysis. It is a particularly suitable approach with desirable properties for mapping complex traits that may be binary, continuous, and partially observed (i.e., censored). It incorporates candidate genes, environmental factors, and their interactions with the putative gene and is expected to be robust and efficient in comparison with likelihood-based methods. The properties of the estimates have been studied in finite samples with a limited simulation study. This method is illustrated with an application to family data contributed to the Breast Cancer Consortium.

Algorithms↗
PubMed2005

Interrelationship of trabecular mechanical and microstructural properties in sheep trabecular bone.

The ability to evaluate fracture risk at an early time point is essential for improved prognostics as well as enhanced treatment in cases of bone loss such as from osteoporosis. Improving the diagnostic ability is inherent upon both high-resolution non-invasive imaging, and a thorough understanding of how the derived indices of structure and density relate to its true mechanical behavior. Using sheep femoral trabecular bone with a range of strength, the interrelationship of mechanical and microstructural parameters was analyzed using multi-directional mechanical testing and micro-computed tomography. Forty-five cubic trabecular bone samples were harvested from 23 adult female sheep, some of whom had received hind-limb vibratory stimuli over the course of 2 years with consequently enhanced mechanical properties. These samples were pooled into a low, medium, or high strength group for further analysis. The findings show that microCT indices that are structural in nature, e.g., structural model index (SMI) (r2=0.85, p<0.0001) is as good as more density oriented indices like bone volume/total volume (BV/TV) (r2=0.81, p<0.0001) in predicting the ultimate strength of a region of trabecular bone. Additionally, those indices more related to global changes in trabecular structure such as connectivity density (ConnD) or degree of anisotropy (DA) are less able to predict the mechanical properties of bone. Interrelationships of trabecular indices such as trabecular number (TbN), thickness (TbTh), and spacing (TbSp) provide clues as to how the trabecular bone will remodel to ultimately achieve differences in the apparent mechanical properties. For instance, the analysis showed that a loss of bone primarily affects the connectedness and overall number of trabeculae, while increased strength results in an increase of the overall thickness of trabeculae while not improving the connectedness. Certainly, the microCT indices studied are able to predict the bulk mechanical properties of a trabecular ROI well, leaving unaccounted only about 15-20% of its inherent variability. Diagnostically, this implies that future work on the early prediction of fracture risk should continue to explore the role of bone quality as the key factors or as an adjuvant to bone quantity (e.g., apparent density).

Absorptiometry, Photon↗
PubMed1998

The strategy of Myxococcus xanthus for group cooperative behavior.

New evidence has been presented from our laboratory that the gliding bacterium, Myxococcus xanthus, does not home by chemotaxis toward a nutrient source. Our experiments, those of others, and the theory presented here combine to suggest a model, called the 'Pied Piper' model. It hypothesizes a gene that has a high mutation rate forward and back (say something in excess 10(-4) mutations per cell generation) which leads to switching between two motility states. Occasionally rare organisms become genetically, but reversibly, changed so that they move unidirectionally instead of mostly forward and back as do the bulk of the cells. When such a 'leader' cell arises, it continues to move in its original orientation, and causes a cohort of cells to move together away from the bulk of the cells. That is, in the less common mutational state it counteracts the usual tendency to just move forward and backward achieving little net movement. The assumption of a genetic element that mutates in a reversible way is suggested by numerous cases of reversible switches now known in a wide range of bacteria serving a variety of functions. A second aspect of the model is that mechanisms exist that cause cells to move in the same direction as their nearby neighbors. This process results in a regular spacing of bands of cells to form mounds in the absence of a leader. The action of C-factor, a factor-secreted by the cells which has been largely studied in the laboratory of Dale Kaiser, and extracellular fibrils, (rod-shaped protein and carbohydrate bodies) largely studied in the laboratory of Martin Dworkin, may be key elements in coordinating (or linking) the movements of neighboring cells. Based on the assumption of the absence of chemotaxis, computer simulations of pattern formation for gliding bacterial swarms and flares are consistent with observed behaviors and thus are additional evidence that chemotactic motility of the type exhibited by Escherichia coli, is not necessary for the group movements of M. xanthus. Some tests for this model are suggested.

Computer Simulation↗
PubMed2006

Phase space warping: nonlinear time-series analysis for slowly drifting systems.

A new general dynamical systems approach to data analysis is presented that allows one to track slowly evolving variables responsible for non-stationarity in a fast subsystem. The method is based on the idea of phase space warping, which refers to the small distortions in the fast subsystem's phase space that results from the slow drift, and uses short-time reference model prediction error as its primary measurement of this phenomenon. The basic theory is presented and the issues associated with its implementation in a practical algorithm are discussed. A vector-tracking version of the procedure, based on smooth orthogonal decomposition analysis, is applied to the study of a nonlinear vibrating beam experiment in which a crack propagates to complete fracture. Our method shows that the damage evolution is governed by a scalar process, and we are able to give real-time estimates of the current damage state and identify the governing damage evolution model. Using a final recursive estimation step based on this model, the time to failure is continuously and accurately predicted well in advance of actual failure.

Algorithms↗
PubMed1986

Decompression sickness and intravenous bubble formation using a 7.8 psia simulated pressure-suit environment.

The purpose of this study was to determine the minimum spacesuit pressure required to prevent decompression sickness (DCS) during operational conditions in a 50% oxygen/50% nitrogen environment. In this study, 30 male volunteer subjects were exposed in groups of three, to three consecutive daily extravehicular activity (EVA) simulations at 7.8 psia (5,031 m altitude equivalent) for a continuous period of 6 h. During each altitude exposure, the subjects participated in similar exercise workloads expected to be experienced by astronauts during a typical EVA scenario. Precordial Doppler monitoring revealed that 73.3% of the subjects had intravenous bubbling during at least 1 d of the 3 d of exposure, with 26.7% remaining bubble-free during the entire study. No correlation was found between either body fat or age and incidence of bubble formation. One case of DCS occurred during the study indicating that 7.8 psia is not sufficient pressure to totally preclude DCS in a 50% oxygen/50% nitrogen environment. The necessary pressure awaits further study.

Adult↗
PubMed2006

Multimillion atom simulations of dynamics of oxidation of an aluminum nanoparticle and nanoindentation on ceramics.

We have developed a first-principles-based hierarchical simulation framework, which seamlessly integrates (1) a quantum mechanical description based on the density functional theory (DFT), (2) multilevel molecular dynamics (MD) simulations based on a reactive force field (ReaxFF) that describes chemical reactions and polarization, a nonreactive force field that employs dynamic atomic charges, and an effective force field (EFF), and (3) an atomistically informed continuum model to reach macroscopic length scales. For scalable hierarchical simulations, we have developed parallel linear-scaling algorithms for (1) DFT calculation based on a divide-and-conquer algorithm on adaptive multigrids, (2) chemically reactive MD based on a fast ReaxFF (F-ReaxFF) algorithm, and (3) EFF-MD based on a space-time multiresolution MD (MRMD) algorithm. On 1920 Intel Itanium2 processors, we have demonstrated 1.4 million atom (0.12 trillion grid points) DFT, 0.56 billion atom F-ReaxFF, and 18.9 billion atom MRMD calculations, with parallel efficiency as high as 0.953. Through the use of these algorithms, multimillion atom MD simulations have been performed to study the oxidation of an aluminum nanoparticle. Structural and dynamic correlations in the oxide region are calculated as well as the evolution of charges, surface oxide thickness, diffusivities of atoms, and local stresses. In the microcanonical ensemble, the oxidizing reaction becomes explosive in both molecular and atomic oxygen environments, due to the enormous energy release associated with Al-O bonding. In the canonical ensemble, an amorphous oxide layer of a thickness of approximately 40 angstroms is formed after 466 ps, in good agreement with experiments. Simulations have been performed to study nanoindentation on crystalline, amorphous, and nanocrystalline silicon nitride and silicon carbide. Simulation on nanocrystalline silicon carbide reveals unusual deformation mechanisms in brittle nanophase materials, due to coexistence of brittle grains and soft amorphous-like grain boundary phases. Simulations predict a crossover from intergranular continuous deformation to intragrain discrete deformation at a critical indentation depth.

Journal Article↗
PubMed1998

Volume changes of the myosin lattice resulting from repetitive stimulation of single muscle fibers.

Single muscle fibers at 1 degreesC were subjected to brief tetani (20 Hz) at intervals of between 20 s and 300 s over a period of up to 2 h. A band lattice spacing increased during this period at a rate inversely dependent on the rest interval between tetani. Spacing increased rapidly during the first 10 tetani at a rate equivalent to the production of 0.04 mOsmol.liter-1 of osmolyte per contraction, then continued to expand at a much slower rate. For short rest intervals, where lattice expansion was largest, spacing increased to a limiting value between 46 and 47 nm (sarcomere length 2.2 micrometer), corresponding to accumulation of 30 mOsmol.liter-1 of osmolytes, where it remained constant until repetitive stimulation was terminated. At this limiting spacing, force was reduced by up to 30%. The effect of lattice swelling on the lattice compression that accompanies isometric force recovery from unloaded shortening was to increase the compression, similar to that observed in hypotonic media at a similar spacing. During recovery from repetitive stimulation, spacing recompressed to its original value with a half-time of 15-30 min. These findings suggest that mechanical activity produces an increase in osmotic pressure within the cell as a result of product accumulation from cross-bridge and sarcoplasmic reticulum ATPases and glycolysis.

Animals↗
PubMed1993

Response of the circadian system to 6 degrees head-down tilt bed rest.

The influence of simulated microgravity and reduced zeitgebers on the circadian system was examined in eight subjects. The 12-d study included a 3-d period for baseline measurements, 7 d of 6 degrees head-down bed rest, and 2 d for recovery. The sleep-wake cycle was kept constant during the study. The state of the circadian system was assessed from continuous measurements of temperature and ECG, and collections of urine at 3-h intervals for the determination of hormone and electrolyte excretions. Results indicate that only minor changes occurred in rhythm acrophases, whereas daily means for several physiological functions and their circadian amplitudes were significantly altered during the bed-rest phase. These studies using head-down tilt confirm previous findings with horizontal bed rest and indicate that rhythm disturbances can occur without change in the sleep-wake cycle. To the degree that bed-rest studies simulate manned spaceflights, results indicate that variations in circadian cycles can occur even during short-term missions and must be taken into account when interpreting subsequently obtained physiological data.

Adult↗
PubMedDate not supplied

A controlled attractor network model of path integration in the rat.

Cells in several areas of the hippocampal formation show place specific firing patterns, and are thought to form a distributed representation of an animal's current location in an environment. Experimental results suggest that this representation is continually updated even in complete darkness, indicating the presence of a path integration mechanism in the rat. Adopting the Neural Engineering Framework (NEF) presented by Eliasmith and Anderson (2003) we derive a novel attractor network model of path integration, using heterogeneous spiking neurons. The network we derive incorporates representation and updating of position into a single layer of neurons, eliminating the need for a large external control population, and without making use of multiplicative synapses. An efficient and biologically plausible control mechanism results directly from applying the principles of the NEF. We simulate the network for a variety of inputs, analyze its performance, and give three testable predictions of our model.

Action Potentials↗