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At least 451 records · Page 25Linked to original sources

Dynamics and the single spike.

Responses of vestibular primary afferent neurons to head rotation exhibit fractional-order dynamics. As a consequence, the head tends to be in a localized region of its state-space at spike times of a particular neuron during arbitrary head movements, and single spikes can be interpreted as state measurements. We are developing a model of neural computations underlying trajectory prediction and control tasks, based on this experimental observation. This is a step toward a formal neural calculus in which single spikes are modeled realistically as the operands of neural computation.

Action Potentials↗

Generative character of perception: a neural architecture for sensorimotor anticipation.

The basic idea of our anticipatory approach to perception is to avoid the common separation of perception and generation of behavior and to fuse both aspects into a consistent neural process. Our approach tries to explain the phenomenon of perception, in particular, of perception at the level of sensorimotor intelligence, from a behavior-oriented point of view. Perception is assumed to be a generative process of anticipating the course of events resulting from alternative sequences of hypothetically executed actions. By means of this sensorimotor anticipation, it is possible to characterize a visual scenery immediately in categories of behavior, i.e. by a set of actions which describe possible methods of interaction with the objects in the environment. Thus, the competence to perceive a complex situation can be understood as the capability to anticipate the course of events caused by different action sequences. Starting from an abstract description of anticipatory perception and the essential biological evidence for internal simulation, we present two biologically motivated computational models that are able to anticipate and evaluate hypothetically sensorimotor sequences. Both models consider functional aspects of those cortical and subcortical systems that are assumed to be involved in the process of sensory prediction and sensorimotor control. Our first approach, the Model for Anticipation based on Sensory IMagination (MASIM), realizes a sequential search in sensorimotor space using a simple model of lateral cerebellum as sensory predictor. We demonstrate the efficiency of this model approach in the light of visually guided local navigation behaviors of a mobile system. The second approach, the Model for Anticipation based on Cortical Representations (MACOR), is actually still at a conceptual level of realization. We postulate that this model allows a completely parallel search at the neocortical level using assemblies of spiking neurons for grouping, separation, and selection of sensorimotor sequences. Both models are intended as general schemes for anticipation based perception at the level of sensorimotor intelligence.

Journal Article↗

Control of yeast cell types by mobile genes: a test.

The yeast Saccharomyces cerevisiae changes cell types by switching the alleles of the mating type locus (MAT) from a to alpha and vice versa. In the cassette model, these switches, --e.g, from a to alpha--occur when a replica of silent alpha information (an alpha "cassette") replaces the resident a cassette at the mating type locus and is thereby expressed. We have identified a mutation in the locus postulated to be the silent alpha information (HMLalpha) and find that a mutation is introduced into the mating type locus as a result of interconversion: HMLalpha(-) MATalpha cells switch to MATa and then to MATalpha(-). The MATalpha(-) mutation leads to defective mating and behaves like some previously identified MATalpha(-) mutations. These observations satisfy the prediction of the cassette and controlling element models that genetic information is transmitted from HMLalpha to the mating type locus.

Cell Cycle↗

Application of slurry bridging experiments at controlled water activities to predict the solid-state conversion between anhydrous and hydrated forms using theophylline as a model drug.

The role of water activity (a(w)), relative humidity (RH) and temperature on the hydration state of theophylline has been investigated. Slurry bridging experiments at controlled water activities, using powder X-ray diffraction (PXRD) and thermogravimetric analysis (TGA) to characterise the solid phase, established that the hydrate is the thermodynamically stable form of theophylline at a(w) > or = 0.5 at 4 degrees C, a(w) > or = 0.64 at 30 degrees C, and a(w) > or = 0.76 at 40 degrees C. These data were used to produce a phase stability diagram for anhydrous/hydrate theophylline versus temperature. Anhydrous theophylline was spray dried in an attempt to reduce crystallinity. The spray dried theophylline was stored at a range of temperatures (4-40 degrees C) and humidities (22-89% RH). Samples were analysed at 3, 6, 9, 26 and 52 weeks using TGA and at the 26 and 52 weeks by PXRD. The solid state stability of the spray dried theophylline closely correlated to the phase stability diagram produced using the slurry bridging experiments. The data suggest that the slurry bridging technique at controlled water activities provides an accurate method of rapidly predicting the physically stable form in anhydrous/hydrate systems.

Drug Storage↗

Prediction of headache response in migraine treatment.

Triptans are efficacious for the acute treatment of migraine attacks. Yet, defining a concentration-effect relation for these compounds is difficult as the dynamics of the migraine attack are not thoroughly understood. The objective of this investigation was to develop a disease model to predict measures of headache in randomized placebo-controlled clinical trials investigating oral sumatriptan as a paradigm compound. A hidden Markov model based on the states of response (no relief, relief, and pain free) and headache scores (observed variable) was used in conjunction with population pharmacokinetics. Model parameters were capable of predicting the course of headache relief, pain-free status and headache recurrence. It was shown that sumatriptan shortens mean transit times between states by up to 5 h. The potency of sumatriptan (EC(50)) was 9 ng/ml. These findings demonstrate the value of combining pharmacokinetic and efficacy information to model disease and characterize time-independent drug properties in a population of migraineurs.

Comorbidity↗

Cortico-striatal circuits and interval timing: coincidence detection of oscillatory processes.

Humans and other animals demonstrate the ability to perceive and respond to temporally relevant information with characteristic behavioral properties. For example, the response time distributions in peak-interval timing tasks are well described by Gaussian functions, and superimpose when scaled by the criterion duration. This superimposition has been referred to as the scalar property and results from the fact that the standard deviation of a temporal estimate is proportional to the duration being timed. Various psychological models have been proposed to account for such responding. These models vary in their success in predicting the temporal control of behavior as well as in the neurobiological feasibility of the mechanisms they postulate. A review of the major interval timing models reveals that no current model is successful on both counts. The neurobiological properties of the basal ganglia, an area known to be necessary for interval timing and motor control, suggests that this set of structures act as a coincidence detector of cortical and thalamic input. The hypothesized functioning of the basal ganglia is similar to the mechanisms proposed in the beat frequency timing model [R.C. Miall, Neural Computation 1 (1989) 359-371], leading to a reevaluation of its capabilities in terms of behavioral prediction. By implementing a probabilistic firing rule, a dynamic response threshold, and adding variance to a number of its components, simulations of the striatal beat frequency model were able to produce output that is functionally equivalent to the expected behavioral response form of peak-interval timing procedures.

Animals↗

Predictive thermal inactivation model for Listeria monocytogenes with temperature, pH, NaCl, and sodium pyrophosphate as controlling factors.

The effects and interactions of heating temperature (55 to 65 degrees C), pH (4 to 8), salt (NaCl; 0 to 6%, wt/vol), and sodium pyrophosphate (SPP; 0 to 0.3%, wt/vol) on the heat inactivation of a four-strain mixture of Listeria monocytogenes in beef gravy were examined. A factorial experimental design comparing 48 combinations of heating temperature, salt concentration, pH value, and SPP content was used. Heating was carried out using a submerged-coil heating apparatus. The recovery medium was plate count agar supplemented with 0.6% yeast extract and 1% sodium pyruvate. Decimal reduction times (D-values) were calculated by fitting a survival model to the data with a curve-fitting program. The D-values were analyzed by second-order response surface regression for temperature, pH, NaCl, and SPP levels. Whereas increasing the NaCl concentration protected L. monocytogenes against the lethal effect of heat, high SPP concentrations increased heat sensitivity. Also, low pH values increased heat sensitivity of L. monocytogenes. The four variables interacted to affect the inactivation of the pathogen. Thermal resistance of L. monocytogenes can be lowered by combining these intrinsic factors. A predictive model that described the combined effect of temperature, pH, NaCl, and SPP levels on thermal resistance of L. monocytogenes was developed. The model can predict D-values for any combination of temperature, pH, NaCl, and SPP that are within the range of those tested. Using this predictive model, food processors should be able to design adequate thermal regimes to eliminate L. monocytogenes in thermally processed foods.

Animals↗

Prediction and analysis model of temperature and its application to a natural ventilation multi-span plastic greenhouse equipped with insect-proof screen.

The natural ventilation widely used in greenhouses has advantages of saving energy and reducing expense. In order to provide information for climate control of greenhouse, a model was developed to predict the variation of air temperature in the naturally ventilated greenhouse equipped with insect-proof screen. Roof ventilation and combined roof and sidewall ventilation were considered in the model. This model was validated against the results of experiments conducted in the greenhouse when the wind was parallel to the gutters. The model parameters were determined by the least squares method. In the used model, effects of wind speed and window opening height on the air temperature variation were analyzed. Comparison between two types of ventilation showed that there existed a necessary ventilation rate which results in air temperature decrease in natural ventilation under special climatic conditions. In our experiments when wind speed was less than 3.2 ms(-1), wind had a more gradual effect on greenhouse temperature for roof ventilation, compared with combined roof and sidewall ventilation, which had greater air temperature decrease than roof ventilation only.

Air Conditioning↗

Attributions of control and seropositivity among Latinos: examining the predictive utility of the locus of control construct.

This investigation explored the utility of the health locus of control construct in predicting the mental health quality of life (MHQOL) ratings of 72 Latinos living with HIV/AIDS. After controlling for patient CD4 count, viral load, time since diagnosis, Physical Health Quality of Life and acculturative status, Powerful Others Locus of Control beliefs accounted for a significant increment of the variance in Mental Health Quality of Life. In a similar model, Internal Locus of Control failed to predict MHQOL. Discussion and implications highlight how cultural considerations may broaden investigations of health among diverse, minority populations.

Adult↗

A prediction-correction scheme for forcing alveolar gases along certain time courses.

A computerized prediction-correction scheme has been devised for the control of alveolar gases. First, a model is run off-line to predict the inspiratory gas tensions at each second that should yield the desired alveolar patterns. Second, during the experiment, there is feedback correction based on the deviation of the actual alveolar values from the desired alveolar values. The actual alveolar values are found by a second computer and passed to the controlling computer using interrupts. The controlling computer has four digital-toi-analog outputs for controlling CO2, O2, N2, and air flows so as to achieve the commanded inspiratory PCO2 and PO2 (CO2 and O2 partial pressures, respectively). The scheme is illustrated for the generation of sinusoidal alveolar PCO2 with alveolar PO2 held constant and for steps of alveolar PCO2 at constant alveolar PO2.

Carbon Dioxide↗

Prognostic factors for recurrence and survival in head and neck soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas of the head and neck represent uncommon malignant neoplasms. With the exception of orbital and parameningeal sites, the treatment of sarcomas in the head and neck has not been standardized. The authors used a prospectively collected database of adult soft tissue sarcomas to identify prognostic factors for local control and survival. METHODS: A prospectively collected database of adult soft tissue sarcoma from 1982 to 1989 was analyzed for the impact of prognostic factors on local control and survival. Factors examined included histologic type, tumor grade, size, and resection margins. RESULTS: The overall and disease free survival at 5 years was 71 and 60%, respectively. Local control was 70% at 5 years. On univariate analysis, grade and margin status were predictors for local control. Analysis based on the Cox proportional hazard model revealed that margin status was the only significant factor in predicting local control. Grade and margin status were significant prognostic indicators for survival both on univariate analysis and in the Cox proportional hazard model. CONCLUSION: Patients with head and neck sarcomas should undergo wide excision with the removal of all gross disease and the acquisition of negative, microscopic surgical margins. Patients with positive margins should receive adjuvant radiotherapy for local control. High grade lesions place patients at risk for local recurrence and distant dissemination. Investigational regimens designed to prevent metastatic disease should be performed.

Adolescent↗

Psychological distress and fatigue predicted recurrence and survival in primary breast cancer patients.

This study examined whether psychological distress in newly diagnosed breast cancer patients was associated with their survival. We analyzed data from 1,588 breast cancer patients who filled in the EORTC QLQ-C30 questionnaire and the Hospital Anxiety and Depression Scale (HADS) 2 months after their primary operation. The median follow-up time was 12.9 years. Psychological distress (EORTC QLQ-C30 emotional function; HADS anxiety; HADS depression) and EORTC fatigue, physical function, and overall ratings were used to predict recurrence-free and overall survival, controlling for the known clinical and histopathological prognostic factors (biological model) using Cox multivariate regression analysis. Low levels of psychological distress (good EORTC emotional function) and low fatigue independently predicted longer recurrence-free and overall survival, controlling for biological factors. Lack of anxiety (HADS) also predicted longer recurrence-free survival. When added in combination to the biological model, fatigue remained a significant predictor of recurrence-free survival (P = 0.0004; risk ratio 1.32 (1.13-1.54)) and emotional function remained a significant predictor of overall survival (P = 0.0074; risk ratio 0.81 (0.70-0.95)). Low psychological distress and a low level of fatigue may cause a greater cancer resistance or may reflect underlying mental and physical robustness.

Adult↗

Disease threats posed by alien species: the role of a poxvirus in the decline of the native red squirrel in Britain.

Red squirrels are declining in the United Kingdom. Competition from, and squirrel poxvirus (SQPV) disease carried by, grey squirrels are assumed to be determining the decline. We analyse the incidence of disease and changes in distribution of the two species in Cumbria, from 1993 to 2003 and compare these to the predictions of an individual-based (IB) spatially explicit disease model simulating the dynamics of both squirrel species and SQPV in the landscape. Grey squirrels increased whilst red squirrels declined over 10 years. The incidence of disease in red squirrels was related to the time since grey squirrels arrived in the landscape. Analysis of rates of decline in red squirrel populations in other areas showed that declines are 17-25 times higher in regions where SQPV is present in grey squirrel populations than in those where it is not. The IB model predicted spatial overlap of 3-4 years between the species that was also observed in the field. The model predictions matched the observed data best when contact rates and rates of infection between the two species were low. The model predicted that a grey squirrel population control of >60% effective kill was needed to stop the decline in red squirrel populations in Cumbria.

Animals↗

Power laws of complex systems from extreme physical information.

Many complex systems obey allometric, or power, laws y=Y x(a) . Here y > or = 0 is the measured value of some system attribute a , Y> or =0 is a constant, and x is a stochastic variable. Remarkably, for many living systems the exponent a is limited to values n/4 , n=0, +/-1, +/-2.... Here x is the mass of a randomly selected creature in the population. These quarter-power laws hold for many attributes, such as pulse rate (n=-1) . Allometry has, in the past, been theoretically justified on a case-by-case basis. An ultimate goal is to find a common cause for allometry of all types and for both living and nonliving systems. The principle I-J=extremum of extreme physical information is found to provide such a cause. It describes the flow of Fisher information J-->I from an attribute value a on the cell level to its exterior observation y . Data y are formed via a system channel function y identical to f (x,a) , with f (x,a) to be found. Extremizing the difference I-J through variation of f (x,a) results in a general allometric law f (x,a) identical to y=Y x(a) . Darwinian evolution is presumed to cause a second extremization of I-J , now with respect to the choice of a . The solution is a=n/4 , n=0,+/-1,+/-2..., defining the particular powers of biological allometry. Under special circumstances, the model predicts that such biological systems are controlled by only two distinct intracellular information sources. These sources are conjectured to be cellular DNA and cellular transmembrane ion gradients.

Algorithms↗

A comparison of absorption rate models in the prediction of steady-state plasma concentrations during oral theophylline administration.

During therapy with oral controlled released theophylline/aminophylline, steady-state plasma drug concentrations may be predicted by fitting estimates of patient pharmacokinetic parameters to a pharmacokinetic model. The choice of model requires an assumption about the type of rate reaction of the drug absorption process (zero order or first order). In 10 subjects, plasma theophylline concentrations after a single intravenous dose of aminophylline were used to make individual estimates of drug clearance and volume of distribution. Each subject then received oral controlled release theophylline ('Theo-Dur', Fisons Pharmaceuticals plc) and steady-state pre-dose and post-dose plasma concentrations were determined. Predictions of steady-state plasma theophylline concentrations using pharmacokinetic models based on first-order (Model A) and zero order (Model 01) drug absorption were compared. Model A and Model 01 each underestimated the pre- and post-dose steady-state plasma drug concentrations. However, Model 01 was more accurate in predicting post-dose drug concentrations, whilst Model A demonstrated better precision in the prediction of pre-dose drug concentrations at steady-state (P less than 0.05).

Administration, Oral↗

Optimization of the kinetics of cooling of kidneys: a pig model.

We determined the kinetics of cooling in multiple organ procurement for the kidney in a pig model. A biometric analysis by regression enables us to define the factors which influence the rate of temperature decrease: weight of the donor, average rate of perfusion and difference of temperature between the rectal temperature and the temperature of the perfusion solution at initiation of cooling. The description of the temperature as a function of time follows an exponential model of the type T(t) = T0. e(dt) where d is the rate of decrease. The rate of decrease varies according to the above factors. The cellular viability ratio (CVR), was correlated to the rate of cooling. The mean CVR was 91% (SD 4.95) when the rate of cooling was more than 1 degrees C/min. This was compared to 75% (SD 11.17) when the rate was less than 1 degrees C/min (p = 0.023). Our experience leads us to believe that the average cooling rate is frequently too low (<1 degrees C/min). This model can be used to predict and control the kinetics of cooling and may help to define the best way of cooling for future xenotransplantation.

Animals↗

Adolescents' as active agents in the socialization process: legitimacy of parental authority and obligation to obey as predictors of obedience.

Adolescents' agreement with parental standards and beliefs about the legitimacy of parental authority and their own obligation to obey were used to predict adolescents' obedience, controlling for parental monitoring, rules, and rule enforcement. Hierarchical linear models were used to predict both between-adolescent and within-adolescent, issue-specific differences in obedience in a sample of 703 Chilean adolescents (M age=15.0 years). Adolescents' global agreement with parents and global beliefs about their obligation to obey predicted between-adolescent obedience, controlling for parental monitoring, age, and gender. Adolescents' issue-specific agreement, legitimacy beliefs, and obligation to obey predicted issue-specific obedience, controlling for rules and parents' reports of rule enforcement. The potential of examining adolescents' agreement and beliefs about authority as a key link between parenting practices and adolescents' decisions to obey is discussed.

Adolescent↗

Modeling of drug release from polymeric delivery systems--a review.

Polymeric drug delivery platforms have been receiving increasing attention in the past decade. The pharmaceutical industry is evaluating modes of delivery for their prized therapeutics at every step of the design cycle. Not only can the drug delivery platform transport drug molecules effectively, it can also improve patient compliance, offer greater patient convenience, and extend product lifecycles as patents expire. A large number of successful drug delivery systems have been developed as a result of an almost arbitrary selection of constituents and configurations. However, the development of advanced drug delivery systems relies on a judicious and careful selection of components, configurations, and geometries, which can be facilitated through mathematical modeling of controlled release systems. Mathematical modeling aids in predicting the drug release rates and diffusion behavior from these systems by the solution of an appropriate model, thereby reducing the number of experiments needed. It also aids in understanding the physics of a particular drug transport phenomenon, thus facilitating the development of new pharmaceutical products. The objective of this article is to review the spectrum of mathematical models that have been developed to describe drug release from polymeric controlled release systems. The mathematical models presented in this article have been grouped under diffusion controlled systems, swelling controlled systems, and erosion controlled systems as proposed by Langer and Peppas. Simple empirical or semi-empirical models and complex mechanistic models that consider diffusion, swelling, and erosion processes simultaneously are presented.

Chemistry, Pharmaceutical↗