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At least 973 records · Page 54Linked to original sources
PubMed2005

The physics of filopodial protrusion.

Filopodium, a spike-like actin protrusion at the leading edge of migrating cells, functions as a sensor of the local environment and has a mechanical role in protrusion. We use modeling to examine mechanics and spatial-temporal dynamics of filopodia. We find that >10 actin filaments have to be bundled to overcome the membrane resistance and that the filopodial length is limited by buckling for 10-30 filaments and by G-actin diffusion for >30 filaments. There is an optimal number of bundled filaments, approximately 30, at which the filopodial length can reach a few microns. The model explains characteristic interfilopodial distance of a few microns as a balance of initiation, lateral drift, and merging of the filopodia. The theory suggests that F-actin barbed ends have to be focused and protected from capping (the capping rate has to decrease one order of magnitude) once every hundred seconds per micron of the leading edge to initiate the observed number of filopodia. The model generates testable predictions about how filopodial length, rate of growth, and interfilopodial distance should depend on the number of bundled filaments, membrane resistance, lamellipodial protrusion rate, and G-actin diffusion coefficient.

Actins↗
PubMed1995

Mathematical model that characterizes transmitral and pulmonary venous flow velocity patterns.

The transmitral and pulmonary venous flow velocity (TMFV and PVFV, respectively) patterns are related to the physiological state of the left heart by use of an electrical analog model. Filling of left ventricle (LV) through the mitral valve is characterized by a quadratic Bernoulli's resistance in series with an inertance. Filling of the left atrium (LA) through the pulmonary veins is represented by a lumped network of linear resistance, capacitance, and inertance. LV and LA are each represented by a time-varying elastance. A volume dependency is incorporated into the LV model to produce physiological pressure-volume loops and Starling curves. The state-space representation of the analog model consists of 10 simultaneous differential equations, which are solved by numerical integration. Model validity is supported by the following. First, the expected effects of aging and decreasing LV compliance on TMFV and PVFV are accurately represented by the model. Second, the model-generated TMFV and PVFV waveforms fit well to pulsed-Doppler recordings in normal and postinfarct patients. It is shown that the TMFV deceleration time is prolonged by the increase in LV compliance and, to a lesser extent, by the increase in LA compliance. A shift from diastolic dominance to systolic dominance in PVFV occurs when LA compliance or pulmonary perfusion pressure increases or when LV compliance or mitral valve area decreases. The present model should serve as a useful theoretical basis for echocardiographic evaluation of LV and LA functions.

Animals↗
PubMed2005

Animal models for the study of adenosine receptor function.

Adenosine receptors represent a family of G-protein coupled receptors that are ubiquitously expressed in a wide variety of tissues. This family contains four receptor subtypes: A1 and A3, which mediate inhibition of adenylyl cyclase; and A2a and A2b, which mediate stimulation of this enzyme. Currently, all receptor subtypes have been genetically deleted in mouse models except for the A2b adenosine receptor, and some have been overexpressed in selective tissues of transgenic mice. Studies involving these transgenic mice indicated that receptor levels are rate limiting, as effects were amplified upon increases in receptor level. The knockout models pointed to clusters of activities related to the physiologies of the cardiovascular and the nervous systems, which are either reduced or enhanced upon specific receptor deletion. Interestingly, the trend of effects on these systems is similar in the A1 and A3 adenosine receptor knockout mice and opposite to the effects observed in the A2a adenosine receptor knockout model. This review summarizes in vitro studies on pathways affected by each adenosine receptor, and primarily focuses on the above in vivo models generated to investigate the physiologic role of adenosine receptors. Furthermore, it illustrates the need for multiple adenosine receptor subtype deficiency studies in mice and the deletion of the A2b subtype.

Adenosine↗
PubMed1995

Trypanosoma brucei: inheritance of kinetoplast DNA maxicircles in a genetic cross and their segregation during vegetative growth.

The inheritance of maxicircle DNA was determined using a polymorphic EcoRI restriction site in the maxicircle variable region. In 11 hybrid progeny from a genetic cross of two stocks of Trypanosoma brucei, 7 progeny apparently inherited maxicircles uniparentally from either parent, in agreement with the results from previous studies, but in 4 progeny inheritance was biparental. Three subclones from 2 of these 4 progeny were made, and in these the maxicircles of only one parental type were detected. These data are considered in terms of a simple model whereby half the maxicircle genomes are inherited from each parent into progeny at meiosis with subsequent stochastic segregation at each mitotic division. This model generates a quantitative prediction as to the period of time required for fixation of inheritance to a uniparental pattern which provides a reasonable fit to the experimental data. These results provide an explanation as to why previous studies have shown that maxicircles are (apparently) inherited uniparentally: the kinetoplast is a unitary organelle inherited faithfully at cell division, but the maxicircles that it contains are best considered as a population that divides stochastically. Consideration of the model also explains why maxicircle populations are homogeneous.

Animals↗
PubMed1995

Effects of drinking pattern on the peak/trough blood concentrations in drinking water studies.

The effects of changes in drinking patterns on the expected peak/trough blood concentrations of test compounds were examined during rodent dosed drinking water studies. They were based on the assumption that the kinetics of the test compound is linear and time-invariant. Results indicate that drinking patterns have minor effects on the expected peak/trough concentrations and the time to reach these concentrations. If a 12-hr light/dark cycle starting at 7.00 is used for all the drinking patterns studied, the peak and trough concentrations will occur in the early morning and late afternoon, respectively. A comparison of the predicted versus experimentally determined pentachlorophenol (PCP) plasma concentrations in a 1-wk rat drinking water study revealed that using a circadian rhythm drinking pattern in the model generated the most satisfactory prediction. Predictions based on a square wave drinking pattern with 90% drinking activities in the night phase were also excellent. Triangular or sinusoidal drinking patterns were least accurate in predictions.

Animals↗
PubMedDate not supplied

Factorial invariance issues in the study of adult personality: an example using Levenson's locus of control scale.

Confirmatory factor analysis was used to examine factorial invariance across young, middle-aged, and elderly age groups, using Levenson's multidimensional locus of control (LoC) scale, which measures beliefs in Internal Control (I), Control by Powerful Others (P), and Chinese (C). Data were obtained from 563 individuals ranging in age from 25 years to 75 years of age who resided in Southeastern Louisiana. Results indicated that Levenson's 3-factor conceptualization of control was not a valid representation of the samples' responses. A model that specified the elimination of 17 unreliable items and the formation of both an internal and an external control factor that was based on the seven remaining I and P items provided an adequate fit to the data for the three age groups, though when additional constraints were specified, factorial invariance was not demonstrated. The 7-item I and P factor model generated a pattern of relationships with other measures which was similar to the pattern found if all items of the I and P scales were used.

Adult↗
PubMed2001

Modeling the 3D structure of GPCRs from sequence.

G-protein-coupled receptors (GPCRs) are a large and functionally diverse protein superfamily, which form a seven transmembrane (TM) helices bundle with alternating extra-cellular and intracellular loops. GPCRs are considered to be one of the most important groups of drug targets because they are involved in a broad range of body functions and processes and are related to major diseases. In this paper we present a new technology, named PREDICT, for modeling the 3D structure of any GPCR from its amino acid sequence. This approach takes into account both internal protein properties (i.e., the amino acid sequence) and the properties of the membrane environment. Unlike competing approaches, the new technology does not rely on the single known structure of rhodopsin, and is thus capable of predicting novel GPCR conformations. We demonstrate the capabilities of PREDICT in reproducing the known experimental structure of rhodopsin. In principle, PREDICT-generated models offer new opportunities for structure-based drug discovery towards GPCR targets.

Amino Acid Sequence↗
PubMed2004

Rapid analysis of large protein-protein complexes using NMR-derived orientational constraints: the 95 kDa complex of LpxA with acyl carrier protein.

Characterization of protein-protein interactions that are critical to the specific function of many biological systems has become a primary goal of structural biology research. Analysis of these interactions by structural techniques is, however, challenging due to inherent limitations of the techniques and because many of the interactions are transient, and suitable complexes are difficult to isolate. In particular, structural studies of large protein complexes by traditional solution NMR methods are difficult due to a priori requirement of extensive assignments and a large number of intermolecular restraints for the complex. An approach overcoming some of these challenges by utilizing orientational restraints from residual dipolar couplings collected on solution NMR samples is presented. The approach exploits existing structures of individual components, including the symmetry properties of some of these structures, to assemble rapidly models for relatively large protein-protein complexes. An application is illustrated with a 95 kDa homotrimeric complex of the acyltransferase protein, LpxA (UDP-N-acetylglucosamine acyltransferase), and acyl carrier protein. LpxA catalyzes the first step in the biosynthesis of the lipid A component of lipopolysaccharide in Gram-negative bacteria. The structural model generated for this complex can be useful in the design of new anti-bacterial agents that inhibit the biosynthesis of lipid A.

Acyl Carrier Protein↗
PubMed2001

Modeling complex disease with demographic and environmental covariates and a candidate gene marker.

We randomly chose replicates 28 and 29 of the simulated data sets of Genetic Analysis Workshop 12 to model the dependence of affection status on covariates, quantitative traits, and genes using all living pedigree members. First we explored the relationship of affection status to demographic and environmental factors using logistic regression and the Cox proportional hazards models. In the second stage of our analyses the generalized transmission disequilibrium test (GTDT) was applied to nuclear families with at least two affected siblings to select single markers and high-risk alleles, which were tested in the population association analyses including all pedigree members. Multiple logistic regression models were fitted to investigate the joint contributions of genetic and nongenetic factors and a block-recursive modeling approach was adopted to study inherent hierarchical dependence structure in the data. We found that allele 2 on marker 35 of chromosome 6 is associated with higher risk compared with the other 3 alleles of this marker. In addition to this significant genetic effect, age at exam and four of the five quantitative traits (QT1, QT2, QT4, and QT5) had a significant association with the disease. Our results were obtained without knowledge of the true disease generating models.

Adolescent↗
PubMed2003

Reproduction of seen actions: stimulus-selective learning.

Subjects observed and reproduced abstract, irregular stimulus models generated by the steady movement of a disk across two-dimensional paths. The paths comprised 3 to 7 randomly oriented linear segments linked head-to-foot. Reproductions were expressed by moving a stylus over the surface of a graphics tablet while the disk was tracing its trajectory (concurrent reproduction), or soon after the disk had finished (delayed reproduction). For both concurrent and delayed conditions, fidelity of reproduction fell with increasing number of segments in the model. Overall quality of reproduction did not differ between the two conditions. When a few models were repeated, interspersed among non-repeated ones, performance improved but only when reproduction was delayed. This improvement was stimulus-selective, not a general improvement with practice. Two additional experiments showed that (i) memory for a seen model is well preserved for at least 6 s, with relatively modest need for rehearsal, and (ii) successful reproduction is possible with remarkably little information having been extracted from key points in the model's trajectory.

Adolescent↗
PubMed2006

A medical imaging and visualization toolkit in Java.

Medical imaging research and clinical applications usually require combination and integration of various techniques ranging from image processing and analysis to realistic visualization to user-friendly interaction. Researchers with different backgrounds coming from diverse areas have been using numerous types of hardware, software, and environments to obtain their results. We also observe that students often build their tools from scratch resulting in redundant work. A generic and flexible medical imaging and visualization toolkit would be helpful in medical research and educational institutes to reduce redundant development work and hence increase research efficiency. This paper presents our experience in developing a Medical Imaging and Visualization Toolkit (BIL-kit) that is a set of comprehensive libraries as well as a number of interactive tools. The BIL-kit covers a wide range of fundamental functions from image conversion and transformation, image segmentation, and analysis to geometric model generation and manipulation, all the way up to 3D visualization and interactive simulation. The toolkit design and implementation emphasize the reusability and flexibility. BIL-kit is implemented in the Java language so that it works in hybrid and dynamic research and educational environments. This also allows the toolkit to extend its usage for the development of Web-based applications. Several BIL-kit-based tools and applications are presented including image converter, image processor, general anatomy model simulator, vascular modeling environment, and volume viewer. BIL-kit is a suitable platform for researchers and students to develop visualization and simulation prototypes, and it can also be used for the development of clinical applications.

Algorithms↗
PubMed2003

Kinetics of inorganic carbon utilization by microalgal biofilm in a flat plate photoreactor.

A kinetic model was developed to describe inorganic carbon utilization by microalgae biofilm in a flat plate photoreactor. The model incorporates the fundamental mechanisms of diffusive mass transport and biological reaction of inorganic carbon by microalgal biofilm. An advanced numerical technique, the orthogonal collocation method and Gear's method, was employed to solve this kinetic model. The model solutions included the concentration profiles of inorganic carbon in the microalgal biofilm, the growths of suspended microalgae and microalgal biofilm, the effluent concentrations of inorganic carbon, and the flux of inorganic carbon from bulk liquid into biofilm. The batch kinetic test was independently conducted to determine biokinetic parameters used in the microalgal biofilm model simulation while initial thickness of microalgal biofilm were assumed. A laboratory-scale flat plate photoreactor with a high recycle flow rate was setup and conducted to verify the model. The volume of photoreactor is 60 l which yields a hydraulic retention time of 1.67 days. The model-generated inorganic carbon and the suspended microalgae concentration curves agreed well with those obtained in the laboratory-scale test. The fixation efficiencies of HCO(3)(-) and CO(2) are 98.5% and 90% at a steady-state condition, respectively. The concentration of suspended microalgal cell reached up to 12 mg/l at a maximum growth rate while the thickness of microalgal biofilm was estimated to be 104 microm at a steady-state condition. The approaches of experiments and model simulation presented in this study could be employed for the design of a flat plate photoreactor to treat CO(2) by microalgal biofilm in a fossil-fuel power plant.

Air Pollutants↗
PubMed2004

Evaluation of a computerized aid for creating human behavioral representations of human-computer interaction.

The research reported herein presents the results of an empirical evaluation that focused on the accuracy and reliability of cognitive models created using a computerized tool: the cognitive analysis tool for human-computer interaction (CAT-HCI). A sample of participants, expert in interacting with a newly developed tactical display for the U.S. Army's Bradley Fighting Vehicle, individually modeled their knowledge of 4 specific tasks employing the CAT-HCI tool. Measures of the accuracy and consistency of task models created by these task domain experts using the tool were compared with task models created by a double expert. The findings indicated a high degree of consistency and accuracy between the different "single experts" in the task domain in terms of the resultant models generated using the tool. Actual or potential applications of this research include assessing human-computer interaction complexity, determining the productivity of human-computer interfaces, and analyzing an interface design to determine whether methods can be automated.

Auditory Perception↗
PubMed2005

Design and synthesis of an optimized positional scanning library of peptoids: identification of novel multidrug resistance reversal agents.

Herein is reported the optimized solid-phase synthesis of a library of 5,120 trimeric N-alkylglycines (peptoids) using the positional scanning format and the submonomer strategy. Diversity at the N-terminal position was generated from 20 commercially available primary amines, whereas 16 primary amines were employed for the middle and C-terminal positions of the trimers. Formation of undesirable side-products observed in a previous library synthesis (Humet, M. et al. J. Comb. Chem. 2003, 5, 597-605) was averted by restricting the use of primary amines functionalized with tertiary amino groups to the third amination step. Screening of the new library for the identification of chemosensitizers yielded two peptoids, compounds 1 and 2, with potent in vitro activity as multidrug resistance (MDR) reversal agents. The structures of the lead peptoids are consistent with a pharmacophore model generated from the interaction of various known inhibitors with the MDR-implicated transmembrane glycoprotein P-gp.

Alkylation↗
PubMed1999

Exploring the role of environmental factors in association and linkage studies.

We analyzed some simulated data to assess the success of statistical methodologies to establish the role of the environmental factors (EF) and to identify associated and linked markers. We considered five replicates for each of the four studies, and, with the knowledge of the generating model, concentrated our analyses on chromosomes (CH) 1, 3, and 5. To determine the influence of EF and associated markers on the affection status (AS), we utilized chi-square tests for independence and recursive partitioning (via the CART software). To identify linked markers, we scanned the relevant chromosomes with nonparametric multipoint linkage (NPL) and transmission/disequilibrium tests. These analyses were performed on the whole data set as well as on subsets of individuals and families defined by exposure to EF. CART correctly selected the associated marker (D1G024) and EF1 for Study (ST) 1 and did not generate trees for the other studies. NPL identified the relevant regions on CH3 and CH5 but failed to do so for CH1, except in ST4. Stratifying families by exposure to EF1 did not consistently increase sensitivity of NPL to the relevant CH3 markers, but did help characterize the genetic heterogeneity and identify linked families.

Chi-Square Distribution↗
PubMed1994

Generating a normalized geometric liver model using warping.

RATIONALE AND OBJECTIVES: Automated liver surface determination in abdominal computed tomography scans, currently difficult to achieve, is of interest to determine liver location and size for various medical applications, including radiation therapy treatment planning, surgical planning, and oncologic monitoring. The authors propose to facilitate automation by the addition of a priori shape information in the form of a liver model. METHODS: The normalized geometric liver model is generated by averaging outlines from a set of normal liver studies previously registered using thin-plate spline warping. The model consists of an averaged liver surface, a set of anatomic landmarks, and a deformation function. RESULTS: A liver model is presented and its ability to represent normal liver shapes is demonstrated. CONCLUSIONS: Liver surface warping provides a means of data normalization for model construction and a means of model deformation for representation of liver organ shapes.

Computer Simulation↗
PubMed2005

A test of the Bruhn and Parcel Model of Health Promotion.

The purposes of this study were to test the Bruhn and Parcel Model of Health Promotion (BPMHP) (1982), which explains how family influences and children's developmental characteristics interact to affect child health behaviors. The descriptive, correlational study was conducted using secondary data from the 117 adolescents included in Adolescents Benefit from Control of Diabetes Study. The results of structural equation modeling analysis indicated that greater parental modeling and positive parental interaction patterns were correlated with higher self-efficacy and lower levels of depressive symptoms among adolescents, which had a direct impact on better adherence. However, more parental modeling and interaction patterns did not have a separate direct effect on better adherence. Thus, the model generated by our data was significantly different from and so only partially supportive of the original BPMHP (1982). In addition, age and Tanner stages that can reflect changes in developmental characteristics were deleted from the concept called "developmental characteristics " in the BPMHP (1982), it may be that that concept should have been termed " psychosocial characteristics " rather than "developmental characteristics". In order to further explore the validity of the BPMHP (1982), future studies should be conducted to re-test this model.

Adaptation, Psychological↗
PubMed1998

Animats: computer-simulated animals in behavioral research.

The term animat refers to a class of simulated animals. This article is intended as a nontechnical introduction to animat research. Animats can be robots interacting with the real world or computer simulations. In this article, the use of computer-generated animats is emphasized. The scientific use of animats has been pioneered by artificial intelligence and artificial life researchers. Behavior-based artificial intelligence uses animats capable of autonomous and adaptive activity as conceptual tools in the design of usefully intelligent systems. Artificial life proponents view some human artifacts, including informational structures that show adaptive behavior and self-replication, as animats may do, as analogous to biological organisms. Animat simulations may be used for rapid and inexpensive evaluation of new livestock environments or management techniques. The animat approach is a powerful heuristic for understanding the mechanisms that underlie behavior. The simple rules and capabilities of animat models generate emergent and sometimes unpredictable behavior. Adaptive variability in animat behavior may be exploited using artificial neural networks. These have computational properties similar to natural neurons and are capable of learning. Artificial neural networks can control behavior at all levels of an animat's functional organization. Improving the performance of animats often requires genetic programming. Genetic algorithms are computer programs that are capable of self-replication, simulating biological reproduction. Animats may thus evolve over generations. Selective forces may be provided by a human overseer or be part of the simulated environment. Animat techniques allow researchers to culture behavior outside the organism that usually produces it. This approach could contribute new insights in theoretical ethology on questions including the origins of social behavior and cooperation, adaptation, and the emergent nature of complex behavior. Animat studies applied to domestic animals have been few so far, and have involved simulations of space use by swine. I suggest other applications, including modeling animal movement during human handling and the effects of environmental enrichment on the satisfaction of behavioral needs. Appropriate use of animat models in a research program could result in savings of time and numbers of animals required. This approach may therefore come to be viewed as both ethically and economically advantageous.

Animal Welfare↗