PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “threshold model”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed2002

Computational antisense oligo prediction with a neural network model.

MOTIVATION: The expression of a gene can be selectively inhibited by antisense oligonucleotides (AOs) targeting the mRNA. However, if the target site in the mRNA is picked randomly, typically 20% or less of the AOs are effective inhibitors in vivo. The sequence properties that make an AO effective are not well understood, thus many AOs need to be tested to find good inhibitors, which is time consuming and costly. So far computational models have been based exclusively on RNA structure prediction or motif searches while ignoring information from other aspects of AO design into the model. RESULTS: We present a computational model for AO prediction based on a neural network approach using a broad range of input parameters. Collecting sequence and efficacy data from AO scanning experiments in the literature generated a database of 490 AO molecules. Using a set of derived parameters based on AO sequence properties we trained a neural network model. The best model, an ensemble of 10 networks, gave an overall correlation coefficient of 0.30 (p=10(-8)). This model can predict effective AOs (>50% inhibition of gene expression) with a success rate of 92%. Using these thresholds the model predicts on average 12 effective AOs per 1000 base pairs, making it a stringent yet practical method for AO prediction.

Algorithms↗
PubMed1997

[Common and current measurement parameters].

The different parameters used in cardiopneumologic exercise tests allow an assessment of exercise tolerance on the basis of the subject's ventilatory response, cardiac and metabolic adaptation and gas exchanges during exercise. VO2max and dyspnea are indicators of good or poor exercise tolerance. Normal values established for adults in three reference articles depend on age, body weight and height. In a 20-year-old non sedentary subject, VO2max is approximately 45 ml/mn/kg and decreases to 25 ml/mn/kg at 65 years of age. Dyspnea is measured on two types of scales, categorical and visual analogue scales. "Minimal dyspnea" at maximal effort is normal in a healthy subject but becomes "very severe" in diseased subjects. A dyspnea threshold can be determined from the evolution of dyspnea during the test and is useful for retraining in patients with chronic obstructive lung disease. The normal ventilatory response always leaves a ventilatory reserve equal to 30% of the theoretical maximal ventilatory output. If the reserve is diminished, exercise is limited by ventilatory capacity. Gas exchanges reflect muscle adaptation to exercise and the homogeneous nature of alveolar ventilation compared with pulmonary perfusion (VA/Q). This depends on the physiological dead space (VD/VT) which is approximately 1/3 at rest decreasing to 1/4 or 1/5 at maximal exercise. VD/VT is high at rest and stays high during exercise in interstitial lung disease and vascular lung disease. VA/Q also depends on the alveo-arterial oxygen differential (P(A-a)O2) which increases two-fold during exercise. Expired gas and arterial gas must be measured simultaneously for the calculation. To measure cardiac adaptation, the ECG, heart rate and oxygen pulse (VO2/HR) must be recorded. The kinetics of oxygen pulse is more important than its maximal value, a decrease with unchanged heart rate suggests early-stage cardiomyopathy. Finally, blood lactate, the metabolic response to exercise, is used to determine the lactate threshold or the anaerobic threshold. Measurement of the ventilatory threshold is less invasive, ventilatory outflow increasing with increasing lactate level as described by the Beaver or Wassermann model. These thresholds indicate the subject's aerobic capacity. The exercise test has diagnostic value but can also be useful for individual patient management, particularly cardiorespiratory rehabilitation.

Adult↗
PubMedDate not supplied

Changes in ventricular fibrillation threshold during acute hypothermia. A model for future studies.

Hypothermia and rewarming are associated with an increased incidence of lethal arrhythmias in man. The relationship between reduction in body temperature and ventricular fibrillation threshold was studied in 7 pentobarbital anaesthetized dogs using programmable electrical stimulation while cooling and rewarming between 37 degrees C and 25 degrees C in steps of 3 degrees C. Fibrillation threshold was defined as the number of extrastimuli required to evoke ventricular fibrillation. QRS-durations and corrected QT-intervals (QTc) were measured from surface electrocardiograms. Monophasic action potential durations were recorded from the base and apex of the heart. Fibrillation threshold decreased with decreasing temperatures; e.g., at 37 degrees C ventricular fibrillation was not inducible after 5 extrastimuli, while at 25 degrees C only 2 extrastimuli were required. From 37 degrees C to 25 degrees C QRS-width, monophasic action potential durations and QTc increased while conduction velocity decreased. The differential effects on conduction and monophasic action potential duration provide a basis for induction of ventricular fibrillation during acute hypothermia. This model of hypothermia-induced ventricular fibrillation should prove useful for future studies aimed at understanding the mechanisms responsible for hypothermia-related deaths.

Action Potentials↗
PubMed2005

Multisensory control of human upright stance.

The interaction of different orientation senses contributing to posture control is not well understood. We therefore performed experiments in which we measured the postural responses of normal subjects and vestibular loss patients during perturbation of their stance. Subjects stood on a motion platform with their eyes closed and auditory cues masked. The perturbing stimuli consisted of either platform tilts or external torque produced by force-controlled pull of the subjects' body on a stationary platform. Furthermore, we presented trials in which these two stimuli were applied when the platform was body-sway referenced (i.e., coupled 1:1 to body position, by which ankle joint proprioceptive feedback is essentially removed). We analyzed subjects' postural responses, i.e., the excursions of their center of mass (COM) and center of pressure (COP), using a systems analysis approach. We found gain and phase of the responses to vary as a function of stimulus frequency and in relation to the absence versus presence of vestibular and proprioceptive cues. In addition, gain depended on stimulus amplitude, reflecting a non-linearity in the control. The experimental results were compared to simulation results obtained from an 'inverted pendulum' model of posture control. In the model, sensor fusion mechanisms yield internal estimates of the external stimuli, i.e., of the external torque (pull), the platform tilt and gravity. These estimates are derived from three sensor systems: ankle proprioceptors, vestibular sensors and plantar pressure sensors (somatosensory graviceptors). They are fed as global set point signals into a local control loop of the ankle joints, which is based on proprioceptive negative feedback. This local loop stabilizes the body-on-foot support, while the set point signals upgrade the loop into a body-in-space control. Amplitude non-linearity was implemented in the model in the form of central threshold mechanisms. In model simulations that combined sensor fusion and thresholds, an automatic context-specific sensory re-weighting across stimulus conditions occurred. Model parameters were identified using an optimization procedure. Results suggested that in the sway-referenced condition normal subjects altered their postural strategy by strongly weighting feedback from plantar somatosensory force sensors. Taking this strategy change into account, the model's simulation results well paralleled all experimental results across all conditions tested.

Adult↗
PubMed1983

Resource availability, maternal effects, and longevity.

Experiments with a clone of the cladoceran Daphnia pulex indicate that the nutritional conditions of the maternal environment play a major role in determining the progeny's phenotype. Apparently, by influencing the physiology and/or morphology of individuals during early development, maternal investment not only enhances juvenile survival but has long-lasting, favorable effects on the progeny's ability to convert resources into growth and reproduction as well as negative repercussions for adult survival of the progeny. Life-span may also be radically altered by modifying food schedules within an individual's life. Neither reproductive effort nor rate of living hypotheses can explain longevity variation within Daphnia clones; rather the onset of senescence appears to be associated with a general breakdown in the ability to incorporate energy into biomass. Analysis of our results as well as earlier data with a "rate of aging-threshold vitality" model suggests that increasing the availability of food to an individual increases the rate of aging while decreasing the threshold vitality necessary for survival and that increasing maternal investment increases both the vitality at birth and the rate of aging of the progeny.

Animals↗
PubMed1992

Calcium balance during human growth: evidence for threshold behavior.

Calcium balances performed on 519 individuals from birth to 30 years of age, derived from 34 published reports, were pooled by age group and the relationship between intake and balance for each group was compared at both extremes of the intake range. At all ages, from infancy through the young adult years, balance values tended to flatten and become constant at higher intakes, while at lower intakes balance was invariably highly correlated with intake. Threshold intakes and balances were estimated by fitting the data to a two-component, split, linear-regression model. The threshold values at which balance no longer rose with intake exceeded the US recommended dietary allowances for calcium for all the age groups concerned.

Adolescent↗
PubMed1986

Extension of a binaural cross-correlation model by contralateral inhibition. II. The law of the first wave front.

This paper explains the "law of the first wave front" and related binaural phenomena on the basis of the model presented in the previous paper [Lindemann, J. Acoust. Soc. Am. 80, 1608-1622 (1986)] in which a contralateral inhibition mechanism was added to the well-known model of binaural cross correlation. In order to verify the predictions of the extended model, psychoacoustic experiments were performed with pairs of narrow-band impulses which were presented through headphones. The test signals consisted of a diotic primary sound and an "echo" with an interaural arrival-time difference. Lateralization was measured as a function of the time delay between primary sound and echo. For delays below the echo threshold, summing localization and the law of the first wave front were simulated; for delays above the echo threshold, the model predicts an influence of the primary sound on the lateralization of the echo.

Auditory Perception↗
PubMed1987

Osteogenesis imperfecta. The set point proposal (a possible causative mechanism).

The minimum effective strain (MES) constitutes a threshold that separates biomechanically acceptable from unacceptable strains on growing bone and fibrous tissues. Strains above that threshold affect modeling and remodeling activities in ways that change the size and configuration of growing bones, tendons, ligaments, and fascia to fit their new mechanical usage and return their strains to the threshold level. Were that threshold set too high from birth, the effects of normal function on remodeling and modeling should lead to thin fibrous tissue structures, to slender, osteopenic diaphyses and spongiosa, and to increased fragility. Those and other predictable set point effects fit so precisely many of the known hard and soft tissue abnormalities of osteogenesis imperfecta patients, that an elevated MES set point may be a heretofore unrecognized basic pathogenetic factor in that disease.

Animals↗
PubMed2000

Cytotoxicity assessment of antibiofouling compounds and by-products in marine bivalve cell cultures.

Short-term primary cell cultures were derived from adult marine bivalve tissues: the heart of oyster Crassostrea gigas and the gill of clam Ruditapes decussatus. These cultures were used as experimental in vitro models to assess the acute cytotoxicity of an organic molluscicide, Mexel-432, used in antibiofouling treatments in industrial cooling water systems. A microplate cell viability assay, based on the enzymatic reduction of tetrazolium dye (MTT) in living bivalve cells, was adapted to test the cytotoxicity of this compound: in both in vitro models, toxicity thresholds of Mexel-432 were compared to those determined in vivo with classic acute toxicity tests. The clam gill cell model was also used to assess the cytotoxicity of by-products of chlorination, a major strategy of biofouling control in the marine environment. The applications and limits of these new in vitro models for monitoring aquatic pollutants were discussed, in reference with the standardized Microtox test.

Animals↗
PubMed2001

Epithelial damage thresholds for multiple-pulse exposures to 80 ns pulses of CO2 laser radiation.

Corneal epithelial damage thresholds for exposures to 80 ns pulses of 10.6 microm infrared radiation produced by a CO2-TEA laser were investigated. Thresholds were determined for sequences of 1, 2, 8, 32, 128, and 1,024 pulses at pulse repetition frequencies of 10 and 16 Hz. Threshold damage is correlated by an empirical power law of the form EDth = CN(-alpha) in which EDth, is the threshold radiant exposure per pulse, and N is the number of pulses. The constants C and alpha are similar for the two pulse repetition frequencies. For the combined data set, C = 2,955 J m(-2) pulse(-1) (295.5 mJ cm(-2) pulse(-1) and alpha = 0.178. This value of the constant C is within 5% of the measured damage threshold for a single 80 ns pulse exposure. Temperature calculations reveal that the maximum temperature increase on the beam axis, 10 microm beneath the anterior tear surface, resulting from the different threshold exposures is constant to within +/-10% of the mean values. This result is consistent with a critical temperature damage model. Damage threshold measurements on cooled corneas indicate that the damage mechanism indeed has a substantial thermal component.

Animals↗
PubMed1976

Mathematical aspects of dose-response studies in carcinogenesis--the concept of thresholds.

Many of the previously proposed theories of carcinogenesis which relate the exposure level of a carcinogen to expected tumor response, are summarized and it is pointed out that these theories assume the existence of no threshold level. A modification of the one-hit carcinogenic model which would incorporate a threshold, is proposed along with a generalization to variable thresholds over the population at risk. The statistical problems of discriminating between threshold and non-threshold models from experimental bioassay data are discussed and an example is given.

Animals↗
PubMed2005

Testing threshold and hormesis in a random effects dose-response model applied to developmental toxicity data.

Here we describe a random effects threshold dose-response model for clustered binary-response data from developmental toxicity studies. For our model we assume that a hormetic effect occurs in addition to a threshold effect. Therefore, the dose-response curve is based on two components: relationships below the threshold (hormetic u-shaped model) and those above the threshold (logistic model). In the absence of hormesis and threshold effects, the estimation procedure is straightforward. We introduce score tests that are derived from a random effects hormetic-threshold dose-response model. The model and tests are applied to clustered binary data from developmental toxicity studies of animals to test for hormesis and threshold effects. We also compare the score test and likelihood ratio test to test for hormesis and threshold effects in a simulated study.

Animals↗
PubMed2000

Time-correlated soliton tunneling in charge and spin density waves

We consider a model in which an electric field induces quantum nucleation of kink-antikink pairs in a pinned charge or spin density wave. Pair nucleation events, prevented by Coulomb blockade below a pair creation threshold, become correlated in time above threshold. The model provides a natural explanation for the observed (i) small density wave polarization below threshold in NbSe (3), (ii) narrow band noise, (iii) coherent oscillations, and (iv) mode-locking at high drift frequencies.

Journal Article↗
PubMed2006

Linear-no-threshold is a radiation-protection standard rather than a mechanistic effect model.

The linear-no-threshold (LNT) controversy covers much more than the mere discussion whether or not "the LNT hypothesis is valid". It is shown that one cannot expect to find only one or even the only one dose-effect relationship. Each element within the biological reaction chain that is affected by ionizing radiation contributes in a specific way to the final biological endpoint of interest. The resulting dose-response relationship represents the superposition of all these effects. Till now there is neither a closed and clear picture of the entirety of radiation action for doses below some 10 mSv, nor does clear epidemiological evidence exist for an increase of risk for stochastic effects, in this dose range. On the other hand, radiation protection demands for quantitative risk estimates as well as for practicable dose concepts. In this respect, the LNT concept is preferred against any alternative concept. However, the LNT concept does not necessarily mean that the mechanism of cancer induction is intrinsically linear. It could hold even if the underlying multi-step mechanisms act in a non-linear way. In this case it would express a certain "attenuation" of non-linearities. Favouring LNT against threshold-, hyper-, or sub-linear models for radiation-protection purposes on the one hand, but preferring one of these models (e.g. for a specific effect) because of biological considerations for scientific purposes on the other hand, does not mean a contradiction.

Body Burden↗
PubMed2005

Saturation of the lactate clearance mechanisms different from the "lactate shuttle" determines the anaerobic threshold: prediction from the bioenergetic model.

It is demonstrated, that the bioenergetic model combined with the mathematical constraints determined by the experimental knowledge of the aerobic metabolism and the Lohmann reaction dictates the exact lactate (La)-time relationship during exercise. The theory predicts that La is necessarily produced (above the resting baseline), even during extremely low work loads, where the metabolism was usually considered in the past to be "pure" aerobic. The La rate of production increases linearly as a function of the work load. The anaerobic threshold is strictly determined by the saturation of the La clearance mechanisms of the body different from the "La shuttle" and not by the involvement of a sudden increased La production at the cellular level. These results imply that the half time of the PCr breakdown kinetics at the onset of a constant load exercise can be expressed as a function of the onset speed of the aerobic and of the anaerobic metabolism, even in the case of a very low mechanical power. The PCr half-time does not depend on the workload and represents a physiological invariant. The bioenergetic model was created during a long historical period, when it was believed that the La production was not present at all for very low exercise levels but, actually, the bioenergetic model predicts exactly the opposite result!

Anaerobic Threshold↗
PubMed2005

The effect of synchronization on genetic parameters of reproductive traits in dairy cattle.

Genetic evaluation and selection is one strategy for improving female reproductive performance. Many producers use synchronization of ovulation or estrus to manage reproduction. The objective of this study was to examine the effects of reproductive synchronization on genetic parameter estimates of days to first breeding (DFB), days open (DO), and pregnancy rate at 120 d postpartum (PR120). Data were collected from 64 producers participating in an artificial insemination progeny testing program and using Dairy Comp 305 herd management software to record reproductive treatments and events. Data included 18,359 records for DFB and 16,379 records for DO and PR120. Synchronization was classified by breeding codes at time of insemination. The traits DFB and DO were analyzed using a linear model with age at calving, herd-year-season, and parity as fixed effects and sire and residual as random effects. For PR120, a threshold sire model was used with fixed effects as in the DFB and DO models. Three models were applied to the complete data sets of all traits; a base model with no synchronization effect, an expanded model with a fixed synchronization effect, and an interaction model with a random sire by herd management interaction. Herd management categories were based on an individual herd's use of synchronization protocols. Also, data subsets were analyzed separately based on cow synchronization treatment and herd management categories. Synchronized records for DFB had on average 40% higher sire variance and 60% lower residual variance than nonsynchronized records. Heritability for DFB ranged from 0.01 to 0.09. Sire variance was 40% lower for DO and 25% lower for PR120 in first synchronized records than either later-synchronized or nonsynchronized records. Residual variances for DO varied by 3% among cow treatment categories and 14% for herd management categories. Heritabilities ranged from 0.03 to 0.07 for DO and 0.10 to 0.26 for PR120. Including a fixed effect for synchronization in the DO model reduced sire variance by 33% and residual variance by 10%. Sire by herd management interactions were less than 2% of the total variance for all traits. Accounting for synchronization, especially for DFB, may improve accuracy of genetic parameter estimates and animal evaluations.

Analysis of Variance↗
PubMed1997

Masking of a brief probe by sinusoidal frequency modulation.

Contrary to level detection models, the thresholds for a brief-duration probe masked by a sinusoidal frequency modulation (FM) masker increases as the modulation index (beta) of FM increases [Zwicker, Acustica 31, 243-256 (1974)]. In this paper the reason for this phenomenon is investigated. In experiment 1, a 10-ms, 1-kHz probe was detected in the presence of an FM masker centered at 1 kHz and sinusoidally modulated at 16 Hz. Thresholds increased by over 15 dB with increasing beta, consistent with Zwicker's findings. In experiment 2, the instantaneous frequency changes of the masker used in experiment 1 were clipped and the resulting thresholds indicated that detection was determined primarily by the masker's total frequency excursion rather than by its instantaneous sweep rate. In experiment 3, the FM maskers from the first two experiments were passed through a roex filter centered at 1 kHz and the resulting envelope was used to amplitude modulate a 1-kHz tone, producing approximately the same effective envelope at 1 kHz as the FM maskers. Threshold functions for the amplitude modulated (AM) maskers were similar to those for their corresponding FM maskers. Thresholds increased by over 15 dB while the total energy of the AM masker decreased by over 10 dB, again contrary to standard level-detection models. The results from these experiments can be explained, at least qualitatively, by a model based on envelope shape discrimination: similarities between the envelopes of the masker alone and masker-plus-probe at the output of an auditory filter centered on the frequency of the probe are primarily responsible for the observed masking, particularly at large beta's.

Auditory Perception↗