Functional Fidelity Research Articles

Subnuclear organization and trafficking of regulatory proteins: Implications for biological control and cancer

The regulated and regulatory components that interrelate nuclear structure and function must be experimentally established. A formidable challenge is to define further the control of transcription factor targeting to acceptor sites associated with the nuclear matrix. It will be important to determine whether acceptor proteins are associated with a pre-existing core-filament structural lattice or whether a compositely organized scaffold of regulatory factors is dynamically assembled. An inclusive model for all steps in the targeting of proteins to subnuclear sites cannot yet be proposed. However, this model must account for the apparent diversity of intranuclear targeting signals. It is also important to assess the extent to which regulatory discrimination is mediated by subnuclear domain-specific trafficking signals. Furthermore, the checkpoints that monitor subnuclear distribution of regulatory factors and the sorting steps that ensure both structural and functional fidelity of nuclear domains in which replication and expression of genes occur must be biochemically and mechanistically defined. There is emerging recognition that placement of regulatory components of gene expression must be temporally and spatially coordinated to facilitate biological control. The consequences of breaches in nuclear structure-function relationships are observed in an expanding series of diseases that include cancer [Weis et al., 1994; Rogaia et al., 1997; Yano et al., 1997; Rowley, 1998; Zeng et al., 1998; McNeil et al., 1999; Tao and Levine, 1999a] and neurological disorders [Skinner et al., 1997]. As the repertoire of architecture-associated regulatory factors and cofactors expands, workers in the field are becoming increasingly confident that nuclear organization contributes significantly to control of transcription. To gain increased appreciation for the complexities of subnuclear organization and gene regulation, we must continue to characterize mechanisms that direct regulatory proteins to specific transcription sites within the nucleus so that these proteins are in the right place at the right time. J. Cell. Biochem. Suppl. 35:84-92, 2000.

The Selective Task Trainer: The Expert Solution

The current focus on using simulators for sustainment training in the squadron or unit is targeted toward an expert user. Past research on the physiology of motor skills, retention, part tasking, the “crutch effect,” automaticity skills, “generative” expert knowledge and ethnographic information support a new simulator design. A comparison of the novice to expert relationship illustrate the differences in performance skill needs. Current part tasking design technology does not support the expert's performance needs. However, new hardware and software technology can provide a low cost, high fidelity solution to the design of unit training devices. The proposed alternative in simulator design is called a selective task trainer. The characteristics of the selective task trainer include high physical and functional fidelity. Significantly lower cost and transportability allow the selective task trainers to be used in multiple player systems for local or long haul networking. The major shift in design focus is from a single high fidelity simulator with supporting part task man-in-the-loop devices to a set of four or more high fidelity devices. This design can be implemented without incurring a significant increase in cost when compared to the current costs of high fidelity simulators. Stand alone or networked operation of a set of devices provides ample opportunity for squadron or unit personnel to sustain a higher level of performance skill within a more realistic multi-ship tactical environment.

Chapter 4 Structural organization of GABAergic circuitry in ectotherm retinas

This chapter discusses visualizing gamma-aminobutyric acid–releasing (GABAergic) neurons, the scope of GABAergic organization throughout all vertebrates, and the general principles of GABAergic control throughout the retina. The first step in describing GABAergic circuits is to provide compelling evidence that GABAergic neurons themselves can be characterized with high functional and structural fidelity. There are three main cell biological mechanisms underlying the rapidity, sustainability, and potency of GABAergic neurotransmission: (1) the abilities of neurons to synthesize and mobilize GABA for release, (2) the precise and rapid control of extracellular neurotransmitter levels by potent pre-synaptic neurotransmitter/Na + symporters, and (3) the mediation of rapid postsynaptic conductance or synaptic efficacy changes by specific GABA receptors. Each of these features can theoretically be associated with visualization techniques. GABA immunoreactivity has been mapped to many vertebrate retinas, but the general patterns of organization in non-mammalians/ectotherms are easily demonstrated. A clear population of GABA immunoreactive horizontal cells can be seen in most species.

Display Design Guide for Visual Media

Visual display systems have become so advanced with available options, it is difficult to decide which type of system is needed. Traditionally, the choice has been to select the system with the greatest level of functional and physical fidelity that can be procured. While most would assume that more realism results in better training and performance, research (Dwyer, 1972; Marsh, 1983; Richey, 1986) suggests otherwise. Realism in a display system may serve to be more distracting than helpful, depending upon the training objective. The initial intent of this project was to locate any and all information pertaining to visual display characteristics as they relate to human visual functions or to visual training requirements. A selected literature search was conducted to locate relevant information, data bases or taxonomies that relate the above information. No current taxonomy of this kind was located; therefore, the efforts of the project turned in the direction of formulating a taxonomic structure based on information derived from various disciplines such as instructional technology, human psychology, and computer engineering. General guidelines only, with no specific information, pertaining to the selection of visual media for given situations were found in the instructional technology literature. Based on those guidelines, four general types of presentation media were selected: alphanumerics, 2-dimensional graphics, 3-dimensional graphics, and scene quality. Next, display specifications for these presentations were identified through the aid of engineering and vendor-provided design parameters. Finally, human limitations were applied and psychophysical transformations allowed the determination of final display descriptions.

Does streptomycin cause an error catastrophe?

We have examined the interpretation that streptomycin kills a bacterial culture by initiating the so-called error catastrophe [8]. In particular, we asked whether the increased translational error rate induced by the antibiotic gives rise to an autocatalytic loss of functional fidelity of the devices responsible for gene expression, which ultimately causes the death of the culture. We have analyzed the performance characteristics of one of these devices, namely the ribosome in streptomycin-treated bacteria. We find that, although the treated ribosomes are constructed from error-containing proteins, they are not significantly different in elongation rate and fidelity from those ribosomes taken from untreated bacteria. We conclude that the bacteriocidal effect of streptomycin is not due to the initiation of an error catastrophe.

Maintenance Training Simulator Fidelity and Individual Differences in Transfer of Training

This study was undertaken to investigate the relationship between simulator fidelity and training effectiveness. Two aspects of simulator fidelity were manipulated, namely, the degree to which a training simulator “looked like” actual equipment (physical fidelity), and the extent to which it “acted like” real equipment (functional fidelity). A transfer of training design was used to assess learning. Performance on an electromechanical troubleshooting task was correlated with a number of individual difference variables. Results indicated that physical and functional fidelity were interdependent and that temporal measures were most sensitive to fidelity manipulations. Low functional fidelity was associated with longer problem solution and inter-response times. Persons with high analytic abilities took longer to solve problems, but required fewer troubleshooting tests and made fewer incorrect solutions.

Simulator Fidelity in Electro-Mechanical Maintenance Training

A program of research aimed at investigating the degree of functional and physical fidelity needed in maintenance training simulators is described. A unique aspect of this work is the use of a generic reference system to serve as both an actual equipment trainer and system for simulation. This system as well as five training simulators differing in their functional and physical resemblance to the reference system are described. Program plans, objectives, and preliminary observations are discussed.