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PubMed2005

Centralized data analysis of a large interlaboratory proteomics project: a feasibility study.

The human Plasma Proteome Project (PPP) is a large-scale collaboration between many laboratories. One of the most demanding tasks in the PPP involved the analysis of very large amounts of raw MS/MS data produced by the participants. The main approach for managing this task was letting the participants analyze their own data and submit the results to the central PPP repository as lists of identified proteins and peptides. To complement this distributed approach, we also performed centralized analysis of the raw MS/MS data provided by the participants. Due to the data redundancy inherent in such a project, centralized analysis has the potential to reduce the computational effort by reducing redundancy before the analysis. Centralized analysis can also unify the process and take advantage of data sharing among laboratories to improve protein identification and validation. The process we employed included removing low-quality spectra, clustering spectra by mutual similarity, and applying uniform peptide and protein identification procedures. To demonstrate the process, we analyzed 5.28 million MS/MS spectra derived by eight laboratories from tryptic peptides of serum and plasma proteins.

Blood Proteins↗

PubMed1993

A modified alkaline lysis method for the preparation of highly purified plasmid DNA from Escherichia coli.

We have developed a very efficient and rapid method for the preparation on a small or large scale of highly purified plasmid DNA from Escherichia coli. The procedure consists of five steps: (1) cell lysis by NaOH-SDS, (2) precipitation of cell lysate with 2 M potassium acetate-1 M acetic acid, (3) precipitation of the resulting supernatant with isopropanol, (4) treatment of the precipitate with RNase, and (5) a second isopropanol precipitation. The new procedure yields a plasmid DNA that is more than 90% in the supercoiled form and virtually free from proteins, RNA, and chromosomal DNA. We have thoroughly tested the method in the preparation of several thousand samples of different plasmids from various E. coli strains. We found that it consistently produced samples of plasmid DNA suitable for all routine uses such as restriction analysis, sequencing, and preparation of DNA probes for cloning and hybridization experiments. Moreover, plasmids purified by this procedure could fully replace plasmids purified on CsCl gradients for more demanding tasks such as the in vitro synthesis of RNA probes by phage RNA polymerases, the generation of deletion mutants with exonuclease III, and the transfection of mammalian cells by the calcium phosphate coprecipitation method, as tested on human fibroblasts and on CV-1 cells.

Animals↗

PubMed1993

Hemisphere and gender differences in mental rotation.

Hemisphere and gender differences in mental rotation for tachistoscopically presented stimuli were assessed in 40 right-handed university students. Twenty male and 20 female subjects each were individually administered (via computer) a mental rotation task which included 10 stimulus presentations at each of eight angular disorientations (0 degrees, 45 degrees, 90 degrees, 135 degrees, 180 degrees, 225 degrees, 270 degrees, and 315 degrees) in each visual half-field (VHF) for a total of 160 trials. Analyses of variance performed on reaction time and accuracy data revealed only a main effect for orientation. A typical mental rotation function for both the left VHF and the right VHF for both genders resulted; however, no gender x visual field interaction was found. Lack of hemisphere and gender differences provide further evidence questioning the interpretation of right-hemisphere male superiority for spatial tasks. Investigation into factors such as task complexity, stimulus familiarity, and task demands may lend further insight into hemisphere and gender differences in mental rotation.

Adolescent↗

PubMed1993

Perceptual processing of pattern goodness by left and right hemispheres.

Two experiments tested perceptual processing of Garner and Clement's (1963) good and poor five-dot patterns by the left and right hemispheres. Two (good) patterns were from four-member equivalence sets, and the other (poor) pattern was from an eight-member equivalence set. One of the good patterns formed a T shape that could be processed as a linguistic unit. In Experiment 1, 80 right-handed subjects made same-different judgments for lateralized 200-msec paired presentations of these patterns. When both presentations were to the RVF/LH, response latency was faster for the T pattern than for the other two. When both presentations were to the LVF/RH, response latency was faster for the two good patterns than for the poor pattern. When the first pattern was presented to the RVF/LH and the second was presented to the LVF/RH, response latencies were lower for the two good patterns than for the poor pattern. Also, when the first pattern was presented to the LVF/RH and the second was presented to the RVF/LH, response latency was faster for the T pattern than for the other good pattern which was, in turn, faster than for the poor pattern. Experiment 2 used a duration judgment task (Avant & Lyman, 1975) to test effects of pattern goodness on apparent durations of pre- and postmasked 10-msec pattern presentations. With left hemisphere inputs, presentations of good patterns were judged to be longer than presentations of the poor pattern. When each hemisphere compared the T and the other good pattern, presentations of the T pattern were judged to be longer, and the right hemisphere further discriminated among pattern orientations. Presentations of the T pattern to each hemisphere were judged to be longer than presentations of the poor pattern, and both hemispheres discriminated among orientations of both patterns. These results indicate that the two hemispheres can, during perceptual processing, function cooperatively, and that both prerecognition and conscious perceptual operations are guided by task demands.

Adult↗

PubMed1997

Letter-case-specific priming in the right cerebral hemisphere with a form-specific perceptual identification task.

In a form-specific perceptual identification task, subjects identify and write letter strings in the same letter case as they appear on a computer display. Letter-case-specific repetition priming was observed in this task when test items were presented directly to the right hemisphere, but not when they were presented directly to the left hemisphere, similar to results in previous word-stem completion experiments. This pattern of results was not obtained in a standard perceptual identification task. Results indicate that a specific visual-form subsystem, but not an abstract visual-form subsystem, operates more effectively in the right hemisphere than in the left, and task demands greatly affect which subsystems are recruited in different priming tests.

Brain↗

PubMed2001

Visual signal detection measured by event-related potentials.

Signal Detection tasks typically involve within-subject signal changes. Such a procedure does not lend itself to event-related potential (ERP) experiments where the need for averaging necessitates the maintenance of consistent stimulus parameters. In the present ERP study we adopt a novel approach to thresholding that allows within-subject signal manipulation. The Signal Detection task required the identification of letter targets, formed from dots, in a random dot field. ERP waveforms were segmented into three windows corresponding to N1, N2, and P300 components. Analysis shows that ERP variations are dependent on both task demands and response characteristics for N1, N2, and P300 components.

Adolescent↗

PubMed1993

An investigation of attention allocation deficits in aphasia.

Nine aphasic and 18 normal adults participated in a dual task with components of phoneme monitoring and semantic judgment. Subjects listened to lists of recorded spoken words and were required to detect semantic and phonetic targets. Two within-subject variables were manipulated: the probability of target occurrence for each dual-task component (.2, .5, and .8) and the explicitness of instruction (explicit vs. implicit). Only in the explicit condition were subjects told about the probability structure and given the attention allocation strategy congruent with that structure. Reaction times were recorded on-line for analysis by an IBM-AT. The results showed that normal subjects' overall latencies in detecting phonetic targets decreased as the target occurrence probability increased in both implicit and explicit instruction conditions. The detection latencies for semantic targets showed a similar probability effect but only in the explicit condition. By contrast, the aphasic subjects did not show the probability effect in any condition, although they performed above the chance level on both semantic and phonetic tasks. The presence of the probability effects for the normal subjects indicated that an efficient attention allocation mechanism was operating so as to optimize the performance level. On the other hand, the absence of probability effects for the aphasic subjects suggests that their attention control system might be inefficient so that task-demand cues (probability and attention allocation instruction) were not utilized properly.

Adult↗

PubMed1995

On the notion of a "subtle phonetic deficit" in fluent/posterior aphasia.

Phonetic investigations in the past decade or so have reported instances of a "subtle phonetic deficit" in the fluent aphasias, thereby challenging the traditional dichotomy of a motoric deficit characterizing the nonfluent aphasias and a selection deficit characterizing the fluent aphasias. This paper critically reviews the acoustic, physiological, and perceptual studies which have attempted to examine this phenomenon. These investigations have been evaluated in terms of differences in subject populations, task demands, subjects' performance, and problematic interpretations. Suggestions are offered for an experimental design which can help us operationalize this term and help us to better understand the speech production deficit in fluent aphasic patients.

Aphasia, Wernicke↗

PubMed2001

Assessing working memory and language comprehension in Alzheimer's disease.

Studies of language impairments in patients with Alzheimer's disease have often assumed that impairments in linguistic working memory underlie comprehension deficits. Assessment of this hypothesis has been hindered both by vagueness of key terms such as "working memory" and by limitations of available working memory tasks, in that many such tasks either seem to have little relationship to language comprehension or are too confusing or difficult for Alzheimer's patients. Four experiments investigated the usefulness of digit ordering, a new task assessing linguistic working memory and/or language processing skill, in normal adults and patients with probable Alzheimer's disease. The digit ordering task was shown to be strongly correlated with the degree of dementia in Alzheimer's patients. The task correlated with measures of language processing on which patients and normal controls performed differently. The results are interpreted as indicating that linguistic representations, linguistic processing, and linguistic working memory are intertwined, such that a deficit of one (e.g., working memory) cannot be said to "cause" a deficit in the other. The implications of this approach are explored in terms of task demands in comprehension and memory measures, and interpretation of previous results in the literature.

Aged↗

PubMed1998

Knowledge enrichment and conceptual change in folkbiology: evidence from Williams syndrome.

Ten participants with Williams syndrome (WS) (average verbal mental age of 11;5) were compared to two groups of normally developing children (average mental ages 10;11 and 6;7 years) with respect to intuitive biological knowledge about people, animals, and plants. Participants in the older control group were individually matched to the participants with WS on verbal mental age. The probes for biological understanding were drawn from the existing literature on the development of folkbiology and were divided into two batteries based on the hypothesized distinction of (1) general knowledge consistent with the conceptual repertoire of normally developing preschool children (the T1/T2-Neutral Animal Knowledge battery) and (2) folkbiological concepts normally acquired between ages 6 and 12 which require conceptual change for their construction (life, death, people-as-one-animal-among-many, species kind as determined by origin of the animal; the T2-Dependent battery). The two task batteries were equated for task demands, differing only in the content of the concepts probed. It was hypothesized that if this distinction is a false one, and the construction of folkbiology is accomplished entirely by enrichment of the preschooler's knowledge, there should never be a population with differential performance on these two batteries. People with WS were nonetheless found to be differentially impaired on the T2-Dependent battery. They performed at the level of the older control group on the T1/T2-Neutral battery, but at the level of the 6-year-olds on the T2-Dependent battery. These data support the distinction between two types of conceptual knowledge acquisition: acquisition of new knowledge formulated over an existing conceptual base (enrichment), on the one hand, and knowledge acquisition that results in genuine conceptual change, on the other. The implication of these results for a precise characterization of how concepts of people with "cocktail party syndrome" may be "superficial" is also discussed.

Adolescent↗

PubMed2002

The human first hypothesis: identification of conspecifics and individuation of objects in the young infant.

How do infants individuate and track objects, and among them objects belonging to their species, when they can only rely on information about the properties of those objects? We propose the Human First Hypothesis (HFH), which posits that infants possess information about their conspecifics and use it to identify and count objects. F. Xu and S. Carey [Cognitive Psychology, 30(2), 111-153, 1996] argued that before the age of 1 year, infants fail to use property information. To explain their results, Xu and Carey proposed the Object First Hypothesis (OFH), according to which infants under 1 year of age have only the general concept of physical object to identify and count objects. We show that infants have a more extensive knowledge of sortals than that claimed by the OFH. When 10-month-olds see one humanlike and one non-humanlike object, they successfully identify and count them by using the contrast in their properties, as predicted by the HFH. We also show that infants succeed even when they make a decision based on differences between two close basic-level categories such as humanlike objects and doglike objects, but fail when they have to use differences within the human category. Thus, infants treat "human" as a basic sortal, as predicted by the HFH. We argue that our results cannot be accounted for by general purpose mechanisms. Neither the strong version of the OFH and its explanation in terms of object indexing mechanisms [A. M. Leslie, F. Xu, P. Tremoulet, & B. J. Scholl, Trends in Cognitive Sciences, 2(1), 10-18, 1998] nor explanations in terms of task demands [T. Wilcox & R. Baillargeon, Cognitive Psychology, 37(2), 97-155, 1998] are sufficient to explain our results.

Child Development↗

PubMed2000

Predictors of Patient Inability to Cooperate during Intraoperative Language Mapping.

We examined the demographic, seizure history, personality, and intellectual variables in seizure surgery patients who underwent intraoperative language mapping to identify variables that may help predict inability to cooperate with intraoperative mapping. Of 26 patients who had intraoperative language testing during left hemisphere lobectomy, 9 were unable to cooperate with language mapping procedures. Mapping "failure" consisted of an inability to conform to task demands due to anxiety, inattention, immaturity, or confusion that necessitated changing from local to general endotracheal anesthesia. Patients who were unable to cooperate with intraoperative mapping had significantly lower IQs, lower educational attainment, and higher Depression scale scores on the Minnesota Multiphasic Personality Inventory (MMPI) relative to cooperative patients. There were no statistically significant differences between groups with respect to age, handedness, sex, age of onset of habitual seizures, seizure type, site of seizure focus, presence of a lesion, or previous psychiatric history.

Journal Article↗

PubMed1993

When is a mug not a mug? Effects of content, naming, and instructions on children's drawings.

Two hundred seventy 5-year-old children produced a copy drawing of a transparent glass mug with its handle turned away. In a factorial design three factors were manipulated to examine their additive or independent influence on the child's production of either view-specific or canonical (i.e., with the handle at the side) depictions: the content of the mug, the label used to describe it, and the explicitness of instruction. The results showed, first, that each of these variations in task demands exerted an influence on the canonicality/view-specificity of the children's drawings. Second, these influences were both facilitative and prohibitive. So, for example, general instructions prompted canonical drawings, while very explicit instructions elicited view-specific depictions. Third, each factor exerted an independent influence upon whether or not the handle was included--there were no interactions between factors on the production of the two types of picture. These results provide further evidence against simple associations between children's drawings and their cognitive abilities. They suggest that what children produce in studies of "drawing" may well simply inform us about the development of an understanding of adults' communicative intent.

Age Factors↗

PubMed1997

Dichotic listening in children: the reflection of verbal and attentional changes with age.

A sample of 290 kindergarten children (147 girls), all native Hebrew speakers, were tested by two dichotic listening tests: (a) a digits test (low verbal workload) and (b) a words test (high verbal workload). The same subjects were tested one year later (at the end of their first year at school) by the same tests. In both tests and both testing sessions the free recall procedure was used. It was found that the performance difference between ears significantly decreased and overall performance significantly increased in the digits test in the second testing session. Differences between sessions in ear difference in the words test were not significant, although overall performance in the second session increased. These data lend support to the hypothesis that the change with age in the between-ears difference is mainly related to an improvement in verbal processing efficiency, which in turn allows the allocation of more verbal resources to the inferior input channel, without a decrease in resources allocated to the preferred one. As expected, increase in available verbal resources was clearly manifested under low verbal workload conditions but not under high workload conditions, where task demands did not allow significant increase in verbal resources to be allocated to the inferior channel. This hypothesis also predicted highly consistent ear preference owing to its being solely determined by the verbal processors of the dominant-to-speech hemisphere. The inconsistent ear preference between tests found in more than a third of the subjects of this sample could not therefore be accounted for by the stated hypothesis. The analysis of performance in subjects who showed left-ear preference in only one test and right-ear advantage on the other occasions indicated that whenever the left ear was preferred it was accompanied by significantly smaller ear difference and lower overall performance compared with those manifested by the same subjects in the same test in the other testing session. These data are better accounted for by the hypothesis that two different pools of resources are involved in splitting attention between ears in the free recall of dichotically presented verbal stimuli: one which is controlled by verbal processors of the dominant-to-speech hemisphere and the other by a spatial attentional mechanism. However, it seems that changes in dichotic test performance within the first year at school can mainly be attributed to increase in verbal resources rather than to improvement in allocation of spatially controlled resources.

Age Factors↗

PubMed1997

Linguistic influences on children's number concepts: methodological and theoretical considerations.

From observations of how children match numerals to number tokens, previous research has suggested that cognitive representations of numbers vary with the linguistic demarcation of numerals. It is argued here that this paradigm does not always support the idea that language affects number concepts and that children's performance is shaped by other constraints. In Experiment 1, increasing the salience of multiple unit tokens significantly altered the distribution of response strategies in 6 1/2- to 7 1/2-year-old children. In Experiments 2 and 3, the importance of instructions in biasing responses is demonstrated, as 5 1/2- to 7 1/2-year-old children's use of multiunit tokens increased when given an example of their potential use. It appears that the task reflects in part children's interpretations and misinterpretations of task demands. Implications for the role of language in acquiring base-10 number concepts are discussed.

Child↗

PubMed1998

Error Correction Processes in Temporal Pattern Production.

A second-order autoregressive model for error correction is applied to measurements of synchronized tapping by an expert and a nonexpert subject for a wide range of patterns, ranging from simple off-beat tapping to a complex polyrhythm. The model can be seen as an extension of the first order approach of Vorberg and Wing and, also, as a linearized version of a general nonlinear model proposed by the author in another publication. The central measured variable is the asynchrony between presented tone and produced tap. General relations for the asynchrony autocovariance functions are derived, as well as covariance-based expressions for first- and second-order autoregressive error correction parameters. A second method of error parameter estimation, based on "local" binned calculations, is also presented. Combination of the two methods, buttressed by simulations, allows effective characterization of the time series' order and parameter values, and experimental support for the model is found to be strong in all cases. Error correction processes prove to be predominantly first order; second (and possibly higher) order effects occur predominantly under conditions of expertise and relatively high task demands. Expertise in tapping (as determined from these two subjects) is found to lead to reduced bias, reduced asynchrony and interonset variance, and, with the exception of a single case, increased values of error correction parameters relative to untrained performance. In a clear majority of cases where it could be tested, both the AR1 error correction parameter alpha, and the asynchrony and interonset standard deviations showed a strong tendency towards a linear relationship with tapping period. Copyright 1998 Academic Press.

Journal Article↗

PubMed1998

The influence of stimulus properties, complexity, and contingency on the stability and variability of ongoing and evoked activity in human auditory cortex.

The real-time, single-trial activity in the human auditory cortex was extracted from magnetoencephalographic signals. A predictor of single-trial activity was defined as the sum of the average response and a mean-free base level computed over a range of base times. For simple stimuli the residual (predicted-actual) activity had a stimulus-independent oscillatory (10 Hz) component. This component was larger and more durable in trained subjects, reaching saturation only in the most trained of the five subjects studied (S1). Changes in variability and associated reduction of the absolute value and duration of the oscillations were evident in experiments with stimuli loaded with information, saliency, or task contingency. Repetition reintroduces stimulus-independent oscillations very slowly. For S1, after training, the stimulus-independent oscillations were reestablished in the auditory cortices to the level seen for simple stimuli, except for the time periods and in the hemisphere associated with the combination of task demands and stimulus processing.

Adult↗

PubMed2000

How good is good enough in path analysis of fMRI data?

This paper is concerned with the problem of evaluating goodness-of-fit of a path analytic model to an interregional correlation matrix derived from functional magnetic resonance imaging (fMRI) data. We argue that model evaluation based on testing the null hypothesis that the correlation matrix predicted by the model equals the population correlation matrix is problematic because P values are conditional on asymptotic distributional results (which may not be valid for fMRI data acquired in less than 10 min), as well as arbitrary specification of residual variances and effective degrees of freedom in each regional fMRI time series. We introduce an alternative approach based on an algorithm for automatic identification of the best fitting model that can be found to account for the data. The algorithm starts from the null model, in which all path coefficients are zero, and iteratively unconstrains the coefficient which has the largest Lagrangian multiplier at each step until a model is identified which has maximum goodness by a parsimonious fit index. Repeating this process after bootstrapping the data generates a confidence interval for goodness-of-fit of the best model. If the goodness of the theoretically preferred model is within this confidence interval we can empirically say that the theoretical model could be the best model. This relativistic and data-based strategy for model evaluation is illustrated by analysis of functional MR images acquired from 20 normal volunteers during periodic performance (for 5 min) of a task demanding semantic decision and subvocal rehearsal. A model including unidirectional connections from frontal to parietal cortex, designed to represent sequential engagement of rehearsal and monitoring components of the articulatory loop, is found to be irrefutable by hypothesis-testing and within confidence limits for the best model that could be fitted to the data.

Adult↗