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A systems model for low vision rehabilitation. I. Basic concepts.

The basic concepts and structure of a hierarchical systems model for low vision rehabilitation is developed and presented. The model is built on the assumption that the patient has a desired life state, which is not realized because of the visual impairment. Life state is defined as a set of activities that the individual wants or needs to perform. The activities that constitute life state are represented hierarchically in a system called the activity breakdown structure (ABS). The highest level of the ABS represents the objectives served by the activities (e.g., daily living, vocational, recreational, social, and educational objectives). Under each objective is a set of goals and serve that objective. Any goal could serve multiple objectives. The requirements for successfully achieving a goal may vary with the objective that goal serves. The lowest level of the ABS consists of tasks that must be performed successfully to achieve particular goals. Any task could serve multiple goals. Each goal and each task has a value to the patient (i.e., level of importance) and also is associated with a level of difficulty. The need for rehabilitation, which is captured in the formal construct rehabilitative demand, for each goal and its subsidiary tasks, scales with the value of the goal or task and with the difficulty in achieving the goal and/or performing the task. Successful rehabilitation will reduce rehabilitative demand by reducing the level of difficulty associated with the goal or task and/or by reducing the value assigned by the patient to the goal or task (as a result of counseling or of learning alternative strategies). Within the framework of the model, changes in rehabilitative demand define effectiveness of intervention.

Activities of Daily Living↗

The chick; a great model system becomes even greater.

The chick embryo has a long and distinguished history as a major model system in developmental biology and has also contributed major concepts to immunology, genetics, virology, cancer, and cell biology. Now, it has become even more powerful thanks to several new technologies: in vivo electroporation (allowing gain- and loss-of-function in vivo in a time- and space-controlled way), embryonic stem (ES) cells, novel methods for transgenesis, and the completion of the first draft of the sequence of its genome along with many new resources to access this information. In combination with classical techniques such as grafting and lineage tracing, the chicken is now one of the most versatile experimental systems available.

Animals↗

DNA-protein cross-linking: model systems for pyrimidine-aromatic amino acid cross-linking.

[reaction: see text] We have synthesized simple model systems to explore the possibility of photo-cross-linking between the pyrimidine bases and the side chains of the aromatic amino acids. Thymine/phenylalanine and thymine/tyrosine models gave cross-links, and thymine/tryptophan models gave complex mixtures; the cytosine/phenylalanine model was unreactive. The quantum yields for the model cross-linking reactions were 18-46 times smaller than those for thymine dimer formation. Biphotonic excitation contributes little to the yield of these reactions.

Amino Acids, Aromatic↗

Leadership-scholarship integration: using the Neuman systems model for 21st-century professional nursing practice.

This article describes leadership and scholarship from the Neuman systems model as requisite for a true practice model necessary for 21st-century scientific professional nursing. A rationale for the integration of leadership and scholarship is provided along with markers to guide the leadership-scholarship protocol, which can be viewed as a scholarly research process. An example from a community nursing center demonstrating the application of the integration of leadership-scholarship is presented to support the proposed integration.

Aged↗

Treatment of nonepileptic psychogenic events in adolescent patients using the systems model for intervention.

Nonepileptic psychogenic events in children, adolescents and adults can be difficult to treat. Using a systems framework intervention method resulted in significant reduction in nonepileptic psychogenic events. This method provides for a continuous flow of interaction, feedback and modification among the health care team, family and community. Common goals and plans are defined and implemented with a mechanism for feedback and modification. Using a systems model approach in educating the caregivers resulted in immediate and long-term reduction in nonepileptic psychogenic events.

Adolescent↗

Arrhythmia curve interpretation using a dynamic system model of the myocardial pacemaker.

A problem of identifying the phase response curve of the myocardial pacemaker was investigated using a simple dynamic system model of cardiac arrhythmia. A hybrid optimization method of a genetic algorithm and a local optimization technique was employed to obtain a solution of the model fitting. The method was applied to two categories of arrhythmias, ventricular parasystole and high-degree AV block. The present study offered a new insight into the mechanism of cardiac arrhythmias.

Animals↗

Mechanical properties of hydroxyapatite-reinforced gelatin as a model system of bone.

The elastic Young's modulus of hydroxyapatite-reinforced gelatin as a mechanical model system of bone was measured as a function of the volume fraction of hydroxyapatite, phi h. Initially, the Young's modulus gradually increased with an increase in phi h and then increased rapidly in the vicinity of phi h approximately 0.2. The phi h dependence of the Young's modulus was analysed by means of the theory of composite materials. It was found that with the increase in phi h the initial uniform stress deformation mode of the sample changed to the uniform strain deformation mode. The non-linear character in phi h dependence of the Young's modulus of this system was considered to reproduce well the novel behaviour of the mechanical properties of bone as a function of the mineral fraction. The situation was considered to be similar to a percolation problem. A preliminary analysis revealed that the critical exponent about the viscosity of the system accorded with the theoretically expected value. The result may present the evidence that the discontinuous point in mechanical properties of bone would be originated from an interaction such as a percolation of mineral particles on a matrix protein.

Biomechanical Phenomena↗

In vivo model systems in P-glycoprotein-mediated multidrug resistance.

In this article we review the in vivo model systems that have been developed for studying P-glycoprotein-mediated multidrug resistance (MDR) in the preclinical setting. Rodents have two mdr genes, both of which confer the MDR phenotype: mdr 1a and mdr 1b. At gene level they show strong homology to the human MDR1 gene and the tissue distribution of their gene product is very similar to P-glycoprotein expression in humans. In vivo studies have shown the physiological roles of P-glycoprotein, including protection of the organism from damage by xenobiotics. Tumors with intrinsic P-glycoprotein expression, induced MDR or transfected with an mdr gene, can be used as syngeneic or xenogenic tumor models. Ascites, leukemia, and solid MDR tumor models have been developed. Molecular engineering has resulted in transgenic mice that express the human MDR1 gene in their bone marrow and in knockout mice missing a murine mdr gene. The data on pharmacokinetics, efficacy, and toxicity of chemosensitizers of P-glycoprotein in vivo are described. Results from studies using monoclonal antibodies directed against P-glycoprotein and other miscellaneous approaches for modulation of MDR are mentioned. The importance of in vivo studies prior to clinical trials is being stressed and potential pitfalls due to differences between species are discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Connectionist networks in auditory system modeling.

Understanding how complex sounds, such as speech, are processed and eventually perceived in the brain is essential for building more effective speech processors. The echolocating bat provides an animal model for complex-sound processing of identified stimulus features at higher levels of the auditory pathway. In this paper, we present the use of connectionist models for modeling cortical neurons that play a key role in our auditory system model of a species of FM bat, Myotis lucifugus. The influence of network related parameters on modeling accuracy is presented, and the response of these models is explained in a behavioral context.

Acoustic Stimulation↗

PC12 cells: a model system for studying drug effects on dopamine synthesis and release.

PC12 cells were used as a model system to examine drug effects on dopamine synthesis and release. It could be demonstrated that KCl treatment induced release of endogenous dopamine, simultaneously DOPA synthesis was increased. Despite of the increase in DOPA synthesis the intracellular concentration of tetrahydrobiopterin (the co-factor of tyrosine hydroxylase) remained stable, indicating that the catalytic recycling of the used tetrahydrobiopterin is much more rapid than the tetrahydrobiopterin consumption by tyrosine hydroxylation. Reserpine induced a decrease of intracellular dopamine but no dopamine reached the extracellular space, instead all dopamine was depleted into the cytoplasma and metabolized to DOPAC. Nitrendipine had no effect on intracellular dopamine storage, Bay K 8644 induced a small decrease of intracellular dopamine and a small increase in DOPA production. N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W7) induced a reserpine-like depletion at concentrations above 1 X 10(-6) M. The KCl-induced dopamine release and the stimulation of DOPA production were blocked by 1 X 10(-7) M nitrendipine and enhanced by 1 X 10(-7) M Bay K 8466, whereas 1 X 10(-6) M W7 had no effect on both parameters. These findings were compared to data obtained in other tissues reported in the literature indicating that PC12 cells are a useful model for studying drug effects on catecholamine synthesis and release.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Systems model for pupil size effect. II. Feedback model.

The human pupillary control system has been the subject of interest to biologists and engineers as an example of a sensorimotor reflex which can be embedded in a control system paradigm. We present a nonlinear feedback model whose compact structure allows us to hypothesize possible physiological mechanisms which generate the proper behavior of the pupil system. The important pupil responses, including pupil size effect, asymmetry, and response the high-frequency stimuli, are defined. This model was simulated on a digital computer and comparisons to the paradigm experimental responses were performed, demonstrating a fit to each of the observed conditions. Improvements on previous models are discussed.

Feedback↗

Use of primate model system to identify Chlamydia trachomatis protein antigens recognized uniquely in the context of infection.

A primate model system was used to identify Chlamydia trachomatis antigens uniquely recognized in the context of infection. Serum antibody titres were measured in cynomolgus monkeys challenged urethrally with C. trachomatis serovar L2 elementary bodies (EBs). High-titre sera from these primates were used, in parallel with antisera against killed C. trachomatis EBs, to differentially screen an expression library of C. trachomatis serovar L2 DNA. Four clones were recognized only by antisera from infected monkeys. Sequence analysis revealed that three of these immunoreactive clones overlap a common ORF, designated ORF D242 (encoding p242), in the C. trachomatis genome database. The fourth clone contains two complete ORFs, each encoding 32 kDa proteins that share identity with Treponema pallidum TroA and TroB (ORFs D067 and D068 in the C. trachomatis database, respectively). Immunoblot analysis of Escherichia coli lysates expressing C. trachomatis TroA, TroB and p242 fusion proteins showed that p242 and TroA, but not TroB, were detected by the sera collected from infected primates. Antibodies directed at TroA and p242 were also detected in sera from several C. trachomatis-infected patients, demonstrating that these proteins are also recognized by humans following infection. Immunoblot analysis with antibody against TroA and p242 also demonstrated that both antigens are present in higher abundance in infected ChoK1 cells relative to purified C. trachomatis EBs. Immunofluorescence microscopy shows that TroA and p242 are both localized to intracellular developmental forms at the margins of growing inclusions. Collectively, these studies identify two C. trachomatis proteins that are under-represented in EBs and are recognized uniquely in the context of infection.

ATP-Binding Cassette Transporters↗

A yeast model system for functional analysis of beta-catenin signaling.

We have developed a novel Saccharomyces cerevisiae model system to dissect the molecular events of beta-catenin (beta-cat) signaling. Coexpression of mammalian beta-cat with TCF4 or LEF1 results in nuclear accumulation of these proteins and a functional complex that activates reporter gene transcription from constructs containing leukocyte enhancer factor (LEF)/T cell factor (TCF) response elements. Reporter transcription is constitutive, requires expression of both beta-cat and TCF4 or LEF1, and is not supported by mutated LEF/TCF binding elements or by TCF4 or LEF1 mutants. A cytoplasmic domain of E-cadherin or a functional fragment of adenomatous polyposis coli (APC) protein (APC-25) complexes with beta-cat, reduces beta-cat binding to TCF4, and leads to increased cytoplasmic localization of beta-cat and a reduction in reporter activation. Systematic mutation of putative nuclear export signal sequences in APC-25 decreases APC-25 binding to beta-cat and restores reporter gene transcription. Additional beta-cat signaling components, Axin and glycogen synthase kinase 3beta, form a multisubunit complex similar to that found in mammalian cells. Coexpression of the F-box protein beta-transducin repeat-containing protein reduces the stability of beta-cat and decreases reporter activation. Thus, we have reconstituted a functional beta-cat signal transduction pathway in yeast and show that beta-cat signaling can be regulated at multiple levels, including protein subcellular localization, protein complex formation, and protein stability.

Active Transport, Cell Nucleus↗

Mass exchange in an experimental new-generation life support system model based on biological regeneration of environment.

An experimental model of a biological life support system was used to evaluate qualitative and quantitative parameters of the internal mass exchange. The photosynthesizing unit included the higher plant component (wheat and radish), and the heterotrophic unit consisted of a soil-like substrate, California worms, mushrooms and microbial microflora. The gas mass exchange involved evolution of oxygen by the photosynthesizing component and its uptake by the heterotroph component along with the formation and maintaining of the SLS structure, growth of mushrooms and California worms, human respiration, and some other processes. Human presence in the system in the form of "virtual human" that at regular intervals took part in the respirative gas exchange during the experiment. Experimental data demonstrated good oxygen/carbon dioxide balance, and the closure of the cycles of these gases was almost complete. The water cycle was nearly 100% closed. The main components in the water mass exchange were transpiration water and the watering solution with mineral elements. Human consumption of the edible plant biomass (grains and roots) was simulated by processing these products by a unique physicochemical method of oxidizing them to inorganic mineral compounds, which were then returned into the system and fully assimilated by the plants. The oxidation was achieved by "wet combustion" of organic biomass, using hydrogen peroxide following a special procedure, which does not require high temperature and pressure. Hydrogen peroxide is produced from the water inside the system. The closure of the cycle was estimated for individual elements and compounds. Stoichiometric proportions are given for the main components included in the experimental model of the system. Approaches to the mathematical modeling of the cycling processes are discussed, using the data of the experimental model. Nitrogen, as a representative of biogenic elements, shows an almost 100% closure of the cycle inside the system. The proposed experimental model of a biological system is discussed as a candidate for potential application in the investigations aimed at creating ecosystems with largely closed cycles of the internal mass exchange. The formation and maintenance of sustainable cycling of vitally important chemical elements and compounds in biological life support systems (BLSS) is an extremely pressing problem. To attain the stable functioning of biological life support systems (BLSS) and to maintain a high degree of closure of material cycles in than, it is essential to understand the character of mass exchange processes and stoichiometnc proportions of the initial and synthesized components of the system.

Ammonia↗

Pharmacodynamics of abacavir in an in vitro hollow-fiber model system.

Abacavir is a potent new carbocyclic nucleoside analogue. We employed our hollow-fiber pharmacodynamic modeling system to examine the antiretroviral effects of different abacavir exposures, as well as the impact of the schedule of drug administration on efficacy. Dose ranging of abacavir revealed that a concentration of four times the 50% effective concentration (EC(50)) (approximately the EC(95)) was required to inhibit the replication of human immunodeficiency virus type 1 (HIV-1) (strain MN) either in a continuous-infusion hollow-fiber experiment or in a classical tissue culture flask experiment. In contrast to earlier work with another drug class (HIV-1 protease inhibitors), addition of physiological amounts of the human drug binding proteins albumin and alpha(1) acid glycoprotein revealed that there was little impact on the antiviral effect of the drug. Comparison of equivalent exposures (an area under the concentration-time curve [AUC] developed by approximately 500 mg per day of orally administered abacavir), either in a continuous-infusion mode or as a single oral dose of abacavir, demonstrated no difference in the ability to suppress either strain III(B) or strain MN. Comparison of administration of 250 mg every 12 h (q12h) versus once-daily administration of 500 mg for strain MN again showed no significant difference in suppressive effect. These experiments were carried out over 8 to 15 days. Because of these promising initial results, we extended the experiment to 30 days and examined three different schedules of administration that generated the same AUC at 24 h (AUC(24)): 300 mg q12h, 600 mg q24h, and 1,200 mg q48h. The aim of the last of these regimens was to definitively demonstrate schedule failure. There was little difference between the 1,200-mg q48h treatment group and the untreated control at 30 days. Likewise, there was little difference between the 600-mg q24h and 300-mg q12h treatment groups. However, at circa day 18 of the experiment, there was a small increase in viral output of p24 in the once-daily dosing unit. Examination of virus from all groups demonstrated no phenotypic or genotypic differences. The small difference in hollow-fiber unit p24 in the once-daily dosing group was not due to emergence of resistance over the 30-day single-drug exposure. We conclude that the dose of abacavir currently being studied in clinical trials (300 mg orally q12h) will be efficacious for the majority of sensitive clinical isolates of HIV-1. These in vitro data also suggest that this drug may be able to be administered to patients on a once-daily basis at a dose of 600 mg.

Anti-HIV Agents↗

A comparison of rotation- and blob-based system models for 3D SPECT with depth-dependent detector response.

We compare two different implementations of a 3D SPECT system model for iterative reconstruction, both of which compensate for non-uniform photon attenuation and depth-dependent system response. One implementation performs fast rotation of images represented using a basis of rectangular voxels, whereas the other represents images using a basis of rotationally symmetric volume elements. In our simulations the blob-based approach was found to slightly outperform the rotation-based one in terms of the bias-variance tradeoff in the reconstructed images. Their difference can be significant, however, in terms of computational load. The rotation-based method is faster for many typical SPECT reconstruction problems, but the blob-based one can be better-suited to cases where the reconstruction algorithm needs to process one volume element at a time.

Algorithms↗