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Statistical models for experimental model membranes.

Henriques, Vera Bohomoletz
Fonte: Águas de Lindóia Publicador: Águas de Lindóia
Tipo: Aula
ENG
Relevância na Pesquisa
45.78%
Biological membranes are constituted from lipid bilayers and proteins. Investigation of protein-membrane interaction, essential for biological function of cells, must rest upon solid knowledge of lipid bilayer behavior. Thus, extensive studies of an experimental model for membranes, lipid bilayers in water solution, have been undertaken in the last decades. These systems present structural, thermal and electrical properties which depend on temperature, ionic strength or concentration. In this talk, we shall discuss statistical models for lipid bilayers, as well as the relation between their properties and results for properties of lipid dispersions investigated by the laboratories supervised by Teresa Lamy (IF-USP) and Amando Ito (FFCL-USP).

Genetic effects on preweaning weight gain of Nelore-Hereford calves according to different models and estimation methods

Carvalheiro, R.; Pimentel, E. C G; Cardoso, V.; Queiroz, S. A.; Friest, L. A.
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 2925-2933
ENG
Relevância na Pesquisa
45.86%
Additive and nonadditive genetic effects on preweaning weight gain (PWG) of a commercial crossbred population were estimated using different genetic models and estimation methods. The data set consisted of 103,445 records on purebred and crossbred Nelore-Hereford calves raised under pasture conditions on farms located in south, southeast, and middle west Brazilian regions. In addition to breed additive and dominance effects, the models including different epistasis covariables were tested. Models considering joint additive and environment (latitude) by genetic effects interactions were also applied. In a first step, analyses were carried out under animal models. In a second step, preadjusted records were analyzed using ordinary least squares (OLS) and ridge regression (RR). The results reinforced evidence that breed additive and dominance effects are not sufficient to explain the observed variability in preweaning traits of Bos taurus x Bos indicus calves, and that genotype x environment interaction plays an important role in the evaluation of crossbred calves. Data were ill-conditioned to estimate the effects of genotype x environment interactions. Models including these effects presented multicolinearity problems. In this case, RR seemed to be a powerful tool for obtaining more plausible and stable estimates. Estimated prediction error variances and variance inflation factors were drastically reduced...

Simulation and optimization tools to study design principles of biological networks

Adiwijaya, Bambang Senoaji
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 146 leaves
ENG
Relevância na Pesquisa
45.84%
Recent studies have developed preliminary wiring diagrams for a number of important biological networks. However, the design principles governing the construction and operation of these networks remain mostly unknown. To discover design principles in these networks, we investigated and developed a set of computational tools described below. First, we looked into the application of optimization techniques to explore network topology, parameterization, or both, and to evaluate relative fitness of networks operational strategies. In particular, we studied the ability of an enzymatic cycle to produce dynamic properties such as responsiveness and transient noise filtering. We discovered that non-linearity of the enzymatic cycle allows more effective filtering of transient noise. Furthermore, we found that networks with multiple activation steps, despite being less responsive, are better in filtering transient noise. Second, we explored a method to construct compact models of signal transduction networks based on a protein-domain network representation. This method generates models whose number of species, in the worst case, scales quadratically to the number of protein-domain sites and modification states, a tremendous saving over the combinatorial scaling in the more standard mass-action model was estimated to consist of more that 10⁷ species and was too large to simulate; however...

Bayesian network models of biological signaling pathways

Sachs, Karen, Ph. D. Massachusetts Institute of Technology
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 165 p.
ENG
Relevância na Pesquisa
45.79%
Cells communicate with other cells, and process cues from their environment, via signaling pathways, in which extracellular cues trigger a cascade of information flow, causing signaling molecules to become chemically, physically or locationally modified, gain new functional capabilities, and affect subsequent molecules in the cascade, culminating in a phenotypic cellular response. Mapping the influence connections among biomolecules in a signaling cascade aids in understanding of the underlying biological process and in development of therapeutics for diseases involving aberrant pathways, such as cancer and autoimmune disease. In this thesis, we present an approach for automatically reverse-engineering the structure of a signaling pathway, from high-throughput data. We apply Bayesian network structure inference to signaling protein measurements performed in thousands of single cells, using a machine called a flow cytorneter. Our de novo reconstruction of a T-cell signaling map was highly accurate, closely reproducing the known pathway structure, and accurately predicted novel pathway connections. The flow cytometry measurements include specific perturbations of signaling molecules, aiding in a causal interpretation of the Bayesian network graph structure.; (cont.) However...

Simulation, models, and refactoring of bacteriophage T7 gene expression

Kosuri, Sriram
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 191 leaves
ENG
Relevância na Pesquisa
45.9%
Our understanding of why biological systems are designed in a particular way would benefit from biophysically-realistic models that can make accurate predictions on the time-evolution of molecular events given arbitrary arrangements of genetic components. This thesis is focused on constructing such models for gene expression during bacteriophage T7 infection. T7 gene expression is a particularly well suited model system because knowledge of how the phage functions is thought to be relatively complete. My work focuses on two questions in particular. First, can we address deficiencies in past simulations and measurements of bacteriophage T7 to improve models of gene expression? Second, can we design and build refactored surrogates of T7 that are easier to understand and model? To address deficiencies in past simulations and measurements, I developed a new single-molecule, base-pair-resolved gene expression simulator named Tabasco that can faithfully represent mechanisms thought to govern phage gene expression. I used Tabasco to construct a model of T7 gene expression that encodes our mechanistic understanding. The model displayed significant discrepancies from new system-wide measurements of absolute T7 mRNA levels during infection.; (cont.) I fit transcript-specific degradation rates to match the measured RNA levels and as a result corrected discrepancies in protein synthesis rates that confounded previous models. I also developed and used a fitting procedure to the data that let us evaluate assumptions related to promoter strengths...

Cartilage response to in vitro models of injury in combination with growth factor and antioxidant treatments

Wheeler, Cameron, 1978-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 2 v. (282 leaves)
ENG
Relevância na Pesquisa
45.88%
Approximately one in five Americans is affected by arthritis, making it one of the most prevalent diseases and the leading cause of disability in the United States. Post-traumatic arthritis occurs after joint injury (e.g., ACL rupture or intraarticular fracture) and makes up a substantial proportion of the population with arthritis. In previous clinical studies, patients suffering from a traumatic joint injury have shown an increased risk in osteoarthritis (OA), independent of surgical intervention to stabilize the joint. Thus, the early events post-injury have an important effect on tissue within the joint in the long term. To understand the processes involved in the onset of OA and factors leading to OA post-traumatic injury, in vitro models have been developed to isolate components of the complex processes occurring in vivo. While in vitro models do not mimic true physiologic conditions in vivo, by isolating the effects of mechanical compression, cytokine treatment, and cartilage co-cultured with adjacent tissue, in vitro models can give insight into key biological and mechanical pathways occurring in vivo. This study focuses on changes in cartilage gene and protein expression and associated cartilage matrix degradation in response to static or injurious compression of the tissue in the presence or absence of cytokines including TNF-a and IL-6. In addition...

Models and analysis of yeast mating response : tools for model building, from documentation to time-dependent stimulation

Thomson, Ty M. (Ty Matthew)
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 350 p.
ENG
Relevância na Pesquisa
45.81%
Molecular signaling systems allow cells to sense and respond to environmental stimuli. Quantitative modeling can be a valuable tool for evaluating and extending our understanding of signaling systems. In particular, studies of the mating pheromone response system in yeast (Saccharomyces cerevisiae) have revealed many protein families and regulatory motifs also found in higher eukaryotes. This thesis develops several computational and experimental approaches that facilitate characterization of cellular signaling systems, and tests these approaches using yeast mating response as a model. Limitations in the current approach to building models of molecular systems were addressed first. For example, published computational models are often difficult to evaluate and extend because researchers rarely make available the information and assumptions generated throughout model building. I developed tools that facilitate model construction, evaluation, and extension. I used these tools to develop the YeastPheromoneModel (YPM) information repository, in which construction of an exhaustive model of the yeast mating system is documented (http://www.YeastPheromoneModel.org). Next, motivated by an ability to rapidly make many derivative models from the YPM repository and by carefully measured abundances of mating system proteins...

Selecting high-confidence predictions from ordinary differential equation models of biological networks

Bever, Caitlin Anne
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 153 p.
ENG
Relevância na Pesquisa
45.87%
Many cellular processes are governed by large and highly-complex networks of chemical interactions and are therefore difficult to intuit. Computational modeling provides a means of encapsulating information about these interactions and can serve as a platform for gaining understanding of the biology and making predictions about cellular response to perturbation. In particular, there has been considerable interest in ordinary differential equation (ODE) models, which have several attractive features: ODEs can describe molecular interactions with mechanistic detail, it is relatively straightforward to implement perturbations, and, in theory, they can predict the concentration and activity of every species as a function of time. However, both the topology and parameters in such models are subject to considerable uncertainty. We explore the ramifications of these sources of uncertainty for making accurate predictions and develop methods of selecting high confidence predictions from uncertain models. In particular, we promote a shift in emphasis from model selection to prediction selection, and use consensus among model ensembles to identify the predictions most likely to be accurate. By constructing decision trees, this consensus can also be used to partition the space of potential perturbations into regions of high and low confidence. We apply our methods to the Fas signaling pathway in apoptosis to satisfy two goals: first...

Perfusion-diffusion compartmental models describe cerebral helium kinetics at high and low cerebral blood flows in sheep

Doolette, D.; Upton, R.; Grant, C.
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Publicado em //2005 EN
Relevância na Pesquisa
45.71%
This study evaluated the relative importance of perfusion and diffusion mechanisms in compartmental models of blood:tissue helium exchange in the brain. Helium has different physiochemical properties from previously studied gases, and is a common diluent gas in underwater diving where decompression schedules are based on theoretical models of inert gas kinetics. Helium kinetics across the cerebrum were determined during and after 15 min of helium inhalation, at separate low and high steady states of cerebral blood flow in seven sheep under isoflurane anaesthesia. Helium concentrations in arterial and sagittal sinus venous blood were determined using gas chromatographic analysis, and sagittal sinus blood flow was monitored continuously. Parameters and model selection criteria of various perfusion-limited or perfusion–diffusion compartmental models of the brain were estimated by simultaneous fitting of the models to the sagittal sinus helium concentrations for both blood flow states. Purely perfusion-limited models fitted the data poorly. Models that allowed a diffusion-limited exchange of helium between a perfusion-limited tissue compartment and an unperfused deep compartment provided better overall fit of the data and credible parameter estimates. Fit to the data was also improved by allowing countercurrent diffusion shunt of helium between arterial and venous blood. These results suggest a role of diffusion in blood:tissue helium equilibration in brain.; David J Doolette...

Countercurrent compartmental models describe hind limb skeletal muscle helium kinetics at resting and low blood flows in sheep

Doolette, D.; Upton, R.; Grant, C.
Fonte: Wiley-Blackwell Publishing Ltd. Publicador: Wiley-Blackwell Publishing Ltd.
Tipo: Artigo de Revista Científica
Publicado em //2005 EN
Relevância na Pesquisa
45.71%
This study evaluated the relative importance of perfusion and diffusion mechanisms in compartmental models of blood : tissue helium exchange in a predominantly skeletal muscle tissue bed in the sheep hind limb. Helium has different physiochemical properties from previously studied gases and is a common diluent gas in underwater diving where decompression schedules are based on theoretical models of inert gas kinetics. Methods:  Helium kinetics across skeletal muscle were determined during and after 20 min of helium inhalation, at separate resting and low steady-states of femoral vein blood flow in six sheep under isoflurane anaesthesia. Helium concentrations in arterial and femoral vein blood were determined using gas chromatographic analysis and femoral vein blood flow was monitored continuously. Parameters and model selection criteria of various perfusion-limited or perfusion-diffusion compartmental models of skeletal muscle were estimated by simultaneous fitting of the models to the femoral vein helium concentrations for both blood flow states. Results:  A model comprising two parallel perfusion-limited compartment models fitted the data well but required a 51-fold difference in relative compartment perfusion that did not seem physiologically plausible. Models that allowed a countercurrent diffusion exchange of helium between arterial and venous vessels outside of the tissue compartments provided better overall fit of the data and credible parameter estimates. Conclusions:  These results suggest a role of arterial–venous diffusion in blood : tissue helium equilibration in skeletal muscle.; The definitive version is available at www.blackwell-synergy.com

Plausibility of inferred andestral phenotypes and the evaluation of alternative models of limb evolution in scincid lizards

Skinner, A.; Lee, M.
Fonte: The Royal Society Publicador: The Royal Society
Tipo: Artigo de Revista Científica
Publicado em //2010 EN
Relevância na Pesquisa
45.73%
Phylogenetic approaches to inferring ancestral character states are becoming increasingly sophisticated; however, the potential remains for available methods to yield strongly supported but inaccurate ancestral state estimates. The consistency of ancestral states inferred for two or more characters affords a useful criterion for evaluating ancestral trait reconstructions. Ancestral state estimates for multiple characters that entail plausible phenotypes when considered together may reasonably be assumed to be reliable. However, the accuracy of inferred ancestral states for one or more characters may be questionable where combined reconstructions imply implausible phenotypes for a proportion of internal nodes. This criterion for assessing reconstructed ancestral states is applied here in evaluating inferences of ancestral limb morphology in the scincid lizard clade Lerista. Ancestral numbers of digits for the manus and pes inferred assuming the models that best fit the data entail ancestral digit configurations for many nodes that differ fundamentally from configurations observed among known species. However, when an alternative model is assumed for the pes, inferred ancestral digit configurations are invariably represented among observed phenotypes. This indicates that a suboptimal model for the pes (and not the model providing the best fit to the data) yields accurate ancestral state estimates.; Adam Skinner and Michael S. Y. Lee

The performance of compartmental and physiologically based recirculatory pharmacokinetic models for propofol: A comparison using bolus, continuous, and target-controlled infusion data

Masui, K.; Upton, R.; Doufas, A.; Johan, F.; Kazama, T.; Mortier, E.; Struys, M.
Fonte: Lippincott Williams & Wilkins Publicador: Lippincott Williams & Wilkins
Tipo: Artigo de Revista Científica
Publicado em //2010 EN
Relevância na Pesquisa
45.74%
BACKGROUND: With the growing use of pharmacokinetic (PK)-driven drug delivery and/or drug advisory displays, identifying the PK model that best characterizes propofol plasma concentration (Cp) across a variety of dosing conditions would be useful. We tested the accuracy of 3 compartmental models and 1 physiologically based recirculatory PK model for propofol to predict the time course of propofol Cp using concentration-time data originated from studies that used different infusion schemes. METHODS: Three compartmental PK models for propofol, called the “Marsh,” the “Schnider,” and the “Schüttler” models, and 1 physiologically based recirculatory model called the “Upton” model, were used to simulate the time course of propofol Cp. To test the accuracy of the models, we used published measured plasma concentration data that originated from studies of manual (bolus and short infusion) and computer-controlled (target-controlled infusion [TCI] and long infusion) propofol dosing schemes. Measured/predicted (M/P) propofol Cp plots were constructed for each dataset. Bias and inaccuracy of each model were assessed by median prediction error (MDPE) and median absolute prediction error (MDAPE), respectively. RESULTS: The M/P propofol Cp in the 4 PK models revealed bias in all 3 compartmental models during the bolus and short infusion regimens. In the long infusion...

Effectiveness of biological surrogates for predicting patterns of marine biodiversity: A global meta-analysis

Mellin, C.; Delean, J.; Caley, M.; Edgar, G.; Meekan, M.; Pitcher, R.; Przeslawski, R.; Williams, A.; Bradshaw, C.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2011 EN
Relevância na Pesquisa
45.74%
The use of biological surrogates as proxies for biodiversity patterns is gaining popularity, particularly in marine systems where field surveys can be expensive and species richness high. Yet, uncertainty regarding their applicability remains because of inconsistency of definitions, a lack of standard methods for estimating effectiveness, and variable spatial scales considered. We present a Bayesian meta-analysis of the effectiveness of biological surrogates in marine ecosystems. Surrogate effectiveness was defined both as the proportion of surrogacy tests where predictions based on surrogates were better than random (i.e., low probability of making a Type I error; P) and as the predictability of targets using surrogates (R2). A total of 264 published surrogacy tests combined with prior probabilities elicited from eight international experts demonstrated that the habitat, spatial scale, type of surrogate and statistical method used all influenced surrogate effectiveness, at least according to either P or R2. The type of surrogate used (higher-taxa, cross-taxa or subset taxa) was the best predictor of P, with the higher-taxa surrogates outperforming all others. The marine habitat was the best predictor of R2, with particularly low predictability in tropical reefs. Surrogate effectiveness was greatest for higher-taxa surrogates at a ...

Probabilistic Models for Genetic and Genomic Data with Missing Information

Hicks, Stephanie
Fonte: Universidade Rice Publicador: Universidade Rice
ENG
Relevância na Pesquisa
45.73%
Genetic and genomic data often contain unobservable or missing information. Applications of probabilistic models such as mixture models and hidden Markov models (HMMs) have been widely used since the 1960s to make inference on unobserved information using some observed information demonstrating the versatility and importance of these models. Biological applications of mixture models include gene expression data, meta-analysis, disease mapping, epidemiology and pharmacology and applications of HMMs include gene finding, linkage analysis, phylogenetic analysis and identifying regions of identity-by-descent. An important statistical and informatics challenge posed by modern genetics is to understand the functional consequences of genetic variation and its relation to phenotypic variation. In the analysis of whole-exome sequencing data, predicting the impact of missense mutations on protein function is an important factor in identifying and determining the clinical importance of disease susceptibility mutations in the absence of independent data determining impact on disease. In addition to the interpretation, identifying co-inherited regions of related individuals with Mendelian disorders can further narrow the search for disease susceptibility mutations. In this thesis...

Dynamical behaviour of epidemiological models with sub-optimal immunity and nonlinear incidence

Gomes, M. G. M.; Margheri, A.; Medley, G. F.; Rebelo, C.
Fonte: Fundação Calouste Gulbenkian Publicador: Fundação Calouste Gulbenkian
Tipo: Artigo de Revista Científica
Publicado em /10/2005 ENG
Relevância na Pesquisa
45.68%
In this paper we analyze the dynamics of two families of epidemiological models which correspond to transitions from the SIR (susceptible-infectious-resistant) to the SIS (susceptible-infectious-susceptible) frameworks. In these models we assume that the force of infection is a nonlinear function of density of infectious individuals, I. Conditions for the existence of backwards bifurcations, oscillations and Bogdanov-Takens points are given

Improving transferability of introduced species' distribution models: new tools to forecast the spread of a highly invasive seaweed

Verbruggen, H.; Tyberghein, L.; Belton, G.; Mineur, F.; Jueterbock, A.; Hoarau, G.; Gurgel, C.; De Clerk, O.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
Relevância na Pesquisa
45.68%
The utility of species distribution models for applications in invasion and global change biology is critically dependent on their transferability between regions or points in time, respectively. We introduce two methods that aim to improve the transferability of presence-only models: density-based occurrence thinning and performance-based predictor selection. We evaluate the effect of these methods along with the impact of the choice of model complexity and geographic background on the transferability of a species distribution model between geographic regions. Our multifactorial experiment focuses on the notorious invasive seaweed Caulerpa cylindracea (previously Caulerpa racemosa var. cylindracea) and uses Maxent, a commonly used presence-only modeling technique. We show that model transferability is markedly improved by appropriate predictor selection, with occurrence thinning, model complexity and background choice having relatively minor effects. The data shows that, if available, occurrence records from the native and invaded regions should be combined as this leads to models with high predictive power while reducing the sensitivity to choices made in the modeling process. The inferred distribution model of Caulerpa cylindracea shows the potential for this species to further spread along the coasts of Western Europe...

Analysis of sequence-selective guanine oxidation by biological agents

Margolin, Yelena, 1977-
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 155 p.
ENG
Relevância na Pesquisa
45.69%
Oxidatively damaged DNA has been strongly associated with cancer, chronic degenerative diseases and aging. Guanine is the most frequently oxidized base in the DNA, and generation of a guanine radical cation (G'") as an intermediate in the oxidation reaction leads to migration of a resulting cationic hole through the DNA n-stack until it is trapped at the lowest-energy sites. These sites reside at runs of guanines, such as 5'-GG-3' sequences, and are characterized by the lowest sequence-specific ionization potentials (IPs). The charge transfer mechanism suggests that hotspots of oxidative DNA damage induced by electron transfer reagents can be predicted based on the primary DNA sequence. However, preliminary data indicated that nitrosoperoxycarbonate (ONOOCO2"), a mediator of chronic inflammation and a one-electron oxidant, displayed unusual guanine oxidation properties that were the focus of present work. As a first step in our study, we determined relative levels of guanine oxidation, induced by ONOOCO2 in all possible three-base sequence contexts (XGY) within double-stranded oligonucleotides. These levels were compared to the relative oxidation induced within the same guanines by photoactivated riboflavin, a one-electron reagent. We found that...

Scalable computational architecture for integrating biological pathway models; IFN response to virus infection

Shiva, V. A
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 2 v. (xvii, 303 leaves)
ENG
Relevância na Pesquisa
45.99%
A grand challenge of systems biology is to model the cell. The cell is an integrated network of cellular functions. Each cellular function, such as immune response, cell division, metabolism or apoptosis, is defined by an interconnected ensemble of biological pathways. Modeling the cell or even one cellular function requires a computational architecture that integrates multiple biological pathway models in a scalable manner while ensuring minimal effort to maintain the resulting integrated model. Scalable is defined as the ease in which more and more biological pathway models can be integrated. Current architectures for integrating biological pathway models are primarily monolithic and involve combining each biological pathway model's software source code to build one large monolithic model that executes on a single computer. Such architectures are not scalable for modeling complex cellular functions or the whole cell. We present Cytosolve, a new computational architecture that integrates a distributed ensemble of biological pathway models and computes solutions in a parallel manner while offering ease of maintenance of the integrated model. The individual biological pathway models can be represented in SBML, CellML or in any number of formats. The EGFR model of Kholodenko with known solutions is used to compare the Cytosolve solution and computational times with a known monolithic approach. A new integrative model of the interferon (IFN) response to virus infection is developed using Cytosolve. Each model within the integrated model...

An evaluation of remifentanil-sevoflurane response surface models in patients emerging from anesthesia: model improvement using effect-site sevoflurane concentrations.

Johnson, KB; Syroid, ND; Gupta, DK; Manyam, SC; Pace, NL; LaPierre, CD; Egan, TD; White, JL; Tyler, D; Westenskow, DR
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Artigo de Revista Científica Formato: 387 - 394
Publicado em /08/2010 ENG
Relevância na Pesquisa
45.7%
INTRODUCTION: We previously reported models that characterized the synergistic interaction between remifentanil and sevoflurane in blunting responses to verbal and painful stimuli. This preliminary study evaluated the ability of these models to predict a return of responsiveness during emergence from anesthesia and a response to tibial pressure when patients required analgesics in the recovery room. We hypothesized that model predictions would be consistent with observed responses. We also hypothesized that under non-steady-state conditions, accounting for the lag time between sevoflurane effect-site concentration (Ce) and end-tidal (ET) concentration would improve predictions. METHODS: Twenty patients received a sevoflurane, remifentanil, and fentanyl anesthetic. Two model predictions of responsiveness were recorded at emergence: an ET-based and a Ce-based prediction. Similarly, 2 predictions of a response to noxious stimuli were recorded when patients first required analgesics in the recovery room. Model predictions were compared with observations with graphical and temporal analyses. RESULTS: While patients were anesthetized, model predictions indicated a high likelihood that patients would be unresponsive (> or = 99%). However...

Tests of Continuum Theories as Models of Ion Channels. I. Poisson-Boltzmann Theory versus Brownian Dynamics

Moy, G; Corry, Ben; Kuyucak, Serdar; Chung, Shin-Ho
Fonte: Biophysical Society Publicador: Biophysical Society
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
45.69%
Continuum theories of electrolytes are widely used to describe physical processes in various biological systems. Although these are well-established theories in macroscopic situations, it is not clear from the outset that they should work in small systems whose dimensions are comparable to or smaller than the Debye length. Here, we test the validity of the mean-field approximation in Poisson-Boltzmann theory by comparing its predictions with those of Brownian dynamics simulations. For this purpose we use spherical and cylindrical boundaries and a catenary shape similar to that of the acetylcholine receptor channel. The interior region filled with electrolyte is assumed to have a high dielectric constant, and the exterior region representing protein a low one. Comparisons of the force on a test ion obtained with the two methods show that the shielding effect due to counterions is overestimated in Poisson-Boltzmann theory when the ion is within a Debye length of the boundary. As the ion gets closer to the boundary, the discrepancy in force grows rapidly. The implication for membrane channels, whose radii are typically smaller than the Debye length, is that Poisson-Boltzmann theory cannot be used to obtain reliable estimates of the electrostatic potential energy and force on an ion in the channel environment.