SEARCH · PubMed Health

Results for “Pathway modelling”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources

PubMed2000

Genetics of testosterone and the aggression-hostility-anger (AHA) syndrome: a study of middle-aged male twins.

The aim of this study was to determine the genetic contribution to the variation in testosterone and the aggression-hostility-anger (AHA) syndrome in middle-aged twins. Moreover, the relation between testosterone and this syndrome, and possible common genetic mechanisms were investigated. Towards this end, blood samples were collected at two time points; the AHA syndrome was measured using three questionnaires: the Buss-Durkee Hostility Inventory with seven subscales, the Jenkins Activity Survey and the Spielberger State-Trait Anger Scale. The results showed substantial heritabilities for testosterone (approximately 60%) and moderate to fair heritabilities for the nine measures of the AHA syndrome (23-53%). The best fitting model for testosterone at two time points included a small age component and additive genetic and unique environmental factors, while a multivariate analysis of the nine AHA subscales resulted in an independent pathway model with two common additive genetic and two common unique environmental factors. No correlation between the common genetic factor influencing testosterone and the AHA subscales was found. We did, however, detect a negative correlation between the common environmental factor underlying testosterone and both common environmental factors influencing the nine AHA subscales, which may reflect a tendency for testosterone levels to rise and hostility to drop (or vice versa) after repeatedly experiencing success (or failure).

Adult↗

PubMed2026

The influence of neuroprotector isatin on haloperidolinduced catalepsy and proteomic profile of mice brain.

Isatin (indol-2,3-dione) is an endogenous regulator found in humans and animals. It interacts with numerous target proteins and exhibits a wide range of biological activities, including neuroprotective action in animal models of Parkinson's disease (PD) induced by administration of neurotoxins MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) or rotenone. An antipsychotic drug haloperidol, which impairs neurotransmitter balance in the nigrostriatal pathway, models dopamine deficiency and promotes the development of motor disorders characteristic of PD. In this work, the effect of two doses of isatin (10 mg/kg and 80 mg/kg) on the haloperidol catalepsy and on the proteomic profile of mice brain was investigated. The pretreatment of animals with isatin (1 h before haloperidol administration) reduced the occurrence of haloperidol catalepsy. The administration of haloperidol and also isatin with haloperidol influenced the relative content of a number of proteins associated with PD and other neurodegenerative diseases.

Animals↗

PubMed2005

Gene function classification using NCI-60 cell line gene expression profiles.

Gene expression patterns from NCI's panel of 60 cell lines were used to train a Neural Network model for classifying genes to pathways. The model assigns probabilities to each gene for each of the 21 modeled pathways assigned by the Kyoto Encyclopedia of Genes and Genomes. Cross-validation of the model showed that 10 of the 21 pathways exhibited good performance in statistical significance and accuracy. The model was designed to output gene probabilities that could be screened for higher probabilities resulting in higher confidence in classification though yielding fewer genes per pathway. The model was deployed on 5798 genes and our approach allowed us to ascertain the most relevant genes above an estimated background. Eight pathways were identified with both good cross-validation and significant numbers above background, TCA Cycle, Oxidative Phosphorylation, Porphyrin Biosynthesis, Ribosome, Polymerases, Proteasome, Cell Cycle, and Cell Adhesion. Gene Ontology (GO) annotation was used for additional validation of gene classification results. A total of 551 GO annotated genes and 468 unannotated genes were classified to the 8 pathways. The primary and secondary classifications of genes revealed known pathway relationships and provide the potential for discovering new pathway relationships.

Cell Line↗

PubMed2005

Computation of inverse functions in a model of cerebellar and reflex pathways allows to control a mobile mechanical segment.

The command and control of limb movements by the cerebellar and reflex pathways are modeled by means of a circuit whose structure is deduced from functional constraints. One constraint is that fast limb movements must be accurate although they cannot be continuously controlled in closed loop by use of sensory signals. Thus, the pathways which process the motor orders must contain approximate inverse functions of the bio-mechanical functions of the limb and of the muscles. This can be achieved by means of parallel feedback loops, whose pattern turns out to be comparable to the anatomy of the cerebellar pathways. They contain neural networks able to anticipate the motor consequences of the motor orders, modeled by artificial neural networks whose connectivity is similar to that of the cerebellar cortex. These networks learn the direct biomechanical functions of the limbs and muscles by means of a supervised learning process. Teaching signals calculated from motor errors are sent to the learning sites, as, in the cerebellum, complex spikes issued from the inferior olive are conveyed to the Purkinje cells by climbing fibers. Learning rules are deduced by a differential calculation, as classical gradient rules, and they account for the long term depression which takes place in the dendritic arborizations of the Purkinje cells. Another constraint is that reflexes must not impede voluntary movements while remaining at any instant ready to oppose perturbations. Therefore, efferent copies of the motor orders are sent to the interneurones of the reflexes, where they cancel the sensory-motor consequences of the voluntary movements. After learning, the model is able to drive accurately, both in velocity and position, angular movements of a rod actuated by two pneumatic McKibben muscles. Reflexes comparable to the myotatic and tendinous reflexes, and stabilizing reactions comparable to the cerebellar sensory-motor reactions, reduce efficiently the effects of perturbing torques. These results allow to link the behavioral concepts of the equilibrium-point "lambda model" [J Motor Behav 18 (1986) 17] with anatomical and physiological features: gains of reflexes and sensori-motor reactions set the slope of the "invariant characteristic," and efferent copies set the "threshold of the stretch reflex." Thus, mathematical and physical laws account for the raison d'etre of the inhibitory nature of Purkinje cells and for the conspicuous anatomical pattern of the cerebellar pathways. These properties of these pathways allow to perform approximate inverse calculations after learning of direct functions, and insure also the coordination of voluntary and reflex motor orders.

Algorithms↗

PubMed2006

Service Utilization among ethnic minority children with ADHD: a model of help-seeking behavior.

Despite a significant increase in the number of children and adolescents who receive clinical services for attention deficit hyperactivity disorder (ADHD), there is still a considerable level of unmet need. Children of ethnic minority status continue to lag well behind their non-minority counterparts in the rate of diagnosis and treatment for the disorder. Racial/ethnic disparities in service use are the result of a combination of access barriers and individual, cultural, and societal factors. The ADHD Help-Seeking Behavior Model is proposed as a framework for understanding factors that may be predictive of service use. Variables specific to ADHD and ethnic-minority populations are integrated within the framework of a four-stage pathway model encompassing problem recognition, decision to seek help, service selection, and service use. The authors argue that by systematically addressing factors related to service use for each ethnic minority group, more effective intervention initiatives can be developed to improve identification and treatment for ADHD among underserved children.

Attention Deficit Disorder with Hyperactivity↗

PubMed2006

Committed to memory: lineage choices for activated T cells.

The mechanisms for the generation of memory T cells and their delineation into heterogeneous subsets remain unknown. The linear model for memory T-cell generation from differentiated effector cells has been favored, although there is evidence that memory T cells can emerge directly from naive T cells undergoing homeostatic expansion and from activated T cells lacking effector functions. Here, we discuss the evidence from diverse studies of memory generation that support a new 'intersecting pathway' model for memory T-cell generation in which antigen-driven effector differentiation and homeostasis-driven memory differentiation follow distinct but analogous pathways. Antigen withdrawal during effector differentiation enables intersection with the memory pathway through a pre-memory intermediate, and memory heterogeneity is influenced by homeostasis, migration and persistence in vivo.

Animals↗

PubMed2001

Cost-effectiveness and cost-efficiency in vascular surgery.

Medical costs have been an increasing focus of attention in medicine in general, particularly in the United States health care environment. Because vascular disease is most prevalent in the elderly, the forecasted growth of this population over the next several decades will put increasing strains on health care financing. Costs will undoubtedly be a major component of any system of outcomes measurement, and it is important for vascular surgeons and others who specialize in vascular disease to be familiar with the definitions and methodology and cost-effectiveness analysis. Similarly, improving cost efficiency within the practice of vascular surgery will be mandated. The purpose of this article is to review systems of cost-effectiveness analysis as they pertain to vascular surgery, as well as to define critical pathway models that have been used to improve cost-efficiency in vascular surgery.

Cost-Benefit Analysis↗

PubMed1978

Evolution of a genetic code simulated with the computer.

A simple selforganizing model system of molecules is considered and it is demonstrated by a computer simulation, that a genetic code of 16 elements (aminoacids) can gradually be formed by such a system in the course of many generations. By a number of rare chance events, each suppressing other events of equal a priori probability, a single code results out of an immense number of possible codes of the same a priori probability. The result is discussed in relation to the uniqueness of the genetic code in living systems. The computer simulation emphasizes a particular step in a model pathway discussed elsewhere consisting of many assumed physicochemical steps leading to a genetic apparatus.

Base Sequence↗

PubMed2006

Loss of caspase-9 provides genetic evidence for the type I/II concept of CD95-mediated apoptosis.

The death receptor CD95 triggers apoptosis upon formation of a death-inducing signaling complex and the activation of caspase-8. Two types of CD95-mediated apoptosis have been distinguished that differ in their efficiency of death-inducing signaling complex formation and the requirement of mitochondria for caspase activation. The validity of the type I/II model, however, has been challenged, as Bcl-2 expression or the use of various CD95 agonists resulted in different apoptosis effects. By identifying a caspase-9-deficient T cell line, we now provide genetic evidence for the two-pathway model of CD95-mediated apoptosis and demonstrate that type II cells strongly depend on caspase-9. Caspase-9-deficient cells revealed strongly impaired apoptosis, caspase activation, and mitochondrial membrane depolarization upon CD95 triggering, whereas, surprisingly, activation of Bak and cytochrome c release were not inhibited. Furthermore, caspase-9-deficient cells did not switch to necrosis, and reconstitution of caspase-9 expression restored CD95 sensitivity. Finally, we also show that different death receptors have a distinct requirement for caspase-9.

Action Potentials↗

PubMed1985

Responses to head tilt in cat central vestibular neurons. II. Frequency dependence of neural response vectors.

The responses of central vestibular neurons in the decerebrate cat subjected to whole-body tilt were examined as a function both of stimulus orientation (with respect to the cat's head) and frequency, with the aim of understanding the neural processing responsible for producing the observed response patterns. Responses to whole-body tilt were recorded from vestibular neurons in and around the lateral vestibular nucleus (LVN). By plugging all six semicircular canals, the otolith contribution was studied in isolation. For each neuron, a response vector was defined as having three components: orientation, gain, and phase. These components were examined using sinusoidal stimulus frequencies of 0.01 to 2 Hz. The orientation component of the neural response vector does not vary as a function of stimulus frequency. Thus response dynamics previously described with a fixed (roll) axis cannot be explained by changes in the angle between the response vector orientation and a fixed stimulus axis. Two major classes of neural responses were observed. One class had a phase lead at low frequencies and gain that showed a modest increase with frequency. It could be described by a model that included a fractional s exponent operator. These response dynamics resemble that of otolith afferents, suggesting that these neurons may be acting as simple relays. The other major response class was characterized by a large gain increase and a phase lag of as much as 180 degrees as frequency increased; such response dynamics have been previously observed in otolith-evoked neck and forelimb reflexes. A more complex model, consisting of a parallel excitatory and high-pass-filtered inhibitory limb, was necessary to describe these responses. The orientation component of the response vector of most of the neurons whose dynamics were best described by the parallel pathway model pointed toward the contralateral side, implying they would be excited by side-up tilt (at low frequencies). Most other neurons had ipsilateral vectors.

Animals↗

PubMed2006

Shared genetic and environmental risk factors between undue influence of body shape and weight on self-evaluation and dimensions of perfectionism.

BACKGROUND: Theory and evidence strongly suggest that perfectionism may be a risk factor for eating disorders. The purpose of the current study was to investigate a model that would explain the relationship between the cognitive diagnostic criterion for both anorexia nervosa and bulimia nervosa, namely undue influence of body weight or shape on self-evaluation, and dimensions of perfectionism. The model of particular interest was the common cause model, which hypothesizes that the phenotypes are caused by the same underlying genetic and environmental risk factors. METHOD: Female twins (n=1002) from the Australian Twin Registry (ATR), aged 28 to 39 years, were interviewed using the Eating Disorder Examination (EDE). In addition, questions relating to the Equal Environment Assumption (EEA) and the Frost Multidimensional Perfectionism Scale, namely concern over mistakes (CM), personal standards (PS) and doubts about actions (DA), were assessed. RESULTS: There was no evidence of violation of the EEA for any of the four phenotypes. Univariate models showed all phenotypes to be influenced by both genetic and non-shared environmental action, where genetic estimates ranged from 25% to 39% of the variance. Multivariate analyses suggested the best explanation of covariation among the phenotypes was an independent pathways, rather than a common pathways, model. CONCLUSIONS: Undue influence of body weight or shape on self-evaluation shared about 10% of its sources of genetic and environmental variance with perfectionism, thus suggesting that a common cause model does not represent the best explanation of the relationship between perfectionism and this cognitive diagnostic criterion for eating disorders.

Adult↗

PubMed2005

Interprotein electron transfer from cytochrome c2 to photosynthetic reaction center: tunneling across an aqueous interface.

Interprotein electron transfer (ET) reactions play an important role in biological energy conversion processes. One of these reactions, the ET between cytochrome c(2) (cyt) and reaction center from photosynthetic bacteria, is the focus of this theoretical study. The changes in the ET rate constant at fixed distances during the association process were calculated as the cyt moved from the electrostatically stabilized encounter complex to the bound state having short range van der Waals contacts in the tunneling region. Multiple conformations of the protein were generated by molecular dynamics simulations including explicit water molecules. For each of these conformations, the ET rate was calculated by using the Pathways model. The ET rate increased smoothly as the cyt approached from the encounter complex to the bound state, with a tunneling decay factor beta = 1.1 A(-1). This relatively efficient coupling between redox centers is due to the ability of interfacial water molecules to form multiple strong hydrogen bonding pathways connecting tunneling pathways on the surfaces of the two proteins. The ET rate determined for the encounter complex ensemble of states is only about a factor of 100 slower than that of the bound state (tau = 100 micros, compared with 1 micros), because of fluctuations of the cyt within the encounter complex ensemble through configurations having strong tunneling pathways. The ET rate for the encounter complex is in agreement with rates observed in mutant reaction centers modified to remove shortrange hydrophobic interactions, suggesting that in this case, ET occurs within the solvent-separated, electrostatically stabilized encounter complex.

Cytochromes c2↗

PubMed2000

Classifying depression: should paradigms lost be regained?

OBJECTIVE: Classification of the depressive disorders has long been controversial. The dominant current model is unitarian, with disorders largely distinguished on the basis of severity. Both the unitarian and the contrasting binarian views (of two principal types) have proved to be unsatisfactory. The binarian model's procrustean requirements are too inflexible to address the evident heterogeneity contributed to by clinical manifestations and underlying personality features. METHOD: This article briefly reviews the historically favored unitarian and binarian viewpoints on classification of depression. RESULTS: The author argues that the "final common pathway" model, articulated in the early 1970s, helped to cement psychiatric classification in subsequent DSM and ICD revisions into a unitarian framework, leading to a relatively sterile period of depression research. Clinically described depressive typologies were obscured rather than refined by appropriate modeling paradigms. A contrasting, empirically based hierarchical model, driven by disorder-specific clinical manifestations such as psychotic features and observable psychomotor disturbance, is proposed as a paradigm for distinguishing psychotic, melancholic, and nonmelancholic classes of depression, while a spectrum model is favored for distinguishing the principal nonmelancholic subclasses. CONCLUSIONS: Resolution of the better paradigm requires that the two models undergo comparative testing in applied studies, particularly ones pursuing neurobiological determinants and differential responses to antidepressant treatments.

Depressive Disorder↗

PubMedDate not supplied

Modelling spatiotemporal olfactory data in two steps: from binary to Hodgkin-Huxley neurones.

Network models of synchronously updated McCulloch-Pitts neurones exhibit complex spatiotemporal patterns that are similar to activities of biological neurones in phase with a periodic local field potential, such as those observed experimentally by Wehr and Laurent (1996, Nature 384, 162-166) in the locust olfactory pathway. Modelling biological neural nets with networks of simple formal units makes the dynamics of the model analytically tractable. It is thus possible to determine the constraints that must be satisfied by its connection matrix in order to make its neurones exhibit a given sequence of activity (see, for instance, Quenet et al., 2001, Neurocomputing 38-40, 831-836). In the present paper, we address the following question: how can one construct a formal network of Hodgkin-Huxley (HH) type neurones that reproduces experimentally observed neuronal codes? A two-step strategy is suggested in the present paper: first, a simple network of binary units is designed, whose activity reproduces the binary experimental codes; second, this model is used as a guide to design a network of more realistic formal HH neurones. We show that such a strategy is indeed fruitful: it allowed us to design a model that reproduces the Wehr-Laurent olfactory codes, and to investigate the robustness of these codes to synaptic noise.

Models, Neurological↗

PubMed1993

GEPASI: a software package for modelling the dynamics, steady states and control of biochemical and other systems.

GEPASI is a software system for modelling chemical and biochemical reaction networks on computers running Microsoft Windows. For any system of up to 45 metabolites and 45 reactions, each with any user-defined or one of 35 predefined rate equations, one can produce trajectories of the metabolite concentrations and obtain a steady state (if it does exist). When steady-state solutions are produced, elasticity and control coefficients, as defined in metabolic control analysis, are calculated. GEPASI also allows the automatic generation of a sequence of simulations with different combinations of parameter values, effectively scanning a hyper-solid in parameter space. Together with the ability to produce user-defined columnar data files, these features allow for both very quick and systematic study of biochemical pathway models. The source code (in C) is available on request from the author, and while the user interface is dependent on having MS-Windows as the operating system, the numerical part is portable to other operating systems. GEPASI is suitable both for research and educational purposes. Although GEPASI was written with biochemical pathways in mind, it can equally be used to stimulate other dynamical systems.

Algorithms↗

PubMed1981

Modeling the metabolic pathways of methylazoxymethanol: a semiempirical molecular orbital study.

The NDDO semiempirical molecular orbital method (Kikuchi, 1977; Kikuchi and Maeda, 1977) was used to model proposed nonenzymatic metabolic pathways for the decomposition of methazoxymethanol (MAM) to a methyldiazonium ion. It was found that the lowest transition path involved protonation of the azoxy oxygen atom to form a six-membered transition state structure which decomposes to the methyldiazonium ion, CH2O, and a hydroxyl ion. This metabolic pathway is consistent with models proposed by Druckrey and Lange (1972) and Miyadera (1975). The calculations also suggest that methylazoxyformaldehyde, an enzymatic product of MAM, may directly alkylate to nucleic acid base sites.

Animals↗

PubMed1989

Water diffusion pathway, swelling pressure, and biomechanical properties of the intervertebral disc during compression load.

The behavior of water in the intervertebral disc of pig tail and its physiologic and biomechanical properties were investigated in relation to compression load. The water content, chemical composition, and swelling pressure in the intervertebral disc were measured, and the mechanism of the generation of the swelling pressure in relation to compression load stress was studied. The swelling pressure, through regulation of the water content of the disc and the resistance of the external load, differs with the region of the intervertebral disc. In the nucleus pulposus and the inner layer of the anulus fibrosus, the swelling pressure rises in proportion to the load, but few changes occur in the outer layer of the anulus fibrosus, and the constant pressure environment is thus maintained. The tritiated water (3H2O) uptake of the disc under various loads was measured. The molar partition coefficient of tritiated water is almost equal to 1 even under a compression load, which suggests that water is freely exchangeable. The diffusion of 3H2O in the intervertebral disc was traced using two pathway models: the perianular route and the end-plate route. The diffusion of water in the unloaded disc for both uptake and washout was about 2 to 3 times larger in the perianular route than in the end-plate route. Under load, the water diffusion was inhibited in both pathways. The relation between the load and displacement revealed viscoelastic properties indicating creep and stress relaxation. Young's modulus and the stiffness increased with a rise in load speed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Model of ion transport regulation in chloride-secreting airway epithelial cells. Integrated description of electrical, chemical, and fluorescence measurements.

An electrokinetic model was developed to calculate the time course of electrical parameters, ion fluxes, and intracellular ion activities for experiments performed in airway epithelial cells. Model variables included cell [Na], [K], [Cl], volume, and membrane potentials. The model contained apical membrane Cl, Na, and K conductances, basolateral membrane K conductance, Na/K/2 Cl and Na/Cl symport, and 3 Na/2 K ATPase, and a paracellular conductance. Transporter permeabilities and ion saturabilities were determined from reported ion flux data and membrane potentials in intact canine trachea. Without additional assumptions, the model predicted accurately the measured short-circuit current (Isc), cellular conductances, voltage-divider ratios, open-circuit potentials, and the time course of cell ion composition in ion substitution experiments. The model was used to examine quantitatively: (a) the effect of transport inhibitors on Isc and membrane potentials, (b) the dual role of apical Cl and basolateral K conductance in cell secretion, (c) whether the basolateral symporter requires K, and (d) the regulation of apical Cl conductance by cAMP and Ca-dependent signaling pathways. Model predictions gave improved understanding of the interrelations among transporting systems and in many cases gave surprising predictions that were not obvious without a detailed model. The model developed here has direct application to secretory or absorptive epithelial cells in the kidney thick ascending limb, cornea, sweat duct, and intestine in normal and pathophysiological states such as cystic fibrosis and cholera.

Animals↗