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PubMed2000

[Influences of chronic stress on central nervous systems].

Chronic mild or moderate stress elicits an adaptive change in central nervous systems that function to maintain homeostasis. The principal components of stress response are the extrahypothalamic corticotropin-releasing hormone (CRH) and the locus coeruleus (LC)-norepinephrine (NE) systems. CRH is known to produce various stress-, anxiety- and arousal-associated behaviors in animals. Moreover, CRH causes an increase in the firing rate and activity of tyrosine hydroxylase in the LC, and NE release in LC projection areas. It is thought that chronic inescapable and unpredictable stress can result in a sustained dysregulation of both CRH neuronal activity and LC-NE systems. One may hypothesize that the NE-CRH interaction occurs in the terminal projection of forebrain NE systems, the hypothalamic paraventricular nucleus (PVN), the bed nucleus of the stria terminalis (BNST) and the central nucleus of the amygdala (CeA) where NE stimulates CRH release. Such CRH-NE-CRH feed-forward systems elicit progressive augmentation of stress responsivity with repeated exposure. The beta-adrenergic receptor down-regulation is induced by acute and chronic exposure to moderate and predictable stress, implying an adaptation to stress. However, chronic unpredictable (variable) stress (CVS), a model for depression, up-regulated the beta-AR. In our laboratory, we found that concurrent treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram caused beta-R down-regulation in the frontal cortex of rats treated with CVS for 14 days. As previously reported by the authors, an increase in 5-HT availability plays a role in preserving beta-R down-regulation by NE potentiating agents. In depressed patients, hyperactivation of the CRH-NE systems caused by the CRH-NE feed-forward system is thought to be involved in generating anxiety, sympathetic activation and hyperarousal. Moreover, a decrease in the 5-HT turnover in depressed patients has been reported. Accordingly, it is proposed that an increase in 5-HT availability by SSRI might contribute to normalize beta-R down-regulation as an adaptive regulatory mechanism against excessive CRH-NE neurotransmission under a "stressful" situation.

Animals↗
PubMed1992

Analysis of knee vibration signals using linear prediction.

Clinical methods used at present for the diagnosis of cartilage pathology in the knee are invasive in nature, and carry some risks. There exists a need for the development of a safe, objective, noninvasive method for early detection, localization, and quantification of cartilage pathology in the knee. This paper investigates the possibility of developing such a method based on an analysis of vibrations produced by joint surfaces rubbing against one another during normal movement. In particular, the method of modeling by linear prediction is used for adaptive segmentation and parameterization of knee vibration signals. Dominant poles are extracted from the model system function for each segment based on their energy contributions and bandwidths. These dominant poles represent the dominant features of the signal segments in the spectral domain. Two-dimensional feature vectors are then constructed using the first dominant pole and the ratio of power in the 40-120 Hz band to the total power of the segment. The potential use of this method to distinguish between vibrations produced by normal volunteers and patients known to have cartilage pathology (chondromalacia) is discussed.

Auscultation↗
PubMed1976

Scotopic and photopic vision in the California ground squirrel: physiological and anatomical evidence.

The California ground squirrel is a highly diurnal species previously thought to have an all-cone retina. This issue was re-examined in physiological and anatomical experiments. The electroretinogram (ERG) was used to measure the spectral sensitivity of the eye under different conditions of adaptation. The occurrence of a Purkinje shift could be demonstrated, although there was some indication that not all members of this species show such a shift. Spectral sensitivity of the dark-adapted eye of this squirrel is close to that predicted by a typical mammalian rhodopsin. Light adaptation produces a shift in spectral sensitivity to a peak location of about 525 nm. It was shown that two mechanisms having different spectral sensitivities contribute to the photopically recorded ERG. The degree to which these two mechanisms contribute to the ERG was found to be strikingly different from the degree to which the two contribute to visual behavior. Our anatomical results indicate that the retina of the California ground squirrel has two structurally distinct photoreceptors which, on the basis of various criteria, can be classified as cone and rod-like. The rod-like receptors comprise about 6-7% of the total. The two photoreceptor types differ in placement of their inner segments, size of their outer segments, outer segment ultrastructure, and terminal structure and organization.

Adaptation, Ocular↗
PubMed1996

Adaptation to myocardial ischemia during repeated dynamic exercise in relation to findings at cardiac catheterization.

It has been suggested that the myocardium is able to recruit endogenous protective mechanisms in response to repeated ischemia and reperfusion. We set out to study whether this is manifested in patients with coronary artery disease in the form of fewer signs of myocardial ischemia during the second of two successive exercise tests and whether any relations exist between ischemia adaptation and findings at cardiac catheterization. Twenty-one patients with typical angina pectoris symptoms underwent two repeated bicycle exercise tests with identical protocols, followed by cardiac catheterization and coronary angiography the next day. The first exercise test was discontinued whenever a 2 mm ST depression in the electrocardiogram (ECG) was achieved or further exercise was limited by symptoms. The second exercise test was performed after disappearance of the symptoms or ST depression or both. Kaplan-Meier survival analysis for the appearance of a 1 mm ST depression demonstrated improved ischemia tolerance during the second test, when the required time for its appearance was significantly longer (6.5 +/- 0.8 min vs 4.5 +/- 0.5 min; p = 0.005). The maximal intensity of anginal pain was lower during the second exercise (2.2 +/- 1.0 min vs 0.7 +/- 0.3 min in Borg's scale; p < 0.001), and the time required for disappearance of the ST depression was shorter after this exercise (3.0 +/- 0.8 min vs 6.2 +/- 0.9 min; p = 0.003), with a similar tendency in the disappearance of angina. The rate-pressure product on the appearance of a 1 mm ST depression was significantly higher during the second test (17,990 +/- 1210 mm Hg x min-1 vs 15,960 +/- 869 mm Hg x min-1; p = 0.009). Eighteen of the patients had three-vessel disease, as evidenced by coronary angiography, and the change in the time required for the appearance of a 1 mm ST depression in the repeated exercise tests was inversely correlated with the severity of the left anterior descending (LAD) coronary artery obstruction (r = -0.61; p = 0.006) and left ventricular end-diastolic pressure (r = -0.50; p = 0.03). No significant correlation with the degree of collateral vessels was found. We conclude that most patients with extensive coronary artery disease are able to increase their tolerance of ischemia during repeated dynamic exercise and that increased vasodilation and oxygen delivery are the major mechanisms for this warm-up phenomenon. On the other hand, collaterals visible in routine resting anglography do not predict the degree of adaptation to ischemia during repeated dynamic exercise.

Angina Pectoris↗
PubMed1996

Smoothness within ruggedness: the role of neutrality in adaptation.

RNA secondary structure folding algorithms predict the existence of connected networks of RNA sequences with identical structure. On such networks, evolving populations split into subpopulations, which diffuse independently in sequence space. This demands a distinction between two mutation thresholds: one at which genotypic information is lost and one at which phenotypic information is lost. In between, diffusion enables the search of vast areas in genotype space while still preserving the dominant phenotype. By this dynamic the success of phenotypic adaptation becomes much less sensitive to the initial conditions in genotype space.

Adaptation, Biological↗
PubMed2025

ESMpHLA: Evolutionary Scale Model-Based Deep Learning Prediction of HLA Class I Binding Peptides.

The recognition of endogenous peptides by HLA class I plays a crucial role in CD8+ T cell immune responses and human adaptive cell immune. Thus, the prediction of HLA class I-peptide binding affinities is always the core issue for the research of immune recognition and vaccine development. In this study, an evolutionary scale model (ESM) combined with parallel CNN blocks and a cross attention mechanism was used to construct a novel ESMpHLA model for predicting HLA class I binding peptides. Based on the 91,560 binding peptides of 41 HLA-A alleles, 56,731 of 50 HLA-B alleles and 2444 of 10 HLA-C alleles, the ESMpHLA model was successfully established and achieved satisfying prediction performances with the overall accuracy and AUC values of 0.874 and 0.938 for the test dataset. The results indicate that the ESMpHLA model performs well in dealing with different HLA class I 2-field alleles as well as the peptides with different lengths. Then, the generalisation ability of the ESMpHLA model was validated by an independent test dataset compiled from recent IEDB weekly benchmark datasets. The results showed that the ESMpHLA model achieved the highest ROC-AUC and PR-AUC values when compared with the latest BVMHC, CapsNet-MHC, STMHCpan and BVLSTM models. In addition, two ensemble models were also established by integrating the above 5 deep learning models using soft-voting and hard-voting strategies.

Humans↗
PubMed2003

Adaptive sex-specific life history plasticity to temperature and photoperiod in a damselfly.

We investigated four predictions about how temperature, photoperiod and sex affect the life history plasticity and foraging activity of a damselfly. (i) As predicted, increased temperatures increased foraging activity and growth rates, but in contrast with the prediction, late photoperiod (high time stress) did not affect foraging activity and growth rate. (ii) Unexpectedly, the increase in growth rate at increasing temperatures was not larger under high time stress. (iii) As predicted, age and size at emergence decreased at higher temperatures and at the late photoperiod. Temperature-induced life history shifts were direct or the result of behavioural growth mediation depending on the temperature range. Photoperiod-induced life history shifts were direct. (iv) As predicted, males emerged before females but at a smaller size. The degree of sexual size dimorphism was influenced by the joint effects of temperature and photoperiod. We could only detect genetic variation in size plasticity to photoperiod. The match between the sex-specific life history responses to temperature and photoperiod and predictions by relevant optimality models suggests adaptive life history plasticity to these variables.

Adaptation, Physiological↗
PubMed1991

Trivers-Willard effect in contemporary North American society.

The Trivers-Willard hypothesis joins the ideas of R.A. Fisher and A.J. Bateman to model parental investment strategies. Trivers and Willard argue that any overall investment bias favoring either daughters or sons would be maladaptive. Nevertheless, they suggest that, in effectively polygynous species, more complex, conditional sex biases could be adaptive. In particular, they predict that parents in good condition will bias their investment toward sons and that parents in poor condition will bias their investment toward daughters. Among a sample of approximately 900 U.S. mothers we examined several measures of maternal investment including birth weight, interbirth interval and lactational commitment. Maternal condition was assessed by income and by the presence or absence of a coresident adult male. Some measures of investment (five of 14 statistical tests) showed marked and significant sex-by-condition interactions of the type and in the direction predicted by Trivers and Willard; none showed significant effects in the opposite direction. No conscious mediation is required to produce the observed investment patterns.

Analysis of Variance↗
PubMed2004

Limitations of codon adaptation index and other coding DNA-based features for prediction of protein expression in Saccharomyces cerevisiae.

The relationship between codon usage and protein/mRNA expression in S. cerevisiae has been extensively studied. Recently, protein expression data for the whole yeast genome was published. We investigate which properties of coding DNA sequences can be used to predict expression levels. The new algorithm by Carbone et al. for computing dominating codon bias in a genome is evaluated. It is concluded that it works at least as well as existing methods, and eliminates the need to arbitrarily choose a set of highly expressed genes. Also, the hypothesis that information on codon pair frequencies can be used to predict expression is investigated. Our conclusion is that codon pairs do not contribute more information than do single codon frequencies. Overall correlation between predicted and actual expression data using properties of coding DNA sequences is around 0.65. Hence, while being a useful source of information, the expression levels predicted by these methods should only be used as a rule of thumb.

Algorithms↗
PubMed2002

Pharmacokinetic and pharmacodynamic study of IST-622, a novel synthetic derivative of chartreusin, by oral administration in a phase II study of patients with breast cancer.

The aim of this study was to analyze the pharmacokinetics and pharmacodynamics (PK/PD) of 6- O-(3-ethoxypropionyl)-3',4'- O-exo-benzylidene-chartreusin (IST-622) and its metabolites, and to develop limited sampling models (LSM). Based on the data from 18 patients with breast cancer who were treated orally with 280 or 525 mg/m(2) of IST-622 once daily after breakfast for five consecutive days, we analyzed the relationship between the area under the plasma concentration versus time curve (AUC) and toxicities using a sigmoid E-max model and logistic regression. Plasma concentrations of IST-622 and its metabolites, 3',4'- O-exo-benzylidene-chartreusin (A-132) and 3"-demethyl-3',4'- O-exo-benzylidene-chartreusin (A-132M), were measured at 1, 2, 4, 8 and 24 h after administration on day 1. The AUC was calculated using the trapezoidal method. We also developed a LSM using stepwise linear regression analysis. IST-622 was detected in very few patients, and its concentration was very low and could be disregarded. It was suggested that meals promoted absorption of IST-622. AUCs of A-132 plus A-132M showed a better correlation with the rates of decrease and nadir counts of leukocytes, neutrophils and platelets than the AUC of each metabolite separately. Patients with the sum of AUCs more than 70 microg.h/ml showed severe myelotoxicities. Moreover, logistic regression analysis showed that grade 4 myelotoxicities would be seen in 30% of patients at an AUC of 65 microg.h/ml. We also developed an unbiased and precise LSM: AUC 0-24h =C 8h x17.6-0.95, where C(8h) denotes the sum of plasma concentrations of A-132 and A-132M. Myelotoxicities showed a good correlation with AUC(0-24h), and based on the results, it was decided that the target AUC was 65 microg.h/ml. The LSM was very convenient for estimating AUC(0-24h) and sufficiently accurate. These results show the possibility of predicting toxicities and dose adaptation for interpatient variability using LSM.

Administration, Oral↗
PubMed2000

A model of motion adaptation and motion after-effects based upon principal component regression.

A computational model to help explain effects of adaptation to moving signals is compared with established energy (linear regression) models of motion detection. The proposed model assumes that processed image signals are subject to error in both dimensions of space and time. This assumption constrains models of motion perception to be based upon principal component regression rather than linear regression. It is shown that response suppression of model complex cell neurons that input into the model may account for (1) increases in perceived speed after adaptation to static patterns and testing with slowly moving patterns, (2) significant increases in perceived speed after adaptation to patterns moving at a medium speed and testing at high speed, and (3) decreases in perceived speed in the opponent direction to a quickly moving adapting signal. Neither of predictions (2) or (3) are general features of established accounts of motion detection by visual processes based upon linear regression. Comparisons of the proposed model's speed transfer function with existing psychophysical data suggests that the visual system processes motion signals with the tacit assumption that image measurements are subject to error in both space and time.

Animals↗
PubMed1977

Human skin burns induced by defibrillator default current: a mathematical simulation model.

A preliminary model was prepared for the development of superficial burns which can result from the interaction of faulty defibrillator and other electrical operating room equipment. A thermal model previously used to predict retinal coagulation was adapted to give temperature rise history of the skin. Skin resistance is assumed to decrease rapidly due to the instability of a small volume near the surface. Heating due to dissipation of the defibrillator capacitor energy in this skin volume is shown to be high enough to cause burns. A sensitivity analysis is included to isolate the dominant input parameters. Recommendations are made for future research.

Burns, Electric↗
PubMed1996

Non-linear algorithms for processing biological signals.

This paper illustrates different approaches to the analysis of biological signals based on non-linear methods. The performance of such approaches, despite the greater methodological and computational complexity is, in many instances, more successful compared to linear approaches, in enhancing important parameters for both physiological studies and clinical protocols. The methods introduced employ median filters for pattern recognition, adaptive segmentation, data compression, prediction and data modelling as well as multivariate estimators in data clustering through median learning vector quantizers. Another approach described uses Wiener-Volterra kernel technique to obtain a satisfactory estimation and causality test among EEG recordings. Finally, methods for the assessment of non-linear dynamic behaviour are discussed and applied to the analysis of heart rate variability signal. In this way invariant parameters are studied which describe non-linear phenomena in the modelling of the physiological systems under investigation.

Algorithms↗
PubMed1987

The role of melatonin and serotonin in aging.

The hypothesis presented in this paper defines aging as a pathological process originating in the pineal gland. This results in a diminished output of melatonin, along with a diminished melatonin to serotonin ratio, leading to a decline in adaptive processes and a predictable syndrome manifested by the "diseases of the aged" (DOA) and subsequent death of the organism. That is, aging is a syndrome of relative melatonin deficiency resulting from the gradual failure of the pineal gland.

Aging↗
PubMed1995

Variations in sensitivity, specificity, and predictive value of a dietary fat screener modified from Block et al.

OBJECTIVE: To evaluate the ability of a fat screener modified from Block et al to discriminate persons whose diets consist of 38% of kilocalories or more from fat from the remainder of the population. DESIGN: Sensitivity, specificity, and positive predictive value of the adapted screener were calculated. Percentage of kilocalories from fat was assessed by means of a semi-quantitative food frequency questionnaire. Three cutoff points from the fat screener were used to examine which best identified those whose diets consisted of 38% of kilocalories or more from fat. SUBJECTS: Nine hundred ninety-seven persons responded to a food frequency questionnaire sent to a random sample of 2,000 members of a health maintenance organization. RESULTS: Sensitivity and specificity varied depending on which cutoff point from the fat screener was used. Sensitivity reached a high of 83.3% and specificity reached a high of 92.1%, but the screener was never highly sensitive and specific simultaneously, and the results did not vary considerably by race. The screener had low rates of gross misclassification into quintiles (< or = 2.7%) and was more effective at classifying respondents into quintiles of total fat intake (64.9% to 85.5% classified in the same quintile) than into quintiles of percentage of kilocalories from fat (43.2% to 60.5% classified in the same quintile). CONCLUSIONS: The adapted fat screener may be used in conjunction with other dietary evaluation methods, but it exhibits insufficient sensitivity and specificity to be used as a single assessment method.

Adult↗
PubMed2003

Water quality in Sepetiba Bay, Brazil.

Sepetiba Bay is located at 23 degrees S, 44 degrees W in Rio de Janeiro State, Brazil. Water samples were taken at eight locations adjacent to the north shore of the Bay, near to villages and towns without sewage treatment provision. The samples were analysed and total and faecal coliform concentrations determined. A hydrodynamic model of the Bay was used together with a species dispersion model based on an adaptive quadtree mesh to predict faecal concentrations in the Bay. Effluent sources used in the model were defined using population data from census returns with flow and concentration values estimated using standard values recommended by the World Bank (WB) and the World Health Organisation (WHO). Sufficient agreement was obtained between the measured and predicted concentrations to support the use of WB and WHO summary statistics to estimate sources of sewage.

Brazil↗
PubMed2002

Comprehensive sequence analysis of translation termination sites in various eukaryotes.

Recent investigations into the translation termination sites of various organisms have revealed that not only stop codons but also sequences around stop codons have an effect on translation termination. To investigate the relationship between these sequence patterns and translation as well as its termination efficiency, we analysed the correlation between strength of consensus and translation efficiency, as predicted according to Codon Adaptation Index (CAI) value. We used RIKEN full-length mouse cDNA sequences and ten other eukaryotic UniGene datasets from NCBI for the analyses. First, we conducted sequence profile analyses following translation termination sites. We found base G and A at position +1 as a strong consensus for mouse cDNA. A similar consensus was found for other mammals, such as Homo sapiens, Rattus norvegicus and Bos taurus. However, some plants had different consensus sequences. We then analysed the correlation between the strength of consensus at each position and the codon biases of whole coding regions, using information content and CAI value. The results showed that in mouse cDNA, CAI value had a positive correlation with information content at positions +1. We also found that, for positions with strong consensus, the strength of the consensus is likely to have a positive correlation with CAI value in some other eukaryotes. Along with these observations, biological insights into the relationship between gene expression level, codon biases and consensus sequence around stop codons will be discussed.

3' Untranslated Regions↗
PubMed1999

HyFIS: adaptive neuro-fuzzy inference systems and their application to nonlinear dynamical systems.

This paper proposes an adaptive neuro-fuzzy system, HyFIS (Hybrid neural Fuzzy Inference System), for building and optimising fuzzy models. The proposed model introduces the learning power of neural networks to fuzzy logic systems and provides linguistic meaning to the connectionist architectures. Heuristic fuzzy logic rules and input-output fuzzy membership functions can be optimally tuned from training examples by a hybrid learning scheme comprised of two phases: rule generation phase from data; and rule tuning phase using error backpropagation learning scheme for a neural fuzzy system. To illustrate the performance and applicability of the proposed neuro-fuzzy hybrid model, extensive simulation studies of nonlinear complex dynamic systems are carried out. The proposed method can be applied to an on-line incremental adaptive learning for the prediction and control of nonlinear dynamical systems. Two benchmark case studies are used to demonstrate that the proposed HyFIS system is a superior neuro-fuzzy modelling technique.

Journal Article↗