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PubMed1999

A model of saccade generation based on parallel processing and competitive inhibition.

During active vision, the eyes continually scan the visual environment using saccadic scanning movements. This target article presents an information processing model for the control of these movements, with some close parallels to established physiological processes in the oculomotor system. Two separate pathways are concerned with the spatial and the temporal programming of the movement. In the temporal pathway there is spatially distributed coding and the saccade target is selected from a "salience map." Both pathways descend through a hierarchy of levels, the lower ones operating automatically. Visual onsets have automatic access to the eye control system via the lower levels. Various centres in each pathway are interconnected via reciprocal inhibition. The model accounts for a number of well-established phenomena in target-elicited saccades: the gap effect, express saccades, the remote distractor effect, and the global effect. High-level control of the pathways in tasks such as visual search and reading is discussed; it operates through spatial selection and search selection, which generally combine in an automated way. The model is examined in relation to data from patients with unilateral neglect.

Attention↗
PubMed1997

Possible mechanism for resistance to Alzheimer's disease (AD) in mice suggests a new approach to generate a mouse model for sporadic AD and may explain familial resistance to AD in man.

An overproduction of beta-amyloid (A beta) is associated with Alzheimer's disease (AD) and appears to be its primary cause. A model has been recently described which accounts for the overproduction of A beta in sporadic AD, this constituting the majority of all cases of AD. The proposed mechanism suggests the antisense RNA-Mediated generation of a 5'-truncated beta-amyloid precursor protein (beta APP) mRNA encoding a 12-kDa C-terminal fragment of beta APP, the immediate precursor of A beta. In the truncated mRNA, the first AUG codon, which contiguously precedes the A beta-coding segment, becomes the site of translation initiation of a polypeptide that can be further processed to generate A beta, this subsequently being secreted. Among the predictions of the proposed model is that mice and rats do not and indeed cannot develop sporadic AD because they lack the crucial component of the proposed mechanism, namely the ability of the beta APP antisense RNA to self-prime the synthesis of a new sense strand. According to the proposed model, however, mice could be rendered susceptible to AD by mutating the beta APP gene so as to confer self-priming ability on the antisense strand. In contrast to existing mouse models which by design are fundamentally unsuitable for study of the mechanism underlying sporadic AD, the AD pathology of the proposed model would be expected to faithfully reflect the human condition. The availability of such an acutely needed, experimental model would allow investigators to study not only the manifestation of the disease but, most significantly, also the factors triggering it. The proposed mouse model may explain familial resistance to AD in man, provide extremely valuable insights into the etiology of AD, and suggest means for its prevention.

Alzheimer Disease↗
PubMed1986

A model of pattern generation of cockroach walking reconsidered.

Cockroaches that have been decapitated or that have cut thoracic connectives can show rhythmic bursting in motoneurons to intrinsic leg muscles. These preparations have been studied as models for walking and to evaluate the functions of leg proprioceptors. The present study demonstrates that headless cockroaches walk extremely poorly and slowly with considerable discoordination of motoneuronal activity, these preparations show rhythmic motoneuron bursting that is similar to righting responses (attempts to turn upright) of intact animals when placed on their backs, and bursting is inhibited when a headless animal is turned or turns itself upright. Thus, rhythmic motoneuron activity of these preparations is most probably attempted righting rather than walking. It is concluded that the headless cockroach is useful for understanding the motor mechanisms underlying righting and walking but is not of value in assessing the functions of proprioceptive feedback.

Animals↗
PubMed1988

Self-organizing system obtaining communication ability. Primitive model for language generation.

As one of the synthetic approaches to brain functions, the possibility is discussed that two intellectual robots could make "words" for themselves and come to communicate with each other. Associatron, a model for associative memory with a neural network structure, is used as the memory in the brain, and information from the outer world is accumulated in it. Concepts regarding objects and attributes are extracted from the stored information, where the Associatron properties are utilized. The robots give specific names to the concepts and interchange them with each other. When the robots have the same experience at the same time, they modify their own words according to what the other robot says. As they repeat common experiences, the differences between the words become smaller and smaller, and finally the robots agree on a word for each object. At this stage, the robots can exchange information with their words and each can act accordingly on the word from the other. This study shows that the self-organizing system with the above function can be constructed as a neural network model.

Artificial Intelligence↗
PubMed1999

Effects of EGb761 and superoxide dismutase in an experimental model of retinopathy generated by intravitreal production of superoxide anion radical.

BACKGROUND: A study was carried out to investigate the effect of two antioxidants--Ginkgo biloba extract (EGb761) and superoxide dismutase (SOD)--in an experimental model of vitreoretinopathy obtained by direct production of oxygen free radicals in the vitreous cavity. METHODS: Twenty-eight pigmented rabbits were used. Vitreoretinopathy was induced by intravitreal injection of 50 microliters of a mixture composed of 40 nmol of xanthine and 0.001 IU of xanthine oxidase. Rabbits were randomly distributed into four groups: Group 1 (n = 8) did not receive any treatment and served as a positive control. Groups 2 (n = 8) and 3 (n = 8) received for 1 month EGb761 given orally at a dose of 100 mg/kg/day, respectively 1 day after and 1 week before induction of retinopathy. Group 4 (n = 4) was treated by three intramuscular injections of 15,000 IU/kg of SOD, 24 h before induction and 24 and 48 h thereafter. Clinical evaluations and electroretinograms (ERG) were repeatedly performed until the animals were killed at day 28. Histological examinations and immunohistological procedures were performed to ascertain the origin and characteristics of the cellular proliferation and to compare vitreoretinal structures in the four groups. RESULTS: Intravitreal injection of xanthine-xanthine oxidase produced a strong inflammatory response with vitreous infiltrates and epiretinal membrane formation, inconstantly associated with retinal detachment. ERG showed a decrease of the a-, b- and c-waves beginning within a few hours after injection. Histologic evaluation found an intravitreal and epiretinal infiltration by leukocytes and epithelial-derived cells, dense vitreoretinal membranes and retinal detachments with occasional neovascularization. In the treated groups (groups 2-4), all clinical, electric and histologic data were significantly improved compared to the control group. However, no difference could be found among the three treated groups. CONCLUSION: This study demonstrates the strong pathologic effects of free radical production on the retina and the close relationships between free radicals, inflammatory pathways and vitreoretinal proliferative disorders. It also confirms the pharmacological interest of prevention by antioxidants and free radical scavengers.

Administration, Oral↗
PubMed2006

Genetic models of homosexuality: generating testable predictions.

Homosexuality is a common occurrence in humans and other species, yet its genetic and evolutionary basis is poorly understood. Here, we formulate and study a series of simple mathematical models for the purpose of predicting empirical patterns that can be used to determine the form of selection that leads to polymorphism of genes influencing homosexuality. Specifically, we develop theory to make contrasting predictions about the genetic characteristics of genes influencing homosexuality including: (i) chromosomal location, (ii) dominance among segregating alleles and (iii) effect sizes that distinguish between the two major models for their polymorphism: the overdominance and sexual antagonism models. We conclude that the measurement of the genetic characteristics of quantitative trait loci (QTLs) found in genomic screens for genes influencing homosexuality can be highly informative in resolving the form of natural selection maintaining their polymorphism.

Alleles↗
PubMed1994

The RAETRAD model of radon generation and transport from soils into slab-on-grade houses.

Remediation planning and 222Rn-related construction zoning require knowledge of how close and strong 226Ra sources can be in different foundation soils under different groundwater conditions without excessively elevating indoor 222Rn levels. A two-dimensional numerical-analytical model was developed to simulate (a) 222Rn emanation, decay, and movement by diffusion and advection in soils around houses and in their understructures; and (b) 222Rn accumulation in a single-zone house. The model represents foundation soils and a house in elliptical-cylindrical geometry. 222Rn may diffuse through its floor slab or may enter via idealized cracks and openings. The model was validated with analytical calculations of two-dimensional air pressure fields and with one-dimensional calculations of 222Rn generation with diffusion and diffusion combined with advection. Agreement generally was within < 1% when finite-difference approximations were minimized. Benchmark comparisons with indoor 222Rn measurements in two test-cell structures under passive and depressurized conditions averaged within 11% of measured values, well within measurement uncertainty. The corresponding average bias was only 3%. Larger variations were observed when applying the model to 50 houses. In this application, a negative bias of nearly 50% was observed due to data gaps and to poorly-characterized floor slabs and crack distributions.

Diffusion↗
PubMed1998

Mathematical modelling of superoxide generation with the bc1 complex of mitochondria

It is widely believed that direct nonenzymatic semiquinone oxidation with oxygen is one of the sources of superoxide in mitochondria. In the present work we developed a mathematical model of coupled functioning of the bc1 complex and ATP producing processes that allows one to obtain the dependence of superoxide production rate on membrane potential (DeltaPsi). Assuming that electron transfer between hemes of cytochrome b is the main electrogenic step of the Q-cycle, we found that rate of superoxide production increased dramatically with increase in DeltaPsi in the range from 170 to 200 mV. This explains experimental observation of a dramatic decrease in the superoxide production with decrease in DeltaPsi in the range from 200 to 170 mV. Generation of superoxide can be diminished with the inhibition of the electron supply to the Q-cycle, with decrease in external potassium, or increase in external inorganic phosphate level.

Journal Article↗
PubMed1988

Associative neural network model for the generation of temporal patterns. Theory and application to central pattern generators.

Cyclic patterns of motor neuron activity are involved in the production of many rhythmic movements, such as walking, swimming, and scratching. These movements are controlled by neural circuits referred to as central pattern generators (CPGs). Some of these circuits function in the absence of both internal pacemakers and external feedback. We describe an associative neural network model whose dynamic behavior is similar to that of CPGs. The theory predicts the strength of all possible connections between pairs of neurons on the basis of the outputs of the CPG. It also allows the mean operating levels of the neurons to be deduced from the measured synaptic strengths between the pairs of neurons. We apply our theory to the CPG controlling escape swimming in the mollusk Tritonia diomedea. The basic rhythmic behavior is shown to be consistent with a simplified model that approximates neurons as threshold units and slow synaptic responses as elementary time delays. The model we describe may have relevance to other fixed action behaviors, as well as to the learning, recall, and recognition of temporally ordered information.

Animals↗
PubMed1993

Hydrogen peroxide generation in a model paediatric parenteral amino acid solution.

1. Parenteral amino acid solutions undergo photooxidation, which may be an important factor in total parenteral nutrition-associated hepatic dysfunction. Light-exposed parenteral solutions containing amino acids, in addition to vitamins and trace minerals, generate free radicals, which, in turn, may contribute to this type of injury. This study examined the characteristics of H2O2 production in a parenteral amino acid solution modelled on a commercially available paediatric parenteral amino acid solution. 2. The solution was exposed to light in the presence of riboflavin-5'-monophosphate (riboflavin), and peroxide formation in the presence and absence of catalase (H2O2 formation) was assayed using potassium iodide/molybdate. 3. Peak H2O2 production occurred at a light intensity of 8 microW cm-2 nm-1 in the 425-475 nm waveband and was linear to 2 h of light exposure. H2O2 production reached 500 mumol/l at 24 h. 4. H2O2 was directly related to a riboflavin concentration of up to 20 mumol/l and was maximal at 30 mumol/l. 5. H2O2 production was greatest in the amino acid/riboflavin solution at a pH of between 5 and 6. 6. Under the conditions of light exposure intensity, light exposure time, riboflavin concentration and pH found during the administration of parenteral nutrition in neonatal intensive care units, net H2O2 production occurs in solutions modelled on a paediatric parenteral amino acid preparation.

Amino Acids↗
PubMed1996

Nonuniformity of the constitutive law parameters for shear rupture and quasistatic nucleation to dynamic rupture: a physical model of earthquake generation processes.

Based on the recent high-resolution laboratory experiments on propagating shear rupture, the constitutive law that governs shear rupture processes is discussed in view of the physical principles and constraints, and a specific constitutive law is proposed for shear rupture. It is demonstrated that nonuniform distributions of the constitutive law parameters on the fault are necessary for creating the nucleation process, which consists of two phases: (i) a stable, quasistatic phase, and (ii) the subsequent accelerating phase. Physical models of the breakdown zone and the nucleation zone are presented for shear rupture in the brittle regime. The constitutive law for shear rupture explicitly includes a scaling parameter Dc that enables one to give a common interpretation to both small scale rupture in the laboratory and large scale rupture as earthquake source in the Earth. Both the breakdown zone size Xc and the nucleation zone size L are prescribed and scaled by Dc, which in turn is prescribed by a characteristic length lambda c representing geometrical irregularities of the fault. The models presented here make it possible to understand the earthquake generation process from nucleation to unstable, dynamic rupture propagation in terms of physics. Since the nucleation process itself is an immediate earthquake precursor, deep understanding of the nucleation process in terms of physics is crucial for the short-term (or immediate) earthquake prediction.

Journal Article↗
PubMed2006

The route to the structure determination of amorphous solids: a case study of the ceramic Si(3)B(3)N(7).

Si(3)B(3)N(7) is the parent compound of a new class of amorphous ceramics containing silicon, boron, nitrogen, and carbon that display a unique spectrum of properties. It consists of a random network in which the constituent elements are linked by predominantly covalent bonds. Similarly to quartz glass, the composition of amorphous Si(3)B(3)N(7) is virtually stoichiometric. As all three of its constituent elements can serve as the objects of various structural probes, Si(3)B(3)N(7) was selected as the basis of a systematic structural investigation, in which methods for the structure determination of solids without translational symmetry could be validated and improved. However, as the complete amorphous structure cannot be deduced from experimental data, these results must be complemented by computer simulations. Thus, five classes of structure models were generated and compared to experimental results. Only the models generated by following the actual synthesis route as closely as possible agreed well with the experimental data.

Journal Article↗
PubMed2002

Conformational studies of Lewis X and Lewis A trisaccharides using NMR residual dipolar couplings.

The conformations of the histo-blood group carbohydrate antigens Lewis X (Le(x)) and Lewis A (Le(a)) were studied by NMR measurements of one-bond C-H residual dipolar couplings in partially oriented liquid crystal solutions. A strategy for rapid calculation of the difference between theoretical and experimental dipolar couplings of a large number of model structures generated by computer simulations was developed, resulting in an accurate model structure for the compounds. Monte Carlo simulations were used to generate models for the trisaccharides, and orientations of each model were sought that could reproduce the experimental residual dipolar coupling values. For both, Le(a) and Le(x), single low energy models giving excellent agreement with experiment were found, implying a compact rigidly folded conformation for both trisaccharides. The new approach was also applied to the pentasaccharides lacto-N-fucopentaose 2 (LNF-2) and lacto-N-fucopentaose 3 (LNF-3) proving its consistency and robustness. For describing the conformation of tightly folded oligosaccharides, a definition for characterization of ring planes in pyranoside chairs is proposed and applied to the analysis of the relation between the fucose and galactose residues in the epitopes, revealing the structural similarity between them.

Carbohydrate Conformation↗
PubMed2001

Inter-generational longitudinal study of social class and depression: a test of social causation and social selection models.

BACKGROUND: Generations of epidemiologists have documented an association between low socio-economic status (SES) and depression (variously defined), but debate continues as to which is the causative factor. AIMS: To test the extent to which social causation (low SES causing depression) and social selection (depression causing low SES) processes are in evidence in an inter-generational longitudinal study. METHOD: Participants (n = 756) were interviewed up to four times over 17 years using the Schedule for Affective Disorders and Schizophrenia (SADS). RESULTS: Low parental education was associated with increased risk for offspring depression, even after controlling for parental depression, offspring gender and offspring age. Neither parental nor offspring depression predicted later levels of offspring occupation, education or income. CONCLUSION: There is evidence for an effect of parental SES on offspring depression (social causation) but not for an effect of either parental or offspring depression on offspring SES (social selection).

Adolescent↗
PubMed2004

Impact of procoagulant concentration on rate, peak and total thrombin generation in a model system.

Using a cell-based model system of coagulation, we performed a systematic examination of the effect of varying individual procoagulant proteins (over the range of 0-200% of pooled plasma levels) on the characteristics of thrombin generation. The results revealed a number of features unique to the different coagulation factors, as well as common features allowing them to be grouped according to the patterns observed. Variation of those factors contributing to formation of the tenase complex, factor (F)VIII, factor (F)IX and factor (F)XI, primarily affected the rate and peak of thrombin production, but had little to no effect on total thrombin production. The effect of decreased FXI was milder than seen with decreased FVIII or FIX, and more variable between platelet donors. In contrast, varying the concentration of factors that contribute to formation of the prothrombinase complex, prothrombin or factor (F)V (with FV-deficient platelets), significantly affected all three measures of thrombin production: rate, peak and total. Additionally, while no thrombin generation was observed with no factor X, only very small amounts (between 1% and < 10% of normal plasma levels) were required to normalize the measured parameters. Finally, our results with this cell-based system highlight differences in thrombin generation on cell surfaces (platelets) compared with phospholipids, and suggest that platelets contribute more than simply a surface for the generation of thrombin.

Blood Coagulation Factors↗