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PubMed1992

Fast visual generation: its nature and chronometrics.

The fast-generation model for the matching of mixed-case letter pairs (e.g., Aa, Ab) states that one or both members of a pair activate visual representations in memory of the opposite case, supporting "same" or "different" responses through crossmatching to representations of the pair members themselves. Here the reaction time and error results of three experiments using simultaneous matches support a specific variant of the model in which generation proceeds from the uppercase letter. Furthermore, a manipulation of stimulus onset asynchrony in a fourth experiment using near-simultaneous matches indicates that fast generation produces a visual representation that occurs within 67 msec of initiation and that decays within 200 msec. A fifth experiment contrasts simultaneous and successive matches and in the case of successive matches finds evidence in support of a regeneration process acting after an initial decay. Models of mixed-case matching that are based on the phonetic representation of letter names, or on abstract-letter identities, completely fail to account for the results. Fast generation is distinguishable from slow generation in that it shows fast (vs. slow) dynamics, rapid decay (vs. maintainability), no imagery (vs. imagery), and (probably) automatic (vs. controlled) processing.

Attention↗
PubMed1990

Generating a model of epileptic stigma: the role of qualitative analysis.

This paper uses an account of the goals, methods and results of a British community study of coping with epilepsy to consider the nature and range of the contributions qualitative analyses can make to theory formation. Different functions and contexts of qualitative analyses are described, and illustrations given of ways in which these helped generate and inform a particular model of the impact of the stigma of epilepsy on day-to-day life.

Adaptation, Psychological↗
PubMed1976

A nonhuman primate vascular shunt model for thrombus generation.

A nonhuman primate model for thrombus generation was developed. Three different types of test devices constructed of polystyrene or polyethylene-Silastic were exposed to flowing blood in arterioarterial or arteriovenous vascular shunts in rhesus monkeys. The test device design included a simple tube, a vortical flow device, and a turbulent flow device. The amount of thrombus deposited within each individual test device after a 15-minute exposure to blood flowing through the shunt was determined gravimetrically. These studies indicate that a test device designed to include an area of vortical flow generated the greatest amount of thrombus. Test devices fabricated from polystyrene consistently generated larger thrombus deposits than did similar test devices fabricated from polyethylene-Silastic. Arteriovenous shunts proved superior to arterioarterial shunts in that flow was predictable in the former and unpredictable in the latter; venovenous shunts thrombosed quickly. Hematologic studies indicated a progressive fall in platelet count during the 4-hour test interval in all animals, whereas in only a few animals were there a shortening of partial thromboplastin time values, a fall in fibrinogen levels, and the appearance of fibrin degradation products. An optimal model for thrombus generation appears to include vortical flow test devices fabricated of polystyrene exposed to flowing blood in an arteriovenous shunt.

Animals↗
PubMed1991

A multi-dimensional coalescent process applied to multi-allelic selection models and migration models.

For a sample of two genes from a population divided into an arbitrary number of allele classes, a general mathematical framework is developed to address the expectation and variance of the time of the most recent common ancestor. Depending on the meaning of allele classes and the manner in which genes can change among them, this framework can be applied to a diversity of population genetic models. By adoption of the infinite sites model, the effect on heterozygosity is modelled for balancing selection among allele classes, mutation between allele classes, migration among populations, and gene conversion between loci. Most results are described for a continuous time approximation to a discrete generation model. It is also shown how the discrete generation model can be used to study the hitch-hiking effect of favorable mutations.

Alleles↗
PubMedDate not supplied

A cortico-subcortical model for generation of spatially accurate sequential saccades.

This article provides a systems framework for the analysis of cortical and subcortical interactions in the control of saccadic eye movements, A major thesis of this model is that a topography of saccade direction and amplitude is preserved through multiple projections between brain regions until they are finally transformed into a temporal pattern of activity that drives the eyes to the target. The control of voluntary saccades to visual and remembered targets is modeled in terms of interactions between posterior parietal cortex, frontal eye fields, the basal ganglia (caudate and substantia nigra), superior colliculus, mediodorsal thalamus, and the saccade generator of the brainstem. Interactions include the modulation of eye movement motor error maps by topographic inhibitory projections, dynamic remapping of spatial target representations in saccade motor error maps, and sustained neural activity that embodies spatial memory. Models of these mechanisms implemented in our Neural Simulation Language simulate behavior and neural activity described in the literature, and suggest new experiments.

Animals↗
PubMed1991

Coevolution of self-fertilization and inbreeding depression. I. Mutation-selection balance at one and two loci.

Simple theories for the evolution of breeding systems suggest that the fate of an allele that modifies the rate of self-fertilization hinges only on the degree to which selfing reduces opportunities for outcrossing ("pollen discounting") and the extent of inbreeding depression. These theories predict that outcrossing evolves whenever deleterious mutations have a more severe effect in combination than expected from their individual effects. We study the evolutionary dynamics of a modifier of the rate of self-fertilization in populations subject to complete pollen discounting and recurrent mutations which impair viability at a single locus in diploids and at two loci in haploids. Our analysis indicates that genetic associations arising immediately upon the introduction of a rare modifier allele generate substantial quantitative and qualitative departures from expectation. Higher rates of segregation under selfing in our one-locus diploid model generate positive associations between enhancers of selfing and wild-type viability alleles, which in turn favor the evolution of selfing under a wider range of conditions than expected. Greater opportunities for recombination under outcrossing in our two-locus haploid model generate positive associations between enhancers of outcrossing and wild-type viability alleles. These associations favor the evolution of outcrossing under a wider range of conditions, and introduce the possibility of stable mixed mating systems involving both selfing and outcrossing. Our explicit analysis of genetic associations between loci affecting viability and the rate of self-fertilization indicates that modifiers that enhance the production of offspring with very high (and very low) viability by promoting segregation or recombination develop positive associations with high viability. This advantage of producing extremes can compensate for an initial disadvantage in offspring number.

Alleles↗
PubMed1992

Conduction of early afterdepolarizations in sheep Purkinje fibers and ventricular muscle. An in vitro arrhythmia model.

To establish an arrhythmia generator model, a double-chambered bath was used in which sheep Purkinje fibers (PF) and ventricular muscle (VM) were placed. The conduction patterns of early afterdepolarization-induced triggered activations (TAs) were examined between normal segments bathed in unmodified Tyrode solution and abnormal segments bathed in ethylenediaminetetraacetate (3.3-5.0 mmol). Three types of preparations were used: PF-PF (n = 10), VM-VM (n = 5), and PF-VM (n = 13). Two types of spontaneous TAs appeared. One type was conducted to normal segments, inducing activations over the entire preparation, while the other type was not conducted. The conducting TAs had significantly more rapid mean dV/dt, larger amplitude, and higher peak transmembrane voltage as compared to nonconducting TAs. While conduction occurred in all PF-PF, VM-VM, and PF-VM preparations, conduction of TAs from abnormal segment VM to normal segment PF was impaired. A low plateau resulting from electrotonic transmission of depolarizing current from abnormal segments was recorded in normal segments near the border. This low plateau probably facilitated the transmission of TAs. In addition to spontaneous TAs, stimulated or spontaneous action potentials from NL were conducted to the not yet fully repolarized ABN and induced activations resembling TAs. These results may be relevant to clinical arrhythmias due to action potential prolongation. The arrhythmia may occur directly as a result of triggered activity or indirectly via slow conducting TAs, creating the possibility for reentry. This type of model may be useful for intervention studies, for example, by identifying agents that block abnormal segment to normal segment conduction.

Action Potentials↗
PubMed1991

The use of structural equation modeling in generative research: toward the design of a preventive intervention for bereaved children.

Describes a generative study of processes which may lead to symptomatology in children who have experienced the death of a parent. Based on existing literature, four putative mediating variables were identified: parental demoralization, family warmth, negative family events, and positive stable family events. Structural equation modeling techniques were used to compare several potential causal models involving these variables. The results were most consistent with a model in which bereavement was not directly related to the child symptomatology, but rather its effects were transmitted through these four mediational mechanisms. The implications of the results of the structural modeling for the design and evaluation of preventive interventions are discussed briefly.

Adaptation, Psychological↗
PubMed1990

Modeling sound generation in stenosed coronary arteries.

Acoustic measurements obtained from sensitive microphones placed on the chest are being used in a procedure to noninvasively diagnose coronary artery disease. Utilizing specially developed signal processing techniques, the spectral content of isolated diastolic heart sounds has been estimated and usually shows an increase in high-frequency components in patients with occlusive coronary arteries. In order to establish a theory for the origin of these spectral features, a sound source model has been developed which combines an incremental network model of the left coronary artery tree with a transfer function model describing arterial chamber resonant characteristics. The network model predicts flow in both normal and stenosed coronary arteries. From this flow information, the arterial chamber transfer function model predicts the development of acoustic signals from the chamber resonant characteristics. The transfer function of a segment of coronary artery demonstrates two resonance frequencies. These resonance frequencies depend upon the length and diameter of the chamber segment, as well as upon the distal hydraulic impedance loading the segment. The lower resonance frequency can be excited by the usual flow fluctuations (low frequency) in the coronary artery. In cases of stenosis, the wideband spectral characteristics of the turbulence produced by the stenosis excites both the low and high resonance frequencies. In a small sample of patients, the spectra obtained from isolated diastolic acoustic signals recorded by a chest microphone agree well with those predicted by this theory.

Coronary Circulation↗
PubMed1992

Production of chickens with marginal vitamin A deficiency.

Marginally vitamin A-deficient 1-d-old chickens capable of remaining healthy for at least 6 weeks were produced using a two-generation model. In this model, hens fed on diets with a limited vitamin A content were used to obtain 1-d-old chickens which were marginally deficient in vitamin A. Only hens with a narrow range of plasma retinol values (0.60-0.85 mumol/l) were satisfactory for this purpose. Above this range the 1-d-old chickens were not marginally vitamin A deficient. Below this range egg production and hatchability were affected to some extent depending on the degree of vitamin A deficiency. Even when egg production and hatchability remained at a high level in such birds, the 1-d-old chickens produced were not sufficiently strong to survive the first weeks of life. The advantages of the two-generation model for producing marginally vitamin A-deficient chickens are the increased uniformity and predictability of the chickens with respect to body-weight, general health and vitamin A status. However, it does take about 3 months to produce such chickens.

Animals↗
PubMed1991

Implementing Boissonnat's method for generating surface models of craniofacial cartilages.

Surface modeling of embryonic craniofacial morphology typically is accomplished using data derived from planar contours. Methods currently available for reconstructing embryonic craniofacial anatomy from contour data rely on shortest-path algorithms in order to interpolate surfaces. However, these techniques either fail or require a considerable amount of user interaction when complex surfaces are modeled since foramina and structural divisions cannot be interpolated properly. Recently, a new approach has been described by Boissonnat that constructs a polyhedral volume between sets of planar contours. Surfaces are interpolated by identifying the planes formed when the contours intersect the polyhedron. The purpose of this study is to determine whether craniofacial cartilages from embryonic mice can be reconstructed in an accurate and reliable fashion using this method. Embryonic mice were collected and processed for routine histological sectioning. Serial sections of the anterior cranial base and nasal capsule were obtained, subjected to videomicroscopy, and modeled. Reconstructions of the anterior cranial base and nasal capsule from embryonic mice were compared to the same structures in age-matched specimens that were processed with whole-mount staining procedures. The models compared well with the whole-mount preparations. In addition, the reconstruction technique accurately rendered complex surface features of the embryonic anterior cranial base and nasal capsule including foramina and structural branches.

Algorithms↗
PubMed1985

Smoking behavior, cessation techniques, and the health decision model.

The magnitude of the problem of smoking challenges health providers to persuade patients of the importance of trying to quit. Smoking behavior and cessation techniques are discussed in terms of the health decision model, a third-generation model combining health beliefs, decision analysis, and behavioral decision theory. This review suggests the need for physicians to emphasize factors such as health beliefs, self-efficacy, social support, and reduction of stress in smoking cessation efforts. Patients experiencing symptoms, particularly relating to the lungs or heart, may have stronger health beliefs and are clearly more likely to quit smoking. In the absence of a clear-cut advantage for any particular smoking cessation technique, physicians should provide advice about smoking as a regular part of every patient visit.

Adult↗
PubMed1978

Computer-generated graphic models of the N2-substituted deoxyguanosine adducts of 2-acetylaminofluorene and benzo[a]pyrene and the O6-substituted deoxyguanosine adduct of 1-naphthylamine in the DNA double helix.

Computer models of three deoxyguanosine-carcinogen adducts in double-helical DNA are presented. The carcinogen moiety is rotated and the best fit within the double helix is evaluated. The 2-acetylaminofluorene (AAF) derivative, 3-(deoxyguanosin-N2-yl)-AAF, is found to be situated within the minor groove, has very little freedom of rotation and causes little helical distortion. The (+)-anti-benzo[a]-pyrene (BP)-diol epoxide-N2 adduct, 10beta-(deoxyguanosin-N2-yl)-7beta, 8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydro-BP, has a similar fit with a greater degree of steric interaction, suggesting that this adduct could cause some local destabilization. The 1-naphthylamine (NA) derivative, N1-(deoxyguanosine-O6-yl)-1-NA, resides within the major groove, does not perturb the helix and has considerable freedom of movement.

1-Naphthylamine↗
PubMed1992

Computer-generated bone models in the planning of osteotomy of multidirectional distal radius malunions.

Computer-assisted design and manufacturing technology has been used to create solid models of five unusually complex, multidirectional malunions of distal radius fractures. Preoperative planning was dramatically enhanced by the ability to perform the surgical procedure on these models, with a model of the uninjured limb used for comparison. All five patients had significant malunions, with malrotation in the horizontal plane in five and an impacted articular fragment in two. A satisfactory outcome was achieved in each case.

Adult↗
PubMed2026

CRISPR/Cpf1-mediated knockout of FLG in human induced pluripotent stem cells generates a model for studying epidermal barrier dysfunction.

Loss of filaggrin (FLG) function impairs skin barrier formation and contributes to common inflammatory skin diseases. In this study, we established a FLG knockout human induced pluripotent stem cell (iPSC) line based on KOLF2.1 J using CRISPR/Cas12a (Cpf1)-mediated genome editing. A guide RNA targeting exon 2 introduced a homozygous mutation, which was confirmed by sequencing. The edited cells maintained typical pluripotent stem cell morphology, expressed key undifferentiated markers, and retained the ability to differentiate into all three germ layers. Karyotype and copy number variation (CNV) analyses confirmed genomic stability and parental origin; the cells were free of mycoplasma. This cell line enables studies of FLG-associated skin biology and pathology.

Humans↗
PubMed2024

Model-directed generation of artificial CRISPR-Cas13a guide RNA sequences improves nucleic acid detection.

CRISPR guide RNA sequences deriving exactly from natural sequences may not perform optimally in every application. Here we implement and evaluate algorithms for designing maximally fit, artificial CRISPR-Cas13a guides with multiple mismatches to natural sequences that are tailored for diagnostic applications. These guides offer more sensitive detection of diverse pathogens and discrimination of pathogen variants compared with guides derived directly from natural sequences and illuminate design principles that broaden Cas13a targeting.

CRISPR-Cas Systems↗