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Biomedical subjects

D E Meyer

Publications and source records attributed to D E Meyer.

At least 19 recordsLinked to original sources
PubMed2004

Effect of protein fusion on the transition temperature of an environmentally responsive elastin-like polypeptide: a role for surface hydrophobicity?

The limited throughput, scalability and high cost of protein purification by chromatography provide motivation for the development of non-chromatographic protein purification technologies that are cheaper and easier to implement in a high-throughput format for proteomics applications and to scale up for industrial bioprocessing. We have shown that genetic fusion of a recombinant protein to an elastin-like polypeptide (ELP) imparts the environmentally sensitive solubility property of the ELP to the fusion protein, and thereby allows selective separation of the fusion protein from Escherichia coli lysate by aggregation above a critical temperature (T(t)). Further development of ELP fusion proteins as widely applicable purification tools necessitates a quantitative understanding of how fused proteins perturb the ELP T(t) such that purification conditions (T(t)) may be predicted a priori for new recombinant proteins. We report here the effect that fusing six different proteins has on the T(t) of an ELP. A negative correlation between T(t) and the fraction hydrophobic surface area on the fused proteins was observed, which was determined from computer modeling of the available three-dimensional structure. The thermally triggered aggregation behavior of ELP-coated, functionalized gold colloids as well as ligand binding to the tendamistat-ELP fusion protein support the hypothesis that hydrophobic surfaces in molecular proximity to ELPs depress the ELP T(t) by a mechanism analogous to hydrophobic residue substitution in the ELP repeat, Val-Pro-Gly-Xaa-Gly.

Amino Acid Sequence↗
PubMed2001

Drug targeting using thermally responsive polymers and local hyperthermia.

We report a new thermal targeting method in which a thermally responsive drug carrier selectively accumulates in a solid tumor that is maintained above physiological temperature by externally applied, focused hyperthermia. We synthesized two thermally responsive polymers that were designed to exhibit a lower critical solution temperature (LCST) transition slightly above physiological temperature: (1) a genetically engineered elastin-like polypeptide (ELP) and (2) a copolymer of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm). The delivery of systemically injected polymer-rhodamine conjugates to solid tumors was investigated by in vivo fluorescence video microscopy of ovarian tumors implanted in dorsal skin fold window chambers in nude mice, with and without local hyperthermia. When tumors were heated to 42 degrees C, the accumulation of a thermally responsive ELP with a LCST of 40 degrees C was approximately twofold greater than the concentration of the same polymer in tumors that were not heated. Similar results were also obtained for a thermally responsive poly(NIPAAM-co-AAm), though the enhanced accumulation of this carrier in heated tumors was lower than that observed for the thermally responsive ELP. These results suggest that enhanced delivery of drugs to solid tumors can be achieved by conjugation to thermally responsive polymers combined with local heating of tumors.

Acrylamides↗
PubMed2001

Targeting a genetically engineered elastin-like polypeptide to solid tumors by local hyperthermia.

Elastin-like polypeptides (ELPs) are biopolymers of the pentapeptide repeat Val-Pro-Gly-Xaa-Gly that undergo an inverse temperature phase transition. They are soluble in aqueous solutions below their transition temperature (T1) but hydrophobically collapse and aggregate at temperatures greater than T1. We hypothesized that ELPs conjugated to drugs would enable thermally targeted drug delivery to solid tumors if their T1 were between body temperature and the temperature in a locally heated region. To test this hypothesis, we synthesized a thermally responsive ELP with a T1 of 41 degrees C and a thermally unresponsive control ELP in Escherichia coli using recombinant DNA techniques. In vivo fluorescence videomicroscopy and radiolabel distribution studies of ELP delivery to human tumors (SKOV-3 ovarian carcinoma and D-54MG glioma) implanted in nude mice demonstrated that hyperthermic targeting of the thermally responsive ELP for 1 h provides a approximately 2-fold increase in tumor localization compared to the same polypeptide without hyperthermia. We observed aggregates of the thermally responsive ELP by fluorescence videomicroscopy within the heated tumor microvasculature but not in control experiments, which demonstrates that the phase transition of the thermally responsive ELP carrier can be engineered to occur in vivo at a specified temperature. By exploiting the phase transition-induced aggregation of these polypeptides, this method provides a new way to thermally target polymer-drug conjugates to solid tumors.

Amino Acid Sequence↗
PubMed2001

Executive control of cognitive processes in task switching.

In 4 experiments, participants alternated between different tasks or performed the same task repeatedly. The tasks for 2 of the experiments required responding to geometric objects in terms of alternative classification rules, and the tasks for the other 2 experiments required solving arithmetic problems in terms of alternative numerical operations. Performance was measured as a function of whether the tasks were familiar or unfamiliar, the rules were simple or complex, and visual cues were present or absent about which tasks should be performed. Task alternation yielded switching-time costs that increased with rule complexity but decreased with task cuing. These factor effects were additive, supporting a model of executive control that has goal-shifting and rule-activation stages for task switching. It appears that rule activation takes more time for switching from familiar to unfamiliar tasks than for switching in the opposite direction.

Cognition↗
PubMed2001

Virtually perfect time sharing in dual-task performance: uncorking the central cognitive bottleneck.

A fundamental issue for psychological science concerns the extent to which people can simultaneously perform two perceptual-motor tasks. Some theorists have hypothesized that such dual-task performance is severely and persistently constrained by a central cognitive "bottle-neck," whereas others have hypothesized that skilled procedural decision making and response selection for two or more tasks can proceed at the same time under adaptive executive control. The three experiments reported here support this latter hypothesis. Their results show that after relatively modest amounts of practice, at least some participants achieve virtually perfect time sharing in the dual-task performance of basic choice reaction tasks. The results also show that observed interference between tasks can be modulated by instructions about differential task priorities and personal preferences for daring (concurrent) or cautious (successive) scheduling of tasks. Given this outcome, future research should investigate exactly when and how such sophisticated skills in dual-task performance are acquired.

Adult↗
PubMed2001

[Care and difference: from integration to fragmentation of being].

With this paper I intend to join to theorists who have discussed issues of difference and identity, with the aim of problematising some of the knowing/doing dimensions of nursing in contemporaneity. I am using as an analytical-theoretical background the Cultural Studies and Gender theories that develop a critical approach to post-structuralism. In the light of such a background I analyse some elements or constitutive aspects of the current theories on Care. I argue that to think care from the perspective of difference is to accept the challenge of not thinking about it as an action underpinned by scientific, philosophical and universal humanitarian assumptions, and start its theorisation and exercise as an action that is fundamentally political.

Cultural Characteristics↗
PubMed2000

Aging and the psychological refractory period: task-coordination strategies in young and old adults.

The apparently deleterious effect of aging on dual-task performance is well established, but there is little agreement about the source of this effect. Studies of the psychological refractory period (PRP) indicate that young adults can flexibly control dual-task performance through task-coordination strategies. Thus, the performance of older adults might differ from young adults because older adults use different task-coordination strategies. To test this hypothesis, the executive-process interactive control (EPIC) architecture was applied to quantify the reaction time data from two PRP experiments conducted with young (age 18-26) and older (age 60-70) adults. The results show that participants' ability to coordinate the processing of two tasks did not decline with age. However, dual-task time costs were greater in the older adults. Three sources for this increase were found: generalized slowing, process-specific slowing, and the use of more cautious task-coordination strategies by the older adults.

Adult↗
PubMed1999

Purification of recombinant proteins by fusion with thermally-responsive polypeptides.

Elastin-like polypeptides (ELPs) undergo a reversible, inverse phase transition. Below their transition temperature (Tt), ELPs are soluble in water, but when the temperature is raised above Tt, phase transition occurs, leading to aggregation of the polypeptide. We demonstrate a method for purification of soluble fusion proteins incorporating an ELP tag. Advantages of this method, termed "inverse transition cycling," include technical simplicity, low cost, ease of scale-up, and capacity for multiplexing. More broadly, the ability to environmentally modulate the physicochemical properties of recombinant proteins by fusion with ELPs will allow diverse applications in bioseparation, immunoassays, biocatalysis, and drug delivery.

Amino Acid Sequence↗
PubMed1997

A computational theory of executive cognitive processes and multiple-task performance: Part 1. Basic mechanisms.

A new theoretical framework, executive-process interactive control (EPIC), is introduced for characterizing human performance of concurrent perceptual-motor and cognitive tasks. On the basis of EPIC, computational models may be formulated to simulate multiple-task performance under a variety of circumstances. These models account well for reaction-time data from representative situations such as the psychological refractory-period procedure. EPIC's goodness of fit supports several key conclusions: (a) At a cognitive level, people can apply distinct sets of production rules simultaneously for executing the procedures of multiple tasks; (b) people's capacity to process information at "peripheral" perceptual-motor levels is limited; (c) to cope with such limits and to satisfy task priorities, flexible scheduling strategies are used; and (d) these strategies are mediated by executive cognitive processes that coordinate concurrent tasks adaptively.

Attention↗
PubMed1993

Spatial and temporal characteristics of rapid cursor-positioning movements with electromechanical mice in human-computer interaction.

This research examines how people make movements with pointing devices during human-computer interaction. It specifically concerns the perceptual-motor processes that mediate the speed and accuracy of cursor positioning with electromechanical mice. In three experiments we investigated the spatial and temporal characteristics of positioning movements made with a mouse, analyzing subjects' speed and accuracy as a function of the types of targets that the movements had to reach. Experiment 1 required rapid and accurate horizontal movements to targets that were vertical ribbons located at various distances from the mouse's starting location. The targets for Experiments 2 and 3, respectively, were vertical lines having various heights and rectangular boxes having various heights and widths. Constraints on movement distance along the primary (that is, horizontal) line of motion had the greatest effects on total positioning times. However, constraints on movement distance along a secondary (vertical) line of motion also affected total positioning times significantly. These effects may be localized in different phases of movements (e.g., movement execution and verification). The duration of movement execution (i.e., physical motion) depends primarily on the target distance, whereas the duration of movement verification (i.e., check for endpoint accuracy) depends primarily on target height and width. A useful account of movement execution is provided by stochastic optimized-submovement models, which have significant implications for designing mice and menu-driven displays.

Adult↗
PubMed1992

On the transmission of partial information: inferences from movement-related brain potentials.

Results are reported from a new paradigm that uses movement-related brain potentials to detect response preparation based on partial information. The paradigm uses a hybrid choice-reaction go/nogo procedure in which decisions about response hand and whether to respond are based on separate stimulus attributes. A lateral asymmetry in the movement-related brain potential was found on nogo trials without overt movement. The direction of this asymmetry depended primarily on the signaled response hand rather than on properties of the stimulus. When the asymmetry first appeared was influenced by the time required to select the signaled hand, and when it began to differ on go and nogo trials was influenced by the time to decide whether to respond. These findings indicate that both stimulus attributes were processed in parallel and that the asymmetry reflected preparation of the response hand that began before the go/nogo decision was completed.

Decision Making↗
PubMed1991

Function learning: induction of continuous stimulus-response relations.

This research investigates how people learn to select particular response magnitudes along one physical dimension (duration) when given stimulus magnitudes from another dimension (spatial extent). Stimuli and correct responses were related by either a power function, a logarithmic function, or a linear function with a positive intercept. The power function was learned quickly and accurately. In contrast, systematic response biases occurred during the early phases of learning the logarithmic and linear functions. As practice progressed, however, the biases gradually disappeared. These results support an adaptive regression model. According to it, people learn functions through a subjective process analogous to statistical regression. There is assumed to be an initial constraint that treats stimulus-response pairs as if a power function characterizes them.

Female↗
PubMed1991

Analyses of multinomial mixture distributions: new tests for stochastic models of cognition and action.

Mixture distributions are formed from a weighted linear combination of 2 or more underlying basis distributions [g(x) = sigma j alpha j fj(x); sigma alpha j = 1]. They arise frequently in stochastic models of perception, cognition, and action in which a finite number of discrete internal states are entered probabilistically over a series of trials. This article reviews various distributional properties that have been examined to test for the presence of mixture distributions. A new multinomial maximum likelihood mixture (MMLM) analysis is discussed for estimating the mixing probabilities alpha j and the basis distributions fj(x) of a hypothesized mixture distribution. The analysis also generates a maximum likelihood goodness-of-fit statistic for testing various mixture hypotheses. Stochastic computer simulations characterize the statistical power of such tests under representative conditions. Two empirical studies of mental processes hypothesized to involve mixture distributions are summarized to illustrate applications of the MMLM analysis.

Arousal↗
PubMed1990

Does motor programming necessitate response execution?

The complexity of a movement is known to affect the time it takes to initiate the movement. This effect is thought to reflect changes in the duration of processes that operate on a motor program. This question addressed here is whether programming a movement compels the start of its overt execution. If it does, then the programming processes may be said to occur after the "point of no return." We report results from an empirical procedure and a theoretical analysis designed to study processes before and after this point separately. According to our results, changes in the complexity of a movement affect only the prior set of processes. From this we argue that motor programming does not necessitate response execution and that the point of no return occurs very late in the information-processing system.

Adult↗
PubMed1990

Eye-hand coordination: oculomotor control in rapid aimed limb movements.

Three experiments are reported in which Ss produced rapid wrist rotations to a target while the position of their eyes was being monitored. In Experiment 1, Ss spontaneously executed a saccadic eye movement to the target around the same time as the wrist began to move. Experiment 2 revealed that wrist-rotation accuracy suffered if Ss were not allowed to move their eyes to the target, even when visual feedback about the moving wrist was unavailable. In Experiment 3, wrist rotations were equally accurate when Ss produced either a saccadic or a smooth-pursuit eye movement to the target. However, differences were observed in the initial-impulse and error-correction phases of the wrist rotations, depending on the type of eye movement involved. The results suggest that aimed limb movements use information from the oculomotor system about both the static position of the eyes and the dynamic characteristics of eye movements. Furthermore, the information that governs the initial impulse is different from that which guides final error corrections.

Adult↗
PubMed1989

Speed and accuracy of saccadic eye movements: characteristics of impulse variability in the oculomotor system.

Dynamic characteristics observed in the trajectories of saccadic eye movements reveal systematic variability of the force pulses used to move the eyes. This variability causes saccades to exhibit a linear speed-accuracy trade-off: As the average distance and duration of saccades toward specified target points increase, the standard deviations of saccadic-movement endpoints increase linearly with the saccades' average velocity. The linear trade-off, and other observed stochastic properties of saccades, may be attributed to noise in neuromotor processes and may be described in terms of an impulse-variability model originally designed for characterizing limb movements. According to the model, both eye and limb movements are controlled through stochastic force and time parameters that govern movement kinematics. Such an account may promote a unified conceptual framework for understanding a wide range of motor behavior.

Acceleration↗