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PubMed1997

Bifurcation, bursting, and spike frequency adaptation.

Many neural systems display adaptive properties that occur on time scales that are slower than the time scales associated with repetitive firing of action potentials or bursting oscillations. Spike frequency adaptation is the name given to processes that reduce the frequency of rhythmic tonic firing of action potentials, sometimes leading to the termination of spiking and the cell becoming quiescent. This article examines these processes mathematically, within the context of singularly perturbed dynamical systems. We place emphasis on the lengths of successive interspike intervals during adaptation. Two different bifurcation mechanisms in singularly perturbed systems that correspond to the termination of firing are distinguished by the rate at which interspike intervals slow near the termination of firing. We compare theoretical predictions to measurement of spike frequency adaptation in a model of the LP cell of the lobster stomatogastric ganglion.

Action Potentials↗

PubMed2006

Genetic clonal diversity predicts progression to esophageal adenocarcinoma.

Neoplasms are thought to progress to cancer through genetic instability generating cellular diversity and clonal expansions driven by selection for mutations in cancer genes. Despite advances in the study of molecular biology of cancer genes, relatively little is known about evolutionary mechanisms that drive neoplastic progression. It is unknown, for example, which may be more predictive of future progression of a neoplasm: genetic homogenization of the neoplasm, possibly caused by a clonal expansion, or the accumulation of clonal diversity. Here, in a prospective study, we show that clonal diversity measures adapted from ecology and evolution can predict progression to adenocarcinoma in the premalignant condition known as Barrett's esophagus, even when controlling for established genetic risk factors, including lesions in TP53 (p53; ref. 6) and ploidy abnormalities. Progression to cancer through accumulation of clonal diversity, on which natural selection acts, may be a fundamental principle of neoplasia with important clinical implications.

Adenocarcinoma↗

PubMed2006

Assessment of human health vulnerability to climate variability and change in Cuba.

In this study we assessed the potential effects of climate variability and change on population health in Cuba. We describe the climate of Cuba as well as the patterns of climate-sensitive diseases of primary concern, particularly dengue fever. Analyses of the associations between climatic anomalies and disease patterns highlight current vulnerability to climate variability. We describe current adaptations, including the application of climate predictions to prevent disease outbreaks. Finally, we present the potential economic costs associated with future impacts due to climate change. The tools used in this study can be useful in the development of appropriate and effective adaptation options to address the increased climate variability associated with climate change.

Climate↗

PubMed2002

Flexible use of recent information in causal and predictive judgments.

Associative and statistical theories of causal and predictive learning make opposite predictions for situations in which the most recent information contradicts the information provided by older trials (e.g., acquisition followed by extinction). Associative theories predict that people will rely on the most recent information to best adapt their behavior to the changing environment. Statistical theories predict that people will integrate what they have learned in the two phases. The results of this study showed one or the other effect as a function of response mode (trial by trial vs. global), type of question (contiguity, causality, or predictiveness), and postacquisition instructions. That is, participants are able to give either an integrative judgment, or a judgment that relies on recent information as a function of test demands. The authors concluded that any model must allow for flexible use of information once it has been acquired.

Association Learning↗

PubMed2004

A quantitative evaluation of the AVITEWRITE model of handwriting learning.

Much sensory-motor behavior develops through imitation, as during the learning of handwriting by children. Such complex sequential acts are broken down into distinct motor control synergies, or muscle groups, whose activities overlap in time to generate continuous, curved movements that obey an inverse relation between curvature and speed. The adaptive vector integration to endpoint handwriting (AVITEWRITE) model of Grossberg and Paine (2000) [A neural model of corticocerebellar interactions during attentive imitation and predictive learning of sequential handwriting movements. Neural Networks, 13, 999-1046] addressed how such complex movements may be learned through attentive imitation. The model suggested how parietal and motor cortical mechanisms, such as difference vector encoding, interact with adaptively-timed, predictive cerebellar learning during movement imitation and predictive performance. Key psychophysical and neural data about learning to make curved movements were simulated, including a decrease in writing time as learning progresses; generation of unimodal, bell-shaped velocity profiles for each movement synergy; size scaling with isochrony, and speed scaling with preservation of the letter shape and the shapes of the velocity profiles; an inverse relation between curvature and tangential velocity; and a two-thirds power law relation between angular velocity and curvature. However, the model learned from letter trajectories of only one subject, and only qualitative kinematic comparisons were made with previously published human data. The present work describes a quantitative test of AVITEWRITE through direct comparison of a corpus of human handwriting data with the model's performance when it learns by tracing the human trajectories. The results show that model performance was variable across the subjects, with an average correlation between the model and human data of 0.89+/-0.10. The present data from simulations using the AVITEWRITE model highlight some of its strengths while focusing attention on areas, such as novel shape learning in children, where all models of handwriting and the learning of other complex sensory-motor skills would benefit from further research.

Attention↗

PubMed2003

Systems modelling of the relationship between training and performance.

Mathematical models may provide a method of describing and predicting the effect of training on performance. The current models attempt to describe the effects of single or multiple bouts of exercise on the performance of a specific task on a given day. These models suggest that any training session increases fitness and provokes a fatigue response. Various methods of quantifying the training stimulus (training impulse, absolute work, psychophysiological rating) and physical performance (criterion scale, arbitrary units) are employed in these models. The models are empirical descriptions and do not use current knowledge regarding the specificity of training adaptations. Tests of these models with published data indicate discrepancies between the predicted and measured time course of physiological adaptations, and between the predicted and measured performance responses to training. The relationship between these models and the underlying physiology requires clarification. New functional models that incorporate specificity of training and known physiology are required to enhance our ability to guide athletic training, rehabilitation and research.

Humans↗

PubMed1980

Orientation-specific adaptation: effects of checkerboards on the detectability of gratings.

The predictive values of Fourier analysis and local-feature analysis of spatial stimuli were compared in an orientation-specific adaptation experiment. Observers adapted to checkerboard patterns, which have fundamental Fourier components oriented 45 degrees away from the edges. Detection of gratings was found to be maximally impaired when fundamental Fourier components of adaptation and test patterns were in the same orientation and minimal when edges were aligned. The orientation spread and amount of adaptation effect were similar to that found in previous experiments which employed sinusoids as adaptation and test stimuli.

Adaptation, Ocular↗

PubMed1999

A longitudinal analysis of maternal abuse potential and developmental delays in children of adolescent mothers.

OBJECTIVE: This project was designed to examine the impact of adolescent mothers' abuse potential on the development of preschool children. The specific aims were to demonstrate relationships between maternal abuse potential and developmental problems in preschool children, to examine these relationships across time, and to determine whether maternal abuse potential predicted developmental delays after controlling for problematic parenting orientations. METHOD: Using a longitudinal design, we examined 146 first time mothers and their children. Maternal abuse potential was assessed when children were 1, 3, and 5 years old; problematic parenting orientation was assessed when the children were 6 months old; and child development (i.e., IQ, adaptive behavior, and behavior problems) was assessed at ages 3 and 5. RESULTS: Regression analyses revealed significant relationships between maternal abuse potential and a variety of developmental problems. Path analyses revealed unidirectional relationships between abuse potential predicting IQ and adaptive behaviors. Further analyses indicated that maternal abuse potential at 1 and 3 years predicted intelligence and adaptive behavior at ages 3 and 5, even when problematic parenting orientation was controlled. In contrast, children's behavioral problems at ages 3 and 5 was better accounted for by problematic parenting orientation than by abuse potential. CONCLUSIONS: The results of this study revealed that developmental delays in children of adolescent are related to abuse potential. Two pathways were found for predicting developmental delays: One pathway linked child abuse potential with IQ and adaptive functioning: the other pathway showed that problematic parenting orientation accounted for the development of emotional and behavioral problems.

Adolescent↗

PubMed1999

The pH partition theory predicts the accumulation and toxicity of doxorubicin in normal and low-pH-adapted cells.

The accumulation and toxicity of the weak base doxorubicin has been investigated as a function of extracellular pH, intracellular pH and the cellular pH gradient in cells previously cultured under normal (pH 7.4) and low-pH (6.8) conditions. Low-pH-adapted cells exhibit transmembrane pH gradients which substantially differ from normal cells at the same extracellular pH. No relationship was obtained between intracellular pH and the uptake or toxicity of doxorubicin in the two cell types. In contrast, doxorubicin accumulation and toxicity increased with increasing extracellular pH in both normal and low-pH-adapted cells. However, at the same extracellular pH, drug cytotoxicity was more pronounced in normal than in low-pH-adapted cells. The difference in doxorubicin accumulation and cytotoxicity at the same extracellular pH was found to be dependent on the difference in the transmembrane pH gradient of the two cell types. As the cellular pH gradient differs between tumour and normal tissue, this observation suggests a basis for enhancing cellular drug uptake in either tissue type.

Animals↗

PubMedDate not supplied

Failure to master early developmental tasks as a predictor of adaptation to cancer in the young adult.

The ability of young adults to adapt to living with a cancer diagnosis and to negotiate the healthcare system is influenced by their level of maturity. If adolescent developmental tasks have been unresolved or pathologically resolved, they are likely to be reenacted during the various stages of the malignancy. Retrospective review of case histories that illustrate the diverse ranges of adaptation to life-threatening illness indicates that success or failure in achieving ego autonomy and continuity in adolescence significantly influences the young adult's capacity to cope with the malignancy. Psychosocial assessment of the young adult patient and spouse, with attention to childhood, adolescent, and family history, will assist the oncology nurse in predicting the individual's capacity for adapting to the illness and complying with treatment. This developmental information will allow clinicians to modify interventions to compensate for earlier stage deficits.

Adaptation, Psychological↗

PubMed1998

Loading Mode Interactions in Simulations of Long Bone Cross-Sectional Adaptation.

Although many bone adaptation theories have been formulated to address both trabecular and cortical adaptation, most applications have focused on trabecular adaptation. Thus far, no thorough investigations of the influence of different types of loading on predicted patterns of long bone cross-sectional adaptation have been reported. In the current study, we present a new model for long bone cross-sectional adaptation that incorporates axial, bending and torsional loading components. We found that bending moments have a strong potential to modulate cross-sectional geometry, but can produce unforseen (and unrealistic) geometric instabilities. Torsional moments have the ability to suppress these instabilities, suggesting that torsion may play a more significant role in guiding long bone development than previously recognized. Our results also call into question the concept of strict "remodeling equilibrium," suggesting that long bones do not necessarily approach a state of uniform mechanical stimulation. This modeling approach provides an additional perspective on experimental studies, and may lead to a greater understanding of the interaction between mechanics and biology in long bone adaptation.

Journal Article↗

PubMed2003

The evolution of enzyme specificity in Fasciola spp.

Fasciola spp., commonly known as liver fluke, are significant trematode parasites of livestock and humans. They secrete several cathepsin L-like cysteine proteases, some of which differ in enzymatic properties and timing of expression in the parasite's life cycle. A detailed sequence and evolutionary analysis is presented, based on 18 cathepsin L-like enzymes isolated from Fasciola spp. (including a novel clone identified in this study). The enzymes form a monophyletic group which has experienced several gene duplication events over the last approximately 135 million years, giving rise to the present-day enzymatic repertoire of the parasite. This timing of these duplications appears to correlate with important points in the evolution of the mammalian hosts. Furthermore, the dates suggest that Fasciola hepatica and Fasciola gigantica diverged around 19 million years ago. A novel analysis, based on the pattern of amino acid diversity, was used to identify sites in the enzyme that are predicted to be subject to positive adaptive evolution. Many of these sites occur within the active site cleft of the enzymes, and hence would be expected to lead to differences in substrate specificity. Using homology modeling, with reference to previously obtained biochemical data, we are able to predict S2 subsite specificity for these enzymes: specifically those that can accommodate bulky hydrophobic residues in the P2 position and those that cannot. A number of other positions subject to evolutionary pressure and potentially significant for enzyme function are also identified, including sites anticipated to diminish cystatin binding affinity.

Amino Acid Sequence↗

PubMed2000

Modeling inhibitory plasticity in the electrosensory system of mormyrid electric fish.

Mathematical analyses and computer simulations are used to study the adaptation induced by plasticity at inhibitory synapses in a cerebellum-like structure, the electrosensory lateral line lobe (ELL) of mormyrid electric fish. Single-cell model results are compared with results obtained at the system level in vivo. The model of system level adaptation uses detailed temporal learning rules of plasticity at excitatory and inhibitory synapses onto Purkinje-like neurons. Synaptic plasticity in this system depends on the time difference between pre- and postsynaptic spikes. Adaptation is measured by the ability of the system to cancel a reafferent electrosensory signal by generating a negative image of the predicted signal. The effects of plasticity are tested for the relative temporal correlation between the inhibitory input and the sensory input, the gain of the sensory signal, and the presence of shunting inhibition. The model suggests that the presence of plasticity at inhibitory synapses improves the function of the system if the inhibitory inputs are temporally correlated with a predictable electrosensory signal. The functional improvements include an increased range of adaptability and a higher rate of system level adaptation. However, the presence of shunting inhibition has little effect on the dynamics of the model. The model quantifies the rate of system level adaptation and the accuracy of the negative image. We find that adaptation proceeds at a rate comparable to results obtained from experiments in vivo if the inhibitory input is correlated with electrosensory input. The mathematical analysis and computer simulations support the hypothesis that inhibitory synapses in the molecular layer of the ELL change their efficacy in response to the timing of pre- and postsynaptic spikes. Predictions include the rate of adaptation to sensory stimuli, the range of stimulus amplitudes for which adaptation is possible, the stability of stored negative images, and the timing relations of a temporal learning rule governing the inhibitory synapses. These results may be generalized to other adaptive systems in which plasticity at inhibitory synapses obeys similar learning rules.

Action Potentials↗

PubMed2004

The use of APACHE II prognostic system in difficult-to-wean patients after long-term mechanical ventilation.

BACKGROUND AND OBJECTIVE: To examine the calibration of the prognostic system Acute Physiology and Chronic Health Evaluation Score (APACHE II) regarding hospital mortality and predicting weaning outcome after long-term mechanical ventilation of the lungs. METHODS: Prospective observational cohort study performed in a respiratory intensive care unit including 246 patients whose lungs were ventilated for 42.1+/-37.8 (median 30) days in the referring hospital. APACHE II (24 h after admission to our respiratory intensive care unit) and the cause of respiratory failure, underlying disease, prior duration of mechanical ventilation and gender were recorded. The predictive power was evaluated with sensitivity and specificity for different cut-off points and summarized in a receiver operating characteristic curve. RESULTS: No difference was found between survivors (APACHE II 16.0+/-4.3) and non-survivors (APACHE II 16.9+/-5.1). In a mean time of 8.0+/-10.3 days, 146 patients (59.3%) were successfully weaned (APACHE II 15.2+/-3.5). One-hundred patients (40.7%) were considered unweanable (APACHE II 17.7+/-5.3). Recalibration of APACHE II to predict weaning failure was possible, resulting in an area under the receiver operating characteristic curve (AUC) of 0.638. Furthermore the AUC improved to 0.723 by changing the weights of selected APACHE items and introducing external factors. Diagnostic accuracy fell from group with mechanical ventilation < or =25 days (AUC 0.770) to group with mechanical ventilation >50 days (AUC 0.517). CONCLUSIONS: APACHE II did not predict hospital mortality after long-term mechanical ventilation of the lungs. Not the original APACHE II but a recalibrated and adapted APACHE II can be useful to predict weaning outcome in patients with less than 25 days of prior lung ventilation.

APACHE↗

PubMed2025

Heat-Induced Secondary Dormancy Contributes to Local Adaptation in Arabidopsis thaliana.

Seeds should not germinate in conditions unsuitable for seedling growth. Dormancy, which allows seeds to remain inactive in an environment that would otherwise enable germination, helps optimise the timing of germination. Primary dormancy, developed during seed maturation on the parent plant, prevents immediate germination post-dispersal, regardless of external conditions. Secondary dormancy, however, is triggered post-dispersal when seeds face unfavourable conditions, enabling them to re-enter dormancy even if initially non-dormant. This mechanism allows seeds to fine-tune germination according to environmental conditions. In this study, we examined the role of heat-induced secondary dormancy in local adaptation by analysing natural variations within 361 Arabidopsis thaliana accessions from across Europe. We discovered that secondary dormancy acquisition varies with primary dormancy levels and after-ripening. Both primary and heat-induced secondary dormancy exhibited adaptive clines along temperature and precipitation gradients, with secondary dormancy showing a steeper cline, indicating its significant role in local adaptation. Using species distribution models, we predicted that genotypes with high secondary dormancy would show greater resilience to future climate changes. Additionally, we identified specific genomic regions controlling secondary dormancy levels including a novel candidate gene for secondary dormancy variation. Our findings show that secondary dormancy is a complex adaptive mechanism and a predominant contributor to the dormancy trait syndrome that favours plant survival in habitats exposed to harsh summers.

Arabidopsis↗

PubMed1983

Mediating factors in the modification of smoking behavior.

This study was designed to investigate two personality variables that may influence the effectiveness of covert sensitization in reducing smoking behavior. These are GSR reactivity to stressors and GSR adaptation to repeated stressors. It was predicted that both high reactivity and nonadaptivity to stressors would facilitate covert sensitization therapy. Fifty-nine subjects underwent treatment and were followed up at 3, 6 and 12 week intervals. Subjects were distributed among four groups: A. High reactors, nonadaptive (15); B. High reactors, adaptive (14); C. Low reactors, nonadaptive (9); D. Low reactors, adaptive (21). The results demonstrate that the measure of reactivity to stressors is significantly related to the success of the treatment, but the relevance of the measure of adaptivity factor was not demonstrated.

Adult↗

PubMed1998

The bottleneck: mitochondrial imperatives in oogenesis and ovarian follicular fate.

Molecular geneticists and ovarian physiologists today face the challenge of defining and reconciling two major biological imperatives that each center on oogenesis, folliculogenesis and competition between ovarian follicles: (1), defining how the mitochondrial genome--important in both aging and a number of serious mitochondrial diseases--is refreshed and purified as it passes, via the oocyte's cytoplasm, from one generation to the next; and (2), endeavouring to discover what cytoplasmic factor(s) it is that permits some eggs but not others to produce viable embryos and ongoing pregnancies. We review here in detail the passage of mitochondria through the female germ cell line. For mitochondria, the processes of oogenesis, follicle formation and loss constitute a restriction/amplification/constraint event of the kind predicted by L. Chao for purification and refinement of a haploid genome. We argue that maintaining the integrity of mitochondrial inheritance is such a strong evolutionary imperative that we should expect at least some features of ovarian follicular formation, function and loss to be primarily adapted to this specific purpose. We predict, moreover, that to prevent accumulation of mild mitochondrial genomes in the population there is a need for physiological female sterility prior to total depletion of ovarian oocytes, a phenomenon for which there is empirical evidence and which we term the oöpause.

DNA, Mitochondrial↗

PubMed1998

A theoretical model to predict distribution of the fabric tensor and apparent density in cancellous bone.

The adaptation of cancellous bone to mechanical forces is well recognized. Theoretical models for predicting cancellous bone architecture have been developed and have mainly focused on the distribution of trabecular mass or the apparent density. The purpose of this study was to develop a theoretical model which can simultaneously predict the distribution of trabecular orthotropy/orientation, as represented by the fabric tensor, along with apparent density. Two sets of equations were derived under the assumption that cancellous bone is a biological self-optimizing material which tends to minimize strain energy. The first set of equations provide the relationship between the fabric tensor and stress tensor, and have been verified to be consistent with Wolff's law of trabecular architecture, that is, the principal directions of the fabric tensor coincide with the principal stress trajectories. The second set of equations yield the apparent density from the stress tensor, which was shown to be identical to those obtained based on local optimization with strain energy density of true bone tissue as the objective function. These two sets of equations, together with elasticity field equations, provide a complete mathematical formulation for the adaptation of cancellous bone.

Bone Density↗