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Biomedical subjects

Jeff Miller

Publications and source records attributed to Jeff Miller.

15 recordsLinked to original sources
PubMed2004

Elimination of an immunodominant CD4+ T cell epitope in human IFN-beta does not result in an in vivo response directed at the subdominant epitope.

The BALB/cByJ mouse strain displays an immunodominant T cell response directed at the same CD4(+) T cell epitope peptide region in human IFN-beta, as detected in a human population-based assay. BALB/cByJ mice also recognize a second region of the protein with a lesser magnitude proliferative response. Critical residue testing of the immunodominant peptide showed that both BALB/cByJ mice and the human population response were dependent on an isoleucine residue at position 129. A variant IFN-beta molecule was constructed containing the single amino acid modification, I129V, in the immunodominant epitope. The variant displayed 100% of control antiproliferation activity. Mice immunized with unmodified IFN-beta responded weakly in vitro to the I129V variant. However, BALB/cByJ mice immunized with the I129V variant were unable to respond to either the I129V variant or the unmodified IFN-beta molecule by either T cell proliferation or Ag-specific IgG1 Ab production. This demonstrates that a single amino acid change in an immunodominant epitope can eliminate an immune response to an otherwise intact therapeutic protein. The elimination of the immunodominant epitope response also eliminated the response to the subdominant epitope in the protein. Modifying functionally immunodominant T cell epitopes within proteins may obviate the need for additional subdominant epitope modifications.

Animals↗
PubMed2004

Exaggerated redundancy gain in the split brain: a hemispheric coactivation account.

Recent studies of redundancy gain indicate that it is especially large when redundant stimuli are presented to different hemispheres of an individual without a functioning corpus callosum. This suggests the hypothesis that responses to redundant stimuli are speeded partly because both hemispheres are involved in the activation of the response. A simple formal model incorporating this idea is developed and then elaborated to account for additional related findings. Predictions of the latter model are in good qualitative agreement with data from a number of sources, and there is neuroanatomic and psychophysiological support for its underlying structure.

Brain↗
PubMed2004

Threshold estimation in two-alternative forced-choice (2AFC) tasks: the Spearman-Kärber method.

The Spearman-Kärber method can be used to estimate the threshold value or difference limen in two-alternative forced-choice tasks. This method yields a simple estimator for the difference limen and its standard error, so that both can be calculated with a pocket calculator. In contrast to previous estimators, the present approach does not require any assumptions about the shape of the true underlying psychometric function. The performance of this new nonparametric estimator is compared with the standard technique of probit analysis. The Spearman-Kärber method appears to be a valuable addition to the toolbox of psychophysical methods, because it is most accurate for estimating the mean (i.e., absolute and difference thresholds) and dispersion of the psychometric function, although it is not optimal for estimating percentile-based parameters of this function.

Choice Behavior↗
PubMed2004

Effects of redundant visual stimuli on temporal order judgments.

Four experiments were conducted in order to compare the effects of stimulus redundancy on temporal order judgments (TOJs) and reaction times (RTs). In Experiments 1 and 2, participants were presented in each trial with a tone and either a single visual stimulus or two redundant visual stimuli. They were asked to judge whether the tone or the visual display was presented first. Judgments of the relative onset times of the visual and the auditory stimuli were virtually unaffected by the presentation of redundant, rather than single, visual stimuli. Experiments 3 and 4 used simple RT tasks with the same stimuli, and responses were much faster to redundant than to single visual stimuli. It appears that the traditional speedup of RT associated with redundant visual stimuli arises after the stimulus detection processes to which TOJs are sensitive.

Adult↗
PubMed2004

A computer program for Spearman-Kärber and probit analysis of psychometric function data.

PMETRIC is a computer program for the analysis of observed psychometric functions. It can estimate the parameters of these functions, using either probit analysis (a parametric technique) or the Spearman-Kärber method (a nonparametric one). For probit analysis, either a maximum likelihood or a minimum chi 2 criterion may be used for parameter estimation. In addition, standard errors of parameter estimates can be estimated via bootstrapping. The program can be used to analyze data obtained from either yes-no or m-alternative forced-choice tasks. To facilitate the use of PMETRIC in simulation work, an associated program, PMETGEN, is provided for the generation of simulated psychometric function data. Use of PMETRIC is illustrated with data from a duration discrimination task.

Computer Simulation↗
PubMed2003

Simple reaction time and statistical facilitation: a parallel grains model.

A race-like model is developed to account for various phenomena arising in simple reaction time (RT) tasks. Within the model, each stimulus is represented by a number of grains of information or activation processed in parallel. The stimulus is detected when a criterion number of activated grains reaches a decision center. Using the concept of statistical facilitation, the model accounts for many classical effects on mean simple RT, including those of stimulus area, stimulus intensity, stimulus duration, criterion manipulations, redundant stimuli, and the dissociation between intensity effects on simple RTs and temporal order judgments. The model is also consistent with distributional properties of simple RTs.

Humans↗
PubMed2003

The locus of redundant-targets and nontargets effects: evidence from the psychological refractory period paradigm.

In target detection tasks, responses are faster when displays have 2 targets (redundant-targets effect; RTE) and slower when they have no targets (nontargets effect; NTE) relative to displays with a single target. The psychological refractory period paradigm was used to localize these effects. In Experiment 1, participants classified tones as high or low and then classified letters as targets or nontargets after a short or long stimulus onset asynchrony (SOA). The magnitudes of the RTE and NTE did not depend on SOA. In Experiment 2, the order of the tasks was reversed, and at short SOAs the RTE and NTE had similar magnitudes for both tone discrimination and target detection responses. These findings suggest that the RTE and NTE arise during response selection. Interactive effects of tone pitch with the number and type of target features were also observed, and these were tentatively interpreted as synesthetic effects.

Humans↗
PubMed2002

Cortical movement preparation before and after a conscious decision to move.

The idea that our conscious decisions determine our actions has been challenged by a report suggesting that the brain starts to prepare for a movement before the person concerned has consciously decided to move (Libet, Gleason, Wright, & Pearl, 1983). Libet et al. claimed that their results show that our actions are not consciously initiated. The current article describes two experiments in which we attempted to replicate Libet et al.'s comparison of participants' movement-related brain activity with the reported times of their decisions to move and also the reported times of their decisions of which hand to move. We also looked at the distribution of participants' reports over time to evaluate an alternative explanation of Libet et al.'s (1983) results. Although the Readiness Potential was usually present before all of the decisions to move, consistent with the findings of Keller and Heckhausen (1990) and Libet et al. (1983), we found that many reported decision times were before the onset of the Lateralized Readiness Potential, which measures hand-specific movement preparation. The latter finding is consistent with the conclusion that the LRP always started after the conscious decision to move. We conclude that even though activity related to movement anticipation may be present before a conscious decision to move, the cortical preparation necessary for the movement to happen immediately may not start until after the conscious decision to move.

Cerebral Cortex↗
PubMed2002

Queuing or sharing? A critical evaluation of the single-bottleneck notion.

The model of a single central bottleneck for human information processing is critically examined. Most evidence cited in support of the model has been observed within the overlapping tasks paradigm. It is shown here that most findings obtained within that paradigm and that were used to support the model are also consistent with a simple resource model. The most prominent findings are the millisecond-for-millisecond slope at the left of the RT2-SOA curve, the high RT1-RT2 correlation, the additivity of the effects on RT2 of SOA and of the difficulty of selecting R2, and the washout of the effect of S2 discriminability on RT2 in a dual-task condition. In addition, the asymmetry of the effects of the dual-task requirement on RT1 and RT2 can be accounted for by the resource model provided that it assumes uneven allocation of resources, which is quite reasonable in view of the task asymmetry inherent in the demand characteristics of the paradigm. The same is true for two other findings that appear to support the single-bottleneck model-that in the dual-task condition, the demand of the first task affects equally RT1 and RT2 and that its effect on RT1 is the same as the corresponding effect in the single-task condition. Furthermore, the single-bottleneck model is hard to reconcile with a negative slope at the left of the RT1-SOA curve or a positive slope at the left of the IRI-SOA curve, unless augmented by ancillary assumptions that are yet to be substantiated. Representative data were fit by each of the models using its optimal set of parameters. Both models achieved quite good degrees of fit. It is further argued that since the overlapping tasks paradigm is heavily biased in favor of a speedy reaction to the stimulus that appears first, it is nonoptimal for testing the central bottleneck model. Finally, the bottleneck model is examined in terms of other scientific criteria.

Humans↗
PubMed2002

Global precedence and response activation: evidence from LRPs.

Lateralized readiness potentials (LRPs) were measured in left/right/no-go tasks using compound global/local stimuli. In Experiment 1, participants responded to local target shapes and ignored global ones. RTs were affected by the congruence of the global shape with the local one, and LRPs indicated that irrelevant global shapes activated the responses with which they were associated. In Experiment 2, participants responded to conjunctions of target shapes at both levels, withholding the response if a target appeared at only one level. Global shapes activated responses in no-go trials, but local shapes did not. The results are consistent with partial-output models in which preliminary information about global shape can partially activate responses that are inconsistent with the local shape. They also demonstrate that part of the global advantage arises early, before response activation begins and probably before recognition of the local shape.

Adolescent↗
PubMed2002

Effects of response readiness on reaction time and force output in people with Parkinson's disease.

Previous research investigated effects of response readiness in neurologically normal subjects by manipulating the probability of responding. With a high probability of responding, reaction time is fast and the level of response force is low compared with conditions with a low probability of responding. An elaborated view of response readiness assumes that these effects reflect properties associated with the transmission of response activation to the motor output system. The present study employed high- and low-probability trials in a go/no-go task, to investigate whether these processes are impaired in people with mild to moderate Parkinson's disease. It was hypothesized that the patients would demonstrate abnormal patterns of response force with manipulations of response readiness. It was further hypothesized that the patients would display evidence of inability to inhibit responses on no-go trials. Both hypotheses were supported, suggesting that a basic deficit associated with Parkinson's disease is related to the transmission of response activation to the motor system. Response modulation appears to depend on the integrity of basal ganglia structures.

Adolescent↗
PubMed2002

Response slowing in Parkinson's disease: a psychophysiological analysis of premotor and motor processes.

The mechanisms responsible for reaction time slowing in Parkinson's disease were investigated using movement-related potentials in a choice reaction time task. Parkinson's disease patients and control subjects were required to respond with the left or right hand to indicate whether a visual stimulus was relatively large or small. The difficulty of the size discrimination was manipulated, as was the complexity of the manual response (single key press versus sequence of three key presses). Behavioural responses of Parkinson's disease patients were slower than those of control subjects, especially when complex responses were required. Moreover, the timing of movement-related potentials indicated that motor processes clearly required extra time, relative to control subjects, for Parkinson's disease patients making complex responses. In addition, delayed onset of the movement-related potentials indicated that one or more premotor processes are also slowed in these patients.

Aged↗
PubMed2002

Communication between animal cells and the plant foods they ingest: phyto-zooidal dependencies and signaling (Review).

The beneficial effect of plant foods on human health is unmistakable. Time and time again, studies have found foods of plant origin to reduce the risk of most major chronic illnesses suffered by the human population. Possible mechanisms for the preventative effects of these foods are discussed. Each of the plant groups reviewed was found to reduce the risk of one or more of the following: cardiovascular disease, cancer (lung, breast, colon, rectal, prostate, epithelial, stomach, esophageal, oral, pharynx, larynx, urinary tract, endometrium, pancreas, thyroid, liver, ovary, gallbladder, bladder, and kidney), diabetes, hypertension, bone degeneration, diverticulitis, constipation, gallstones, age-related blindness. Almost no evidence was found to suggest a negative effect on health due to consumption of these plant foods. Based on this material and a review of conserved animal signaling molecules we surmise that animals require these chemicals to enhance specific mammalian cellular processes, demonstrating phyto-zooidal signaling. Further, this diet dependency coupling between plants and animals probably evolved because of the abundance of a particular plant material in a local environment, which is now broken because of technological advances. In conclusion, the overwhelming majority of evidence shows that people may significantly decrease their risks of the aforementioned diseases by increasing their intake of these foods since they represent a natural method to enhance animal processes and signaling.

Animal Population Groups↗
PubMed2002

Online response preparation in a rapid serial visual search task.

Online response preparation was assessed in a visual search task using rapid serial visual presentation. In each trial, a series of letters was presented sequentially, and participants were instructed to make a target-present response if a prespecified target letter was presented or a target-absent response if it was not. Measurements of response preparation using both probe reaction time and the lateralized readiness potential indicated that preparation of the target-absent response increased near the end of the sequence. Most of the increase appeared to be due to direct priming of the target-absent response by nontarget letters, but part was due to the increased conditional probability of this response near the end of the sequence. These results extend previous studies of response preparation by showing online response preparation during a temporally extended reaction time task.

Adolescent↗