PubMed Health⌕ Search

Biomedical subjects

L A Thompson

Publications and source records attributed to L A Thompson.

At least 19 recordsLinked to original sources
PubMed2006

Geoacoustic inversion of short range source data using a plane wave reflection coefficient approach.

Acoustic time series data were collected in a shallow, hard bottom lake environment located in central Texas using both short range (2 m) implosive data, obtained with the source and a single hydrophone located near mid-depth in the waveguide, along with longer range implosive and explosive data from a near surface source to a bottom mounted hydrophone. Matched field inversions using simulated annealing were performed with a ray trace plus complex plane wave reflection coefficient forward propagation model that was validated in previous work. Isolating bottom interacting paths to perform the inversions is shown to be essential to reduce parameter uncertainties in the hard bottom environment and enables a systematic approach to the inversions which establishes the number of layers needed to represent the lake environment. Measured transmission loss data from a towed source were compared through a RMS error analysis to modeled transmission loss, constructed with the parameters from inversions of data from several source types, to further establish the validity of the inversion approach for this environment. Geoacoustic parameters obtained by inversions of short range, low frequency impulsive data are used to predict transmission loss at longer ranges and higher frequencies. The range dependence of the global minimum is discussed.

Acoustics↗
PubMed2003

Broadband sound propagation in shallow water and geoacoustic inversion.

Part of an experiment to test a measurement package in a shallow water region in the Gulf of Mexico was designed to gather broadband acoustic data suitable for inversion to estimate seabed geoacoustic parameters. Continuous wave tow acoustic signals at multiple frequencies and broadband impulsive source signals were recorded on a horizontal line array in a high-noise environment. Simulated annealing with a normal mode forward propagation model is utilized to invert for a geoacoustic representation of the seabed. Several inversions are made from different data samples of two light bulb implosions, the measured sound speed profiles at the HLA and at the positions of the light bulb deployments, and for two different cost functions. The different cost functions, measured sound speed profiles, and measured time series result in different inverted geoacoustic profiles from which transmission loss is generated for comparison with measurements. On the basis of physical consistency and from the comparison of the transmission loss and time series, a best estimate geoacoustic profile is selected and compared to those obtained from previously reported inversions. Uncertainties in the sound speed profile are shown to affect the uncertainties of the estimated seabed parameters.

Journal Article↗
PubMed2001

Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-alpha.

The binding of tumor necrosis factor alpha (TNF-alpha) to the type-1 TNF receptor (TNFRc1) plays an important role in inflammation. Despite the clinical success of biologics (antibodies, soluble receptors) for treating TNF-based autoimmune conditions, no potent small molecule antagonists have been developed. Our screening of chemical libraries revealed that N-alkyl 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones were antagonists of this protein-protein interaction. After chemical optimization, we discovered IW927, which potently disrupted the binding of TNF-alpha to TNFRc1 (IC(50) = 50 nM) and also blocked TNF-stimulated phosphorylation of Ikappa-B in Ramos cells (IC(50) = 600 nM). This compound did not bind detectably to the related cytokine receptors TNFRc2 or CD40, and did not display any cytotoxicity at concentrations as high as 100 microM. Detailed evaluation of this and related molecules revealed that compounds in this class are "photochemically enhanced" inhibitors, in that they bind reversibly to the TNFRc1 with weak affinity (ca. 40-100 microM) and then covalently modify the receptor via a photochemical reaction. We obtained a crystal structure of IV703 (a close analog of IW927) bound to the TNFRc1. This structure clearly revealed that one of the aromatic rings of the inhibitor was covalently linked to the receptor through the main-chain nitrogen of Ala-62, a residue that has already been implicated in the binding of TNF-alpha to the TNFRc1. When combined with the fact that our inhibitors are reversible binders in light-excluded conditions, the results of the crystallography provide the basis for the rational design of nonphotoreactive inhibitors of the TNF-alpha-TNFRc1 interaction.

Antigens, CD↗
PubMed2001

A genome-wide scan of 1842 DNA markers for allelic associations with general cognitive ability: a five-stage design using DNA pooling and extreme selected groups.

All measures of cognitive processes correlate moderately at the phenotypic level and correlate substantially at the genetic level. General cognitive ability (g) refers to what diverse cognitive processes have in common. Our goal is to identify quantitative trait loci (QTLs) associated with high g compared with average g. In order to detect QTLs of small effect size, we used extreme selected samples and a five-stage design with nominal alpha levels that permit false positive results in early stages but remove false positives in later stages. As a first step toward a systematic genome scan for allelic association, we used DNA pooling to screen 1842 simple sequence repeat (SSR) markers approximately evenly spaced at 2 cM throughout the genome in a five-stage design: (1) case-control DNA pooling (101 cases with mean IQ of 136 and 101 controls with mean IQ of 100), (2) case-control DNA pooling (96 cases with IQ > 160 and 100 controls with mean IQ of 102), (3) individual genotyping of Stage 1 sample, (4) individual genotyping of Stage 2 sample, (5) transmission disequilibrium test (TDT; 196 parent-child trios for offspring with IQ > 160). The over all Type I error rate is 0.000125, which robustly protects against false positive results. The numbers of markers surviving each stage using a conservative allele-specific directional test were 108, 6, 4, 2, and 0, respectively, for the five stages. A genomic control test using DNA pooling suggested that the failure to replicate the positive case-control results in the TDT analysis was not due to ethnic stratification. Several markers that were close to significance at all stages are being investigated further. Relying on indirect association based on linkage disequilibrium between markers and QTLs means that 100,000 markers may be needed to exclude QTL associations. Because power drops off precipitously for indirect association approaches when a marker is not close to the QTL, we are not planning to genotype additional SSR markers. Instead we are using the same design to screen markers such as cSNPs and SNPs in regulatory regions that are likely to include functional polymorphisms in which the marker can be presumed to be the QTL.

Adolescent↗
PubMed2001

Context-dependent memory under stressful conditions: the case of skydiving.

Two experiments examined the effect of differing levels of emotional arousal on learning and memory for words in matching and mismatching contexts. In Experiment 1, experienced skydivers learned words either in the air or on the ground and recalled them in the same context or in the other context. Experiment 2 replicated the stimuli and design of the first experiment except that participants were shown a skydiving video in lieu of skydiving. Recall was poor in air-learning conditions with actual skydiving, but when lists were learned on land, recall was higher in the matching context than in the mismatching context. In the skydiving video experiment, recall was higher in matching learn-recall contexts regardless of the situation in which learning occurred. We propose that under extremely emotionally arousing circumstances, environmental and/or mood cues are unlikely to become encoded or linked to newly acquired information and thus cannot serve as cues to retrieval. Results can be applied to understanding variations in context-dependent memory in occupations (e.g., police, military special operations, and Special Weapons and Tactics teams) in which the worker experiences considerable emotional stress while learning or recalling new information.

Adolescent↗
PubMed2001

Infants attend to second-order relational properties of faces.

Two experiments investigated whether 7-month-old infants attend to the spatial distance measurements relating internal features of the human face. A visual preference paradigm was used, in which two versions of the same female face (one either lengthened or shortened, and one nonmodified) were presented simultaneously. In Experiment 1, infants looked longer at the nonmodified faces, which were determined to match the average distance relationships found in a sample of faces drawn from the same population. Longer looking times for modified faces were found in Experiment 2, in which the nonmodified faces were unusually long and the modified faces conformed to average distance measurements. It is proposed that infants' attention to the spatial relations of internal face features is an optimal tool for lifelong face recognition.

Attention↗
PubMed2000

Presenilin-1 and -2 are molecular targets for gamma-secretase inhibitors.

Presenilins are integral membrane protein involved in the production of amyloid beta-protein. Mutations of the presenilin-1 and -2 gene are associated with familial Alzheimer's disease and are thought to alter gamma-secretase cleavage of the beta-amyloid precursor protein, leading to increased production of longer and more amyloidogenic forms of A beta, the 4-kDa beta-peptide. Here, we show that radiolabeled gamma-secretase inhibitors bind to mammalian cell membranes, and a benzophenone analog specifically photocross-links three major membrane polypeptides. A positive correlation is observed among these compounds for inhibition of cellular A beta formation, inhibition of membrane binding and cross-linking. Immunological techniques establish N- and C-terminal fragments of presenilin-1 as specifically cross-linked polypeptides. Furthermore, binding of gamma-secretase inhibitors to embryonic membranes derived from presenilin-1 knockout embryos is reduced in a gene dose-dependent manner. In addition, C-terminal fragments of presenilin-2 are specifically cross-linked. Taken together, these results indicate that potent and selective gamma-secretase inhibitors block A beta formation by binding to presenilin-1 and -2.

Amyloid Precursor Protein Secretases↗
PubMed2000

A counterselection for the tryptophan pathway in yeast: 5-fluoroanthranilic acid resistance.

The ability to counterselect, as well as to select for, a genetic marker has numerous applications in microbial genetics. Described here is the use of 5-fluoroanthranilic acid for the counterselection of TRP1, a commonly used genetic marker in the yeast Saccharomyces cerevisiae. Counterselection using 5-fluoroanthranilic acid involves antimetabolism by the enzymes of the tryptophan biosynthetic pathway, such that trp1, trp3, trp4 or trp5 strains, which lack enzymes required for the conversion of anthranilic acid to tryptophan, are resistant to 5-fluoroanthranilic acid. Commonly used genetic procedures, such as selection for loss of a chromosomally integrated plasmid, and a replica-plating method to rapidly assess genetic linkage in self-replicating shuttle vectors, can now be carried out using the TRP1 marker gene. In addition, novel tryptophan auxotrophs can be selected using 5-fluoroanthranilic acid.

Aldose-Ketose Isomerases↗
PubMed2000

Recent applications of polymer-supported reagents and scavengers in combinatorial, parallel, or multistep synthesis.

There has been a wealth of recent reports concerning support-bound reagents and scavengers in the solution-phase synthesis of compound libraries and natural products. Important advances in 1999 include the continued development and use of novel reagents for heterocycle synthesis, the increased use of catch-and-release purification, and the development of increasingly sophisticated techniques to allow sequestering of many types of impurities from desired compounds. These techniques have all been combined to enable the complicated multistep synthesis of natural products and of libraries of novel drug-like molecules, without conventional purification.

Combinatorial Chemistry Techniques↗
PubMed2000

The salience of temporal cues in the developing structure of event knowledge.

Two experiments used a novel method called Pathfinder to examine whether the salience of temporal cues embedded in event structure increases developmentally and whether people link event actions by simple adjacency relationships or embed them in an organized whole. A sequential format for eliciting knowledge was compared with a less structured format for dinner and bedtime events. Adults and their 8- and 10-year-old children demonstrated well-developed script organizations regardless of format, and organization improved across this age range. In Experiment 1, temporal cues were not a salient basis of comparison for 6-year-olds, but in Experiment 2 they could use temporal cues when instructed to do so. The results suggest that temporal salience increases between 6 and 10 years and that temporal knowledge of event actions is highly organized in this age range. Furthermore, children's event knowledge functions partly in the interaction between their developing event knowledge and the support provided by sequential constraints in the environment.

Association Learning↗
PubMed1999

DNA pooling and dense marker maps: a systematic search for genes for cognitive ability.

Pooling DNA from subjects within a group and comparing the pooled DNA across groups for a dense map of DNA markers offers a solution to the conundrum that linkage is systematic but not powerful whereas allelic association is powerful but not systematic. We used DNA pooling to screen 66 markers on chromosome 22 in original and replication samples of children of high general cognitive ability (g) and controls of average g. Although none of these markers survived our three-stage screening design (original pooling, replication pooling, individual genotyping), the results of DNA pooling were largely confirmed by individual genotyping. We can therefore exclude associations of major effect size on chromosome 22 for g, a key variable for cognitive neuroscience research on learning and memory.

Alleles↗
PubMed1999

Neurotic butterflies in my stomach: the role of anxiety, anxiety sensitivity and depression in functional gastrointestinal disorders.

This study examined the prevalence of functional gastrointestinal (FGI) disorders, and the association between FGI disorders and measures of affective distress, among a sample of 127 university students. Subjects completed a questionnaire battery including Research Diagnostic Questions for Functional Gastrointestinal Disorders, the Beck Anxiety Inventory, the Anxiety Sensitivity Index, the Beck Depression Inventory, and a medical utilization questionnaire. FGI disorders were diagnosed in 51.2% of the sample. Functional dyspepsia (22.8%), dyschezia (20.5%), functional heartburn (19.7%), functional chest pain (18.1%), and globus (12.6%) were the most frequently diagnosed disorders. Participants experiencing globus, functional dyspepsia, or functional heartburn showed significant differences in terms of anxiety, anxiety sensitivity, depression, and/or physician visits, when compared with participants without these disorders. Our results suggest that FGI disorders are strikingly prevalent among young adults, and specific FGI disorders are associated with affective distress. Implications of the observed association between psychological factors and FGI disorders are discussed.

Adolescent↗
PubMed1999

Some limits on encoding visible speech and gestures using a dichotic shadowing task.

Visible speech and gestures are two forms of available language information that can be used by listeners to help them understand the speaker's meaning. Previous research has shown that older adults are particularly dependent on visible speech, yet seem to profit less than younger adults from the speaker's gestures. To understand how visible speech and gestures are used when listening becomes difficult, the authors conducted an experiment with a dichotic shadowing task. The experiment examined how accurately participants could shadow the right- or left-ear input when instructed to attend selectively to a particular ear and whether performance benefited from visual input. The results indicate that older adults' shadowing performance was unaffected by visible speech and gestures. Younger adults did benefit by both visible speech and gestures. Thus, under extremely attention-demanding listening conditions, older adults are unable to use a compensatory mechanism for encoding visual language.

Adult↗
PubMed1998

Dopamine markers and general cognitive ability.

Because general cognitive ability (g) is among the most heritable behavioural traits, it is a reasonable target for a search for quantitative trait loci (QTLs). We used a selected-extremes design to test candidate genes for allelic association with g. Polymorphisms in four genes in the dopamine system (DRD2, DRD3, DRD4, DAT1) were genotyped for 51 high g children with IQ scores > 130 and for 51 average g control children. No significant allelic or genotypic differences were found between the high g and average g groups for these markers of the dopamine system, even though the selected-extremes design provides power to detect QTL associations that involve a relative risk of about 1.5.

Adolescent↗
PubMed1998

Developmental changes in the effect of dimensional salience on the discriminability of object relations.

Two experiments explored three issues regarding the nature of perceptual development in 5- and 10-year-old children and adults: (a) the role of featural discriminability, (b) the facilitatory role of identity relations, and (c) the role of salience in a task context designed to minimize the likelihood of attention-switching between dimensions during perceptual processing. In Experiment 1, perceptual salience for size and achromatic color dimensions was determined for each participant based on their best-fitting triad classification task response pattern. These same persons participated in Experiment 2, which employed a speeded visual discrimination task. The primary finding was that preassessed salience significantly influenced the 5-year-olds' ability to discriminate between two objects, while salience did not affect 10-year-olds' or adults' response times. The results of both experiments support Odom & Cook's (1992) differential-sensitivity view of perceptual development, but these data contribute important information by showing that salience effects in perceptual processing occur even when the observer is selectively attending to a particular dimension, likely during early component processes prior to classification.

Adult↗
PubMed1997

No association between general cognitive ability and the A1 allele of the D2 dopamine receptor gene.

Berman and Noble (1995) reported significantly reduced visuospatial performance in children with the TAQI A1 allele of the D2 dopamine receptor (DRD2) gene. Given that visuospatial performance loads highly on an unrotated principal component indexing general cognitive ability, we tested the association between DRD2 and WISC-R IQ comparing 51 high-IQ, 51 average-IQ, and 35 low-IQ children in the IQ Quantitative Trait Loci (QTL) Project. No statistically significant association between the TAQI A DRD2 alleles and IQ was found. Given that a statistically significant portion of genetic variance for specific cognitive abilities is independent of general cognitive ability, it is possible that the TAQI DRD2 association is specific to visuospatial performance and independent of general cognitive ability.

Adolescent↗
PubMed1997

What is so special about special education?

There is nothing special about special education. Educational methods have not changed significantly in at least 2,500 years. IQ tests were developed to identify those in need of special education, with the intention of developing appropriate educational methods. Effective special educational methods have yet to be developed. IQ tests are diagnostic but not prescriptive. Effective special educational methods will not be developed until (a) individual differences in student characteristics beyond IQ scores are recognized and understood and (b) educators focus on specific and realistic goals for outcome.

Adolescent↗