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Differential regulation of c-fos expression after cortical brain injury during development.

Unilateral cortical brain injury is accompanied by widespread expression of c-fos protein(s) throughout the wounded cortex, including areas far from the lesion site. Here we report that this phenomenon is differentially regulated during development. At postnatal day (PD) 10 or 15, when rats were sacrificed 1.5 h after a mechanical cortical injury, they did not show an increase in c-fos immunoreactivity far from the wound, despite the fact that some of these animals (PD 15) displayed a positive response close to the lesion. At PD 22, the same injury induced an increase in c-fos-immunoreactive nuclei in the piriform cortex ipsilateral, but not contralateral, to the lesion. This pattern was maintained up to at least PD 360. Similarly, the presence of c-fos-immunoreactive cells was observed in the ipsilateral cingulate cortex in animals 22 days old and older. The pattern of c-fos expression in adult animals after mechanical damage was compared with other models of focal brain injury: application of potassium to the cortical surface and devascularization. Though all models generated c-fos expression far from the lesion site, potassium application resulted in higher numbers of c-fos-positive cells, particularly in the cingulate cortex. This study shows that c-fos expression after cortical brain injury is regulated differently during development, and that dissimilar models of cortical injury induce qualitatively similar responses although c-fos-like protein expression differs quantitatively.

Animals↗

An evolutionary approach to constructing prognostic models.

A prognostic model is sought to determine whether or not patients suffering from an uncommon form of cancer will survive. Given a set of case histories, we attempt to find the relative weightings of the different variables that are used to describe the cases. Our first innovation is to use a diffusion genetic algorithm (DGA) to find weightings which will give optimal survival predictions. The DGA enables a number of criteria to be satisfied simultaneously, making it particularly suitable for model building. A further innovation is a method of representing synergies between interacting factors. The evolved model correctly predicts 90% of the survivors and 87% of deaths, an improvement over the current model. More significantly, the method enables a simple model to be evolved, one that produces well-balanced predictions, and one that is relatively easy for clinicians to use. The method was validated by running it on a training set made up of 90% of the original database and then studying the performance of the generated models on a test set consisting of the remaining 10% of the cases.

Adolescent↗

Saturation transfer difference NMR and computational modeling of a sialoadhesin-sialyl lactose complex.

The siglecs are a family of I-type lectins binding to sialic acids on the cell surface. Sialoadhesin (siglec-1) is expressed at much higher levels in inflammatory macrophages and specifically binds to alpha-2,3-sialylated N-acetyl lactosamine residues of glycan chains. The terminal disaccharide alpha-D-Neu5Ac-(2-->3)-beta-D-Gal is thought to be the main epitope recognized by sialoadhesin. To understand the basis of this biological recognition reaction we combined NMR experiments with a molecular modeling study. We employed saturation transfer difference (STD) NMR experiments to characterize the binding epitope of alpha-2,3-sialylated lactose, alpha-D-Neu5Ac-(2-->3)-beta-D-Gal-(1-->4)-D-Glc 1 to sialoadhesin at atomic resolution. The experimental results were compared to a computational docking model and to X-ray data of a complex of sialyl lactose and sialoadhesin. The data reveal that sialoadhesin mainly recognizes the N-acetyl neuraminic acid and a small part of the galactose moiety of 1. The crystal structure of a complex of sialoadhesin with sialyl lactose 1 was used as a basis for a modeling study using the FlexiDock algorithm. The model generated was very similar to the original crystal structure. Therefore, the X-ray data were used to predict theoretical STD values utilizing the CORCEMA-STD protocol. The good agreement between experimental and theoretical STD values indicates that a combined modeling/STD NMR approach yields a reliable structural model for the complex of sialoadhesin with alpha-D-Neu5Ac-(2-->3)-beta-D-Gal-(1-->4)-D-Glc 1 in aqueous solution.

Carbohydrate Sequence↗

A predictive model that evaluates the effect of growth conditions on the thermal resistance of Listeria monocytogenes.

A predictive model for Listeria monocytogenes was developed using cells grown in different pH and milkfat levels before subsequent thermal inactivation in identical pH and milkfat conditions. Inactivation of the cells used combinations of temperature (55, 60, 65 degrees C), pH (5.0, 6.0, 7.0), and milkfat (0%, 2.5%, 5.0%) in a complete 3 x 3 x 3 factorial design with each test done in triplicate. A modified Gompertz equation was used to model nonlinear survival curves with the following three parameter estimates: A for the shouldering region, B for the maximum death rate, and C for the tailing region. All treatment sets were analyzed together in a regression model using the modified Gompertz equation. There was good confidence in the overall model when it was used to predict values for the entire data set. The correlation of determination, R2, between the observed log surviving fraction (LSF) of cells from each of the conditions studied in the experiment, for the overall model was 0.811. For the A and B parameter estimates, temperature or milkfat alone, and the interaction of temperature and milkfat significantly (p < 0.05) affected the shouldering region and maximum death rate of a survival curve, respectively. These results were compared to a previously published predictive model, generated for cells grown under optimum conditions (pH 7.0, 0% milkfat), where pH was the only significant (p < 0.05) factor affecting the shoulder region. These results suggested that the conditions of the growth environment had an important impact on survival curve shape and the estimates of the predictive model. Specifically, there were more factor interactions involving temperature and milkfat level. These growth factors affected the shoulder region and maximum rate of death of the survival curve when cells were grown in identical medium conditions to which they were heated. Differences related to shouldering and inactivation rates for cells grown in different conditions may have important and practical importance for estimating inactivation of L. monocytogenes. This study provides some evidence on the importance of growing conditions when evaluating microbial heat resistance.

Animals↗

Atomistic models for CeO(2)(111), (110), and (100) nanoparticles, supported on yttrium-stabilized zirconia.

Ceria is an important component in three-way catalysts for the treatment of automobile exhaust gases owing to its ability to store and release oxygen, a property known as the oxygen storage capacity. Much effort has been focused on increasing the OSC of ceria, and one avenue of exploration is the ability to fabricate CeO(2)-based catalysts, which expose reactive surfaces. Here we show how models for a polycrystalline CeO(2) thin film, which expose the (111), (110), and dipolar (100) surfaces, can be synthesized. This is achieved by supporting the CeO(2) thin film on an yttrium-stabilized zirconia substrate using a simulated amorphization and recrystallization strategy. In particular, the methodology generates models which reveal the atomistic structures present on the surface of the reactive faces and provides details of the grain-boundary structures, defects (vacancies, substitutionals, and clustering), and epitaxial relationships. Such models are an important first step in understanding the active sites at the surface of a catalytic material.

Journal Article↗

A knowledge-based model of DNA hydration.

The aqueous hydration of DNA is an important aspect of its structure, which is of direct relevance to mechanisms of radiation damage. We have made a quantitative analysis of solvent interactions within hydrogen bonding distance of polar atoms of oligonucleotides using 12 B-DNA oligonucleotide crystal structures. The distribution of water molecules around the four bases, the sugar residues and the phosphate groups were generated and analysed both qualitatively and quantitatively. These data have then been used in a knowledge-based method to generate the likely hydration sites around a canonical B-DNA conformation in order to generate models of use in track studies of radiation damage.

Base Sequence↗

Effects of presurgical orthopedic treatment in infants with complete bilateral cleft lip and palate.

OBJECTIVE: To align the protruding premaxilla in infants with bilateral cleft lip and palate (BCLP), an intraoral appliance (i.e., Hotz plate) and an extraoral appliance consisting of a band covering the head and elastics are used as a presurgical orthopedic treatment in our clinic. The aim of this study was to analyze the configuration and position of the premaxilla and the vomer in infants with BCLP and to investigate the factors generating deviation and bending of the vomer and twisting of the premaxilla. PATIENTS: Palatal casts were obtained serially from 10 infants with complete BCLP from 1 to 3 months of age. MEASUREMENTS: These casts were automatically measured using a highly accurate contact-type measuring apparatus. After three-dimensional wire frame models generated from the serial casts were automatically superimposed, the magnitude and direction of the shift were calculated. A discriminant analysis was used for investigation of predictor variables generating the twisting or bending vomer. RESULTS AND CONCLUSIONS: The vomer was found to be bent in two infants and the premaxilla was twisted in three infants. In the infants whose vomers were bent, the magnitude of the posterior shift of the premaxilla was greater than that of the inferior shift. A discriminant analysis indicated that at 1 month of age, a greater inclination and a smaller deviation of the vomer and a longer distance between the cleft edges of the lateral segments had a tendency to be associated with bending of the vomer or twisting of the premaxilla.

Cleft Lip↗

Applications of the Vitamin D sterol-Vitamin D receptor (VDR) conformational ensemble model.

Over the past 20 years much has been learned about the cellular actions of the steroid hormone 1alpha,25(OH)2-Vitamin D3 (1,25D). Perhaps most importantly structure-function studies led to the discovery that different chemical and physical features of 1,25D are preferred to initiate either exonuclear, non-genomic or endonuclear, genomic cellular signaling. It is well documented that both a 1alpha-OH and 25-OH, and a 6-s-trans, bowl-shaped, sterol conformation are absolutely required for efficient gene transcription, while 6-s-cis locked analogs and 1-deoxy, 25(OH)D3 metabolites activate a variety of non-genomic, rapid responses. These results and the observation that S237 (helix-3; H3) and R274 (H5) are the most static residues in the human 1,25D-Vitamin D receptor (VDR) X-ray construct (see B-values in pdb: 1DB1) and form H-bonds with the 1alpha-OH of 1,25D in the X-ray, genomic pocket (G-pocket), provided the basis for the molecular modeling experiments that led to the discovery of a putative VDR alternative ligand binding pocket (A-pocket). The conformational ensemble model generated from the in silico results provides an explanation for how the VDR can function as a receptor propagating both genomic and non-genomic signaling events. In this report the theoretical gating properties controlling ligand access to the A- and G-pockets will be compared and the model will be used to provide a molecular explanation for the confusing structure-function results pertaining to 1,25D, its side-chain metabolite, 23S,25R-1alpha,25(OH)2-D3-26,23-lactone (BS), and its synthetic two side-chain analog, 21-(3'-hydroxy-3'-methylbutyl)-1alpha,25(OH)2-D3 (KH or Gemini). In addition, evidence that the model is consistent with the pH requirement for Vitamin D sterol-VDR crystallization will be presented.

Arginine↗

Growth behavior of helical cellular automata.

A helical cellular automata (HCA) model constructed on a two-dimensional grid of cells with a helical structure is presented and the pattern formation of this model studied by numerous computer simulations. It is found that the evolutions of the HCA are sensitive to the circumference of the helix p. With various p, the initial growth of the model generates various patterns ranging from Sierpinski triangle gasket, complex textured pattern, to lateral quasiperiodic structure. A sudden transition from regular fractal to compact pattern occurs near the point where p is equal to a positive integer power of 2. With increasing height of the patterns (increasing growth time), the model also exhibits different growth behaviors in the vertical direction for various p, including the formation of regular periodic patterns and the evolution from initial regular patterns to eventual random structures. Fractal dimension analysis is used to characterize these different evolution processes quantitatively.

Journal Article↗

Mental health professional support in families with a member suffering from severe mental illness: a grounded theory model.

The aim of this study was to develop a model of mental health professional (MHP) support based on the needs of families with a member suffering from severe mental illness (SMI). Twelve family members were interviewed with the focus on their needs of support by MHP, then the interviews were analyzed according to the grounded theory method. The generated model of MHP support had two core categories: the family members' process from crisis to recovery and their interaction with the MHP about mental health/illness and daily living of the person with SMI. Interaction based on ongoing contact between MHP and family members influenced the family members' process from crisis towards recovery. Four MHP strategies--being present, listening, sharing and empowering--met the family members' needs of support in the different stages of the crisis. Being present includes early contact, early information and protection by MHP at onset of illness or relapse. Listening includes assessing burden, maintaining contact and confirmation in daily living for the person with SMI. Sharing between MHP and family members includes co-ordination, open communication and security in daily living for the person with SMI. Finally, the MHP strategy empowering includes creating a context, counselling and encouraging development for the family members. The present model has a holistic approach and can be used as an overall guide for MHP support in clinical care of families of persons with SMI. For future studies, it is important to study the interaction of the family with SMI and the connection between hope, coping and empowerment.

Adaptation, Psychological↗

Formal analysis of the urban 'Dutch model' with aims of re-formulating spatial quality concerns for pedestrian precincts in current New Town developments.

In the Japanese post WWII urban planning and design field, concerns for formal features regarding the sequential street-front visual image in new high-density urban spaces have been a rather subordinated subject. Famous New Town schemes such as Tsukuba Science City (1963), or Minato Mirai 21 (1965) for instance, are typical inland and reclaimed land examples that summarize the validity and limitations of functional zoning systems applied to these artificial urban developments for the last half century. In those examples, the interaction between space mobility and land use has not been explored sufficiently in order to create attractive street-front images, yet such interaction is essential to the way the cityscape and its character are perceived by the eye. However, current insight regarding the sustainable New Town paradigm has brought a renewed perspective regarding design policy of the pedestrian precinct. This study investigates the formal features of the sequential street-front image of Dutch late-medieval town examples which could help re-formulate the existing design policies regarding the quality of pedestrian space especially in the artificial reclaimed land design field. The purpose is to find out how the principles of those old high-density artificial environmental design models generate such effective interaction between mobility and land usage, creating an enriched aesthetic visual image of street-front space as a result.

City Planning↗

Kinetic model of the inositol trisphosphate receptor that shows both steady-state and quantal patterns of Ca2+ release from intracellular stores.

The release of Ca(2+) from intracellular stores via InsP(3) receptors shows anomalous kinetics. Successive additions of low concentrations of InsP(3) cause successive rapid transients of Ca(2+) release. These quantal responses have been ascribed to all-or-none release from stores with differing sensitivities to InsP(3) or, alternatively, to a steady-state mechanism where complex kinetic properties of the InsP(3) receptor allow partial emptying of all the stores. We present here an adaptive model of the InsP(3) receptor that can show either pattern, depending on the imposed experimental conditions. The model proposes two interconvertible conformational states of the receptor: one state binds InsP(3) rapidly, but with low affinity, whereas the other state binds slowly, but with high affinity. The model shows repetitive increments of Ca(2+) release in the absence of a Ca(2+) gradient, but more pronounced incremental behaviour when released Ca(2+) builds up at the mouth of the channel. The sensitivity to Ins P (3) is critically dependent on the density of InsP(3) receptors, so that different stores can respond to different concentration ranges of Ins P (3). Since the model generates very high Hill coefficients (h approximately 7), it allows all-or-none release of Ca(2+) from stores of differing receptor density, but questions the validity of the use of h values as a guide to the number of InsP(3) molecules needed to open the channel. The model presents a mechanism for terminating Ca(2+) release in the presence of positive feedback from released Ca(2+), thereby providing an explanation of why elementary Ca(2+) signals ('blips' and 'puffs') do not inevitably turn into regenerative waves.

Calcium↗

The cost-effectiveness of different management strategies for patients on chronic warfarin therapy.

OBJECTIVE: To examine the cost-effectiveness of moving from usual care to more organized management strategies for patients on chronic warfarin therapy. DESIGN: Using information available in the scientific literature, supplemented with data from a large health system and, when necessary, expert opinion, we constructed a 5-year Markov model to evaluate the health and economic outcomes associated with each of three different anticoagulation management approaches: usual care, anticoagulation clinic testing with a capillary monitor, and patient self-testing with a capillary monitor. PATIENTS: Three hypothetical cohorts of patients beginning long-term warfarin therapy were used to generate model results. MAIN RESULTS: Model results indicated that moving from usual care to anticoagulation clinic testing would result in a total of 1.7 thromboembolic events and 2.0 hemorrhagic events avoided per 100 patients over 5 years. Another 4.0 thromboembolic events and 0.8 hemorrhagic events would be avoided by moving to patient self-testing. When direct medical care costs and those incurred by patients and their caregivers in receiving care were considered, patient self-testing was the most cost-effective alternative, resulting in an overall cost saving. CONCLUSIONS: Results illustrate the potential health and economic benefits of organized care management approaches and capillary monitors in the management of patients receiving warfarin therapy.

Anticoagulants↗

Modeling SAR images with a generalization of the Rayleigh distribution.

Synthetic aperture radar (SAR) imagery has found important applications due to its clear advantages over optical satellite imagery one of them being able to operate in various weather conditions. However, due to the physics of the radar imaging process, SAR images contain unwanted artifacts in the form of a granular look which is called speckle. The assumptions of the classical SAR image generation model lead to a Rayleigh distribution model for the histogram of the SAR image. However, some experimental data such as images of urban areas show impulsive characteristics that correspond to underlying heavy-tailed distributions, which are clearly non-Rayleigh. Some alternative distributions have been suggested such as the Weibull, log-normal, and the k-distribution which had success in varying degrees depending on the application. Recently, an alternative model namely the alpha-stable distribution has been suggested for modeling radar clutter. In this paper, we show that the amplitude distribution of the complex wave, the real and the imaginery components of which are assumed to be distributed by the alpha-stable distribution, is a generalization of the Rayleigh distribution. We demonstrate that the amplitude distribution is a mixture of Rayleighs as is the k-distribution in accordance with earlier work on modeling SAR images which showed that almost all successful SAR image models could be expressed as mixtures of Rayleighs. We also present parameter estimation techniques based on negative order moments for the new model. Finally, we test the performance of the model on urban images and compare with other models such as Rayleigh, Weibull, and the k-distribution.

Journal Article↗

Mapping of phase response properties of monopolar ECG voltages.

In the present investigation an attempt has been made to study the phase response properties of monopolar chest lead ECG voltages. Using a generator model of the heart an equivalent circuit of ECG network has been developed. The equivalent impedance between WCT and probe electrode has been determined by reduction techniques. From this equivalent impedance the phaser characteristics of monopolar ECG voltages have been analysed for change in probe electrode locations. The source of the generated voltage, i.e., the heart, will develop a different voltage for its different condition. There will also be a change in impedances. Thus for the normal subject the distribution of the phaser of the ECG voltages will be different from that of the abnormal one. A software tool has been developed to evaluate the relative phase response of ECG voltages. The data acquisition of monopolar ECG records of chest leads V1 to V6 from chart recorder has been done with the help of AutoCAD application package. The harmonic constituents of ECG voltages have been evaluated at each harmonic plane and the phase characteristics have been studied in polar coordinate for normal subjects as well as for a typical case. An interesting result has been observed in typical cases which are indicated in the paper.

Algorithms↗

Structural modeling of dual-affinity purified Pho84 phosphate transporter.

The phosphate transporter Pho84 of Saccharomyces cerevisiae is predicted to contain 12 transmembrane (TM) regions, divided into two partially duplicated parts of 6 TM segments. The three-dimensional (3D) organization of the Pho84 protein has not yet been determined. However, the 3D crystal structure of the Escherichia coli MFS glycerol-3-phosphate/phosphate antiporter, GlpT, and lactose transporter, LacY, has recently been determined. On the basis of extensive prediction and fold recognition analyses (at the MetaServer), GlpT was proposed as the best structural template on which the arrangement of TM segments of the Pho84 transporter was fit, using the comparative structural modeling program MODELLER. To initiate an evaluation of the appropriateness of the Pho84 model, we have performed two direct tests by targeting spin labels to putative TM segments 8 and 12. Electron paramagnetic resonance spectroscopy was then applied on purified and spin labeled Pho84. The line shape from labels located at both positions is consistent with the structural environment predicted by the template-generated model, thus supporting the model.

Amino Acid Sequence↗

Satiety threshold: a quantitative model of maintained cocaine self-administration.

The intervals between self-injections of cocaine by rats are defined by an equation that contains only three parameters: the dose of cocaine administered, the elimination half-life of cocaine, and an amount of cocaine in the body, which we have termed the cocaine satiety threshold. This latter parameter is defined as the maximal level of cocaine at which the probability of self-administration approximates one and above which the probability of self-administration is low. The mathematical model generated mean values for the satiety threshold and the functional elimination half-life of cocaine of approximately 1.7 mg/kg (i.v.) and 8.2 min, respectively. Therefore, the simple equations presented here permit the measurement of the pharmacokinetics and pharmacodynamics of cocaine using self-administration behavior as a bioassay. Our satiety model predicts that when cocaine levels are maintained above the satiety threshold, rats would not self-administer cocaine. The elimination rate of cocaine at the satiety threshold was calculated to be approximately 2 microg kg(-1) s(-1). Therefore, an infusion of cocaine at this rate should maintain cocaine levels fractionally above the satiety threshold. A continuous infusion of cocaine at this rate prevented cocaine self-administration for the duration of the infusion, thereby confirming the validity of the satiety model. These equations provide a quantitative description of cocaine self-administration and contain no subjective terms, implying that concepts such as "craving", drug "wanting" and "liking" and "reinforcement", used in psychologically oriented models, are not necessary for descriptions of this behavior in rats.

Animals↗

Numerical simulation of nonlinear feedback model of saccade generation circuit implemented in the LabView graphical programming language.

The object-oriented graphical programming language LabView was used to implement the numerical solution to a computational model of saccade generation in primates. The computational model simulates the activity and connectivity of anatomical strictures known to be involved in saccadic eye movements. The LabView program provides a graphical user interface to the model that makes it easy to observe and modify the behavior of each element of the model. Essential elements of the source code of the LabView program are presented and explained. A copy of the model is available for download from the internet.

Animals↗