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PubMed2004

[A three dimensional fractal simulation of the lung bronchial tree].

The lungs are naturally irregular and asymmetrical organ in anatomy. The conducting bronchial trees in the lungs display complex self-similar structure. We have established the host mesh coordinates of the right lung on the basis of the anatomical data from the literature. A three-dimensional fractal model of the conducting airways was set up by calculating the coordinates of the mass centers of the divided blocks, searching the branch direction and determining branch lengths with the use of the drawing tool OpenGL. Specific data of the lengths at various grades, branching angles, and capillary diameters were obtained. As a result, the computed data were identical with those of the existing statistical data. The fractal covering dimensionality obtained in the computation of this model was 2.19, which is very close to the ideal dimensionality, 2.17, from the literature. The present model has laid the foundation for further research of the gas diffusion and transfer performance in the lungs using the fractal concept, and furthermore, it helps to save the computer memories and fastening the graphic transfer.

Algorithms↗
PubMed1996

The transition from a neutral-pH double helix to a low-pH triple helix induces a conformational switch in the CCCG tetraloop closing a Watson-Crick stem.

The CCCG-loop in a DNA fragment, which is capable of forming an intramolecular triple helix as well as a hairpin structure, was investigated by NMR and molecular modeling studies. The structure of this loop is found as a type II conformation, one of the three commonly observed folding patterns of tetraloops, irrespective of the geometry of the underlying helix. In each situation, the loop exhibits a base-pair between the first cytosine and the guanine residue of the loop. The geometry of this base-pair, however, depends upon the circumstances. At neutral pH, in the hairpin form of the molecule, a Watson-Crick C.G base-pair is formed, whereas at low pH, when the strand exists as an intramolecular triple helix, a Hoogsteen C(+)-G base-pair is present. We used molecular modeling to lay the foundations for understanding the observed conformational switch. A lower amount of strain, related to the short C1'-C1' of the base-pair, and protonation effects of the structure comprising the Hoogsteen base-pair turn out to outweigh the effects of a more stable base-pair, improved stacking and more favorable interactions in the minor groove of the structure comprising the Watson-Crick C.G base-pair. The models also provide an explanation for the general preference of loops meeting the consensus sequence--d(CYNG)--to fold into a type II conformation, i.e. with the base of second loop residue turned into the minor groove.

DNA↗
PubMed2004

Use of a quantitative gene expression assay based on micro-array techniques and a mathematical model for the investigation of chlamydial generation time.

Chlamydia is an important pathogen which possesses a unique developmental cycle. We used real-time PCR technology to measure gene transcript levels in Chlamydia trachomatis strain L2. By measuring 16S rRNA transcript levels, and developing a mathematical model of the chlamydial developmental cycle fitting the data, we predict an average generation time of approximately 2.6 h. Additionally, potentially this modelling also provides the foundation for the application of emerging micro-array technology in which identification of the gene signals that trigger a chlamydial body to start replicating or transform to its infectious form can be made possible.

Chlamydia trachomatis↗
PubMed1991

A perspective on the selection of experimental models.

We are entering an age when advances in biotechnology, greater communication among teams of scientists using multiple model systems, and the power of the computer will dwarf the great advances of the mid-20th century. Advances in medicine rest largely on the use of models of biological systems, including animal models. Model systems used by most biomedical scientists can be considered in four categories: theoretical, in vitro, nonmammalian and mammalian. Each category has advantages and limitations in describing the dynamic milieu of events that characterize human biologic response. Although individual models can be good predictors, multiple models are better than single models; the most critical drawback is lack of human information for comparison. The scientific community must improve the methodologies necessary to extrapolate data from the various model systems to the human, because these model systems are the foundation of discovery in biomedicine and the bedrock upon which to base valid risk assessments. It is vital that we communicate the importance of these techniques to the general public. Advances in science and improved quality of life for the human race depend on these principles.

Animals↗
PubMed1991

Staff development through analysis of practice.

Dreyfus and Dreyfus's (1986) five-stage model of skill acquisition is integrated with findings from the American Occupational Therapy Association/American Occupational Therapy Foundation Clinical Reasoning Study. This model is presented as an organizing framework for staff development. Strategies for the recognition and retention of experienced clinicians who can serve as mentors for newer colleagues are identified.

Clinical Competence↗
PubMed2002

[Current status of study on animal models of osteoporosis].

Animal models of osteoporosis lay the foundation of sophisticated studies on osteoporosis. This article reviews the currently most widely-used animal models of osteoporosis and their essential features, arriving at the conclusion that future studies of osteoporosis will be conducted more and more in large animals as ewes and gilts etc.

Animals↗
PubMed2005

A quantitative model to evaluate solubility relationship of polymorphs from their thermal properties.

PURPOSE: The objective of the study is to develop a model to estimate the solubility ratio of two polymorphic forms based on the calculation of the free energy difference of two forms at any temperature. This model can be used for compounds with low solubility (a few mole percent) in which infinite dilution can be approximated. METHODS: The model is derived using the melting temperature and heat of fusion for apparent monotropic systems, and the solid-solid transition temperature and heat of transition for apparent enantiotropic systems. A rigorous derivation also requires heat capacity (Cp) measurement of liquid and two solid forms. This model is validated by collecting thermal properties of polymorphs for several drugs using conventional or modulated differential scanning calorimetry. From these properties the solubility ratio of two polymorphs is evaluated using the model and compared with the experimental value at different temperatures. RESULTS: The predicted values using the full model agree well with the experimental ones. For the purpose of easy measurement, working equations without Cp terms are also applied. Ignoring Cp may result in an error of 10% or less, suggesting that the working equation is applicable in practice. Additional error may be generated for the apparent enantiotropic systems due to the inconsistency between the observed solid-solid transition temperature and the true thermodynamic transition temperature. This inconsistency allows the predicted solubility ratios (low melt/high melt) to be smaller. Therefore, a correction factor of 1.1 is recommended to reduce the error when the working equation is used to estimate the solubility ratio of an enantiotropic system. CONCLUSIONS: The study of the free energy changes of two crystalline forms of a drug allows for the development of a model that successfully predicts the solubility ratio at any temperature from their thermal properties. This model provides a thermodynamic foundation as to how the free energy difference of two polymorphs is reflected by their equilibrium solubilities. It also provides a quick and practical way of evaluating the relative solubility of two polymorphs from single differential scanning calorimetry runs.

Calorimetry, Differential Scanning↗
PubMed2005

Drawing lines and borders: how the dehiscent fruit of Arabidopsis is patterned.

The advent of fruits marked a key innovation in the evolution of flowering plants and helped generate a diverse array of mechanisms for seed dispersal. In the model plant, Arabidopsis thaliana, seed dispersal occurs through a process known as "pod-shatter" in which the fruit structure falls to pieces upon light mechanical pressures. This dispersal mechanism is dependent on the careful patterning of tissues in the fruit, which perform diverse functions that enable the fruit to open at maturation. Using the genetic power of Arabidopsis, many of the molecular components that help specify these tissues have been identified. Studies of the interactions among these genes have revealed a regulatory network that limits processes such as cell-cell separation and lignification to discreet regions of the fruit. Knowledge of these processes in a model fruit creates a foundation on which to build an understanding of the evolution of fruit form in other species and provides tools to engineer shatter-resistant seed pods to prevent crop loss in plants of agronomic importance such as canola.

Arabidopsis↗
PubMed2005

Non-linear fluid-coupled computational model of the mitral valve.

BACKGROUND AND AIM OF THE STUDY: The dynamics of the mitral valve result from the synergy of left heart geometry, local blood flow and tissue integrity. Herein is presented the first coupled fluid-structure computational model of the mitral valve in which valvular kinematics result from the interaction of local blood flow and a continuum representation of valvular microstructure. METHODS: The diastolic geometry of the mitral valve was assembled from previously published experimental data. Anterior and posterior leaflets were modeled as networks of entangled collagen fibers, embedded in an isotropic matrix. The resulting non-linear continuum description of mitral tissue was implemented in a three-dimensional membrane formulation. Chordal tension-only behavior was defined from experimental tensile tests. The computational model considered the valve immersed in a domain of Newtonian blood, with an experimentally determined viscosity corresponding to a shear rate of 180 s(-1) at 37 degrees C. Ventricular and atrial pressure curves were applied to ventricular and atrial surfaces of the blood domain. RESULTS: Peak closing flow and volume were 51 ml/s and 1.17 ml, respectively. Papillary muscle force ranged dynamically between 0.0 and 2.6 N. Acoustic pressure (RMS) was found to be 3.3 Pa, with a peak frequency of 72 Hz at 0.064 s from the onset of systole. Model predictions showed excellent agreement with available transmitral flow, papillary force and first heart sound (S1) acoustic data. CONCLUSION: The addition of blood flow and an experimentally driven microstructural description of mitral tissue represent a significant advance in computational studies of the mitral valve. This model will be the foundation for future computational studies on the effect of pathophysiological tissue alterations on mitral valve competence.

Algorithms↗
PubMed2002

Functional morphology of proximal hindlimb muscles in the frog Rana pipiens.

Musculoskeletal models have become important tools in understanding motor control issues ranging from how muscles power movement to how sensory feedback supports movements. In the present study, we developed the initial musculotendon subsystem of a realistic model of the frog Rana pipiens. We measured the anatomical properties of 13 proximal muscles in the frog hindlimb and incorporated these measurements into a set of musculotendon actuators. We examined whether the interaction between this musculotendon subsystem and a previously developed skeleton/joint subsystem captured the passive behavior of the real frog's musculoskeletal system. To do this, we compared the moment arms of musculotendon complexes measured experimentally with moment arms predicted by the model. We also compared sarcomere lengths measured experimentally at the starting and take-off positions of a jump with sarcomere lengths predicted by the model at these same limb positions. On the basis of the good fit of the experimental data, we used the model to describe the multi-joint mechanical effects produced by contraction of each hindlimb muscle and to predict muscle trajectories during a range of limb behaviors (wiping, defensive kicking, swimming and jumping). Through these analyses, we show that all hindlimb muscles have multiple functions with respect to accelerating the limb in its three-dimensional workspace and that the balance of functions depends greatly on limb configuration. In addition, we show that muscles have multiple, task-specific functions with respect to the type of contraction performed. The results of this study provide important data regarding the multifunctional role of hindlimb muscles in the frog and form a foundation upon which additional model subsystems (e.g. neural) and more sophisticated muscle models can be appended.

Animals↗
PubMed2002

Validation of fentanyl pharmacokinetics in patients undergoing coronary artery bypass grafting.

PURPOSE: The current emphasis on more rapid recovery and earlier tracheal extubation after cardiac surgery requires greater precision in administering opioids to reap their benefits while minimizing the duration of postoperative respiratory depression. Therefore, we aimed to define a pharmacokinetic model that accurately predicts fentanyl concentrations before, during, and after cardiopulmonary bypass (CPB) in patients undergoing coronary artery bypass grafting (CABG). METHODS: Parameters for two-compartment and three-compartment models were estimated by applying population pharmacokinetic modelling to fentanyl concentration vs time data measured in 29 patients undergoing elective, primary CABG. The ability of these models to predict fentanyl concentrations in a second series of ten patients undergoing CABG was then assessed. RESULTS: A simple, three-compartment model had excellent predictive ability, with a median prediction error (PE = ([Fentanyl]meas - [Fentanyl]pred)/[Fentanyl]pred x 100%) of -0.5%, and a median absolute PE (APE = /PE/) of 14.0%. In comparison to the two-compartment models, linear regression of measured:predicted concentration ratios indicated that the three-compartment model was free of systematic and time-related changes in bias (P < 0.05). The parameters of this three-compartment model are: V1 15.0 l, V2 20.0 l, V3 86.1 l, Cl1 1.08 L x min(-1), Cl2 4.90 L x min(-1), and Cl3 2.60 L x min(-1). CONCLUSIONS: Our pharmacokinetic model provides a rational foundation for designing fentanyl dose regimens for patients undergoing CABG. When combined with previously published information regarding intraoperative fentanyl pharmacodynamics, dose regimens that reliably achieve and maintain desired fentanyl concentrations throughout the intraoperative period can be designed to achieve specific therapeutic goals.

Aged↗
PubMed2002

Toward a model for effectiveness. What Alberta occupational health nurses think.

Effectiveness is difficult to define or measure, but is frequently associated with cost. A two phase study conducted with occupational health nurses in Alberta, Canada resulted in a beginning model for effectiveness. In 1997, Phase One of an exploratory descriptive study focused on physical assessment by occupational health nurses (N = 137) and perceptions of effectiveness in practice (n = 104). In 2001, Phase Two used focus groups (n = 7) to determine occupational health nurses' reactions to the preliminary analysis of questionnaire responses on effectiveness. The focus groups confirmed and expanded categories, and reconfigured the developing model. The model makes explicit the foundations, functions, relationships, and goals for effectiveness in occupational health nursing practice. The foundation includes registered nurse (RN) experience and baseline competence comprising occupational health nursing education, RN and occupational health nurse experience, and multidisciplinary knowledge. Ten specific functions and nine relationships describe the occupational health nursing specialty practice and promote achievement of five goals: balance, communication, continuing competence, leadership, and trust. The goal of balance needs articulation in the nursing literature.

Adult↗
PubMed1993

Electromyographic analysis and its role in the athletic shoulder.

In 1944, Inman made some conclusions regarding shoulder function that have become the foundation of a classic model. Clinical observations of the athletic shoulder and its associated common injuries have demonstrated selective weakness of specific rotator cuff muscles rather than generalized muscle impairment. Shoulder mechanics during athletic activities have been evaluated dynamically with electromyography (EMG), which has helped to formulate a base for optimal rehabilitation. Dynamic EMG and high-speed film analysis have been used to evaluate the shoulder during throwing, swimming, tennis, and golf. Evaluation of shoulder function in these various sports revealed that although rotator cuff function is important in all, the emphasis and role of individual muscles varied. The importance of serratus anterior muscle activity to stabilization and protraction of the scapula has been consistently reported. The muscles about the shoulder act according to their mechanical qualities and are function- or sport-specific. A thorough understanding of the mechanics of the normal and pathologic shoulder constitutes the foundation for training and rehabilitation strategies.

Baseball↗
PubMed1993

Receptor mechanisms and dose-response models for the effects of dioxins.

There is increasing evidence that receptor-mediated events impact one or more stages responsible for tumor development in experimental animals and humans. Although many chemicals and endogenous hormones require receptor interactions as a necessary event in their carcinogenic activity, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its structural analogs are the most visible examples of receptor-mediated carcinogens. TCDD, or dioxin as it is frequently called, interacts with the Ah receptor (AhR), which functions in a manner analogous to receptors for steroids. TCDD produces a wide spectrum of biochemical and toxic responses in in vitro and in vivo systems, and the Ah receptor is generally considered necessary for most if not all of these responses. Risk assessments for dioxin made by the United States and other countries throughout the world have been based on its carcinogenecity in experimental animals. Recently, epidemiology studies have indicated that TCDD is a human carcinogen at high doses. Because TCDD appears to be acting like a potent and persistent hormone agonist, it appears reasonable to incorporate mechanistic information on receptor-mediated events in risk assessments for TCDD. This information may be obtained from steroid receptor action and from molecular data on the Ah receptor. In this paper, we evaluate the scientific foundation on which mechanistic models for estimating dioxin's risks should be based. These models need to recognize the mechanisms possible for the diversity of biological responses that are initiated by a single receptor interacting with a single ligand. The U.S. EPA is currently reevaluating dioxin's risks by examining the possibility of developing biologically based models.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Comparative physical mapping links conservation of microsynteny to chromosome structure and recombination in grasses.

Nearly finished sequences for model organisms provide a foundation from which to explore genomic diversity among other taxonomic groups. We explore genome-wide microsynteny patterns between the rice sequence and two sorghum physical maps that integrate genetic markers, bacterial artificial chromosome (BAC) fingerprints, and BAC hybridization data. The sorghum maps largely tile a genomic component containing 41% of BACs but 80% of single-copy genes that shows conserved microsynteny with rice and partially tile a nonsyntenic component containing 46% of BACs but only 13% of single-copy genes. The remaining BACs are centromeric (4%) or unassigned (8%). The two genomic components correspond to cytologically discernible "euchromatin" and "heterochromatin." Gene and repetitive DNA distributions support this classification. Greater microcolinearity in recombinogenic (euchromatic) than nonrecombinogenic (heterochromatic) regions is consistent with the hypothesis that genomic rearrangements are usually deleterious, thus more likely to persist in nonrecombinogenic regions by virtue of Muller's ratchet. Interchromosomal centromeric rearrangements may have fostered diploidization of a polyploid cereal progenitor. Model plant sequences better guide studies of related genomes in recombinogenic than nonrecombinogenic regions. Bridging of 35 physical gaps in the rice sequence by sorghum BAC contigs illustrates reciprocal benefits of comparative approaches that extend at least across the cereals and perhaps beyond.

Base Sequence↗
PubMed2002

Dignity in the terminally ill: a developing empirical model.

Despite use of the term dignity in arguments for and against a patient's self-governance in matters pertaining to death, there is little empirical research on how this term has been used by patients who are nearing death. The objective of this study was to determine how dying patients understand and define the term dignity, in order to develop a model of dignity in the terminally ill. A semi-structured interview was designed to explore how patients cope with their advanced cancer and to detail their perceptions of dignity. Interviews were audiotaped and transcribed verbatim. A consecutive sample of 50 consenting patients with advanced terminal cancer were recruited over a 15-month period of time from an urban extended care hospital housing a specialized unit for palliative care. This unit provides both inpatient services. and coordinates end-of-life care community based programming. Data were analysed using latent content analysis and constant comparison techniques. Four members of the research team independently coded the transcribed data, to develop conceptually meaningful categories of responses. Operational definitions were written for major categories, themes and sub-themes. Three major categories emerged from the qualitative analysis, including illness-related concerns; dignity conserving repertoire; and social dignity inventory. These broad categories and their carefully defined themes and sub-themes form the foundation for an emerging model of dignity amongst the dying. The concept of dignity and the dignity model offer a way of understanding how patients face advancing terminal illness. This will serve to promote dignity and the quality of life of patients nearing death.

Activities of Daily Living↗
PubMed1993

Freud's speech apparatus and spontaneous speech.

Freud's first book published in 1891 was a monograph entitled On Aphasia. In it he challenges the main authorities of the time by asserting that their manner of understanding aphasias is no longer tenable. Freud proves their theories wrong and presents his own conception of a speech apparatus. The apparatus is the foundation of his clinical and theoretical explanations about the speech function and its pathological manifestations. He built the model of an apparatus capable of explaining spontaneous speech, a function that the competing models of his contemporaries could not fully integrate. Freud's speech apparatus is the first of several models he created to facilitate the understanding of psychic functions. This paper is part of a series dedicated to an in-depth study of the earliest model which would provide the foundations for the understanding of its reappearance in Freud's later theories, and in particular in his analytic technique.

Aphasia↗
PubMed2002

Jumping in frogs: assessing the design of the skeletal system by anatomically realistic modeling and forward dynamic simulation.

Comparative musculoskeletal modeling represents a tool to understand better how motor system parameters are fine-tuned for specific behaviors. Frog jumping is a behavior in which the physical properties of the body and musculotendon actuators may have evolved specifically to extend the limits of performance. Little is known about how the joints of the frog contribute to and limit jumping performance. To address these issues, we developed a skeletal model of the frog Rana pipiens that contained realistic bones, joints and body-segment properties. We performed forward dynamic simulations of jumping to determine the minimal number of joint degrees of freedom required to produce maximal-distance jumps and to produce jumps of varied take-off angles. The forward dynamics of the models was driven with joint torque patterns determined from inverse dynamic analysis of jumping in experimental frogs. When the joints were constrained to rotate in the extension-flexion plane, the simulations produced short jumps with a fixed angle of take-off. We found that, to produce maximal-distance jumping, the skeletal system of the frog must minimally include a gimbal joint at the hip (three rotational degrees of freedom), a universal Hooke's joint at the knee (two rotational degrees of freedom) and pin joints at the ankle, tarsometatarsal, metatarsophalangeal and iliosacral joints (one rotational degree of freedom). One of the knee degrees of freedom represented a unique kinematic mechanism (internal rotation about the long axis of the tibiofibula) and played a crucial role in bringing the feet under the body so that maximal jump distances could be attained. Finally, the out-of-plane degrees of freedom were found to be essential to enable the frog to alter the angle of take-off and thereby permit flexible neuromotor control. The results of this study form a foundation upon which additional model subsystems (e.g. musculotendon and neural) can be added to test the integrative action of the neuromusculoskeletal system during frog jumping.

Animals↗