Modeling learning in brain stem and cerebellar sites responsible for VOR plasticity

NASA Technical Reports Server (NTRS)

Quinn, K. J.; Didier, A. J.; Baker, J. F.; Peterson, B. W.

1998-01-01

A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

Physiological and Psychophysical Modeling of the Precedence Effect

PubMed Central

Xia, Jing; Brughera, Andrew; Colburn, H. Steven

2010-01-01

Many past studies of sound localization explored the precedence effect (PE), in which a pair of brief, temporally close sounds from different directions is perceived as coming from a location near that of the first-arriving sound. Here, a computational model of low-frequency inferior colliculus (IC) neurons accounts for both physiological and psychophysical responses to PE click stimuli. In the model, IC neurons have physiologically plausible inputs, receiving excitation from the ipsilateral medial superior olive (MSO) and long-lasting inhibition from both ipsilateral and contralateral MSOs, relayed through the dorsal nucleus of the lateral lemniscus. In this model, physiological suppression of the lagging response depends on the inter-stimulus delay (ISD) between the lead and lag as well as their relative locations. Psychophysical predictions are generated from a population of model neurons. At all ISDs, predicted lead localization is good. At short ISDs, the estimated location of the lag is near that of the lead, consistent with subjects perceiving both lead and lag from the lead location. As ISD increases, the estimated lag location moves closer to the true lag location, consistent with listeners’ perception of two sounds from separate locations. Together, these simulations suggest that location-dependent suppression in IC neurons can explain the behavioral phenomenon known as the precedence effect. PMID:20358242

Inferring Nonlinear Neuronal Computation Based on Physiologically Plausible Inputs

PubMed Central

McFarland, James M.; Cui, Yuwei; Butts, Daniel A.

2013-01-01

The computation represented by a sensory neuron's response to stimuli is constructed from an array of physiological processes both belonging to that neuron and inherited from its inputs. Although many of these physiological processes are known to be nonlinear, linear approximations are commonly used to describe the stimulus selectivity of sensory neurons (i.e., linear receptive fields). Here we present an approach for modeling sensory processing, termed the Nonlinear Input Model (NIM), which is based on the hypothesis that the dominant nonlinearities imposed by physiological mechanisms arise from rectification of a neuron's inputs. Incorporating such ‘upstream nonlinearities’ within the standard linear-nonlinear (LN) cascade modeling structure implicitly allows for the identification of multiple stimulus features driving a neuron's response, which become directly interpretable as either excitatory or inhibitory. Because its form is analogous to an integrate-and-fire neuron receiving excitatory and inhibitory inputs, model fitting can be guided by prior knowledge about the inputs to a given neuron, and elements of the resulting model can often result in specific physiological predictions. Furthermore, by providing an explicit probabilistic model with a relatively simple nonlinear structure, its parameters can be efficiently optimized and appropriately regularized. Parameter estimation is robust and efficient even with large numbers of model components and in the context of high-dimensional stimuli with complex statistical structure (e.g. natural stimuli). We describe detailed methods for estimating the model parameters, and illustrate the advantages of the NIM using a range of example sensory neurons in the visual and auditory systems. We thus present a modeling framework that can capture a broad range of nonlinear response functions while providing physiologically interpretable descriptions of neural computation. PMID:23874185

EEG-Based Quantification of Cortical Current Density and Dynamic Causal Connectivity Generalized across Subjects Performing BCI-Monitored Cognitive Tasks

PubMed Central

Courellis, Hristos; Mullen, Tim; Poizner, Howard; Cauwenberghs, Gert; Iversen, John R.

2017-01-01

Quantification of dynamic causal interactions among brain regions constitutes an important component of conducting research and developing applications in experimental and translational neuroscience. Furthermore, cortical networks with dynamic causal connectivity in brain-computer interface (BCI) applications offer a more comprehensive view of brain states implicated in behavior than do individual brain regions. However, models of cortical network dynamics are difficult to generalize across subjects because current electroencephalography (EEG) signal analysis techniques are limited in their ability to reliably localize sources across subjects. We propose an algorithmic and computational framework for identifying cortical networks across subjects in which dynamic causal connectivity is modeled among user-selected cortical regions of interest (ROIs). We demonstrate the strength of the proposed framework using a “reach/saccade to spatial target” cognitive task performed by 10 right-handed individuals. Modeling of causal cortical interactions was accomplished through measurement of cortical activity using (EEG), application of independent component clustering to identify cortical ROIs as network nodes, estimation of cortical current density using cortically constrained low resolution electromagnetic brain tomography (cLORETA), multivariate autoregressive (MVAR) modeling of representative cortical activity signals from each ROI, and quantification of the dynamic causal interaction among the identified ROIs using the Short-time direct Directed Transfer function (SdDTF). The resulting cortical network and the computed causal dynamics among its nodes exhibited physiologically plausible behavior, consistent with past results reported in the literature. This physiological plausibility of the results strengthens the framework's applicability in reliably capturing complex brain functionality, which is required by applications, such as diagnostics and BCI. PMID:28566997

Testing the physiological plausibility of conflicting psychological models of response inhibition: A forward inference fMRI study.

PubMed

Criaud, Marion; Longcamp, Marieke; Anton, Jean-Luc; Nazarian, Bruno; Roth, Muriel; Sescousse, Guillaume; Strafella, Antonio P; Ballanger, Bénédicte; Boulinguez, Philippe

2017-08-30

The neural mechanisms underlying response inhibition and related disorders are unclear and controversial for several reasons. First, it is a major challenge to assess the psychological bases of behaviour, and ultimately brain-behaviour relationships, of a function which is precisely intended to suppress overt measurable behaviours. Second, response inhibition is difficult to disentangle from other parallel processes involved in more general aspects of cognitive control. Consequently, different psychological and anatomo-functional models coexist, which often appear in conflict with each other even though they are not necessarily mutually exclusive. The standard model of response inhibition in go/no-go tasks assumes that inhibitory processes are reactively and selectively triggered by the stimulus that participants must refrain from reacting to. Recent alternative models suggest that action restraint could instead rely on reactive but non-selective mechanisms (all automatic responses are automatically inhibited in uncertain contexts) or on proactive and non-selective mechanisms (a gating function by which reaction to any stimulus is prevented in anticipation of stimulation when the situation is unpredictable). Here, we assessed the physiological plausibility of these different models by testing their respective predictions regarding event-related BOLD modulations (forward inference using fMRI). We set up a single fMRI design which allowed for us to record simultaneously the different possible forms of inhibition while limiting confounds between response inhibition and parallel cognitive processes. We found BOLD dynamics consistent with non-selective models. These results provide new theoretical and methodological lines of inquiry for the study of basic functions involved in behavioural control and related disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

An integrated approach to develop, validate and operate thermo-physiological human simulator for the development of protective clothing.

PubMed

Psikuta, Agnes; Koelblen, Barbara; Mert, Emel; Fontana, Piero; Annaheim, Simon

2017-12-07

Following the growing interest in the further development of manikins to simulate human thermal behaviour more adequately, thermo-physiological human simulators have been developed by coupling a thermal sweating manikin with a thermo-physiology model. Despite their availability and obvious advantages, the number of studies involving these devices is only marginal, which plausibly results from the high complexity of the development and evaluation process and need of multi-disciplinary expertise. The aim of this paper is to present an integrated approach to develop, validate and operate such devices including technical challenges and limitations of thermo-physiological human simulators, their application and measurement protocol, strategy for setting test scenarios, and the comparison to standard methods and human studies including details which have not been published so far. A physical manikin controlled by a human thermoregulation model overcame the limitations of mathematical clothing models and provided a complementary method to investigate thermal interactions between the human body, protective clothing, and its environment. The opportunities of these devices include not only realistic assessment of protective clothing assemblies and equipment but also potential application in many research fields ranging from biometeorology, automotive industry, environmental engineering, and urban climate to clinical and safety applications.

An integrated approach to develop, validate and operate thermo-physiological human simulator for the development of protective clothing

PubMed Central

PSIKUTA, Agnes; KOELBLEN, Barbara; MERT, Emel; FONTANA, Piero; ANNAHEIM, Simon

2017-01-01

Following the growing interest in the further development of manikins to simulate human thermal behaviour more adequately, thermo-physiological human simulators have been developed by coupling a thermal sweating manikin with a thermo-physiology model. Despite their availability and obvious advantages, the number of studies involving these devices is only marginal, which plausibly results from the high complexity of the development and evaluation process and need of multi-disciplinary expertise. The aim of this paper is to present an integrated approach to develop, validate and operate such devices including technical challenges and limitations of thermo-physiological human simulators, their application and measurement protocol, strategy for setting test scenarios, and the comparison to standard methods and human studies including details which have not been published so far. A physical manikin controlled by a human thermoregulation model overcame the limitations of mathematical clothing models and provided a complementary method to investigate thermal interactions between the human body, protective clothing, and its environment. The opportunities of these devices include not only realistic assessment of protective clothing assemblies and equipment but also potential application in many research fields ranging from biometeorology, automotive industry, environmental engineering, and urban climate to clinical and safety applications. PMID:28966294

Entrainment to the CIECAM02 and CIELAB colour appearance models in the human cortex.

PubMed

Thwaites, Andrew; Wingfield, Cai; Wieser, Eric; Soltan, Andrew; Marslen-Wilson, William D; Nimmo-Smith, Ian

2018-04-01

In human visual processing, information from the visual field passes through numerous transformations before perceptual attributes such as colour are derived. The sequence of transforms involved in constructing perceptions of colour can be approximated by colour appearance models such as the CIE (2002) colour appearance model, abbreviated as CIECAM02. In this study, we test the plausibility of CIECAM02 as a model of colour processing by looking for evidence of its cortical entrainment. The CIECAM02 model predicts that colour is split in to two opposing chromatic components, red-green and cyan-yellow (termed CIECAM02-a and CIECAM02-b respectively), and an achromatic component (termed CIECAM02-A). Entrainment of cortical activity to the outputs of these components was estimated using measurements of electro- and magnetoencephalographic (EMEG) activity, recorded while healthy subjects watched videos of dots changing colour. We find entrainment to chromatic component CIECAM02-a at approximately 35 ms latency bilaterally in occipital lobe regions, and entrainment to achromatic component CIECAM02-A at approximately 75 ms latency, also bilaterally in occipital regions. For comparison, transforms from a less physiologically plausible model (CIELAB) were also tested, with no significant entrainment found. Copyright © 2018 Elsevier Ltd. All rights reserved.

An action potential-driven model of soleus muscle activation dynamics for locomotor-like movements

NASA Astrophysics Data System (ADS)

Kim, Hojeong; Sandercock, Thomas G.; Heckman, C. J.

2015-08-01

Objective. The goal of this study was to develop a physiologically plausible, computationally robust model for muscle activation dynamics (A(t)) under physiologically relevant excitation and movement. Approach. The interaction of excitation and movement on A(t) was investigated comparing the force production between a cat soleus muscle and its Hill-type model. For capturing A(t) under excitation and movement variation, a modular modeling framework was proposed comprising of three compartments: (1) spikes-to-[Ca2+]; (2) [Ca2+]-to-A; and (3) A-to-force transformation. The individual signal transformations were modeled based on physiological factors so that the parameter values could be separately determined for individual modules directly based on experimental data. Main results. The strong dependency of A(t) on excitation frequency and muscle length was found during both isometric and dynamically-moving contractions. The identified dependencies of A(t) under the static and dynamic conditions could be incorporated in the modular modeling framework by modulating the model parameters as a function of movement input. The new modeling approach was also applicable to cat soleus muscles producing waveforms independent of those used to set the model parameters. Significance. This study provides a modeling framework for spike-driven muscle responses during movement, that is suitable not only for insights into molecular mechanisms underlying muscle behaviors but also for large scale simulations.

Direction-dependent regularization for improved estimation of liver and lung motion in 4D image data

NASA Astrophysics Data System (ADS)

Schmidt-Richberg, Alexander; Ehrhardt, Jan; Werner, René; Handels, Heinz

2010-03-01

The estimation of respiratory motion is a fundamental requisite for many applications in the field of 4D medical imaging, for example for radiotherapy of thoracic and abdominal tumors. It is usually done using non-linear registration of time frames of the sequence without further modelling of physiological motion properties. In this context, the accurate calculation of liver und lung motion is especially challenging because the organs are slipping along the surrounding tissue (i.e. the rib cage) during the respiratory cycle, which leads to discontinuities in the motion field. Without incorporating this specific physiological characteristic, common smoothing mechanisms cause an incorrect estimation along the object borders. In this paper, we present an extended diffusion-based model for incorporating physiological knowledge in image registration. By decoupling normal- and tangential-directed smoothing, we are able to estimate slipping motion at the organ borders while preventing gaps and ensuring smooth motion fields inside. We evaluate our model for the estimation of lung and liver motion on the basis of publicly accessible 4D CT and 4D MRI data. The results show a considerable increase of registration accuracy with respect to the target registration error and a more plausible motion estimation.

The Role of ERK1/2 in the Progression of Anti-Androgen Resistance of MtDNA Deficient Prostate Cancer

DTIC Science & Technology

2012-03-01

proto-oncogenic pathway, it is plausible that the mitoGPS is a ubiquitous (patho) physiological response to the etiology and/or progression of a broad...the mitochondrion as a direct physiological source of hypoxia in an in vitro system. Our results demonstrate that the reduction of the mitochondrial...ubiquitous (patho) physiological response to the etiology and/or progression of a broad spectrum of human diseases that are attributed to respiratory

The Utility of Cognitive Plausibility in Language Acquisition Modeling: Evidence From Word Segmentation.

PubMed

Phillips, Lawrence; Pearl, Lisa

2015-11-01

The informativity of a computational model of language acquisition is directly related to how closely it approximates the actual acquisition task, sometimes referred to as the model's cognitive plausibility. We suggest that though every computational model necessarily idealizes the modeled task, an informative language acquisition model can aim to be cognitively plausible in multiple ways. We discuss these cognitive plausibility checkpoints generally and then apply them to a case study in word segmentation, investigating a promising Bayesian segmentation strategy. We incorporate cognitive plausibility by using an age-appropriate unit of perceptual representation, evaluating the model output in terms of its utility, and incorporating cognitive constraints into the inference process. Our more cognitively plausible model shows a beneficial effect of cognitive constraints on segmentation performance. One interpretation of this effect is as a synergy between the naive theories of language structure that infants may have and the cognitive constraints that limit the fidelity of their inference processes, where less accurate inference approximations are better when the underlying assumptions about how words are generated are less accurate. More generally, these results highlight the utility of incorporating cognitive plausibility more fully into computational models of language acquisition. Copyright © 2015 Cognitive Science Society, Inc.

Role of the locus coeruleus in the emergence of power law wake bouts in a model of the brainstem sleep-wake system through early infancy.

PubMed

Patel, Mainak; Rangan, Aaditya

2017-08-07

Infant rats randomly cycle between the sleeping and waking states, which are tightly correlated with the activity of mutually inhibitory brainstem sleep and wake populations. Bouts of sleep and wakefulness are random; from P2-P10, sleep and wake bout lengths are exponentially distributed with increasing means, while during P10-P21, the sleep bout distribution remains exponential while the distribution of wake bouts gradually transforms to power law. The locus coeruleus (LC), via an undeciphered interaction with sleep and wake populations, has been shown experimentally to be responsible for the exponential to power law transition. Concurrently during P10-P21, the LC undergoes striking physiological changes - the LC exhibits strong global 0.3 Hz oscillations up to P10, but the oscillation frequency gradually rises and synchrony diminishes from P10-P21, with oscillations and synchrony vanishing at P21 and beyond. In this work, we construct a biologically plausible Wilson Cowan-style model consisting of the LC along with sleep and wake populations. We show that external noise and strong reciprocal inhibition can lead to switching between sleep and wake populations and exponentially distributed sleep and wake bout durations as during P2-P10, with the parameters of inhibition between the sleep and wake populations controlling mean bout lengths. Furthermore, we show that the changing physiology of the LC from P10-P21, coupled with reciprocal excitation between the LC and wake population, can explain the shift from exponential to power law of the wake bout distribution. To our knowledge, this is the first study that proposes a plausible biological mechanism, which incorporates the known changing physiology of the LC, for tying the developing sleep-wake circuit and its interaction with the LC to the transformation of sleep and wake bout dynamics from P2-P21. Copyright © 2017 Elsevier Ltd. All rights reserved.

Physiome-model-based state-space framework for cardiac deformation recovery.

PubMed

Wong, Ken C L; Zhang, Heye; Liu, Huafeng; Shi, Pengcheng

2007-11-01

To more reliably recover cardiac information from noise-corrupted, patient-specific measurements, it is essential to employ meaningful constraining models and adopt appropriate optimization criteria to couple the models with the measurements. Although biomechanical models have been extensively used for myocardial motion recovery with encouraging results, the passive nature of such constraints limits their ability to fully count for the deformation caused by active forces of the myocytes. To overcome such limitations, we propose to adopt a cardiac physiome model as the prior constraint for cardiac motion analysis. The cardiac physiome model comprises an electric wave propagation model, an electromechanical coupling model, and a biomechanical model, which are connected through a cardiac system dynamics for a more complete description of the macroscopic cardiac physiology. Embedded within a multiframe state-space framework, the uncertainties of the model and the patient's measurements are systematically dealt with to arrive at optimal cardiac kinematic estimates and possibly beyond. Experiments have been conducted to compare our proposed cardiac-physiome-model-based framework with the solely biomechanical model-based framework. The results show that our proposed framework recovers more accurate cardiac deformation from synthetic data and obtains more sensible estimates from real magnetic resonance image sequences. With the active components introduced by the cardiac physiome model, cardiac deformations recovered from patient's medical images are more physiologically plausible.

Polarization-Sensitive Hyperspectral Imaging in vivo: A Multimode Dermoscope for Skin Analysis

NASA Astrophysics Data System (ADS)

Vasefi, Fartash; MacKinnon, Nicholas; Saager, Rolf B.; Durkin, Anthony J.; Chave, Robert; Lindsley, Erik H.; Farkas, Daniel L.

2014-05-01

Attempts to understand the changes in the structure and physiology of human skin abnormalities by non-invasive optical imaging are aided by spectroscopic methods that quantify, at the molecular level, variations in tissue oxygenation and melanin distribution. However, current commercial and research systems to map hemoglobin and melanin do not correlate well with pathology for pigmented lesions or darker skin. We developed a multimode dermoscope that combines polarization and hyperspectral imaging with an efficient analytical model to map the distribution of specific skin bio-molecules. This corrects for the melanin-hemoglobin misestimation common to other systems, without resorting to complex and computationally intensive tissue optical models. For this system's proof of concept, human skin measurements on melanocytic nevus, vitiligo, and venous occlusion conditions were performed in volunteers. The resulting molecular distribution maps matched physiological and anatomical expectations, confirming a technologic approach that can be applied to next generation dermoscopes and having biological plausibility that is likely to appeal to dermatologists.

Influence of Resting Venous Blood Volume Fraction on Dynamic Causal Modeling and System Identifiability.

PubMed

Hu, Zhenghui; Ni, Pengyu; Wan, Qun; Zhang, Yan; Shi, Pengcheng; Lin, Qiang

2016-07-08

Changes in BOLD signals are sensitive to the regional blood content associated with the vasculature, which is known as V0 in hemodynamic models. In previous studies involving dynamic causal modeling (DCM) which embodies the hemodynamic model to invert the functional magnetic resonance imaging signals into neuronal activity, V0 was arbitrarily set to a physiolog-ically plausible value to overcome the ill-posedness of the inverse problem. It is interesting to investigate how the V0 value influences DCM. In this study we addressed this issue by using both synthetic and real experiments. The results show that the ability of DCM analysis to reveal information about brain causality depends critically on the assumed V0 value used in the analysis procedure. The choice of V0 value not only directly affects the strength of system connections, but more importantly also affects the inferences about the network architecture. Our analyses speak to a possible refinement of how the hemody-namic process is parameterized (i.e., by making V0 a free parameter); however, the conditional dependencies induced by a more complex model may create more problems than they solve. Obtaining more realistic V0 information in DCM can improve the identifiability of the system and would provide more reliable inferences about the properties of brain connectivity.

NICE: A Computational Solution to Close the Gap from Colour Perception to Colour Categorization

PubMed Central

Parraga, C. Alejandro; Akbarinia, Arash

2016-01-01

The segmentation of visible electromagnetic radiation into chromatic categories by the human visual system has been extensively studied from a perceptual point of view, resulting in several colour appearance models. However, there is currently a void when it comes to relate these results to the physiological mechanisms that are known to shape the pre-cortical and cortical visual pathway. This work intends to begin to fill this void by proposing a new physiologically plausible model of colour categorization based on Neural Isoresponsive Colour Ellipsoids (NICE) in the cone-contrast space defined by the main directions of the visual signals entering the visual cortex. The model was adjusted to fit psychophysical measures that concentrate on the categorical boundaries and are consistent with the ellipsoidal isoresponse surfaces of visual cortical neurons. By revealing the shape of such categorical colour regions, our measures allow for a more precise and parsimonious description, connecting well-known early visual processing mechanisms to the less understood phenomenon of colour categorization. To test the feasibility of our method we applied it to exemplary images and a popular ground-truth chart obtaining labelling results that are better than those of current state-of-the-art algorithms. PMID:26954691

NICE: A Computational Solution to Close the Gap from Colour Perception to Colour Categorization.

PubMed

Parraga, C Alejandro; Akbarinia, Arash

2016-01-01

The segmentation of visible electromagnetic radiation into chromatic categories by the human visual system has been extensively studied from a perceptual point of view, resulting in several colour appearance models. However, there is currently a void when it comes to relate these results to the physiological mechanisms that are known to shape the pre-cortical and cortical visual pathway. This work intends to begin to fill this void by proposing a new physiologically plausible model of colour categorization based on Neural Isoresponsive Colour Ellipsoids (NICE) in the cone-contrast space defined by the main directions of the visual signals entering the visual cortex. The model was adjusted to fit psychophysical measures that concentrate on the categorical boundaries and are consistent with the ellipsoidal isoresponse surfaces of visual cortical neurons. By revealing the shape of such categorical colour regions, our measures allow for a more precise and parsimonious description, connecting well-known early visual processing mechanisms to the less understood phenomenon of colour categorization. To test the feasibility of our method we applied it to exemplary images and a popular ground-truth chart obtaining labelling results that are better than those of current state-of-the-art algorithms.

Single Canonical Model of Reflexive Memory and Spatial Attention

PubMed Central

Patel, Saumil S.; Red, Stuart; Lin, Eric; Sereno, Anne B.

2015-01-01

Many neurons in the dorsal and ventral visual stream have the property that after a brief visual stimulus presentation in their receptive field, the spiking activity in these neurons persists above their baseline levels for several seconds. This maintained activity is not always correlated with the monkey’s task and its origin is unknown. We have previously proposed a simple neural network model, based on shape selective neurons in monkey lateral intraparietal cortex, which predicts the valence and time course of reflexive (bottom-up) spatial attention. In the same simple model, we demonstrate here that passive maintained activity or short-term memory of specific visual events can result without need for an external or top-down modulatory signal. Mutual inhibition and neuronal adaptation play distinct roles in reflexive attention and memory. This modest 4-cell model provides the first simple and unified physiologically plausible mechanism of reflexive spatial attention and passive short-term memory processes. PMID:26493949

Generalised filtering and stochastic DCM for fMRI.

PubMed

Li, Baojuan; Daunizeau, Jean; Stephan, Klaas E; Penny, Will; Hu, Dewen; Friston, Karl

2011-09-15

This paper is about the fitting or inversion of dynamic causal models (DCMs) of fMRI time series. It tries to establish the validity of stochastic DCMs that accommodate random fluctuations in hidden neuronal and physiological states. We compare and contrast deterministic and stochastic DCMs, which do and do not ignore random fluctuations or noise on hidden states. We then compare stochastic DCMs, which do and do not ignore conditional dependence between hidden states and model parameters (generalised filtering and dynamic expectation maximisation, respectively). We first characterise state-noise by comparing the log evidence of models with different a priori assumptions about its amplitude, form and smoothness. Face validity of the inversion scheme is then established using data simulated with and without state-noise to ensure that DCM can identify the parameters and model that generated the data. Finally, we address construct validity using real data from an fMRI study of internet addiction. Our analyses suggest the following. (i) The inversion of stochastic causal models is feasible, given typical fMRI data. (ii) State-noise has nontrivial amplitude and smoothness. (iii) Stochastic DCM has face validity, in the sense that Bayesian model comparison can distinguish between data that have been generated with high and low levels of physiological noise and model inversion provides veridical estimates of effective connectivity. (iv) Relaxing conditional independence assumptions can have greater construct validity, in terms of revealing group differences not disclosed by variational schemes. Finally, we note that the ability to model endogenous or random fluctuations on hidden neuronal (and physiological) states provides a new and possibly more plausible perspective on how regionally specific signals in fMRI are generated. Copyright © 2011. Published by Elsevier Inc.

Schopenhauer on Sense Perception and Aesthetic Cognition

ERIC Educational Resources Information Center

Vandenabeele, Bart

2011-01-01

Schopenhauer's account of sense perception contains an acute critique of Kant's theory of cognition. His analysis of the role of the understanding in perception may be closer to Kant's than he conceded, but his physiological analysis of the role of the senses nonetheless proffers a more plausible account than Kant's transcendental conception of…

Predictions of the Contribution of HCN Half-Maximal Activation Potential Heterogeneity to Variability in Intrinsic Adaptation of Spiral Ganglion Neurons.

PubMed

Boulet, Jason; Bruce, Ian C

2017-04-01

Spiral ganglion neurons (SGNs) exhibit a wide range in their strength of intrinsic adaptation on a timescale of 10s to 100s of milliseconds in response to electrical stimulation from a cochlear implant (CI). The purpose of this study was to determine how much of that variability could be caused by the heterogeneity in half-maximal activation potentials of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels, which are known to produce intrinsic adaptation. In this study, a computational membrane model of cat type I SGN was developed based on the Hodgkin-Huxley model plus HCN and low-threshold potassium (KLT) conductances in which the half-maximal activation potential of the HCN channel was varied and the response of the SGN to pulse train and paired-pulse stimulation was simulated. Physiologically plausible variation of HCN half-maximal activation potentials could indeed determine the range of adaptation on the timescale of 10s to 100s of milliseconds and recovery from adaptation seen in the physiological data while maintaining refractoriness within physiological bounds. This computational model demonstrates that HCN channels may play an important role in regulating the degree of adaptation in response to pulse train stimulation and therefore contribute to variable constraints on acoustic information coding by CIs. This finding has broad implications for CI stimulation paradigms in that cell-to-cell variation of HCN channel properties are likely to significantly alter SGN excitability and therefore auditory perception.

The Universal Plausibility Metric (UPM) & Principle (UPP).

PubMed

Abel, David L

2009-12-03

Mere possibility is not an adequate basis for asserting scientific plausibility. A precisely defined universal bound is needed beyond which the assertion of plausibility, particularly in life-origin models, can be considered operationally falsified. But can something so seemingly relative and subjective as plausibility ever be quantified? Amazingly, the answer is, "Yes." A method of objectively measuring the plausibility of any chance hypothesis (The Universal Plausibility Metric [UPM]) is presented. A numerical inequality is also provided whereby any chance hypothesis can be definitively falsified when its UPM metric of xi is < 1 (The Universal Plausibility Principle [UPP]). Both UPM and UPP pre-exist and are independent of any experimental design and data set. No low-probability hypothetical plausibility assertion should survive peer-review without subjection to the UPP inequality standard of formal falsification (xi < 1).

The Utility of Cognitive Plausibility in Language Acquisition Modeling: Evidence from Word Segmentation

ERIC Educational Resources Information Center

Phillips, Lawrence; Pearl, Lisa

2015-01-01

The informativity of a computational model of language acquisition is directly related to how closely it approximates the actual acquisition task, sometimes referred to as the model's "cognitive plausibility." We suggest that though every computational model necessarily idealizes the modeled task, an informative language acquisition…

Pharmacometric Models for Characterizing the Pharmacokinetics of Orally Inhaled Drugs.

PubMed

Borghardt, Jens Markus; Weber, Benjamin; Staab, Alexander; Kloft, Charlotte

2015-07-01

During the last decades, the importance of modeling and simulation in clinical drug development, with the goal to qualitatively and quantitatively assess and understand mechanisms of pharmacokinetic processes, has strongly increased. However, this increase could not equally be observed for orally inhaled drugs. The objectives of this review are to understand the reasons for this gap and to demonstrate the opportunities that mathematical modeling of pharmacokinetics of orally inhaled drugs offers. To achieve these objectives, this review (i) discusses pulmonary physiological processes and their impact on the pharmacokinetics after drug inhalation, (ii) provides a comprehensive overview of published pharmacokinetic models, (iii) categorizes these models into physiologically based pharmacokinetic (PBPK) and (clinical data-derived) empirical models, (iv) explores both their (mechanistic) plausibility, and (v) addresses critical aspects of different pharmacometric approaches pertinent for drug inhalation. In summary, pulmonary deposition, dissolution, and absorption are highly complex processes and may represent the major challenge for modeling and simulation of PK after oral drug inhalation. Challenges in relating systemic pharmacokinetics with pulmonary efficacy may be another factor contributing to the limited number of existing pharmacokinetic models for orally inhaled drugs. Investigations comprising in vitro experiments, clinical studies, and more sophisticated mathematical approaches are considered to be necessary for elucidating these highly complex pulmonary processes. With this additional knowledge, the PBPK approach might gain additional attractiveness. Currently, (semi-)mechanistic modeling offers an alternative to generate and investigate hypotheses and to more mechanistically understand the pulmonary and systemic pharmacokinetics after oral drug inhalation including the impact of pulmonary diseases.

Influence of Resting Venous Blood Volume Fraction on Dynamic Causal Modeling and System Identifiability

PubMed Central

Hu, Zhenghui; Ni, Pengyu; Wan, Qun; Zhang, Yan; Shi, Pengcheng; Lin, Qiang

2016-01-01

Changes in BOLD signals are sensitive to the regional blood content associated with the vasculature, which is known as V0 in hemodynamic models. In previous studies involving dynamic causal modeling (DCM) which embodies the hemodynamic model to invert the functional magnetic resonance imaging signals into neuronal activity, V0 was arbitrarily set to a physiolog-ically plausible value to overcome the ill-posedness of the inverse problem. It is interesting to investigate how the V0 value influences DCM. In this study we addressed this issue by using both synthetic and real experiments. The results show that the ability of DCM analysis to reveal information about brain causality depends critically on the assumed V0 value used in the analysis procedure. The choice of V0 value not only directly affects the strength of system connections, but more importantly also affects the inferences about the network architecture. Our analyses speak to a possible refinement of how the hemody-namic process is parameterized (i.e., by making V0 a free parameter); however, the conditional dependencies induced by a more complex model may create more problems than they solve. Obtaining more realistic V0 information in DCM can improve the identifiability of the system and would provide more reliable inferences about the properties of brain connectivity. PMID:27389074

Using a Thyroid Case Study and Error Plausibility to Introduce Basic Lab Skills

ERIC Educational Resources Information Center

Browning, Samantha; Urschler, Margaret; Meidl, Katherine; Peculis, Brenda; Milanick, Mark

2017-01-01

We describe a 3-hour session that provides students with the opportunity to review basic lab concepts and important techniques using real life scenarios. We began with two separate student-engaged discussions to remind/reinforce some basic concepts in physiology and review calculations with respect to chemical compounds. This was followed by…

Physiological models of the lateral superior olive

PubMed Central

2017-01-01

In computational biology, modeling is a fundamental tool for formulating, analyzing and predicting complex phenomena. Most neuron models, however, are designed to reproduce certain small sets of empirical data. Hence their outcome is usually not compatible or comparable with other models or datasets, making it unclear how widely applicable such models are. In this study, we investigate these aspects of modeling, namely credibility and generalizability, with a specific focus on auditory neurons involved in the localization of sound sources. The primary cues for binaural sound localization are comprised of interaural time and level differences (ITD/ILD), which are the timing and intensity differences of the sound waves arriving at the two ears. The lateral superior olive (LSO) in the auditory brainstem is one of the locations where such acoustic information is first computed. An LSO neuron receives temporally structured excitatory and inhibitory synaptic inputs that are driven by ipsi- and contralateral sound stimuli, respectively, and changes its spike rate according to binaural acoustic differences. Here we examine seven contemporary models of LSO neurons with different levels of biophysical complexity, from predominantly functional ones (‘shot-noise’ models) to those with more detailed physiological components (variations of integrate-and-fire and Hodgkin-Huxley-type). These models, calibrated to reproduce known monaural and binaural characteristics of LSO, generate largely similar results to each other in simulating ITD and ILD coding. Our comparisons of physiological detail, computational efficiency, predictive performances, and further expandability of the models demonstrate (1) that the simplistic, functional LSO models are suitable for applications where low computational costs and mathematical transparency are needed, (2) that more complex models with detailed membrane potential dynamics are necessary for simulation studies where sub-neuronal nonlinear processes play important roles, and (3) that, for general purposes, intermediate models might be a reasonable compromise between simplicity and biological plausibility. PMID:29281618

The Universal Plausibility Metric (UPM) & Principle (UPP)

PubMed Central

2009-01-01

Background Mere possibility is not an adequate basis for asserting scientific plausibility. A precisely defined universal bound is needed beyond which the assertion of plausibility, particularly in life-origin models, can be considered operationally falsified. But can something so seemingly relative and subjective as plausibility ever be quantified? Amazingly, the answer is, "Yes." A method of objectively measuring the plausibility of any chance hypothesis (The Universal Plausibility Metric [UPM]) is presented. A numerical inequality is also provided whereby any chance hypothesis can be definitively falsified when its UPM metric of ξ is < 1 (The Universal Plausibility Principle [UPP]). Both UPM and UPP pre-exist and are independent of any experimental design and data set. Conclusion No low-probability hypothetical plausibility assertion should survive peer-review without subjection to the UPP inequality standard of formal falsification (ξ < 1). PMID:19958539

A Workflow for Global Sensitivity Analysis of PBPK Models

PubMed Central

McNally, Kevin; Cotton, Richard; Loizou, George D.

2011-01-01

Physiologically based pharmacokinetic (PBPK) models have a potentially significant role in the development of a reliable predictive toxicity testing strategy. The structure of PBPK models are ideal frameworks into which disparate in vitro and in vivo data can be integrated and utilized to translate information generated, using alternative to animal measures of toxicity and human biological monitoring data, into plausible corresponding exposures. However, these models invariably include the description of well known non-linear biological processes such as, enzyme saturation and interactions between parameters such as, organ mass and body mass. Therefore, an appropriate sensitivity analysis (SA) technique is required which can quantify the influences associated with individual parameters, interactions between parameters and any non-linear processes. In this report we have defined the elements of a workflow for SA of PBPK models that is computationally feasible, accounts for interactions between parameters, and can be displayed in the form of a bar chart and cumulative sum line (Lowry plot), which we believe is intuitive and appropriate for toxicologists, risk assessors, and regulators. PMID:21772819

Applying generalized linear models as an explanatory tool of sex steroids, thyroid hormones and their relationships with environmental and physiologic factors in immature East Pacific green sea turtles (Chelonia mydas).

PubMed

Labrada-Martagón, Vanessa; Méndez-Rodríguez, Lia C; Mangel, Marc; Zenteno-Savín, Tania

2013-09-01

Generalized linear models were fitted to evaluate the relationship between 17β-estradiol (E2), testosterone (T) and thyroxine (T4) levels in immature East Pacific green sea turtles (Chelonia mydas) and their body condition, size, mass, blood biochemistry parameters, handling time, year, season and site of capture. According to external (tail size) and morphological (<77.3 straight carapace length) characteristics, 95% of the individuals were juveniles. Hormone levels, assessed on sea turtles subjected to a capture stress protocol, were <34.7nmolTL(-1), <532.3pmolE2 L(-1) and <43.8nmolT4L(-1). The statistical model explained biologically plausible metabolic relationships between hormone concentrations and blood biochemistry parameters (e.g. glucose, cholesterol) and the potential effect of environmental variables (season and study site). The variables handling time and year did not contribute significantly to explain hormone levels. Differences in sex steroids between season and study sites found by the models coincided with specific nutritional, physiological and body condition differences related to the specific habitat conditions. The models correctly predicted the median levels of the measured hormones in green sea turtles, which confirms the fitted model's utility. It is suggested that quantitative predictions could be possible when the model is tested with additional data. Copyright © 2013 Elsevier Inc. All rights reserved.

Reinforcement Learning Using a Continuous Time Actor-Critic Framework with Spiking Neurons

PubMed Central

Frémaux, Nicolas; Sprekeler, Henning; Gerstner, Wulfram

2013-01-01

Animals repeat rewarded behaviors, but the physiological basis of reward-based learning has only been partially elucidated. On one hand, experimental evidence shows that the neuromodulator dopamine carries information about rewards and affects synaptic plasticity. On the other hand, the theory of reinforcement learning provides a framework for reward-based learning. Recent models of reward-modulated spike-timing-dependent plasticity have made first steps towards bridging the gap between the two approaches, but faced two problems. First, reinforcement learning is typically formulated in a discrete framework, ill-adapted to the description of natural situations. Second, biologically plausible models of reward-modulated spike-timing-dependent plasticity require precise calculation of the reward prediction error, yet it remains to be shown how this can be computed by neurons. Here we propose a solution to these problems by extending the continuous temporal difference (TD) learning of Doya (2000) to the case of spiking neurons in an actor-critic network operating in continuous time, and with continuous state and action representations. In our model, the critic learns to predict expected future rewards in real time. Its activity, together with actual rewards, conditions the delivery of a neuromodulatory TD signal to itself and to the actor, which is responsible for action choice. In simulations, we show that such an architecture can solve a Morris water-maze-like navigation task, in a number of trials consistent with reported animal performance. We also use our model to solve the acrobot and the cartpole problems, two complex motor control tasks. Our model provides a plausible way of computing reward prediction error in the brain. Moreover, the analytically derived learning rule is consistent with experimental evidence for dopamine-modulated spike-timing-dependent plasticity. PMID:23592970

Reinforcement learning using a continuous time actor-critic framework with spiking neurons.

PubMed

Frémaux, Nicolas; Sprekeler, Henning; Gerstner, Wulfram

2013-04-01

Animals repeat rewarded behaviors, but the physiological basis of reward-based learning has only been partially elucidated. On one hand, experimental evidence shows that the neuromodulator dopamine carries information about rewards and affects synaptic plasticity. On the other hand, the theory of reinforcement learning provides a framework for reward-based learning. Recent models of reward-modulated spike-timing-dependent plasticity have made first steps towards bridging the gap between the two approaches, but faced two problems. First, reinforcement learning is typically formulated in a discrete framework, ill-adapted to the description of natural situations. Second, biologically plausible models of reward-modulated spike-timing-dependent plasticity require precise calculation of the reward prediction error, yet it remains to be shown how this can be computed by neurons. Here we propose a solution to these problems by extending the continuous temporal difference (TD) learning of Doya (2000) to the case of spiking neurons in an actor-critic network operating in continuous time, and with continuous state and action representations. In our model, the critic learns to predict expected future rewards in real time. Its activity, together with actual rewards, conditions the delivery of a neuromodulatory TD signal to itself and to the actor, which is responsible for action choice. In simulations, we show that such an architecture can solve a Morris water-maze-like navigation task, in a number of trials consistent with reported animal performance. We also use our model to solve the acrobot and the cartpole problems, two complex motor control tasks. Our model provides a plausible way of computing reward prediction error in the brain. Moreover, the analytically derived learning rule is consistent with experimental evidence for dopamine-modulated spike-timing-dependent plasticity.

The hippocampo-prefrontal pathway: a possible therapeutic target for negative and cognitive symptoms of schizophrenia

PubMed Central

Ghoshal, Ayan; Conn, P Jeffrey

2015-01-01

The hippocampo-prefrontal (H-PFC) pathway has been linked to cognitive and emotional disturbances in several psychiatric disorders including schizophrenia. Preclinical evidence from the NMDA receptor antagonism rodent model of schizophrenia shows severe pathology selective to the H-PFC pathway. It is speculated that there is an increased excitatory drive from the hippocampus to the prefrontal cortex due to dysfunctions in the H-PFC plasticity, which may serve as the basis for the behavioral consequences observed in this rodent model. Thus, the H-PFC pathway is currently emerging as a promising therapeutic target for the negative and cognitive symptom clusters of schizophrenia. Here, we have reviewed the physiological, pharmacological and functional characteristics of the H-PFC pathway and we propose that allosteric activation of glutamatergic and cholinergic neurotransmission can serve as a plausible therapeutic approach. PMID:25825588

PyMUS: Python-Based Simulation Software for Virtual Experiments on Motor Unit System

PubMed Central

Kim, Hojeong; Kim, Minjung

2018-01-01

We constructed a physiologically plausible computationally efficient model of a motor unit and developed simulation software that allows for integrative investigations of the input–output processing in the motor unit system. The model motor unit was first built by coupling the motoneuron model and muscle unit model to a simplified axon model. To build the motoneuron model, we used a recently reported two-compartment modeling approach that accurately captures the key cell-type-related electrical properties under both passive conditions (somatic input resistance, membrane time constant, and signal attenuation properties between the soma and the dendrites) and active conditions (rheobase current and afterhyperpolarization duration at the soma and plateau behavior at the dendrites). To construct the muscle unit, we used a recently developed muscle modeling approach that reflects the experimentally identified dependencies of muscle activation dynamics on isometric, isokinetic and dynamic variation in muscle length over a full range of stimulation frequencies. Then, we designed the simulation software based on the object-oriented programing paradigm and developed the software using open-source Python language to be fully operational using graphical user interfaces. Using the developed software, separate simulations could be performed for a single motoneuron, muscle unit and motor unit under a wide range of experimental input protocols, and a hierarchical analysis could be performed from a single channel to the entire system behavior. Our model motor unit and simulation software may represent efficient tools not only for researchers studying the neural control of force production from a cellular perspective but also for instructors and students in motor physiology classroom settings. PMID:29695959

PyMUS: Python-Based Simulation Software for Virtual Experiments on Motor Unit System.

PubMed

Kim, Hojeong; Kim, Minjung

2018-01-01

We constructed a physiologically plausible computationally efficient model of a motor unit and developed simulation software that allows for integrative investigations of the input-output processing in the motor unit system. The model motor unit was first built by coupling the motoneuron model and muscle unit model to a simplified axon model. To build the motoneuron model, we used a recently reported two-compartment modeling approach that accurately captures the key cell-type-related electrical properties under both passive conditions (somatic input resistance, membrane time constant, and signal attenuation properties between the soma and the dendrites) and active conditions (rheobase current and afterhyperpolarization duration at the soma and plateau behavior at the dendrites). To construct the muscle unit, we used a recently developed muscle modeling approach that reflects the experimentally identified dependencies of muscle activation dynamics on isometric, isokinetic and dynamic variation in muscle length over a full range of stimulation frequencies. Then, we designed the simulation software based on the object-oriented programing paradigm and developed the software using open-source Python language to be fully operational using graphical user interfaces. Using the developed software, separate simulations could be performed for a single motoneuron, muscle unit and motor unit under a wide range of experimental input protocols, and a hierarchical analysis could be performed from a single channel to the entire system behavior. Our model motor unit and simulation software may represent efficient tools not only for researchers studying the neural control of force production from a cellular perspective but also for instructors and students in motor physiology classroom settings.

Impaired associative learning in schizophrenia: behavioral and computational studies

PubMed Central

Diwadkar, Vaibhav A.; Flaugher, Brad; Jones, Trevor; Zalányi, László; Ujfalussy, Balázs; Keshavan, Matcheri S.

2008-01-01

Associative learning is a central building block of human cognition and in large part depends on mechanisms of synaptic plasticity, memory capacity and fronto–hippocampal interactions. A disorder like schizophrenia is thought to be characterized by altered plasticity, and impaired frontal and hippocampal function. Understanding the expression of this dysfunction through appropriate experimental studies, and understanding the processes that may give rise to impaired behavior through biologically plausible computational models will help clarify the nature of these deficits. We present a preliminary computational model designed to capture learning dynamics in healthy control and schizophrenia subjects. Experimental data was collected on a spatial-object paired-associate learning task. The task evinces classic patterns of negatively accelerated learning in both healthy control subjects and patients, with patients demonstrating lower rates of learning than controls. Our rudimentary computational model of the task was based on biologically plausible assumptions, including the separation of dorsal/spatial and ventral/object visual streams, implementation of rules of learning, the explicit parameterization of learning rates (a plausible surrogate for synaptic plasticity), and learning capacity (a plausible surrogate for memory capacity). Reductions in learning dynamics in schizophrenia were well-modeled by reductions in learning rate and learning capacity. The synergy between experimental research and a detailed computational model of performance provides a framework within which to infer plausible biological bases of impaired learning dynamics in schizophrenia. PMID:19003486

Advanced glycation endproducts form during ovalbumin digestion in the presence of fructose: Inhibition by chlorogenic acid.

PubMed

Bains, Yasmin; Gugliucci, Alejandro; Caccavello, Russell

2017-07-01

One mechanism by which fructose could exert deleterious effects is through intestinal formation and absorption of pro-inflammatory advanced glycation endproducts via the Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin (OVA) to test the hypothesis that advanced glycation endproducts (AGEs) are formed by fructose during simulated digestion of a ubiquitous food protein under model physiological conditions. OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370nm, Emission: λ 440nm. AGE adducts formed between fructose and OVA, evidenced by the peptide fractions (<5kDa) at times (30min) and concentration ranges (10mM) plausibly found in the intestines, whereas no reaction occurs with glucose. The reaction was inhibited by chlorogenic acid at concentrations compatible with those found in the gut. The reaction was also inhibited by aminoguanidine, a specific antiglycation agent. Our study showed fructose-AGE formation on a ubiquitous dietary protein under model physiological conditions. Our study also suggests ways to decrease the damage: enteral fructose-AGE formation may be partially inhibited by co-intake of beverages, fruits and vegetables with concentrations of phenolics high enough to serve as anti-glycation agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuronal activity-regulated gene transcription: how are distant synaptic signals conveyed to the nucleus?

PubMed Central

Matamales, Miriam

2012-01-01

Synaptic activity can trigger gene expression programs that are required for the stable change of neuronal properties, a process that is essential for learning and memory. Currently, it is still unclear how the stimulation of dendritic synapses can be coupled to transcription in the nucleus in a timely way given that large distances can separate these two cellular compartments. Although several mechanisms have been proposed to explain long distance communication between synapses and the nucleus, the possible co-existence of these models and their relevance in physiological conditions remain elusive. One model suggests that synaptic activation triggers the translocation to the nucleus of certain transcription regulators localised at postsynaptic sites that function as synapto-nuclear messengers. Alternatively, it has been hypothesised that synaptic activity initiates propagating regenerative intracellular calcium waves that spread through dendrites into the nucleus where nuclear transcription machinery is thereby regulated. It has also been postulated that membrane depolarisation of voltage-gated calcium channels on the somatic membrane is sufficient to increase intracellular calcium concentration and activate transcription without the need for transported signals from distant synapses. Here I provide a critical overview of the suggested mechanisms for coupling synaptic stimulation to transcription, the underlying assumptions behind them and their plausible physiological significance. PMID:24327840

Neuronal activity-regulated gene transcription: how are distant synaptic signals conveyed to the nucleus?

PubMed

Matamales, Miriam

2012-12-19

Synaptic activity can trigger gene expression programs that are required for the stable change of neuronal properties, a process that is essential for learning and memory. Currently, it is still unclear how the stimulation of dendritic synapses can be coupled to transcription in the nucleus in a timely way given that large distances can separate these two cellular compartments. Although several mechanisms have been proposed to explain long distance communication between synapses and the nucleus, the possible co-existence of these models and their relevance in physiological conditions remain elusive. One model suggests that synaptic activation triggers the translocation to the nucleus of certain transcription regulators localised at postsynaptic sites that function as synapto-nuclear messengers. Alternatively, it has been hypothesised that synaptic activity initiates propagating regenerative intracellular calcium waves that spread through dendrites into the nucleus where nuclear transcription machinery is thereby regulated. It has also been postulated that membrane depolarisation of voltage-gated calcium channels on the somatic membrane is sufficient to increase intracellular calcium concentration and activate transcription without the need for transported signals from distant synapses. Here I provide a critical overview of the suggested mechanisms for coupling synaptic stimulation to transcription, the underlying assumptions behind them and their plausible physiological significance.

Neuronal activity-regulated gene transcription: how are distant synaptic signals conveyed to the nucleus?

PubMed

Matamales, Miriam

2012-01-01

Synaptic activity can trigger gene expression programs that are required for the stable change of neuronal properties, a process that is essential for learning and memory. Currently, it is still unclear how the stimulation of dendritic synapses can be coupled to transcription in the nucleus in a timely way given that large distances can separate these two cellular compartments. Although several mechanisms have been proposed to explain long distance communication between synapses and the nucleus, the possible co-existence of these models and their relevance in physiological conditions remain elusive. One model suggests that synaptic activation triggers the translocation to the nucleus of certain transcription regulators localised at postsynaptic sites that function as synapto-nuclear messengers. Alternatively, it has been hypothesised that synaptic activity initiates propagating regenerative intracellular calcium waves that spread through dendrites into the nucleus where nuclear transcription machinery is thereby regulated. It has also been postulated that membrane depolarisation of voltage-gated calcium channels on the somatic membrane is sufficient to increase intracellular calcium concentration and activate transcription without the need for transported signals from distant synapses. Here I provide a critical overview of the suggested mechanisms for coupling synaptic stimulation to transcription, the underlying assumptions behind them and their plausible physiological significance.

Joint independent component analysis for simultaneous EEG-fMRI: principle and simulation.

PubMed

Moosmann, Matthias; Eichele, Tom; Nordby, Helge; Hugdahl, Kenneth; Calhoun, Vince D

2008-03-01

An optimized scheme for the fusion of electroencephalography and event related potentials with functional magnetic resonance imaging (BOLD-fMRI) data should simultaneously assess all available electrophysiologic and hemodynamic information in a common data space. In doing so, it should be possible to identify features of latent neural sources whose trial-to-trial dynamics are jointly reflected in both modalities. We present a joint independent component analysis (jICA) model for analysis of simultaneous single trial EEG-fMRI measurements from multiple subjects. We outline the general idea underlying the jICA approach and present results from simulated data under realistic noise conditions. Our results indicate that this approach is a feasible and physiologically plausible data-driven way to achieve spatiotemporal mapping of event related responses in the human brain.

Understanding Karma Police: The Perceived Plausibility of Noun Compounds as Predicted by Distributional Models of Semantic Representation

PubMed Central

Günther, Fritz; Marelli, Marco

2016-01-01

Noun compounds, consisting of two nouns (the head and the modifier) that are combined into a single concept, differ in terms of their plausibility: school bus is a more plausible compound than saddle olive. The present study investigates which factors influence the plausibility of attested and novel noun compounds. Distributional Semantic Models (DSMs) are used to obtain formal (vector) representations of word meanings, and compositional methods in DSMs are employed to obtain such representations for noun compounds. From these representations, different plausibility measures are computed. Three of those measures contribute in predicting the plausibility of noun compounds: The relatedness between the meaning of the head noun and the compound (Head Proximity), the relatedness between the meaning of modifier noun and the compound (Modifier Proximity), and the similarity between the head noun and the modifier noun (Constituent Similarity). We find non-linear interactions between Head Proximity and Modifier Proximity, as well as between Modifier Proximity and Constituent Similarity. Furthermore, Constituent Similarity interacts non-linearly with the familiarity with the compound. These results suggest that a compound is perceived as more plausible if it can be categorized as an instance of the category denoted by the head noun, if the contribution of the modifier to the compound meaning is clear but not redundant, and if the constituents are sufficiently similar in cases where this contribution is not clear. Furthermore, compounds are perceived to be more plausible if they are more familiar, but mostly for cases where the relation between the constituents is less clear. PMID:27732599

Role of Tumor Collagenase Stimulating Factor in Breast Cancer Invasion and Metastasis.

DTIC Science & Technology

1997-12-01

propose that in physiologic processes, the presence of an intact basement membrane separating the normal/benign epithelium from underlying stromal...second Ig domain is a junctional exon encoding the transmembrane domain and part of the cytoplasmic domain as well. Most members of the Ig...produce EMMPRIN. A role for EMMPRIN at epithelial dermal junctions in tissue repair during wound healing seems highly plausible. Taken together

Modeling the adenosine system as a modulator of cognitive performance and sleep patterns during sleep restriction and recovery.

PubMed

Phillips, Andrew J K; Klerman, Elizabeth B; Butler, James P

2017-10-01

Sleep loss causes profound cognitive impairments and increases the concentrations of adenosine and adenosine A1 receptors in specific regions of the brain. Time courses for performance impairment and recovery differ between acute and chronic sleep loss, but the physiological basis for these time courses is unknown. Adenosine has been implicated in pathways that generate sleepiness and cognitive impairments, but existing mathematical models of sleep and cognitive performance do not explicitly include adenosine. Here, we developed a novel receptor-ligand model of the adenosine system to test the hypothesis that changes in both adenosine and A1 receptor concentrations can capture changes in cognitive performance during acute sleep deprivation (one prolonged wake episode), chronic sleep restriction (multiple nights with insufficient sleep), and subsequent recovery. Parameter values were estimated using biochemical data and reaction time performance on the psychomotor vigilance test (PVT). The model closely fit group-average PVT data during acute sleep deprivation, chronic sleep restriction, and recovery. We tested the model's ability to reproduce timing and duration of sleep in a separate experiment where individuals were permitted to sleep for up to 14 hours per day for 28 days. The model accurately reproduced these data, and also correctly predicted the possible emergence of a split sleep pattern (two distinct sleep episodes) under these experimental conditions. Our findings provide a physiologically plausible explanation for observed changes in cognitive performance and sleep during sleep loss and recovery, as well as a new approach for predicting sleep and cognitive performance under planned schedules.

Extraction of Inter-Aural Time Differences Using a Spiking Neuron Network Model of the Medial Superior Olive.

PubMed

Encke, Jörg; Hemmert, Werner

2018-01-01

The mammalian auditory system is able to extract temporal and spectral features from sound signals at the two ears. One important cue for localization of low-frequency sound sources in the horizontal plane are inter-aural time differences (ITDs) which are first analyzed in the medial superior olive (MSO) in the brainstem. Neural recordings of ITD tuning curves at various stages along the auditory pathway suggest that ITDs in the mammalian brainstem are not represented in form of a Jeffress-type place code. An alternative is the hemispheric opponent-channel code, according to which ITDs are encoded as the difference in the responses of the MSO nuclei in the two hemispheres. In this study, we present a physiologically-plausible, spiking neuron network model of the mammalian MSO circuit and apply two different methods of extracting ITDs from arbitrary sound signals. The network model is driven by a functional model of the auditory periphery and physiological models of the cochlear nucleus and the MSO. Using a linear opponent-channel decoder, we show that the network is able to detect changes in ITD with a precision down to 10 μs and that the sensitivity of the decoder depends on the slope of the ITD-rate functions. A second approach uses an artificial neuronal network to predict ITDs directly from the spiking output of the MSO and ANF model. Using this predictor, we show that the MSO-network is able to reliably encode static and time-dependent ITDs over a large frequency range, also for complex signals like speech.

Using critical evaluation to reappraise plausibility judgments: A critical cognitive component of conceptual change

NASA Astrophysics Data System (ADS)

Lombardi, D.

2011-12-01

Plausibility judgments-although well represented in conceptual change theories (see, for example, Chi, 2005; diSessa, 1993; Dole & Sinatra, 1998; Posner et al., 1982)-have received little empirical attention until our recent work investigating teachers' and students' understanding of and perceptions about human-induced climate change (Lombardi & Sinatra, 2010, 2011). In our first study with undergraduate students, we found that greater plausibility perceptions of human-induced climate accounted for significantly greater understanding of weather and climate distinctions after instruction, even after accounting for students' prior knowledge (Lombardi & Sinatra, 2010). In a follow-up study with inservice science and preservice elementary teachers, we showed that anger about the topic of climate change and teaching about climate change was significantly related to implausible perceptions about human-induced climate change (Lombardi & Sinatra, 2011). Results from our recent studies helped to inform our development of a model of the role of plausibility judgments in conceptual change situations. The model applies to situations involving cognitive dissonance, where background knowledge conflicts with an incoming message. In such situations, we define plausibility as a judgment on the relative potential truthfulness of incoming information compared to one's existing mental representations (Rescher, 1976). Students may not consciously think when making plausibility judgments, expending only minimal mental effort in what is referred to as an automatic cognitive process (Stanovich, 2009). However, well-designed instruction could facilitate students' reappraisal of plausibility judgments in more effortful and conscious cognitive processing. Critical evaluation specifically may be one effective method to promote plausibility reappraisal in a classroom setting (Lombardi & Sinatra, in progress). In science education, critical evaluation involves the analysis of how evidentiary data support a hypothesis and its alternatives. The presentation will focus on how instruction promoting critical evaluation can encourage individuals to reappraise their plausibility judgments and initiate knowledge reconstruction. In a recent pilot study, teachers experienced an instructional scaffold promoting critical evaluation of two competing climate change theories (i.e., human-induced and increasing solar irradiance) and significantly changed both their plausibility judgments and perceptions of correctness toward the scientifically-accepted model of human-induced climate change. A comparison group of teachers who did not experience the critical evaluation activity showed no significant change. The implications of these studies for future research and instruction will be discussed in the presentation, including effective ways to increase students' and teachers' ability to be critically evaluative and reappraise their plausibility judgments. With controversial science issues, such as climate change, such abilities may be necessary to facilitate conceptual change.

Eigen-disfigurement model for simulating plausible facial disfigurement after reconstructive surgery.

PubMed

Lee, Juhun; Fingeret, Michelle C; Bovik, Alan C; Reece, Gregory P; Skoracki, Roman J; Hanasono, Matthew M; Markey, Mia K

2015-03-27

Patients with facial cancers can experience disfigurement as they may undergo considerable appearance changes from their illness and its treatment. Individuals with difficulties adjusting to facial cancer are concerned about how others perceive and evaluate their appearance. Therefore, it is important to understand how humans perceive disfigured faces. We describe a new strategy that allows simulation of surgically plausible facial disfigurement on a novel face for elucidating the human perception on facial disfigurement. Longitudinal 3D facial images of patients (N = 17) with facial disfigurement due to cancer treatment were replicated using a facial mannequin model, by applying Thin-Plate Spline (TPS) warping and linear interpolation on the facial mannequin model in polar coordinates. Principal Component Analysis (PCA) was used to capture longitudinal structural and textural variations found within each patient with facial disfigurement arising from the treatment. We treated such variations as disfigurement. Each disfigurement was smoothly stitched on a healthy face by seeking a Poisson solution to guided interpolation using the gradient of the learned disfigurement as the guidance field vector. The modeling technique was quantitatively evaluated. In addition, panel ratings of experienced medical professionals on the plausibility of simulation were used to evaluate the proposed disfigurement model. The algorithm reproduced the given face effectively using a facial mannequin model with less than 4.4 mm maximum error for the validation fiducial points that were not used for the processing. Panel ratings of experienced medical professionals on the plausibility of simulation showed that the disfigurement model (especially for peripheral disfigurement) yielded predictions comparable to the real disfigurements. The modeling technique of this study is able to capture facial disfigurements and its simulation represents plausible outcomes of reconstructive surgery for facial cancers. Thus, our technique can be used to study human perception on facial disfigurement.

A model of aging as accumulated damage matches observed mortality patterns and predicts the life-extending effects of prospective interventions

PubMed Central

Phoenix, Chris

2007-01-01

The relative insensitivity of lifespan to environmental factors constitutes compelling evidence that the physiological decline associated with aging derives primarily from the accumulation of intrinsic molecular and cellular side-effects of metabolism. Here we model that accumulation starting from a biologically based interpretation of the way in which those side-effects interact. We first validate this model by showing that it very accurately reproduces the distribution of ages at death seen in typical populations that are well protected from age-independent causes of death. We then exploit the mechanistic basis of this model to explore the impact on lifespans of interventions that combat aging, with an emphasis on interventions that repair (rather than merely retard) the direct molecular or cellular consequences of metabolism and thus prevent them from accumulating to pathogenic levels. Our results strengthen the case that an indefinite extension of healthy and total life expectancy can be achieved by a plausible rate of progress in the development of such therapies, once a threshold level of efficacy of those therapies has been reached. PMID:19424837

Passive Electroreception in Fish: AN Analog Model of the Spike Generation Zone.

NASA Astrophysics Data System (ADS)

Harvey, James Robert

Sensory transduction begins in receptor cells specialized to the sensory modality involved and proceeds to the more generalized stage of the first afferent fiber, converting the initial sensory information into neural spikes for transmittal to the central nervous system. We have developed a unique analog electronic model of the generalized step (also known as the spike generation zone (SGZ)) using a tunnel diode, an operational amplifier, resistors, and capacitors. With no externally applied simulated postsynaptic input current, our model represents a 10^{-3}cm^2 patch (100 times the typical in vivo area) of tonically active, nonadaptive, postsynaptic neural membrane that behaves as a pacemaker cell. Similar to the FitzHugh-Nagumo equations, our model is shown to be a simplification of the Hodgkin-Huxley parallel conductance model and can be analyzed by the methods of van der Pol. Measurements using the model yield results which compare favorably to physiological stimulus-response data gathered by Murray for elasmobranch electroreceptors. We then use the model to show that the main contribution to variance in the rate of neural spike output is provided by coincident inputs to the SGZ oscillator (i.e., by synaptic input noise) and not by inherent instability of the SGZ oscillator. Configured for maximum sensitivity, our model is capable of detecting stimulus changes as low as 50 fA in less than a second and this corresponds to a fractional frequency change of Delta f/f ~ 2 times 10^{-3}. Much data exists implying that in vivo detection of Delta f/f is limited to the range of one to ten percent (Weber-Fechner criterion). We propose the variance induced by the synaptic input noise provides a plausible physiological basis for the Weber-Fechner criterion.

High School Students' Evaluations, Plausibility (Re) Appraisals, and Knowledge about Topics in Earth Science

ERIC Educational Resources Information Center

Lombardi, Doug; Bickel, Elliot S.; Bailey, Janelle M.; Burrell, Shondricka

2018-01-01

Evaluation is an important aspect of science and is receiving increasing attention in science education. The present study investigated (1) changes to plausibility judgments and knowledge as a result of a series of instructional scaffolds, called model-evidence link activities, that facilitated evaluation of scientific and alternative models in…

A one-dimensional model of solid-earth electrical resistivity beneath Florida

USGS Publications Warehouse

Blum, Cletus; Love, Jeffrey J.; Pedrie, Kolby; Bedrosian, Paul A.; Rigler, E. Joshua

2015-11-19

An estimated one-dimensional layered model of electrical resistivity beneath Florida was developed from published geological and geophysical information. The resistivity of each layer is represented by plausible upper and lower bounds as well as a geometric mean resistivity. Corresponding impedance transfer functions, Schmucker-Weidelt transfer functions, apparent resistivity, and phase responses are calculated for inducing geomagnetic frequencies ranging from 10−5 to 100 hertz. The resulting one-dimensional model and response functions can be used to make general estimates of time-varying electric fields associated with geomagnetic storms such as might represent induction hazards for electric-power grid operation. The plausible upper- and lower-bound resistivity structures show the uncertainty, giving a wide range of plausible time-varying electric fields.

Modeling the adenosine system as a modulator of cognitive performance and sleep patterns during sleep restriction and recovery

PubMed Central

Phillips, Andrew J. K.

2017-01-01

Sleep loss causes profound cognitive impairments and increases the concentrations of adenosine and adenosine A1 receptors in specific regions of the brain. Time courses for performance impairment and recovery differ between acute and chronic sleep loss, but the physiological basis for these time courses is unknown. Adenosine has been implicated in pathways that generate sleepiness and cognitive impairments, but existing mathematical models of sleep and cognitive performance do not explicitly include adenosine. Here, we developed a novel receptor-ligand model of the adenosine system to test the hypothesis that changes in both adenosine and A1 receptor concentrations can capture changes in cognitive performance during acute sleep deprivation (one prolonged wake episode), chronic sleep restriction (multiple nights with insufficient sleep), and subsequent recovery. Parameter values were estimated using biochemical data and reaction time performance on the psychomotor vigilance test (PVT). The model closely fit group-average PVT data during acute sleep deprivation, chronic sleep restriction, and recovery. We tested the model’s ability to reproduce timing and duration of sleep in a separate experiment where individuals were permitted to sleep for up to 14 hours per day for 28 days. The model accurately reproduced these data, and also correctly predicted the possible emergence of a split sleep pattern (two distinct sleep episodes) under these experimental conditions. Our findings provide a physiologically plausible explanation for observed changes in cognitive performance and sleep during sleep loss and recovery, as well as a new approach for predicting sleep and cognitive performance under planned schedules. PMID:29073206

An optimization formulation for characterization of pulsatile cortisol secretion.

PubMed

Faghih, Rose T; Dahleh, Munther A; Brown, Emery N

2015-01-01

Cortisol is released to relay information to cells to regulate metabolism and reaction to stress and inflammation. In particular, cortisol is released in the form of pulsatile signals. This low-energy method of signaling seems to be more efficient than continuous signaling. We hypothesize that there is a controller in the anterior pituitary that leads to pulsatile release of cortisol, and propose a mathematical formulation for such controller, which leads to impulse control as opposed to continuous control. We postulate that this controller is minimizing the number of secretory events that result in cortisol secretion, which is a way of minimizing the energy required for cortisol secretion; this controller maintains the blood cortisol levels within a specific circadian range while complying with the first order dynamics underlying cortisol secretion. We use an ℓ0-norm cost function for this controller, and solve a reweighed ℓ1-norm minimization algorithm for obtaining the solution to this optimization problem. We use four examples to illustrate the performance of this approach: (i) a toy problem that achieves impulse control, (ii) two examples that achieve physiologically plausible pulsatile cortisol release, (iii) an example where the number of pulses is not within the physiologically plausible range for healthy subjects while the cortisol levels are within the desired range. This novel approach results in impulse control where the impulses and the obtained blood cortisol levels have a circadian rhythm and an ultradian rhythm that are in agreement with the known physiology of cortisol secretion. The proposed formulation is a first step in developing intermittent controllers for curing cortisol deficiency. This type of bio-inspired pulse controllers can be employed for designing non-continuous controllers in brain-machine interface design for neuroscience applications.

Biologically Plausible, Human-scale Knowledge Representation

ERIC Educational Resources Information Center

Crawford, Eric; Gingerich, Matthew; Eliasmith, Chris

2016-01-01

Several approaches to implementing symbol-like representations in neurally plausible models have been proposed. These approaches include binding through synchrony (Shastri & Ajjanagadde, 1993), "mesh" binding (van der Velde & de Kamps, 2006), and conjunctive binding (Smolensky, 1990). Recent theoretical work has suggested that…

Neocytolysis: physiological down-regulator of red-cell mass

NASA Technical Reports Server (NTRS)

Alfrey, C. P.; Rice, L.; Udden, M. M.; Driscoll, T. B.

1997-01-01

It is usually considered that red-cell mass is controlled by erythropoietin-driven bone marrow red-cell production, and no physiological mechanisms can shorten survival of circulating red cells. In adapting to acute plethora in microgravity, astronauts' red-cell mass falls too rapidly to be explained by diminished red-cell production. Ferrokinetics show no early decline in erythropolesis, but red cells radiolabelled 12 days before launch survive normally. Selective destruction of the youngest circulating red cells-a process we call neocytolysis-is the only plausible explanation. A fall in erythropoietin below a threshold is likely to initiate neocytolysis, probably by influencing surface-adhesion molecules. Recognition of neocytolysis will require re-examination of the pathophysiology and treatment of several blood disorders, including the anaemia of renal disease.

Evaluation of risk from acts of terrorism :the adversary/defender model using belief and fuzzy sets.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Darby, John L.

Risk from an act of terrorism is a combination of the likelihood of an attack, the likelihood of success of the attack, and the consequences of the attack. The considerable epistemic uncertainty in each of these three factors can be addressed using the belief/plausibility measure of uncertainty from the Dempster/Shafer theory of evidence. The adversary determines the likelihood of the attack. The success of the attack and the consequences of the attack are determined by the security system and mitigation measures put in place by the defender. This report documents a process for evaluating risk of terrorist acts using anmore » adversary/defender model with belief/plausibility as the measure of uncertainty. Also, the adversary model is a linguistic model that applies belief/plausibility to fuzzy sets used in an approximate reasoning rule base.« less

A hypothetical complex between crystalline flavocytochrome b2 and cytochrome c.

PubMed

Tegoni, M; White, S A; Roussel, A; Mathews, F S; Cambillau, C

1993-08-01

Flavocytochrome b2 and cytochrome c are physiological electron transfer partners in yeast mitochondria. The formation of a stable complex between them has been demonstrated both in solution and in the crystalline state. On the basis of the three-dimensional structures, using molecular modeling and energy minimization, we have generated a hypothetical model for the interaction of these redox partners in the crystal lattice. General criteria such as good charge and surface complementarity, plausible orientation, and separation distance of the prosthetic groups, as well as more specific criteria such as the stoichiometry determined in the crystal, and the involvement of both domains and of more than one subunit of flavocytochrome b2 led us to discriminate between several possible interaction sites. In the hypothetical model we present, four cytochrome c molecules interact with a tetramer of flavocytochrome b2. The b2 and c hemes are coplanar, with an edge-to-edge distance of 14 A. The contact surface area is ca. 800 A2. Several electrostatic interactions involving the flavin and the heme domains of flavocytochrome b2 stabilize the binding of cytochrome c.

Neurophysiology of Drosophila Models of Parkinson's Disease

PubMed Central

West, Ryan J. H.; Furmston, Rebecca; Williams, Charles A. C.; Elliott, Christopher J. H.

2015-01-01

We provide an insight into the role Drosophila has played in elucidating neurophysiological perturbations associated with Parkinson's disease- (PD-) related genes. Synaptic signalling deficits are observed in motor, central, and sensory systems. Given the neurological impact of disease causing mutations within these same genes in humans the phenotypes observed in fly are of significant interest. As such we observe four unique opportunities provided by fly nervous system models of Parkinson's disease. Firstly, Drosophila models are instrumental in exploring the mechanisms of neurodegeneration, with several PD-related mutations eliciting related phenotypes including sensitivity to energy supply and vesicular deformities. These are leading to the identification of plausible cellular mechanisms, which may be specific to (dopaminergic) neurons and synapses rather than general cellular phenotypes. Secondly, models show noncell autonomous signalling within the nervous system, offering the opportunity to develop our understanding of the way pathogenic signalling propagates, resembling Braak's scheme of spreading pathology in PD. Thirdly, the models link physiological deficits to changes in synaptic structure. While the structure-function relationship is complex, the genetic tractability of Drosophila offers the chance to separate fundamental changes from downstream consequences. Finally, the strong neuronal phenotypes permit relevant first in vivo drug testing. PMID:25960916

Control of the exercise hyperpnoea in humans: a modeling perspective.

PubMed

Ward, S A

2000-09-01

Models of the exercise hyperpnoea have classically incorporated elements of proportional feedback (carotid and medullary chemosensory) and feedforward (central and/or peripheral neurogenic) control. However, the precise details of the control process remain unresolved, reflecting in part both technical and interpretational limitations inherent in isolating putative control mechanisms in the intact human, and also the challenges to linear control theory presented by multiple-input integration, especially with regard to the ventilatory and gas-exchange complexities encountered at work rates which engender a metabolic acidosis. While some combination of neurogenic, chemoreflex and circulatory-coupled processes are likely to contribute to the control, the system appears to evidence considerable redundancy. This, coupled with the lack of appreciable error signals in the mean levels of arterial blood gas tensions and pH over a wide range of work rates, has motivated the formulation of innovative control models that reflect not only spatial interactions but also temporal interactions (i.e. memory). The challenge is to discriminate between robust competing control models that: (a) integrate such processes within plausible physiological equivalents; and (b) account for both the dynamic and steady-state system response over a range of exercise intensities. Such models are not yet available.

GCM Studies on the Interactions Between Photosynthesis and Climate at Diurnal to Decadal Time Scales

NASA Technical Reports Server (NTRS)

Collatz, G. James; Bounoua, Lahouari; Sellers, Piers; Los, Sietse; Randall, David; Berry, Joseph; Tucker, Compton J.

1998-01-01

Transpiration, a major component of total evaporation from vegetated surfaces, is an unavoidable consequence of photosynthetic carbon fixation. Because of limiting soil moisture and competition for solar radiation plants invest most of their fixed carbon into structural and hydraulic functions (roots and stems) and solar radiation absorption (leaves). These investments permit individuals to overshadow competitors and provide for transport of water from the soil to the leaves where photosynthesis and transpiration occur. Often low soil moisture or high evaporative demand limit the supply of water to leaves reducing photosynthesis and thus transpiration. The absorption of solar radiation for photosynthesis and dissipation of this energy via radiation, heat, mass and momentum fluxes represents the link between photosynthesis and climate. Recognition of these relationships has led to the development of hydro/energy balance models that are based on the physiological ecology of photosynthesis. We discuss an approach to study vegetation-climate interactions using photosynthesis-centric models embedded in a GCM. The rate at which a vegetated area transpires and photosynthesizes is determined by the physiological state of the vegetation, its amount and its type. The latter two are specified from global satellite data collected since 1982. Climate simulations have been carried out to study how this simulated climate system responds to changes in radiative forcing, physiological capacity, atmospheric CO2, vegetation type and variable vegetation cover observed from satellites during the 1980's. Results from these studies reveal significant feedbacks between the vegetation activity and climate. For example, vegetation cover and physiological activity increases cause the total latent heat flux and precipitation to increase while mean and maximum air temperatures decrease. The reverse occurs if cover or activity'decreases. In general climate response of a particular region was dominated by local processes but we also find evidence that plausible climate-vegetation scenarios lead to changes in global atmospheric circulation and strong non-local influences in some cases.

Adaptive selection and validation of models of complex systems in the presence of uncertainty

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farrell-Maupin, Kathryn; Oden, J. T.

This study describes versions of OPAL, the Occam-Plausibility Algorithm in which the use of Bayesian model plausibilities is replaced with information theoretic methods, such as the Akaike Information Criterion and the Bayes Information Criterion. Applications to complex systems of coarse-grained molecular models approximating atomistic models of polyethylene materials are described. All of these model selection methods take into account uncertainties in the model, the observational data, the model parameters, and the predicted quantities of interest. A comparison of the models chosen by Bayesian model selection criteria and those chosen by the information-theoretic criteria is given.

Adaptive selection and validation of models of complex systems in the presence of uncertainty

DOE PAGES

Farrell-Maupin, Kathryn; Oden, J. T.

2017-08-01

This study describes versions of OPAL, the Occam-Plausibility Algorithm in which the use of Bayesian model plausibilities is replaced with information theoretic methods, such as the Akaike Information Criterion and the Bayes Information Criterion. Applications to complex systems of coarse-grained molecular models approximating atomistic models of polyethylene materials are described. All of these model selection methods take into account uncertainties in the model, the observational data, the model parameters, and the predicted quantities of interest. A comparison of the models chosen by Bayesian model selection criteria and those chosen by the information-theoretic criteria is given.

Simulating human behavior for national security human interactions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernard, Michael Lewis; Hart, Dereck H.; Verzi, Stephen J.

2007-01-01

This 3-year research and development effort focused on what we believe is a significant technical gap in existing modeling and simulation capabilities: the representation of plausible human cognition and behaviors within a dynamic, simulated environment. Specifically, the intent of the ''Simulating Human Behavior for National Security Human Interactions'' project was to demonstrate initial simulated human modeling capability that realistically represents intra- and inter-group interaction behaviors between simulated humans and human-controlled avatars as they respond to their environment. Significant process was made towards simulating human behaviors through the development of a framework that produces realistic characteristics and movement. The simulated humansmore » were created from models designed to be psychologically plausible by being based on robust psychological research and theory. Progress was also made towards enhancing Sandia National Laboratories existing cognitive models to support culturally plausible behaviors that are important in representing group interactions. These models were implemented in the modular, interoperable, and commercially supported Umbra{reg_sign} simulation framework.« less

Complex coacervates as a foundation for synthetic underwater adhesives

PubMed Central

Stewart, Russell J.; Wang, Ching Shuen; Shao, Hui

2011-01-01

Complex coacervation was proposed to play a role in the formation of the underwater bioadhesive of the Sandcastle worm (Phragmatopoma californica) based on the polyacidic and polybasic nature of the glue proteins and the balance of opposite charges at physiological pH. Morphological studies of the secretory system suggested the natural process does not involve complex coacervation as commonly defined. The distinction may not be important because electrostatic interactions likely play an important role in formation of the sandcastle glue. Complex coacervation has also been invoked in the formation of adhesive underwater silk fibers of caddisfly larvae and the adhesive plaques of mussels. A process similar to complex coacervation, that is, condensation and dehydration of biopolyelectrolytes through electrostatic associations, seems plausible for the caddisfly silk. This much is clear, the sandcastle glue complex coacervation model provided a valuable blueprint for the synthesis of a biomimetic, waterborne, underwater adhesive with demonstrated potential for repair of wet tissue. PMID:21081223

Intraneural stimulation elicits discrimination of textural features by artificial fingertip in intact and amputee humans.

PubMed

Oddo, Calogero Maria; Raspopovic, Stanisa; Artoni, Fiorenzo; Mazzoni, Alberto; Spigler, Giacomo; Petrini, Francesco; Giambattistelli, Federica; Vecchio, Fabrizio; Miraglia, Francesca; Zollo, Loredana; Di Pino, Giovanni; Camboni, Domenico; Carrozza, Maria Chiara; Guglielmelli, Eugenio; Rossini, Paolo Maria; Faraguna, Ugo; Micera, Silvestro

2016-03-08

Restoration of touch after hand amputation is a desirable feature of ideal prostheses. Here, we show that texture discrimination can be artificially provided in human subjects by implementing a neuromorphic real-time mechano-neuro-transduction (MNT), which emulates to some extent the firing dynamics of SA1 cutaneous afferents. The MNT process was used to modulate the temporal pattern of electrical spikes delivered to the human median nerve via percutaneous microstimulation in four intact subjects and via implanted intrafascicular stimulation in one transradial amputee. Both approaches allowed the subjects to reliably discriminate spatial coarseness of surfaces as confirmed also by a hybrid neural model of the median nerve. Moreover, MNT-evoked EEG activity showed physiologically plausible responses that were superimposable in time and topography to the ones elicited by a natural mechanical tactile stimulation. These findings can open up novel opportunities for sensory restoration in the next generation of neuro-prosthetic hands.

Identification and characterisation of midbrain nuclei using optimised functional magnetic resonance imaging

PubMed Central

Limbrick-Oldfield, Eve H.; Brooks, Jonathan C.W.; Wise, Richard J.S.; Padormo, Francesco; Hajnal, Jo V.; Beckmann, Christian F.; Ungless, Mark A.

2012-01-01

Localising activity in the human midbrain with conventional functional MRI (fMRI) is challenging because the midbrain nuclei are small and located in an area that is prone to physiological artefacts. Here we present a replicable and automated method to improve the detection and localisation of midbrain fMRI signals. We designed a visual fMRI task that was predicted would activate the superior colliculi (SC) bilaterally. A limited number of coronal slices were scanned, orientated along the long axis of the brainstem, whilst simultaneously recording cardiac and respiratory traces. A novel anatomical registration pathway was used to optimise the localisation of the small midbrain nuclei in stereotactic space. Two additional structural scans were used to improve registration between functional and structural T1-weighted images: an echo-planar image (EPI) that matched the functional data but had whole-brain coverage, and a whole-brain T2-weighted image. This pathway was compared to conventional registration pathways, and was shown to significantly improve midbrain registration. To reduce the physiological artefacts in the functional data, we estimated and removed structured noise using a modified version of a previously described physiological noise model (PNM). Whereas a conventional analysis revealed only unilateral SC activity, the PNM analysis revealed the predicted bilateral activity. We demonstrate that these methods improve the measurement of a biologically plausible fMRI signal. Moreover they could be used to investigate the function of other midbrain nuclei. PMID:21867762

Isotherm ranking and selection using thirteen literature datasets involving hydrophobic organic compounds.

PubMed

Matott, L Shawn; Jiang, Zhengzheng; Rabideau, Alan J; Allen-King, Richelle M

2015-01-01

Numerous isotherm expressions have been developed for describing sorption of hydrophobic organic compounds (HOCs), including "dual-mode" approaches that combine nonlinear behavior with a linear partitioning component. Choosing among these alternative expressions for describing a given dataset is an important task that can significantly influence subsequent transport modeling and/or mechanistic interpretation. In this study, a series of numerical experiments were undertaken to identify "best-in-class" isotherms by refitting 10 alternative models to a suite of 13 previously published literature datasets. The corrected Akaike Information Criterion (AICc) was used for ranking these alternative fits and distinguishing between plausible and implausible isotherms for each dataset. The occurrence of multiple plausible isotherms was inversely correlated with dataset "richness", such that datasets with fewer observations and/or a narrow range of aqueous concentrations resulted in a greater number of plausible isotherms. Overall, only the Polanyi-partition dual-mode isotherm was classified as "plausible" across all 13 of the considered datasets, indicating substantial statistical support consistent with current advances in sorption theory. However, these findings are predicated on the use of the AICc measure as an unbiased ranking metric and the adoption of a subjective, but defensible, threshold for separating plausible and implausible isotherms. Copyright © 2015 Elsevier B.V. All rights reserved.

A border-ownership model based on computational electromagnetism.

PubMed

Zainal, Zaem Arif; Satoh, Shunji

2018-03-01

The mathematical relation between a vector electric field and its corresponding scalar potential field is useful to formulate computational problems of lower/middle-order visual processing, specifically related to the assignment of borders to the side of the object: so-called border ownership (BO). BO coding is a key process for extracting the objects from the background, allowing one to organize a cluttered scene. We propose that the problem is solvable simultaneously by application of a theorem of electromagnetism, i.e., "conservative vector fields have zero rotation, or "curl." We hypothesize that (i) the BO signal is definable as a vector electric field with arrowheads pointing to the inner side of perceived objects, and (ii) its corresponding scalar field carries information related to perceived order in depth of occluding/occluded objects. A simple model was developed based on this computational theory. Model results qualitatively agree with object-side selectivity of BO-coding neurons, and with perceptions of object order. The model update rule can be reproduced as a plausible neural network that presents new interpretations of existing physiological results. Results of this study also suggest that T-junction detectors are unnecessary to calculate depth order. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spatio-temporal Model of Xenobiotic Distribution and Metabolism in an in Silico Mouse Liver Lobule

NASA Astrophysics Data System (ADS)

Fu, Xiao; Sluka, James; Clendenon, Sherry; Glazier, James; Ryan, Jennifer; Dunn, Kenneth; Wang, Zemin; Klaunig, James

Our study aims to construct a structurally plausible in silico model of a mouse liver lobule to simulate the transport of xenobiotics and the production of their metabolites. We use a physiologically-based model to calculate blood-flow rates in a network of mouse liver sinusoids and simulate transport, uptake and biotransformation of xenobiotics within the in silico lobule. Using our base model, we then explore the effects of variations of compound-specific (diffusion, transport and metabolism) and compound-independent (temporal alteration of blood flow pattern) parameters, and examine their influence on the distribution of xenobiotics and metabolites. Our simulations show that the transport mechanism (diffusive and transporter-mediated) of xenobiotics and blood flow both impact the regional distribution of xenobiotics in a mouse hepatic lobule. Furthermore, differential expression of metabolic enzymes along each sinusoid's portal to central axis, together with differential cellular availability of xenobiotics, induce non-uniform production of metabolites. Thus, the heterogeneity of the biochemical and biophysical properties of xenobiotics, along with the complexity of blood flow, result in different exposures to xenobiotics for hepatocytes at different lobular locations. We acknowledge support from National Institute of Health GM 077138 and GM 111243.

From information processing to decisions: Formalizing and comparing psychologically plausible choice models.

PubMed

Heck, Daniel W; Hilbig, Benjamin E; Moshagen, Morten

2017-08-01

Decision strategies explain how people integrate multiple sources of information to make probabilistic inferences. In the past decade, increasingly sophisticated methods have been developed to determine which strategy explains decision behavior best. We extend these efforts to test psychologically more plausible models (i.e., strategies), including a new, probabilistic version of the take-the-best (TTB) heuristic that implements a rank order of error probabilities based on sequential processing. Within a coherent statistical framework, deterministic and probabilistic versions of TTB and other strategies can directly be compared using model selection by minimum description length or the Bayes factor. In an experiment with inferences from given information, only three of 104 participants were best described by the psychologically plausible, probabilistic version of TTB. Similar as in previous studies, most participants were classified as users of weighted-additive, a strategy that integrates all available information and approximates rational decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of multisensor data fusion in neuromuscular control of a sagittal arm with a pair of muscles using actor-critic reinforcement learning method.

PubMed

Golkhou, V; Parnianpour, M; Lucas, C

2004-01-01

In this study, we consider the role of multisensor data fusion in neuromuscular control using an actor-critic reinforcement learning method. The model we use is a single link system actuated by a pair of muscles that are excited with alpha and gamma signals. Various physiological sensor information such as proprioception, spindle sensors, and Golgi tendon organs have been integrated to achieve an oscillatory movement with variable amplitude and frequency, while achieving a stable movement with minimum metabolic cost and coactivation. The system is highly nonlinear in all its physical and physiological attributes. Transmission delays are included in the afferent and efferent neural paths to account for a more accurate representation of the reflex loops. This paper proposes a reinforcement learning method with an Actor-Critic architecture instead of middle and low level of central nervous system (CNS). The Actor in this structure is a two layer feedforward neural network and the Critic is a model of the cerebellum. The Critic is trained by the State-Action-Reward-State-Action (SARSA) method. The Critic will train the Actor by supervisory learning based on previous experiences. The reinforcement signal in SARSA is evaluated based on available alternatives concerning the concept of multisensor data fusion. The effectiveness and the biological plausibility of the present model are demonstrated by several simulations. The system showed excellent tracking capability when we integrated the available sensor information. Addition of a penalty for activation of muscles resulted in much lower muscle coactivation while keeping the movement stable.

Mathematical Methods of Subjective Modeling in Scientific Research: I. The Mathematical and Empirical Basis

NASA Astrophysics Data System (ADS)

Pyt'ev, Yu. P.

2018-01-01

mathematical formalism for subjective modeling, based on modelling of uncertainty, reflecting unreliability of subjective information and fuzziness that is common for its content. The model of subjective judgments on values of an unknown parameter x ∈ X of the model M( x) of a research object is defined by the researcher-modeler as a space1 ( X, p( X), P{I^{\\bar x}}, Be{l^{\\bar x}}) with plausibility P{I^{\\bar x}} and believability Be{l^{\\bar x}} measures, where x is an uncertain element taking values in X that models researcher—modeler's uncertain propositions about an unknown x ∈ X, measures P{I^{\\bar x}}, Be{l^{\\bar x}} model modalities of a researcher-modeler's subjective judgments on the validity of each x ∈ X: the value of P{I^{\\bar x}}(\\tilde x = x) determines how relatively plausible, in his opinion, the equality (\\tilde x = x) is, while the value of Be{l^{\\bar x}}(\\tilde x = x) determines how the inequality (\\tilde x = x) should be relatively believed in. Versions of plausibility Pl and believability Bel measures and pl- and bel-integrals that inherit some traits of probabilities, psychophysics and take into account interests of researcher-modeler groups are considered. It is shown that the mathematical formalism of subjective modeling, unlike "standard" mathematical modeling, •enables a researcher-modeler to model both precise formalized knowledge and non-formalized unreliable knowledge, from complete ignorance to precise knowledge of the model of a research object, to calculate relative plausibilities and believabilities of any features of a research object that are specified by its subjective model M(\\tilde x), and if the data on observations of a research object is available, then it: •enables him to estimate the adequacy of subjective model to the research objective, to correct it by combining subjective ideas and the observation data after testing their consistency, and, finally, to empirically recover the model of a research object.

A physics-based model for maintenance of the pH gradient in the gastric mucus layer.

PubMed

Lewis, Owen L; Keener, James P; Fogelson, Aaron L

2017-12-01

It is generally accepted that the gastric mucus layer provides a protective barrier between the lumen and the mucosa, shielding the mucosa from acid and digestive enzymes and preventing autodigestion of the stomach epithelium. However, the precise mechanisms that contribute to this protective function are still up for debate. In particular, it is not clear what physical processes are responsible for transporting hydrogen protons, secreted within the gastric pits, across the mucus layer to the lumen without acidifying the environment adjacent to the epithelium. One hypothesis is that hydrogen may be bound to the mucin polymers themselves as they are convected away from the mucosal surface and eventually degraded in the stomach lumen. It is also not clear what mechanisms prevent hydrogen from diffusing back toward the mucosal surface, thereby lowering the local pH. In this work we investigate a physics-based model of ion transport within the mucosal layer based on a Nernst-Planck-like equation. Analysis of this model shows that the mechanism of transporting protons bound to the mucus gel is capable of reproducing the trans-mucus pH gradients reported in the literature. Furthermore, when coupled with ion exchange at the epithelial surface, our analysis shows that bicarbonate secretion alone is capable of neutralizing the epithelial pH, even in the face of enormous diffusive gradients of hydrogen. Maintenance of the pH gradient is found to be robust to a wide array of perturbations in both physiological and phenomenological model parameters, suggesting a robust physiological control mechanism. NEW & NOTEWORTHY This work combines modeling techniques based on physical principles, as well as novel numerical simulations to test the plausibility of one hypothesized mechanism for proton transport across the gastric mucus layer. Results show that this mechanism is able to maintain the extreme pH gradient seen in in vivo experiments and suggests a highly robust regulation mechanism to maintain this gradient in the face of dynamic lumen composition. Copyright © 2017 the American Physiological Society.

A stand-alone tree demography and landscape structure module for Earth system models: integration with inventory data from temperate and boreal forests

NASA Astrophysics Data System (ADS)

Haverd, V.; Smith, B.; Nieradzik, L. P.; Briggs, P. R.

2014-08-01

Poorly constrained rates of biomass turnover are a key limitation of Earth system models (ESMs). In light of this, we recently proposed a new approach encoded in a model called Populations-Order-Physiology (POP), for the simulation of woody ecosystem stand dynamics, demography and disturbance-mediated heterogeneity. POP is suitable for continental to global applications and designed for coupling to the terrestrial ecosystem component of any ESM. POP bridges the gap between first-generation dynamic vegetation models (DVMs) with simple large-area parameterisations of woody biomass (typically used in current ESMs) and complex second-generation DVMs that explicitly simulate demographic processes and landscape heterogeneity of forests. The key simplification in the POP approach, compared with second-generation DVMs, is to compute physiological processes such as assimilation at grid-scale (with CABLE (Community Atmosphere Biosphere Land Exchange) or a similar land surface model), but to partition the grid-scale biomass increment among age classes defined at sub-grid-scale, each subject to its own dynamics. POP was successfully demonstrated along a savanna transect in northern Australia, replicating the effects of strong rainfall and fire disturbance gradients on observed stand productivity and structure. Here, we extend the application of POP to wide-ranging temporal and boreal forests, employing paired observations of stem biomass and density from forest inventory data to calibrate model parameters governing stand demography and biomass evolution. The calibrated POP model is then coupled to the CABLE land surface model, and the combined model (CABLE-POP) is evaluated against leaf-stem allometry observations from forest stands ranging in age from 3 to 200 year. Results indicate that simulated biomass pools conform well with observed allometry. We conclude that POP represents an ecologically plausible and efficient alternative to large-area parameterisations of woody biomass turnover, typically used in current ESMs.

Families of Plausible Solutions to the Puzzle of Boyajian’s Star

NASA Astrophysics Data System (ADS)

Wright, Jason T.; Sigurdsson, Steinn

2016-09-01

Good explanations for the unusual light curve of Boyajian's Star have been hard to find. Recent results by Montet & Simon lend strength and plausibility to the conclusion of Schaefer that in addition to short-term dimmings, the star also experiences large, secular decreases in brightness on decadal timescales. This, combined with a lack of long-wavelength excess in the star's spectral energy distribution, strongly constrains scenarios involving circumstellar material, including hypotheses invoking a spherical cloud of artifacts. We show that the timings of the deepest dimmings appear consistent with being randomly distributed, and that the star's reddening and narrow sodium absorption is consistent with the total, long-term dimming observed. Following Montet & Simon's encouragement to generate alternative hypotheses, we attempt to circumscribe the space of possible explanations with a range of plausibilities, including: a cloud in the outer solar system, structure in the interstellar medium (ISM), natural and artificial material orbiting Boyajian's Star, an intervening object with a large disk, and variations in Boyajian's Star itself. We find the ISM and intervening disk models more plausible than the other natural models.

Dehydration: physiology, assessment, and performance effects.

PubMed

Cheuvront, Samuel N; Kenefick, Robert W

2014-01-01

This article provides a comprehensive review of dehydration assessment and presents a unique evaluation of the dehydration and performance literature. The importance of osmolality and volume are emphasized when discussing the physiology, assessment, and performance effects of dehydration. The underappreciated physiologic distinction between a loss of hypo-osmotic body water (intracellular dehydration) and an iso-osmotic loss of body water (extracellular dehydration) is presented and argued as the single most essential aspect of dehydration assessment. The importance of diagnostic and biological variation analyses to dehydration assessment methods is reviewed and their use in gauging the true potential of any dehydration assessment method highlighted. The necessity for establishing proper baselines is discussed, as is the magnitude of dehydration required to elicit reliable and detectable osmotic or volume-mediated compensatory physiologic responses. The discussion of physiologic responses further helps inform and explain our analysis of the literature suggesting a ≥ 2% dehydration threshold for impaired endurance exercise performance mediated by volume loss. In contrast, no clear threshold or plausible mechanism(s) support the marginal, but potentially important, impairment in strength, and power observed with dehydration. Similarly, the potential for dehydration to impair cognition appears small and related primarily to distraction or discomfort. The impact of dehydration on any particular sport skill or task is therefore likely dependent upon the makeup of the task itself (e.g., endurance, strength, cognitive, and motor skill). © 2014 American Physiological Society.

Assessing Land Management Change Effects on Forest Carbon and Emissions Under Changing Climate

NASA Astrophysics Data System (ADS)

Law, B. E.

2014-12-01

There has been limited focus on fine-scale land management change effects on forest carbon under future environmental conditions (climate, nitrogen deposition, increased atmospheric CO2). Forest management decisions are often made at the landscape to regional levels before analyses have been conducted to determine the potential outcomes and effectiveness of such actions. Scientists need to evaluate plausible land management actions in a timely manner to help shape policy and strategic land management. Issues of interest include species-level adaptation to climate, resilience and vulnerability to mortality within forested landscapes and regions. Efforts are underway to improve land system model simulation of future mortality related to climate, and to develop and evaluate plausible land management options that could help mitigate or avoid future die-offs. Vulnerability to drought-related mortality varies among species and with tree size or age. Predictors of species ability to survive in specific environments are still not resolved. A challenge is limited observations for fine-scale (e.g. 4 km2) modeling, particularly physiological parameters. Uncertainties are primarily associated with future land management and policy decisions. They include the interface with economic factors and with other ecosystem services (biodiversity, water availability, wildlife habitat). The outcomes of future management scenarios should be compared with business-as-usual management under the same environmental conditions to determine the effects of management changes on forest carbon and net emissions to the atmosphere. For example, in the western U.S., land system modeling and life cycle assessment of several management options to reduce impacts of fire reduced long-term forest carbon gain and increased carbon emissions compared with business-as-usual management under future environmental conditions. The enhanced net carbon uptake with climate and reduced fire emissions after thinning did not compensate for the increased wood removals over 90 years, leading to reduced net biome production. Analysis of land management change scenarios at fine scales is needed, and should consider other ecological values in addition to carbon.

Temporal processing asymmetries between the cerebral hemispheres: evidence and implications.

PubMed

Nicholls, M E

1996-07-01

This paper reviews a large body of research which has investigated the capacities of the cerebral hemispheres to process temporal information. This research includes clinical, non-clinical, and electrophysiological experimentation. On the whole, the research supports the notion of a left hemisphere advantage for temporal resolution. The existence of such an asymmetry demonstrates that cerebral lateralisation is not limited to the higher-order functions such as language. The capacity for the resolution of fine temporal events appears to play an important role in other left hemisphere functions which require a rapid sequential processor. The functions that are facilitated by such a processor include verbal, textual, and fine movement skills. The co-development of these functions with an efficient temporal processor can be accounted for with reference to a number of evolutionary scenarios. Physiological evidence favours a temporal processing mechanism located within the left temporal cortex. The function of this mechanism may be described in terms of intermittency or travelling moment models of temporal processing. The travelling moment model provides the most plausible account of the asymmetry.

Promoting Scientific Thinking and Conceptual Change about Alternative Explanations of Climate Change and Other Controversial Socio-scientific Topics

NASA Astrophysics Data System (ADS)

Lombardi, D.; Sinatra, G. M.

2013-12-01

Critical evaluation and plausibility reappraisal of scientific explanations have been underemphasized in many science classrooms (NRC, 2012). Deep science learning demands that students increase their ability to critically evaluate the quality of scientific knowledge, weigh alternative explanations, and explicitly reappraise their plausibility judgments. Therefore, this lack of instruction about critical evaluation and plausibility reappraisal has, in part, contributed to diminished understanding about complex and controversial topics, such as global climate change. The Model-Evidence Link (MEL) diagram (originally developed by researchers at Rutgers University under an NSF-supported project; Chinn & Buckland, 2012) is an instructional scaffold that promotes students to critically evaluate alternative explanations. We recently developed a climate change MEL and found that the students who used the MEL experienced a significant shift in their plausibility judgments toward the scientifically accepted model of human-induced climate change. Using the MEL for instruction also resulted in conceptual change about the causes of global warming that reflected greater understanding of fundamental scientific principles. Furthermore, students sustained this conceptual change six months after MEL instruction (Lombardi, Sinatra, & Nussbaum, 2013). This presentation will discuss recent educational research that supports use of the MEL to promote critical evaluation, plausibility reappraisal, and conceptual change, and also, how the MEL may be particularly effective for learning about global climate change and other socio-scientific topics. Such instruction to develop these fundamental thinking skills (e.g., critical evaluation and plausibility reappraisal) is demanded by both the Next Generation Science Standards (Achieve, 2013) and the Common Core State Standards for English Language Arts and Mathematics (CCSS Initiative-ELA, 2010; CCSS Initiative-Math, 2010), as well as a society that is equipped to deal with challenges in a way that is beneficial to our national and global community.

A two component model for thermal emission from organic grains in Comet Halley

NASA Technical Reports Server (NTRS)

Chyba, Christopher; Sagan, Carl

1988-01-01

Observations of Comet Halley in the near infrared reveal a triple-peaked emission feature near 3.4 micrometer, characteristic of C-H stretching in hydrocarbons. A variety of plausible cometary materials exhibit these features, including the organic residue of irradiated candidate cometary ices (such as the residue of irradiated methane ice clathrate, and polycyclic aromatic hydrocarbons. Indeed, any molecule containing -CH3 and -CH2 alkanes will emit at 3.4 micrometer under suitable conditions. Therefore tentative identifications must rest on additional evidence, including a plausible account of the origins of the organic material, a plausible model for the infrared emission of this material, and a demonstration that this conjunction of material and model not only matches the 3 to 4 micrometer spectrum, but also does not yield additional emission features where none is observed. In the case of the residue of irradiated low occupancy methane ice clathrate, it is argued that the lab synthesis of the organic residue well simulates the radiation processing experienced by Comet Halley.

Biologically Plausible, Human-Scale Knowledge Representation.

PubMed

Crawford, Eric; Gingerich, Matthew; Eliasmith, Chris

2016-05-01

Several approaches to implementing symbol-like representations in neurally plausible models have been proposed. These approaches include binding through synchrony (Shastri & Ajjanagadde, ), "mesh" binding (van der Velde & de Kamps, ), and conjunctive binding (Smolensky, ). Recent theoretical work has suggested that most of these methods will not scale well, that is, that they cannot encode structured representations using any of the tens of thousands of terms in the adult lexicon without making implausible resource assumptions. Here, we empirically demonstrate that the biologically plausible structured representations employed in the Semantic Pointer Architecture (SPA) approach to modeling cognition (Eliasmith, ) do scale appropriately. Specifically, we construct a spiking neural network of about 2.5 million neurons that employs semantic pointers to successfully encode and decode the main lexical relations in WordNet, which has over 100,000 terms. In addition, we show that the same representations can be employed to construct recursively structured sentences consisting of arbitrary WordNet concepts, while preserving the original lexical structure. We argue that these results suggest that semantic pointers are uniquely well-suited to providing a biologically plausible account of the structured representations that underwrite human cognition. Copyright © 2015 Cognitive Science Society, Inc.

A Biomass-based Model to Estimate the Plausibility of Exoplanet Biosignature Gases

NASA Astrophysics Data System (ADS)

Seager, S.; Bains, W.; Hu, R.

2013-10-01

Biosignature gas detection is one of the ultimate future goals for exoplanet atmosphere studies. We have created a framework for linking biosignature gas detectability to biomass estimates, including atmospheric photochemistry and biological thermodynamics. The new framework is intended to liberate predictive atmosphere models from requiring fixed, Earth-like biosignature gas source fluxes. New biosignature gases can be considered with a check that the biomass estimate is physically plausible. We have validated the models on terrestrial production of NO, H2S, CH4, CH3Cl, and DMS. We have applied the models to propose NH3 as a biosignature gas on a "cold Haber World," a planet with a N2-H2 atmosphere, and to demonstrate why gases such as CH3Cl must have too large of a biomass to be a plausible biosignature gas on planets with Earth or early-Earth-like atmospheres orbiting a Sun-like star. To construct the biomass models, we developed a functional classification of biosignature gases, and found that gases (such as CH4, H2S, and N2O) produced from life that extracts energy from chemical potential energy gradients will always have false positives because geochemistry has the same gases to work with as life does, and gases (such as DMS and CH3Cl) produced for secondary metabolic reasons are far less likely to have false positives but because of their highly specialized origin are more likely to be produced in small quantities. The biomass model estimates are valid to one or two orders of magnitude; the goal is an independent approach to testing whether a biosignature gas is plausible rather than a precise quantification of atmospheric biosignature gases and their corresponding biomasses.

Estimated Tissue and Blood N(2) Levels and Risk of Decompression Sickness in Deep-, Intermediate-, and Shallow-Diving Toothed Whales during Exposure to Naval Sonar.

PubMed

Kvadsheim, P H; Miller, P J O; Tyack, P L; Sivle, L D; Lam, F P A; Fahlman, A

2012-01-01

Naval sonar has been accused of causing whale stranding by a mechanism which increases formation of tissue N(2) gas bubbles. Increased tissue and blood N(2) levels, and thereby increased risk of decompression sickness (DCS), is thought to result from changes in behavior or physiological responses during diving. Previous theoretical studies have used hypothetical sonar-induced changes in both behavior and physiology to model blood and tissue N(2) tension [Formula: see text], but this is the first attempt to estimate the changes during actual behavioral responses to sonar. We used an existing mathematical model to estimate blood and tissue N(2) tension [Formula: see text] from dive data recorded from sperm, killer, long-finned pilot, Blainville's beaked, and Cuvier's beaked whales before and during exposure to Low- (1-2 kHz) and Mid- (2-7 kHz) frequency active sonar. Our objectives were: (1) to determine if differences in dive behavior affects risk of bubble formation, and if (2) behavioral- or (3) physiological responses to sonar are plausible risk factors. Our results suggest that all species have natural high N(2) levels, with deep diving generally resulting in higher end-dive [Formula: see text] as compared with shallow diving. Sonar exposure caused some changes in dive behavior in both killer whales, pilot whales and beaked whales, but this did not lead to any increased risk of DCS. However, in three of eight exposure session with sperm whales, the animal changed to shallower diving, and in all these cases this seem to result in an increased risk of DCS, although risk was still within the normal risk range of this species. When a hypothetical removal of the normal dive response (bradycardia and peripheral vasoconstriction), was added to the behavioral response during model simulations, this led to an increased variance in the estimated end-dive N(2) levels, but no consistent change of risk. In conclusion, we cannot rule out the possibility that a combination of behavioral and physiological responses to sonar have the potential to alter the blood and tissue end-dive N(2) tension to levels which could cause DCS and formation of in vivo bubbles, but the actually observed behavioral responses of cetaceans to sonar in our study, do not imply any significantly increased risk of DCS.

A plausible mechanism of biosorption in dual symbioses by vesicular-arbuscular mycorrhizal in plants.

PubMed

Azmat, Rafia; Hamid, Neelofer

2015-03-01

Dual symbioses of vesicular-arbuscular mycorrhizal (VAM) fungi with growth of Momordica charantia were elucidated in terms of plausible mechanism of biosorption in this article. The experiment was conducted in green house and mixed inoculum of the VAM fungi was used in the three replicates. Results demonstrated that the starch contents were the main source of C for the VAM to builds their hyphae. The increased plant height and leaves surface area were explained in relation with an increase in the photosynthetic rates to produce rapid sugar contents for the survival of plants. A decreased in protein, and amino acid contents and increased proline and protease activity in VAM plants suggested that these contents were the main bio-indicators of the plants under biotic stress. The decline in protein may be due to the degradation of these contents, which later on converted into dextrose where it can easily be absorbed by for the period of symbioses. A mechanism of C chemisorption in relation with physiology and morphology of plant was discussed.

The missing link between sleep disorders and age-related dementia: recent evidence and plausible mechanisms.

PubMed

Zhang, Feng; Zhong, Rujia; Li, Song; Chang, Raymond Chuen-Chung; Le, Weidong

2017-05-01

Sleep disorders are among the most common clinical problems and possess a significant concern for the geriatric population. More importantly, while around 40% of elderly adults have sleep-related complaints, sleep disorders are more frequently associated with co-morbidities including age-related neurodegenerative diseases and mild cognitive impairment. Recently, increasing evidence has indicated that disturbed sleep may not only serve as the consequence of brain atrophy, but also contribute to the pathogenesis of dementia and, therefore, significantly increase dementia risk. Since the current therapeutic interventions lack efficacies to prevent, delay or reverse the pathological progress of dementia, a better understanding of underlying mechanisms by which sleep disorders interact with the pathogenesis of dementia will provide possible targets for the prevention and treatment of dementia. In this review, we briefly describe the physiological roles of sleep in learning/memory, and specifically update the recent research evidence demonstrating the association between sleep disorders and dementia. Plausible mechanisms are further discussed. Moreover, we also evaluate the possibility of sleep therapy as a potential intervention for dementia.

On the quantification and efficient propagation of imprecise probabilities resulting from small datasets

NASA Astrophysics Data System (ADS)

Zhang, Jiaxin; Shields, Michael D.

2018-01-01

This paper addresses the problem of uncertainty quantification and propagation when data for characterizing probability distributions are scarce. We propose a methodology wherein the full uncertainty associated with probability model form and parameter estimation are retained and efficiently propagated. This is achieved by applying the information-theoretic multimodel inference method to identify plausible candidate probability densities and associated probabilities that each method is the best model in the Kullback-Leibler sense. The joint parameter densities for each plausible model are then estimated using Bayes' rule. We then propagate this full set of probability models by estimating an optimal importance sampling density that is representative of all plausible models, propagating this density, and reweighting the samples according to each of the candidate probability models. This is in contrast with conventional methods that try to identify a single probability model that encapsulates the full uncertainty caused by lack of data and consequently underestimate uncertainty. The result is a complete probabilistic description of both aleatory and epistemic uncertainty achieved with several orders of magnitude reduction in computational cost. It is shown how the model can be updated to adaptively accommodate added data and added candidate probability models. The method is applied for uncertainty analysis of plate buckling strength where it is demonstrated how dataset size affects the confidence (or lack thereof) we can place in statistical estimates of response when data are lacking.

Endogenous and Exogenous Estrogen, Cognitive Function and Dementia in Postmenopausal Women: Evidence from Epidemiologic Studies and Clinical Trials

PubMed Central

Laughlin, Gail A.

2009-01-01

There are more than 200 published scientific papers showing that estrogen has favorable effects on brain tissue and physiology in cell culture and animal models including nonhuman primates. The biological plausibility for a neuroprotective estrogen effect is overwhelming. However, most studies of endogenous estrogen and cognitive decline or dementia fail to show protection, and some suggest harm. Failure to find any consistent association might reflect the limitations of a single time of estrogen assay or poor assay sensitivity. More than half of the observational studies of hormone therapy suggest benefit. Nearly all long term clinical trials fail to show benefit and the longer trials tend to show harm. Failure to adequately adjust for self-selection of healthier and wealthier women and publication bias could account for some, or all, of the protective effect attributed to estrogen in observational studies. Overall, the evidence does not convincingly support the prescription of early or late postmenopausal estrogen therapy to preserve cognitive function or prevent dementia. PMID:19401958

Antioxidative mechanisms in chlorogenic acid.

PubMed

Tošović, Jelena; Marković, Svetlana; Dimitrić Marković, Jasmina M; Mojović, Miloš; Milenković, Dejan

2017-12-15

Although chlorogenic acid (5CQA) is an important ingredient of various foods and beverages, mechanisms of its antioxidative action have not been fully clarified. Besides electron spin resonance experiment, this study includes thermodynamic and mechanistic investigations of the hydrogen atom transfer (HAT), radical adduct formation (RAF), sequential proton loss electron transfer (SPLET), and single electron transfer - proton transfer (SET-PT) mechanisms of 5CQA in benzene, ethanol, and water solutions. The calculations were performed using the M06-2X/6-311++G(d,p) level of theory and CPCM solvation model. It was found that SET-PT is not a plausible antioxidative mechanism of 5CQA. RAF pathways are faster, but HAT yields thermodynamically more stable radical products, indicating that in acidic and neutral media 5CQA can take either HAT or RAF pathways. In basic environment (e.g. at physiological pH) SPLET is the likely antioxidative mechanism of 5CQA with extremely high rate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lacosamide and Levetiracetam Have No Effect on Sharp-Wave Ripple Rate.

PubMed

Kudlacek, Jan; Chvojka, Jan; Posusta, Antonin; Kovacova, Lubica; Hong, Seung Bong; Weiss, Shennan; Volna, Kamila; Marusic, Petr; Otahal, Jakub; Jiruska, Premysl

2017-01-01

Pathological high-frequency oscillations are a novel marker used to improve the delineation of epileptogenic tissue and, hence, the outcome of epilepsy surgery. Their practical clinical utilization is curtailed by the inability to discriminate them from physiological oscillations due to frequency overlap. Although it is well documented that pathological HFOs are suppressed by antiepileptic drugs (AEDs), the effect of AEDs on normal HFOs is not well known. In this experimental study, we have explored whether physiological HFOs (sharp-wave ripples) of hippocampal origin respond to AED treatment. The results show that application of a single dose of levetiracetam or lacosamide does not reduce the rate of sharp-wave ripples. In addition, it seems that these new generation drugs do not negatively affect the cellular and network mechanisms involved in sharp-wave ripple generation, which may provide a plausible explanation for the absence of significant negative effects on cognitive functions of these drugs, particularly on memory.

Shift work and cardiovascular disease - pathways from circadian stress to morbidity.

PubMed

Puttonen, Sampsa; Härmä, Mikko; Hublin, Christer

2010-03-01

In order to establish a causal relation between shift work and cardiovascular disease (CVD), we need to verify the pathways from the former to the latter. This paper aims to review the current knowledge of the mechanisms between shift work and CVD. Shift work can increase the risk of CVD by several interrelated psychosocial, behavioral, and physiological mechanisms. The psychosocial mechanisms relate to difficulties in controlling working hours, decreased work-life balance, and poor recovery following work. The most probable behavioral changes are weight gain and smoking. The plausible physiological and biological mechanisms are related to the activation of the autonomic nervous system, inflammation, changed lipid and glucose metabolism, and related changes in the risk for atherosclerosis, metabolic syndrome, and type II diabetes. The data provide evidence for possible disease mechanisms between shift work and CVD, but compelling evidence on any specific mechanism is missing.

Shift work, cancer and "white-box" epidemiology: Association and causation.

PubMed

Erren, Thomas C

2010-11-30

This commentary intends to instigate discussions about upcoming epidemiologic research, and its interpretation, into putative links between shift work, involving circadian disruption or chronodisruption [CD], and the development of internal cancers.In 2007, the International Agency for Research on Cancer (IARC) convened an expert group to examine the carcinogenicity of shift work, inter alia characterized by light exposures at unusual times. After a critical review of published data, the following was stated: "There is sufficient evidence in experimental animals for the carcinogenicity of light during the daily dark period (biological night)". However, in view of limited epidemiological evidence, it was overall concluded: "Shiftwork that involves circadian disruption is probably carcinogenic to humans (Group 2A)".Remarkably, the scenario around shift work, CD and internal cancers provides a unique case for "white-box" epidemiology: Research at many levels - from sub-cellular biochemistry, to whole cells, to organs, to organisms, including animals and humans - has suggested a series of quite precise and partly related causal mechanisms. This is in stark contrast to instances of "black box" or "stabs in the dark" epidemiology where causal mechanisms are neither known nor hypothesized or only poorly defined. The overriding theme that an adequate chronobiological organization of physiology can be critical for the protection against cancer builds the cornerstone of biological plausibility in this case.We can now benefit from biological plausibility in two ways: First, epidemiology should use biologically plausible insights into putative chains of causation between shift work and cancer to design future investigations. Second, when significant new data were to become available in coming years, IARC will re-evaluate cancer hazards associated with shift work. Biological plausibility may then be a key viewpoint to consider and, ultimately, to decide whether (or not) to pass from statistical associations, possibly detected in observational studies by then, to a verdict of causation.In the meantime, biological plausibility should not be invoked to facilitate publication of epidemiological research of inappropriate quality. Specific recommendations as to how to design, report and interpret epidemiological research into biologically plausible links between shift work and cancer are provided.Epidemiology is certainly a poor toolfor learning about the mechanismby which a disease is produced,but it has the tremendous advantagethat it focuses on the diseases and the deathsthat actually occur,and experience has shown that it continues to be second to none asa means of discovering linksin the chain of causationthat are capable of being broken.-Sir Richard Doll 1.

A Comparative Data-Based Modeling Study on Respiratory CO2 Gas Exchange during Mechanical Ventilation

PubMed Central

Kim, Chang-Sei; Ansermino, J. Mark; Hahn, Jin-Oh

2016-01-01

The goal of this study is to derive a minimally complex but credible model of respiratory CO2 gas exchange that may be used in systematic design and pilot testing of closed-loop end-tidal CO2 controllers in mechanical ventilation. We first derived a candidate model that captures the essential mechanisms involved in the respiratory CO2 gas exchange process. Then, we simplified the candidate model to derive two lower-order candidate models. We compared these candidate models for predictive capability and reliability using experimental data collected from 25 pediatric subjects undergoing dynamically varying mechanical ventilation during surgical procedures. A two-compartment model equipped with transport delay to account for CO2 delivery between the lungs and the tissues showed modest but statistically significant improvement in predictive capability over the same model without transport delay. Aggregating the lungs and the tissues into a single compartment further degraded the predictive fidelity of the model. In addition, the model equipped with transport delay demonstrated superior reliability to the one without transport delay. Further, the respiratory parameters derived from the model equipped with transport delay, but not the one without transport delay, were physiologically plausible. The results suggest that gas transport between the lungs and the tissues must be taken into account to accurately reproduce the respiratory CO2 gas exchange process under conditions of wide-ranging and dynamically varying mechanical ventilation conditions. PMID:26870728

New methods in hydrologic modeling and decision support for culvert flood risk under climate change

NASA Astrophysics Data System (ADS)

Rosner, A.; Letcher, B. H.; Vogel, R. M.; Rees, P. S.

2015-12-01

Assessing culvert flood vulnerability under climate change poses an unusual combination of challenges. We seek a robust method of planning for an uncertain future, and therefore must consider a wide range of plausible future conditions. Culverts in our case study area, northwestern Massachusetts, USA, are predominantly found in small, ungaged basins. The need to predict flows both at numerous sites and under numerous plausible climate conditions requires a statistical model with low data and computational requirements. We present a statistical streamflow model that is driven by precipitation and temperature, allowing us to predict flows without reliance on reference gages of observed flows. The hydrological analysis is used to determine each culvert's risk of failure under current conditions. We also explore the hydrological response to a range of plausible future climate conditions. These results are used to determine the tolerance of each culvert to future increases in precipitation. In a decision support context, current flood risk as well as tolerance to potential climate changes are used to provide a robust assessment and prioritization for culvert replacements.

Single-trial lie detection using a combined fNIRS-polygraph system

PubMed Central

Bhutta, M. Raheel; Hong, Melissa J.; Kim, Yun-Hee; Hong, Keum-Shik

2015-01-01

Deception is a human behavior that many people experience in daily life. It involves complex neuronal activities in addition to several physiological changes in the body. A polygraph, which can measure some of the physiological responses from the body, has been widely employed in lie-detection. Many researchers, however, believe that lie detection can become more precise if the neuronal changes that occur in the process of deception can be isolated and measured. In this study, we combine both measures (i.e., physiological and neuronal changes) for enhanced lie-detection. Specifically, to investigate the deception-related hemodynamic response, functional near-infrared spectroscopy (fNIRS) is applied at the prefrontal cortex besides a commercially available polygraph system. A mock crime scenario with a single-trial stimulus is set up as a deception protocol. The acquired data are classified into “true” and “lie” classes based on the fNIRS-based hemoglobin-concentration changes and polygraph-based physiological signal changes. Linear discriminant analysis is utilized as a classifier. The results indicate that the combined fNIRS-polygraph system delivers much higher classification accuracy than that of a singular system. This study demonstrates a plausible solution toward single-trial lie-detection by combining fNIRS and the polygraph. PMID:26082733

Children and guns: The detection of recent contact with firearms on children's hands by the PDT reagent.

PubMed

Bar-Or, Karni L; Almog, Joseph

2015-08-01

Throughout the world, young children are worryingly found to be involved in both unintentional and intentional gun violence, rendering the forensic investigation of gun handling by children a highly important matter. The effectiveness of the PDT reaction for mapping iron traces on hands of children has been tested and compared to its application on adults. Counter-intuitively, children were found to produce considerably more intense PDT impressions than adults. A plausible explanation which is based on physiological differences between children and adolescents is suggested. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Determination of nitric oxide metabolites, nitrate and nitrite, in Anopheles culicifacies mosquito midgut and haemolymph by anion exchange high-performance liquid chromatography: plausible mechanism of refractoriness

PubMed Central

Sharma, Arun; Raghavendra, Kamaraju; Adak, Tridibesh; Dash, Aditya P

2008-01-01

Background The diverse physiological and pathological role of nitric oxide in innate immune defenses against many intra and extracellular pathogens, have led to the development of various methods for determining nitric oxide (NO) synthesis. NO metabolites, nitrite (NO2-) and nitrate (NO3-) are produced by the action of an inducible Anopheles culicifacies NO synthase (AcNOS) in mosquito mid-guts and may be central to anti-parasitic arsenal of these mosquitoes. Method While exploring a plausible mechanism of refractoriness based on nitric oxide synthase physiology among the sibling species of An. culicifacies, a sensitive, specific and cost effective high performance liquid chromatography (HPLC) method was developed, which is not influenced by the presence of biogenic amines, for the determination of NO2- and NO3- from mosquito mid-guts and haemolymph. Results This method is based on extraction, efficiency, assay reproducibility and contaminant minimization. It entails de-proteinization by centrifugal ultra filtration through ultracel 3 K filter and analysis by high performance anion exchange liquid chromatography (Sphereclone, 5 μ SAX column) with UV detection at 214 nm. The lower detection limit of the assay procedure is 50 pmoles in all midgut and haemolymph samples. Retention times for NO2- and NO3- in standards and in mid-gut samples were 3.42 and 4.53 min. respectively. Assay linearity for standards ranged between 50 nM and 1 mM. Recoveries of NO2- and NO3- from spiked samples (1–100 μM) and from the extracted standards (1–100 μM) were calculated to be 100%. Intra-assay and inter assay variations and relative standard deviations (RSDs) for NO2- and NO3- in spiked and un-spiked midgut samples were 5.7% or less. Increased levels NO2- and NO3- in midguts and haemolymph of An. culicifacies sibling species B in comparison to species A reflect towards a mechanism of refractoriness based on AcNOS physiology. Conclusion HPLC is a sensitive and accurate technique for identification and quantifying pmole levels of NO metabolites in mosquito midguts and haemolymph samples that can be useful for clinical investigations of NO biochemistry, physiology and pharmacology in various biological samples. PMID:18442373

Arterial viscoelasticity: role in the dependency of pulse wave velocity on heart rate in conduit arteries.

PubMed

Xiao, Hanguang; Tan, Isabella; Butlin, Mark; Li, Decai; Avolio, Alberto P

2017-06-01

Experimental investigations have established that the stiffness of large arteries has a dependency on acute heart rate (HR) changes. However, the possible underlying mechanisms inherent in this HR dependency have not been well established. This study aimed to explore a plausible viscoelastic mechanism by which HR exerts an influence on arterial stiffness. A multisegment transmission line model of the human arterial tree incorporating fractional viscoelastic components in each segment was used to investigate the effect of varying fractional order parameter (α) of viscoelasticity on the dependence of aortic arch to femoral artery pulse wave velocity (afPWV) on HR. HR was varied from 60 to 100 beats/min at a fixed mean flow of 100 ml/s. PWV was calculated by intersecting tangent method (afPWV Tan ) and by phase velocity from the transfer function (afPWV TF ) in the time and frequency domain, respectively. PWV was significantly and positively associated with HR for α ≥ 0.6; for α = 0.6, 0.8, and 1, HR-dependent changes in afPWV Tan were 0.01 ± 0.02, 0.07 ± 0.04, and 0.22 ± 0.09 m/s per 5 beats/min; HR-dependent changes in afPWV TF were 0.02 ± 0.01, 0.12 ± 0.00, and 0.34 ± 0.01 m/s per 5 beats/min, respectively. This crosses the range of previous physiological studies where the dependence of PWV on HR was found to be between 0.08 and 0.10 m/s per 5 beats/min. Therefore, viscoelasticity of the arterial wall could contribute to mechanisms through which large artery stiffness changes with changing HR. Physiological studies are required to confirm this mechanism. NEW & NOTEWORTHY This study used a transmission line model to elucidate the role of arterial viscoelasticity in the dependency of pulse wave velocity on heart rate. The model uses fractional viscoelasticity concepts, which provided novel insights into arterial hemodynamics. This study also provides a means of assessing the clinical manifestation of the association of pulse wave velocity and heart rate. Copyright © 2017 the American Physiological Society.

Autonomic nervous system profile in fibromyalgia patients and its modulation by exercise: a mini review.

PubMed

Kulshreshtha, Poorvi; Deepak, Kishore K

2013-03-01

This review imparts an impressionistic tone to our current understanding of autonomic nervous system abnormalities in fibromyalgia. In the wake of symptoms present in patients with fibromyalgia (FM), autonomic dysfunction seems plausible in fibromyalgia. A popular notion is that of a relentless sympathetic hyperactivity and hyporeactivity based on heart rate variability (HRV) analyses and responses to various physiological stimuli. However, some exactly opposite findings suggesting normal/hypersympathetic reactivity in patients with fibromyalgia do exist. This heterogeneous picture along with multiple comorbidities accounts for the quantitative and qualitative differences in the degree of dysautonomia present in patients with FM. We contend that HRV changes in fibromyalgia may not actually represent increased cardiac sympathetic tone. Normal muscle sympathetic nerve activity (MSNA) and normal autonomic reactivity tests in patients with fibromyalgia suggest defective vascular end organ in fibromyalgia. Previously, we proposed a model linking deconditioning with physical inactivity resulting from widespread pain in patients with fibromyalgia. Deconditioning also modulates the autonomic nervous system (high sympathetic tone and a low parasympathetic tone). A high peripheral sympathetic tone causes regional ischaemia, which in turn results in widespread pain. Thus, vascular dysregulation and hypoperfusion in patients with FM give rise to ischaemic pain leading to physical inactivity. Microvascular abnormalities are also found in patients with FM. Therapeutic interventions (e.g. exercise) that result in vasodilatation and favourable autonomic alterations have proven to be effective. In this review, we focus on the vascular end organ in patients with fibromyalgia in particular and its modulation by exercise in general. © 2012 The Authors Clinical Physiology and Functional Imaging © 2012 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

Flood hydrology for Dry Creek, Lake County, Northwestern Montana

USGS Publications Warehouse

Parrett, C.; Jarrett, R.D.

2004-01-01

Dry Creek drains about 22.6 square kilometers of rugged mountainous terrain upstream from Tabor Dam in the Mission Range near St. Ignatius, Montana. Because of uncertainty about plausible peak discharges and concerns regarding the ability of the Tabor Dam spillway to safely convey these discharges, the flood hydrology for Dry Creek was evaluated on the basis of three hydrologic and geologic methods. The first method involved determining an envelope line relating flood discharge to drainage area on the basis of regional historical data and calculating a 500-year flood for Dry Creek using a regression equation. The second method involved paleoflood methods to estimate the maximum plausible discharge for 35 sites in the study area. The third method involved rainfall-runoff modeling for the Dry Creek basin in conjunction with regional precipitation information to determine plausible peak discharges. All of these methods resulted in estimates of plausible peak discharges that are substantially less than those predicted by the more generally applied probable maximum flood technique. Copyright ASCE 2004.

Exploring discrepancies between quantitative validation results and the geomorphic plausibility of statistical landslide susceptibility maps

NASA Astrophysics Data System (ADS)

Steger, Stefan; Brenning, Alexander; Bell, Rainer; Petschko, Helene; Glade, Thomas

2016-06-01

Empirical models are frequently applied to produce landslide susceptibility maps for large areas. Subsequent quantitative validation results are routinely used as the primary criteria to infer the validity and applicability of the final maps or to select one of several models. This study hypothesizes that such direct deductions can be misleading. The main objective was to explore discrepancies between the predictive performance of a landslide susceptibility model and the geomorphic plausibility of subsequent landslide susceptibility maps while a particular emphasis was placed on the influence of incomplete landslide inventories on modelling and validation results. The study was conducted within the Flysch Zone of Lower Austria (1,354 km2) which is known to be highly susceptible to landslides of the slide-type movement. Sixteen susceptibility models were generated by applying two statistical classifiers (logistic regression and generalized additive model) and two machine learning techniques (random forest and support vector machine) separately for two landslide inventories of differing completeness and two predictor sets. The results were validated quantitatively by estimating the area under the receiver operating characteristic curve (AUROC) with single holdout and spatial cross-validation technique. The heuristic evaluation of the geomorphic plausibility of the final results was supported by findings of an exploratory data analysis, an estimation of odds ratios and an evaluation of the spatial structure of the final maps. The results showed that maps generated by different inventories, classifiers and predictors appeared differently while holdout validation revealed similar high predictive performances. Spatial cross-validation proved useful to expose spatially varying inconsistencies of the modelling results while additionally providing evidence for slightly overfitted machine learning-based models. However, the highest predictive performances were obtained for maps that explicitly expressed geomorphically implausible relationships indicating that the predictive performance of a model might be misleading in the case a predictor systematically relates to a spatially consistent bias of the inventory. Furthermore, we observed that random forest-based maps displayed spatial artifacts. The most plausible susceptibility map of the study area showed smooth prediction surfaces while the underlying model revealed a high predictive capability and was generated with an accurate landslide inventory and predictors that did not directly describe a bias. However, none of the presented models was found to be completely unbiased. This study showed that high predictive performances cannot be equated with a high plausibility and applicability of subsequent landslide susceptibility maps. We suggest that greater emphasis should be placed on identifying confounding factors and biases in landslide inventories. A joint discussion between modelers and decision makers of the spatial pattern of the final susceptibility maps in the field might increase their acceptance and applicability.

Profiling outcomes of ambulatory care: casemix affects perceived performance.

PubMed

Berlowitz, D R; Ash, A S; Hickey, E C; Kader, B; Friedman, R; Moskowitz, M A

1998-06-01

The authors explored the role of casemix adjustment when profiling outcomes of ambulatory care. The authors reviewed the medical records of 656 patients with hypertension, diabetes, or chronic obstructive pulmonary disease (COPD) receiving care at one of three Department of Veterans Affairs medical centers. Outcomes included measures of physiological control for hypertension and diabetes, and of exacerbations for COPD. Predictors of poor outcomes, including physical examination findings, symptoms, and comorbidities, were identified and entered into regression models. Observed minus expected performance was described for each site, both before and after casemix adjustment. Risk-adjustment models were developed that were clinically plausible and had good performance properties. Differences existed among the three sites in the severity of the patients being cared for. For example, the percentage of patients expected to have poor blood pressure control were 35% at site 1, 37% at site 2, and 44% at site 3 (P < 0.01). Casemix-adjusted measures of performance were different from unadjusted measures. Sites that were outliers (P < 0.05) with one approach had observed performance no different from expected with another approach. Casemix adjustment models can be developed for outpatient medical conditions. Sites differ in the severity of patients they treat, and adjusting for these differences can alter judgments of site performance. Casemix adjustment is necessary when profiling outpatient medical conditions.

Biologically plausible learning in recurrent neural networks reproduces neural dynamics observed during cognitive tasks

PubMed Central

Miconi, Thomas

2017-01-01

Neural activity during cognitive tasks exhibits complex dynamics that flexibly encode task-relevant variables. Chaotic recurrent networks, which spontaneously generate rich dynamics, have been proposed as a model of cortical computation during cognitive tasks. However, existing methods for training these networks are either biologically implausible, and/or require a continuous, real-time error signal to guide learning. Here we show that a biologically plausible learning rule can train such recurrent networks, guided solely by delayed, phasic rewards at the end of each trial. Networks endowed with this learning rule can successfully learn nontrivial tasks requiring flexible (context-dependent) associations, memory maintenance, nonlinear mixed selectivities, and coordination among multiple outputs. The resulting networks replicate complex dynamics previously observed in animal cortex, such as dynamic encoding of task features and selective integration of sensory inputs. We conclude that recurrent neural networks offer a plausible model of cortical dynamics during both learning and performance of flexible behavior. DOI: http://dx.doi.org/10.7554/eLife.20899.001 PMID:28230528

Biologically plausible learning in recurrent neural networks reproduces neural dynamics observed during cognitive tasks.

PubMed

Miconi, Thomas

2017-02-23

Neural activity during cognitive tasks exhibits complex dynamics that flexibly encode task-relevant variables. Chaotic recurrent networks, which spontaneously generate rich dynamics, have been proposed as a model of cortical computation during cognitive tasks. However, existing methods for training these networks are either biologically implausible, and/or require a continuous, real-time error signal to guide learning. Here we show that a biologically plausible learning rule can train such recurrent networks, guided solely by delayed, phasic rewards at the end of each trial. Networks endowed with this learning rule can successfully learn nontrivial tasks requiring flexible (context-dependent) associations, memory maintenance, nonlinear mixed selectivities, and coordination among multiple outputs. The resulting networks replicate complex dynamics previously observed in animal cortex, such as dynamic encoding of task features and selective integration of sensory inputs. We conclude that recurrent neural networks offer a plausible model of cortical dynamics during both learning and performance of flexible behavior.

The plausibility of a role for mercury in the etiology of autism: a cellular perspective

PubMed Central

Garrecht, Matthew; Austin, David W.

2011-01-01

Autism is defined by a behavioral set of stereotypic and repetitious behavioral patterns in combination with social and communication deficits. There is emerging evidence supporting the hypothesis that autism may result from a combination of genetic susceptibility and exposure to environmental toxins at critical moments in development. Mercury (Hg) is recognized as a ubiquitous environmental neurotoxin and there is mounting evidence linking it to neurodevelopmental disorders, including autism. Of course, the evidence is not derived from experimental trials with humans but rather from methods focusing on biomarkers of Hg damage, measurements of Hg exposure, epidemiological data, and animal studies. For ethical reasons, controlled Hg exposure in humans will never be conducted. Therefore, to properly evaluate the Hg-autism etiological hypothesis, it is essential to first establish the biological plausibility of the hypothesis. This review examines the plausibility of Hg as the primary etiological agent driving the cellular mechanisms by which Hg-induced neurotoxicity may result in the physiological attributes of autism. Key areas of focus include: (1) route and cellular mechanisms of Hg exposure in autism; (2) current research and examples of possible genetic variables that are linked to both Hg sensitivity and autism; (3) the role Hg may play as an environmental toxin fueling the oxidative stress found in autism; (4) role of mitochondrial dysfunction; and (5) possible role of Hg in abnormal neuroexcitory and excitotoxity that may play a role in the immune dysregulation found in autism. Future research directions that would assist in addressing the gaps in our knowledge are proposed. PMID:22163375

Selection, calibration, and validation of models of tumor growth.

PubMed

Lima, E A B F; Oden, J T; Hormuth, D A; Yankeelov, T E; Almeida, R C

2016-11-01

This paper presents general approaches for addressing some of the most important issues in predictive computational oncology concerned with developing classes of predictive models of tumor growth. First, the process of developing mathematical models of vascular tumors evolving in the complex, heterogeneous, macroenvironment of living tissue; second, the selection of the most plausible models among these classes, given relevant observational data; third, the statistical calibration and validation of models in these classes, and finally, the prediction of key Quantities of Interest (QOIs) relevant to patient survival and the effect of various therapies. The most challenging aspects of this endeavor is that all of these issues often involve confounding uncertainties: in observational data, in model parameters, in model selection, and in the features targeted in the prediction. Our approach can be referred to as "model agnostic" in that no single model is advocated; rather, a general approach that explores powerful mixture-theory representations of tissue behavior while accounting for a range of relevant biological factors is presented, which leads to many potentially predictive models. Then representative classes are identified which provide a starting point for the implementation of OPAL, the Occam Plausibility Algorithm (OPAL) which enables the modeler to select the most plausible models (for given data) and to determine if the model is a valid tool for predicting tumor growth and morphology ( in vivo ). All of these approaches account for uncertainties in the model, the observational data, the model parameters, and the target QOI. We demonstrate these processes by comparing a list of models for tumor growth, including reaction-diffusion models, phase-fields models, and models with and without mechanical deformation effects, for glioma growth measured in murine experiments. Examples are provided that exhibit quite acceptable predictions of tumor growth in laboratory animals while demonstrating successful implementations of OPAL.

Physiologically Based Simulations of Deuterated Glucose for Quantifying Cell Turnover in Humans

PubMed Central

Lahoz-Beneytez, Julio; Schaller, Stephan; Macallan, Derek; Eissing, Thomas; Niederalt, Christoph; Asquith, Becca

2017-01-01

In vivo [6,6-2H2]-glucose labeling is a state-of-the-art technique for quantifying cell proliferation and cell disappearance in humans. However, there are discrepancies between estimates of T cell proliferation reported in short (1-day) versus long (7-day) 2H2-glucose studies and very-long (9-week) 2H2O studies. It has been suggested that these discrepancies arise from underestimation of true glucose exposure from intermittent blood sampling in the 1-day study. Label availability in glucose studies is normally approximated by a “square pulse” (Sq pulse). Since the body glucose pool is small and turns over rapidly, the availability of labeled glucose can be subject to large fluctuations and the Sq pulse approximation may be very inaccurate. Here, we model the pharmacokinetics of exogenous labeled glucose using a physiologically based pharmacokinetic (PBPK) model to assess the impact of a more complete description of label availability as a function of time on estimates of CD4+ and CD8+ T cell proliferation and disappearance. The model enabled us to predict the exposure to labeled glucose during the fasting and de-labeling phases, to capture the fluctuations of labeled glucose availability caused by the intake of food or high-glucose beverages, and to recalculate the proliferation and death rates of immune cells. The PBPK model was used to reanalyze experimental data from three previously published studies using different labeling protocols. Although using the PBPK enrichment profile decreased the 1-day proliferation estimates by about 4 and 7% for CD4 and CD8+ T cells, respectively, differences with the 7-day and 9-week studies remained significant. We conclude that the approximations underlying the “square pulse” approach—recently suggested as the most plausible hypothesis—only explain a component of the discrepancy in published T cell proliferation rate estimates. PMID:28487698

Biomechanical regulation of in vitro cardiogenesis for tissue-engineered heart repair.

PubMed

Zimmermann, Wolfram-Hubertus

2013-01-01

The heart is a continuously pumping organ with an average lifespan of eight decades. It develops from the onset of embryonic cardiogenesis under biomechanical load, performs optimally within a defined range of hemodynamic load, and fails if acutely or chronically overloaded. Unloading of the heart leads to defective cardiogenesis in utero, but can also lead to a desired therapeutic outcome (for example, in patients with heart failure under left ventricular assist device therapy). In light of the well-documented relevance of mechanical loading for cardiac physiology and pathology, it is plausible that tissue engineers have integrated mechanical stimulation regimens into protocols for heart muscle construction. To achieve optimal results, physiological principles of beat-to-beat myocardial loading and unloading should be simulated. In addition, heart muscle engineering, in particular if based on pluripotent stem cell-derived cardiomyocytes, may benefit from staggered tonic loading protocols to simulate viscoelastic properties of the prenatal and postnatal myocardial stroma. This review will provide an overview of heart muscle mechanics, summarize observations on the role of mechanical loading for heart development and postnatal performance, and discuss how physiological loading regimens can be exploited to advance myocardial tissue engineering towards a therapeutic application.

Biomechanical regulation of in vitro cardiogenesis for tissue-engineered heart repair

PubMed Central

2013-01-01

The heart is a continuously pumping organ with an average lifespan of eight decades. It develops from the onset of embryonic cardiogenesis under biomechanical load, performs optimally within a defined range of hemodynamic load, and fails if acutely or chronically overloaded. Unloading of the heart leads to defective cardiogenesis in utero, but can also lead to a desired therapeutic outcome (for example, in patients with heart failure under left ventricular assist device therapy). In light of the well-documented relevance of mechanical loading for cardiac physiology and pathology, it is plausible that tissue engineers have integrated mechanical stimulation regimens into protocols for heart muscle construction. To achieve optimal results, physiological principles of beat-to-beat myocardial loading and unloading should be simulated. In addition, heart muscle engineering, in particular if based on pluripotent stem cell-derived cardiomyocytes, may benefit from staggered tonic loading protocols to simulate viscoelastic properties of the prenatal and postnatal myocardial stroma. This review will provide an overview of heart muscle mechanics, summarize observations on the role of mechanical loading for heart development and postnatal performance, and discuss how physiological loading regimens can be exploited to advance myocardial tissue engineering towards a therapeutic application. PMID:24229468

Wolf Howling Is Mediated by Relationship Quality Rather Than Underlying Emotional Stress

PubMed Central

Mazzini, Francesco; Townsend, Simon W.; Virányi, Zsófia; Range, Friederike

2013-01-01

Summary While considerable research has addressed the function of animal vocalizations, the proximate mechanisms driving call production remain surprisingly unclear. Vocalizations may be driven by emotions and the physiological state evoked by changes in the social-ecological environment [1, 2], or animals may have more control over their vocalizations, using them in flexible ways mediated by the animal’s understanding of its surrounding social world [3, 4]. While both explanations are plausible and neither excludes the other, to date no study has attempted to experimentally investigate the influence of both emotional and cognitive factors on animal vocal usage. We aimed to disentangle the relative contribution of both mechanisms by examining howling in captive wolves. Using a separation experiment and by measuring cortisol levels, we specifically investigated whether howling is a physiological stress response to group fragmentation [5] and whether it is driven by social factors, particularly relationship quality [6, 7]. Results showed that relationship quality between the howler and the leaving individual better predicted howling than did the current physiological state. Our findings shed important light on the degree to which animal vocal production can be considered as voluntary. Video Abstract PMID:23973297

Boric acid induces cytoplasmic stress granule formation, eIF2α phosphorylation, and ATF4 in prostate DU-145 cells.

PubMed

Henderson, Kimberly A; Kobylewski, Sarah E; Yamada, Kristin E; Eckhert, Curtis D

2015-02-01

Dietary boron intake is associated with reduced prostate and lung cancer risk and increased bone mass. Boron is absorbed and circulated as boric acid (BA) and at physiological concentrations is a reversible competitive inhibitor of cyclic ADP ribose, the endogenous agonist of the ryanodine receptor calcium (Ca(+2)) channel, and lowers endoplasmic reticulum (ER) [Ca(2+)]. Low ER [Ca(2+)] has been reported to induce ER stress and activate the eIF2α/ATF4 pathway. Here we report that treatment of DU-145 prostate cells with physiological levels of BA induces ER stress with the formation of stress granules and mild activation of eIF2α, GRP78/BiP, and ATF4. Mild activation of eIF2α and its downstream transcription factor, ATF4, enables cells to reconfigure gene expression to manage stress conditions and mild activation of ATF4 is also required for the differentiation of osteoblast cells. Our results using physiological levels of boric acid identify the eIF2α/ATF pathway as a plausible mode of action that underpins the reported health effects of dietary boron.

A statistical model of false negative and false positive detection of phase singularities.

PubMed

Jacquemet, Vincent

2017-10-01

The complexity of cardiac fibrillation dynamics can be assessed by analyzing the distribution of phase singularities (PSs) observed using mapping systems. Interelectrode distance, however, limits the accuracy of PS detection. To investigate in a theoretical framework the PS false negative and false positive rates in relation to the characteristics of the mapping system and fibrillation dynamics, we propose a statistical model of phase maps with controllable number and locations of PSs. In this model, phase maps are generated from randomly distributed PSs with physiologically-plausible directions of rotation. Noise and distortion of the phase are added. PSs are detected using topological charge contour integrals on regular grids of varying resolutions. Over 100 × 10 6 realizations of the random field process are used to estimate average false negative and false positive rates using a Monte-Carlo approach. The false detection rates are shown to depend on the average distance between neighboring PSs expressed in units of interelectrode distance, following approximately a power law with exponents in the range of 1.14 to 2 for false negatives and around 2.8 for false positives. In the presence of noise or distortion of phase, false detection rates at high resolution tend to a non-zero noise-dependent lower bound. This model provides an easy-to-implement tool for benchmarking PS detection algorithms over a broad range of configurations with multiple PSs.

Climate Change Impacts on Agriculture and Food Security in 2050 under a Range of Plausible Socioeconomic and Emissions Scenarios

NASA Astrophysics Data System (ADS)

Wiebe, K.; Lotze-Campen, H.; Bodirsky, B.; Kavallari, A.; Mason-d'Croz, D.; van der Mensbrugghe, D.; Robinson, S.; Sands, R.; Tabeau, A.; Willenbockel, D.; Islam, S.; van Meijl, H.; Mueller, C.; Robertson, R.

2014-12-01

Previous studies have combined climate, crop and economic models to examine the impact of climate change on agricultural production and food security, but results have varied widely due to differences in models, scenarios and data. Recent work has examined (and narrowed) these differences through systematic model intercomparison using a high-emissions pathway to highlight the differences. New work extends that analysis to cover a range of plausible socioeconomic scenarios and emission pathways. Results from three general circulation models are combined with one crop model and five global economic models to examine the global and regional impacts of climate change on yields, area, production, prices and trade for coarse grains, rice, wheat, oilseeds and sugar to 2050. Results show that yield impacts vary with changes in population, income and technology as well as emissions, but are reduced in all cases by endogenous changes in prices and other variables.

Comparing supply and demand models for future photovoltaic power generation in the USA

DOE PAGES

Basore, Paul A.; Cole, Wesley J.

2018-02-22

We explore the plausible range of future deployment of photovoltaic generation capacity in the USA using a supply-focused model based on supply-chain growth constraints and a demand-focused model based on minimizing the overall cost of the electricity system. Both approaches require assumptions based on previous experience and anticipated trends. For each of the models, we assign plausible ranges for the key assumptions and then compare the resulting PV deployment over time. Each model was applied to 2 different future scenarios: one in which PV market penetration is ultimately constrained by the uncontrolled variability of solar power and one in whichmore » low-cost energy storage or some equivalent measure largely alleviates this constraint. The supply-focused and demand-focused models are in substantial agreement, not just in the long term, where deployment is largely determined by the assumed market penetration constraints, but also in the interim years. For the future scenario without low-cost energy storage or equivalent measures, the 2 models give an average plausible range of PV generation capacity in the USA of 150 to 530 GWdc in 2030 and 260 to 810 GWdc in 2040. With low-cost energy storage or equivalent measures, the corresponding ranges are 160 to 630 GWdc in 2030 and 280 to 1200 GWdc in 2040. The latter range is enough to supply 10% to 40% of US electricity demand in 2040, based on current demand growth.« less

Comparing supply and demand models for future photovoltaic power generation in the USA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Basore, Paul A.; Cole, Wesley J.

We explore the plausible range of future deployment of photovoltaic generation capacity in the USA using a supply-focused model based on supply-chain growth constraints and a demand-focused model based on minimizing the overall cost of the electricity system. Both approaches require assumptions based on previous experience and anticipated trends. For each of the models, we assign plausible ranges for the key assumptions and then compare the resulting PV deployment over time. Each model was applied to 2 different future scenarios: one in which PV market penetration is ultimately constrained by the uncontrolled variability of solar power and one in whichmore » low-cost energy storage or some equivalent measure largely alleviates this constraint. The supply-focused and demand-focused models are in substantial agreement, not just in the long term, where deployment is largely determined by the assumed market penetration constraints, but also in the interim years. For the future scenario without low-cost energy storage or equivalent measures, the 2 models give an average plausible range of PV generation capacity in the USA of 150 to 530 GWdc in 2030 and 260 to 810 GWdc in 2040. With low-cost energy storage or equivalent measures, the corresponding ranges are 160 to 630 GWdc in 2030 and 280 to 1200 GWdc in 2040. The latter range is enough to supply 10% to 40% of US electricity demand in 2040, based on current demand growth.« less

Routine OGTT: a robust model including incretin effect for precise identification of insulin sensitivity and secretion in a single individual.

PubMed

De Gaetano, Andrea; Panunzi, Simona; Matone, Alice; Samson, Adeline; Vrbikova, Jana; Bendlova, Bela; Pacini, Giovanni

2013-01-01

In order to provide a method for precise identification of insulin sensitivity from clinical Oral Glucose Tolerance Test (OGTT) observations, a relatively simple mathematical model (Simple Interdependent glucose/insulin MOdel SIMO) for the OGTT, which coherently incorporates commonly accepted physiological assumptions (incretin effect and saturating glucose-driven insulin secretion) has been developed. OGTT data from 78 patients in five different glucose tolerance groups were analyzed: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IFG+IGT, and Type 2 Diabetes Mellitus (T2DM). A comparison with the 2011 Salinari (COntinuos GI tract MOdel, COMO) and the 2002 Dalla Man (Dalla Man MOdel, DMMO) models was made with particular attention to insulin sensitivity indices ISCOMO, ISDMMO and kxgi (the insulin sensitivity index for SIMO). ANOVA on kxgi values across groups resulted significant overall (P<0.001), and post-hoc comparisons highlighted the presence of three different groups: NGT (8.62×10(-5)±9.36×10(-5) min(-1)pM(-1)), IFG (5.30×10(-5)±5.18×10(-5)) and combined IGT, IFG+IGT and T2DM (2.09×10(-5)±1.95×10(-5), 2.38×10(-5)±2.28×10(-5) and 2.38×10(-5)±2.09×10(-5) respectively). No significance was obtained when comparing ISCOMO or ISDMMO across groups. Moreover, kxgi presented the lowest sample average coefficient of variation over the five groups (25.43%), with average CVs for ISCOMO and ISDMMO of 70.32% and 57.75% respectively; kxgi also presented the strongest correlations with all considered empirical measures of insulin sensitivity. While COMO and DMMO appear over-parameterized for fitting single-subject clinical OGTT data, SIMO provides a robust, precise, physiologically plausible estimate of insulin sensitivity, with which habitual empirical insulin sensitivity indices correlate well. The kxgi index, reflecting insulin secretion dependency on glycemia, also significantly differentiates clinically diverse subject groups. The SIMO model may therefore be of value for the quantification of glucose homeostasis from clinical OGTT data.

Basic research on design analysis methods for rotorcraft vibrations

NASA Technical Reports Server (NTRS)

Hanagud, S.

1991-01-01

The objective of the present work was to develop a method for identifying physically plausible finite element system models of airframe structures from test data. The assumed models were based on linear elastic behavior with general (nonproportional) damping. Physical plausibility of the identified system matrices was insured by restricting the identification process to designated physical parameters only and not simply to the elements of the system matrices themselves. For example, in a large finite element model the identified parameters might be restricted to the moduli for each of the different materials used in the structure. In the case of damping, a restricted set of damping values might be assigned to finite elements based on the material type and on the fabrication processes used. In this case, different damping values might be associated with riveted, bolted and bonded elements. The method itself is developed first, and several approaches are outlined for computing the identified parameter values. The method is applied first to a simple structure for which the 'measured' response is actually synthesized from an assumed model. Both stiffness and damping parameter values are accurately identified. The true test, however, is the application to a full-scale airframe structure. In this case, a NASTRAN model and actual measured modal parameters formed the basis for the identification of a restricted set of physically plausible stiffness and damping parameters.

Metabolic regulation of ghrelin O-acyl transferase (GOAT) expression in the mouse hypothalamus, pituitary, and stomach.

PubMed

Gahete, Manuel D; Córdoba-Chacón, Jose; Salvatori, Roberto; Castaño, Justo P; Kineman, Rhonda D; Luque, Raul M

2010-04-12

Ghrelin acts as an endocrine link connecting physiological processes regulating food intake, body composition, growth, and energy balance. Ghrelin is the only peptide known to undergo octanoylation. The enzyme mediating this process, ghrelin O-acyltransferase (GOAT), is expressed in the gastrointestinal tract (GI; primary source of circulating ghrelin) as well as other tissues. The present study demonstrates that stomach GOAT mRNA levels correlate with circulating acylated-ghrelin levels in fasted and diet-induced obese mice. In addition, GOAT was found to be expressed in both the pituitary and hypothalamus (two target tissues of ghrelin's actions), and regulated in response to metabolic status. Using primary pituitary cell cultures as a model system to study the regulation of GOAT expression, we found that acylated-ghrelin, but not desacyl-ghrelin, increased GOAT expression. In addition, growth-hormone-releasing hormone (GHRH) and leptin increased, while somatostatin (SST) decreased GOAT expression. The physiologic relevance of these later results is supported by the observation that pituitary GOAT expression in mice lacking GHRH, SST and leptin showed opposite changes to those observed after in vitro treatment with the corresponding peptides. Therefore, it seems plausible that these hormones directly contribute to the regulation of pituitary GOAT. Interestingly, in all the models studied, pituitary GOAT expression paralleled changes in the expression of a dominant spliced-variant of ghrelin (In2-ghrelin) and therefore this transcript may be a primary substrate for pituitary GOAT. Collectively, these observations support the notion that the GI tract is not the only source of acylated-ghrelin, but in fact locally produced des-acylated-ghrelin could be converted to acylated-ghrelin within target tissues by locally active GOAT, to mediate its tissue-specific effects.

Nonlinear Dynamic Modeling of Neuron Action Potential Threshold During Synaptically Driven Broadband Intracellular Activity

PubMed Central

Roach, Shane M.; Song, Dong; Berger, Theodore W.

2012-01-01

Activity-dependent variation of neuronal thresholds for action potential (AP) generation is one of the key determinants of spike-train temporal-pattern transformations from presynaptic to postsynaptic spike trains. In this study, we model the nonlinear dynamics of the threshold variation during synaptically driven broadband intracellular activity. First, membrane potentials of single CA1 pyramidal cells were recorded under physiologically plausible broadband stimulation conditions. Second, a method was developed to measure AP thresholds from the continuous recordings of membrane potentials. It involves measuring the turning points of APs by analyzing the third-order derivatives of the membrane potentials. Four stimulation paradigms with different temporal patterns were applied to validate this method by comparing the measured AP turning points and the actual AP thresholds estimated with varying stimulation intensities. Results show that the AP turning points provide consistent measurement of the AP thresholds, except for a constant offset. It indicates that 1) the variation of AP turning points represents the nonlinearities of threshold dynamics; and 2) an optimization of the constant offset is required to achieve accurate spike prediction. Third, a nonlinear dynamical third-order Volterra model was built to describe the relations between the threshold dynamics and the AP activities. Results show that the model can predict threshold accurately based on the preceding APs. Finally, the dynamic threshold model was integrated into a previously developed single neuron model and resulted in a 33% improvement in spike prediction. PMID:22156947

Climate change or climate cycles? Snowpack trends in the Olympic and Cascade Mountains, Washington, USA.

PubMed

Barry, Dwight; McDonald, Shea

2013-01-01

Climate change could significantly influence seasonal streamflow and water availability in the snowpack-fed watersheds of Washington, USA. Descriptions of snowpack decline often use linear ordinary least squares (OLS) models to quantify this change. However, the region's precipitation is known to be related to climate cycles. If snowpack decline is more closely related to these cycles, an OLS model cannot account for this effect, and thus both descriptions of trends and estimates of decline could be inaccurate. We used intervention analysis to determine whether snow water equivalent (SWE) in 25 long-term snow courses within the Olympic and Cascade Mountains are more accurately described by OLS (to represent gradual change), stationary (to represent no change), or step-stationary (to represent climate cycling) models. We used Bayesian information-theoretic methods to determine these models' relative likelihood, and we found 90 models that could plausibly describe the statistical structure of the 25 snow courses' time series. Posterior model probabilities of the 29 "most plausible" models ranged from 0.33 to 0.91 (mean = 0.58, s = 0.15). The majority of these time series (55%) were best represented as step-stationary models with a single breakpoint at 1976/77, coinciding with a major shift in the Pacific Decadal Oscillation. However, estimates of SWE decline differed by as much as 35% between statistically plausible models of a single time series. This ambiguity is a critical problem for water management policy. Approaches such as intervention analysis should become part of the basic analytical toolkit for snowpack or other climatic time series data.

Cerebrovascular Hemodynamics in Women.

PubMed

Duque, Cristina; Feske, Steven K; Sorond, Farzaneh A

2017-12-01

Sex and gender, as biological and social factors, significantly influence health outcomes. Among the biological factors, sex differences in vascular physiology may be one specific mechanism contributing to the observed differences in clinical presentation, response to treatment, and clinical outcomes in several vascular disorders. This review focuses on the cerebrovascular bed and summarizes the existing literature on sex differences in cerebrovascular hemodynamics to highlight the knowledge deficit that exists in this domain. The available evidence is used to generate mechanistically plausible and testable hypotheses to underscore the unmet need in understanding sex-specific mechanisms as targets for more effective therapeutic and preventive strategies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A temperature rise reduces trial-to-trial variability of locust auditory neuron responses.

PubMed

Eberhard, Monika J B; Schleimer, Jan-Hendrik; Schreiber, Susanne; Ronacher, Bernhard

2015-09-01

The neurophysiology of ectothermic animals, such as insects, is affected by environmental temperature, as their body temperature fluctuates with ambient conditions. Changes in temperature alter properties of neurons and, consequently, have an impact on the processing of information. Nevertheless, nervous system function is often maintained over a broad temperature range, exhibiting a surprising robustness to variations in temperature. A special problem arises for acoustically communicating insects, as in these animals mate recognition and mate localization typically rely on the decoding of fast amplitude modulations in calling and courtship songs. In the auditory periphery, however, temporal resolution is constrained by intrinsic neuronal noise. Such noise predominantly arises from the stochasticity of ion channel gating and potentially impairs the processing of sensory signals. On the basis of intracellular recordings of locust auditory neurons, we show that intrinsic neuronal variability on the level of spikes is reduced with increasing temperature. We use a detailed mathematical model including stochastic ion channel gating to shed light on the underlying biophysical mechanisms in auditory receptor neurons: because of a redistribution of channel-induced current noise toward higher frequencies and specifics of the temperature dependence of the membrane impedance, membrane potential noise is indeed reduced at higher temperatures. This finding holds under generic conditions and physiologically plausible assumptions on the temperature dependence of the channels' kinetics and peak conductances. We demonstrate that the identified mechanism also can explain the experimentally observed reduction of spike timing variability at higher temperatures. Copyright © 2015 the American Physiological Society.

Molecular profile of the unique species of traditional Chinese medicine, Chinese seahorse (Hippocampus kuda Bleeker).

PubMed

Zhang, Ning; Xu, Bin; Mou, Chunyan; Yang, Wenli; Wei, Jianwen; Lu, Liang; Zhu, Junjie; Du, Jingchun; Wu, Xiaokun; Ye, Lanting; Fu, Zhiyan; Lu, Yang; Lin, Jianghai; Sun, Zizi; Su, Jing; Dong, Meiling; Xu, Anlong

2003-08-28

A cDNA library of male Chinese seahorse (Hippocampus kuda Bleeker) was constructed to investigate the molecular profile of seahorse as one of the most famous traditional Chinese medicine materials, and to reveal immunological and physiological mechanisms of seahorse as one of the most primitive vertebrates at molecular level. A total of 3372 expressed sequence tags (ESTs) consisting of 1911 unique genes (345 clusters and 1566 singletons) were examined in the present study. Identification of the genes related to immune system, paternal brooding and physiological regulation provides not only valuable insights into the molecular mechanism of immune system in teleost fish but also plausible explanations for pharmacological activities of Chinese seahorse. Furthermore, the occurrence of high prevalent C-type lectins suggested that a lectin-complement pathway might exert a more dominant function in the innate immune system of teleost than mammal. Carbohydrate recognition domain (CRD) without a collagen-like region in the lectins of seahorse was likely an ancient characteristic of lectins similar to invertebrates.

Giant impactors - Plausible sizes and populations

NASA Technical Reports Server (NTRS)

Hartmann, William K.; Vail, S. M.

1986-01-01

The largest sizes of planetesimals required to explain spin properties of planets are investigated in the context of the impact-trigger hypothesis of lunar origin. Solar system models with different large impactor sources are constructed and stochastic variations in obliquities and rotation periods resulting from each source are studied. The present study finds it highly plausible that earth was struck by a body of about 0.03-0.12 earth masses with enough energy and angular momentum to dislodge mantle material and form the present earth-moon system.

Estimated Tissue and Blood N2 Levels and Risk of Decompression Sickness in Deep-, Intermediate-, and Shallow-Diving Toothed Whales during Exposure to Naval Sonar

PubMed Central

Kvadsheim, P. H.; Miller, P. J. O.; Tyack, P. L.; Sivle, L. D.; Lam, F. P. A.; Fahlman, A.

2012-01-01

Naval sonar has been accused of causing whale stranding by a mechanism which increases formation of tissue N2 gas bubbles. Increased tissue and blood N2 levels, and thereby increased risk of decompression sickness (DCS), is thought to result from changes in behavior or physiological responses during diving. Previous theoretical studies have used hypothetical sonar-induced changes in both behavior and physiology to model blood and tissue N2 tension PN2, but this is the first attempt to estimate the changes during actual behavioral responses to sonar. We used an existing mathematical model to estimate blood and tissue N2 tension PN2 from dive data recorded from sperm, killer, long-finned pilot, Blainville’s beaked, and Cuvier’s beaked whales before and during exposure to Low- (1–2 kHz) and Mid- (2–7 kHz) frequency active sonar. Our objectives were: (1) to determine if differences in dive behavior affects risk of bubble formation, and if (2) behavioral- or (3) physiological responses to sonar are plausible risk factors. Our results suggest that all species have natural high N2 levels, with deep diving generally resulting in higher end-dive PN2 as compared with shallow diving. Sonar exposure caused some changes in dive behavior in both killer whales, pilot whales and beaked whales, but this did not lead to any increased risk of DCS. However, in three of eight exposure session with sperm whales, the animal changed to shallower diving, and in all these cases this seem to result in an increased risk of DCS, although risk was still within the normal risk range of this species. When a hypothetical removal of the normal dive response (bradycardia and peripheral vasoconstriction), was added to the behavioral response during model simulations, this led to an increased variance in the estimated end-dive N2 levels, but no consistent change of risk. In conclusion, we cannot rule out the possibility that a combination of behavioral and physiological responses to sonar have the potential to alter the blood and tissue end-dive N2 tension to levels which could cause DCS and formation of in vivo bubbles, but the actually observed behavioral responses of cetaceans to sonar in our study, do not imply any significantly increased risk of DCS. PMID:22590458

SOME USES OF MODELS OF QUANTITATIVE GENETIC SELECTION IN SOCIAL SCIENCE.

PubMed

Weight, Michael D; Harpending, Henry

2017-01-01

The theory of selection of quantitative traits is widely used in evolutionary biology, agriculture and other related fields. The fundamental model known as the breeder's equation is simple, robust over short time scales, and it is often possible to estimate plausible parameters. In this paper it is suggested that the results of this model provide useful yardsticks for the description of social traits and the evaluation of transmission models. The differences on a standard personality test between samples of Old Order Amish and Indiana rural young men from the same county and the decline of homicide in Medieval Europe are used as illustrative examples of the overall approach. It is shown that the decline of homicide is unremarkable under a threshold model while the differences between rural Amish and non-Amish young men are too large to be a plausible outcome of simple genetic selection in which assortative mating by affiliation is equivalent to truncation selection.

Isolating the anthropogenic component of Arctic warming

DOE PAGES

Chylek, Petr; Hengartner, Nicholas; Lesins, Glen; ...

2014-05-28

Structural equation modeling is used in statistical applications as both confirmatory and exploratory modeling to test models and to suggest the most plausible explanation for a relationship between the independent and the dependent variables. Although structural analysis cannot prove causation, it can suggest the most plausible set of factors that influence the observed variable. Here, we apply structural model analysis to the annual mean Arctic surface air temperature from 1900 to 2012 to find the most effective set of predictors and to isolate the anthropogenic component of the recent Arctic warming by subtracting the effects of natural forcing and variabilitymore » from the observed temperature. We also find that anthropogenic greenhouse gases and aerosols radiative forcing and the Atlantic Multidecadal Oscillation internal mode dominate Arctic temperature variability. Finally, our structural model analysis of observational data suggests that about half of the recent Arctic warming of 0.64 K/decade may have anthropogenic causes.« less

Morality Principles for Risk Modelling: Needs and Links with the Origins of Plausible Inference

NASA Astrophysics Data System (ADS)

Solana-Ortega, Alberto; Solana, Vicente

2009-12-01

In comparison with the foundations of probability calculus, the inescapable and controversial issue of how to assign probabilities has only recently become a matter of formal study. The introduction of information as a technical concept was a milestone, but the most promising entropic assignment methods still face unsolved difficulties, manifesting the incompleteness of plausible inference theory. In this paper we examine the situation faced by risk analysts in the critical field of extreme events modelling, where the former difficulties are especially visible, due to scarcity of observational data, the large impact of these phenomena and the obligation to assume professional responsibilities. To respond to the claim for a sound framework to deal with extremes, we propose a metafoundational approach to inference, based on a canon of extramathematical requirements. We highlight their strong moral content, and show how this emphasis in morality, far from being new, is connected with the historic origins of plausible inference. Special attention is paid to the contributions of Caramuel, a contemporary of Pascal, unfortunately ignored in the usual mathematical accounts of probability.

Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

NASA Astrophysics Data System (ADS)

Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.

2015-06-01

Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

Behavioral effect of knee joint motion on body's center of mass during human quiet standing.

PubMed

Yamamoto, Akio; Sasagawa, Shun; Oba, Naoko; Nakazawa, Kimitaka

2015-01-01

The balance control mechanism during upright standing has often been investigated using single- or double-link inverted pendulum models, involving the ankle joint only or both the ankle and hip joints, respectively. Several studies, however, have reported that knee joint motion during quiet standing cannot be ignored. This study aimed to investigate the degree to which knee joint motion contributes to the center of mass (COM) kinematics during quiet standing. Eight healthy adults were asked to stand quietly for 30s on a force platform. Angular displacements and accelerations of the ankle, knee, and hip joints were calculated from kinematic data obtained by a motion capture system. We found that the amplitude of the angular acceleration was smallest in the ankle joint and largest in the hip joint (ankle < knee < hip). These angular accelerations were then substituted into three biomechanical models with or without the knee joint to estimate COM acceleration in the anterior-posterior direction. Although the "without-knee" models greatly overestimated the COM acceleration, the COM acceleration estimated by the "with-knee" model was similar to the actual acceleration obtained from force platform measurement. These results indicate substantial effects of knee joint motion on the COM kinematics during quiet standing. We suggest that investigations based on the multi-joint model, including the knee joint, are required to reveal the physiologically plausible balance control mechanism implemented by the central nervous system. Copyright © 2014 Elsevier B.V. All rights reserved.

Utility-free heuristic models of two-option choice can mimic predictions of utility-stage models under many conditions

PubMed Central

Piantadosi, Steven T.; Hayden, Benjamin Y.

2015-01-01

Economists often model choices as if decision-makers assign each option a scalar value variable, known as utility, and then select the option with the highest utility. It remains unclear whether as-if utility models describe real mental and neural steps in choice. Although choices alone cannot prove the existence of a utility stage, utility transformations are often taken to provide the most parsimonious or psychologically plausible explanation for choice data. Here, we show that it is possible to mathematically transform a large set of common utility-stage two-option choice models (specifically ones in which dimensions are can be decomposed into additive functions) into a heuristic model (specifically, a dimensional prioritization heuristic) that has no utility computation stage. We then show that under a range of plausible assumptions, both classes of model predict similar neural responses. These results highlight the difficulties in using neuroeconomic data to infer the existence of a value stage in choice. PMID:25914613

511, America's traveler information number. Deployment assistance report #1, Business models and cost considerations

DOT National Transportation Integrated Search

2002-01-01

Business models and cost recovery are the critical factors for determining the sustainability of the traveler information service, and 511. In March 2001 the Policy Committee directed the 511 Working Group to investigate plausible business models and...

A mathematical model for filtration and macromolecule transport across capillary walls.

PubMed

Facchini, L; Bellin, A; Toro, E F

2014-07-01

Metabolic substrates, such as oxygen and glucose, are rapidly delivered to the cells of large organisms through filtration across microvessels walls. Modelling this important process is complicated by the strong coupling between flow and transport equations, which are linked through the osmotic pressure induced by the colloidal plasma proteins. The microvessel wall is a composite media with the internal glycocalyx layer exerting a strong sieving effect on macromolecules, with respect to the external layer composed by the endothelial cells. The physiological structure of the microvessel is represented as the superimposition of two membranes with different properties; the inner membrane represents the glycocalyx, while the outer membrane represents the surrounding endothelial cells. Application of the mass conservation principle and thermodynamic considerations lead to a model composed of two coupled second-order ordinary differential equations for the hydrostatic and osmotic pressures, one, expressing volumetric mass conservation and the other, which is non-linear in the unknown osmotic pressure, expressing macromolecules mass conservation. Despite the complexity of the system, the assumption that the properties of the layers are piece-wise constant allows us to obtain analytical solutions for the two pressures. This solution is in agreement with experimental observations, which contrary to common belief, show that flow reversal cannot occur in steady-state conditions unless the hydrostatic pressure in the lumen drops below physiologically plausible values. The observed variations of the volumetric flux and the solute mass flux in case of a significant reduction of the hydrostatic pressure at the lumen are in qualitative agreement with observed variations during detailed experiments reported in the literature. On the other hand, homogenising the microvessel wall into a single-layer membrane with equivalent properties leads to a very different distribution of pressure across the microvessel walls, not consistent with observations. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of probiotic administration on zebrafish development and reproduction.

PubMed

Carnevali, O; Avella, M A; Gioacchini, G

2013-07-01

As the consumption of probiotics increases worldwide, scientists focus on identifying bacterial strains able to improve human life quality and evidence the biological pathways affected by probiotic treatment. In this review, some recent observations on the effects of changes of microbiota on zebrafish metabolism were discussed. In addition, the effects of Lactobacillus rhamnosus - a component of the human gut microflora - as a diet supplement on Danio rerio were presented. When administered chronically, L. rhamnosus may affect larval development and the physiology of reproductive system in the zebrafish model. It was hypothesized exogenous L. rhamnosus accelerates larval growth and backbone development by acting on insulin-like growth factors-I (igfI) and -II (igfII), peroxisome proliferator activated receptors-α and -β, (pparα,β) vitamin D receptor-α (vdrα) and retinoic acid receptor-γ (rarγ). Gonadal differentiation was anticipated at 6weeks together with a higher expression of gnrh3 at the larval stage when L. rhamnosus was administered throughout development. Moreover, brood stock alimented with a L. rhamnosus-supplemented diet showed better reproductive performances as per follicles development, ovulated oocytes quantification and embryos quality. A plausible involvement of factors such as leptin, and kiss1 and 2 in the improvements was concluded. The observations made on the physiology of female reproduction were correlated with the gene expression of a gigantic number of factors as the aromatase cytochrome p 19 (cyp19a), the vitellogenin (vtg) and the α isoform of the E2 receptor (erα), luteinizing hormone receptor (lhr), 20-β hydroxysteroid dehydrogenase (20β-hsd), membrane progesterone receptors α and β, cyclin B, activinβA1, smad2, transforming growth factor β1 (tgfβ1), growth differentiation factor9 (gdf9) and bone morphogenetic protein15 (bmp15.) A model in which the exogenous L. rhamnosus in the digestive tract of zebrafish from the first days of life through sexual maturation positively influences the physiological performances of zebrafish was evidenced and a number of pathways that might be influenced by the presence of this human probiotic strain were proposed. Copyright © 2013 Elsevier Inc. All rights reserved.

Cranial biomechanics of Diplodocus (Dinosauria, Sauropoda): testing hypotheses of feeding behaviour in an extinct megaherbivore

NASA Astrophysics Data System (ADS)

Young, Mark T.; Rayfield, Emily J.; Holliday, Casey M.; Witmer, Lawrence M.; Button, David J.; Upchurch, Paul; Barrett, Paul M.

2012-08-01

Sauropod dinosaurs were the largest terrestrial herbivores and pushed at the limits of vertebrate biomechanics and physiology. Sauropods exhibit high craniodental diversity in ecosystems where numerous species co-existed, leading to the hypothesis that this biodiversity is linked to niche subdivision driven by ecological specialisation. Here, we quantitatively investigate feeding behaviour hypotheses for the iconic sauropod Diplodocus. Biomechanical modelling, using finite element analysis, was used to examine the performance of the Diplodocus skull. Three feeding behaviours were modelled: muscle-driven static biting, branch stripping and bark stripping. The skull was found to be `over engineered' for static biting, overall experiencing low stress with only the dentition enduring high stress. When branch stripping, the skull, similarly, is under low stress, with little appreciable difference between those models. When simulated for bark stripping, the skull experiences far greater stresses, especially in the teeth and at the jaw joint. Therefore, we refute the bark-stripping hypothesis, while the hypotheses of branch stripping and/or precision biting are both consistent with our findings, showing that branch stripping is a biomechanically plausible feeding behaviour for diplodocids. Interestingly, in all simulations, peak stress is observed in the premaxillary-maxillary `lateral plates', supporting the hypothesis that these structures evolved to dissipate stress induced while feeding. These results lead us to conclude that the aberrant craniodental form of Diplodocus was adapted for food procurement rather than resisting high bite forces.

Cortical Components of Reaction-Time during Perceptual Decisions in Humans.

PubMed

Dmochowski, Jacek P; Norcia, Anthony M

2015-01-01

The mechanisms of perceptual decision-making are frequently studied through measurements of reaction time (RT). Classical sequential-sampling models (SSMs) of decision-making posit RT as the sum of non-overlapping sensory, evidence accumulation, and motor delays. In contrast, recent empirical evidence hints at a continuous-flow paradigm in which multiple motor plans evolve concurrently with the accumulation of sensory evidence. Here we employ a trial-to-trial reliability-based component analysis of encephalographic data acquired during a random-dot motion task to directly image continuous flow in the human brain. We identify three topographically distinct neural sources whose dynamics exhibit contemporaneous ramping to time-of-response, with the rate and duration of ramping discriminating fast and slow responses. Only one of these sources, a parietal component, exhibits dependence on strength-of-evidence. The remaining two components possess topographies consistent with origins in the motor system, and their covariation with RT overlaps in time with the evidence accumulation process. After fitting the behavioral data to a popular SSM, we find that the model decision variable is more closely matched to the combined activity of the three components than to their individual activity. Our results emphasize the role of motor variability in shaping RT distributions on perceptual decision tasks, suggesting that physiologically plausible computational accounts of perceptual decision-making must model the concurrent nature of evidence accumulation and motor planning.

Prediction of renal crystalline size distributions in space using a PBE analytic model. 2. Effect of dietary countermeasures.

PubMed

Kassemi, Mohammad; Thompson, David

2016-09-01

An analytic Population Balance Equation model is used to assess the efficacy of citrate, pyrophosphate, and augmented fluid intake as dietary countermeasures aimed at reducing the risk of renal stone formation for astronauts. The model uses the measured biochemical profile of the astronauts as input and predicts the steady-state size distribution of the nucleating, growing, and agglomerating renal calculi subject to biochemical changes brought about by administration of these dietary countermeasures. Numerical predictions indicate that an increase in citrate levels beyond its average normal ground-based urinary values is beneficial but only to a limited extent. Unfortunately, results also indicate that any decline in the citrate levels during space travel below its normal urinary values on Earth can easily move the astronaut into the stone-forming risk category. Pyrophosphate is found to be an effective inhibitor since numerical predictions indicate that even at quite small urinary concentrations, it has the potential of shifting the maximum crystal aggregate size to a much smaller and plausibly safer range. Finally, our numerical results predict a decline in urinary volume below 1.5 liters/day can act as a dangerous promoter of renal stone development in microgravity while urinary volume levels of 2.5-3 liters/day can serve as effective space countermeasures. Copyright © 2016 the American Physiological Society.

Evaluation of the efficacy and safety of rivaroxaban using a computer model for blood coagulation.

PubMed

Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Kuepfer, Lars; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Lippert, Joerg

2011-04-22

Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration-effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies.

Evaluation of the Efficacy and Safety of Rivaroxaban Using a Computer Model for Blood Coagulation

PubMed Central

Burghaus, Rolf; Coboeken, Katrin; Gaub, Thomas; Kuepfer, Lars; Sensse, Anke; Siegmund, Hans-Ulrich; Weiss, Wolfgang; Mueck, Wolfgang; Lippert, Joerg

2011-01-01

Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery and is in advanced clinical development for the treatment of thromboembolic disorders. Its mechanism of action is antithrombin independent and differs from that of other anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor Xa inhibitor) and dabigatran (a direct thrombin inhibitor). A blood coagulation computer model has been developed, based on several published models and preclinical and clinical data. Unlike previous models, the current model takes into account both the intrinsic and extrinsic pathways of the coagulation cascade, and possesses some unique features, including a blood flow component and a portfolio of drug action mechanisms. This study aimed to use the model to compare the mechanism of action of rivaroxaban with that of warfarin, and to evaluate the efficacy and safety of different rivaroxaban doses with other anticoagulants included in the model. Rather than reproducing known standard clinical measurements, such as the prothrombin time and activated partial thromboplastin time clotting tests, the anticoagulant benchmarking was based on a simulation of physiologically plausible clotting scenarios. Compared with warfarin, rivaroxaban showed a favourable sensitivity for tissue factor concentration inducing clotting, and a steep concentration–effect relationship, rapidly flattening towards higher inhibitor concentrations, both suggesting a broad therapeutic window. The predicted dosing window is highly accordant with the final dose recommendation based upon extensive clinical studies. PMID:21526168

Of paradox and plausibility: the dynamic of change in medical law.

PubMed

Harrington, John

2014-01-01

This article develops a model of change in medical law. Drawing on systems theory, it argues that medical law participates in a dynamic of 'deparadoxification' and 'reparadoxification' whereby the underlying contingency of the law is variously concealed through plausible argumentation, or revealed by critical challenge. Medical law is, thus, thoroughly rhetorical. An examination of the development of the law on abortion and on the sterilization of incompetent adults shows that plausibility is achieved through the deployment of substantive common sense and formal stylistic devices. It is undermined where these elements are shown to be arbitrary and constructed. In conclusion, it is argued that the politics of medical law are constituted by this antagonistic process of establishing and challenging provisionally stable normative regimes. © The Author [2014]. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.

Utilization of Prosodic Information in Syntactic Ambiguity Resolution

PubMed Central

2010-01-01

Two self paced listening experiments examined the role of prosodic phrasing in syntactic ambiguity resolution. In Experiment 1, the stimuli consisted of early closure sentences (e.g., “While the parents watched, the child sang a song.”) containing transitive-biased subordinate verbs paired with plausible direct objects or intransitive-biased subordinate verbs paired with implausible direct objects. Experiment 2 also contained early closure sentences with transitively and intransitive-biased subordinate verbs, but the subordinate verbs were always followed by plausible direct objects. In both experiments, there were two prosodic conditions. In the subject-biased prosodic condition, an intonational phrase boundary marked the clausal boundary following the subordinate verb. In the object-biased prosodic condition, the clause boundary was unmarked. The results indicate that lexical and prosodic cues interact at the subordinate verb and plausibility further affects processing at the ambiguous noun. Results are discussed with respect to models of the role of prosody in sentence comprehension. PMID:20033849

Physiological stress and Hendra virus in flying-foxes (Pteropus spp.), Australia.

PubMed

McMichael, Lee; Edson, Daniel; Smith, Craig; Mayer, David; Smith, Ina; Kopp, Steven; Meers, Joanne; Field, Hume

2017-01-01

Pteropid bats (flying-foxes) are the natural reservoir of Hendra virus, an emergent paramyxovirus responsible for fatal infection in horses and humans in Australia. Pteropus alecto (the Black flying-fox) and the paraphyletic P. conspicillatus (the Spectacled flying-fox) appear to be the primary reservoir hosts. Previous studies have suggested that physiological and ecological factors may underpin infection dynamics in flying-foxes, and subsequent spillover to horses and in turn humans. We sought to examine temporal trends in urinary cortisol concentration in wild Australian flying-fox populations, to elucidate the putative relationship between Hendra virus infection and physiological stress. Pooled and individual urine samples were non-invasively collected from under roosting flying-foxes at two latitudinally disparate regions in the eastern Australian state of Queensland. Hendra virus detection, and (in individual urine samples) sex and species determination were PCR-based. Urinary cortisol measurement used a validated enzyme immunoassay. We found no direct correlation between increased urinary cortisol and Hendra virus excretion, but our findings do suggest a biologically plausible association between low winter temperatures and elevated cortisol levels in P. alecto in the lower latitude Southeast Queensland roosts. We hypothesize an indirect association between low winter temperatures and increased Hendra virus infection and excretion, mediated by the physiological cost of thermoregulation. Our findings and our approach are directly relevant to elaboration of the disease ecology of Nipah virus and other emerging henipaviruses in bats. More broadly, they inform investigation of emerging disease infection dynamics across the wildlife/livestock/human interface.

A mathematical model of diurnal variations in human plasma melatonin levels

NASA Technical Reports Server (NTRS)

Brown, E. N.; Choe, Y.; Shanahan, T. L.; Czeisler, C. A.

1997-01-01

Studies in animals and humans suggest that the diurnal pattern in plasma melatonin levels is due to the hormone's rates of synthesis, circulatory infusion and clearance, circadian control of synthesis onset and offset, environmental lighting conditions, and error in the melatonin immunoassay. A two-dimensional linear differential equation model of the hormone is formulated and is used to analyze plasma melatonin levels in 18 normal healthy male subjects during a constant routine. Recently developed Bayesian statistical procedures are used to incorporate correctly the magnitude of the immunoassay error into the analysis. The estimated parameters [median (range)] were clearance half-life of 23.67 (14.79-59.93) min, synthesis onset time of 2206 (1940-0029), synthesis offset time of 0621 (0246-0817), and maximum N-acetyltransferase activity of 7.17(2.34-17.93) pmol x l(-1) x min(-1). All were in good agreement with values from previous reports. The difference between synthesis offset time and the phase of the core temperature minimum was 1 h 15 min (-4 h 38 min-2 h 43 min). The correlation between synthesis onset and the dim light melatonin onset was 0.93. Our model provides a more physiologically plausible estimate of the melatonin synthesis onset time than that given by the dim light melatonin onset and the first reliable means of estimating the phase of synthesis offset. Our analysis shows that the circadian and pharmacokinetics parameters of melatonin can be reliably estimated from a single model.

A homeostatic-driven turnover remodelling constitutive model for healing in soft tissues

PubMed Central

Gasser, T. Christian; Bellomo, Facundo J.

2016-01-01

Remodelling of soft biological tissue is characterized by interacting biochemical and biomechanical events, which change the tissue's microstructure, and, consequently, its macroscopic mechanical properties. Remodelling is a well-defined stage of the healing process, and aims at recovering or repairing the injured extracellular matrix. Like other physiological processes, remodelling is thought to be driven by homeostasis, i.e. it tends to re-establish the properties of the uninjured tissue. However, homeostasis may never be reached, such that remodelling may also appear as a continuous pathological transformation of diseased tissues during aneurysm expansion, for example. A simple constitutive model for soft biological tissues that regards remodelling as homeostatic-driven turnover is developed. Specifically, the recoverable effective tissue damage, whose rate is the sum of a mechanical damage rate and a healing rate, serves as a scalar internal thermodynamic variable. In order to integrate the biochemical and biomechanical aspects of remodelling, the healing rate is, on the one hand, driven by mechanical stimuli, but, on the other hand, subjected to simple metabolic constraints. The proposed model is formulated in accordance with continuum damage mechanics within an open-system thermodynamics framework. The numerical implementation in an in-house finite-element code is described, particularized for Ogden hyperelasticity. Numerical examples illustrate the basic constitutive characteristics of the model and demonstrate its potential in representing aspects of remodelling of soft tissues. Simulation results are verified for their plausibility, but also validated against reported experimental data. PMID:27009177

A homeostatic-driven turnover remodelling constitutive model for healing in soft tissues.

PubMed

Comellas, Ester; Gasser, T Christian; Bellomo, Facundo J; Oller, Sergio

2016-03-01

Remodelling of soft biological tissue is characterized by interacting biochemical and biomechanical events, which change the tissue's microstructure, and, consequently, its macroscopic mechanical properties. Remodelling is a well-defined stage of the healing process, and aims at recovering or repairing the injured extracellular matrix. Like other physiological processes, remodelling is thought to be driven by homeostasis, i.e. it tends to re-establish the properties of the uninjured tissue. However, homeostasis may never be reached, such that remodelling may also appear as a continuous pathological transformation of diseased tissues during aneurysm expansion, for example. A simple constitutive model for soft biological tissues that regards remodelling as homeostatic-driven turnover is developed. Specifically, the recoverable effective tissue damage, whose rate is the sum of a mechanical damage rate and a healing rate, serves as a scalar internal thermodynamic variable. In order to integrate the biochemical and biomechanical aspects of remodelling, the healing rate is, on the one hand, driven by mechanical stimuli, but, on the other hand, subjected to simple metabolic constraints. The proposed model is formulated in accordance with continuum damage mechanics within an open-system thermodynamics framework. The numerical implementation in an in-house finite-element code is described, particularized for Ogden hyperelasticity. Numerical examples illustrate the basic constitutive characteristics of the model and demonstrate its potential in representing aspects of remodelling of soft tissues. Simulation results are verified for their plausibility, but also validated against reported experimental data. © 2016 The Author(s).

A recurrent network mechanism of time integration in perceptual decisions.

PubMed

Wong, Kong-Fatt; Wang, Xiao-Jing

2006-01-25

Recent physiological studies using behaving monkeys revealed that, in a two-alternative forced-choice visual motion discrimination task, reaction time was correlated with ramping of spike activity of lateral intraparietal cortical neurons. The ramping activity appears to reflect temporal accumulation, on a timescale of hundreds of milliseconds, of sensory evidence before a decision is reached. To elucidate the cellular and circuit basis of such integration times, we developed and investigated a simplified two-variable version of a biophysically realistic cortical network model of decision making. In this model, slow time integration can be achieved robustly if excitatory reverberation is primarily mediated by NMDA receptors; our model with only fast AMPA receptors at recurrent synapses produces decision times that are not comparable with experimental observations. Moreover, we found two distinct modes of network behavior, in which decision computation by winner-take-all competition is instantiated with or without attractor states for working memory. Decision process is closely linked to the local dynamics, in the "decision space" of the system, in the vicinity of an unstable saddle steady state that separates the basins of attraction for the two alternative choices. This picture provides a rigorous and quantitative explanation for the dependence of performance and response time on the degree of task difficulty, and the reason for which reaction times are longer in error trials than in correct trials as observed in the monkey experiment. Our reduced two-variable neural model offers a simple yet biophysically plausible framework for studying perceptual decision making in general.

Semimechanistic Bone Marrow Exhaustion Pharmacokinetic/Pharmacodynamic Model for Chemotherapy-Induced Cumulative Neutropenia.

PubMed

Henrich, Andrea; Joerger, Markus; Kraff, Stefanie; Jaehde, Ulrich; Huisinga, Wilhelm; Kloft, Charlotte; Parra-Guillen, Zinnia Patricia

2017-08-01

Paclitaxel is a commonly used cytotoxic anticancer drug with potentially life-threatening toxicity at therapeutic doses and high interindividual pharmacokinetic variability. Thus, drug and effect monitoring is indicated to control dose-limiting neutropenia. Joerger et al. (2016) developed a dose individualization algorithm based on a pharmacokinetic (PK)/pharmacodynamic (PD) model describing paclitaxel and neutrophil concentrations. Furthermore, the algorithm was prospectively compared in a clinical trial against standard dosing (Central European Society for Anticancer Drug Research Study of Paclitaxel Therapeutic Drug Monitoring; 365 patients, 720 cycles) but did not substantially improve neutropenia. This might be caused by misspecifications in the PK/PD model underlying the algorithm, especially without consideration of the observed cumulative pattern of neutropenia or the platinum-based combination therapy, both impacting neutropenia. This work aimed to externally evaluate the original PK/PD model for potential misspecifications and to refine the PK/PD model while considering the cumulative neutropenia pattern and the combination therapy. An underprediction was observed for the PK (658 samples), the PK parameters, and these parameters were re-estimated using the original estimates as prior information. Neutrophil concentrations (3274 samples) were overpredicted by the PK/PD model, especially for later treatment cycles when the cumulative pattern aggravated neutropenia. Three different modeling approaches (two from the literature and one newly developed) were investigated. The newly developed model, which implemented the bone marrow hypothesis semiphysiologically, was superior. This model further included an additive effect for toxicity of carboplatin combination therapy. Overall, a physiologically plausible PK/PD model was developed that can be used for dose adaptation simulations and prospective studies to further improve paclitaxel/carboplatin combination therapy. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Causal Models of Role Stressor Antecedents and Consequences: The Importance of Occupational Differences.

ERIC Educational Resources Information Center

Bacharach, Samuel; Bamberger, Peter

1992-01-01

Survey data from 215 nurses (10 male) and 430 civil engineers (10 female) supported the plausibility of occupation-specific models (positing direct paths between role stressors, antecedents, and consequences) compared to generic models. A weakness of generic models is the tendency to ignore differences in occupational structure and culture. (SK)

Further Studies into Synthetic Image Generation using CameoSim

DTIC Science & Technology

2011-08-01

preparation of the validation effort a study of BRDF models has been completed, which includes the physical plausibility of models , how measured data...the visible to shortwave infrared. In preparation of the validation effort a study of BRDF models has been completed, which includes the physical...Example..................................................................................................................... 17 4. MODELLING BRDFS

Modelling unsupervised online-learning of artificial grammars: linking implicit and statistical learning.

PubMed

Rohrmeier, Martin A; Cross, Ian

2014-07-01

Humans rapidly learn complex structures in various domains. Findings of above-chance performance of some untrained control groups in artificial grammar learning studies raise questions about the extent to which learning can occur in an untrained, unsupervised testing situation with both correct and incorrect structures. The plausibility of unsupervised online-learning effects was modelled with n-gram, chunking and simple recurrent network models. A novel evaluation framework was applied, which alternates forced binary grammaticality judgments and subsequent learning of the same stimulus. Our results indicate a strong online learning effect for n-gram and chunking models and a weaker effect for simple recurrent network models. Such findings suggest that online learning is a plausible effect of statistical chunk learning that is possible when ungrammatical sequences contain a large proportion of grammatical chunks. Such common effects of continuous statistical learning may underlie statistical and implicit learning paradigms and raise implications for study design and testing methodologies. Copyright © 2014 Elsevier Inc. All rights reserved.

Sulfidic Anion Concentrations on Early Earth for Surficial Origins-of-Life Chemistry.

PubMed

Ranjan, Sukrit; Todd, Zoe R; Sutherland, John D; Sasselov, Dimitar D

2018-04-08

A key challenge in origin-of-life studies is understanding the environmental conditions on early Earth under which abiogenesis occurred. While some constraints do exist (e.g., zircon evidence for surface liquid water), relatively few constraints exist on the abundances of trace chemical species, which are relevant to assessing the plausibility and guiding the development of postulated prebiotic chemical pathways which depend on these species. In this work, we combine literature photochemistry models with simple equilibrium chemistry calculations to place constraints on the plausible range of concentrations of sulfidic anions (HS - , HSO 3 - , SO 3 2- ) available in surficial aquatic reservoirs on early Earth due to outgassing of SO 2 and H 2 S and their dissolution into small shallow surface water reservoirs like lakes. We find that this mechanism could have supplied prebiotically relevant levels of SO 2 -derived anions, but not H 2 S-derived anions. Radiative transfer modeling suggests UV light would have remained abundant on the planet surface for all but the largest volcanic explosions. We apply our results to the case study of the proposed prebiotic reaction network of Patel et al. ( 2015 ) and discuss the implications for improving its prebiotic plausibility. In general, epochs of moderately high volcanism could have been especially conducive to cyanosulfidic prebiotic chemistry. Our work can be similarly applied to assess and improve the prebiotic plausibility of other postulated surficial prebiotic chemistries that are sensitive to sulfidic anions, and our methods adapted to study other atmospherically derived trace species. Key Words: Early Earth-Origin of life-Prebiotic chemistry-Volcanism-UV radiation-Planetary environments. Astrobiology 18, xxx-xxx.

The Variance Reaction Time Model

ERIC Educational Resources Information Center

Sikstrom, Sverker

2004-01-01

The variance reaction time model (VRTM) is proposed to account for various recognition data on reaction time, the mirror effect, receiver-operating-characteristic (ROC) curves, etc. The model is based on simple and plausible assumptions within a neural network: VRTM is a two layer neural network where one layer represents items and one layer…

An Embodied Model for Sensorimotor Grounding and Grounding Transfer: Experiments with Epigenetic Robots

ERIC Educational Resources Information Center

Cangelosi, Angelo; Riga, Thomas

2006-01-01

The grounding of symbols in computational models of linguistic abilities is one of the fundamental properties of psychologically plausible cognitive models. In this article, we present an embodied model for the grounding of language in action based on epigenetic robots. Epigenetic robotics is one of the new cognitive modeling approaches to…

A Method to Estimate the Size and Characteristics of HIV-positive Populations Using an Individual-based Stochastic Simulation Model.

PubMed

Nakagawa, Fumiyo; van Sighem, Ard; Thiebaut, Rodolphe; Smith, Colette; Ratmann, Oliver; Cambiano, Valentina; Albert, Jan; Amato-Gauci, Andrew; Bezemer, Daniela; Campbell, Colin; Commenges, Daniel; Donoghoe, Martin; Ford, Deborah; Kouyos, Roger; Lodwick, Rebecca; Lundgren, Jens; Pantazis, Nikos; Pharris, Anastasia; Quinten, Chantal; Thorne, Claire; Touloumi, Giota; Delpech, Valerie; Phillips, Andrew

2016-03-01

It is important not only to collect epidemiologic data on HIV but to also fully utilize such information to understand the epidemic over time and to help inform and monitor the impact of policies and interventions. We describe and apply a novel method to estimate the size and characteristics of HIV-positive populations. The method was applied to data on men who have sex with men living in the UK and to a pseudo dataset to assess performance for different data availability. The individual-based simulation model was calibrated using an approximate Bayesian computation-based approach. In 2013, 48,310 (90% plausibility range: 39,900-45,560) men who have sex with men were estimated to be living with HIV in the UK, of whom 10,400 (6,160-17,350) were undiagnosed. There were an estimated 3,210 (1,730-5,350) infections per year on average between 2010 and 2013. Sixty-two percent of the total HIV-positive population are thought to have viral load <500 copies/ml. In the pseudo-epidemic example, HIV estimates have narrower plausibility ranges and are closer to the true number, the greater the data availability to calibrate the model. We demonstrate that our method can be applied to settings with less data, however plausibility ranges for estimates will be wider to reflect greater uncertainty of the data used to fit the model.

Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework.

PubMed

Ruiter, Sander; Sippel, Josefine; Bouwmeester, Manon C; Lommelaars, Tobias; Beekhof, Piet; Hodemaekers, Hennie M; Bakker, Frank; van den Brandhof, Evert-Jan; Pennings, Jeroen L A; van der Ven, Leo T M

2016-11-02

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50-3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S -adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes.

Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration

PubMed Central

Dinan, Timothy G.

2016-01-01

Abstract There is a growing realisation that the gut–brain axis and its regulation by the microbiota may play a key role in the biological and physiological basis of neurodevelopmental, age‐related and neurodegenerative disorders. The routes of communication between the microbiota and brain are being unravelled and include the vagus nerve, gut hormone signalling, the immune system, tryptophan metabolism or by way of microbial metabolites such as short chain fatty acids. The importance of early life gut microbiota in shaping future health outcomes is also emerging. Disturbances of this composition by way of antibiotic exposure, lack of breastfeeding, infection, stress and the environmental influences coupled with the influence of host genetics can result in long‐term effects on physiology and behaviour, at least in animal models. It is also worth noting that mode of delivery at birth influences microbiota composition with those born by Caesarean section having a distinctly different microbiota in early life to those born per vaginum. At the other extreme of life, ageing is associated with a narrowing in microbial diversity and healthy ageing correlates with a diverse microbiome. Recently, the gut microbiota has been implicated in a variety of conditions including depression, autism, schizophrenia and Parkinson's disease. There is still considerable debate as to whether or not the gut microbiota changes are core to the pathophysiology of such conditions or are merely epiphenomenal. It is plausible that such neuropsychiatric disorders might be treated in the future by targeting the microbiota either by microbiota transplantation, antibiotics or psychobiotics. PMID:27641441

Heart Rate Variability Reflects the Natural History of Physiological Development in Healthy Children and Is Not Associated with Quality of Life

PubMed Central

Seifert, Georg; Calaminus, Gabriele; Wiener, Andreas; Cysarz, Dirk

2014-01-01

Background Quality of life (QoL), being the sum expression of diverse influencing factors, is not easy to determine. A clinically relevant option would be to identify and measure quality of life on the basis of physiological parameters which correlate plausibly and statistically with psychometrically measured QoL. Analysis of heart rate variability (HRV) offers readily measurable physiological parameters which could be of use here. A correlation of HRV with both course of disease and QoL has been reported in patients with chronic illness. Various psychometric instruments have been developed for use in paediatric oncology. The aim of this study was to obtain data on HRV and QoL and their correlations, initially in healthy children. Methods Holter ECG and quality of life were examined in 160 children and adolescents (72 male) aged between 8 and 18 years. QoL was determined with the established questionnaire PEDQoL. Standard parameters of HRV from the frequency domain were calculated and correlated with QoL domains using Spearman (nonparametric) correlation analysis. Results Minor but significant associations were revealed only with regard to the PEDQoL domain “autonomy” on the one hand and heart rate and HRV (e.g. MRR, MRRn, MRRd, HRV_ULF, SDNN) parameters which evidently reflect distinct physiological functions on the other. Conclusions In healthy children and adolescents we have a first indication that there is a correlation between parameters of HRV and QoL. However, to a greater extent, HRV reflects associated physiological processes of the autonomic nervous system. A higher correlation is more likely to be found in chronically ill children. PMID:24625571

Coincidence detection in the medial superior olive: mechanistic implications of an analysis of input spiking patterns

PubMed Central

Franken, Tom P.; Bremen, Peter; Joris, Philip X.

2014-01-01

Coincidence detection by binaural neurons in the medial superior olive underlies sensitivity to interaural time difference (ITD) and interaural correlation (ρ). It is unclear whether this process is akin to a counting of individual coinciding spikes, or rather to a correlation of membrane potential waveforms resulting from converging inputs from each side. We analyzed spike trains of axons of the cat trapezoid body (TB) and auditory nerve (AN) in a binaural coincidence scheme. ITD was studied by delaying “ipsi-” vs. “contralateral” inputs; ρ was studied by using responses to different noises. We varied the number of inputs; the monaural and binaural threshold and the coincidence window duration. We examined physiological plausibility of output “spike trains” by comparing their rate and tuning to ITD and ρ to those of binaural cells. We found that multiple inputs are required to obtain a plausible output spike rate. In contrast to previous suggestions, monaural threshold almost invariably needed to exceed binaural threshold. Elevation of the binaural threshold to values larger than 2 spikes caused a drastic decrease in rate for a short coincidence window. Longer coincidence windows allowed a lower number of inputs and higher binaural thresholds, but decreased the depth of modulation. Compared to AN fibers, TB fibers allowed higher output spike rates for a low number of inputs, but also generated more monaural coincidences. We conclude that, within the parameter space explored, the temporal patterns of monaural fibers require convergence of multiple inputs to achieve physiological binaural spike rates; that monaural coincidences have to be suppressed relative to binaural ones; and that the neuron has to be sensitive to single binaural coincidences of spikes, for a number of excitatory inputs per side of 10 or less. These findings suggest that the fundamental operation in the mammalian binaural circuit is coincidence counting of single binaural input spikes. PMID:24822037

Macroecological analyses support an overkill scenario for late Pleistocene extinctions.

PubMed

Diniz-Filho, J A F

2004-08-01

The extinction of megafauna at the end of Pleistocene has been traditionally explained by environmental changes or overexploitation by human hunting (overkill). Despite difficulties in choosing between these alternative (and not mutually exclusive) scenarios, the plausibility of the overkill hypothesis can be established by ecological models of predator-prey interactions. In this paper, I have developed a macroecological model for the overkill hypothesis, in which prey population dynamic parameters, including abundance, geographic extent, and food supply for hunters, were derived from empirical allometric relationships with body mass. The last output correctly predicts the final destiny (survival or extinction) for 73% of the species considered, a value only slightly smaller than those obtained by more complex models based on detailed archaeological and ecological data for each species. This illustrates the high selectivity of Pleistocene extinction in relation to body mass and confers more plausibility on the overkill scenario.

Multilevel models for estimating incremental net benefits in multinational studies.

PubMed

Grieve, Richard; Nixon, Richard; Thompson, Simon G; Cairns, John

2007-08-01

Multilevel models (MLMs) have been recommended for estimating incremental net benefits (INBs) in multicentre cost-effectiveness analysis (CEA). However, these models have assumed that the INBs are exchangeable and that there is a common variance across all centres. This paper examines the plausibility of these assumptions by comparing various MLMs for estimating the mean INB in a multinational CEA. The results showed that the MLMs that assumed the INBs were exchangeable and had a common variance led to incorrect inferences. The MLMs that included covariates to allow for systematic differences across the centres, and estimated different variances in each centre, made more plausible assumptions, fitted the data better and led to more appropriate inferences. We conclude that the validity of assumptions underlying MLMs used in CEA need to be critically evaluated before reliable conclusions can be drawn. Copyright 2006 John Wiley & Sons, Ltd.

Strong systematicity through sensorimotor conceptual grounding: an unsupervised, developmental approach to connectionist sentence processing

NASA Astrophysics Data System (ADS)

Jansen, Peter A.; Watter, Scott

2012-03-01

Connectionist language modelling typically has difficulty with syntactic systematicity, or the ability to generalise language learning to untrained sentences. This work develops an unsupervised connectionist model of infant grammar learning. Following the semantic boostrapping hypothesis, the network distils word category using a developmentally plausible infant-scale database of grounded sensorimotor conceptual representations, as well as a biologically plausible semantic co-occurrence activation function. The network then uses this knowledge to acquire an early benchmark clausal grammar using correlational learning, and further acquires separate conceptual and grammatical category representations. The network displays strongly systematic behaviour indicative of the general acquisition of the combinatorial systematicity present in the grounded infant-scale language stream, outperforms previous contemporary models that contain primarily noun and verb word categories, and successfully generalises broadly to novel untrained sensorimotor grounded sentences composed of unfamiliar nouns and verbs. Limitations as well as implications to later grammar learning are discussed.

Modeling Collective Animal Behavior with a Cognitive Perspective: A Methodological Framework

PubMed Central

Weitz, Sebastian; Blanco, Stéphane; Fournier, Richard; Gautrais, Jacques; Jost, Christian; Theraulaz, Guy

2012-01-01

The last decades have seen an increasing interest in modeling collective animal behavior. Some studies try to reproduce as accurately as possible the collective dynamics and patterns observed in several animal groups with biologically plausible, individual behavioral rules. The objective is then essentially to demonstrate that the observed collective features may be the result of self-organizing processes involving quite simple individual behaviors. Other studies concentrate on the objective of establishing or enriching links between collective behavior researches and cognitive or physiological ones, which then requires that each individual rule be carefully validated. Here we discuss the methodological consequences of this additional requirement. Using the example of corpse clustering in ants, we first illustrate that it may be impossible to discriminate among alternative individual rules by considering only observational data collected at the group level. Six individual behavioral models are described: They are clearly distinct in terms of individual behaviors, they all reproduce satisfactorily the collective dynamics and distribution patterns observed in experiments, and we show theoretically that it is strictly impossible to discriminate two of these models even in the limit of an infinite amount of data whatever the accuracy level. A set of methodological steps are then listed and discussed as practical ways to partially overcome this problem. They involve complementary experimental protocols specifically designed to address the behavioral rules successively, conserving group-level data for the overall model validation. In this context, we highlight the importance of maintaining a sharp distinction between model enunciation, with explicit references to validated biological concepts, and formal translation of these concepts in terms of quantitative state variables and fittable functional dependences. Illustrative examples are provided of the benefits expected during the often long and difficult process of refining a behavioral model, designing adapted experimental protocols and inversing model parameters. PMID:22761685

Modeling collective animal behavior with a cognitive perspective: a methodological framework.

PubMed

Weitz, Sebastian; Blanco, Stéphane; Fournier, Richard; Gautrais, Jacques; Jost, Christian; Theraulaz, Guy

2012-01-01

The last decades have seen an increasing interest in modeling collective animal behavior. Some studies try to reproduce as accurately as possible the collective dynamics and patterns observed in several animal groups with biologically plausible, individual behavioral rules. The objective is then essentially to demonstrate that the observed collective features may be the result of self-organizing processes involving quite simple individual behaviors. Other studies concentrate on the objective of establishing or enriching links between collective behavior researches and cognitive or physiological ones, which then requires that each individual rule be carefully validated. Here we discuss the methodological consequences of this additional requirement. Using the example of corpse clustering in ants, we first illustrate that it may be impossible to discriminate among alternative individual rules by considering only observational data collected at the group level. Six individual behavioral models are described: They are clearly distinct in terms of individual behaviors, they all reproduce satisfactorily the collective dynamics and distribution patterns observed in experiments, and we show theoretically that it is strictly impossible to discriminate two of these models even in the limit of an infinite amount of data whatever the accuracy level. A set of methodological steps are then listed and discussed as practical ways to partially overcome this problem. They involve complementary experimental protocols specifically designed to address the behavioral rules successively, conserving group-level data for the overall model validation. In this context, we highlight the importance of maintaining a sharp distinction between model enunciation, with explicit references to validated biological concepts, and formal translation of these concepts in terms of quantitative state variables and fittable functional dependences. Illustrative examples are provided of the benefits expected during the often long and difficult process of refining a behavioral model, designing adapted experimental protocols and inversing model parameters.

NEMA, a functional-structural model of nitrogen economy within wheat culms after flowering. II. Evaluation and sensitivity analysis.

PubMed

Bertheloot, Jessica; Wu, Qiongli; Cournède, Paul-Henry; Andrieu, Bruno

2011-10-01

Simulating nitrogen economy in crop plants requires formalizing the interactions between soil nitrogen availability, root nitrogen acquisition, distribution between vegetative organs and remobilization towards grains. This study evaluates and analyses the functional-structural and mechanistic model of nitrogen economy, NEMA (Nitrogen Economy Model within plant Architecture), developed for winter wheat (Triticum aestivum) after flowering. NEMA was calibrated for field plants under three nitrogen fertilization treatments at flowering. Model behaviour was investigated and sensitivity to parameter values was analysed. Nitrogen content of all photosynthetic organs and in particular nitrogen vertical distribution along the stem and remobilization patterns in response to fertilization were simulated accurately by the model, from Rubisco turnover modulated by light intercepted by the organ and a mobile nitrogen pool. This pool proved to be a reliable indicator of plant nitrogen status, allowing efficient regulation of nitrogen acquisition by roots, remobilization from vegetative organs and accumulation in grains in response to nitrogen treatments. In our simulations, root capacity to import carbon, rather than carbon availability, limited nitrogen acquisition and ultimately nitrogen accumulation in grains, while Rubisco turnover intensity mostly affected dry matter accumulation in grains. NEMA enabled interpretation of several key patterns usually observed in field conditions and the identification of plausible processes limiting for grain yield, protein content and root nitrogen acquisition that could be targets for plant breeding; however, further understanding requires more mechanistic formalization of carbon metabolism. Its strong physiological basis and its realistic behaviour support its use to gain insights into nitrogen economy after flowering.

Using Dirichlet Priors to Improve Model Parameter Plausibility

ERIC Educational Resources Information Center

Rai, Dovan; Gong, Yue; Beck, Joseph E.

2009-01-01

Student modeling is a widely used approach to make inference about a student's attributes like knowledge, learning, etc. If we wish to use these models to analyze and better understand student learning there are two problems. First, a model's ability to predict student performance is at best weakly related to the accuracy of any one of its…

Expanding the Role of Connectionism in SLA Theory

ERIC Educational Resources Information Center

Language Learning, 2013

2013-01-01

In this article, I explore how connectionism might expand its role in second language acquisition (SLA) theory by showing how some symbolic models of bilingual and second language lexical memory can be reduced to a biologically realistic (i.e., neurally plausible) connectionist model. This integration or hybridization of the two models follows the…

A Neurally Plausible Parallel Distributed Processing Model of Event-Related Potential Word Reading Data

ERIC Educational Resources Information Center

Laszlo, Sarah; Plaut, David C.

2012-01-01

The Parallel Distributed Processing (PDP) framework has significant potential for producing models of cognitive tasks that approximate how the brain performs the same tasks. To date, however, there has been relatively little contact between PDP modeling and data from cognitive neuroscience. In an attempt to advance the relationship between…

Efficient design based on perturbed parameter ensembles to identify plausible and diverse variants of a model for climate change projections

NASA Astrophysics Data System (ADS)

Karmalkar, A.; Sexton, D.; Murphy, J.

2017-12-01

We present exploratory work towards developing an efficient strategy to select variants of a state-of-the-art but expensive climate model suitable for climate projection studies. The strategy combines information from a set of idealized perturbed parameter ensemble (PPE) and CMIP5 multi-model ensemble (MME) experiments, and uses two criteria as basis to select model variants for a PPE suitable for future projections: a) acceptable model performance at two different timescales, and b) maintaining diversity in model response to climate change. We demonstrate that there is a strong relationship between model errors at weather and climate timescales for a variety of key variables. This relationship is used to filter out parts of parameter space that do not give credible simulations of historical climate, while minimizing the impact on ranges in forcings and feedbacks that drive model responses to climate change. We use statistical emulation to explore the parameter space thoroughly, and demonstrate that about 90% can be filtered out without affecting diversity in global-scale climate change responses. This leads to identification of plausible parts of parameter space from which model variants can be selected for projection studies.

Efficient reinforcement learning of a reservoir network model of parametric working memory achieved with a cluster population winner-take-all readout mechanism.

PubMed

Cheng, Zhenbo; Deng, Zhidong; Hu, Xiaolin; Zhang, Bo; Yang, Tianming

2015-12-01

The brain often has to make decisions based on information stored in working memory, but the neural circuitry underlying working memory is not fully understood. Many theoretical efforts have been focused on modeling the persistent delay period activity in the prefrontal areas that is believed to represent working memory. Recent experiments reveal that the delay period activity in the prefrontal cortex is neither static nor homogeneous as previously assumed. Models based on reservoir networks have been proposed to model such a dynamical activity pattern. The connections between neurons within a reservoir are random and do not require explicit tuning. Information storage does not depend on the stable states of the network. However, it is not clear how the encoded information can be retrieved for decision making with a biologically realistic algorithm. We therefore built a reservoir-based neural network to model the neuronal responses of the prefrontal cortex in a somatosensory delayed discrimination task. We first illustrate that the neurons in the reservoir exhibit a heterogeneous and dynamical delay period activity observed in previous experiments. Then we show that a cluster population circuit decodes the information from the reservoir with a winner-take-all mechanism and contributes to the decision making. Finally, we show that the model achieves a good performance rapidly by shaping only the readout with reinforcement learning. Our model reproduces important features of previous behavior and neurophysiology data. We illustrate for the first time how task-specific information stored in a reservoir network can be retrieved with a biologically plausible reinforcement learning training scheme. Copyright © 2015 the American Physiological Society.

Parameter and model uncertainty in a life-table model for fine particles (PM2.5): a statistical modeling study

PubMed Central

Tainio, Marko; Tuomisto, Jouni T; Hänninen, Otto; Ruuskanen, Juhani; Jantunen, Matti J; Pekkanen, Juha

2007-01-01

Background The estimation of health impacts involves often uncertain input variables and assumptions which have to be incorporated into the model structure. These uncertainties may have significant effects on the results obtained with model, and, thus, on decision making. Fine particles (PM2.5) are believed to cause major health impacts, and, consequently, uncertainties in their health impact assessment have clear relevance to policy-making. We studied the effects of various uncertain input variables by building a life-table model for fine particles. Methods Life-expectancy of the Helsinki metropolitan area population and the change in life-expectancy due to fine particle exposures were predicted using a life-table model. A number of parameter and model uncertainties were estimated. Sensitivity analysis for input variables was performed by calculating rank-order correlations between input and output variables. The studied model uncertainties were (i) plausibility of mortality outcomes and (ii) lag, and parameter uncertainties (iii) exposure-response coefficients for different mortality outcomes, and (iv) exposure estimates for different age groups. The monetary value of the years-of-life-lost and the relative importance of the uncertainties related to monetary valuation were predicted to compare the relative importance of the monetary valuation on the health effect uncertainties. Results The magnitude of the health effects costs depended mostly on discount rate, exposure-response coefficient, and plausibility of the cardiopulmonary mortality. Other mortality outcomes (lung cancer, other non-accidental and infant mortality) and lag had only minor impact on the output. The results highlight the importance of the uncertainties associated with cardiopulmonary mortality in the fine particle impact assessment when compared with other uncertainties. Conclusion When estimating life-expectancy, the estimates used for cardiopulmonary exposure-response coefficient, discount rate, and plausibility require careful assessment, while complicated lag estimates can be omitted without this having any major effect on the results. PMID:17714598

Parameter and model uncertainty in a life-table model for fine particles (PM2.5): a statistical modeling study.

PubMed

Tainio, Marko; Tuomisto, Jouni T; Hänninen, Otto; Ruuskanen, Juhani; Jantunen, Matti J; Pekkanen, Juha

2007-08-23

The estimation of health impacts involves often uncertain input variables and assumptions which have to be incorporated into the model structure. These uncertainties may have significant effects on the results obtained with model, and, thus, on decision making. Fine particles (PM2.5) are believed to cause major health impacts, and, consequently, uncertainties in their health impact assessment have clear relevance to policy-making. We studied the effects of various uncertain input variables by building a life-table model for fine particles. Life-expectancy of the Helsinki metropolitan area population and the change in life-expectancy due to fine particle exposures were predicted using a life-table model. A number of parameter and model uncertainties were estimated. Sensitivity analysis for input variables was performed by calculating rank-order correlations between input and output variables. The studied model uncertainties were (i) plausibility of mortality outcomes and (ii) lag, and parameter uncertainties (iii) exposure-response coefficients for different mortality outcomes, and (iv) exposure estimates for different age groups. The monetary value of the years-of-life-lost and the relative importance of the uncertainties related to monetary valuation were predicted to compare the relative importance of the monetary valuation on the health effect uncertainties. The magnitude of the health effects costs depended mostly on discount rate, exposure-response coefficient, and plausibility of the cardiopulmonary mortality. Other mortality outcomes (lung cancer, other non-accidental and infant mortality) and lag had only minor impact on the output. The results highlight the importance of the uncertainties associated with cardiopulmonary mortality in the fine particle impact assessment when compared with other uncertainties. When estimating life-expectancy, the estimates used for cardiopulmonary exposure-response coefficient, discount rate, and plausibility require careful assessment, while complicated lag estimates can be omitted without this having any major effect on the results.

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

PubMed

Rivas-Santiago, Bruno; Torres-Juarez, Flor

2018-03-27

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of world health organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the antimicrobial peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cardiac Aging: From Molecular Mechanisms to Significance in Human Health and Disease

PubMed Central

Dai, Dao-Fu; Chen, Tony; Johnson, Simon C.; Szeto, Hazel

2012-01-01

Abstract Cardiovascular diseases (CVDs) are the major causes of death in the western world. The incidence of cardiovascular disease as well as the rate of cardiovascular mortality and morbidity increase exponentially in the elderly population, suggesting that age per se is a major risk factor of CVDs. The physiologic changes of human cardiac aging mainly include left ventricular hypertrophy, diastolic dysfunction, valvular degeneration, increased cardiac fibrosis, increased prevalence of atrial fibrillation, and decreased maximal exercise capacity. Many of these changes are closely recapitulated in animal models commonly used in an aging study, including rodents, flies, and monkeys. The application of genetically modified aged mice has provided direct evidence of several critical molecular mechanisms involved in cardiac aging, such as mitochondrial oxidative stress, insulin/insulin-like growth factor/PI3K pathway, adrenergic and renin angiotensin II signaling, and nutrient signaling pathways. This article also reviews the central role of mitochondrial oxidative stress in CVDs and the plausible mechanisms underlying the progression toward heart failure in the susceptible aging hearts. Finally, the understanding of the molecular mechanisms of cardiac aging may support the potential clinical application of several “anti-aging” strategies that treat CVDs and improve healthy cardiac aging. PMID:22229339

Linking assumptions in amblyopia

PubMed Central

LEVI, DENNIS M.

2017-01-01

Over the last 35 years or so, there has been substantial progress in revealing and characterizing the many interesting and sometimes mysterious sensory abnormalities that accompany amblyopia. A goal of many of the studies has been to try to make the link between the sensory losses and the underlying neural losses, resulting in several hypotheses about the site, nature, and cause of amblyopia. This article reviews some of these hypotheses, and the assumptions that link the sensory losses to specific physiological alterations in the brain. Despite intensive study, it turns out to be quite difficult to make a simple linking hypothesis, at least at the level of single neurons, and the locus of the sensory loss remains elusive. It is now clear that the simplest notion—that reduced contrast sensitivity of neurons in cortical area V1 explains the reduction in contrast sensitivity—is too simplistic. Considerations of noise, noise correlations, pooling, and the weighting of information also play a critically important role in making perceptual decisions, and our current models of amblyopia do not adequately take these into account. Indeed, although the reduction of contrast sensitivity is generally considered to reflect “early” neural changes, it seems plausible that it reflects changes at many stages of visual processing. PMID:23879956

Anatomically constrained dipole adjustment (ANACONDA) for accurate MEG/EEG focal source localizations

NASA Astrophysics Data System (ADS)

Im, Chang-Hwan; Jung, Hyun-Kyo; Fujimaki, Norio

2005-10-01

This paper proposes an alternative approach to enhance localization accuracy of MEG and EEG focal sources. The proposed approach assumes anatomically constrained spatio-temporal dipoles, initial positions of which are estimated from local peak positions of distributed sources obtained from a pre-execution of distributed source reconstruction. The positions of the dipoles are then adjusted on the cortical surface using a novel updating scheme named cortical surface scanning. The proposed approach has many advantages over the conventional ones: (1) as the cortical surface scanning algorithm uses spatio-temporal dipoles, it is robust with respect to noise; (2) it requires no a priori information on the numbers and initial locations of the activations; (3) as the locations of dipoles are restricted only on a tessellated cortical surface, it is physiologically more plausible than the conventional ECD model. To verify the proposed approach, it was applied to several realistic MEG/EEG simulations and practical experiments. From the several case studies, it is concluded that the anatomically constrained dipole adjustment (ANACONDA) approach will be a very promising technique to enhance accuracy of focal source localization which is essential in many clinical and neurological applications of MEG and EEG.

Desynchronization of cells on the developmental path triggers the formation of spiral waves of cAMP during Dictyostelium aggregation.

PubMed

Lauzeral, J; Halloy, J; Goldbeter, A

1997-08-19

Whereas it is relatively easy to account for the formation of concentric (target) waves of cAMP in the course of Dictyostelium discoideum aggregation after starvation, the origin of spiral waves remains obscure. We investigate a physiologically plausible mechanism for the spontaneous formation of spiral waves of cAMP in D. discoideum. The scenario relies on the developmental path associated with the continuous changes in the activity of enzymes such as adenylate cyclase and phosphodiesterase observed during the hours that follow starvation. These changes bring the cells successively from a nonexcitable state to an excitable state in which they relay suprathreshold cAMP pulses, and then to autonomous oscillations of cAMP, before the system returns to an excitable state. By analyzing a model for cAMP signaling based on receptor desensitization, we show that the desynchronization of cells on this developmental path triggers the formation of fully developed spirals of cAMP. Developmental paths that do not correspond to the sequence of dynamic transitions no relay-relay-oscillations-relay are less able or fail to give rise to the formation of spirals.

Desynchronization of cells on the developmental path triggers the formation of spiral waves of cAMP during Dictyostelium aggregation

PubMed Central

Lauzeral, Jacques; Halloy, José; Goldbeter, Albert

1997-01-01

Whereas it is relatively easy to account for the formation of concentric (target) waves of cAMP in the course of Dictyostelium discoideum aggregation after starvation, the origin of spiral waves remains obscure. We investigate a physiologically plausible mechanism for the spontaneous formation of spiral waves of cAMP in D. discoideum. The scenario relies on the developmental path associated with the continuous changes in the activity of enzymes such as adenylate cyclase and phosphodiesterase observed during the hours that follow starvation. These changes bring the cells successively from a nonexcitable state to an excitable state in which they relay suprathreshold cAMP pulses, and then to autonomous oscillations of cAMP, before the system returns to an excitable state. By analyzing a model for cAMP signaling based on receptor desensitization, we show that the desynchronization of cells on this developmental path triggers the formation of fully developed spirals of cAMP. Developmental paths that do not correspond to the sequence of dynamic transitions no relay-relay-oscillations-relay are less able or fail to give rise to the formation of spirals. PMID:9256451

Scenario planning: a tool for academic health sciences libraries.

PubMed

Ludwig, Logan; Giesecke, Joan; Walton, Linda

2010-03-01

Review the International Campaign to Revitalise Academic Medicine (ICRAM) Future Scenarios as a potential starting point for developing scenarios to envisage plausible futures for health sciences libraries. At an educational workshop, 15 groups, each composed of four to seven Association of Academic Health Sciences Libraries (AAHSL) directors and AAHSL/NLM Fellows, created plausible stories using the five ICRAM scenarios. Participants created 15 plausible stories regarding roles played by health sciences librarians, how libraries are used and their physical properties in response to technology, scholarly communication, learning environments and health care economic changes. Libraries are affected by many forces, including economic pressures, curriculum and changes in technology, health care delivery and scholarly communications business models. The future is likely to contain ICRAM scenario elements, although not all, and each, if they come to pass, will impact health sciences libraries. The AAHSL groups identified common features in their scenarios to learn lessons for now. The hope is that other groups find the scenarios useful in thinking about academic health science library futures.

The Central Role of Recognition in Auditory Perception: A Neurobiological Model

ERIC Educational Resources Information Center

McLachlan, Neil; Wilson, Sarah

2010-01-01

The model presents neurobiologically plausible accounts of sound recognition (including absolute pitch), neural plasticity involved in pitch, loudness and location information integration, and streaming and auditory recall. It is proposed that a cortical mechanism for sound identification modulates the spectrotemporal response fields of inferior…

Estimation of slipping organ motion by registration with direction-dependent regularization.

PubMed

Schmidt-Richberg, Alexander; Werner, René; Handels, Heinz; Ehrhardt, Jan

2012-01-01

Accurate estimation of respiratory motion is essential for many applications in medical 4D imaging, for example for radiotherapy of thoracic and abdominal tumors. It is usually done by non-linear registration of image scans at different states of the breathing cycle but without further modeling of specific physiological motion properties. In this context, the accurate computation of respiration-driven lung motion is especially challenging because this organ is sliding along the surrounding tissue during the breathing cycle, leading to discontinuities in the motion field. Without considering this property in the registration model, common intensity-based algorithms cause incorrect estimation along the object boundaries. In this paper, we present a model for incorporating slipping motion in image registration. Extending the common diffusion registration by distinguishing between normal- and tangential-directed motion, we are able to estimate slipping motion at the organ boundaries while preventing gaps and ensuring smooth motion fields inside and outside. We further present an algorithm for a fully automatic detection of discontinuities in the motion field, which does not rely on a prior segmentation of the organ. We evaluate the approach for the estimation of lung motion based on 23 inspiration/expiration pairs of thoracic CT images. The results show a visually more plausible motion estimation. Moreover, the target registration error is quantified using manually defined landmarks and a significant improvement over the standard diffusion regularization is shown. Copyright © 2011 Elsevier B.V. All rights reserved.

Pedestrian evacuation modeling to reduce vehicle use for distant tsunami evacuations in Hawaiʻi

USGS Publications Warehouse

Wood, Nathan J.; Jones, Jamie; Peters, Jeff; Richards, Kevin

2018-01-01

Tsunami waves that arrive hours after generation elsewhere pose logistical challenges to emergency managers due to the perceived abundance of time and inclination of evacuees to use vehicles. We use coastal communities on the island of Oʻahu (Hawaiʻi, USA) to demonstrate regional evacuation modeling that can identify where successful pedestrian-based evacuations are plausible and where vehicle use could be discouraged. The island of Oʻahu has two tsunami-evacuation zones (standard and extreme), which provides the opportunity to examine if recommended travel modes vary based on zone. Geospatial path distance models are applied to estimate population exposure as a function of pedestrian travel time and speed out of evacuation zones. The use of the extreme zone triples the number of residents, employees, and facilities serving at-risk populations that would be encouraged to evacuate and slightly reduces the percentage of residents (98–76%) that could evacuate in less than 15 min at a plausible speed (with similar percentages for employees). Areas with lengthy evacuations are concentrated in the North Shore region for the standard zone but found all around the Oʻahu coastline for the extreme zone. The use of the extreme zone results in a 26% increase in the number of hotel visitors that would be encouraged to evacuate, and a 76% increase in the number of them that may require more than 15 min. Modeling can identify where pedestrian evacuations are plausible; however, there are logistical and behavioral issues that warrant attention before localized evacuation procedures may be realistic.

An exploration of the relationship among valence, fading affect, rehearsal frequency, and memory vividness for past personal events.

PubMed

Lindeman, Meghan I H; Zengel, Bettina; Skowronski, John J

2017-07-01

The affect associated with negative (or unpleasant) memories typically tends to fade faster than the affect associated with positive (or pleasant) memories, a phenomenon called the fading affect bias (FAB). We conducted a study to explore the mechanisms related to the FAB. A retrospective recall procedure was used to obtain three self-report measures (memory vividness, rehearsal frequency, affective fading) for both positive events and negative events. Affect for positive events faded less than affect for negative events, and positive events were recalled more vividly than negative events. The perceived vividness of an event (memory vividness) and the extent to which an event has been rehearsed (rehearsal frequency) were explored as possible mediators of the relation between event valence and affect fading. Additional models conceived of affect fading and rehearsal frequency as contributors to a memory's vividness. Results suggested that memory vividness was a plausible mediator of the relation between an event's valence and affect fading. Rehearsal frequency was also a plausible mediator of this relation, but only via its effects on memory vividness. Additional modelling results suggested that affect fading and rehearsal frequency were both plausible mediators of the relation between an event's valence and the event's rated memory vividness.

Urate as a Physiological Substrate for Myeloperoxidase

PubMed Central

Meotti, Flavia C.; Jameson, Guy N. L.; Turner, Rufus; Harwood, D. Tim; Stockwell, Samantha; Rees, Martin D.; Thomas, Shane R.; Kettle, Anthony J.

2011-01-01

Urate and myeloperoxidase (MPO) are associated with adverse outcomes in cardiovascular disease. In this study, we assessed whether urate is a likely physiological substrate for MPO and if the products of their interaction have the potential to exacerbate inflammation. Urate was readily oxidized by MPO and hydrogen peroxide to 5-hydroxyisourate, which decayed to predominantly allantoin. The redox intermediates of MPO were reduced by urate with rate constants of 4.6 × 105 m−1 s−1 for compound I and 1.7 × 104 m−1 s−1 for compound II. Urate competed with chloride for oxidation by MPO and at hyperuricemic levels is expected to be a substantive substrate for the enzyme. Oxidation of urate promoted super-stoichiometric consumption of glutathione, which indicates that it is converted to a free radical intermediate. In combination with superoxide and hydrogen peroxide, MPO oxidized urate to a reactive hydroperoxide. This would form by addition of superoxide to the urate radical. Urate also enhanced MPO-dependent consumption of nitric oxide. In human plasma, stimulated neutrophils produced allantoin in a reaction dependent on the NADPH oxidase, MPO and superoxide. We propose that urate is a physiological substrate for MPO that is oxidized to the urate radical. The reactions of this radical with superoxide and nitric oxide provide a plausible link between urate and MPO in cardiovascular disease. PMID:21266577

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seager, S.; Bains, W.; Hu, R.

Biosignature gas detection is one of the ultimate future goals for exoplanet atmosphere studies. We have created a framework for linking biosignature gas detectability to biomass estimates, including atmospheric photochemistry and biological thermodynamics. The new framework is intended to liberate predictive atmosphere models from requiring fixed, Earth-like biosignature gas source fluxes. New biosignature gases can be considered with a check that the biomass estimate is physically plausible. We have validated the models on terrestrial production of NO, H{sub 2}S, CH{sub 4}, CH{sub 3}Cl, and DMS. We have applied the models to propose NH{sub 3} as a biosignature gas on amore » 'cold Haber World', a planet with a N{sub 2}-H{sub 2} atmosphere, and to demonstrate why gases such as CH{sub 3}Cl must have too large of a biomass to be a plausible biosignature gas on planets with Earth or early-Earth-like atmospheres orbiting a Sun-like star. To construct the biomass models, we developed a functional classification of biosignature gases, and found that gases (such as CH{sub 4}, H{sub 2}S, and N{sub 2}O) produced from life that extracts energy from chemical potential energy gradients will always have false positives because geochemistry has the same gases to work with as life does, and gases (such as DMS and CH{sub 3}Cl) produced for secondary metabolic reasons are far less likely to have false positives but because of their highly specialized origin are more likely to be produced in small quantities. The biomass model estimates are valid to one or two orders of magnitude; the goal is an independent approach to testing whether a biosignature gas is plausible rather than a precise quantification of atmospheric biosignature gases and their corresponding biomasses.« less

Vectorial Representations of Meaning for a Computational Model of Language Comprehension

ERIC Educational Resources Information Center

Wu, Stephen Tze-Inn

2010-01-01

This thesis aims to define and extend a line of computational models for text comprehension that are humanly plausible. Since natural language is human by nature, computational models of human language will always be just that--models. To the degree that they miss out on information that humans would tap into, they may be improved by considering…

Resolving Conflicts Between Syntax and Plausibility in Sentence Comprehension

PubMed Central

Andrews, Glenda; Ogden, Jessica E.; Halford, Graeme S.

2017-01-01

Comprehension of plausible and implausible object- and subject-relative clause sentences with and without prepositional phrases was examined. Undergraduates read each sentence then evaluated a statement as consistent or inconsistent with the sentence. Higher acceptance of consistent than inconsistent statements indicated reliance on syntactic analysis. Higher acceptance of plausible than implausible statements reflected reliance on semantic plausibility. There was greater reliance on semantic plausibility and lesser reliance on syntactic analysis for more complex object-relatives and sentences with prepositional phrases than for less complex subject-relatives and sentences without prepositional phrases. Comprehension accuracy and confidence were lower when syntactic analysis and semantic plausibility yielded conflicting interpretations. The conflict effect on comprehension was significant for complex sentences but not for less complex sentences. Working memory capacity predicted resolution of the syntax-plausibility conflict in more and less complex items only when sentences and statements were presented sequentially. Fluid intelligence predicted resolution of the conflict in more and less complex items under sequential and simultaneous presentation. Domain-general processes appear to be involved in resolving syntax-plausibility conflicts in sentence comprehension. PMID:28458748

Counterfactual Plausibility and Comparative Similarity.

PubMed

Stanley, Matthew L; Stewart, Gregory W; Brigard, Felipe De

2017-05-01

Counterfactual thinking involves imagining hypothetical alternatives to reality. Philosopher David Lewis (1973, 1979) argued that people estimate the subjective plausibility that a counterfactual event might have occurred by comparing an imagined possible world in which the counterfactual statement is true against the current, actual world in which the counterfactual statement is false. Accordingly, counterfactuals considered to be true in possible worlds comparatively more similar to ours are judged as more plausible than counterfactuals deemed true in possible worlds comparatively less similar. Although Lewis did not originally develop his notion of comparative similarity to be investigated as a psychological construct, this study builds upon his idea to empirically investigate comparative similarity as a possible psychological strategy for evaluating the perceived plausibility of counterfactual events. More specifically, we evaluate judgments of comparative similarity between episodic memories and episodic counterfactual events as a factor influencing people's judgments of plausibility in counterfactual simulations, and we also compare it against other factors thought to influence judgments of counterfactual plausibility, such as ease of simulation and prior simulation. Our results suggest that the greater the perceived similarity between the original memory and the episodic counterfactual event, the greater the perceived plausibility that the counterfactual event might have occurred. While similarity between actual and counterfactual events, ease of imagining, and prior simulation of the counterfactual event were all significantly related to counterfactual plausibility, comparative similarity best captured the variance in ratings of counterfactual plausibility. Implications for existing theories on the determinants of counterfactual plausibility are discussed. Copyright © 2016 Cognitive Science Society, Inc.

The impact of variation in scaling factors on the estimation of ...

EPA Pesticide Factsheets

Many physiologically based pharmacokinetic (PBPK) models include values for metabolic rate parameters extrapolated from in vitro metabolism studies using scaling factors such as mg of microsomal protein per gram of liver (MPPGL) and liver mass (FVL). Variation in scaling factor values impacts metabolic rate parameter estimates (Vmax) and hence estimates of internal dose used in dose response analysis. The impacts of adult human variation in MPPGL and FVL on estimates of internal dose were assessed using a human PBPK model for BDCM for several internal dose metrics for two exposure scenarios (single 0.25 liter drink of water or 10 minute shower) under plausible (5 micrograms/L) and high level (20 micrograms/L) water concentrations. For both concentrations, all internal dose metrics were changed less than 5% for the showering scenario (combined inhalation and dermal exposure). In contrast, a 27-fold variation in area under the curve for BDCM in venous blood was observed at both oral exposure concentrations, whereas total amount of BDCM metabolized in liver was relatively unchanged. This analysis demonstrates that variability in the scaling factors used for in vitro to in vivo extrapolation (IVIVE) for metabolic rate parameters can have a significant route-dependent impact on estimates of internal dose under environmentally relevant exposure scenarios. This indicates the need to evaluate both uncertainty and variability for scaling factors used for IVIVE. Sca

Boosting for detection of gene-environment interactions.

PubMed

Pashova, H; LeBlanc, M; Kooperberg, C

2013-01-30

In genetic association studies, it is typically thought that genetic variants and environmental variables jointly will explain more of the inheritance of a phenotype than either of these two components separately. Traditional methods to identify gene-environment interactions typically consider only one measured environmental variable at a time. However, in practice, multiple environmental factors may each be imprecise surrogates for the underlying physiological process that actually interacts with the genetic factors. In this paper, we develop a variant of L(2) boosting that is specifically designed to identify combinations of environmental variables that jointly modify the effect of a gene on a phenotype. Because the effect modifiers might have a small signal compared with the main effects, working in a space that is orthogonal to the main predictors allows us to focus on the interaction space. In a simulation study that investigates some plausible underlying model assumptions, our method outperforms the least absolute shrinkage and selection and Akaike Information Criterion and Bayesian Information Criterion model selection procedures as having the lowest test error. In an example for the Women's Health Initiative-Population Architecture using Genomics and Epidemiology study, the dedicated boosting method was able to pick out two single-nucleotide polymorphisms for which effect modification appears present. The performance was evaluated on an independent test set, and the results are promising. Copyright © 2012 John Wiley & Sons, Ltd.

Stochastic modelling suggests that an elevated superoxide anion - hydrogen peroxide ratio can drive extravascular phagocyte transmigration by lamellipodium formation.

PubMed

Kundu, Siddhartha

2016-10-21

Chemotaxis, integrates diverse intra- and inter-cellular molecular processes into a purposeful patho-physiological response; the operatic rules of which, remain speculative. Here, I surmise, that superoxide anion induced directional motility, in a responding cell, results from a quasi pathway between the stimulus, surrounding interstitium, and its biochemical repertoire. The epochal event in the mounting of an inflammatory response, is the extravascular transmigration of a phagocyte competent cell towards the site of injury, secondary to the development of a lamellipodium. This stochastic-to-markovian process conversion, is initiated by the cytosolic-ROS of the damaged cell, but is maintained by the inverse association of a de novo generated pool of self-sustaining superoxide anions and sub-critical hydrogen peroxide levels. Whilst, the exponential rise of O2(.-) is secondary to the focal accumulation of higher order lipid raft-Rac1/2-actin oligomers; O2(.-) mediated inactivation and redistribution of ECSOD, accounts for the minimal concentration of H2O2 that the phagocyte experiences. The net result of this reciprocal association between ROS/ RNS members, is the prolonged perturbation and remodeling of the cytoskeleton and plasma membrane, a prelude to chemotactic migration. The manuscript also describes the significance of stochastic modeling, in the testing of plausible molecular hypotheses of observable phenomena in complex biological systems. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Synchronization Account of False Recognition

ERIC Educational Resources Information Center

Johns, Brendan T.; Jones, Michael N.; Mewhort, Douglas J. K.

2012-01-01

We describe a computational model to explain a variety of results in both standard and false recognition. A key attribute of the model is that it uses plausible semantic representations for words, built through exposure to a linguistic corpus. A study list is encoded in the model as a gist trace, similar to the proposal of fuzzy trace theory…

New Views of the Moon's Spin

NASA Astrophysics Data System (ADS)

Keane, J. T.; Johnson, B. C.; Matsuyama, I.; Siegler, M. A.

2018-04-01

New geophysical data and numerical models reveal that basin-scale impacts routinely caused the Moon to tumble (non principal axis rotation) early in its history — plausibly driving magnetic fields, erasing primordial volatiles, and more.

MODELING HEXAVALENT CHROMIUM REDUCTION IN GROUND- WATER IN FIELD-SCALE TRANSPORT AND LABORATORY BATCH EXPERIMENTS

EPA Science Inventory

A plausible and consistent model is developed to obtain a quantitative description of the gradual disappearance of hexavalent chromium (Cr(VI)) from groundwater in a small-scale field tracer test and in batch kinetic experiments using aquifer sediments under similar chemical cond...

MODELING WILDLIFE RESPONSE TO LANDSCAPE CHANGE IN OREGON'S WILLAMETTE RIVER BASIN

EPA Science Inventory

The PATCH simulation model was used to predict the response of 17 wildlife species to
three plausible scenarios of habitat change in Oregon's Willamette River Basin. This 30
thousand square-kilometer basin comprises about 12% of the state of Oregon, encompasses extensive f...

MRI Proton Density Fat Fraction Is Robust Across the Biologically Plausible Range of Triglyceride Spectra in Adults With Nonalcoholic Steatohepatitis

PubMed Central

Hong, Cheng William; Mamidipalli, Adrija; Hooker, Jonathan C.; Hamilton, Gavin; Wolfson, Tanya; Chen, Dennis H.; Dehkordy, Soudabeh Fazeli; Middleton, Michael S.; Reeder, Scott B.; Loomba, Rohit; Sirlin, Claude B.

2017-01-01

Background Proton density fat fraction (PDFF) estimation requires spectral modeling of the hepatic triglyceride (TG) signal. Deviations in the TG spectrum may occur, leading to bias in PDFF quantification. Purpose To investigate the effects of varying six-peak TG spectral models on PDFF estimation bias. Study Type Retrospective secondary analysis of prospectively acquired clinical research data. Population Forty-four adults with biopsy-confirmed nonalcoholic steatohepatitis. Field Strength/Sequence Confounder-corrected chemical-shift-encoded 3T MRI (using a 2D multiecho gradient-recalled echo technique with magnitude reconstruction) and MR spectroscopy. Assessment In each patient, 61 pairs of colocalized MRI-PDFF and MRS-PDFF values were estimated: one pair used the standard six-peak spectral model, the other 60 were six-peak variants calculated by adjusting spectral model parameters over their biologically plausible ranges. MRI-PDFF values calculated using each variant model and the standard model were compared, and the agreement between MRI-PDFF and MRS-PDFF was assessed. Statistical Tests MRS-PDFF and MRI-PDFF were summarized descriptively. Bland–Altman (BA) analyses were performed between PDFF values calculated using each variant model and the standard model. Linear regressions were performed between BA biases and mean PDFF values for each variant model, and between MRI-PDFF and MRS-PDFF. Results Using the standard model, mean MRS-PDFF of the study population was 17.9±8.0% (range: 4.1–34.3%). The difference between the highest and lowest mean variant MRI-PDFF values was 1.5%. Relative to the standard model, the model with the greatest absolute BA bias overestimated PDFF by 1.2%. Bias increased with increasing PDFF (P < 0.0001 for 59 of the 60 variant models). MRI-PDFF and MRS-PDFF agreed closely for all variant models (R2=0.980, P < 0.0001). Data Conclusion Over a wide range of hepatic fat content, PDFF estimation is robust across the biologically plausible range of TG spectra. Although absolute estimation bias increased with higher PDFF, its magnitude was small and unlikely to be clinically meaningful. Level of Evidence 3 Technical Efficacy Stage 2 PMID:28851124

A combined model of sensory and cognitive representations underlying tonal expectations in music: from audio signals to behavior.

PubMed

Collins, Tom; Tillmann, Barbara; Barrett, Frederick S; Delbé, Charles; Janata, Petr

2014-01-01

Listeners' expectations for melodies and harmonies in tonal music are perhaps the most studied aspect of music cognition. Long debated has been whether faster response times (RTs) to more strongly primed events (in a music theoretic sense) are driven by sensory or cognitive mechanisms, such as repetition of sensory information or activation of cognitive schemata that reflect learned tonal knowledge, respectively. We analyzed over 300 stimuli from 7 priming experiments comprising a broad range of musical material, using a model that transforms raw audio signals through a series of plausible physiological and psychological representations spanning a sensory-cognitive continuum. We show that RTs are modeled, in part, by information in periodicity pitch distributions, chroma vectors, and activations of tonal space--a representation on a toroidal surface of the major/minor key relationships in Western tonal music. We show that in tonal space, melodies are grouped by their tonal rather than timbral properties, whereas the reverse is true for the periodicity pitch representation. While tonal space variables explained more of the variation in RTs than did periodicity pitch variables, suggesting a greater contribution of cognitive influences to tonal expectation, a stepwise selection model contained variables from both representations and successfully explained the pattern of RTs across stimulus categories in 4 of the 7 experiments. The addition of closure--a cognitive representation of a specific syntactic relationship--succeeded in explaining results from all 7 experiments. We conclude that multiple representational stages along a sensory-cognitive continuum combine to shape tonal expectations in music. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Robust encoding of stimulus identity and concentration in the accessory olfactory system.

PubMed

Arnson, Hannah A; Holy, Timothy E

2013-08-14

Sensory systems represent stimulus identity and intensity, but in the neural periphery these two variables are typically intertwined. Moreover, stable detection may be complicated by environmental uncertainty; stimulus properties can differ over time and circumstance in ways that are not necessarily biologically relevant. We explored these issues in the context of the mouse accessory olfactory system, which specializes in detection of chemical social cues and infers myriad aspects of the identity and physiological state of conspecifics from complex mixtures, such as urine. Using mixtures of sulfated steroids, key constituents of urine, we found that spiking responses of individual vomeronasal sensory neurons encode both individual compounds and mixtures in a manner consistent with a simple model of receptor-ligand interactions. Although typical neurons did not accurately encode concentration over a large dynamic range, from population activity it was possible to reliably estimate the log-concentration of pure compounds over several orders of magnitude. For binary mixtures, simple models failed to accurately segment the individual components, largely because of the prevalence of neurons responsive to both components. By accounting for such overlaps during model tuning, we show that, from neuronal firing, one can accurately estimate log-concentration of both components, even when tested across widely varying concentrations. With this foundation, the difference of logarithms, log A - log B = log A/B, provides a natural mechanism to accurately estimate concentration ratios. Thus, we show that a biophysically plausible circuit model can reconstruct concentration ratios from observed neuronal firing, representing a powerful mechanism to separate stimulus identity from absolute concentration.

Application of decision-making theory to the regulation of muscular work rate during self-paced competitive endurance activity.

PubMed

Renfree, Andrew; Martin, Louise; Micklewright, Dominic; St Clair Gibson, Alan

2014-02-01

Successful participation in competitive endurance activities requires continual regulation of muscular work rate in order to maximise physiological performance capacities, meaning that individuals must make numerous decisions with regards to the muscular work rate selected at any point in time. Decisions relating to the setting of appropriate goals and the overall strategic approach to be utilised are made prior to the commencement of an event, whereas tactical decisions are made during the event itself. This review examines current theories of decision-making in an attempt to explain the manner in which regulation of muscular work is achieved during athletic activity. We describe rational and heuristic theories, and relate these to current models of regulatory processes during self-paced exercise in an attempt to explain observations made in both laboratory and competitive environments. Additionally, we use rational and heuristic theories in an attempt to explain the influence of the presence of direct competitors on the quality of the decisions made during these activities. We hypothesise that although both rational and heuristic models can plausibly explain many observed behaviours in competitive endurance activities, the complexity of the environment in which such activities occur would imply that effective rational decision-making is unlikely. However, at present, many proposed models of the regulatory process share similarities with rational models. We suggest enhanced understanding of the decision-making process during self-paced activities is crucial in order to improve the ability to understand regulation of performance and performance outcomes during athletic activity.

Plausibility and parameter sensitivity of micro-finite element-based joint load prediction at the proximal femur.

PubMed

Synek, Alexander; Pahr, Dieter H

2018-06-01

A micro-finite element-based method to estimate the bone loading history based on bone architecture was recently presented in the literature. However, a thorough investigation of the parameter sensitivity and plausibility of this method to predict joint loads is still missing. The goals of this study were (1) to analyse the parameter sensitivity of the joint load predictions at one proximal femur and (2) to assess the plausibility of the results by comparing load predictions of ten proximal femora to in vivo hip joint forces measured with instrumented prostheses (available from www.orthoload.com ). Joint loads were predicted by optimally scaling the magnitude of four unit loads (inclined [Formula: see text] to [Formula: see text] with respect to the vertical axis) applied to micro-finite element models created from high-resolution computed tomography scans ([Formula: see text]m voxel size). Parameter sensitivity analysis was performed by varying a total of nine parameters and showed that predictions of the peak load directions (range 10[Formula: see text]-[Formula: see text]) are more robust than the predicted peak load magnitudes (range 2344.8-4689.5 N). Comparing the results of all ten femora with the in vivo loading data of ten subjects showed that peak loads are plausible both in terms of the load direction (in vivo: [Formula: see text], predicted: [Formula: see text]) and magnitude (in vivo: [Formula: see text], predicted: [Formula: see text]). Overall, this study suggests that micro-finite element-based joint load predictions are both plausible and robust in terms of the predicted peak load direction, but predicted load magnitudes should be interpreted with caution.

Newberry Volcano EGS Demonstration Stimulation Modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trenton T. Cladouhos, Matthew Clyne, Maisie Nichols,; Susan Petty, William L. Osborn, Laura Nofziger

2011-10-23

As a part of Phase I of the Newberry Volcano EGS Demonstration project, several data sets were collected to characterize the rock volume around the well. Fracture, fault, stress, and seismicity data has been collected by borehole televiewer, LiDAR elevation maps, and microseismic monitoring. Well logs and cuttings from the target well (NWG 55-29) and core from a nearby core hole (USGS N-2) have been analyzed to develop geothermal, geochemical, mineralogical and strength models of the rock matrix, altered zones, and fracture fillings (see Osborn et al., this volume). These characterization data sets provide inputs to models used to planmore » and predict EGS reservoir creation and productivity. One model used is AltaStim, a stochastic fracture and flow software model developed by AltaRock. The software's purpose is to model and visualize EGS stimulation scenarios and provide guidance for final planning. The process of creating an AltaStim model requires synthesis of geologic observations at the well, the modeled stress conditions, and the stimulation plan. Any geomechanical model of an EGS stimulation will require many assumptions and unknowns; thus, the model developed here should not be considered a definitive prediction, but a plausible outcome given reasonable assumptions. AltaStim is a tool for understanding the effect of known constraints, assumptions, and conceptual models on plausible outcomes.« less

COLLABORATION ON NHEERL EPIDEMIOLOGY STUDIES

EPA Science Inventory

This task will continue ORD's efforts to develop a biologically plausible, quantitative health risk model for particulate matter (PM) based on epidemiological, toxicological, and mechanistic studies using matched exposure assessments. The NERL, in collaboration with the NHEERL, ...

When plausibility manipulations work: an examination of their role in the development of false beliefs and memories.

PubMed

Bays, Rebecca B; Zabrucky, Karen M; Gagne, Phill

2012-01-01

In the current study we examined whether prevalence information and imagery encoding influence participants' general plausibility, personal plausibility, belief, and memory ratings for suggested childhood events. Results showed decreases in general and personal plausibility ratings for low prevalence events when encoding instructions were not elaborate; however, instructions to repeatedly imagine suggested events elicited personal plausibility increases for low-prevalence events, evidence that elaborate imagery negated the effect of our prevalence manipulation. We found no evidence of imagination inflation or false memory construction. We discuss critical differences in researchers' manipulations of plausibility and imagery that may influence results of false memory studies in the literature. In future research investigators should focus on the specific nature of encoding instructions when examining the development of false memories.

Real-time physics-based 3D biped character animation using an inverted pendulum model.

PubMed

Tsai, Yao-Yang; Lin, Wen-Chieh; Cheng, Kuangyou B; Lee, Jehee; Lee, Tong-Yee

2010-01-01

We present a physics-based approach to generate 3D biped character animation that can react to dynamical environments in real time. Our approach utilizes an inverted pendulum model to online adjust the desired motion trajectory from the input motion capture data. This online adjustment produces a physically plausible motion trajectory adapted to dynamic environments, which is then used as the desired motion for the motion controllers to track in dynamics simulation. Rather than using Proportional-Derivative controllers whose parameters usually cannot be easily set, our motion tracking adopts a velocity-driven method which computes joint torques based on the desired joint angular velocities. Physically correct full-body motion of the 3D character is computed in dynamics simulation using the computed torques and dynamical model of the character. Our experiments demonstrate that tracking motion capture data with real-time response animation can be achieved easily. In addition, physically plausible motion style editing, automatic motion transition, and motion adaptation to different limb sizes can also be generated without difficulty.

The Prospects of Whole Brain Emulation within the next Half- Century

NASA Astrophysics Data System (ADS)

Eth, Daniel; Foust, Juan-Carlos; Whale, Brandon

2013-12-01

Whole Brain Emulation (WBE), the theoretical technology of modeling a human brain in its entirety on a computer-thoughts, feelings, memories, and skills intact-is a staple of science fiction. Recently, proponents of WBE have suggested that it will be realized in the next few decades. In this paper, we investigate the plausibility of WBE being developed in the next 50 years (by 2063). We identify four essential requisite technologies: scanning the brain, translating the scan into a model, running the model on a computer, and simulating an environment and body. Additionally, we consider the cultural and social effects of WBE. We find the two most uncertain factors for WBE's future to be the development of advanced miniscule probes that can amass neural data in vivo and the degree to which the culture surrounding WBE becomes cooperative or competitive. We identify four plausible scenarios from these uncertainties and suggest the most likely scenario to be one in which WBE is realized, and the technology is used for moderately cooperative ends

Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework

PubMed Central

Ruiter, Sander; Sippel, Josefine; Bouwmeester, Manon C.; Lommelaars, Tobias; Beekhof, Piet; Hodemaekers, Hennie M.; Bakker, Frank; van den Brandhof, Evert-Jan; Pennings, Jeroen L. A.; van der Ven, Leo T. M.

2016-01-01

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50–3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S-adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes. PMID:27827847

Role Stress Revisited: Job Structuring Antecedents, Work Outcomes, and Moderating Effects of Locus of Control

ERIC Educational Resources Information Center

Conley, Sharon; You, Sukkyung

2014-01-01

A previous study examined role stress in relation to work outcomes; in this study, we added job structuring antecedents to a model of role stress and examined the moderating effects of locus of control. Structural equation modeling was used to assess the plausibility of our conceptual model, which specified hypothesized linkages among teachers'…

Investigating the Theoretical Structure of the DAS-II Core Battery at School Age Using Bayesian Structural Equation Modeling

ERIC Educational Resources Information Center

Dombrowski, Stefan C.; Golay, Philippe; McGill, Ryan J.; Canivez, Gary L.

2018-01-01

Bayesian structural equation modeling (BSEM) was used to investigate the latent structure of the Differential Ability Scales-Second Edition core battery using the standardization sample normative data for ages 7-17. Results revealed plausibility of a three-factor model, consistent with publisher theory, expressed as either a higher-order (HO) or a…

Force-induced bone growth and adaptation: A system theoretical approach to understanding bone mechanotransduction

NASA Astrophysics Data System (ADS)

Maldonado, Solvey; Findeisen, Rolf

2010-06-01

The modeling, analysis, and design of treatment therapies for bone disorders based on the paradigm of force-induced bone growth and adaptation is a challenging task. Mathematical models provide, in comparison to clinical, medical and biological approaches an structured alternative framework to understand the concurrent effects of the multiple factors involved in bone remodeling. By now, there are few mathematical models describing the appearing complex interactions. However, the resulting models are complex and difficult to analyze, due to the strong nonlinearities appearing in the equations, the wide range of variability of the states, and the uncertainties in parameters. In this work, we focus on analyzing the effects of changes in model structure and parameters/inputs variations on the overall steady state behavior using systems theoretical methods. Based on an briefly reviewed existing model that describes force-induced bone adaptation, the main objective of this work is to analyze the stationary behavior and to identify plausible treatment targets for remodeling related bone disorders. Identifying plausible targets can help in the development of optimal treatments combining both physical activity and drug-medication. Such treatments help to improve/maintain/restore bone strength, which deteriorates under bone disorder conditions, such as estrogen deficiency.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farrell, Kathryn, E-mail: kfarrell@ices.utexas.edu; Oden, J. Tinsley, E-mail: oden@ices.utexas.edu; Faghihi, Danial, E-mail: danial@ices.utexas.edu

A general adaptive modeling algorithm for selection and validation of coarse-grained models of atomistic systems is presented. A Bayesian framework is developed to address uncertainties in parameters, data, and model selection. Algorithms for computing output sensitivities to parameter variances, model evidence and posterior model plausibilities for given data, and for computing what are referred to as Occam Categories in reference to a rough measure of model simplicity, make up components of the overall approach. Computational results are provided for representative applications.

Delinquency, Social Skills and the Structure of Peer Relations: Assessing Criminological Theories by Social Network Theory

ERIC Educational Resources Information Center

Smangs, Mattias

2010-01-01

This article explores the plausibility of the conflicting theoretical assumptions underlying the main criminological perspectives on juvenile delinquents, their peer relations and social skills: the social ability model, represented by Sutherland's theory of differential associations, and the social disability model, represented by Hirschi's…

Exemplar-Based Clustering via Simulated Annealing

ERIC Educational Resources Information Center

Brusco, Michael J.; Kohn, Hans-Friedrich

2009-01-01

Several authors have touted the p-median model as a plausible alternative to within-cluster sums of squares (i.e., K-means) partitioning. Purported advantages of the p-median model include the provision of "exemplars" as cluster centers, robustness with respect to outliers, and the accommodation of a diverse range of similarity data. We developed…

Conductive Critical Thinking

ERIC Educational Resources Information Center

Paetkau, Mark

2007-01-01

One of my goals as an instructor is to teach students critical thinking skills. This paper presents an example of a student-led discussion of heat conduction at the first-year level. Heat loss from a human head is calculated using conduction and radiation models. The results of these plausible (but wrong) models of heat transfer contradict what…

A model of proto-object based saliency

PubMed Central

Russell, Alexander F.; Mihalaş, Stefan; von der Heydt, Rudiger; Niebur, Ernst; Etienne-Cummings, Ralph

2013-01-01

Organisms use the process of selective attention to optimally allocate their computational resources to the instantaneously most relevant subsets of a visual scene, ensuring that they can parse the scene in real time. Many models of bottom-up attentional selection assume that elementary image features, like intensity, color and orientation, attract attention. Gestalt psychologists, how-ever, argue that humans perceive whole objects before they analyze individual features. This is supported by recent psychophysical studies that show that objects predict eye-fixations better than features. In this report we present a neurally inspired algorithm of object based, bottom-up attention. The model rivals the performance of state of the art non-biologically plausible feature based algorithms (and outperforms biologically plausible feature based algorithms) in its ability to predict perceptual saliency (eye fixations and subjective interest points) in natural scenes. The model achieves this by computing saliency as a function of proto-objects that establish the perceptual organization of the scene. All computational mechanisms of the algorithm have direct neural correlates, and our results provide evidence for the interface theory of attention. PMID:24184601

Single variant bottleneck in the early dynamics of H. influenzae bacteremia in neonatal rats questions the theory of independent action

NASA Astrophysics Data System (ADS)

Shao, Xinxian; Levin, Bruce; Nemenman, Ilya

2017-08-01

There is an abundance of information about the genetic basis, physiological and molecular mechanisms of bacterial pathogenesis. In contrast, relatively little is known about population dynamic processes, by which bacteria colonize hosts and invade tissues and cells and thereby cause disease. In an article published in 1978, Moxon and Murphy presented evidence that, when inoculated intranasally with a mixture streptomycin sensitive and resistant (Sm S and Sm R ) and otherwise isogenic strains of Haemophilus influenzae type b (Hib), neonatal rats develop a bacteremic infection that often is dominated by only one strain, Sm S or Sm R . After ruling out other possibilities through years of related experiments, the field seems to have settled on a plausible explanation for this phenomenon: the first bacterium to invade the host activates the host immune response that ‘shuts the door’ on the second invading strain. To explore this hypothesis in a necessarily quantitative way, we modeled this process with a set of mixed stochastic and deterministic differential equations. Our analysis of the properties of this model with realistic parameters suggests that this hypothesis cannot explain the experimental results of Moxon and Murphy, and in particular the observed relationship between the frequency of different types of blood infections (bacteremias) and the inoculum size. We propose modifications to the model that come closer to explaining these data. However, the modified and better fitting model contradicts the common theory of independent action of individual bacteria in establishing infections. We suggest possible experiments that would be able to confirm or reject our proposed modification of the early infection model.

Encoding Sequential Information in Semantic Space Models: Comparing Holographic Reduced Representation and Random Permutation

PubMed Central

Recchia, Gabriel; Sahlgren, Magnus; Kanerva, Pentti; Jones, Michael N.

2015-01-01

Circular convolution and random permutation have each been proposed as neurally plausible binding operators capable of encoding sequential information in semantic memory. We perform several controlled comparisons of circular convolution and random permutation as means of encoding paired associates as well as encoding sequential information. Random permutations outperformed convolution with respect to the number of paired associates that can be reliably stored in a single memory trace. Performance was equal on semantic tasks when using a small corpus, but random permutations were ultimately capable of achieving superior performance due to their higher scalability to large corpora. Finally, “noisy” permutations in which units are mapped to other units arbitrarily (no one-to-one mapping) perform nearly as well as true permutations. These findings increase the neurological plausibility of random permutations and highlight their utility in vector space models of semantics. PMID:25954306

Multiple regimes of robust patterns between network structure and biodiversity

NASA Astrophysics Data System (ADS)

Jover, Luis F.; Flores, Cesar O.; Cortez, Michael H.; Weitz, Joshua S.

2015-12-01

Ecological networks such as plant-pollinator and host-parasite networks have structured interactions that define who interacts with whom. The structure of interactions also shapes ecological and evolutionary dynamics. Yet, there is significant ongoing debate as to whether certain structures, e.g., nestedness, contribute positively, negatively or not at all to biodiversity. We contend that examining variation in life history traits is key to disentangling the potential relationship between network structure and biodiversity. Here, we do so by analyzing a dynamic model of virus-bacteria interactions across a spectrum of network structures. Consistent with prior studies, we find plausible parameter domains exhibiting strong, positive relationships between nestedness and biodiversity. Yet, the same model can exhibit negative relationships between nestedness and biodiversity when examined in a distinct, plausible region of parameter space. We discuss steps towards identifying when network structure could, on its own, drive the resilience, sustainability, and even conservation of ecological communities.

Multiple regimes of robust patterns between network structure and biodiversity

PubMed Central

Jover, Luis F.; Flores, Cesar O.; Cortez, Michael H.; Weitz, Joshua S.

2015-01-01

Ecological networks such as plant-pollinator and host-parasite networks have structured interactions that define who interacts with whom. The structure of interactions also shapes ecological and evolutionary dynamics. Yet, there is significant ongoing debate as to whether certain structures, e.g., nestedness, contribute positively, negatively or not at all to biodiversity. We contend that examining variation in life history traits is key to disentangling the potential relationship between network structure and biodiversity. Here, we do so by analyzing a dynamic model of virus-bacteria interactions across a spectrum of network structures. Consistent with prior studies, we find plausible parameter domains exhibiting strong, positive relationships between nestedness and biodiversity. Yet, the same model can exhibit negative relationships between nestedness and biodiversity when examined in a distinct, plausible region of parameter space. We discuss steps towards identifying when network structure could, on its own, drive the resilience, sustainability, and even conservation of ecological communities. PMID:26632996

Calibration and validation of coarse-grained models of atomic systems: application to semiconductor manufacturing

NASA Astrophysics Data System (ADS)

Farrell, Kathryn; Oden, J. Tinsley

2014-07-01

Coarse-grained models of atomic systems, created by aggregating groups of atoms into molecules to reduce the number of degrees of freedom, have been used for decades in important scientific and technological applications. In recent years, interest in developing a more rigorous theory for coarse graining and in assessing the predictivity of coarse-grained models has arisen. In this work, Bayesian methods for the calibration and validation of coarse-grained models of atomistic systems in thermodynamic equilibrium are developed. For specificity, only configurational models of systems in canonical ensembles are considered. Among major challenges in validating coarse-grained models are (1) the development of validation processes that lead to information essential in establishing confidence in the model's ability predict key quantities of interest and (2), above all, the determination of the coarse-grained model itself; that is, the characterization of the molecular architecture, the choice of interaction potentials and thus parameters, which best fit available data. The all-atom model is treated as the "ground truth," and it provides the basis with respect to which properties of the coarse-grained model are compared. This base all-atom model is characterized by an appropriate statistical mechanics framework in this work by canonical ensembles involving only configurational energies. The all-atom model thus supplies data for Bayesian calibration and validation methods for the molecular model. To address the first challenge, we develop priors based on the maximum entropy principle and likelihood functions based on Gaussian approximations of the uncertainties in the parameter-to-observation error. To address challenge (2), we introduce the notion of model plausibilities as a means for model selection. This methodology provides a powerful approach toward constructing coarse-grained models which are most plausible for given all-atom data. We demonstrate the theory and methods through applications to representative atomic structures and we discuss extensions to the validation process for molecular models of polymer structures encountered in certain semiconductor nanomanufacturing processes. The powerful method of model plausibility as a means for selecting interaction potentials for coarse-grained models is discussed in connection with a coarse-grained hexane molecule. Discussions of how all-atom information is used to construct priors are contained in an appendix.

Ling's Adsorption Theory as a Mechanism of Membrane Potential Generation Observed in Both Living and Nonliving Systems.

PubMed

Tamagawa, Hirohisa; Funatani, Makoto; Ikeda, Kota

2016-01-26

The potential between two electrolytic solutions separated by a membrane impermeable to ions was measured and the generation mechanism of potential measured was investigated. From the physiological point of view, a nonzero membrane potential or action potential cannot be observed across the impermeable membrane. However, a nonzero membrane potential including action potential-like potential was clearly observed. Those observations gave rise to a doubt concerning the validity of currently accepted generation mechanism of membrane potential and action potential of cell. As an alternative theory, we found that the long-forgotten Ling's adsorption theory was the most plausible theory. Ling's adsorption theory suggests that the membrane potential and action potential of a living cell is due to the adsorption of mobile ions onto the adsorption site of cell, and this theory is applicable even to nonliving (or non-biological) system as well as living system. Through this paper, the authors emphasize that it is necessary to reconsider the validity of current membrane theory and also would like to urge the readers to pay keen attention to the Ling's adsorption theory which has for long years been forgotten in the history of physiology.

Attention versus consciousness in the visual brain: differences in conception, phenomenology, behavior, neuroanatomy, and physiology.

PubMed

Baars, B J

1999-07-01

A common confound between consciousness and attention makes it difficult to think clearly about recent advances in the understanding of the visual brain. Visual consciousness involves phenomenal experience of the visual world, but visual attention is more plausibly treated as a function that selects and maintains the selection of potential conscious contents, often unconsciously. In the same sense, eye movements select conscious visual events, which are not the same as conscious visual experience. According to common sense, visual experience is consciousness, and selective processes are labeled as attention. The distinction is reflected in very different behavioral measures and in very different brain anatomy and physiology. Visual consciousness tends to be associated with the "what" stream of visual feature neurons in the ventral temporal lobe. In contrast, attentional selection and maintenance are mediated by other brain regions, ranging from superior colliculi to thalamus, prefrontal cortex, and anterior cingulate. The author applied the common-sense distinction between attention and consciousness to the theoretical positions of M. I. Posner (1992, 1994) and D. LaBerge (1997, 1998) to show how it helps to clarify the evidence. He concluded that clarity of thought is served by calling a thing by its proper name.

Investigating expectation effects using multiple physiological measures

PubMed Central

Siller, Alexander; Ambach, Wolfgang; Vaitl, Dieter

2015-01-01

The study aimed at experimentally investigating whether the human body can anticipate future events under improved methodological conditions. Previous studies have reported contradictory results for the phenomenon typically called presentiment. If the positive findings are accurate, they call into doubt our views about human perception, and if they are inaccurate, a plausible conventional explanation might be based on the experimental design of the previous studies, in which expectation due to item sequences was misinterpreted as presentiment. To address these points, we opted to collect several physiological variables, to test different randomization types and to manipulate subjective significance individually. For the latter, we combined a mock crime scenario, in which participants had to steal specific items, with a concealed information test (CIT), in which the participants had to conceal their knowledge when interrogated about items they had stolen or not stolen. We measured electrodermal activity, respiration, finger pulse, heart rate (HR), and reaction times. The participants (n = 154) were assigned randomly to four different groups. Items presented in the CIT were either drawn with replacement (full) or without replacement (pseudo) and were either presented category-wise (cat) or regardless of categories (nocat). To understand how these item sequences influence expectation and modulate physiological reactions, we compared the groups with respect to effect sizes for stolen vs. not stolen items. Group pseudo_cat yielded the highest effect sizes, and pseudo_nocat yielded the lowest. We could not find any evidence of presentiment but did find evidence of physiological correlates of expectation. Due to the design differing fundamentally from previous studies, these findings do not allow for conclusions on the question whether the expectation bias is being confounded with presentiment. PMID:26500600

Metabolomics of Ramadan fasting: an opportunity for the controlled study of physiological responses to food intake

PubMed Central

2014-01-01

High-throughput screening techniques that analyze the metabolic endpoints of biological processes can identify the contributions of genetic predisposition and environmental factors to the development of common diseases. Studies applying controlled physiological challenges can reveal dysregulation in metabolic responses that may be predictive for or associated with these diseases. However, large-scale epidemiological studies with well controlled physiological challenge conditions, such as extended fasting periods and defined food intake, pose logistic challenges. Culturally and religiously motivated behavioral patterns of life style changes provide a natural setting that can be used to enroll a large number of study volunteers. Here we report a proof of principle study conducted within a Muslim community, showing that a metabolomics study during the Holy Month of Ramadan can provide a unique opportunity to explore the pre-prandial and postprandial response of human metabolism to nutritional challenges. Up to five blood samples were obtained from eleven healthy male volunteers, taken directly before and two hours after consumption of a controlled meal in the evening on days 7 and 26 of Ramadan, and after an over-night fast several weeks after Ramadan. The observed increases in glucose, insulin and lactate levels at the postprandial time point confirm the expected physiological response to food intake. Targeted metabolomics further revealed significant and physiologically plausible responses to food intake by an increase in bile acid and amino acid levels and a decrease in long-chain acyl-carnitine and polyamine levels. A decrease in the concentrations of a number of phospholipids between samples taken on days 7 and 26 of Ramadan shows that the long-term response to extended fasting may differ from the response to short-term fasting. The present study design is scalable to larger populations and may be extended to the study of the metabolic response in defined patient groups such as individuals with type 2 diabetes. PMID:24906381

Metabolomics of Ramadan fasting: an opportunity for the controlled study of physiological responses to food intake.

PubMed

Mathew, Sweety; Krug, Susanne; Skurk, Thomas; Halama, Anna; Stank, Antonia; Artati, Anna; Prehn, Cornelia; Malek, Joel A; Kastenmüller, Gabi; Römisch-Margl, Werner; Adamski, Jerzy; Hauner, Hans; Suhre, Karsten

2014-06-06

High-throughput screening techniques that analyze the metabolic endpoints of biological processes can identify the contributions of genetic predisposition and environmental factors to the development of common diseases. Studies applying controlled physiological challenges can reveal dysregulation in metabolic responses that may be predictive for or associated with these diseases. However, large-scale epidemiological studies with well controlled physiological challenge conditions, such as extended fasting periods and defined food intake, pose logistic challenges. Culturally and religiously motivated behavioral patterns of life style changes provide a natural setting that can be used to enroll a large number of study volunteers. Here we report a proof of principle study conducted within a Muslim community, showing that a metabolomics study during the Holy Month of Ramadan can provide a unique opportunity to explore the pre-prandial and postprandial response of human metabolism to nutritional challenges. Up to five blood samples were obtained from eleven healthy male volunteers, taken directly before and two hours after consumption of a controlled meal in the evening on days 7 and 26 of Ramadan, and after an over-night fast several weeks after Ramadan. The observed increases in glucose, insulin and lactate levels at the postprandial time point confirm the expected physiological response to food intake. Targeted metabolomics further revealed significant and physiologically plausible responses to food intake by an increase in bile acid and amino acid levels and a decrease in long-chain acyl-carnitine and polyamine levels. A decrease in the concentrations of a number of phospholipids between samples taken on days 7 and 26 of Ramadan shows that the long-term response to extended fasting may differ from the response to short-term fasting. The present study design is scalable to larger populations and may be extended to the study of the metabolic response in defined patient groups such as individuals with type 2 diabetes.

Simulation-based sensitivity analysis for non-ignorably missing data.

PubMed

Yin, Peng; Shi, Jian Q

2017-01-01

Sensitivity analysis is popular in dealing with missing data problems particularly for non-ignorable missingness, where full-likelihood method cannot be adopted. It analyses how sensitively the conclusions (output) may depend on assumptions or parameters (input) about missing data, i.e. missing data mechanism. We call models with the problem of uncertainty sensitivity models. To make conventional sensitivity analysis more useful in practice we need to define some simple and interpretable statistical quantities to assess the sensitivity models and make evidence based analysis. We propose a novel approach in this paper on attempting to investigate the possibility of each missing data mechanism model assumption, by comparing the simulated datasets from various MNAR models with the observed data non-parametrically, using the K-nearest-neighbour distances. Some asymptotic theory has also been provided. A key step of this method is to plug in a plausibility evaluation system towards each sensitivity parameter, to select plausible values and reject unlikely values, instead of considering all proposed values of sensitivity parameters as in the conventional sensitivity analysis method. The method is generic and has been applied successfully to several specific models in this paper including meta-analysis model with publication bias, analysis of incomplete longitudinal data and mean estimation with non-ignorable missing data.

Toward a Developmental/Contextual Model of the Effects of Parental Spanking on Children's Aggression.

ERIC Educational Resources Information Center

Gunnoe, Marjorie Lindner; Mariner, Carrie Lea

Researchers who employ contextual models of parenting contend that it is not spanking per se, but rather the context in which spanking occurs and the meanings children ascribe to spanking, that predict child outcomes. This study proposed two plausible meanings that children may ascribe to spanking--a legitimate expression of parental authority or…

Psychological Plausibility of the Theory of Probabilistic Mental Models and the Fast and Frugal Heuristics

ERIC Educational Resources Information Center

Dougherty, Michael R.; Franco-Watkins, Ana M.; Thomas, Rick

2008-01-01

The theory of probabilistic mental models (PMM; G. Gigerenzer, U. Hoffrage, & H. Kleinbolting, 1991) has had a major influence on the field of judgment and decision making, with the most recent important modifications to PMM theory being the identification of several fast and frugal heuristics (G. Gigerenzer & D. G. Goldstein, 1996). These…

Interval Estimation of Revision Effect on Scale Reliability via Covariance Structure Modeling

ERIC Educational Resources Information Center

Raykov, Tenko

2009-01-01

A didactic discussion of a procedure for interval estimation of change in scale reliability due to revision is provided, which is developed within the framework of covariance structure modeling. The method yields ranges of plausible values for the population gain or loss in reliability of unidimensional composites, which results from deletion or…

State-of-the-Art Review on Physiologically Based Pharmacokinetic Modeling in Pediatric Drug Development.

PubMed

Yellepeddi, Venkata; Rower, Joseph; Liu, Xiaoxi; Kumar, Shaun; Rashid, Jahidur; Sherwin, Catherine M T

2018-05-18

Physiologically based pharmacokinetic modeling and simulation is an important tool for predicting the pharmacokinetics, pharmacodynamics, and safety of drugs in pediatrics. Physiologically based pharmacokinetic modeling is applied in pediatric drug development for first-time-in-pediatric dose selection, simulation-based trial design, correlation with target organ toxicities, risk assessment by investigating possible drug-drug interactions, real-time assessment of pharmacokinetic-safety relationships, and assessment of non-systemic biodistribution targets. This review summarizes the details of a physiologically based pharmacokinetic modeling approach in pediatric drug research, emphasizing reports on pediatric physiologically based pharmacokinetic models of individual drugs. We also compare and contrast the strategies employed by various researchers in pediatric physiologically based pharmacokinetic modeling and provide a comprehensive overview of physiologically based pharmacokinetic modeling strategies and approaches in pediatrics. We discuss the impact of physiologically based pharmacokinetic models on regulatory reviews and product labels in the field of pediatric pharmacotherapy. Additionally, we examine in detail the current limitations and future directions of physiologically based pharmacokinetic modeling in pediatrics with regard to the ability to predict plasma concentrations and pharmacokinetic parameters. Despite the skepticism and concern in the pediatric community about the reliability of physiologically based pharmacokinetic models, there is substantial evidence that pediatric physiologically based pharmacokinetic models have been used successfully to predict differences in pharmacokinetics between adults and children for several drugs. It is obvious that the use of physiologically based pharmacokinetic modeling to support various stages of pediatric drug development is highly attractive and will rapidly increase, provided the robustness and reliability of these techniques are well established.

DigitalHuman (DH): An Integrative Mathematical Model ofHuman Physiology

NASA Technical Reports Server (NTRS)

Hester, Robert L.; Summers, Richard L.; lIescu, Radu; Esters, Joyee; Coleman, Thomas G.

2010-01-01

Mathematical models and simulation are important tools in discovering the key causal relationships governing physiological processes and improving medical intervention when physiological complexity is a central issue. We have developed a model of integrative human physiology called DigitalHuman (DH) consisting of -5000 variables modeling human physiology describing cardiovascular, renal, respiratory, endocrine, neural and metabolic physiology. Users can view time-dependent solutions and interactively introduce perturbations by altering numerical parameters to investigate new hypotheses. The variables, parameters and quantitative relationships as well as all other model details are described in XML text files. All aspects of the model, including the mathematical equations describing the physiological processes are written in XML open source, text-readable files. Model structure is based upon empirical data of physiological responses documented within the peer-reviewed literature. The model can be used to understand proposed physiological mechanisms and physiological interactions that may not be otherwise intUitively evident. Some of the current uses of this model include the analyses of renal control of blood pressure, the central role of the liver in creating and maintaining insulin resistance, and the mechanisms causing orthostatic hypotension in astronauts. Additionally the open source aspect of the modeling environment allows any investigator to add detailed descriptions of human physiology to test new concepts. The model accurately predicts both qualitative and more importantly quantitative changes in clinically and experimentally observed responses. DigitalHuman provides scientists a modeling environment to understand the complex interactions of integrative physiology. This research was supported by.NIH HL 51971, NSF EPSCoR, and NASA

In vivo characterization of structural and optical properties of human skin by combined photothermal radiometry and diffuse reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Verdel, Nina; Marin, Ana; Vidovič, Luka; Milanič, Matija; Majaron, Boris

2017-02-01

We have combined two optical techniques to enable simultaneous assessment of structure and composition of human skin in vivo: Pulsed photothermal radiometry (PPTR), which involves measurements of transient dynamics in midinfrared emission from sample surface after exposure to a light pulse, and diffuse reflectance spectroscopy (DRS) in visible part of the spectrum. Namely, while PPTR is highly sensitive to depth distribution of selected absorbers, DRS provides spectral information and thus enables differentiation between various chromophores. The accuracy and robustness of the inverse analysis is thus considerably improved compared to use of either technique on its own. Our analysis approach is simultaneous multi-dimensional fitting of the measured PPTR signals and DRS with predictions from a numerical model of light-tissue interaction (a.k.a. inverse Monte Carlo). By using a three-layer skin model (epidermis, dermis, and subcutis), we obtain a good match between the experimental and modeling data. However, dividing the dermis into two separate layers (i.e., papillary and reticular dermis) helps to bring all assessed parameter values within anatomically and physiologically plausible intervals. Both the quality of the fit and the assessed parameter values depend somewhat on the assumed scattering properties for skin, which vary in literature and likely depend on subject's age and gender, anatomical site, etc. In our preliminary experience, simultaneous fitting of the scattering properties is possible and leads to considerable improvement of the fit. The described approach may thus have a potential for simultaneous determination of absorption and scattering properties of human skin in vivo.

Mechanisms Behind Pyrroloquinoline Quinone Supplementation on Skeletal Muscle Mitochondrial Biogenesis: Possible Synergistic Effects with Exercise.

PubMed

Hwang, Paul; Willoughby, Darryn S

2018-05-01

There is clear evidence that endurance exercise training elicits intramuscular adaptations that can lead to elevations in mitochondrial biogenesis, oxidative capacity, mitochondrial density, and mitochondrial function. Mitochondrial biogenesis is regulated by the activation of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha. This master regulator of mitochondrial biogenesis activates nuclear respiratory factors (NRF-1, NRF-2) and mitochondrial transcription factor A, which enables the expansion of mitochondrial size and transcription of mitochondrial DNA. Pyrroloquinoline quinone (PQQ) has been identified as a novel supplement that is involved in various physiological processes such as redox modulation, cellular energy metabolism, and mitochondrial biogenesis and is a potent antioxidant. Since both exercise and supplemental PQQ have mechanisms associated with mitochondrial biogenesis, it is plausible that a differential additive ergogenic benefit with PQQ can ensue. However, there is a major paucity of research exploring the role of PQQ in conjunction with exercise. In this respect, the purpose of the critical literature review will be to present a comprehensive overview of PQQ and the proposed mechanisms underlying mitochondrial biogenesis. Because exercise can instigate the molecular responses indicative of mitochondrial biogenesis, it is plausible that PQQ and exercise may instigate a synergistic response. Key teaching points • Endurance exercise training enables skeletal muscle adaptations that can induce increases in mitochondrial biogenesis, improve oxidative capacity, mitochondrial density, and mitochondrial function. • Pyrroloquinoline quinone (PQQ) has been identified as a novel supplement that is involved in physiological processes including redox modulation, cellular energy metabolism, mitochondrial biogenesis, and antioxidant potential. • There is emerging evidence to support that PQQ supplementation can upregulate the molecular signaling responses indicative of mitochondrial biogenesis within skeletal muscle. • If both endurance exercise and PQQ supplementation can elicit increases in the molecular responses indicative of mitochondrial biogenesis, it is possible that both PQQ and exercise may instigate a synergistic ergogenic response. • There is a scarcity of research exploring the possible role of PQQ supplementation with concomitant endurance exercise. Therefore, future research is necessary to investigate the ergogenic potential behind PQQ supplementation in conjunction with endurance exercise.

Regulated Extracellular Choline Acetyltransferase Activity— The Plausible Missing Link of the Distant Action of Acetylcholine in the Cholinergic Anti-Inflammatory Pathway

PubMed Central

Aeinehband, Shahin; Behbahani, Homira; Grandien, Alf; Nilsson, Bo; Ekdahl, Kristina N.; Lindblom, Rickard P. F.; Piehl, Fredrik; Darreh-Shori, Taher

2013-01-01

Acetylcholine (ACh), the classical neurotransmitter, also affects a variety of nonexcitable cells, such as endothelia, microglia, astrocytes and lymphocytes in both the nervous system and secondary lymphoid organs. Most of these cells are very distant from cholinergic synapses. The action of ACh on these distant cells is unlikely to occur through diffusion, given that ACh is very short-lived in the presence of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), two extremely efficient ACh-degrading enzymes abundantly present in extracellular fluids. In this study, we show compelling evidence for presence of a high concentration and activity of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT) in human cerebrospinal fluid (CSF) and plasma. We show that ChAT levels are physiologically balanced to the levels of its counteracting enzymes, AChE and BuChE in the human plasma and CSF. Equilibrium analyses show that soluble ChAT maintains a steady-state ACh level in the presence of physiological levels of fully active ACh-degrading enzymes. We show that ChAT is secreted by cultured human-brain astrocytes, and that activated spleen lymphocytes release ChAT itself rather than ACh. We further report differential CSF levels of ChAT in relation to Alzheimer’s disease risk genotypes, as well as in patients with multiple sclerosis, a chronic neuroinflammatory disease, compared to controls. Interestingly, soluble CSF ChAT levels show strong correlation with soluble complement factor levels, supporting a role in inflammatory regulation. This study provides a plausible explanation for the long-distance action of ACh through continuous renewal of ACh in extracellular fluids by the soluble ChAT and thereby maintenance of steady-state equilibrium between hydrolysis and synthesis of this ubiquitous cholinergic signal substance in the brain and peripheral compartments. These findings may have important implications for the role of cholinergic signaling in states of inflammation in general and in neurodegenerative disease, such as Alzheimer’s disease and multiple sclerosis in particular. PMID:23840379

Plausibility and the Theoreticians' Regress: Constructing the evolutionary fate of stars

NASA Astrophysics Data System (ADS)

Ipe, Alex Ike

2002-10-01

This project presents a case-study of a scientific controversy that occurred in theoretical astrophysics nearly seventy years ago following the conceptual discovery of a novel phenomenon relating to the evolution and structure of stellar matter, known as the limiting mass. The ensuing debate between the author of the finding, Subrahmanyan Chandrasekhar and his primary critic, Arthur Stanley Eddington, witnessed both scientists trying to convince one another, as well as the astrophysical community, that their respective positions on the issue was the correct one. Since there was no independent criterion—that is, no observational evidence—at the time of the dispute that could have been drawn upon to test the validity of the limiting mass concept, a logical, objective resolution to the controversy was not possible. In this respect, I argue that the dynamics of the Chandrasekhar-Eddington debate succinctly resonates with Kennefick's notion of the Theoreticians' Regress. However, whereas this model predicts that such a regress can be broken if both parties in a dispute come to agree on who was in error and collaborate on a calculation whose technical foundation can be agreed to, I argue that a more pragmatic path by which the Theoreticians' Regress is broken is when one side in a dispute is able to construct its argument as being more plausible than that of its opponent, and is so successful in doing so, that its opposition is subsequently forced to withdraw from the debate. In order to adequately deal with the construction of plausibility in the context of scientific controversies, I draw upon Harvey's Plausibility Model as well as Pickering's work on the role socio-cultural factors play in the resolution of intellectual disputes. It is believed that the ideas embedded in these social- relativist-constructivist perspectives provide the most parsimonious explanation as to the reasons for the genesis and ultimate closure of this particular scientific controversy.

Design of a framework for modeling, integration and simulation of physiological models.

PubMed

Erson, E Zeynep; Cavuşoğlu, M Cenk

2012-09-01

Multiscale modeling and integration of physiological models carry challenges due to the complex nature of physiological processes. High coupling within and among scales present a significant challenge in constructing and integrating multiscale physiological models. In order to deal with such challenges in a systematic way, there is a significant need for an information technology framework together with related analytical and computational tools that will facilitate integration of models and simulations of complex biological systems. Physiological Model Simulation, Integration and Modeling Framework (Phy-SIM) is an information technology framework providing the tools to facilitate development, integration and simulation of integrated models of human physiology. Phy-SIM brings software level solutions to the challenges raised by the complex nature of physiological systems. The aim of Phy-SIM, and this paper is to lay some foundation with the new approaches such as information flow and modular representation of the physiological models. The ultimate goal is to enhance the development of both the models and the integration approaches of multiscale physiological processes and thus this paper focuses on the design approaches that would achieve such a goal. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Pilgrims sailing the Titanic: plausibility effects on memory for misinformation.

PubMed

Hinze, Scott R; Slaten, Daniel G; Horton, William S; Jenkins, Ryan; Rapp, David N

2014-02-01

People rely on information they read even when it is inaccurate (Marsh, Meade, & Roediger, Journal of Memory and Language 49:519-536, 2003), but how ubiquitous is this phenomenon? In two experiments, we investigated whether this tendency to encode and rely on inaccuracies from text might be influenced by the plausibility of misinformation. In Experiment 1, we presented stories containing inaccurate plausible statements (e.g., "The Pilgrims' ship was the Godspeed"), inaccurate implausible statements (e.g., . . . the Titanic), or accurate statements (e.g., . . . the Mayflower). On a subsequent test of general knowledge, participants relied significantly less on implausible than on plausible inaccuracies from the texts but continued to rely on accurate information. In Experiment 2, we replicated these results with the addition of a think-aloud procedure to elicit information about readers' noticing and evaluative processes for plausible and implausible misinformation. Participants indicated more skepticism and less acceptance of implausible than of plausible inaccuracies. In contrast, they often failed to notice, completely ignored, and at times even explicitly accepted the misinformation provided by plausible lures. These results offer insight into the conditions under which reliance on inaccurate information occurs and suggest potential mechanisms that may underlie reported misinformation effects.

Faints, fits, and fatalities from emotion in Shakespeare's characters: survey of the canon

PubMed Central

2006-01-01

Objectives To determine how often Shakespeare's characters faint, fit, or die from extreme emotion; to assess Shakespeare's uniqueness in this regard; and to examine the plausibility of these dramatised events. Design Line by line search through modern editions of these late 16th and early 17th century works for accounts of characters fainting, fitting, or dying while under strong emotion and for no other apparent reason. Data sources All 39 canonical plays by Shakespeare and his three long narrative poems; 18 similar works by seven of Shakespeare's best known contemporaries. Results 10 deaths from strong emotion are recorded by Shakespeare (three occur on stage); all are due to grief, typically at the loss of a loved one. All but two of the deaths are in the playwright's late works. Some deaths are sudden. Another 29 emotion induced deaths are mentioned as possible, but the likelihood of some can be challenged. Transient loss of consciousness is staged or reported in 18 cases (sounding like epilepsy in two) and near fainting in a further 13. Extreme joy is sometimes depicted as a factor in these events. Emotional death and fainting also occur occasionally in works by Shakespeare's contemporaries. Conclusions These dramatic phenomena are part of the early modern belief system but are also plausible by modern understanding of physiology and disease. They teach us not to underestimate the power of the emotions to disturb bodily functions. PMID:17185734

Spectral reconstruction of phase response curves reveals the synchronization properties of mouse globus pallidus neurons

PubMed Central

Atherton, Jeremy F.; Surmeier, D. James

2013-01-01

The propensity of a neuron to synchronize is captured by its infinitesimal phase response curve (iPRC). Determining whether an iPRC is biphasic, meaning that small depolarizing perturbations can actually delay the next spike, if delivered at appropriate phases, is a daunting experimental task because negative lobes in the iPRC (unlike positive ones) tend to be small and may be occluded by the normal discharge variability of a neuron. To circumvent this problem, iPRCs are commonly derived from numerical models of neurons. Here, we propose a novel and natural method to estimate the iPRC by direct estimation of its spectral modes. First, we show analytically that the spectral modes of the iPRC of an arbitrary oscillator are readily measured by applying weak harmonic perturbations. Next, applying this methodology to biophysical neuronal models, we show that a low-dimensional spectral reconstruction is sufficient to capture the structure of the iPRC. This structure was preserved reasonably well even with added physiological scale jitter in the neuronal models. To validate the methodology empirically, we applied it first to a low-noise electronic oscillator with a known design and then to cortical pyramidal neurons, recorded in whole cell configuration, that are known to possess a monophasic iPRC. Finally, using the methodology in conjunction with perforated-patch recordings from pallidal neurons, we show, in contrast to recent modeling studies, that these neurons have biphasic somatic iPRCs. Biphasic iPRCs would cause lateral somatically targeted pallidal inhibition to desynchronize pallidal neurons, providing a plausible explanation for their lack of synchrony in vivo. PMID:23966679

Polyamines: naturally occurring small molecule modulators of electrostatic protein-protein interactions.

PubMed

Berwanger, Anja; Eyrisch, Susanne; Schuster, Inge; Helms, Volkhard; Bernhardt, Rita

2010-02-01

Modulations of protein-protein interactions are a key step in regulating protein function, especially in networks. Modulators of these interactions are supposed to be candidates for the development of novel drugs. Here, we describe the role of the small, polycationic and highly abundant natural polyamines that could efficiently bind to charged spots at protein interfaces as modulators of such protein-protein interactions. Using the mitochondrial cytochrome P45011A1 (CYP11A1) electron transfer system as a model, we have analyzed the capability of putrescine, spermidine, and spermine at physiologically relevant concentrations to affect the protein-protein interactions between adrenodoxin reductase (AdR), adrenodoxin (Adx), and CYP11A1. The actions of polyamines on the individual components, on their association/dissociation, on electron transfer, and on substrate conversion were examined. These studies revealed modulating effects of polyamines on distinct interactions and on the entire system in a complex way. Modulation via changed protein-protein interactions appeared plausible from docking experiments that suggested favourable high-affinity binding sites of polyamines (spermine>spermidine>putrescine) at the AdR-Adx interface. Our findings imply for the first time that small endogenous compounds are capable of interfering with distinct components of transient protein complexes and might control protein functions by modulating electrostatic protein-protein interactions.

Concise Review: Conceptualizing Paralogous Stem-Cell Niches and Unfolding Bone Marrow Progenitor Cell Identities.

PubMed

Chen, Kevin G; Johnson, Kory R; McKay, Ronald D G; Robey, Pamela G

2018-01-01

Lineage commitment and differentiation of skeletal stem cells/bone marrow stromal cells (SSCs/BMSCs, often called bone marrow-derived "mesenchymal stem/stromal" cells) offer an important opportunity to study skeletal and hematopoietic diseases, and for tissue engineering and regenerative medicine. Currently, many studies in this field have relied on cell lineage tracing methods in mouse models, which have provided a significant advancement in our knowledge of skeletal and hematopoietic stem-cell niches in bone marrow (BM). However, there is a lack of agreement in numerous fundamental areas, including origins of various BM stem-cell niches, cell identities, and their physiological roles in the BM. In order to resolve these issues, we propose a new hypothesis of "paralogous" stem-cell niches (PSNs); that is, progressively altered parallel niches within an individual species throughout the life span of the organism. A putative PSN code seems to be plausible based on analysis of transcriptional signatures in two representative genes that encode Nes-GFP and leptin receptors, which are frequently used to monitor SSC lineage development in BM. Furthermore, we suggest a dynamic paralogous BM niche (PBMN) model that elucidates the coupling and uncoupling mechanisms between BM stem-cell niches and their zones of active regeneration during different developmental stages. Elucidation of these PBMNs would enable us to resolve the existing controversies, thus paving the way to achieving precision regenerative medicine and pharmaceutical applications based on these BM cell resources. Stem Cells 2018;36:11-21. © 2017 AlphaMed Press.

Neural theory for the perception of causal actions.

PubMed

Fleischer, Falk; Christensen, Andrea; Caggiano, Vittorio; Thier, Peter; Giese, Martin A

2012-07-01

The efficient prediction of the behavior of others requires the recognition of their actions and an understanding of their action goals. In humans, this process is fast and extremely robust, as demonstrated by classical experiments showing that human observers reliably judge causal relationships and attribute interactive social behavior to strongly simplified stimuli consisting of simple moving geometrical shapes. While psychophysical experiments have identified critical visual features that determine the perception of causality and agency from such stimuli, the underlying detailed neural mechanisms remain largely unclear, and it is an open question why humans developed this advanced visual capability at all. We created pairs of naturalistic and abstract stimuli of hand actions that were exactly matched in terms of their motion parameters. We show that varying critical stimulus parameters for both stimulus types leads to very similar modulations of the perception of causality. However, the additional form information about the hand shape and its relationship with the object supports more fine-grained distinctions for the naturalistic stimuli. Moreover, we show that a physiologically plausible model for the recognition of goal-directed hand actions reproduces the observed dependencies of causality perception on critical stimulus parameters. These results support the hypothesis that selectivity for abstract action stimuli might emerge from the same neural mechanisms that underlie the visual processing of natural goal-directed action stimuli. Furthermore, the model proposes specific detailed neural circuits underlying this visual function, which can be evaluated in future experiments.

Eocene Paleoclimate: Incredible or Uncredible? Model data syntheses raise questions.

NASA Astrophysics Data System (ADS)

Huber, M.

2012-04-01

Reconstructions of Eocene paleoclimate have pushed on the boundaries of climate dynamics theory for generations. While significant improvements in theory and models have brought them closer to the proxy data, the data themselves have shifted considerably. Tropical temperatures and greenhouse gas concentrations are now reconstructed to be higher than once thought--in agreement with models--but, many polar temperature reconstructions are even warmer than the eye popping numbers from only a decade ago. These interpretations of subtropical-to-tropical polar conditions once again challenge models and theory. But, the devil, is as always in the details and it is worthwhile to consider the range of potential uncertainties and biases in the paleoclimate record interpretations to evaluate the proposition that models and data may not materially disagree. It is necessary to ask whether current Eocene paleoclimate reconstructions are accurate enough to compellingly argue for a complete failure of climate models and theory. Careful consideration of Eocene model output and proxy data reveals that over most of the Earth the model agrees with the upper range of plausible tropical proxy data and the lower range of plausible high latitude proxy reconstructions. Implications for the sensitivity of global climate to greenhouse gas forcing are drawn for a range of potential Eocene climate scenarios ranging from a literal interpretation of one particular model to a literal interpretation of proxy data. Hope for a middle ground is found.

Bayesian learning and the psychology of rule induction

PubMed Central

Endress, Ansgar D.

2014-01-01

In recent years, Bayesian learning models have been applied to an increasing variety of domains. While such models have been criticized on theoretical grounds, the underlying assumptions and predictions are rarely made concrete and tested experimentally. Here, I use Frank and Tenenbaum's (2011) Bayesian model of rule-learning as a case study to spell out the underlying assumptions, and to confront them with the empirical results Frank and Tenenbaum (2011) propose to simulate, as well as with novel experiments. While rule-learning is arguably well suited to rational Bayesian approaches, I show that their models are neither psychologically plausible nor ideal observer models. Further, I show that their central assumption is unfounded: humans do not always preferentially learn more specific rules, but, at least in some situations, those rules that happen to be more salient. Even when granting the unsupported assumptions, I show that all of the experiments modeled by Frank and Tenenbaum (2011) either contradict their models, or have a large number of more plausible interpretations. I provide an alternative account of the experimental data based on simple psychological mechanisms, and show that this account both describes the data better, and is easier to falsify. I conclude that, despite the recent surge in Bayesian models of cognitive phenomena, psychological phenomena are best understood by developing and testing psychological theories rather than models that can be fit to virtually any data. PMID:23454791

A Stochastic Model of Plausibility in Live Virtual Constructive Environments

DTIC Science & Technology

2017-09-14

objective in virtual environment research and design is the maintenance of adequate consistency levels in the face of limited system resources such as...provides some commentary with regard to system design considerations and future research directions. II. SYSTEM MODEL DVEs are often designed as a...exceed the system’s requirements. Research into predictive models of virtual environment consistency is needed to provide designers the tools to

A One-System Theory Which is Not Propositional.

PubMed

Witnauer, James E; Urcelay, Gonzalo P; Miller, Ralph R

2009-04-01

We argue that the propositional and link-based approaches to human contingency learning represent different levels of analysis because propositional reasoning requires a basis, which is plausibly provided by a link-based architecture. Moreover, in their attempt to compare two general classes of models (link-based and propositional), Mitchell et al. have referred to only two generic models and ignore the large variety of different models within each class.

Cure models for the analysis of time-to-event data in cancer studies.

PubMed

Jia, Xiaoyu; Sima, Camelia S; Brennan, Murray F; Panageas, Katherine S

2013-11-01

In settings when it is biologically plausible that some patients are cured after definitive treatment, cure models present an alternative to conventional survival analysis. Cure models can inform on the group of patients cured, by estimating the probability of cure, and identifying factors that influence it; while simultaneously focusing on time to recurrence and associated factors for the remaining patients. © 2013 Wiley Periodicals, Inc.

A Biologically Plausible Architecture of the Striatum to Solve Context-Dependent Reinforcement Learning Tasks.

PubMed

Shivkumar, Sabyasachi; Muralidharan, Vignesh; Chakravarthy, V Srinivasa

2017-01-01

Basal ganglia circuit is an important subcortical system of the brain thought to be responsible for reward-based learning. Striatum, the largest nucleus of the basal ganglia, serves as an input port that maps cortical information. Microanatomical studies show that the striatum is a mosaic of specialized input-output structures called striosomes and regions of the surrounding matrix called the matrisomes. We have developed a computational model of the striatum using layered self-organizing maps to capture the center-surround structure seen experimentally and explain its functional significance. We believe that these structural components could build representations of state and action spaces in different environments. The striatum model is then integrated with other components of basal ganglia, making it capable of solving reinforcement learning tasks. We have proposed a biologically plausible mechanism of action-based learning where the striosome biases the matrisome activity toward a preferred action. Several studies indicate that the striatum is critical in solving context dependent problems. We build on this hypothesis and the proposed model exploits the modularity of the striatum to efficiently solve such tasks.

A Biologically Plausible Architecture of the Striatum to Solve Context-Dependent Reinforcement Learning Tasks

PubMed Central

Shivkumar, Sabyasachi; Muralidharan, Vignesh; Chakravarthy, V. Srinivasa

2017-01-01

Basal ganglia circuit is an important subcortical system of the brain thought to be responsible for reward-based learning. Striatum, the largest nucleus of the basal ganglia, serves as an input port that maps cortical information. Microanatomical studies show that the striatum is a mosaic of specialized input-output structures called striosomes and regions of the surrounding matrix called the matrisomes. We have developed a computational model of the striatum using layered self-organizing maps to capture the center-surround structure seen experimentally and explain its functional significance. We believe that these structural components could build representations of state and action spaces in different environments. The striatum model is then integrated with other components of basal ganglia, making it capable of solving reinforcement learning tasks. We have proposed a biologically plausible mechanism of action-based learning where the striosome biases the matrisome activity toward a preferred action. Several studies indicate that the striatum is critical in solving context dependent problems. We build on this hypothesis and the proposed model exploits the modularity of the striatum to efficiently solve such tasks. PMID:28680395

Delta: a new web-based 3D genome visualization and analysis platform.

PubMed

Tang, Bixia; Li, Feifei; Li, Jing; Zhao, Wenming; Zhang, Zhihua

2018-04-15

Delta is an integrative visualization and analysis platform to facilitate visually annotating and exploring the 3D physical architecture of genomes. Delta takes Hi-C or ChIA-PET contact matrix as input and predicts the topologically associating domains and chromatin loops in the genome. It then generates a physical 3D model which represents the plausible consensus 3D structure of the genome. Delta features a highly interactive visualization tool which enhances the integration of genome topology/physical structure with extensive genome annotation by juxtaposing the 3D model with diverse genomic assay outputs. Finally, by visually comparing the 3D model of the β-globin gene locus and its annotation, we speculated a plausible transitory interaction pattern in the locus. Experimental evidence was found to support this speculation by literature survey. This served as an example of intuitive hypothesis testing with the help of Delta. Delta is freely accessible from http://delta.big.ac.cn, and the source code is available at https://github.com/zhangzhwlab/delta. zhangzhihua@big.ac.cn. Supplementary data are available at Bioinformatics online.

Computational analyses in cognitive neuroscience: in defense of biological implausibility.

PubMed

Dror, I E; Gallogly, D P

1999-06-01

Because cognitive neuroscience researchers attempt to understand the human mind by bridging behavior and brain, they expect computational analyses to be biologically plausible. In this paper, biologically implausible computational analyses are shown to have critical and essential roles in the various stages and domains of cognitive neuroscience research. Specifically, biologically implausible computational analyses can contribute to (1) understanding and characterizing the problem that is being studied, (2) examining the availability of information and its representation, and (3) evaluating and understanding the neuronal solution. In the context of the distinct types of contributions made by certain computational analyses, the biological plausibility of those analyses is altogether irrelevant. These biologically implausible models are nevertheless relevant and important for biologically driven research.

Plausibility Judgments in Conceptual Change and Epistemic Cognition

ERIC Educational Resources Information Center

Lombardi, Doug; Nussbaum, E. Michael; Sinatra, Gale M.

2016-01-01

Plausibility judgments rarely have been addressed empirically in conceptual change research. Recent research, however, suggests that these judgments may be pivotal to conceptual change about certain topics where a gap exists between what scientists and laypersons find plausible. Based on a philosophical and empirical foundation, this article…

Are more complex physiological models of forest ecosystems better choices for plot and regional predictions?

Treesearch

Wenchi Jin; Hong S. He; Frank R. Thompson

2016-01-01

Process-based forest ecosystem models vary from simple physiological, complex physiological, to hybrid empirical-physiological models. Previous studies indicate that complex models provide the best prediction at plot scale with a temporal extent of less than 10 years, however, it is largely untested as to whether complex models outperform the other two types of models...

Identifying Asteroidal Parent Bodies of the Meteorites: The Last Lap

NASA Technical Reports Server (NTRS)

Gaffey, M. J.

2000-01-01

Spectral studies of asteroids and dynamical models have converged to yield, at last, a clear view of asteroid-meteorite linkages. Plausible parent bodies for most meteorite types have either been identified or it has become evident where to search for them.

The Graphical Representation of the Digital Astronaut Physiology Backbone

NASA Technical Reports Server (NTRS)

Briers, Demarcus

2010-01-01

This report summarizes my internship project with the NASA Digital Astronaut Project to analyze the Digital Astronaut (DA) physiology backbone model. The Digital Astronaut Project (DAP) applies integrated physiology models to support space biomedical operations, and to assist NASA researchers in closing knowledge gaps related to human physiologic responses to space flight. The DA physiology backbone is a set of integrated physiological equations and functions that model the interacting systems of the human body. The current release of the model is HumMod (Human Model) version 1.5 and was developed over forty years at the University of Mississippi Medical Center (UMMC). The physiology equations and functions are scripted in an XML schema specifically designed for physiology modeling by Dr. Thomas G. Coleman at UMMC. Currently it is difficult to examine the physiology backbone without being knowledgeable of the XML schema. While investigating and documenting the tags and algorithms used in the XML schema, I proposed a standard methodology for a graphical representation. This standard methodology may be used to transcribe graphical representations from the DA physiology backbone. In turn, the graphical representations can allow examination of the physiological functions and equations without the need to be familiar with the computer programming languages or markup languages used by DA modeling software.

Estimates of live-tree carbon stores in the Pacific Northwest are sensitive to model selection

Treesearch

Susanna L. Melson; Mark E. Harmon; Jeremy S. Fried; James B. Domingo

2011-01-01

Estimates of live-tree carbon stores are influenced by numerous uncertainties. One of them is model-selection uncertainty: one has to choose among multiple empirical equations and conversion factors that can be plausibly justified as locally applicable to calculate the carbon store from inventory measurements such as tree height and diameter at breast height (DBH)....

Alternative supply specifications and estimates of regional supply and demand for stumpage.

Treesearch

Kent P. Connaughton; David H. Jackson; Gerard A. Majerus

1988-01-01

Four plausible sets of stumpage supply and demand equations were developed and estimated; the demand equation was the same for each set, although the supply equation differed. The supply specifications varied from the model of regional excess demand in which National Forest harvest levels were assumed fixed to a more realistic model in which the harvest on the National...

On the biological plausibility of grandmother cells: implications for neural network theories in psychology and neuroscience.

PubMed

Bowers, Jeffrey S

2009-01-01

A fundamental claim associated with parallel distributed processing (PDP) theories of cognition is that knowledge is coded in a distributed manner in mind and brain. This approach rejects the claim that knowledge is coded in a localist fashion, with words, objects, and simple concepts (e.g. "dog"), that is, coded with their own dedicated representations. One of the putative advantages of this approach is that the theories are biologically plausible. Indeed, advocates of the PDP approach often highlight the close parallels between distributed representations learned in connectionist models and neural coding in brain and often dismiss localist (grandmother cell) theories as biologically implausible. The author reviews a range a data that strongly challenge this claim and shows that localist models provide a better account of single-cell recording studies. The author also contrast local and alternative distributed coding schemes (sparse and coarse coding) and argues that common rejection of grandmother cell theories in neuroscience is due to a misunderstanding about how localist models behave. The author concludes that the localist representations embedded in theories of perception and cognition are consistent with neuroscience; biology only calls into question the distributed representations often learned in PDP models.

Dynamical simulation priors for human motion tracking.

PubMed

Vondrak, Marek; Sigal, Leonid; Jenkins, Odest Chadwicke

2013-01-01

We propose a simulation-based dynamical motion prior for tracking human motion from video in presence of physical ground-person interactions. Most tracking approaches to date have focused on efficient inference algorithms and/or learning of prior kinematic motion models; however, few can explicitly account for the physical plausibility of recovered motion. Here, we aim to recover physically plausible motion of a single articulated human subject. Toward this end, we propose a full-body 3D physical simulation-based prior that explicitly incorporates a model of human dynamics into the Bayesian filtering framework. We consider the motion of the subject to be generated by a feedback “control loop” in which Newtonian physics approximates the rigid-body motion dynamics of the human and the environment through the application and integration of interaction forces, motor forces, and gravity. Interaction forces prevent physically impossible hypotheses, enable more appropriate reactions to the environment (e.g., ground contacts), and are produced from detected human-environment collisions. Motor forces actuate the body, ensure that proposed pose transitions are physically feasible, and are generated using a motion controller. For efficient inference in the resulting high-dimensional state space, we utilize an exemplar-based control strategy that reduces the effective search space of motor forces. As a result, we are able to recover physically plausible motion of human subjects from monocular and multiview video. We show, both quantitatively and qualitatively, that our approach performs favorably with respect to Bayesian filtering methods with standard motion priors.

A swarm intelligence framework for reconstructing gene networks: searching for biologically plausible architectures.

PubMed

Kentzoglanakis, Kyriakos; Poole, Matthew

2012-01-01

In this paper, we investigate the problem of reverse engineering the topology of gene regulatory networks from temporal gene expression data. We adopt a computational intelligence approach comprising swarm intelligence techniques, namely particle swarm optimization (PSO) and ant colony optimization (ACO). In addition, the recurrent neural network (RNN) formalism is employed for modeling the dynamical behavior of gene regulatory systems. More specifically, ACO is used for searching the discrete space of network architectures and PSO for searching the corresponding continuous space of RNN model parameters. We propose a novel solution construction process in the context of ACO for generating biologically plausible candidate architectures. The objective is to concentrate the search effort into areas of the structure space that contain architectures which are feasible in terms of their topological resemblance to real-world networks. The proposed framework is initially applied to the reconstruction of a small artificial network that has previously been studied in the context of gene network reverse engineering. Subsequently, we consider an artificial data set with added noise for reconstructing a subnetwork of the genetic interaction network of S. cerevisiae (yeast). Finally, the framework is applied to a real-world data set for reverse engineering the SOS response system of the bacterium Escherichia coli. Results demonstrate the relative advantage of utilizing problem-specific knowledge regarding biologically plausible structural properties of gene networks over conducting a problem-agnostic search in the vast space of network architectures.

Plausible carrier transport model in organic-inorganic hybrid perovskite resistive memory devices

NASA Astrophysics Data System (ADS)

Park, Nayoung; Kwon, Yongwoo; Choi, Jaeho; Jang, Ho Won; Cha, Pil-Ryung

2018-04-01

We demonstrate thermally assisted hopping (TAH) as an appropriate carrier transport model for CH3NH3PbI3 resistive memories. Organic semiconductors, including organic-inorganic hybrid perovskites, have been previously speculated to follow the space-charge-limited conduction (SCLC) model. However, the SCLC model cannot reproduce the temperature dependence of experimental current-voltage curves. Instead, the TAH model with temperature-dependent trap densities and a constant trap level are demonstrated to well reproduce the experimental results.

Computational modeling of peripheral pain: a commentary.

PubMed

Argüello, Erick J; Silva, Ricardo J; Huerta, Mónica K; Avila, René S

2015-06-11

This commentary is intended to find possible explanations for the low impact of computational modeling on pain research. We discuss the main strategies that have been used in building computational models for the study of pain. The analysis suggests that traditional models lack biological plausibility at some levels, they do not provide clinically relevant results, and they cannot capture the stochastic character of neural dynamics. On this basis, we provide some suggestions that may be useful in building computational models of pain with a wider range of applications.

Source Effects and Plausibility Judgments When Reading about Climate Change

ERIC Educational Resources Information Center

Lombardi, Doug; Seyranian, Viviane; Sinatra, Gale M.

2014-01-01

Gaps between what scientists and laypeople find plausible may act as a barrier to learning complex and/or controversial socioscientific concepts. For example, individuals may consider scientific explanations that human activities are causing current climate change as implausible. This plausibility judgment may be due-in part-to individuals'…

Plausibility and Perspective Influence the Processing of Counterfactual Narratives

ERIC Educational Resources Information Center

Ferguson, Heather J.; Jayes, Lewis T.

2018-01-01

Previous research has established that readers' eye movements are sensitive to the difficulty with which a word is processed. One important factor that influences processing is the fit of a word within the wider context, including its plausibility. Here we explore the influence of plausibility in counterfactual language processing. Counterfactuals…

Hydrocode modeling of the spallation process during hypervelocity impacts: Implications for the ejection of Martian meteorites

NASA Astrophysics Data System (ADS)

Kurosawa, Kosuke; Okamoto, Takaya; Genda, Hidenori

2018-02-01

Hypervelocity ejection of material by impact spallation is considered a plausible mechanism for material exchange between two planetary bodies. We have modeled the spallation process during vertical impacts over a range of impact velocities from 6 to 21 km/s using both grid- and particle-based hydrocode models. The Tillotson equations of state, which are able to treat the nonlinear dependence of density on pressure and thermal pressure in strongly shocked matter, were used to study the hydrodynamic-thermodynamic response after impacts. The effects of material strength and gravitational acceleration were not considered. A two-dimensional time-dependent pressure field within a 1.5-fold projectile radius from the impact point was investigated in cylindrical coordinates to address the generation of spalled material. A resolution test was also performed to reject ejected materials with peak pressures that were too low due to artificial viscosity. The relationship between ejection velocity veject and peak pressure Ppeak was also derived. Our approach shows that "late-stage acceleration" in an ejecta curtain occurs due to the compressible nature of the ejecta, resulting in an ejection velocity that can be higher than the ideal maximum of the resultant particle velocity after passage of a shock wave. We also calculate the ejecta mass that can escape from a planet like Mars (i.e., veject > 5 km/s) that matches the petrographic constraints from Martian meteorites, and which occurs when Ppeak = 30-50 GPa. Although the mass of such ejecta is limited to 0.1-1 wt% of the projectile mass in vertical impacts, this is sufficient for spallation to have been a plausible mechanism for the ejection of Martian meteorites. Finally, we propose that impact spallation is a plausible mechanism for the generation of tektites.

Empirical agreement in model validation.

PubMed

Jebeile, Julie; Barberousse, Anouk

2016-04-01

Empirical agreement is often used as an important criterion when assessing the validity of scientific models. However, it is by no means a sufficient criterion as a model can be so adjusted as to fit available data even though it is based on hypotheses whose plausibility is known to be questionable. Our aim in this paper is to investigate into the uses of empirical agreement within the process of model validation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of Damping Mechanisms for Transverse Waves in Solar Coronal Loops

NASA Astrophysics Data System (ADS)

Montes-Solís, María; Arregui, Iñigo

2017-09-01

We present a method to assess the plausibility of alternative mechanisms to explain the damping of magnetohydrodynamic transverse waves in solar coronal loops. The considered mechanisms are resonant absorption of kink waves in the Alfvén continuum, phase mixing of Alfvén waves, and wave leakage. Our methods make use of Bayesian inference and model comparison techniques. We first infer the values for the physical parameters that control the wave damping, under the assumption of a particular mechanism, for typically observed damping timescales. Then, the computation of marginal likelihoods and Bayes factors enable us to quantify the relative plausibility between the alternative mechanisms. We find that, in general, the evidence is not large enough to support a single particular damping mechanism as the most plausible one. Resonant absorption and wave leakage offer the most probable explanations in strong damping regimes, while phase mixing is the best candidate for weak/moderate damping. When applied to a selection of 89 observed transverse loop oscillations, with their corresponding measurements of damping timescales and taking into account data uncertainties, we find that positive evidence for a given damping mechanism is only available in a few cases.

Comparison of Damping Mechanisms for Transverse Waves in Solar Coronal Loops

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montes-Solís, María; Arregui, Iñigo, E-mail: mmsolis@iac.es

We present a method to assess the plausibility of alternative mechanisms to explain the damping of magnetohydrodynamic transverse waves in solar coronal loops. The considered mechanisms are resonant absorption of kink waves in the Alfvén continuum, phase mixing of Alfvén waves, and wave leakage. Our methods make use of Bayesian inference and model comparison techniques. We first infer the values for the physical parameters that control the wave damping, under the assumption of a particular mechanism, for typically observed damping timescales. Then, the computation of marginal likelihoods and Bayes factors enable us to quantify the relative plausibility between the alternativemore » mechanisms. We find that, in general, the evidence is not large enough to support a single particular damping mechanism as the most plausible one. Resonant absorption and wave leakage offer the most probable explanations in strong damping regimes, while phase mixing is the best candidate for weak/moderate damping. When applied to a selection of 89 observed transverse loop oscillations, with their corresponding measurements of damping timescales and taking into account data uncertainties, we find that positive evidence for a given damping mechanism is only available in a few cases.« less

Subsurface Scenarios: What are We Trying to Model?

EPA Science Inventory

In collaboration with the Lawrence Berkeley National Lab (George Moridis and team),and after a thorough review of the scientific literature and data and interviews with a selection of experts on the topic, a finite number of plausible scenarios were selected for more quantitative...

Embodied Design: Constructing Means for Constructing Meaning

ERIC Educational Resources Information Center

Abrahamson, Dor

2009-01-01

Design-based research studies are conducted as iterative implementation-analysis-modification cycles, in which emerging theoretical models and pedagogically plausible activities are reciprocally tuned toward each other as a means of investigating conjectures pertaining to mechanisms underlying content teaching and learning. Yet this approach, even…

Multidecadal Scale Detection Time for Potentially Increasing Atlantic Storm Surges in a Warming Climate

NASA Astrophysics Data System (ADS)

Lee, Benjamin Seiyon; Haran, Murali; Keller, Klaus

2017-10-01

Storm surges are key drivers of coastal flooding, which generate considerable risks. Strategies to manage these risks can hinge on the ability to (i) project the return periods of extreme storm surges and (ii) detect potential changes in their statistical properties. There are several lines of evidence linking rising global average temperatures and increasingly frequent extreme storm surges. This conclusion is, however, subject to considerable structural uncertainty. This leads to two main questions: What are projections under various plausible statistical models? How long would it take to distinguish among these plausible statistical models? We address these questions by analyzing observed and simulated storm surge data. We find that (1) there is a positive correlation between global mean temperature rise and increasing frequencies of extreme storm surges; (2) there is considerable uncertainty underlying the strength of this relationship; and (3) if the frequency of storm surges is increasing, this increase can be detected within a multidecadal timescale (≈20 years from now).

Modeling protein homopolymeric repeats: possible polyglutamine structural motifs for Huntington's disease.

PubMed

Lathrop, R H; Casale, M; Tobias, D J; Marsh, J L; Thompson, L M

1998-01-01

We describe a prototype system (Poly-X) for assisting an expert user in modeling protein repeats. Poly-X reduces the large number of degrees of freedom required to specify a protein motif in complete atomic detail. The result is a small number of parameters that are easily understood by, and under the direct control of, a domain expert. The system was applied to the polyglutamine (poly-Q) repeat in the first exon of huntingtin, the gene implicated in Huntington's disease. We present four poly-Q structural motifs: two poly-Q beta-sheet motifs (parallel and antiparallel) that constitute plausible alternatives to a similar previously published poly-Q beta-sheet motif, and two novel poly-Q helix motifs (alpha-helix and pi-helix). To our knowledge, helical forms of polyglutamine have not been proposed before. The motifs suggest that there may be several plausible aggregation structures for the intranuclear inclusion bodies which have been found in diseased neurons, and may help in the effort to understand the structural basis for Huntington's disease.

Semantic and Plausibility Preview Benefit Effects in English: Evidence from Eye Movements

PubMed Central

Schotter, Elizabeth R.; Jia, Annie

2016-01-01

Theories of preview benefit in reading hinge on integration across saccades and the idea that preview benefit is greater the more similar the preview and target are. Schotter (2013) reported preview benefit from a synonymous preview, but it is unclear whether this effect occurs because of similarity between the preview and target (integration), or because of contextual fit of the preview—synonyms satisfy both accounts. Studies in Chinese have found evidence for preview benefit for words that are unrelated to the target, but are contextually plausible (Yang, Li, Wang, Slattery, & Rayner, 2014; Yang, Wang, Tong, & Rayner, 2012), which is incompatible with an integration account but supports a contextual fit account. Here, we used plausible and implausible unrelated previews in addition to plausible synonym, antonym, and identical previews to further investigate these accounts for readers of English. Early reading measures were shorter for all plausible preview conditions compared to the implausible preview condition. In later reading measures, a benefit for the plausible unrelated preview condition was not observed. In a second experiment, we asked questions that probed whether the reader encoded the preview or target. Readers were more likely to report the preview when they had skipped the word and not regressed to it, and when the preview was plausible. Thus, under certain circumstances, the preview word is processed to a high level of representation (i.e., semantic plausibility) regardless of its relationship to the target, but its influence on reading is relatively short-lived, being replaced by the target word, when fixated. PMID:27123754

A Bayesian framework for adaptive selection, calibration, and validation of coarse-grained models of atomistic systems

NASA Astrophysics Data System (ADS)

Farrell, Kathryn; Oden, J. Tinsley; Faghihi, Danial

2015-08-01

A general adaptive modeling algorithm for selection and validation of coarse-grained models of atomistic systems is presented. A Bayesian framework is developed to address uncertainties in parameters, data, and model selection. Algorithms for computing output sensitivities to parameter variances, model evidence and posterior model plausibilities for given data, and for computing what are referred to as Occam Categories in reference to a rough measure of model simplicity, make up components of the overall approach. Computational results are provided for representative applications.

Making More Plausible What is Hard To Believe: Historical Justifications and Illustrations of Newton's Third Law.

ERIC Educational Resources Information Center

Gauld, Colin

1998-01-01

Reports that many students do not believe Newton's law of action and reaction and suggests ways in which its plausibility might be enhanced. Reviews how this law has been made more plausible over time by Newton and those who succeeded him. Contains 25 references. (DDR)

Plausibility Reappraisals and Shifts in Middle School Students' Climate Change Conceptions

ERIC Educational Resources Information Center

Lombardi, Doug; Sinatra, Gale M.; Nussbaum, E. Michael

2013-01-01

Plausibility is a central but under-examined topic in conceptual change research. Climate change is an important socio-scientific topic; however, many view human-induced climate change as implausible. When learning about climate change, students need to make plausibility judgments but they may not be sufficiently critical or reflective. The…

Using an agent-based model to simulate children’s active travel to school

PubMed Central

2013-01-01

Background Despite the multiple advantages of active travel to school, only a small percentage of US children and adolescents walk or bicycle to school. Intervention studies are in a relatively early stage and evidence of their effectiveness over long periods is limited. The purpose of this study was to illustrate the utility of agent-based models in exploring how various policies may influence children’s active travel to school. Methods An agent-based model was developed to simulate children’s school travel behavior within a hypothetical city. The model was used to explore the plausible implications of policies targeting two established barriers to active school travel: long distance to school and traffic safety. The percent of children who walk to school was compared for various scenarios. Results To maximize the percent of children who walk to school the school locations should be evenly distributed over space and children should be assigned to the closest school. In the case of interventions to improve traffic safety, targeting a smaller area around the school with greater intensity may be more effective than targeting a larger area with less intensity. Conclusions Despite the challenges they present, agent based models are a useful complement to other analytical strategies in studying the plausible impact of various policies on active travel to school. PMID:23705953

Using an agent-based model to simulate children's active travel to school.

PubMed

Yang, Yong; Diez-Roux, Ana V

2013-05-26

Despite the multiple advantages of active travel to school, only a small percentage of US children and adolescents walk or bicycle to school. Intervention studies are in a relatively early stage and evidence of their effectiveness over long periods is limited. The purpose of this study was to illustrate the utility of agent-based models in exploring how various policies may influence children's active travel to school. An agent-based model was developed to simulate children's school travel behavior within a hypothetical city. The model was used to explore the plausible implications of policies targeting two established barriers to active school travel: long distance to school and traffic safety. The percent of children who walk to school was compared for various scenarios. To maximize the percent of children who walk to school the school locations should be evenly distributed over space and children should be assigned to the closest school. In the case of interventions to improve traffic safety, targeting a smaller area around the school with greater intensity may be more effective than targeting a larger area with less intensity. Despite the challenges they present, agent based models are a useful complement to other analytical strategies in studying the plausible impact of various policies on active travel to school.

Framework for Uncertainty Assessment - Hanford Site-Wide Groundwater Flow and Transport Modeling

NASA Astrophysics Data System (ADS)

Bergeron, M. P.; Cole, C. R.; Murray, C. J.; Thorne, P. D.; Wurstner, S. K.

2002-05-01

Pacific Northwest National Laboratory is in the process of development and implementation of an uncertainty estimation methodology for use in future site assessments that addresses parameter uncertainty as well as uncertainties related to the groundwater conceptual model. The long-term goals of the effort are development and implementation of an uncertainty estimation methodology for use in future assessments and analyses being made with the Hanford site-wide groundwater model. The basic approach in the framework developed for uncertainty assessment consists of: 1) Alternate conceptual model (ACM) identification to identify and document the major features and assumptions of each conceptual model. The process must also include a periodic review of the existing and proposed new conceptual models as data or understanding become available. 2) ACM development of each identified conceptual model through inverse modeling with historical site data. 3) ACM evaluation to identify which of conceptual models are plausible and should be included in any subsequent uncertainty assessments. 4) ACM uncertainty assessments will only be carried out for those ACMs determined to be plausible through comparison with historical observations and model structure identification measures. The parameter uncertainty assessment process generally involves: a) Model Complexity Optimization - to identify the important or relevant parameters for the uncertainty analysis; b) Characterization of Parameter Uncertainty - to develop the pdfs for the important uncertain parameters including identification of any correlations among parameters; c) Propagation of Uncertainty - to propagate parameter uncertainties (e.g., by first order second moment methods if applicable or by a Monte Carlo approach) through the model to determine the uncertainty in the model predictions of interest. 5)Estimation of combined ACM and scenario uncertainty by a double sum with each component of the inner sum (an individual CCDF) representing parameter uncertainty associated with a particular scenario and ACM and the outer sum enumerating the various plausible ACM and scenario combinations in order to represent the combined estimate of uncertainty (a family of CCDFs). A final important part of the framework includes identification, enumeration, and documentation of all the assumptions, which include those made during conceptual model development, required by the mathematical model, required by the numerical model, made during the spatial and temporal descretization process, needed to assign the statistical model and associated parameters that describe the uncertainty in the relevant input parameters, and finally those assumptions required by the propagation method. Pacific Northwest National Laboratory is operated for the U.S. Department of Energy under Contract DE-AC06-76RL01830.

Anticipating and Communicating Plausible Environmental and Health Concerns Associated with Future Disasters: The ShakeOut and ARkStorm Scenarios as Examples

NASA Astrophysics Data System (ADS)

Plumlee, G. S.; Morman, S. A.; Alpers, C. N.; Hoefen, T. M.; Meeker, G. P.

2010-12-01

Disasters commonly pose immediate threats to human safety, but can also produce hazardous materials (HM) that pose short- and long-term environmental-health threats. The U.S. Geological Survey (USGS) has helped assess potential environmental health characteristics of HM produced by various natural and anthropogenic disasters, such as the 2001 World Trade Center collapse, 2005 hurricanes Katrina and Rita, 2007-2009 southern California wildfires, various volcanic eruptions, and others. Building upon experience gained from these responses, we are now developing methods to anticipate plausible environmental and health implications of the 2008 Great Southern California ShakeOut scenario (which modeled the impacts of a 7.8 magnitude earthquake on the southern San Andreas fault, http://urbanearth.gps.caltech.edu/scenario08/), and the recent ARkStorm scenario (modeling the impacts of a major, weeks-long winter storm hitting nearly all of California, http://urbanearth.gps.caltech.edu/winter-storm/). Environmental-health impacts of various past earthquakes and extreme storms are first used to identify plausible impacts that could be associated with the disaster scenarios. Substantial insights can then be gleaned using a Geographic Information Systems (GIS) approach to link ShakeOut and ARkStorm effects maps with data extracted from diverse database sources containing geologic, hazards, and environmental information. This type of analysis helps constrain where potential geogenic (natural) and anthropogenic sources of HM (and their likely types of contaminants or pathogens) fall within areas of predicted ShakeOut-related shaking, firestorms, and landslides, and predicted ARkStorm-related precipitation, flooding, and winds. Because of uncertainties in the event models and many uncertainties in the databases used (e.g., incorrect location information, lack of detailed information on specific facilities, etc.) this approach should only be considered as the first of multiple steps toward a more quantitative, predictive approach to understanding the potential sources, types, environmental behavior, and health implications of HM predicted to result from these disaster scenarios. Although only a first step, this qualitative approach will help enhance planning for, mitigation of, and resilience to environmental-health consequences of future disasters. This qualitative approach also requires careful communication to stakeholders that does not sensationalize or overstate potential problems, but rather conveys plausible impacts and next steps to improve understanding of potential risks and their mitigation.

Using a Modification of the Capture-Recapture Model To Estimate the Need for Substance Abuse Treatment.

ERIC Educational Resources Information Center

Maxwell, Jane Carlisle; Pullum, Thomas W.

2001-01-01

Applied the capture-recapture model, through a Poisson regression to a time series of data for admissions to treatment from 1987 to 1996 to estimate the number of heroin addicts in Texas who are "at-risk" for treatment. The entire data set produced estimates that were lower and more plausible than those produced by drawing samples,…

Significance of microbial asynchronous anabolism to soil carbon dynamics driven by litter inputs

PubMed Central

Fan, Zhaosheng; Liang, Chao

2015-01-01

Soil organic carbon (SOC) plays an important role in the global carbon cycle. However, it remains largely unknown how plant litter inputs impact magnitude, composition and source configuration of the SOC stocks over long term through microbial catabolism and anabolism, mostly due to uncoupled research on litter decomposition and SOC formation. This limits our ability to predict soil system responses to changes in land-use and climate. Here, we examine how microbes act as a valve controlling carbon sequestrated from plant litters versus released to the atmosphere in natural ecosystems amended with plant litters varying in quantity and quality. We find that litter quality – not quantity – regulates long-term SOC dynamics under different plausible scenarios. Long-term changes in bulk SOC stock occur only when the quality of carbon inputs causes asynchronous change in a microbial physiological trait, defined as “microbial biosynthesis acceleration” (MBA). This is the first theoretical demonstration that the response of the SOC stocks to litter inputs is critically determined by the microbial physiology. Our work suggests that total SOC at an equilibrium state may be an intrinsic property of a given ecosystem, which ultimately is controlled by the asynchronous MBA between microbial functional groups. PMID:25849864

Significance of microbial asynchronous anabolism to soil carbon dynamics driven by litter inputs

DOE PAGES

Fan, Zhaosheng; Liang, Chao

2015-04-02

Soil organic carbon (SOC) plays an important role in the global carbon cycle. However, it remains largely unknown how plant litter inputs impact magnitude, composition and source configuration of the SOC stocks over long term through microbial catabolism and anabolism, mostly due to uncoupled research on litter decomposition and SOC formation. This limits our ability to predict soil system responses to changes in land-use and climate. Here, we examine how microbes act as a valve controlling carbon sequestrated from plant litters versus released to the atmosphere in natural ecosystems amended with plant litters varying in quantity and quality. We findmore » that litter quality – not quantity – regulates long-term SOC dynamics under different plausible scenarios. Long-term changes in bulk SOC stock occur only when the quality of carbon inputs causes asynchronous change in a microbial physiological trait, defined as ‘‘microbial biosynthesis acceleration’’ (MBA). This is the first theoretical demonstration that the response of the SOC stocks to litter inputs is critically determined by the microbial physiology. Our work suggests that total SOC at an equilibrium state may be an intrinsic property of a given ecosystem, which ultimately is controlled by the asynchronous MBA between microbial functional groups.« less

Effects of heat and cold on health, with special reference to Finnish sauna bathing.

PubMed

Heinonen, Ilkka; Laukkanen, Jari A

2018-05-01

Environmental stress such as extremely warm or cold temperature is often considered a challenge to human health and body homeostasis. However, the human body can adapt relatively well to heat and cold environments, and recent studies have also elucidated that particularly heat stress might be even highly beneficial for human health. Consequently, the aim of the present brief review is first to discuss general cardiovascular and other responses to acute heat stress, followed by a review of beneficial effects of Finnish sauna bathing on general and cardiovascular health and mortality as well as dementia and Alzheimer's disease risk. Plausible mechanisms included are improved endothelial and microvascular function, reduced blood pressure and arterial stiffness, and possibly increased angiogenesis in humans, which are likely to mediate the health benefits of sauna bathing. In addition to heat exposure with physiological adaptations, cold stress-induced physiological responses and brown fat activation on health are also discussed. This is important to take into consideration, as sauna bathing is frequently associated with cooling periods in cold(er) environments, but their combination remains poorly investigated. We finally propose, therefore, that possible additive effects of heat- and cold-stress-induced adaptations and effects on health would be worthy of further investigation.

A MULTIMODEL APPROACH FOR CALCULATING BENCHMARK DOSE

EPA Science Inventory

A Multimodel Approach for Calculating Benchmark Dose
Ramon I. Garcia and R. Woodrow Setzer

In the assessment of dose response, a number of plausible dose- response models may give fits that are consistent with the data. If no dose response formulation had been speci...

A biologically plausible computational model for auditory object recognition.

PubMed

Larson, Eric; Billimoria, Cyrus P; Sen, Kamal

2009-01-01

Object recognition is a task of fundamental importance for sensory systems. Although this problem has been intensively investigated in the visual system, relatively little is known about the recognition of complex auditory objects. Recent work has shown that spike trains from individual sensory neurons can be used to discriminate between and recognize stimuli. Multiple groups have developed spike similarity or dissimilarity metrics to quantify the differences between spike trains. Using a nearest-neighbor approach the spike similarity metrics can be used to classify the stimuli into groups used to evoke the spike trains. The nearest prototype spike train to the tested spike train can then be used to identify the stimulus. However, how biological circuits might perform such computations remains unclear. Elucidating this question would facilitate the experimental search for such circuits in biological systems, as well as the design of artificial circuits that can perform such computations. Here we present a biologically plausible model for discrimination inspired by a spike distance metric using a network of integrate-and-fire model neurons coupled to a decision network. We then apply this model to the birdsong system in the context of song discrimination and recognition. We show that the model circuit is effective at recognizing individual songs, based on experimental input data from field L, the avian primary auditory cortex analog. We also compare the performance and robustness of this model to two alternative models of song discrimination: a model based on coincidence detection and a model based on firing rate.

Incorporating drug delivery into an imaging-driven, mechanics-coupled reaction diffusion model for predicting the response of breast cancer to neoadjuvant chemotherapy: theory and preliminary clinical results

NASA Astrophysics Data System (ADS)

Jarrett, Angela M.; Hormuth, David A.; Barnes, Stephanie L.; Feng, Xinzeng; Huang, Wei; Yankeelov, Thomas E.

2018-05-01

Clinical methods for assessing tumor response to therapy are largely rudimentary, monitoring only temporal changes in tumor size. Our goal is to predict the response of breast tumors to therapy using a mathematical model that utilizes magnetic resonance imaging (MRI) data obtained non-invasively from individual patients. We extended a previously established, mechanically coupled, reaction-diffusion model for predicting tumor response initialized with patient-specific diffusion weighted MRI (DW-MRI) data by including the effects of chemotherapy drug delivery, which is estimated using dynamic contrast-enhanced (DCE-) MRI data. The extended, drug incorporated, model is initialized using patient-specific DW-MRI and DCE-MRI data. Data sets from five breast cancer patients were used—obtained before, after one cycle, and at mid-point of neoadjuvant chemotherapy. The DCE-MRI data was used to estimate spatiotemporal variations in tumor perfusion with the extended Kety–Tofts model. The physiological parameters derived from DCE-MRI were used to model changes in delivery of therapy drugs within the tumor for incorporation in the extended model. We simulated the original model and the extended model in both 2D and 3D and compare the results for this five-patient cohort. Preliminary results show reductions in the error of model predicted tumor cellularity and size compared to the experimentally-measured results for the third MRI scan when therapy was incorporated. Comparing the two models for agreement between the predicted total cellularity and the calculated total cellularity (from the DW-MRI data) reveals an increased concordance correlation coefficient from 0.81 to 0.98 for the 2D analysis and 0.85 to 0.99 for the 3D analysis (p  <  0.01 for each) when the extended model was used in place of the original model. This study demonstrates the plausibility of using DCE-MRI data as a means to estimate drug delivery on a patient-specific basis in predictive models and represents a step toward the goal of achieving individualized prediction of tumor response to therapy.

Hyperpolarization-Activated Current Induces Period-Doubling Cascades and Chaos in a Cold Thermoreceptor Model

PubMed Central

Xu, Kesheng; Maidana, Jean P.; Caviedes, Mauricio; Quero, Daniel; Aguirre, Pablo; Orio, Patricio

2017-01-01

In this article, we describe and analyze the chaotic behavior of a conductance-based neuronal bursting model. This is a model with a reduced number of variables, yet it retains biophysical plausibility. Inspired by the activity of cold thermoreceptors, the model contains a persistent Sodium current, a Calcium-activated Potassium current and a hyperpolarization-activated current (Ih) that drive a slow subthreshold oscillation. Driven by this oscillation, a fast subsystem (fast Sodium and Potassium currents) fires action potentials in a periodic fashion. Depending on the parameters, this model can generate a variety of firing patterns that includes bursting, regular tonic and polymodal firing. Here we show that the transitions between different firing patterns are often accompanied by a range of chaotic firing, as suggested by an irregular, non-periodic firing pattern. To confirm this, we measure the maximum Lyapunov exponent of the voltage trajectories, and the Lyapunov exponent and Lempel-Ziv's complexity of the ISI time series. The four-variable slow system (without spiking) also generates chaotic behavior, and bifurcation analysis shows that this is often originated by period doubling cascades. Either with or without spikes, chaos is no longer generated when the Ih is removed from the system. As the model is biologically plausible with biophysically meaningful parameters, we propose it as a useful tool to understand chaotic dynamics in neurons. PMID:28344550

Dynamic physiological modeling for functional diffuse optical tomography

PubMed Central

Diamond, Solomon Gilbert; Huppert, Theodore J.; Kolehmainen, Ville; Franceschini, Maria Angela; Kaipio, Jari P.; Arridge, Simon R.; Boas, David A.

2009-01-01

Diffuse optical tomography (DOT) is a noninvasive imaging technology that is sensitive to local concentration changes in oxy- and deoxyhemoglobin. When applied to functional neuroimaging, DOT measures hemodynamics in the scalp and brain that reflect competing metabolic demands and cardiovascular dynamics. The diffuse nature of near-infrared photon migration in tissue and the multitude of physiological systems that affect hemodynamics motivate the use of anatomical and physiological models to improve estimates of the functional hemodynamic response. In this paper, we present a linear state-space model for DOT analysis that models the physiological fluctuations present in the data with either static or dynamic estimation. We demonstrate the approach by using auxiliary measurements of blood pressure variability and heart rate variability as inputs to model the background physiology in DOT data. We evaluate the improvements accorded by modeling this physiology on ten human subjects with simulated functional hemodynamic responses added to the baseline physiology. Adding physiological modeling with a static estimator significantly improved estimates of the simulated functional response, and further significant improvements were achieved with a dynamic Kalman filter estimator (paired t tests, n = 10, P < 0.05). These results suggest that physiological modeling can improve DOT analysis. The further improvement with the Kalman filter encourages continued research into dynamic linear modeling of the physiology present in DOT. Cardiovascular dynamics also affect the blood-oxygen-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI). This state-space approach to DOT analysis could be extended to BOLD fMRI analysis, multimodal studies and real-time analysis. PMID:16242967

Maximum urine concentrating capability in a mathematical model of the inner medulla of the rat kidney.

PubMed

Marcano, Mariano; Layton, Anita T; Layton, Harold E

2010-02-01

In a mathematical model of the urine concentrating mechanism of the inner medulla of the rat kidney, a nonlinear optimization technique was used to estimate parameter sets that maximize the urine-to-plasma osmolality ratio (U/P) while maintaining the urine flow rate within a plausible physiologic range. The model, which used a central core formulation, represented loops of Henle turning at all levels of the inner medulla and a composite collecting duct (CD). The parameters varied were: water flow and urea concentration in tubular fluid entering the descending thin limbs and the composite CD at the outer-inner medullary boundary; scaling factors for the number of loops of Henle and CDs as a function of medullary depth; location and increase rate of the urea permeability profile along the CD; and a scaling factor for the maximum rate of NaCl transport from the CD. The optimization algorithm sought to maximize a quantity E that equaled U/P minus a penalty function for insufficient urine flow. Maxima of E were sought by changing parameter values in the direction in parameter space in which E increased. The algorithm attained a maximum E that increased urine osmolality and inner medullary concentrating capability by 37.5% and 80.2%, respectively, above base-case values; the corresponding urine flow rate and the concentrations of NaCl and urea were all within or near reported experimental ranges. Our results predict that urine osmolality is particularly sensitive to three parameters: the urea concentration in tubular fluid entering the CD at the outer-inner medullary boundary, the location and increase rate of the urea permeability profile along the CD, and the rate of decrease of the CD population (and thus of CD surface area) along the cortico-medullary axis.

Habitability for Complex Life and the Development and Self-Limitations of the Biotic Enhancement of Weathering

NASA Astrophysics Data System (ADS)

Schwartzman, D. W.; Volk, T.

2014-12-01

We submit that the tightly coupled coevolution of biota and climate is a critical driver of the self-organization of the biosphere over geologic time. The long-term carbon biogeochemical cycle includes a major influence of biology relevant to climatic, namely the biotic enhancement of weathering (BEW). According to a meta-analysis of field and experimental evidence, the likely magnitude of the present BEW is roughly two orders of magnitude, the culmination of its progressive increase over geologic time. Within the context of modeling this long-term cycle, this value can be used to estimate the likely abiotic temperature history of the Earth's surface, assuming plausible initial temperatures, and histories of volcanic outgassing and continental crust growth. The result of this modeling is that the Earth would have been habitable for thermophilic life (growing above 50 deg C) for the past 4.4 billion years, but not for low-temperature life, including plants and animals. Hence biospheric cooling due to biotic actions allowed the emergence of complex life. Much larger increases in BEW are self-limiting, since the atmospheric CO2 level would plunge below the lower limit potentially for photosynthesis, thereby driving a decline in the biological productivity and global BEW, related to reduced plant and soil activities, with the system being kept at this threshold or going back to higher CO2 levels, with scenarios dependent on volcanic outgassing and solar inputs. We will present astrobiological implications of this modeling. References: Schwartzman D (1999, 2002) Life, Temperature, and the Earth: The Self Organizing Biosphere. Columbia Univ. Press; Schwartzman, D. (2013) Keynote: The Geobiology of Weathering: The 13th Hypothesis. Goldschmidt Conference. (Schwartzman D. and Brantley S. (2013) Mineral. Mag. 77(5): 2170); Volk T (1998) Gaia's Body: Toward a Physiology of Earth. Copernicus.

Negotiating plausibility: intervening in the future of nanotechnology.

PubMed

Selin, Cynthia

2011-12-01

The national-level scenarios project NanoFutures focuses on the social, political, economic, and ethical implications of nanotechnology, and is initiated by the Center for Nanotechnology in Society at Arizona State University (CNS-ASU). The project involves novel methods for the development of plausible visions of nanotechnology-enabled futures, elucidates public preferences for various alternatives, and, using such preferences, helps refine future visions for research and outreach. In doing so, the NanoFutures project aims to address a central question: how to deliberate the social implications of an emergent technology whose outcomes are not known. The solution pursued by the NanoFutures project is twofold. First, NanoFutures limits speculation about the technology to plausible visions. This ambition introduces a host of concerns about the limits of prediction, the nature of plausibility, and how to establish plausibility. Second, it subjects these visions to democratic assessment by a range of stakeholders, thus raising methodological questions as to who are relevant stakeholders and how to activate different communities so as to engage the far future. This article makes the dilemmas posed by decisions about such methodological issues transparent and therefore articulates the role of plausibility in anticipatory governance.

Assembling and processing freight shipment data : developing a GIS-based origin-destination matrix for Southern California freight flows

DOT National Transportation Integrated Search

2001-06-30

Freight movements within large metropolitan areas are much less studied and analyzed than personal travel. This casts doubt on the results of much conventional travel demand modeling and planning. With so much traffic overlooked, how plausible are th...

Testing Adaptive Toolbox Models: A Bayesian Hierarchical Approach

ERIC Educational Resources Information Center

Scheibehenne, Benjamin; Rieskamp, Jorg; Wagenmakers, Eric-Jan

2013-01-01

Many theories of human cognition postulate that people are equipped with a repertoire of strategies to solve the tasks they face. This theoretical framework of a cognitive toolbox provides a plausible account of intra- and interindividual differences in human behavior. Unfortunately, it is often unclear how to rigorously test the toolbox…

Integrating Brain and Biomechanical Models—A New Paradigm for Understanding Neuro-muscular Control

PubMed Central

James, Sebastian S.; Papapavlou, Chris; Blenkinsop, Alexander; Cope, Alexander J.; Anderson, Sean R.; Moustakas, Konstantinos; Gurney, Kevin N.

2018-01-01

To date, realistic models of how the central nervous system governs behavior have been restricted in scope to the brain, brainstem or spinal column, as if these existed as disembodied organs. Further, the model is often exercised in relation to an in vivo physiological experiment with input comprising an impulse, a periodic signal or constant activation, and output as a pattern of neural activity in one or more neural populations. Any link to behavior is inferred only indirectly via these activity patterns. We argue that to discover the principles of operation of neural systems, it is necessary to express their behavior in terms of physical movements of a realistic motor system, and to supply inputs that mimic sensory experience. To do this with confidence, we must connect our brain models to neuro-muscular models and provide relevant visual and proprioceptive feedback signals, thereby closing the loop of the simulation. This paper describes an effort to develop just such an integrated brain and biomechanical system using a number of pre-existing models. It describes a model of the saccadic oculomotor system incorporating a neuromuscular model of the eye and its six extraocular muscles. The position of the eye determines how illumination of a retinotopic input population projects information about the location of a saccade target into the system. A pre-existing saccadic burst generator model was incorporated into the system, which generated motoneuron activity patterns suitable for driving the biomechanical eye. The model was demonstrated to make accurate saccades to a target luminance under a set of environmental constraints. Challenges encountered in the development of this model showed the importance of this integrated modeling approach. Thus, we exposed shortcomings in individual model components which were only apparent when these were supplied with the more plausible inputs available in a closed loop design. Consequently we were able to suggest missing functionality which the system would require to reproduce more realistic behavior. The construction of such closed-loop animal models constitutes a new paradigm of computational neurobehavior and promises a more thoroughgoing approach to our understanding of the brain's function as a controller for movement and behavior. PMID:29467606

Global warming and hepatotoxin production by cyanobacteria: what can we learn from experiments?

PubMed

El-Shehawy, Rehab; Gorokhova, Elena; Fernández-Piñas, Francisca; del Campo, Francisca F

2012-04-01

Global temperature is expected to rise throughout this century, and blooms of cyanobacteria in lakes and estuaries are predicted to increase with the current level of global warming. The potential environmental, economic and sanitation repercussions of these blooms have attracted considerable attention among the world's scientific communities, water management agencies and general public. Of particular concern is the worldwide occurrence of hepatotoxic cyanobacteria posing a serious threat to global public health. Here, we highlight plausible effects of global warming on physiological and molecular changes in these cyanobacteria and resulting effects on hepatotoxin production. We also emphasize the importance of understanding the natural biological function(s) of hepatotoxins, various mechanisms governing their synthesis, and climate-driven changes in food-web interactions, if we are to predict consequences of the current and projected levels of global warming for production and accumulation of hepatotoxins in aquatic ecosystems. Copyright © 2011 Elsevier Ltd. All rights reserved.

Minireview: The Roles of Small RNA Pathways in Reproductive Medicine

PubMed Central

Buchold, Gregory M.

2011-01-01

The discovery of small noncoding RNA, including P-element-induced wimpy testis-interacting RNA, small interfering RNA, and microRNA, has energized research in reproductive medicine. In the two decades since the identification of small RNA, first in Caenorhabditis elegans and then in other animals, scientists in many disciplines have made significant progress in elucidating their biology. A powerful battery of tools, including knockout mice and small RNA mimics and antagonists, has facilitated investigation into the functional roles and therapeutic potential of these small RNA pathways. Current data indicate that small RNA play significant roles in normal development and physiology and pathological conditions of the reproductive tracts of females and males. Biologically plausible mRNA targets for these microRNA are aggressively being discovered. The next phase of research will focus on elucidating the clinical utility of small RNA-selective agonists and antagonists. PMID:21546411

Tumor necrosis factor-α: regulation of renal function and blood pressure

PubMed Central

Garvin, Jeffrey L.

2013-01-01

Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine that becomes elevated in chronic inflammatory states such as hypertension and diabetes and has been found to mediate both increases and decreases in blood pressure. High levels of TNF-α decrease blood pressure, whereas moderate increases in TNF-α have been associated with increased NaCl retention and hypertension. The explanation for these disparate effects is not clear but could simply be due to different concentrations of TNF-α within the kidney, the physiological status of the subject, or the type of stimulus initiating the inflammatory response. TNF-α alters renal hemodynamics and nephron transport, affecting both activity and expression of transporters. It also mediates organ damage by stimulating immune cell infiltration and cell death. Here we will summarize the available findings and attempt to provide plausible explanations for such discrepancies. PMID:23515717

Update on zinc biology.

PubMed

Solomons, Noel W

2013-01-01

Zinc has become a prominent nutrient of clinical and public health interest in the new millennium. Functions and actions for zinc emerge as increasingly ubiquitous in mammalian anatomy, physiology and metabolism. There is undoubtedly an underpinning in fundamental biology for all of the aspects of zinc in human health (clinical and epidemiological) in pediatric and public health practice. Unfortunately, basic science research may not have achieved a full understanding as yet. As a complement to the applied themes in the companion articles, a selection of recent advances in the domains homeostatic regulation and transport of zinc is presented; they are integrated, in turn, with findings on genetic expression, intracellular signaling, immunity and host defense, and bone growth. The elements include ionic zinc, zinc transporters, metallothioneins, zinc metalloenzymes and zinc finger proteins. In emerging basic research, we find some plausible mechanistic explanations for delayed linear growth with zinc deficiency and increased infectious disease resistance with zinc supplementation. Copyright © 2013 S. Karger AG, Basel.

Diesel exhaust exposure, its multi-system effects, and the effect of new technology diesel exhaust.

PubMed

Reis, Haley; Reis, Cesar; Sharip, Akbar; Reis, Wenes; Zhao, Yong; Sinclair, Ryan; Beeson, Lawrence

2018-05-01

Exposure to diesel exhaust (DE) from vehicles and industry is hazardous and affects proper function of organ systems. DE can interfere with normal physiology after acute and chronic exposure to particulate matter (PM). Exposure leads to potential systemic disease processes in the central nervous, visual, hematopoietic, respiratory, cardiovascular, and renal systems. In this review, we give an overview of the epidemiological evidence supporting the harmful effects of diesel exhaust, and the numerous animal studies conducted to investigate the specific pathophysiological mechanisms behind DE exposure. Additionally, this review includes a summary of studies that used biomarkers as an indication of biological plausibility, and also studies evaluating new technology diesel exhaust (NTDE) and its systemic effects. Lastly, this review includes new approaches to improving DE emissions, and emphasizes the importance of ongoing study in this field of environmental health. Copyright © 2018 Elsevier Ltd. All rights reserved.

Capacitive Sensing for Non-Invasive Breathing and Heart Monitoring in Non-Restrained, Non-Sedated Laboratory Mice.

PubMed

González-Sánchez, Carlos; Fraile, Juan-Carlos; Pérez-Turiel, Javier; Damm, Ellen; Schneider, Jochen G; Zimmermann, Heiko; Schmitt, Daniel; Ihmig, Frank R

2016-07-07

Animal testing plays a vital role in biomedical research. Stress reduction is important for improving research results and increasing the welfare and the quality of life of laboratory animals. To estimate stress we believe it is of great importance to develop non-invasive techniques for monitoring physiological signals during the transport of laboratory animals, thereby allowing the gathering of information on the transport conditions, and, eventually, the improvement of these conditions. Here, we study the suitability of commercially available electric potential integrated circuit (EPIC) sensors, using both contact and contactless techniques, for monitoring the heart rate and breathing rate of non-restrained, non-sedated laboratory mice. The design has been tested under different scenarios with the aim of checking the plausibility of performing contactless capture of mouse heart activity (ideally with an electrocardiogram). First experimental results are shown.

Clinical review: Neuromonitoring - an update

PubMed Central

2013-01-01

Critically ill patients are frequently at risk of neurological dysfunction as a result of primary neurological conditions or secondary insults. Determining which aspects of brain function are affected and how best to manage the neurological dysfunction can often be difficult and is complicated by the limited information that can be gained from clinical examination in such patients and the effects of therapies, notably sedation, on neurological function. Methods to measure and monitor brain function have evolved considerably in recent years and now play an important role in the evaluation and management of patients with brain injury. Importantly, no single technique is ideal for all patients and different variables will need to be monitored in different patients; in many patients, a combination of monitoring techniques will be needed. Although clinical studies support the physiologic feasibility and biologic plausibility of management based on information from various monitors, data supporting this concept from randomized trials are still required. PMID:23320763

Muscle, bone, and the Utah paradigm: a 1999 overview.

PubMed

Frost, H M

2000-05-01

The still-evolving Utah paradigm of skeletal physiology supplements former ideas about the control of postnatal bone strength and "mass" in health and disease, on earth and in orbit, and as functions of physical activities including sports. In its view, peak muscle forces on bone dominate control of the biologic mechanisms that control changes in our postnatal whole-bone strength and mass. This contrasts with former ideas that chiefly nonmechanical factors dominate that control and mechanical factors have little influence on it. The newer view begs the question of how such a bone-muscle relationship would work, and the Utah paradigm offers plausible explanations for that. Whereas many biomechanicians, orthopedists, and sports medicine experts might find the newer view sensible, some people in other disciplines may not. This article summarizes some evidence that support the Utah paradigm and the above-stated view and explores some of the paradigm's features and implications.

The S-Lagrangian and a theory of homeostasis in living systems

NASA Astrophysics Data System (ADS)

Sandler, U.; Tsitolovsky, L.

2017-04-01

A major paradox of living things is their ability to actively counteract degradation in a continuously changing environment or being injured through homeostatic protection. In this study, we propose a dynamic theory of homeostasis based on a generalized Lagrangian approach (S-Lagrangian), which can be equally applied to physical and nonphysical systems. Following discoverer of homeostasis Cannon (1935), we assume that homeostasis results from tendency of the organisms to decrease of the stress and avoid of death. We show that the universality of homeostasis is a consequence of analytical properties of the S-Lagrangian, while peculiarities of the biochemical and physiological mechanisms of homeostasis determine phenomenological parameters of the S-Lagrangian. Additionally, we reveal that plausible assumptions about S-Lagrangian features lead to good agreement between theoretical descriptions and observed homeostatic behavior. Here, we have focused on homeostasis of living systems, however, the proposed theory is also capable of being extended to social systems.

Decoding thalamic afferent input using microcircuit spiking activity.

PubMed

Sederberg, Audrey J; Palmer, Stephanie E; MacLean, Jason N

2015-04-01

A behavioral response appropriate to a sensory stimulus depends on the collective activity of thousands of interconnected neurons. The majority of cortical connections arise from neighboring neurons, and thus understanding the cortical code requires characterizing information representation at the scale of the cortical microcircuit. Using two-photon calcium imaging, we densely sampled the thalamically evoked response of hundreds of neurons spanning multiple layers and columns in thalamocortical slices of mouse somatosensory cortex. We then used a biologically plausible decoder to characterize the representation of two distinct thalamic inputs, at the level of the microcircuit, to reveal those aspects of the activity pattern that are likely relevant to downstream neurons. Our data suggest a sparse code, distributed across lamina, in which a small population of cells carries stimulus-relevant information. Furthermore, we find that, within this subset of neurons, decoder performance improves when noise correlations are taken into account. Copyright © 2015 the American Physiological Society.

X-ray spectroscopic study of amorphous and polycrystalline PbO films, α-PbO, and β-PbO for direct conversion imaging.

PubMed

Qamar, A; LeBlanc, K; Semeniuk, O; Reznik, A; Lin, J; Pan, Y; Moewes, A

2017-10-13

We investigated the electronic structure of Lead Oxide (PbO) - one of the most promising photoconductor materials for direct conversion x-ray imaging detectors, using soft x-ray emission and absorption spectroscopy. Two structural configurations of thin PbO layers, namely the polycrystalline and the amorphous phase, were studied, and compared to the properties of powdered α-PbO and β-PbO samples. In addition, we performed calculations within the framework of density functional theory and found an excellent agreement between the calculated and the measured absorption and emission spectra, which indicates high accuracy of our structural models. Our work provides strong evidence that the electronic structure of PbO layers, specifically the width of the band gap and the presence of additional interband and intraband states in both conduction and valence band, depend on the deposition conditions. We tested several model structures using DFT simulations to understand what the origin of these states is. The presence of O vacancies is the most plausible explanation for these additional electronic states. Several other plausible models were ruled out including interstitial O, dislocated O and the presence of significant lattice stress in PbO.

An analytical model for the distribution of CO2 sources and sinks, fluxes, and mean concentration within the roughness sub-layer

NASA Astrophysics Data System (ADS)

Siqueira, M. B.; Katul, G. G.

2009-12-01

A one-dimensional analytical model that predicts foliage CO2 uptake rates, turbulent fluxes, and mean concentration throughout the roughness sub-layer (RSL), a layer that extends from the ground surface up to 5 times the canopy height (h), is proposed. The model combines the mean continuity equation for CO2 with first-order closure principles for turbulent fluxes and simplified physiological and radiative transfer schemes for foliage uptake. This combination results in a second-order ordinary differential equation in which it is imposed soil respiration (RE) as lower and CO2 concentration well above the RSL as upper boundary conditions. An inverse version of the model was tested against data sets from two contrasting ecosystems: a tropical forest (TF, h=40 m) and a managed irrigated rice canopy (RC, h=0.7 m) - with good agreement noted between modeled and measured mean CO2 concentration profiles within the entire RSL (see figure). Sensitivity analysis on the model parameters revealed a plausible scaling regime between them and a dimensionless parameter defined by the ratio between external (RE) and internal (stomatal conductance) characteristics controlling the CO2 exchange process. The model can be used to infer the thickness of the RSL for CO2 exchange, the inequality in zero-plane displacement between CO2 and momentum, and its consequences on modeled CO2 fluxes. A simplified version of the solution is well suited for being incorporated into large-scale climate models. Furthermore, the model framework here can be used to a priori estimate relative contributions from the soil surface and the atmosphere to canopy-air CO2 concentration thereby making it synergetic to stable isotopes studies. Panels a) and c): Profiles of normalized measured leaf area density distribution (a) for TF and RC, respectively. Continuous lines are the constant a used in the model and dashed lines represent data-derived profiles. Panels b) and d) are modeled and ensemble-averaged measured CO2 profiles reference to the uppermost measured point for TF and RC, respectively.

Modeling complex treatment strategies: construction and validation of a discrete event simulation model for glaucoma.

PubMed

van Gestel, Aukje; Severens, Johan L; Webers, Carroll A B; Beckers, Henny J M; Jansonius, Nomdo M; Schouten, Jan S A G

2010-01-01

Discrete event simulation (DES) modeling has several advantages over simpler modeling techniques in health economics, such as increased flexibility and the ability to model complex systems. Nevertheless, these benefits may come at the cost of reduced transparency, which may compromise the model's face validity and credibility. We aimed to produce a transparent report on the construction and validation of a DES model using a recently developed model of ocular hypertension and glaucoma. Current evidence of associations between prognostic factors and disease progression in ocular hypertension and glaucoma was translated into DES model elements. The model was extended to simulate treatment decisions and effects. Utility and costs were linked to disease status and treatment, and clinical and health economic outcomes were defined. The model was validated at several levels. The soundness of design and the plausibility of input estimates were evaluated in interdisciplinary meetings (face validity). Individual patients were traced throughout the simulation under a multitude of model settings to debug the model, and the model was run with a variety of extreme scenarios to compare the outcomes with prior expectations (internal validity). Finally, several intermediate (clinical) outcomes of the model were compared with those observed in experimental or observational studies (external validity) and the feasibility of evaluating hypothetical treatment strategies was tested. The model performed well in all validity tests. Analyses of hypothetical treatment strategies took about 30 minutes per cohort and lead to plausible health-economic outcomes. There is added value of DES models in complex treatment strategies such as glaucoma. Achieving transparency in model structure and outcomes may require some effort in reporting and validating the model, but it is feasible.

The Time Course of Plausibility Effects on Eye Movements in Reading: Evidence from Noun-Noun Compounds

ERIC Educational Resources Information Center

Staub, Adrian; Rayner, Keith; Pollatsek, Alexander; Hyona, Jukka; Majewski, Helen

2007-01-01

Readers' eye movements were monitored as they read sentences containing noun-noun compounds that varied in frequency (e.g., elevator mechanic, mountain lion). The left constituent of the compound was either plausible or implausible as a head noun at the point at which it appeared, whereas the compound as a whole was always plausible. When the head…

Comparison of the Mortality Probability Admission Model III, National Quality Forum, and Acute Physiology and Chronic Health Evaluation IV hospital mortality models: implications for national benchmarking*.

PubMed

Kramer, Andrew A; Higgins, Thomas L; Zimmerman, Jack E

2014-03-01

To examine the accuracy of the original Mortality Probability Admission Model III, ICU Outcomes Model/National Quality Forum modification of Mortality Probability Admission Model III, and Acute Physiology and Chronic Health Evaluation IVa models for comparing observed and risk-adjusted hospital mortality predictions. Retrospective paired analyses of day 1 hospital mortality predictions using three prognostic models. Fifty-five ICUs at 38 U.S. hospitals from January 2008 to December 2012. Among 174,001 intensive care admissions, 109,926 met model inclusion criteria and 55,304 had data for mortality prediction using all three models. None. We compared patient exclusions and the discrimination, calibration, and accuracy for each model. Acute Physiology and Chronic Health Evaluation IVa excluded 10.7% of all patients, ICU Outcomes Model/National Quality Forum 20.1%, and Mortality Probability Admission Model III 24.1%. Discrimination of Acute Physiology and Chronic Health Evaluation IVa was superior with area under receiver operating curve (0.88) compared with Mortality Probability Admission Model III (0.81) and ICU Outcomes Model/National Quality Forum (0.80). Acute Physiology and Chronic Health Evaluation IVa was better calibrated (lowest Hosmer-Lemeshow statistic). The accuracy of Acute Physiology and Chronic Health Evaluation IVa was superior (adjusted Brier score = 31.0%) to that for Mortality Probability Admission Model III (16.1%) and ICU Outcomes Model/National Quality Forum (17.8%). Compared with observed mortality, Acute Physiology and Chronic Health Evaluation IVa overpredicted mortality by 1.5% and Mortality Probability Admission Model III by 3.1%; ICU Outcomes Model/National Quality Forum underpredicted mortality by 1.2%. Calibration curves showed that Acute Physiology and Chronic Health Evaluation performed well over the entire risk range, unlike the Mortality Probability Admission Model and ICU Outcomes Model/National Quality Forum models. Acute Physiology and Chronic Health Evaluation IVa had better accuracy within patient subgroups and for specific admission diagnoses. Acute Physiology and Chronic Health Evaluation IVa offered the best discrimination and calibration on a large common dataset and excluded fewer patients than Mortality Probability Admission Model III or ICU Outcomes Model/National Quality Forum. The choice of ICU performance benchmarks should be based on a comparison of model accuracy using data for identical patients.

A Biomechanical Paradigm for Axonal Insult Within the Optic Nerve Head

PubMed Central

Burgoyne, Claude F.

2010-01-01

Rosario Hernandez This article is dedicated to Rosario Hernandez for her warm support of my own work and her genuine enthusiasm for the work of her colleagues throughout her career. I first met Rosario as a research fellow in Harry Quigley’s laboratory between 1991 and 1993. Along with Harry, John Morrison, Elaine Johnson, Abe Clark, Colm O’Brien and many others, Rosario’s work has provided lamina cribrosa astrocyte cellular mechanisms that are biomechanically plausible and in so doing provided credibility to early notions of the optic nerve head (ONH) as a biomechanical structure. We owe a large intellectual debt to Rosario for her dogged persistence in the characterization of the ONH astrocyte and lamina cribrosacyte in age and disease. Two questions run through her work and remain of central importance today. First, how do astrocytes respond to and alter the biomechanical environment of the ONH and the physiologic stresses created therein? Second, how do these physiologic demands on the astrocyte influence their ability to deliver the support to retinal ganglion cell axon transport and flow against the translaminar pressure gradient? The purpose of this article is to summarize what is known about the biomechanical determinants of retinal ganglion cell axon physiology within the ONH in the optic neuropathy of aging and Glaucoma. My goal is to provide a biomechanical framework for this discussion. This framework assumes that the ONH astrocytes and glia fundamentally support and influence both the lamina cribrosa extracellular matrix and retinal ganglion cell axon physiology. Rosario Hernandez was one of the first investigators to recognize the implications of this unique circumstance. Many of the ideas contained herein have been initially presented within or derived from her work (Hernandez, M.R., 2000. The optic nerve head in glaucoma: role of astrocytes in tissue remodeling. Prog Retin Eye Res. 19, 297–321.; Hernandez, M.R., Pena, J.D., 1997. The optic nerve head in glaucomatous optic neuropathy. Arch Ophthalmol. 115, 389–395.). PMID:20849846

How delusion is formed?

PubMed

Park, Jong Suk; Kang, Ung Gu

2016-02-01

Traditionally, delusions have been considered to be the products of misinterpretation and irrationality. However, some theorists have argued that delusions are normal or rational cognitive responses to abnormal experiences. That is, when a recently experienced peculiar event is more plausibly explained by an extraordinary hypothesis, confidence in the veracity of this extraordinary explanation is reinforced. As the number of such experiences, driven by the primary disease process in the perceptual domain, increases, this confidence builds and solidifies, forming a delusion. We tried to understand the formation of delusions using a simulation based on Bayesian inference. We found that (1) even if a delusional explanation is only marginally more plausible than a non-delusional one, the repetition of the same experience results in a firm belief in the delusion. (2) The same process explains the systematization of delusions. (3) If the perceived plausibility of the explanation is not consistent but varies over time, the development of a delusion is delayed. Additionally, this model may explain why delusions are not corrected by persuasion or rational explanation. This Bayesian inference perspective can be considered a way to understand delusions in terms of rational human heuristics. However, such experiences of "rationality" can lead to irrational conclusions, depending on the characteristics of the subject. Copyright © 2015 Elsevier Ltd. All rights reserved.

Source counting in MEG neuroimaging

NASA Astrophysics Data System (ADS)

Lei, Tianhu; Dell, John; Magee, Ralphy; Roberts, Timothy P. L.

2009-02-01

Magnetoencephalography (MEG) is a multi-channel, functional imaging technique. It measures the magnetic field produced by the primary electric currents inside the brain via a sensor array composed of a large number of superconducting quantum interference devices. The measurements are then used to estimate the locations, strengths, and orientations of these electric currents. This magnetic source imaging technique encompasses a great variety of signal processing and modeling techniques which include Inverse problem, MUltiple SIgnal Classification (MUSIC), Beamforming (BF), and Independent Component Analysis (ICA) method. A key problem with Inverse problem, MUSIC and ICA methods is that the number of sources must be detected a priori. Although BF method scans the source space on a point-to-point basis, the selection of peaks as sources, however, is finally made by subjective thresholding. In practice expert data analysts often select results based on physiological plausibility. This paper presents an eigenstructure approach for the source number detection in MEG neuroimaging. By sorting eigenvalues of the estimated covariance matrix of the acquired MEG data, the measured data space is partitioned into the signal and noise subspaces. The partition is implemented by utilizing information theoretic criteria. The order of the signal subspace gives an estimate of the number of sources. The approach does not refer to any model or hypothesis, hence, is an entirely data-led operation. It possesses clear physical interpretation and efficient computation procedure. The theoretical derivation of this method and the results obtained by using the real MEG data are included to demonstrates their agreement and the promise of the proposed approach.

Weak signal amplification and detection by higher-order sensory neurons.

PubMed

Jung, Sarah N; Longtin, Andre; Maler, Leonard

2016-04-01

Sensory systems must extract behaviorally relevant information and therefore often exhibit a very high sensitivity. How the nervous system reaches such high sensitivity levels is an outstanding question in neuroscience. Weakly electric fish (Apteronotus leptorhynchus/albifrons) are an excellent model system to address this question because detailed background knowledge is available regarding their behavioral performance and its underlying neuronal substrate. Apteronotus use their electrosense to detect prey objects. Therefore, they must be able to detect electrical signals as low as 1 μV while using a sensory integration time of <200 ms. How these very weak signals are extracted and amplified by the nervous system is not yet understood. We studied the responses of cells in the early sensory processing areas, namely, the electroreceptor afferents (EAs) and pyramidal cells (PCs) of the electrosensory lobe (ELL), the first-order electrosensory processing area. In agreement with previous work we found that EAs cannot encode very weak signals with a spike count code. However, PCs can encode prey mimic signals by their firing rate, revealing a huge signal amplification between EAs and PCs and also suggesting differences in their stimulus encoding properties. Using a simple leaky integrate-and-fire (LIF) model we predict that the target neurons of PCs in the midbrain torus semicircularis (TS) are able to detect very weak signals. In particular, TS neurons could do so by assuming biologically plausible convergence rates as well as very simple decoding strategies such as temporal integration, threshold crossing, and combining the inputs of PCs. Copyright © 2016 the American Physiological Society.

A quantitative dynamic systems model of health-related quality of life among older adults

PubMed Central

Roppolo, Mattia; Kunnen, E Saskia; van Geert, Paul L; Mulasso, Anna; Rabaglietti, Emanuela

2015-01-01

Health-related quality of life (HRQOL) is a person-centered concept. The analysis of HRQOL is highly relevant in the aged population, which is generally suffering from health decline. Starting from a conceptual dynamic systems model that describes the development of HRQOL in individuals over time, this study aims to develop and test a quantitative dynamic systems model, in order to reveal the possible dynamic trends of HRQOL among older adults. The model is tested in different ways: first, with a calibration procedure to test whether the model produces theoretically plausible results, and second, with a preliminary validation procedure using empirical data of 194 older adults. This first validation tested the prediction that given a particular starting point (first empirical data point), the model will generate dynamic trajectories that lead to the observed endpoint (second empirical data point). The analyses reveal that the quantitative model produces theoretically plausible trajectories, thus providing support for the calibration procedure. Furthermore, the analyses of validation show a good fit between empirical and simulated data. In fact, no differences were found in the comparison between empirical and simulated final data for the same subgroup of participants, whereas the comparison between different subgroups of people resulted in significant differences. These data provide an initial basis of evidence for the dynamic nature of HRQOL during the aging process. Therefore, these data may give new theoretical and applied insights into the study of HRQOL and its development with time in the aging population. PMID:26604722

Effects of plausibility on structural priming.

PubMed

Christianson, Kiel; Luke, Steven G; Ferreira, Fernanda

2010-03-01

We report a replication and extension of Ferreira (2003), in which it was observed that native adult English speakers misinterpret passive sentences that relate implausible but not impossible semantic relationships (e.g., The angler was caught by the fish) significantly more often than they do plausible passives or plausible or implausible active sentences. In the experiment reported here, participants listened to the same plausible and implausible passive and active sentences as in Ferreira (2003), answered comprehension questions, and then orally described line drawings of simple transitive actions. The descriptions were analyzed as a measure of structural priming (Bock, 1986). Question accuracy data replicated Ferreira (2003). Production data yielded an interaction: Passive descriptions were produced more often after plausible passives and implausible actives. We interpret these results as indicative of a language processor that proceeds along differentiated morphosyntactic and semantic routes. The processor may end up adjudicating between conflicting outputs from these routes by settling on a "good enough" representation that is not completely faithful to the input.

A computational model of visual marking using an inter-connected network of spiking neurons: the spiking search over time & space model (sSoTS).

PubMed

Mavritsaki, Eirini; Heinke, Dietmar; Humphreys, Glyn W; Deco, Gustavo

2006-01-01

In the real world, visual information is selected over time as well as space, when we prioritise new stimuli for attention. Watson and Humphreys [Watson, D., Humphreys, G.W., 1997. Visual marking: prioritizing selection for new objects by top-down attentional inhibition of old objects. Psychological Review 104, 90-122] presented evidence that new information in search tasks is prioritised by (amongst other processes) active ignoring of old items - a process they termed visual marking. In this paper we present, for the first time, an explicit computational model of visual marking using biologically plausible activation functions. The "spiking search over time and space" model (sSoTS) incorporates different synaptic components (NMDA, AMPA, GABA) and a frequency adaptation mechanism based on [Ca(2+)] sensitive K(+) current. This frequency adaptation current can act as a mechanism that suppresses the previously attended items. We show that, when coupled with a process of active inhibition applied to old items, frequency adaptation leads to old items being de-prioritised (and new items prioritised) across time in search. Furthermore, the time course of these processes mimics the time course of the preview effect in human search. The results indicate that the sSoTS model can provide a biologically plausible account of human search over time as well as space.

Modelling Trial-by-Trial Changes in the Mismatch Negativity

PubMed Central

Lieder, Falk; Daunizeau, Jean; Garrido, Marta I.; Friston, Karl J.; Stephan, Klaas E.

2013-01-01

The mismatch negativity (MMN) is a differential brain response to violations of learned regularities. It has been used to demonstrate that the brain learns the statistical structure of its environment and predicts future sensory inputs. However, the algorithmic nature of these computations and the underlying neurobiological implementation remain controversial. This article introduces a mathematical framework with which competing ideas about the computational quantities indexed by MMN responses can be formalized and tested against single-trial EEG data. This framework was applied to five major theories of the MMN, comparing their ability to explain trial-by-trial changes in MMN amplitude. Three of these theories (predictive coding, model adjustment, and novelty detection) were formalized by linking the MMN to different manifestations of the same computational mechanism: approximate Bayesian inference according to the free-energy principle. We thereby propose a unifying view on three distinct theories of the MMN. The relative plausibility of each theory was assessed against empirical single-trial MMN amplitudes acquired from eight healthy volunteers in a roving oddball experiment. Models based on the free-energy principle provided more plausible explanations of trial-by-trial changes in MMN amplitude than models representing the two more traditional theories (change detection and adaptation). Our results suggest that the MMN reflects approximate Bayesian learning of sensory regularities, and that the MMN-generating process adjusts a probabilistic model of the environment according to prediction errors. PMID:23436989

An object-oriented software for fate and exposure assessments.

PubMed

Scheil, S; Baumgarten, G; Reiter, B; Schwartz, S; Wagner, J O; Trapp, S; Matthies, M

1995-07-01

The model system CemoS(1) (Chemical Exposure Model System) was developed for the exposure prediction of hazardous chemicals released to the environment. Eight different models were implemented involving chemicals fate simulation in air, water, soil and plants after continuous or single emissions from point and diffuse sources. Scenario studies are supported by a substance and an environmental data base. All input data are checked on their plausibility. Substance and environmental process estimation functions facilitate generic model calculations. CemoS is implemented in a modular structure using object-oriented programming.

The Big Bang and Cosmic Inflation

NASA Astrophysics Data System (ADS)

Guth, Alan H.

2014-03-01

A summary is given of the key developments of cosmology in the 20th century, from the work of Albert Einstein to the emergence of the generally accepted hot big bang model. The successes of this model are reviewed, but emphasis is placed on the questions that the model leaves unanswered. The remainder of the paper describes the inflationary universe model, which provides plausible answers to a number of these questions. It also offers a possible explanation for the origin of essentially all the matter and energy in the observed universe.

The Plausibility of a String Quartet Performance in Virtual Reality.

PubMed

Bergstrom, Ilias; Azevedo, Sergio; Papiotis, Panos; Saldanha, Nuno; Slater, Mel

2017-04-01

We describe an experiment that explores the contribution of auditory and other features to the illusion of plausibility in a virtual environment that depicts the performance of a string quartet. 'Plausibility' refers to the component of presence that is the illusion that the perceived events in the virtual environment are really happening. The features studied were: Gaze (the musicians ignored the participant, the musicians sometimes looked towards and followed the participant's movements), Sound Spatialization (Mono, Stereo, Spatial), Auralization (no sound reflections, reflections corresponding to a room larger than the one perceived, reflections that exactly matched the virtual room), and Environment (no sound from outside of the room, birdsong and wind corresponding to the outside scene). We adopted the methodology based on color matching theory, where 20 participants were first able to assess their feeling of plausibility in the environment with each of the four features at their highest setting. Then five times participants started from a low setting on all features and were able to make transitions from one system configuration to another until they matched their original feeling of plausibility. From these transitions a Markov transition matrix was constructed, and also probabilities of a match conditional on feature configuration. The results show that Environment and Gaze were individually the most important factors influencing the level of plausibility. The highest probability transitions were to improve Environment and Gaze, and then Auralization and Spatialization. We present this work as both a contribution to the methodology of assessing presence without questionnaires, and showing how various aspects of a musical performance can influence plausibility.

What if? Neural activity underlying semantic and episodic counterfactual thinking.

PubMed

Parikh, Natasha; Ruzic, Luka; Stewart, Gregory W; Spreng, R Nathan; De Brigard, Felipe

2018-05-25

Counterfactual thinking (CFT) is the process of mentally simulating alternative versions of known facts. In the past decade, cognitive neuroscientists have begun to uncover the neural underpinnings of CFT, particularly episodic CFT (eCFT), which activates regions in the default network (DN) also activated by episodic memory (eM) recall. However, the engagement of DN regions is different for distinct kinds of eCFT. More plausible counterfactuals and counterfactuals about oneself show stronger activity in DN regions compared to implausible and other- or object-focused counterfactuals. The current study sought to identify a source for this difference in DN activity. Specifically, self-focused counterfactuals may also be more plausible, suggesting that DN core regions are sensitive to the plausibility of a simulation. On the other hand, plausible and self-focused counterfactuals may involve more episodic information than implausible and other-focused counterfactuals, which would imply DN sensitivity to episodic information. In the current study, we compared episodic and semantic counterfactuals generated to be plausible or implausible against episodic and semantic memory reactivation using fMRI. Taking multivariate and univariate approaches, we found that the DN is engaged more during episodic simulations, including eM and all eCFT, than during semantic simulations. Semantic simulations engaged more inferior temporal and lateral occipital regions. The only region that showed strong plausibility effects was the hippocampus, which was significantly engaged for implausible CFT but not for plausible CFT, suggestive of binding more disparate information. Consequences of these findings for the cognitive neuroscience of mental simulation are discussed. Published by Elsevier Inc.

The double crush syndrome revisited--a Delphi study to reveal current expert views on mechanisms underlying dual nerve disorders.

PubMed

Schmid, Annina B; Coppieters, Michel W

2011-12-01

A high prevalence of dual nerve disorders is frequently reported. How a secondary nerve disorder may develop following a primary nerve disorder remains largely unknown. Although still frequently cited, most explanatory theories were formulated many years ago. Considering recent advances in neuroscience, it is uncertain whether these theories still reflect current expert opinion. A Delphi study was conducted to update views on potential mechanisms underlying dual nerve disorders. In three rounds, seventeen international experts in the field of peripheral nerve disorders were asked to list possible mechanisms and rate their plausibility. Mechanisms with a median plausibility rating of ≥7 out of 10 were considered highly plausible. The experts identified fourteen mechanisms associated with a first nerve disorder that may predispose to the development of another nerve disorder. Of these fourteen mechanisms, nine have not previously been linked to double crush. Four mechanisms were considered highly plausible (impaired axonal transport, ion channel up or downregulation, inflammation in the dorsal root ganglia and neuroma-in-continuity). Eight additional mechanisms were listed which are not triggered by a primary nerve disorder, but may render the nervous system more vulnerable to multiple nerve disorders, such as systemic diseases and neurotoxic medication. Even though many mechanisms were classified as plausible or highly plausible, overall plausibility ratings varied widely. Experts indicated that a wide range of mechanisms has to be considered to better understand dual nerve disorders. Previously listed theories cannot be discarded, but may be insufficient to explain the high prevalence of dual nerve disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Interface Prostheses With Classifier-Feedback-Based User Training.

PubMed

Fang, Yinfeng; Zhou, Dalin; Li, Kairu; Liu, Honghai

2017-11-01

It is evident that user training significantly affects performance of pattern-recognition-based myoelectric prosthetic device control. Despite plausible classification accuracy on offline datasets, online accuracy usually suffers from the changes in physiological conditions and electrode displacement. The user ability in generating consistent electromyographic (EMG) patterns can be enhanced via proper user training strategies in order to improve online performance. This study proposes a clustering-feedback strategy that provides real-time feedback to users by means of a visualized online EMG signal input as well as the centroids of the training samples, whose dimensionality is reduced to minimal number by dimension reduction. Clustering feedback provides a criterion that guides users to adjust motion gestures and muscle contraction forces intentionally. The experiment results have demonstrated that hand motion recognition accuracy increases steadily along the progress of the clustering-feedback-based user training, while conventional classifier-feedback methods, i.e., label feedback, hardly achieve any improvement. The result concludes that the use of proper classifier feedback can accelerate the process of user training, and implies prosperous future for the amputees with limited or no experience in pattern-recognition-based prosthetic device manipulation.It is evident that user training significantly affects performance of pattern-recognition-based myoelectric prosthetic device control. Despite plausible classification accuracy on offline datasets, online accuracy usually suffers from the changes in physiological conditions and electrode displacement. The user ability in generating consistent electromyographic (EMG) patterns can be enhanced via proper user training strategies in order to improve online performance. This study proposes a clustering-feedback strategy that provides real-time feedback to users by means of a visualized online EMG signal input as well as the centroids of the training samples, whose dimensionality is reduced to minimal number by dimension reduction. Clustering feedback provides a criterion that guides users to adjust motion gestures and muscle contraction forces intentionally. The experiment results have demonstrated that hand motion recognition accuracy increases steadily along the progress of the clustering-feedback-based user training, while conventional classifier-feedback methods, i.e., label feedback, hardly achieve any improvement. The result concludes that the use of proper classifier feedback can accelerate the process of user training, and implies prosperous future for the amputees with limited or no experience in pattern-recognition-based prosthetic device manipulation.

Zinc oxide nanoflowers make new blood vessels

NASA Astrophysics Data System (ADS)

Barui, Ayan Kumar; Veeriah, Vimal; Mukherjee, Sudip; Manna, Joydeb; Patel, Ajay Kumar; Patra, Sujata; Pal, Krishnendu; Murali, Shruthi; Rana, Rohit K.; Chatterjee, Suvro; Patra, Chitta Ranjan

2012-11-01

It is well established that angiogenesis is the process of formation of new capillaries from pre-existing blood vessels. It is a complex process, involving both pro- and anti-angiogenic factors, and plays a significant role in physiological and pathophysiological processes such as embryonic development, atherosclerosis, post-ischemic vascularization of the myocardium, tumor growth and metastasis, rheumatoid arthritis etc. This is the first report of zinc oxide (ZnO) nanoflowers that show significant pro-angiogenic properties (formation of new capillaries from pre-existing blood vessels), observed by in vitro and in vivo angiogenesis assays. The egg yolk angiogenesis assay using ZnO nanoflowers indicates the presence of matured blood vessels formation. Additionally, it helps to promote endothelial cell (EA.hy926 cells) migration in wound healing assays. Formation of reactive oxygen species (ROS), especially hydrogen peroxide (H2O2)--a redox signaling molecule, might be the plausible mechanism for nanoflower-based angiogenesis. Angiogenesis by nanoflowers may provide the basis for the future development of new alternative therapeutic treatment strategies for cardiovascular and ischemic diseases, where angiogenesis plays a significant role.It is well established that angiogenesis is the process of formation of new capillaries from pre-existing blood vessels. It is a complex process, involving both pro- and anti-angiogenic factors, and plays a significant role in physiological and pathophysiological processes such as embryonic development, atherosclerosis, post-ischemic vascularization of the myocardium, tumor growth and metastasis, rheumatoid arthritis etc. This is the first report of zinc oxide (ZnO) nanoflowers that show significant pro-angiogenic properties (formation of new capillaries from pre-existing blood vessels), observed by in vitro and in vivo angiogenesis assays. The egg yolk angiogenesis assay using ZnO nanoflowers indicates the presence of matured blood vessels formation. Additionally, it helps to promote endothelial cell (EA.hy926 cells) migration in wound healing assays. Formation of reactive oxygen species (ROS), especially hydrogen peroxide (H2O2)--a redox signaling molecule, might be the plausible mechanism for nanoflower-based angiogenesis. Angiogenesis by nanoflowers may provide the basis for the future development of new alternative therapeutic treatment strategies for cardiovascular and ischemic diseases, where angiogenesis plays a significant role. Electronic supplementary information (ESI) available: See DOI: 10.1039/c2nr32369a

Computational approaches to cognition: the bottom-up view.

PubMed

Koch, C

1993-04-01

How can higher level aspects of cognition, such as figure-ground segregation, object recognition, selective focal attention and ultimately even awareness, be implemented at the level of synapses and neurons? A number of theoretical studies emerging out of the connectionist and the computational neuroscience communities are starting to address these issues using neural plausible models.

Memory colours affect colour appearance.

PubMed

Witzel, Christoph; Olkkonen, Maria; Gegenfurtner, Karl R

2016-01-01

Memory colour effects show that colour perception is affected by memory and prior knowledge and hence by cognition. None of Firestone & Scholl's (F&S's) potential pitfalls apply to our work on memory colours. We present a Bayesian model of colour appearance to illustrate that an interaction between perception and memory is plausible from the perspective of vision science.

Topic Models in Information Retrieval

DTIC Science & Technology

2007-08-01

Information Processing Systems, Cambridge, MA, MIT Press, 2004. Brown, P.F., Della Pietra, V.J., deSouza, P.V., Lai, J.C. and Mercer, R.L., Class-based...2003. http://www.wkap.nl/prod/b/1-4020-1216-0. Croft, W.B., Lucia , T.J., Cringean, J., and Willett, P., Retrieving Documents By Plausible Inference

Some Additional Lessons from the Wechsler Scales: A Rejoinder to Kaufman and Keith.

ERIC Educational Resources Information Center

Macmann, Gregg M.; Barnett, David W.

1994-01-01

Reacts to previous arguments regarding verbal and performance constructs of Wechsler Scales. Contends that general factor model is more plausible representation of data for these scales. Suggests issue is moot when considered in regards to practical applications. Supports analysis of needed skills and instructional environments in educational…

Enrollment Simulation and Planning. Strategies & Solutions Series, No. 3.

ERIC Educational Resources Information Center

McIntyre, Chuck

Enrollment simulation and planning (ESP) is centered on the use of statistical models to describe how and why college enrollments fluctuate. College planners may use this approach with confidence to simulate any number of plausible future scenarios. Planners can then set a variety of possible college actions against these scenarios, and examine…

Diagnosis of Cognitive Errors by Statistical Pattern Recognition Methods.

ERIC Educational Resources Information Center

Tatsuoka, Kikumi K.; Tatsuoka, Maurice M.

The rule space model permits measurement of cognitive skill acquisition, diagnosis of cognitive errors, and detection of the strengths and weaknesses of knowledge possessed by individuals. Two ways to classify an individual into his or her most plausible latent state of knowledge include: (1) hypothesis testing--Bayes' decision rules for minimum…

'Where's the flux' star: Exocomets, or Giant Impact?

NASA Astrophysics Data System (ADS)

Meng, Huan; Boyajian, Tabetha; Kennedy, Grant; Lisse, Carey; Marengo, Massimo; Wright, Jason; Wyatt, Mark

2015-12-01

The discovery of an unusual stellar light curve in the Kepler data of KIC 8462852 has sparked a media frenzy about 'alien megastructures' orbiting that star. Behind the public's excitement about 'aliens,' there is however a true science story: KIC 8462852 offers us a unique window to observe, in real time, the rare cataclysmic events happening in a mature extrasolar planetary system. After analysis of the existing constraints of the system, two possible models stand out as the plausible explanations for the light curve anomaly: immediate aftermath of a large planetary or planetesimal impact, or apparitions of a family of comets or comet fragments. The two plausible models predict very different IR evolution over the years following the transit events, providing a good diagnostic to distinguish them. With shallow mapping of the Kepler field in January 2015, Spitzer/IRAC has found KIC 8462852 with a marginal excess at 4.5 micron. Here, we propose to monitor KIC 8462852 on a regular basis to identify and track its IR excess evolution with deeper images and more accurate photometry.

Controls on the Archean climate system investigated with a global climate model.

PubMed

Wolf, E T; Toon, O B

2014-03-01

The most obvious means of resolving the faint young Sun paradox is to invoke large quantities of greenhouse gases, namely, CO2 and CH4. However, numerous changes to the Archean climate system have been suggested that may have yielded additional warming, thus easing the required greenhouse gas burden. Here, we use a three-dimensional climate model to examine some of the factors that controlled Archean climate. We examine changes to Earth's rotation rate, surface albedo, cloud properties, and total atmospheric pressure following proposals from the recent literature. While the effects of increased planetary rotation rate on surface temperature are insignificant, plausible changes to the surface albedo, cloud droplet number concentrations, and atmospheric nitrogen inventory may each impart global mean warming of 3-7 K. While none of these changes present a singular solution to the faint young Sun paradox, a combination can have a large impact on climate. Global mean surface temperatures at or above 288 K could easily have been maintained throughout the entirety of the Archean if plausible changes to clouds, surface albedo, and nitrogen content occurred.

Developing and applying uncertain global climate change projections for regional water management planning

NASA Astrophysics Data System (ADS)

Groves, David G.; Yates, David; Tebaldi, Claudia

2008-12-01

Climate change may impact water resources management conditions in difficult-to-predict ways. A key challenge for water managers is how to incorporate highly uncertain information about potential climate change from global models into local- and regional-scale water management models and tools to support local planning. This paper presents a new method for developing large ensembles of local daily weather that reflect a wide range of plausible future climate change scenarios while preserving many statistical properties of local historical weather patterns. This method is demonstrated by evaluating the possible impact of climate change on the Inland Empire Utilities Agency service area in southern California. The analysis shows that climate change could impact the region, increasing outdoor water demand by up to 10% by 2040, decreasing local water supply by up to 40% by 2040, and decreasing sustainable groundwater yields by up to 15% by 2040. The range of plausible climate projections suggests the need for the region to augment its long-range water management plans to reduce its vulnerability to climate change.

High-Throughput Physiologically Based Toxicokinetic Models for ToxCast Chemicals

EPA Science Inventory

Physiologically based toxicokinetic (PBTK) models aid in predicting exposure doses needed to create tissue concentrations equivalent to those identified as bioactive by ToxCast. We have implemented four empirical and physiologically-based toxicokinetic (TK) models within a new R ...

A PHYSIOLOGICALLY BASED TOXICOKINETIC MODEL FOR LAKE TROUT (SALVELINUS NAMAYCUSH)

EPA Science Inventory

A physiologically based toxicokinetic (PB-TK) model for fish, incorporating chemical exchange at the gill and accumulation in five tissue compartments, was used to examine the effect of natural variability in physiological, morphological, and physico-chemical parameters on model ...

Models, Data, and War: a Critique of the Foundation for Defense Analyses.

DTIC Science & Technology

1980-03-12

scientific formulation 6 An "objective" solution 8 Analysis of a squishy problem 9 A judgmental formulation 9 A potential for distortion 11 A subjective...inextricably tied to those judgments. Different analysts, with apparently identical knowledge of a real world problem, may develop plausible formulations ...configured is a concrete theoretical statement." 2/ The formulation of a computer model--conceiving a mathematical representation of the real world

Projections of Rapidly Rising Temperatures over Africa Under Low Mitigation

NASA Technical Reports Server (NTRS)

Engelbrecht, Francois; Adegoke, Jimmy; Bopape, Mary-Jane; Naidoo, Mogesh; Garland, Rebecca; Thatcher, Marcus; McGregor, John; Katzfe, Jack; Werner, Micha; Ichoku, Charles;

Amblyomma americanum tick calreticulin binds C1q but does not inhibit activation of the classical complement cascade

PubMed Central

Kim, Tae Kwon; Ibelli, Adriana Mércia Guaratini; Mulenga, Albert

2014-01-01

In this study we characterized Amblyomma americanum (Aam) tick calreticulin (CRT) homolog in tick feeding physiology. In nature, different tick species can be found feeding on the same animal host. This suggests that different tick species found feeding on the same host can modulate the same host anti-tick defense pathways to successfully feed. From this perspective it’s plausible that different tick species can utilize universally conserved proteins such as CRT to regulate and facilitate feeding. CRT is a multi-functional protein found in most taxa that is injected into the vertebrate host during tick feeding. Apart from it’s current use as a biomarker for human tick bites, role(s) of this protein in tick feeding physiology have not been elucidated. Here we show that annotated functional CRT amino acid motifs are well conserved in tick CRT. However our data show that despite high amino acid identity levels to functionally characterized CRT homologs in other organisms, AamCRT is apparently functionally different. Pichia pastoris expressed recombinant (r) AamCRT bound C1q, the first component of the classical complement system, but it did not inhibit activation of this pathway. This contrast with reports of other parasite CRT that inhibited activation of the classical complement pathway through sequestration of C1q. Furthermore rAamCRT did not bind factor Xa in contrast to reports of parasite CRT binding factor Xa, an important protease in the blood clotting system. Consistent with this observation, rAamCRT did not affect plasma clotting or platelet aggregation aggregation. We discuss our findings in the context of tick feeding physiology. PMID:25454607

Unsupervised Learning in an Ensemble of Spiking Neural Networks Mediated by ITDP.

PubMed

Shim, Yoonsik; Philippides, Andrew; Staras, Kevin; Husbands, Phil

2016-10-01

We propose a biologically plausible architecture for unsupervised ensemble learning in a population of spiking neural network classifiers. A mixture of experts type organisation is shown to be effective, with the individual classifier outputs combined via a gating network whose operation is driven by input timing dependent plasticity (ITDP). The ITDP gating mechanism is based on recent experimental findings. An abstract, analytically tractable model of the ITDP driven ensemble architecture is derived from a logical model based on the probabilities of neural firing events. A detailed analysis of this model provides insights that allow it to be extended into a full, biologically plausible, computational implementation of the architecture which is demonstrated on a visual classification task. The extended model makes use of a style of spiking network, first introduced as a model of cortical microcircuits, that is capable of Bayesian inference, effectively performing expectation maximization. The unsupervised ensemble learning mechanism, based around such spiking expectation maximization (SEM) networks whose combined outputs are mediated by ITDP, is shown to perform the visual classification task well and to generalize to unseen data. The combined ensemble performance is significantly better than that of the individual classifiers, validating the ensemble architecture and learning mechanisms. The properties of the full model are analysed in the light of extensive experiments with the classification task, including an investigation into the influence of different input feature selection schemes and a comparison with a hierarchical STDP based ensemble architecture.

The neural optimal control hierarchy for motor control

NASA Astrophysics Data System (ADS)

DeWolf, T.; Eliasmith, C.

2011-10-01

Our empirical, neuroscientific understanding of biological motor systems has been rapidly growing in recent years. However, this understanding has not been systematically mapped to a quantitative characterization of motor control based in control theory. Here, we attempt to bridge this gap by describing the neural optimal control hierarchy (NOCH), which can serve as a foundation for biologically plausible models of neural motor control. The NOCH has been constructed by taking recent control theoretic models of motor control, analyzing the required processes, generating neurally plausible equivalent calculations and mapping them on to the neural structures that have been empirically identified to form the anatomical basis of motor control. We demonstrate the utility of the NOCH by constructing a simple model based on the identified principles and testing it in two ways. First, we perturb specific anatomical elements of the model and compare the resulting motor behavior with clinical data in which the corresponding area of the brain has been damaged. We show that damaging the assigned functions of the basal ganglia and cerebellum can cause the movement deficiencies seen in patients with Huntington's disease and cerebellar lesions. Second, we demonstrate that single spiking neuron data from our model's motor cortical areas explain major features of single-cell responses recorded from the same primate areas. We suggest that together these results show how NOCH-based models can be used to unify a broad range of data relevant to biological motor control in a quantitative, control theoretic framework.

Unsupervised Learning in an Ensemble of Spiking Neural Networks Mediated by ITDP

PubMed Central

Staras, Kevin

2016-01-01

We propose a biologically plausible architecture for unsupervised ensemble learning in a population of spiking neural network classifiers. A mixture of experts type organisation is shown to be effective, with the individual classifier outputs combined via a gating network whose operation is driven by input timing dependent plasticity (ITDP). The ITDP gating mechanism is based on recent experimental findings. An abstract, analytically tractable model of the ITDP driven ensemble architecture is derived from a logical model based on the probabilities of neural firing events. A detailed analysis of this model provides insights that allow it to be extended into a full, biologically plausible, computational implementation of the architecture which is demonstrated on a visual classification task. The extended model makes use of a style of spiking network, first introduced as a model of cortical microcircuits, that is capable of Bayesian inference, effectively performing expectation maximization. The unsupervised ensemble learning mechanism, based around such spiking expectation maximization (SEM) networks whose combined outputs are mediated by ITDP, is shown to perform the visual classification task well and to generalize to unseen data. The combined ensemble performance is significantly better than that of the individual classifiers, validating the ensemble architecture and learning mechanisms. The properties of the full model are analysed in the light of extensive experiments with the classification task, including an investigation into the influence of different input feature selection schemes and a comparison with a hierarchical STDP based ensemble architecture. PMID:27760125

Neural network modeling of associative memory: Beyond the Hopfield model

NASA Astrophysics Data System (ADS)

Dasgupta, Chandan

1992-07-01

A number of neural network models, in which fixed-point and limit-cycle attractors of the underlying dynamics are used to store and associatively recall information, are described. In the first class of models, a hierarchical structure is used to store an exponentially large number of strongly correlated memories. The second class of models uses limit cycles to store and retrieve individual memories. A neurobiologically plausible network that generates low-amplitude periodic variations of activity, similar to the oscillations observed in electroencephalographic recordings, is also described. Results obtained from analytic and numerical studies of the properties of these networks are discussed.

Fractional Brownian motion and multivariate-t models for longitudinal biomedical data, with application to CD4 counts in HIV-positive patients.

PubMed

Stirrup, Oliver T; Babiker, Abdel G; Carpenter, James R; Copas, Andrew J

2016-04-30

Longitudinal data are widely analysed using linear mixed models, with 'random slopes' models particularly common. However, when modelling, for example, longitudinal pre-treatment CD4 cell counts in HIV-positive patients, the incorporation of non-stationary stochastic processes such as Brownian motion has been shown to lead to a more biologically plausible model and a substantial improvement in model fit. In this article, we propose two further extensions. Firstly, we propose the addition of a fractional Brownian motion component, and secondly, we generalise the model to follow a multivariate-t distribution. These extensions are biologically plausible, and each demonstrated substantially improved fit on application to example data from the Concerted Action on SeroConversion to AIDS and Death in Europe study. We also propose novel procedures for residual diagnostic plots that allow such models to be assessed. Cohorts of patients were simulated from the previously reported and newly developed models in order to evaluate differences in predictions made for the timing of treatment initiation under different clinical management strategies. A further simulation study was performed to demonstrate the substantial biases in parameter estimates of the mean slope of CD4 decline with time that can occur when random slopes models are applied in the presence of censoring because of treatment initiation, with the degree of bias found to depend strongly on the treatment initiation rule applied. Our findings indicate that researchers should consider more complex and flexible models for the analysis of longitudinal biomarker data, particularly when there are substantial missing data, and that the parameter estimates from random slopes models must be interpreted with caution. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Semantics-based plausible reasoning to extend the knowledge coverage of medical knowledge bases for improved clinical decision support.

PubMed

Mohammadhassanzadeh, Hossein; Van Woensel, William; Abidi, Samina Raza; Abidi, Syed Sibte Raza

2017-01-01

Capturing complete medical knowledge is challenging-often due to incomplete patient Electronic Health Records (EHR), but also because of valuable, tacit medical knowledge hidden away in physicians' experiences. To extend the coverage of incomplete medical knowledge-based systems beyond their deductive closure, and thus enhance their decision-support capabilities, we argue that innovative, multi-strategy reasoning approaches should be applied. In particular, plausible reasoning mechanisms apply patterns from human thought processes, such as generalization, similarity and interpolation, based on attributional, hierarchical, and relational knowledge. Plausible reasoning mechanisms include inductive reasoning , which generalizes the commonalities among the data to induce new rules, and analogical reasoning , which is guided by data similarities to infer new facts. By further leveraging rich, biomedical Semantic Web ontologies to represent medical knowledge, both known and tentative, we increase the accuracy and expressivity of plausible reasoning, and cope with issues such as data heterogeneity, inconsistency and interoperability. In this paper, we present a Semantic Web-based, multi-strategy reasoning approach, which integrates deductive and plausible reasoning and exploits Semantic Web technology to solve complex clinical decision support queries. We evaluated our system using a real-world medical dataset of patients with hepatitis, from which we randomly removed different percentages of data (5%, 10%, 15%, and 20%) to reflect scenarios with increasing amounts of incomplete medical knowledge. To increase the reliability of the results, we generated 5 independent datasets for each percentage of missing values, which resulted in 20 experimental datasets (in addition to the original dataset). The results show that plausibly inferred knowledge extends the coverage of the knowledge base by, on average, 2%, 7%, 12%, and 16% for datasets with, respectively, 5%, 10%, 15%, and 20% of missing values. This expansion in the KB coverage allowed solving complex disease diagnostic queries that were previously unresolvable, without losing the correctness of the answers. However, compared to deductive reasoning, data-intensive plausible reasoning mechanisms yield a significant performance overhead. We observed that plausible reasoning approaches, by generating tentative inferences and leveraging domain knowledge of experts, allow us to extend the coverage of medical knowledge bases, resulting in improved clinical decision support. Second, by leveraging OWL ontological knowledge, we are able to increase the expressivity and accuracy of plausible reasoning methods. Third, our approach is applicable to clinical decision support systems for a range of chronic diseases.

Plausible rice yield losses under future climate warming.

PubMed

Zhao, Chuang; Piao, Shilong; Wang, Xuhui; Huang, Yao; Ciais, Philippe; Elliott, Joshua; Huang, Mengtian; Janssens, Ivan A; Li, Tao; Lian, Xu; Liu, Yongwen; Müller, Christoph; Peng, Shushi; Wang, Tao; Zeng, Zhenzhong; Peñuelas, Josep

2016-12-19

Rice is the staple food for more than 50% of the world's population 1-3 . Reliable prediction of changes in rice yield is thus central for maintaining global food security. This is an extraordinary challenge. Here, we compare the sensitivity of rice yield to temperature increase derived from field warming experiments and three modelling approaches: statistical models, local crop models and global gridded crop models. Field warming experiments produce a substantial rice yield loss under warming, with an average temperature sensitivity of -5.2 ± 1.4% K -1 . Local crop models give a similar sensitivity (-6.3 ± 0.4% K -1 ), but statistical and global gridded crop models both suggest less negative impacts of warming on yields (-0.8 ± 0.3% and -2.4 ± 3.7% K -1 , respectively). Using data from field warming experiments, we further propose a conditional probability approach to constrain the large range of global gridded crop model results for the future yield changes in response to warming by the end of the century (from -1.3% to -9.3% K -1 ). The constraint implies a more negative response to warming (-8.3 ± 1.4% K -1 ) and reduces the spread of the model ensemble by 33%. This yield reduction exceeds that estimated by the International Food Policy Research Institute assessment (-4.2 to -6.4% K -1 ) (ref. 4). Our study suggests that without CO 2 fertilization, effective adaptation and genetic improvement, severe rice yield losses are plausible under intensive climate warming scenarios.

Application of plausible reasoning to AI-based control systems

NASA Technical Reports Server (NTRS)

Berenji, Hamid; Lum, Henry, Jr.

1987-01-01

Some current approaches to plausible reasoning in artificial intelligence are reviewed and discussed. Some of the most significant recent advances in plausible and approximate reasoning are examined. A synergism among the techniques of uncertainty management is advocated, and brief discussions on the certainty factor approach, probabilistic approach, Dempster-Shafer theory of evidence, possibility theory, linguistic variables, and fuzzy control are presented. Some extensions to these methods are described, and the applications of the methods are considered.

Using models to manage systems subject to sustainability indicators

USGS Publications Warehouse

Hill, M.C.

2006-01-01

Mathematical and numerical models can provide insight into sustainability indicators using relevant simulated quantities, which are referred to here as predictions. To be useful, many concerns need to be considered. Four are discussed here: (a) mathematical and numerical accuracy of the model; (b) the accuracy of the data used in model development, (c) the information observations provide to aspects of the model important to predictions of interest as measured using sensitivity analysis; and (d) the existence of plausible alternative models for a given system. The four issues are illustrated using examples from conservative and transport modelling, and using conceptual arguments. Results suggest that ignoring these issues can produce misleading conclusions.

Coadaptive aiding and automation enhance operator performance.

PubMed

Christensen, James C; Estepp, Justin R

2013-10-01

In this work, we expand on the theory of adaptive aiding by measuring the effectiveness of coadaptive aiding, wherein we explicitly allow for both system and user to adapt to each other. Adaptive aiding driven by psychophysiological monitoring has been demonstrated to be a highly effective means of controlling task allocation and system functioning. Psychophysiological monitoring is uniquely well suited for coadaptation, as malleable brain activity may be used as a continuous input to the adaptive system. To establish the efficacy of the coadaptive system, physiological activation of adaptation was directly compared with manual activation or no activation of the same automation and cuing systems. We used interface adaptations and automation that are plausible for real-world operations, presented in the context of a multi-remotely piloted aircraft control simulation. Each participant completed 3 days of testing during 1 week. Performance was assessed via proportion of targets successfully engaged. In the first 2 days of testing, there were no significant differences in performance between the conditions. However, in the third session, physiological adaptation produced the highest performance. By extending the data collection across multiple days, we offered enough time and repeated experience for user adaptation as well as online system adaptation, hence demonstrating coadaptive aiding. The results of this work may be employed to implement more effective adaptive workstations in a variety of work domains.

Oxygen and Early Animal Evolution

NASA Astrophysics Data System (ADS)

Xiao, S.

2012-12-01

It is often hypothesized that the rise of animals was triggered by an increase in O2 levels in the atmosphere and oceans. However, this hypothesis is remarkably difficult to test, because the timing of animal divergences is poorly resolved, the physiology of early animals is often unknown, estimates of past pO2 levels come with large error bars, and causal relationships between oxygenation and animal evolution are difficult to establish. Nonetheless, existing phylogenetic, paleontological, and geochemical data indicate that the evolution of macroscopic animals and motile macrometazoans with energetically expensive lifestyles may be temporally coupled with ocean oxygenation events in the Ediacaran Period. Thus, it is plausible that ocean oxygenation may have been a limiting factor in the early evolution of macroscopic, complex, and metabolically aggressive animals (particularly bilaterian animals). However, ocean oxygenation and animal evolution were likely engaged in two-way interactions: Ediacaran oxygenation may have initially lifted a physiological barrier for the evolution of animal size, motility, and active lifestyles, but subsequent animal diversification in the Paleozoic may have also changed oceanic redox structures. Viewed in a broader context, the early evolutionary history of animals was contingent upon a series of events, including genetic preparation (developmental genetics), environmental facilitation (oceanic oxygenation), and ecological escalation (Cambrian explosion), but the rise of animals to ecological importance also had important geobiological impacts on oceanic redox structures, sedimentary fabrics, and global geochemical cycles.

Nest ectoparasites increase physiological stress in breeding birds: an experiment.

PubMed

Martínez-de la Puente, Josué; Merino, Santiago; Tomás, Gustavo; Moreno, Juan; Morales, Judith; Lobato, Elisa; Martínez, Javier

2011-02-01

Parasites are undoubtedly a biotic factor that produces stress. Heat shock proteins (HSPs) are important molecules buffering cellular damage under adverse conditions. During the breeding season, blue tit Cyanistes caeruleus (L.) adults are affected by blood parasites, nest-dwelling parasites and biting flies, potentially affecting their HSP-mediated responses. Here, we treated females with primaquine to reduce blood parasites and fumigated nests with permethrin to reduce nest-dwelling parasites to test whether these treatments affect HSP60 level during the breeding season. Medicated females, but not controls, had a significant reduction of the intensity of infection by Haemoproteus spp. blood parasites. However, final intensity of infection did not differ significantly between groups, and we did not find an effect of medication on change in HSP60 level. Fumigation reduced the abundance of nest-dwelling parasites (mites, fleas and blowfly larvae) and engorged biting midges in nests. Females breeding in non-fumigated nests increased HSP60 levels during the season more than those breeding in fumigated nests. Furthermore, the change in HSP60 level was positively correlated with the abundance of biting midges. These results show how infections by nest ectoparasites during the breeding period can increase the level of HSPs and suggest that biting midges impose physiological costs on breeding female blue tits. Although plausible, the alternative that biting midges prefer to feed on more stressed birds is poorly supported by previous studies.

Proceedings of the Conference on Toxicology: Applications of Advances in Toxicology to Risk Assessment. Held at Wright-Patterson AFB, Ohio on 19-21 May 1992

DTIC Science & Technology

1993-01-01

animals in toxicology research, the application of pharmacokinetics and physiologically based pharmacokinetic mdels in chemical risk assessment, selected...metaplasia Neurotoxicity Nonmutagenic carcinogens Ozone P450 PBPK modeling Perfluorohexane Peroxisome proliferators Pharmacokinetics Pharmacokinetic models...Physiological modeling Physiologically based pharmacokinetic modeling Polycyclic organic matter Quantitative risk assessment RAIRM model Rats

A three-dimensional virtual environment for modeling mechanical cardiopulmonary interactions.

PubMed

Kaye, J M; Primiano, F P; Metaxas, D N

1998-06-01

We have developed a real-time computer system for modeling mechanical physiological behavior in an interactive, 3-D virtual environment. Such an environment can be used to facilitate exploration of cardiopulmonary physiology, particularly in situations that are difficult to reproduce clinically. We integrate 3-D deformable body dynamics with new, formal models of (scalar) cardiorespiratory physiology, associating the scalar physiological variables and parameters with the corresponding 3-D anatomy. Our framework enables us to drive a high-dimensional system (the 3-D anatomical models) from one with fewer parameters (the scalar physiological models) because of the nature of the domain and our intended application. Our approach is amenable to modeling patient-specific circumstances in two ways. First, using CT scan data, we apply semi-automatic methods for extracting and reconstructing the anatomy to use in our simulations. Second, our scalar physiological models are defined in terms of clinically measurable, patient-specific parameters. This paper describes our approach, problems we have encountered and a sample of results showing normal breathing and acute effects of pneumothoraces.

Uncertainty and Variability in Physiologically-Based ...

EPA Pesticide Factsheets

EPA announced the availability of the final report, Uncertainty and Variability in Physiologically-Based Pharmacokinetic (PBPK) Models: Key Issues and Case Studies. This report summarizes some of the recent progress in characterizing uncertainty and variability in physiologically-based pharmacokinetic models and their predictions for use in risk assessment. This report summarizes some of the recent progress in characterizing uncertainty and variability in physiologically-based pharmacokinetic models and their predictions for use in risk assessment.

Don't Underestimate the Benefits of Being Misunderstood.

PubMed

Gibson, Edward; Tan, Caitlin; Futrell, Richard; Mahowald, Kyle; Konieczny, Lars; Hemforth, Barbara; Fedorenko, Evelina

2017-06-01

Being a nonnative speaker of a language poses challenges. Individuals often feel embarrassed by the errors they make when talking in their second language. However, here we report an advantage of being a nonnative speaker: Native speakers give foreign-accented speakers the benefit of the doubt when interpreting their utterances; as a result, apparently implausible utterances are more likely to be interpreted in a plausible way when delivered in a foreign than in a native accent. Across three replicated experiments, we demonstrated that native English speakers are more likely to interpret implausible utterances, such as "the mother gave the candle the daughter," as similar plausible utterances ("the mother gave the candle to the daughter") when the speaker has a foreign accent. This result follows from the general model of language interpretation in a noisy channel, under the hypothesis that listeners assume a higher error rate in foreign-accented than in nonaccented speech.

A Comparison of Different Methods for Evaluating Diet, Physical Activity, and Long-Term Weight Gain in 3 Prospective Cohort Studies123

PubMed Central

Smith, Jessica D; Hou, Tao; Hu, Frank B; Rimm, Eric B; Spiegelman, Donna; Willett, Walter C; Mozaffarian, Dariush

2015-01-01

Background: The insidious pace of long-term weight gain (∼1 lb/y or 0.45 kg/y) makes it difficult to study in trials; long-term prospective cohorts provide crucial evidence on its key contributors. Most previous studies have evaluated how prevalent lifestyle habits relate to future weight gain rather than to lifestyle changes, which may be more temporally and physiologically relevant. Objective: Our objective was to evaluate and compare different methodological approaches for investigating diet, physical activity (PA), and long-term weight gain. Methods: In 3 prospective cohorts (total n = 117,992), we assessed how lifestyle relates to long-term weight change (up to 24 y of follow-up) in 4-y periods by comparing 3 analytic approaches: 1) prevalent diet and PA and 4-y weight change (prevalent analysis); 2) 4-y changes in diet and PA with a 4-y weight change (change analysis); and 3) 4-y change in diet and PA with weight change in the subsequent 4 y (lagged-change analysis). We compared these approaches and evaluated the consistency across cohorts, magnitudes of associations, and biological plausibility of findings. Results: Across the 3 methods, consistent, robust, and biologically plausible associations were seen only for the change analysis. Results for prevalent or lagged-change analyses were less consistent across cohorts, smaller in magnitude, and biologically implausible. For example, for each serving of a sugar-sweetened beverage, the observed weight gain was 0.01 lb (95% CI: −0.08, 0.10) [0.005 kg (95% CI: −0.04, 0.05)] based on prevalent analysis; 0.99 lb (95% CI: 0.83, 1.16) [0.45 kg (95% CI: 0.38, 0.53)] based on change analysis; and 0.05 lb (95% CI: −0.10, 0.21) [0.02 kg (95% CI: −0.05, 0.10)] based on lagged-change analysis. Findings were similar for other foods and PA. Conclusions: Robust, consistent, and biologically plausible relations between lifestyle and long-term weight gain are seen when evaluating lifestyle changes and weight changes in discrete periods rather than in prevalent lifestyle or lagged changes. These findings inform the optimal methods for evaluating lifestyle and long-term weight gain and the potential for bias when other methods are used. PMID:26377763

A Comparison of Different Methods for Evaluating Diet, Physical Activity, and Long-Term Weight Gain in 3 Prospective Cohort Studies.

PubMed

Smith, Jessica D; Hou, Tao; Hu, Frank B; Rimm, Eric B; Spiegelman, Donna; Willett, Walter C; Mozaffarian, Dariush

2015-11-01

The insidious pace of long-term weight gain (∼ 1 lb/y or 0.45 kg/y) makes it difficult to study in trials; long-term prospective cohorts provide crucial evidence on its key contributors. Most previous studies have evaluated how prevalent lifestyle habits relate to future weight gain rather than to lifestyle changes, which may be more temporally and physiologically relevant. Our objective was to evaluate and compare different methodological approaches for investigating diet, physical activity (PA), and long-term weight gain. In 3 prospective cohorts (total n = 117,992), we assessed how lifestyle relates to long-term weight change (up to 24 y of follow-up) in 4-y periods by comparing 3 analytic approaches: 1) prevalent diet and PA and 4-y weight change (prevalent analysis); 2) 4-y changes in diet and PA with a 4-y weight change (change analysis); and 3) 4-y change in diet and PA with weight change in the subsequent 4 y (lagged-change analysis). We compared these approaches and evaluated the consistency across cohorts, magnitudes of associations, and biological plausibility of findings. Across the 3 methods, consistent, robust, and biologically plausible associations were seen only for the change analysis. Results for prevalent or lagged-change analyses were less consistent across cohorts, smaller in magnitude, and biologically implausible. For example, for each serving of a sugar-sweetened beverage, the observed weight gain was 0.01 lb (95% CI: -0.08, 0.10) [0.005 kg (95% CI: -0.04, 0.05)] based on prevalent analysis; 0.99 lb (95% CI: 0.83, 1.16) [0.45 kg (95% CI: 0.38, 0.53)] based on change analysis; and 0.05 lb (95% CI: -0.10, 0.21) [0.02 kg (95% CI: -0.05, 0.10)] based on lagged-change analysis. Findings were similar for other foods and PA. Robust, consistent, and biologically plausible relations between lifestyle and long-term weight gain are seen when evaluating lifestyle changes and weight changes in discrete periods rather than in prevalent lifestyle or lagged changes. These findings inform the optimal methods for evaluating lifestyle and long-term weight gain and the potential for bias when other methods are used. © 2015 American Society for Nutrition.

Four Frames Suffice. A Provisionary Model of Vision and Space,

DTIC Science & Technology

1982-09-01

0 * / Justifi ati AvailabilitY Codes 1. Introduction This paper is an attempt to specify’ a computationally and scientifically plausible model of how...abstract neural compuiting unit and a variety of construtions built of these units and their properties. All of this is part of the connectionist...chosen are inlerided to elucidate the nia’or scientific problems in intermediate level vision and would not be the best choice or a practical computer

The method of constant stimuli is inefficient

NASA Technical Reports Server (NTRS)

Watson, Andrew B.; Fitzhugh, Andrew

1990-01-01

Simpson (1988) has argued that the method of constant stimuli is as efficient as adaptive methods of threshold estimation and has supported this claim with simulations. It is shown that Simpson's simulations are not a reasonable model of the experimental process and that more plausible simulations confirm that adaptive methods are much more efficient that the method of constant stimuli.

The Organization and Dissolution of Semantic-Conceptual Knowledge: Is the "Amodal Hub" the Only Plausible Model?

ERIC Educational Resources Information Center

Gainotti, Guido

2011-01-01

In recent years, the anatomical and functional bases of conceptual activity have attracted a growing interest. In particular, Patterson and Lambon-Ralph have proposed the existence, in the anterior parts of the temporal lobes, of a mechanism (the "amodal semantic hub") supporting the interactive activation of semantic representations in all…

What Does Quantum Physics Have to Do with Behavior Disorders?

ERIC Educational Resources Information Center

Center, David B.

This paper argues that human agency as a causal factor in behavior must be considered in any model of behavior and behavior disorders. Since human agency is historically tied to the issue of consciousness, to argue that consciousness plays a causal role in behavior requires a plausible explanation of consciousness. This paper proposes that…

Heat Flow, Thermal Conductivity, and the Plausibility of the White Mars Hypothesis

NASA Technical Reports Server (NTRS)

Urquhart, M. L.; Gulick, V. C.

2002-01-01

Due to the low thermal conductivity of CO2 ice and clathrate vs. water ice, we find that liquid water reservoirs would not be confined to the deep subsurface as predicted by the controversial White Mars model, even assuming low global heat flow. Additional information is contained in the original extended abstract.

Randomization-Based Inference about Latent Variables from Complex Samples: The Case of Two-Stage Sampling

ERIC Educational Resources Information Center

Li, Tiandong

2012-01-01

In large-scale assessments, such as the National Assessment of Educational Progress (NAEP), plausible values based on Multiple Imputations (MI) have been used to estimate population characteristics for latent constructs under complex sample designs. Mislevy (1991) derived a closed-form analytic solution for a fixed-effect model in creating…

Workplace Predictors of Secondary School Teachers' Intention to Leave: An Exploration of Career Stages

ERIC Educational Resources Information Center

You, Sukkyung; Conley, Sharon

2015-01-01

The subject of teachers' intentions to leave has recently captured the attention of researchers and practitioners. This paper reports on a study that examined the workplace predictors of teachers' intentions to leave for teachers in different career stages. Structural equation modeling was used to assess the plausibility of a conceptual model…

Selecting climate change scenarios using impact-relevant sensitivities

Treesearch

Julie A. Vano; John B. Kim; David E. Rupp; Philip W. Mote

2015-01-01

Climate impact studies often require the selection of a small number of climate scenarios. Ideally, a subset would have simulations that both (1) appropriately represent the range of possible futures for the variable/s most important to the impact under investigation and (2) come from global climate models (GCMs) that provide plausible results for future climate in the...

Do Dogs Know Related Rates Rather than Optimization?

ERIC Educational Resources Information Center

Perruchet, Pierre; Gallego, Jorge

2006-01-01

Although dogs seemingly follow the optimal path where they get to a ball thrown into the water, they certainly do not know the minimization function proposed in the calculus books. Trading the optimization problem for a related rates problem leads to a mathematically identical solution, which, it is argued here, is a more plausible model for the…

Detailed Spectral Analysis of the 260 ks XMM-Newton Data of 1E 1207.4-5209 and Significance of a 2.1 keV Absorption Feature

NASA Astrophysics Data System (ADS)

Mori, Kaya; Chonko, James C.; Hailey, Charles J.

2005-10-01

We have reanalyzed the 260 ks XMM-Newton observation of 1E 1207.4-5209. There are several significant improvements over previous work. First, a much broader range of physically plausible spectral models was used. Second, we have used a more rigorous statistical analysis. The standard F-distribution was not employed, but rather the exact finite statistics F-distribution was determined by Monte Carlo simulations. This approach was motivated by the recent work of Protassov and coworkers and Freeman and coworkers. They demonstrated that the standard F-distribution is not even asymptotically correct when applied to assess the significance of additional absorption features in a spectrum. With our improved analysis we do not find a third and fourth spectral feature in 1E 1207.4-5209 but only the two broad absorption features previously reported. Two additional statistical tests, one line model dependent and the other line model independent, confirmed our modified F-test analysis. For all physically plausible continuum models in which the weak residuals are strong enough to fit, the residuals occur at the instrument Au M edge. As a sanity check we confirmed that the residuals are consistent in strength and position with the instrument Au M residuals observed in 3C 273.

Avoidable Burden of Risk Factors for Serious Road Traffic Crashes in Iran: A Modeling Study.

PubMed

Khosravi Shadmani, Fatemeh; Mansori, Kamyar; Karami, Manoochehr; Zayeri, Farid; Shadman, Reza Khosravi; Hanis, Shiva Mansouri; Soori, Hamid

2017-03-01

The aim of this study was to model the avoidable burden of the risk factors of road traffic crashes in Iran and to prioritize interventions to reduce that burden. The prevalence and the effect size of the risk factors were obtained from data documented by the traffic police of Iran in 2013. The effect size was estimated using an ordinal regression model. The potential impact fraction index was applied to calculate the avoidable burden in order to prioritize interventions. This index was calculated for theoretical, plausible, and feasible minimum risk level scenarios. The joint effects of the risk factors were then estimated for all the scenarios. The highest avoidable burdens in the theoretical, plausible, and feasible minimum risk level scenarios for the non-use of child restraints on urban roads were 52.25, 28.63, and 46.67, respectively. In contrast, the value of this index for speeding was 76.24, 37.00, and 62.23, respectively, for rural roads. On the basis of the different scenarios considered in this research, we suggest focusing on future interventions to decrease the prevalence of speeding, the non-use of child restraints, the use of cell phones while driving, and helmet disuse, and the laws related to these items should be considered seriously.

How many kinds of reasoning? Inference, probability, and natural language semantics.

PubMed

Lassiter, Daniel; Goodman, Noah D

2015-03-01

The "new paradigm" unifying deductive and inductive reasoning in a Bayesian framework (Oaksford & Chater, 2007; Over, 2009) has been claimed to be falsified by results which show sharp differences between reasoning about necessity vs. plausibility (Heit & Rotello, 2010; Rips, 2001; Rotello & Heit, 2009). We provide a probabilistic model of reasoning with modal expressions such as "necessary" and "plausible" informed by recent work in formal semantics of natural language, and show that it predicts the possibility of non-linear response patterns which have been claimed to be problematic. Our model also makes a strong monotonicity prediction, while two-dimensional theories predict the possibility of reversals in argument strength depending on the modal word chosen. Predictions were tested using a novel experimental paradigm that replicates the previously-reported response patterns with a minimal manipulation, changing only one word of the stimulus between conditions. We found a spectrum of reasoning "modes" corresponding to different modal words, and strong support for our model's monotonicity prediction. This indicates that probabilistic approaches to reasoning can account in a clear and parsimonious way for data previously argued to falsify them, as well as new, more fine-grained, data. It also illustrates the importance of careful attention to the semantics of language employed in reasoning experiments. Copyright © 2014 Elsevier B.V. All rights reserved.

Physiologically grounded metrics of model skill: a case study estimating heat stress in intertidal populations

PubMed Central

Kish, Nicole E.; Helmuth, Brian; Wethey, David S.

2016-01-01

Models of ecological responses to climate change fundamentally assume that predictor variables, which are often measured at large scales, are to some degree diagnostic of the smaller-scale biological processes that ultimately drive patterns of abundance and distribution. Given that organisms respond physiologically to stressors, such as temperature, in highly non-linear ways, small modelling errors in predictor variables can potentially result in failures to predict mortality or severe stress, especially if an organism exists near its physiological limits. As a result, a central challenge facing ecologists, particularly those attempting to forecast future responses to environmental change, is how to develop metrics of forecast model skill (the ability of a model to predict defined events) that are biologically meaningful and reflective of underlying processes. We quantified the skill of four simple models of body temperature (a primary determinant of physiological stress) of an intertidal mussel, Mytilus californianus, using common metrics of model performance, such as root mean square error, as well as forecast verification skill scores developed by the meteorological community. We used a physiologically grounded framework to assess each model's ability to predict optimal, sub-optimal, sub-lethal and lethal physiological responses. Models diverged in their ability to predict different levels of physiological stress when evaluated using skill scores, even though common metrics, such as root mean square error, indicated similar accuracy overall. Results from this study emphasize the importance of grounding assessments of model skill in the context of an organism's physiology and, especially, of considering the implications of false-positive and false-negative errors when forecasting the ecological effects of environmental change. PMID:27729979

Exploring Vital Sign Data Quality in Electronic Health Records with Focus on Emergency Care Warning Scores.

PubMed

Skyttberg, Niclas; Chen, Rong; Blomqvist, Hans; Koch, Sabine

2017-08-30

Computerized clinical decision support and automation of warnings have been advocated to assist clinicians in detecting patients at risk of physiological instability. To provide reliable support such systems are dependent on high-quality vital sign data. Data quality depends on how, when and why the data is captured and/or documented. This study aims to describe the effects on data quality of vital signs by three different types of documentation practices in five Swedish emergency hospitals, and to assess data fitness for calculating warning and triage scores. The study also provides reference data on triage vital signs in Swedish emergency care. We extracted a dataset including vital signs, demographic and administrative data from emergency care visits (n=335027) at five Swedish emergency hospitals during 2013 using either completely paper-based, completely electronic or mixed documentation practices. Descriptive statistics were used to assess fitness for use in emergency care decision support systems aiming to calculate warning and triage scores, and data quality was described in three categories: currency, completeness and correctness. To estimate correctness, two further categories - plausibility and concordance - were used. The study showed an acceptable correctness of the registered vital signs irrespectively of the type of documentation practice. Completeness was high in sites where registrations were routinely entered into the Electronic Health Record (EHR). The currency was only acceptable in sites with a completely electronic documentation practice. Although vital signs that were recorded in completely electronic documentation practices showed plausible results regarding correctness, completeness and currency, the study concludes that vital signs documented in Swedish emergency care EHRs cannot generally be considered fit for use for calculation of triage and warning scores. Low completeness and currency were found if the documentation was not completely electronic.

Terrestrial implications of mathematical modeling developed for space biomedical research

NASA Technical Reports Server (NTRS)

Lujan, Barbara F.; White, Ronald J.; Leonard, Joel I.; Srinivasan, R. Srini

1988-01-01

This paper summarizes several related research projects supported by NASA which seek to apply computer models to space medicine and physiology. These efforts span a wide range of activities, including mathematical models used for computer simulations of physiological control systems; power spectral analysis of physiological signals; pattern recognition models for detection of disease processes; and computer-aided diagnosis programs.

Biological data assimilation for parameter estimation of a phytoplankton functional type model for the western North Pacific

NASA Astrophysics Data System (ADS)

Hoshiba, Yasuhiro; Hirata, Takafumi; Shigemitsu, Masahito; Nakano, Hideyuki; Hashioka, Taketo; Masuda, Yoshio; Yamanaka, Yasuhiro

2018-06-01

Ecosystem models are used to understand ecosystem dynamics and ocean biogeochemical cycles and require optimum physiological parameters to best represent biological behaviours. These physiological parameters are often tuned up empirically, while ecosystem models have evolved to increase the number of physiological parameters. We developed a three-dimensional (3-D) lower-trophic-level marine ecosystem model known as the Nitrogen, Silicon and Iron regulated Marine Ecosystem Model (NSI-MEM) and employed biological data assimilation using a micro-genetic algorithm to estimate 23 physiological parameters for two phytoplankton functional types in the western North Pacific. The estimation of the parameters was based on a one-dimensional simulation that referenced satellite data for constraining the physiological parameters. The 3-D NSI-MEM optimized by the data assimilation improved the timing of a modelled plankton bloom in the subarctic and subtropical regions compared to the model without data assimilation. Furthermore, the model was able to improve not only surface concentrations of phytoplankton but also their subsurface maximum concentrations. Our results showed that surface data assimilation of physiological parameters from two contrasting observatory stations benefits the representation of vertical plankton distribution in the western North Pacific.

The lunar crust - A product of heterogeneous accretion or differentiation of a homogeneous moon

NASA Technical Reports Server (NTRS)

Brett, R.

1973-01-01

The outer portion of the moon (including the aluminum-rich crust and the source regions of mare basalts) was either accreted heterogeneously or was the product of widespread differentiation of an originally homogeneous source. Existing evidence for and against each of these two models is reviewed. It is concluded that the accretionary model presents more problems than it solves, and the model involving differentiation of an originally homogeneous moon is considered to be more plausible. A hypothesis for the formation of mare basalts is advanced.

Rapid Debris Analysis Project Task 3 Final Report - Sensitivity of Fallout to Source Parameters, Near-Detonation Environment Material Properties, Topography, and Meteorology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldstein, Peter

2014-01-24

This report describes the sensitivity of predicted nuclear fallout to a variety of model input parameters, including yield, height of burst, particle and activity size distribution parameters, wind speed, wind direction, topography, and precipitation. We investigate sensitivity over a wide but plausible range of model input parameters. In addition, we investigate a specific example with a relatively narrow range to illustrate the potential for evaluating uncertainties in predictions when there are more precise constraints on model parameters.

Stochastic Dynamics Underlying Cognitive Stability and Flexibility

PubMed Central

Ueltzhöffer, Kai; Armbruster-Genç, Diana J. N.; Fiebach, Christian J.

2015-01-01

Cognitive stability and flexibility are core functions in the successful pursuit of behavioral goals. While there is evidence for a common frontoparietal network underlying both functions and for a key role of dopamine in the modulation of flexible versus stable behavior, the exact neurocomputational mechanisms underlying those executive functions and their adaptation to environmental demands are still unclear. In this work we study the neurocomputational mechanisms underlying cue based task switching (flexibility) and distractor inhibition (stability) in a paradigm specifically designed to probe both functions. We develop a physiologically plausible, explicit model of neural networks that maintain the currently active task rule in working memory and implement the decision process. We simplify the four-choice decision network to a nonlinear drift-diffusion process that we canonically derive from a generic winner-take-all network model. By fitting our model to the behavioral data of individual subjects, we can reproduce their full behavior in terms of decisions and reaction time distributions in baseline as well as distractor inhibition and switch conditions. Furthermore, we predict the individual hemodynamic response timecourse of the rule-representing network and localize it to a frontoparietal network including the inferior frontal junction area and the intraparietal sulcus, using functional magnetic resonance imaging. This refines the understanding of task-switch-related frontoparietal brain activity as reflecting attractor-like working memory representations of task rules. Finally, we estimate the subject-specific stability of the rule-representing attractor states in terms of the minimal action associated with a transition between different rule states in the phase-space of the fitted models. This stability measure correlates with switching-specific thalamocorticostriatal activation, i.e., with a system associated with flexible working memory updating and dopaminergic modulation of cognitive flexibility. These results show that stochastic dynamical systems can implement the basic computations underlying cognitive stability and flexibility and explain neurobiological bases of individual differences. PMID:26068119

Crop-model assisted phenomics and genome-wide association study for climate adaptation of indica rice. 2. Thermal stress and spikelet sterility.

PubMed

Dingkuhn, Michael; Pasco, Richard; Pasuquin, Julie Mae; Damo, Jean; Soulié, Jean-Christophe; Raboin, Louis-Marie; Dusserre, Julie; Sow, Abdoulaye; Manneh, Baboucarr; Shrestha, Suchit; Kretzschmar, Tobias

2017-07-10

Low night and high day temperatures during sensitive reproductive stages cause spikelet sterility in rice. Phenotyping of tolerance traits in the field is difficult because of temporal interactions with phenology and organ temperature differing from ambient. Physiological models can be used to separate these effects. A 203-accession indica rice diversity panel was phenotyped for sterility in ten environments in Senegal and Madagascar and climate data were recorded. Here we report on sterility responses while a companion study reported on phenology. The objectives were to improve the RIDEV model of rice thermal sterility, to estimate response traits by fitting model parameters, and to link the response traits to genomic regions through genome-wide association studies (GWAS). RIDEV captured 64% of variation of sterility when cold acclimation during vegetative stage was simulated, but only 38% when it was not. The RIDEV parameters gave more and stronger quantitative trait loci (QTLs) than index variables derived more directly from observation. The 15 QTLs identified at P<1 × 10-5 (33 at P<1 × 10-4) were related to sterility effects of heat, cold, cold acclimation, or unexplained causes (baseline sterility). Nine annotated genes were found on average within the 50% linkage disequilibrium (LD) region. Among them, one to five plausible candidate genes per QTL were identified based on known expression profiles (organ, stage, stress factors) and function. Meiosis-, development- and flowering-related genes were frequent, as well a stress signaling kinases and transcription factors. Putative epigenetic factors such as DNA methylases or histone-related genes were frequent in cold-acclimation QTLs, and positive-effect alleles were frequent in cold-tolerant highland rice from Madagascar. The results indicate that epigenetic control of acclimation may be important in indica rice genotypes adapted to cool environments. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Analytic expressions for the black-sky and white-sky albedos of the cosine lobe model.

PubMed

Goodin, Christopher

2013-05-01

The cosine lobe model is a bidirectional reflectance distribution function (BRDF) that is commonly used in computer graphics to model specular reflections. The model is both simple and physically plausible, but physical quantities such as albedo have not been related to the parameterization of the model. In this paper, analytic expressions for calculating the black-sky and white-sky albedos from the cosine lobe BRDF model with integer exponents will be derived, to the author's knowledge for the first time. These expressions for albedo can be used to place constraints on physics-based simulations of radiative transfer such as high-fidelity ray-tracing simulations.

Folk-Psychological Interpretation of Human vs. Humanoid Robot Behavior: Exploring the Intentional Stance toward Robots.

PubMed

Thellman, Sam; Silvervarg, Annika; Ziemke, Tom

2017-01-01

People rely on shared folk-psychological theories when judging behavior. These theories guide people's social interactions and therefore need to be taken into consideration in the design of robots and other autonomous systems expected to interact socially with people. It is, however, not yet clear to what degree the mechanisms that underlie people's judgments of robot behavior overlap or differ from the case of human or animal behavior. To explore this issue, participants ( N = 90) were exposed to images and verbal descriptions of eight different behaviors exhibited either by a person or a humanoid robot. Participants were asked to rate the intentionality, controllability and desirability of the behaviors, and to judge the plausibility of seven different types of explanations derived from a recently proposed psychological model of lay causal explanation of human behavior. Results indicate: substantially similar judgments of human and robot behavior, both in terms of (1a) ascriptions of intentionality/controllability/desirability and in terms of (1b) plausibility judgments of behavior explanations; (2a) high level of agreement in judgments of robot behavior - (2b) slightly lower but still largely similar to agreement over human behaviors; (3) systematic differences in judgments concerning the plausibility of goals and dispositions as explanations of human vs. humanoid behavior. Taken together, these results suggest that people's intentional stance toward the robot was in this case very similar to their stance toward the human.

Retrospective Correction of Physiological Noise in DTI Using an Extended Tensor Model and Peripheral Measurements

PubMed Central

Mohammadi, Siawoosh; Hutton, Chloe; Nagy, Zoltan; Josephs, Oliver; Weiskopf, Nikolaus

2013-01-01

Diffusion tensor imaging is widely used in research and clinical applications, but this modality is highly sensitive to artefacts. We developed an easy-to-implement extension of the original diffusion tensor model to account for physiological noise in diffusion tensor imaging using measures of peripheral physiology (pulse and respiration), the so-called extended tensor model. Within the framework of the extended tensor model two types of regressors, which respectively modeled small (linear) and strong (nonlinear) variations in the diffusion signal, were derived from peripheral measures. We tested the performance of four extended tensor models with different physiological noise regressors on nongated and gated diffusion tensor imaging data, and compared it to an established data-driven robust fitting method. In the brainstem and cerebellum the extended tensor models reduced the noise in the tensor-fit by up to 23% in accordance with previous studies on physiological noise. The extended tensor model addresses both large-amplitude outliers and small-amplitude signal-changes. The framework of the extended tensor model also facilitates further investigation into physiological noise in diffusion tensor imaging. The proposed extended tensor model can be readily combined with other artefact correction methods such as robust fitting and eddy current correction. PMID:22936599

Use of Physiologically Based Pharmacokinetic (PBPK) Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk (Final Report)

EPA Science Inventory

EPA announced the availability of the final report, Use of Physiologically Based Pharmacokinetic (PBPK) Models to Quantify the Impact of Human Age and Interindividual Differences in Physiology and Biochemistry Pertinent to Risk Final Report for Cooperative Agreement. Th...

Two Strain Dengue Model with Temporary Cross Immunity and Seasonality

NASA Astrophysics Data System (ADS)

Aguiar, Maíra; Ballesteros, Sebastien; Stollenwerk, Nico

2010-09-01

Models on dengue fever epidemiology have previously shown critical fluctuations with power law distributions and also deterministic chaos in some parameter regions due to the multi-strain structure of the disease pathogen. In our first model including well known biological features, we found a rich dynamical structure including limit cycles, symmetry breaking bifurcations, torus bifurcations, coexisting attractors including isola solutions and deterministic chaos (as indicated by positive Lyapunov exponents) in a much larger parameter region, which is also biologically more plausible than the previous results of other researches. Based on these findings we will investigate the model structures further including seasonality.

Teacher role stress, satisfaction, commitment, and intentions to leave: a structural model.

PubMed

Conley, Sharon; You, Sukkyung

2009-12-01

Structural equation modeling was used to assess the plausibility of a conceptual model specifying hypothesized linkages among teachers' perceptions of the role stresses of role ambiguity, role conflict, and role overload and commitment, satisfaction, and intentions to leave their employing school. 178 teachers in four high schools in a southern coastal region of California responded to survey questions designed to capture the above constructs. Confirmatory factor analysis was used to assess whether the role-stress items fit hypothesized constructs. Structural equation modeling results indicated that satisfaction and commitment are two mediators in the role stresses-intentions to leave relationship.

Two Strain Dengue Model with Temporary Cross Immunity and Seasonality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aguiar, Maira; Ballesteros, Sebastien; Stollenwerk, Nico

Models on dengue fever epidemiology have previously shown critical fluctuations with power law distributions and also deterministic chaos in some parameter regions due to the multi-strain structure of the disease pathogen. In our first model including well known biological features, we found a rich dynamical structure including limit cycles, symmetry breaking bifurcations, torus bifurcations, coexisting attractors including isola solutions and deterministic chaos (as indicated by positive Lyapunov exponents) in a much larger parameter region, which is also biologically more plausible than the previous results of other researches. Based on these findings we will investigate the model structures further including seasonality.

A 3D model of polarized dust emission in the Milky Way

NASA Astrophysics Data System (ADS)

Martínez-Solaeche, Ginés; Karakci, Ata; Delabrouille, Jacques

2018-05-01

We present a three-dimensional model of polarized galactic dust emission that takes into account the variation of the dust density, spectral index and temperature along the line of sight, and contains randomly generated small-scale polarization fluctuations. The model is constrained to match observed dust emission on large scales, and match on smaller scales extrapolations of observed intensity and polarization power spectra. This model can be used to investigate the impact of plausible complexity of the polarized dust foreground emission on the analysis and interpretation of future cosmic microwave background polarization observations.

Application of the Regional Atmospheric Modeling System to the Martian Atmosphere

NASA Technical Reports Server (NTRS)

Rafkin, Scot C. R.

1998-01-01

The core dynamics of the Regional Atmospheric Modeling System (RAMS), a widely used and powerful mesoscale Earth model, is adapted to the Martian Atmosphere and applied in the study of aeolian surface features. In particular, research efforts focused on the substitution of Martian planetary and atmospheric properties such as rotation rate, and thermodynamic constants in place of hard-wired Earth properties. Application of the model was restricted to three-dimensional flow impinging upon impact craters, and the search for plausible wind patterns that could produce the so-called light and dark streaks downwind of topographic barriers.

Would a madman have been so wise as this?" The effects of source credibility and message credibility on validation.

PubMed

Foy, Jeffrey E; LoCasto, Paul C; Briner, Stephen W; Dyar, Samantha

2017-02-01

Readers rapidly check new information against prior knowledge during validation, but research is inconsistent as to whether source credibility affects validation. We argue that readers are likely to accept highly plausible assertions regardless of source, but that high source credibility may boost acceptance of claims that are less plausible based on general world knowledge. In Experiment 1, participants read narratives with assertions for which the plausibility varied depending on the source. For high credibility sources, we found that readers were faster to read information confirming these assertions relative to contradictory information. We found the opposite patterns for low credibility characters. In Experiment 2, readers read claims from the same high or low credibility sources, but the claims were always plausible based on general world knowledge. Readers consistently took longer to read contradictory information, regardless of source. In Experiment 3, participants read modified versions of "The Tell-Tale Heart," which was narrated entirely by an unreliable source. We manipulated the plausibility of a target event, as well as whether high credibility characters within the story provided confirmatory or contradictory information about the narrator's description of the target event. Though readers rated the narrator as being insane, they were more likely to believe the narrator's assertions about the target event when it was plausible and corroborated by other characters. We argue that sourcing research would benefit from focusing on the relationship between source credibility, message credibility, and multiple sources within a text.

A student-centered approach for developing active learning: the construction of physical models as a teaching tool in medical physiology.

PubMed

Rezende-Filho, Flávio Moura; da Fonseca, Lucas José Sá; Nunes-Souza, Valéria; Guedes, Glaucevane da Silva; Rabelo, Luiza Antas

2014-09-15

Teaching physiology, a complex and constantly evolving subject, is not a simple task. A considerable body of knowledge about cognitive processes and teaching and learning methods has accumulated over the years, helping teachers to determine the most efficient way to teach, and highlighting student's active participation as a means to improve learning outcomes. In this context, this paper describes and qualitatively analyzes an experience of a student-centered teaching-learning methodology based on the construction of physiological-physical models, focusing on their possible application in the practice of teaching physiology. After having Physiology classes and revising the literature, students, divided in small groups, built physiological-physical models predominantly using low-cost materials, for studying different topics in Physiology. Groups were followed by monitors and guided by teachers during the whole process, finally presenting the results in a Symposium on Integrative Physiology. Along the proposed activities, students were capable of efficiently creating physiological-physical models (118 in total) highly representative of different physiological processes. The implementation of the proposal indicated that students successfully achieved active learning and meaningful learning in Physiology while addressing multiple learning styles. The proposed method has proved to be an attractive, accessible and relatively simple approach to facilitate the physiology teaching-learning process, while facing difficulties imposed by recent requirements, especially those relating to the use of experimental animals and professional training guidelines. Finally, students' active participation in the production of knowledge may result in a holistic education, and possibly, better professional practices.

A hydraulic-photosynthetic model based on extended HLH and its application to Coast redwood (Sequoia sempervirens).

PubMed

Du, Ning; Fan, Jintu; Chen, Shuo; Liu, Yang

2008-07-21

Although recent investigations [Ryan, M.G., Yoder, B.J., 1997. Hydraulic limits to tree height and tree growth. Bioscience 47, 235-242; Koch, G.W., Sillett, S.C.,Jennings, G.M.,Davis, S.D., 2004. The limits to tree height. Nature 428, 851-854; Niklas, K.J., Spatz, H., 2004. Growth and hydraulic (not mechanical) constraints govern the scaling of tree height and mass. Proc. Natl Acad. Sci. 101, 15661-15663; Ryan, M.G., Phillips, N., Bond, B.J., 2006. Hydraulic limitation hypothesis revisited. Plant Cell Environ. 29, 367-381; Niklas, K.J., 2007. Maximum plant height and the biophysical factors that limit it. Tree Physiol. 27, 433-440; Burgess, S.S.O., Dawson, T.E., 2007. Predicting the limits to tree height using statistical regressions of leaf traits. New Phytol. 174, 626-636] suggested that the hydraulic limitation hypothesis (HLH) is the most plausible theory to explain the biophysical limits to maximum tree height and the decline in tree growth rate with age, the analysis is largely qualitative or based on statistical regression. Here we present an integrated biophysical model based on the principle that trees develop physiological compensations (e.g. the declined leaf water potential and the tapering of conduits with heights [West, G.B., Brown, J.H., Enquist, B.J., 1999. A general model for the structure and allometry of plant vascular systems. Nature 400, 664-667]) to resist the increasing water stress with height, the classical HLH and the biochemical limitations on photosynthesis [von Caemmerer, S., 2000. Biochemical Models of Leaf Photosynthesis. CSIRO Publishing, Australia]. The model has been applied to the tallest trees in the world (viz. Coast redwood (Sequoia sempervirens)). Xylem water potential, leaf carbon isotope composition, leaf mass to area ratio at different heights derived from the model show good agreements with the experimental measurements of Koch et al. [2004. The limits to tree height. Nature 428, 851-854]. The model also well explains the universal trend of declining growth rate with age.

Neuronal modelling of baroreflex response to orthostatic stress

NASA Astrophysics Data System (ADS)

Samin, Azfar

The accelerations experienced in aerial combat can cause pilot loss of consciousness (GLOC) due to a critical reduction in cerebral blood circulation. The development of smart protective equipment requires understanding of how the brain processes blood pressure (BP) information in response to acceleration. We present a biologically plausible model of the Baroreflex to investigate the neural correlates of short-term BP control under acceleration or orthostatic stress. The neuronal network model, which employs an integrate-and-fire representation of a biological neuron, comprises the sensory, motor, and the central neural processing areas that form the Baroreflex. Our modelling strategy is to test hypotheses relating to the encoding mechanisms of multiple sensory inputs to the nucleus tractus solitarius (NTS), the site of central neural processing. The goal is to run simulations and reproduce model responses that are consistent with the variety of available experimental data. Model construction and connectivity are inspired by the available anatomical and neurophysiological evidence that points to a barotopic organization in the NTS, and the presence of frequency-dependent synaptic depression, which provides a mechanism for generating non-linear local responses in NTS neurons that result in quantifiable dynamic global baroreflex responses. The entire physiological range of BP and rate of change of BP variables is encoded in a palisade of NTS neurons in that the spike responses approximate Gaussian 'tuning' curves. An adapting weighted-average decoding scheme computes the motor responses and a compensatory signal regulates the heart rate (HR). Model simulations suggest that: (1) the NTS neurons can encode the hydrostatic pressure difference between two vertically separated sensory receptor regions at +Gz, and use changes in that difference for the regulation of HR; (2) even though NTS neurons do not fire with a cardiac rhythm seen in the afferents, pulse-rhythmic activity is regained downstream provided the input phase information in preserved centrally; (3) frequency-dependent synaptic depression, which causes temporal variations in synaptic strength due to changes in input frequency, is a possible mechanism of non-linear dynamic baroreflex gain control. Synaptic depression enables the NTS neuron to encode dBP/dt but to lose information about the steady state firing of the afferents.

Mode-of-Action Uncertainty for Dual-Mode Carcinogens:Lower Bounds for Naphthalene-Induced Nasal Tumors in Rats Implied byPBPK and 2-Stage Stochastic Cancer Risk Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bogen, K T

2007-01-30

As reflected in the 2005 USEPA Guidelines for Cancer Risk Assessment, some chemical carcinogens may have a site-specific mode of action (MOA) that is dual, involving mutation in addition to cell-killing induced hyperplasia. Although genotoxicity may contribute to increased risk at all doses, the Guidelines imply that for dual MOA (DMOA) carcinogens, judgment be used to compare and assess results obtained using separate ''linear'' (genotoxic) vs. ''nonlinear'' (nongenotoxic) approaches to low-level risk extrapolation. However, the Guidelines allow the latter approach to be used only when evidence is sufficient to parameterize a biologically based model that reliably extrapolates risk to lowmore » levels of concern. The Guidelines thus effectively prevent MOA uncertainty from being characterized and addressed when data are insufficient to parameterize such a model, but otherwise clearly support a DMOA. A bounding factor approach--similar to that used in reference dose procedures for classic toxicity endpoints--can address MOA uncertainty in a way that avoids explicit modeling of low-dose risk as a function of administered or internal dose. Even when a ''nonlinear'' toxicokinetic model cannot be fully validated, implications of DMOA uncertainty on low-dose risk may be bounded with reasonable confidence when target tumor types happen to be extremely rare. This concept was illustrated for the rodent carcinogen naphthalene. Bioassay data, supplemental toxicokinetic data, and related physiologically based pharmacokinetic and 2-stage stochastic carcinogenesis modeling results all clearly indicate that naphthalene is a DMOA carcinogen. Plausibility bounds on rat-tumor-type specific DMOA-related uncertainty were obtained using a 2-stage model adapted to reflect the empirical link between genotoxic and cytotoxic effects of the most potent identified genotoxic naphthalene metabolites, 1,2- and 1,4-naphthoquinone. Resulting bounds each provided the basis for a corresponding ''uncertainty'' factor <1 appropriate to apply to estimates of naphthalene risk obtained by linear extrapolation under a default genotoxic MOA assumption. This procedure is proposed as scientifically credible method to address MOA uncertainty for DMOA carcinogens.« less

Employee subjective well-being and physiological functioning: An integrative model

PubMed Central

Tay, Louis

2015-01-01

Research shows that worker subjective well-being influences physiological functioning—an early signal of poor health outcomes. While several theoretical perspectives provide insights on this relationship, the literature lacks an integrative framework explaining the relationship. We develop a conceptual model explaining the link between subjective well-being and physiological functioning in the context of work. Integrating positive psychology and occupational stress perspectives, our model explains the relationship between subjective well-being and physiological functioning as a result of the direct influence of subjective well-being on physiological functioning and of their common relationships with work stress and personal resources, both of which are influenced by job conditions. PMID:28070359

Employee subjective well-being and physiological functioning: An integrative model.

PubMed

Kuykendall, Lauren; Tay, Louis

2015-01-01

Research shows that worker subjective well-being influences physiological functioning-an early signal of poor health outcomes. While several theoretical perspectives provide insights on this relationship, the literature lacks an integrative framework explaining the relationship. We develop a conceptual model explaining the link between subjective well-being and physiological functioning in the context of work. Integrating positive psychology and occupational stress perspectives, our model explains the relationship between subjective well-being and physiological functioning as a result of the direct influence of subjective well-being on physiological functioning and of their common relationships with work stress and personal resources, both of which are influenced by job conditions.

Improving the physiological realism of experimental models.

PubMed

Vinnakota, Kalyan C; Cha, Chae Y; Rorsman, Patrik; Balaban, Robert S; La Gerche, Andre; Wade-Martins, Richard; Beard, Daniel A; Jeneson, Jeroen A L

2016-04-06

The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging from in vitro non-human cell organelles to in vivo human organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease.

Modeling drug release from functionalized magnetic nanoparticles actuated by non-heating low frequency magnetic field

NASA Astrophysics Data System (ADS)

Golovin, Y.; Golovin, D.; Klyachko, N.; Majouga, A.; Kabanov, A.

2017-02-01

Various plausible acceleration mechanisms of drug release from nanocarriers composed of a single-domain magnetic nanoparticle core with attached long macromolecule chains activated by low frequency non-heating alternating magnetic field (AMF) are discussed. The most important system characteristics affecting the AMF exposure impact are determined. Impact of several reasonable mechanisms is estimated analytically or obtained using numerical modeling. Some conditions providing manifold release acceleration as a result from exposure in AMF are found.

Like-Me Simulation as an Effective and Cognitively Plausible Basis for Social Robotics

DTIC Science & Technology

2009-02-24

sec- onds, and when productions were available , the model re- sponds in 2.3 seconds. 4.4 Perspective Taking Discussion In experiments testing human...behavior. First, if there are existing productions for the specific situation, they provide the re- sponse. If no productions are available , the model...1. REPORT DATE FEB 2009 2. REPORT TYPE 3. DATES COVERED 00-00-2009 to 00-00-2009 4. TITLE AND SUBTITLE ’Like-Me’ Simulation as an Effective

Mechanistic species distribution modelling as a link between physiology and conservation.

PubMed

Evans, Tyler G; Diamond, Sarah E; Kelly, Morgan W

2015-01-01

Climate change conservation planning relies heavily on correlative species distribution models that estimate future areas of occupancy based on environmental conditions encountered in present-day ranges. The approach benefits from rapid assessment of vulnerability over a large number of organisms, but can have poor predictive power when transposed to novel environments and reveals little in the way of causal mechanisms that define changes in species distribution or abundance. Having conservation planning rely largely on this single approach also increases the risk of policy failure. Mechanistic models that are parameterized with physiological information are expected to be more robust when extrapolating distributions to future environmental conditions and can identify physiological processes that set range boundaries. Implementation of mechanistic species distribution models requires knowledge of how environmental change influences physiological performance, and because this information is currently restricted to a comparatively small number of well-studied organisms, use of mechanistic modelling in the context of climate change conservation is limited. In this review, we propose that the need to develop mechanistic models that incorporate physiological data presents an opportunity for physiologists to contribute more directly to climate change conservation and advance the field of conservation physiology. We begin by describing the prevalence of species distribution modelling in climate change conservation, highlighting the benefits and drawbacks of both mechanistic and correlative approaches. Next, we emphasize the need to expand mechanistic models and discuss potential metrics of physiological performance suitable for integration into mechanistic models. We conclude by summarizing other factors, such as the need to consider demography, limiting broader application of mechanistic models in climate change conservation. Ideally, modellers, physiologists and conservation practitioners would work collaboratively to build models, interpret results and consider conservation management options, and articulating this need here may help to stimulate collaboration.

Strategy for modeling putative multilevel ecosystems on Europa.

PubMed

Irwin, Louis N; Schulze-Makuch, Dirk

2003-01-01

A general strategy for modeling ecosystems on other worlds is described. Two alternative biospheres beneath the ice surface of Europa are modeled, based on analogous ecosystems on Earth in potentially comparable habitats, with reallocation of biomass quantities consistent with different sources of energy and chemical constituents. The first ecosystem models a benthic biosphere supported by chemoautotrophic producers. The second models two concentrations of biota at the top and bottom of the subsurface water column supported by energy harvested from transmembrane ionic gradients. Calculations indicate the plausibility of both ecosystems, including small macroorganisms at the highest trophic levels, with ionotrophy supporting a larger biomass than chemoautotrophy.

Quantifying Direct and Indirect Effects of Elevated CO2 on Ecosystem Response

NASA Astrophysics Data System (ADS)

Fatichi, S.; Leuzinger, S.; Paschalis, A.; Donnellan-Barraclough, A.; Hovenden, M. J.; Langley, J. A.

2015-12-01

Increasing concentrations of atmospheric carbon dioxide are expected to affect carbon assimilation, evapotranspiration (ET) and ultimately plant growth. Direct leaf biochemical effects have been widely investigated, while indirect effects, although documented, are very difficult to quantify in experiments. We hypothesize that the interaction of direct and indirect effects is a possible reason for conflicting results concerning the magnitude of CO2 fertilization effects across different climates and ecosystems. A mechanistic ecohydrological model (Tethys-Chloris) is used to investigate the relative contribution of direct (through plant physiology) and indirect (via stomatal closure and thus soil moisture, and changes in Leaf Area Index, LAI) effects of elevated CO2 across a number of ecosystems. We specifically ask in which ecosystems and climate indirect effects are expected to be largest. Data and boundary conditions from flux-towers and free air CO2 enrichment (FACE) experiments are used to force the model and evaluate its performance. Numerical results suggest that indirect effects of elevated CO2, through water savings and increased LAI, are very significant and sometimes larger than direct effects. Indirect effects tend to be considerably larger in water-limited ecosystems, while direct effects correlate positively with mean air temperature. Increasing CO2 from 375 to 550 ppm causes a total effect on Net Primary Production in the order of 15 to 40% and on ET from 0 to -8%, depending on climate and ecosystem type. The total CO2 effect has a significant negative correlation with the wetness index and positive correlation with vapor pressure deficit. These results provide a more general mechanistic understanding of relatively short-term (less than 20 years) implications of elevated CO2 on ecosystem response and suggest plausible magnitudes for the expected changes.

Neuronal variability in orbitofrontal cortex during economic decisions.

PubMed

Conen, Katherine E; Padoa-Schioppa, Camillo

2015-09-01

Neuroeconomic models assume that economic decisions are based on the activity of offer value cells in the orbitofrontal cortex (OFC), but testing this assertion has proven difficult. In principle, the decision made on a given trial should correlate with the stochastic fluctuations of these cells. However, this correlation, measured as a choice probability (CP), is small. Importantly, a neuron's CP reflects not only its individual contribution to the decision (termed readout weight), but also the intensity and the structure of correlated variability across the neuronal population (termed noise correlation). A precise mathematical relation between CPs, noise correlations, and readout weights was recently derived by Haefner and colleagues (Haefner RM, Gerwinn S, Macke JH, Bethge M. Nat Neurosci 16: 235-242, 2013) for a linear decision model. In this framework, concurrent measurements of noise correlations and CPs can provide quantitative information on how a population of cells contributes to a decision. Here we examined neuronal variability in the OFC of rhesus monkeys during economic decisions. Noise correlations had similar structure but considerably lower strength compared with those typically measured in sensory areas during perceptual decisions. In contrast, variability in the activity of individual cells was high and comparable to that recorded in other cortical regions. Simulation analyses based on Haefner's equation showed that noise correlations measured in the OFC combined with a plausible readout of offer value cells reproduced the experimental measures of CPs. In other words, the results obtained for noise correlations and those obtained for CPs taken together support the hypothesis that economic decisions are primarily based on the activity of offer value cells. Copyright © 2015 the American Physiological Society.

Physiological Parameters Database for PBPK Modeling (External Review Draft)

EPA Science Inventory

EPA released for public comment a physiological parameters database (created using Microsoft ACCESS) intended to be used in PBPK modeling. The database contains physiological parameter values for humans from early childhood through senescence. It also contains similar data for an...

Fast and Frugal Heuristics Are Plausible Models of Cognition: Reply to Dougherty, Franco-Watkins, and Thomas (2008)

ERIC Educational Resources Information Center

Gigerenzer, Gerd; Hoffrage, Ulrich; Goldstein, Daniel G.

2008-01-01

M. R. Dougherty, A. M. Franco-Watkins, and R. Thomas (2008) conjectured that fast and frugal heuristics need an automatic frequency counter for ordering cues. In fact, only a few heuristics order cues, and these orderings can arise from evolutionary, social, or individual learning, none of which requires automatic frequency counting. The idea that…

The Teachers' Sense of Efficacy Scale: Confirming the Factor Structure with Beginning Pre-Service Teachers

ERIC Educational Resources Information Center

Duffin, Lisa C.; French, Brian F.; Patrick, Helen

2012-01-01

This study examined the factor structure of the Teachers' Sense of Efficacy Scale (TSES; Tschannen-Moran & Woolfolk Hoy, 2001) using the scores of pre-service teachers at the beginning stage of teacher development to gather internal structure score validity evidence. Two plausible rival models derived from prior research were tested using CFA.…

A Biologically Plausible Action Selection System for Cognitive Architectures: Implications of Basal Ganglia Anatomy for Learning and Decision-Making Models

ERIC Educational Resources Information Center

Stocco, Andrea

2018-01-01

Several attempts have been made previously to provide a biological grounding for cognitive architectures by relating their components to the computations of specific brain circuits. Often, the architecture's action selection system is identified with the basal ganglia. However, this identification overlooks one of the most important features of…

The Mediating Effect of Organizational Trust on the Link between the Areas of Work Life and Emotional Exhaustion

ERIC Educational Resources Information Center

Bayhan Karapinar, Pinar; Metin Camgoz, Selin; Tayfur Ekmekci, Ozge

2016-01-01

The study tests an integrative model that considers the plausible effects of different areas of work life on emotional exhaustion. It also tests the mediating effect of organizational trust on this relationship. More specifically, while perceived incongruence in six areas of work life (workload, fairness, reward, community, control and value) is…

How Students and Field Geologists Reason in Integrating Spatial Observations from Outcrops to Visualize a 3-D Geological Structure

ERIC Educational Resources Information Center

Kastens, Kim A.; Agrawal, Shruti; Liben, Lynn S.

2009-01-01

Geologists and undergraduate students observed eight artificial "rock outcrops" in a realistically scaled field area, and then tried to envision a geological structure that might plausibly be formed by the layered rocks in the set of outcrops. Students were videotaped as they selected which of fourteen 3-D models they thought best…

Approximate reasoning using terminological models

NASA Technical Reports Server (NTRS)

Yen, John; Vaidya, Nitin

1992-01-01

Term Subsumption Systems (TSS) form a knowledge-representation scheme in AI that can express the defining characteristics of concepts through a formal language that has a well-defined semantics and incorporates a reasoning mechanism that can deduce whether one concept subsumes another. However, TSS's have very limited ability to deal with the issue of uncertainty in knowledge bases. The objective of this research is to address issues in combining approximate reasoning with term subsumption systems. To do this, we have extended an existing AI architecture (CLASP) that is built on the top of a term subsumption system (LOOM). First, the assertional component of LOOM has been extended for asserting and representing uncertain propositions. Second, we have extended the pattern matcher of CLASP for plausible rule-based inferences. Third, an approximate reasoning model has been added to facilitate various kinds of approximate reasoning. And finally, the issue of inconsistency in truth values due to inheritance is addressed using justification of those values. This architecture enhances the reasoning capabilities of expert systems by providing support for reasoning under uncertainty using knowledge captured in TSS. Also, as definitional knowledge is explicit and separate from heuristic knowledge for plausible inferences, the maintainability of expert systems could be improved.

Computer simulated modeling of healthy and diseased right ventricular and pulmonary circulation.

PubMed

Chou, Jody; Rinehart, Joseph B

2018-01-12

We have previously developed a simulated cardiovascular physiology model for in-silico testing and validation of novel closed-loop controllers. To date, a detailed model of the right heart and pulmonary circulation was not needed, as previous controllers were not intended for use in patients with cardiac or pulmonary pathology. With new development of controllers for vasopressors, and looking forward, for combined vasopressor-fluid controllers, modeling of right-sided and pulmonary pathology is now relevant to further in-silico validation, so we aimed to expand our existing simulation platform to include these elements. Our hypothesis was that the completed platform could be tuned and stabilized such that the distributions of a randomized sample of simulated patients' baseline characteristics would be similar to reported population values. Our secondary outcomes were to further test the system in representing acute right heart failure and pulmonary artery hypertension. After development and tuning of the right-sided circulation, the model was validated against clinical data from multiple previously published articles. The model was considered 'tuned' when 100% of generated randomized patients converged to stability (steady, physiologically-plausible compartmental volumes, flows, and pressures) and 'valid' when the means for the model data in each health condition were contained within the standard deviations for the published data for the condition. A fully described right heart and pulmonary circulation model including non-linear pressure/volume relationships and pressure dependent flows was created over a 6-month span. The model was successfully tuned such that 100% of simulated patients converged into a steady state within 30 s. Simulation results in the healthy state for central venous volume (3350 ± 132 ml) pulmonary blood volume (405 ± 39 ml), pulmonary artery pressures (systolic 20.8 ± 4.1 mmHg and diastolic 9.4 ± 1.8 mmHg), left atrial pressure (4.6 ± 0.8 mmHg), PVR (1.0 ± 0.2 wood units), and CI (3.8 ± 0.5 l/min/m 2 ) all met criteria for acceptance of the model, though the standard deviations of LAP and CI were somewhat narrower than published comparators. The simulation results for right ventricular infarction also fell within the published ranges: pulmonary blood volume (727 ± 102 ml), pulmonary arterial pressures (30 ± 4 mmHg systolic, 12 ± 2 mmHg diastolic), left atrial pressure (13 ± 2 mmHg), PVR (1.6 ± 0.3 wood units), and CI (2.0 ± 0.4 l/min/m 2 ) all fell within one standard deviation of the reported population values and vice-versa. In the pulmonary hypertension model, pulmonary blood volume of 615 ± 90 ml, pulmonary arterial pressures of 80 ± 14 mmHg systolic, 36 ± 7 mmHg diastolic, and the left atrial pressure of 11 ± 2 mmHg all met criteria for acceptance. For CI, the simulated value of 2.8 ± 0.4 l/min/m 2 once again had a narrower spread than most of the published data, but fell inside of the SD of all published data, and the PVR value of 7.5 ± 1.6 wood units fell in the middle of the four published studies. The right-ventricular and pulmonary circulation simulation appears to be a reasonable approximation of the right-sided circulation for healthy physiology as well as the pathologic conditions tested.

Computer support for physiological cell modelling using an ontology on cell physiology.

PubMed

Takao, Shimayoshi; Kazuhiro, Komurasaki; Akira, Amano; Takeshi, Iwashita; Masanori, Kanazawa; Tetsuya, Matsuda

2006-01-01

The development of electrophysiological whole cell models to support the understanding of biological mechanisms is increasing rapidly. Due to the complexity of biological systems, comprehensive cell models, which are composed of many imported sub-models of functional elements, can get quite complicated as well, making computer modification difficult. Here, we propose a computer support to enhance structural changes of cell models, employing the markup languages CellML and our original PMSML (physiological model structure markup language), in addition to a new ontology for cell physiological modelling. In particular, a method to make references from CellML files to the ontology and a method to assist manipulation of model structures using markup languages together with the ontology are reported. Using these methods three software utilities, including a graphical model editor, are implemented. Experimental results proved that these methods are effective for the modification of electrophysiological models.

Evaluating and improving count-based population inference: A case study from 31 years of monitoring Sandhill Cranes

USGS Publications Warehouse

Gerber, Brian D.; Kendall, William L.

2017-01-01

Monitoring animal populations can be difficult. Limited resources often force monitoring programs to rely on unadjusted or smoothed counts as an index of abundance. Smoothing counts is commonly done using a moving-average estimator to dampen sampling variation. These indices are commonly used to inform management decisions, although their reliability is often unknown. We outline a process to evaluate the biological plausibility of annual changes in population counts and indices from a typical monitoring scenario and compare results with a hierarchical Bayesian time series (HBTS) model. We evaluated spring and fall counts, fall indices, and model-based predictions for the Rocky Mountain population (RMP) of Sandhill Cranes (Antigone canadensis) by integrating juvenile recruitment, harvest, and survival into a stochastic stage-based population model. We used simulation to evaluate population indices from the HBTS model and the commonly used 3-yr moving average estimator. We found counts of the RMP to exhibit biologically unrealistic annual change, while the fall population index was largely biologically realistic. HBTS model predictions suggested that the RMP changed little over 31 yr of monitoring, but the pattern depended on assumptions about the observational process. The HBTS model fall population predictions were biologically plausible if observed crane harvest mortality was compensatory up to natural mortality, as empirical evidence suggests. Simulations indicated that the predicted mean of the HBTS model was generally a more reliable estimate of the true population than population indices derived using a moving 3-yr average estimator. Practitioners could gain considerable advantages from modeling population counts using a hierarchical Bayesian autoregressive approach. Advantages would include: (1) obtaining measures of uncertainty; (2) incorporating direct knowledge of the observational and population processes; (3) accommodating missing years of data; and (4) forecasting population size.

An Integrated Analysis of the Physiological Effects of Space Flight: Executive Summary

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1985-01-01

A large array of models were applied in a unified manner to solve problems in space flight physiology. Mathematical simulation was used as an alternative way of looking at physiological systems and maximizing the yield from previous space flight experiments. A medical data analysis system was created which consist of an automated data base, a computerized biostatistical and data analysis system, and a set of simulation models of physiological systems. Five basic models were employed: (1) a pulsatile cardiovascular model; (2) a respiratory model; (3) a thermoregulatory model; (4) a circulatory, fluid, and electrolyte balance model; and (5) an erythropoiesis regulatory model. Algorithms were provided to perform routine statistical tests, multivariate analysis, nonlinear regression analysis, and autocorrelation analysis. Special purpose programs were prepared for rank correlation, factor analysis, and the integration of the metabolic balance data.

Minireview: Dopaminergic Regulation of Insulin Secretion from the Pancreatic Islet

PubMed Central

Ustione, Alessandro

2013-01-01

Exogenous dopamine inhibits insulin secretion from pancreatic β-cells, but the lack of dopaminergic neurons in pancreatic islets has led to controversy regarding the importance of this effect. Recent data, however, suggest a plausible physiologic role for dopamine in the regulation of insulin secretion. We review the literature underlying our current understanding of dopaminergic signaling that can down-regulate glucose-stimulated insulin secretion from pancreatic islets. In this negative feedback loop, dopamine is synthesized in the β-cells from circulating l-dopa, serves as an autocrine signal that is cosecreted with insulin, and causes a tonic inhibition on glucose-stimulated insulin secretion. On the whole animal scale, l-dopa is produced by cells in the gastrointestinal tract, and its concentration in the blood plasma increases following a mixed meal. By reviewing the outcome of certain types of bariatric surgery that result in rapid amelioration of glucose tolerance, we hypothesize that dopamine serves as an “antiincretin” signal that counterbalances the stimulatory effect of glucagon-like peptide 1. PMID:23744894

Does the Concept of “Sensitization” Provide a Plausible Mechanism for the Putative Link Between the Environment and Schizophrenia?

PubMed Central

Collip, Dina; Myin-Germeys, Inez; Van Os, Jim

2008-01-01

Previous evidence reviewed in Schizophrenia Bulletin suggests the importance of a range of different environmental factors in the development of psychotic illness. It is unlikely, however, that the diversity of environmental influences associated with schizophrenia can be linked to as many different underlying mechanisms. There is evidence that environmental exposures may induce, in interaction with (epi)genetic factors, psychological or physiological alterations that can be traced to a final common pathway of cognitive biases and/or altered dopamine neurotransmission, broadly referred to as “sensitization,” facilitating the onset and persistence of psychotic symptoms. At the population level, the behavioral phenotype for sensitization may be examined by quantifying, in populations exposed to environmental risk factors associated with stress or dopamine-agonist drugs, (1) the increased rate of persistence (indicating lasting sensitization) of normally transient developmental expressions of subclinical psychotic experiences and (2) the subsequent increased rate of transition to clinical psychotic disorder. PMID:18203757

Site-specific acid-base properties of pholcodine and related compounds.

PubMed

Kovács, Z; Hosztafi, S; Noszál, B

2006-11-01

The acid-base properties of pholcodine, a cough-depressant agent, and related compounds including metabolites were studied by 1H NMR-pH titrations, and are characterised in terms of macroscopic and microscopic protonation constants. New N-methylated derivatives were also synthesized in order to quantitate site- and nucleus-specific protonation shifts and to unravel microscopic acid-base equilibria. The piperidine nitrogen was found to be 38 and 400 times more basic than its morpholine counterpart in pholcodine and norpholcodine, respectively. The protonation data show that the molecule of pholcodine bears an average of positive charge of 1.07 at physiological pH, preventing it from entering the central nervous system, a plausible reason for its lack of analgesic or addictive properties. The protonation constants of pholcodine and its derivatives are interpreted by comparing with related molecules of pharmaceutical interest. The pH-dependent relative concentrations of the variously protonated forms of pholcodine and morphine are depicted in distribution diagrams.

Perspectives of breast cancer etiology: synergistic interaction between smoking and exogenous hormone use

PubMed Central

Zhu, Hong-Hong; Hu, Cao-Hui; Strickland, Paul

2011-01-01

To explore breast cancer etiology, literature was searched using Medline. We explored the (1) plausibility of smoking in breast Carcinogenesis; (2) physiological properties, susceptibility windows, and exposure timing of breast cells; (3) role of exogenous hormones in breast Carcinogenesis; (4) biological mechanism of synergistic interactions between smoking and exogenous hormones in breast Carcinogenesis; and (5) evidence from epidemiologic studies and the fitted secular trend between smoking rate, exogenous hormone use, and breast cancer incidence in past decades. We deduced that exogenous hormone use per se is not a significant cause and its association with breast cancer is distorted by chronic exposure to environmental carcinogens, especially smoking. We hypothesize that smoking is one of the causes of breast cancer and that this causality is strengthened by synergistic interaction between smoking and exogenous hormone use. Physicians should be cautious of prescribing exogenous hormones for those with chronic exposure to environmental carcinogens to prevent breast cancer. PMID:21718589

Protein S-sulfenylation is a fleeting molecular switch that regulates non-enzymatic oxidative folding

NASA Astrophysics Data System (ADS)

Beedle, Amy E. M.; Lynham, Steven; Garcia-Manyes, Sergi

2016-08-01

The post-translational modification S-sulfenylation functions as a key sensor of oxidative stress. Yet the dynamics of sulfenic acid in proteins remains largely elusive due to its fleeting nature. Here we use single-molecule force-clamp spectroscopy and mass spectrometry to directly capture the reactivity of an individual sulfenic acid embedded within the core of a single Ig domain of the titin protein. Our results demonstrate that sulfenic acid is a crucial short-lived intermediate that dictates the protein's fate in a conformation-dependent manner. When exposed to the solution, sulfenic acid rapidly undergoes further chemical modification, leading to irreversible protein misfolding; when cryptic in the protein's microenvironment, it readily condenses with a neighbouring thiol to create a protective disulfide bond, which assists the functional folding of the protein. This mechanism for non-enzymatic oxidative folding provides a plausible explanation for redox-modulated stiffness of proteins that are physiologically exposed to mechanical forces, such as cardiac titin.

Do US Black Women Experience Stress-Related Accelerated Biological Aging?

PubMed Central

Hicken, Margaret T.; Pearson, Jay A.; Seashols, Sarah J.; Brown, Kelly L.; Cruz, Tracey Dawson

2010-01-01

We hypothesize that black women experience accelerated biological aging in response to repeated or prolonged adaptation to subjective and objective stressors. Drawing on stress physiology and ethnographic, social science, and public health literature, we lay out the rationale for this hypothesis. We also perform a first population-based test of its plausibility, focusing on telomere length, a biomeasure of aging that may be shortened by stressors. Analyzing data from the Study of Women's Health Across the Nation (SWAN), we estimate that at ages 49–55, black women are 7.5 years biologically “older” than white women. Indicators of perceived stress and poverty account for 27% of this difference. Data limitations preclude assessing objective stressors and also result in imprecise estimates, limiting our ability to draw firm inferences. Further investigation of black-white differences in telomere length using large-population-based samples of broad age range and with detailed measures of environmental stressors is merited. PMID:20436780

Does docosahexaenoic acid supplementation in term infants enhance neurocognitive functioning in infancy?

PubMed

Heaton, Alexandra E; Meldrum, Suzanne J; Foster, Jonathan K; Prescott, Susan L; Simmer, Karen

2013-11-20

The proposal that dietary docosahexaenoic acid (DHA) enhances neurocognitive functioning in term infants is controversial. Theoretical evidence, laboratory research and human epidemiological studies have convincingly demonstrated that DHA deficiency can negatively impact neurocognitive development. However, the results from randomized controlled trials (RCTs) of DHA supplementation in human term-born infants have been inconsistent. This article will (i) discuss the role of DHA in the human diet, (ii) explore the physiological mechanisms by which DHA plausibly influences neurocognitive capacity, and (iii) seek to characterize the optimal intake of DHA during infancy for neurocognitive functioning, based on existing research that has been undertaken in developed countries (specifically, within Australia). The major observational studies and RCTs that have examined dietary DHA in human infants and animals are presented, and we consider suggestions that DHA requirements vary across individuals according to genetic profile. It is important that the current evidence concerning DHA supplementation is carefully evaluated so that appropriate recommendations can be made and future directions of research can be strategically planned.

Does docosahexaenoic acid supplementation in term infants enhance neurocognitive functioning in infancy?

PubMed Central

Heaton, Alexandra E.; Meldrum, Suzanne J.; Foster, Jonathan K.; Prescott, Susan L.; Simmer, Karen

2013-01-01

The proposal that dietary docosahexaenoic acid (DHA) enhances neurocognitive functioning in term infants is controversial. Theoretical evidence, laboratory research and human epidemiological studies have convincingly demonstrated that DHA deficiency can negatively impact neurocognitive development. However, the results from randomized controlled trials (RCTs) of DHA supplementation in human term-born infants have been inconsistent. This article will (i) discuss the role of DHA in the human diet, (ii) explore the physiological mechanisms by which DHA plausibly influences neurocognitive capacity, and (iii) seek to characterize the optimal intake of DHA during infancy for neurocognitive functioning, based on existing research that has been undertaken in developed countries (specifically, within Australia). The major observational studies and RCTs that have examined dietary DHA in human infants and animals are presented, and we consider suggestions that DHA requirements vary across individuals according to genetic profile. It is important that the current evidence concerning DHA supplementation is carefully evaluated so that appropriate recommendations can be made and future directions of research can be strategically planned. PMID:24312040

Subcutaneous white adipocytes express a light sensitive signaling pathway mediated via a melanopsin/TRPC channel axis.

PubMed

Ondrusova, Katarina; Fatehi, Mohammad; Barr, Amy; Czarnecka, Zofia; Long, Wentong; Suzuki, Kunimasa; Campbell, Scott; Philippaert, Koenraad; Hubert, Matthew; Tredget, Edward; Kwan, Peter; Touret, Nicolas; Wabitsch, Martin; Lee, Kevin Y; Light, Peter E

2017-11-27

Subcutaneous white adipose tissue (scWAT) is the major fat depot in humans and is a central player in regulating whole body metabolism. Skin exposure to UV wavelengths from sunlight is required for Vitamin D synthesis and pigmentation, although it is plausible that longer visible wavelengths that penetrate the skin may regulate scWAT function. In this regard, we discovered a novel blue light-sensitive current in human scWAT that is mediated by melanopsin coupled to transient receptor potential canonical cation channels. This pathway is activated at physiological intensities of light that penetrate the skin on a sunny day. Daily exposure of differentiated adipocytes to blue light resulted in decreased lipid droplet size, increased basal lipolytic rate and alterations in adiponectin and leptin secretion. Our results suggest that scWAT function may be directly under the influence of ambient sunlight exposure and may have important implications for our current understanding of adipocyte biology. (150 words).

In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide

PubMed Central

2011-01-01

Background Hydrogen peroxide (H2O2) produced by vaginal lactobacilli is generally believed to protect against bacteria associated with bacterial vaginosis (BV), and strains of lactobacilli that can produce H2O2 are being developed as vaginal probiotics. However, evidence that led to this belief was based in part on non-physiological conditions, antioxidant-free aerobic conditions selected to maximize both production and microbicidal activity of H2O2. Here we used conditions more like those in vivo to compare the effects of physiologically plausible concentrations of H2O2 and lactic acid on a broad range of BV-associated bacteria and vaginal lactobacilli. Methods Anaerobic cultures of seventeen species of BV-associated bacteria and four species of vaginal lactobacilli were exposed to H2O2, lactic acid, or acetic acid at pH 7.0 and pH 4.5. After two hours, the remaining viable bacteria were enumerated by growth on agar media plates. The effect of vaginal fluid (VF) on the microbicidal activities of H2O2 and lactic acid was also measured. Results Physiological concentrations of H2O2 (< 100 μM) failed to inactivate any of the BV-associated bacteria tested, even in the presence of human myeloperoxidase (MPO) that increases the microbicidal activity of H2O2. At 10 mM, H2O2 inactivated all four species of vaginal lactobacilli but only one of seventeen species of BV-associated bacteria. Moreover, the addition of just 1% vaginal fluid (VF) blocked the microbicidal activity of 1 M H2O2. In contrast, lactic acid at physiological concentrations (55-111 mM) and pH (4.5) inactivated all the BV-associated bacteria tested, and had no detectable effect on the vaginal lactobacilli. Also, the addition of 10% VF did not block the microbicidal activity of lactic acid. Conclusions Under optimal, anaerobic growth conditions, physiological concentrations of lactic acid inactivated BV-associated bacteria without affecting vaginal lactobacilli, whereas physiological concentrations of H2O2 produced no detectable inactivation of either BV-associated bacteria or vaginal lactobacilli. Moreover, at very high concentrations, H2O2 was more toxic to vaginal lactobacilli than to BV-associated bacteria. On the basis of these in vitro observations, we conclude that lactic acid, not H2O2, is likely to suppress BV-associated bacteria in vivo. PMID:21771337

Applications of physiologically based pharmacokinetic modeling for the optimization of anti-infective therapies.

PubMed

Moss, Darren Michael; Marzolini, Catia; Rajoli, Rajith K R; Siccardi, Marco

2015-01-01

The pharmacokinetic properties of anti-infective drugs are a determinant part of treatment success. Pathogen replication is inhibited if adequate drug levels are achieved in target sites, whereas excessive drug concentrations linked to toxicity are to be avoided. Anti-infective distribution can be predicted by integrating in vitro drug properties and mathematical descriptions of human anatomy in physiologically based pharmacokinetic models. This method reduces the need for animal and human studies and is used increasingly in drug development and simulation of clinical scenario such as, for instance, drug-drug interactions, dose optimization, novel formulations and pharmacokinetics in special populations. We have assessed the relevance of physiologically based pharmacokinetic modeling in the anti-infective research field, giving an overview of mechanisms involved in model design and have suggested strategies for future applications of physiologically based pharmacokinetic models. Physiologically based pharmacokinetic modeling provides a powerful tool in anti-infective optimization, and there is now no doubt that both industry and regulatory bodies have recognized the importance of this technology. It should be acknowledged, however, that major challenges remain to be addressed and that information detailing disease group physiology and anti-infective pharmacodynamics is required if a personalized medicine approach is to be achieved.

Improving the physiological realism of experimental models

PubMed Central

Vinnakota, Kalyan C.; Cha, Chae Y.; Rorsman, Patrik; Balaban, Robert S.; La Gerche, Andre; Wade-Martins, Richard; Beard, Daniel A.

2016-01-01

The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging from in vitro non-human cell organelles to in vivo human organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease. PMID:27051507

Structural analysis of thermostabilizing mutations of cocaine esterase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Narasimhan, Diwahar; Nance, Mark R.; Gao, Daquan

Cocaine is considered to be the most addictive of all substances of abuse and mediates its effects by inhibiting monoamine transporters, primarily the dopamine transporters. There are currently no small molecules that can be used to combat its toxic and addictive properties, in part because of the difficulty of developing compounds that inhibit cocaine binding without having intrinsic effects on dopamine transport. Most of the effective cocaine inhibitors also display addictive properties. We have recently reported the use of cocaine esterase (CocE) to accelerate the removal of systemic cocaine and to prevent cocaine-induced lethality. However, wild-type CocE is relatively unstablemore » at physiological temperatures ({tau}{sub 1/2} {approx} 13 min at 37 C), presenting challenges for its development as a viable therapeutic agent. We applied computational approaches to predict mutations to stabilize CocE and showed that several of these have increased stability both in vitro and in vivo, with the most efficacious mutant (T172R/G173Q) extending half-life up to 370 min. Here we present novel X-ray crystallographic data on these mutants that provide a plausible model for the observed enhanced stability. We also more extensively characterize the previously reported variants and report on a new stabilizing mutant, L169K. The improved stability of these engineered CocE enzymes will have a profound influence on the use of this protein to combat cocaine-induced toxicity and addiction in humans.« less

High-Throughput Sequencing of RNA Silencing-Associated Small RNAs in Olive (Olea europaea L.)

PubMed Central

Donaire, Livia; Pedrola, Laia; de la Rosa, Raúl; Llave, César

2011-01-01

Small RNAs (sRNAs) of 20 to 25 nucleotides (nt) in length maintain genome integrity and control gene expression in a multitude of developmental and physiological processes. Despite RNA silencing has been primarily studied in model plants, the advent of high-throughput sequencing technologies has enabled profiling of the sRNA component of more than 40 plant species. Here, we used deep sequencing and molecular methods to report the first inventory of sRNAs in olive (Olea europaea L.). sRNA libraries prepared from juvenile and adult shoots revealed that the 24-nt class dominates the sRNA transcriptome and atypically accumulates to levels never seen in other plant species, suggesting an active role of heterochromatin silencing in the maintenance and integrity of its large genome. A total of 18 known miRNA families were identified in the libraries. Also, 5 other sRNAs derived from potential hairpin-like precursors remain as plausible miRNA candidates. RNA blots confirmed miRNA expression and suggested tissue- and/or developmental-specific expression patterns. Target mRNAs of conserved miRNAs were computationally predicted among the olive cDNA collection and experimentally validated through endonucleolytic cleavage assays. Finally, we use expression data to uncover genetic components of the miR156, miR172 and miR390/TAS3-derived trans-acting small interfering RNA (tasiRNA) regulatory nodes, suggesting that these interactive networks controlling developmental transitions are fully operational in olive. PMID:22140484

Predicting future threats to the long-term survival of Gila Trout using a high-resolution simulation of climate change

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kennedy, Thomas L.; Gutzler, David S.; Leung, Lai R.

2008-11-20

Regional climates are a major factor in determining the distribution of many species. Anthropogenic inputs of greenhouse gases into the atmosphere have been predicted to cause rapid climatic changes in the next 50-100 years. Species such as the Gila Trout (Onchorhynchus gilae) that have small ranges, limited dispersal capabilities, and narrow physiological tolerances will become increasingly susceptible to extinction as their climate envelope changes. This study uses a regional climate change simulation (Leung et al. 2004) to determine changes in the climate envelope for Gila Trout, which is sensitive to maximum temperature, associated with a plausible scenario for greenhouse gasmore » increases. The model predicts approximately a 2° C increase in temperature and a doubling by the mid 21st Century in the annual number of days during which temperature exceeds 37°C, and a 25% increase in the number of days above 32°C, across the current geographical range of Gila Trout. At the same time summer rainfall decreases by more than 20%. These climate changes would reduce their available habitat by decreasing the size of their climate envelope. Warmer temperatures coupled with a decrease in summer precipitation would also tend to increase the intensity and frequency of forest fires that are a major threat to their survival. The climate envelope approach utilized here could be used to assess climate change threats to other rare species with limited ranges and dispersal capabilities.« less

A temperature rise reduces trial-to-trial variability of locust auditory neuron responses

PubMed Central

Schleimer, Jan-Hendrik; Schreiber, Susanne; Ronacher, Bernhard

2015-01-01

The neurophysiology of ectothermic animals, such as insects, is affected by environmental temperature, as their body temperature fluctuates with ambient conditions. Changes in temperature alter properties of neurons and, consequently, have an impact on the processing of information. Nevertheless, nervous system function is often maintained over a broad temperature range, exhibiting a surprising robustness to variations in temperature. A special problem arises for acoustically communicating insects, as in these animals mate recognition and mate localization typically rely on the decoding of fast amplitude modulations in calling and courtship songs. In the auditory periphery, however, temporal resolution is constrained by intrinsic neuronal noise. Such noise predominantly arises from the stochasticity of ion channel gating and potentially impairs the processing of sensory signals. On the basis of intracellular recordings of locust auditory neurons, we show that intrinsic neuronal variability on the level of spikes is reduced with increasing temperature. We use a detailed mathematical model including stochastic ion channel gating to shed light on the underlying biophysical mechanisms in auditory receptor neurons: because of a redistribution of channel-induced current noise toward higher frequencies and specifics of the temperature dependence of the membrane impedance, membrane potential noise is indeed reduced at higher temperatures. This finding holds under generic conditions and physiologically plausible assumptions on the temperature dependence of the channels' kinetics and peak conductances. We demonstrate that the identified mechanism also can explain the experimentally observed reduction of spike timing variability at higher temperatures. PMID:26041833

USE OF A PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODEL TO ESTIMATE ABSORBED CARBARYL DOSE IN CHILDREN AFTER TURF APPLICATION

EPA Science Inventory

A physiologically based pharmacokinetic (PBPK) model was developed to investigate exposure scenarios of children to carbaryl following turf application. Physiological, pharmacokinetic and pharmacodynamic parameters describing the fate and effects of carbaryl in rats were scaled ...

Predicting Age-Appropriate Pharmacokinetics of Six Volatile Organic Compounds in the Rat Utilizing Physiologically Based Pharmacokinetic Modeling

EPA Science Inventory

The capability of physiologically based pharmacokinetic models to incorporate age-appropriate physiological and chemical-specific parameters was utilized to predict changes in internal dosimetry for six volatile organic compounds (VOCs) across different ages of rats.

Singularity now: using the ventricular assist device as a model for future human-robotic physiology.

PubMed

Martin, Archer K

2016-04-01

In our 21 st century world, human-robotic interactions are far more complicated than Asimov predicted in 1942. The future of human-robotic interactions includes human-robotic machine hybrids with an integrated physiology, working together to achieve an enhanced level of baseline human physiological performance. This achievement can be described as a biological Singularity. I argue that this time of Singularity cannot be met by current biological technologies, and that human-robotic physiology must be integrated for the Singularity to occur. In order to conquer the challenges we face regarding human-robotic physiology, we first need to identify a working model in today's world. Once identified, this model can form the basis for the study, creation, expansion, and optimization of human-robotic hybrid physiology. In this paper, I present and defend the line of argument that currently this kind of model (proposed to be named "IshBot") can best be studied in ventricular assist devices - VAD.

Singularity now: using the ventricular assist device as a model for future human-robotic physiology

PubMed Central

Martin, Archer K.

2016-01-01

In our 21st century world, human-robotic interactions are far more complicated than Asimov predicted in 1942. The future of human-robotic interactions includes human-robotic machine hybrids with an integrated physiology, working together to achieve an enhanced level of baseline human physiological performance. This achievement can be described as a biological Singularity. I argue that this time of Singularity cannot be met by current biological technologies, and that human-robotic physiology must be integrated for the Singularity to occur. In order to conquer the challenges we face regarding human-robotic physiology, we first need to identify a working model in today’s world. Once identified, this model can form the basis for the study, creation, expansion, and optimization of human-robotic hybrid physiology. In this paper, I present and defend the line of argument that currently this kind of model (proposed to be named “IshBot”) can best be studied in ventricular assist devices – VAD. PMID:28913480

A feedback model of visual attention.

PubMed

Spratling, M W; Johnson, M H

2004-03-01

Feedback connections are a prominent feature of cortical anatomy and are likely to have a significant functional role in neural information processing. We present a neural network model of cortical feedback that successfully simulates neurophysiological data associated with attention. In this domain, our model can be considered a more detailed, and biologically plausible, implementation of the biased competition model of attention. However, our model is more general as it can also explain a variety of other top-down processes in vision, such as figure/ground segmentation and contextual cueing. This model thus suggests that a common mechanism, involving cortical feedback pathways, is responsible for a range of phenomena and provides a unified account of currently disparate areas of research.

Determination of Uncertainties for the New SSME Model

NASA Technical Reports Server (NTRS)

Coleman, Hugh W.; Hawk, Clark W.

1996-01-01

This report discusses the uncertainty analysis performed in support of a new test analysis and performance prediction model for the Space Shuttle Main Engine. The new model utilizes uncertainty estimates for experimental data and for the analytical model to obtain the most plausible operating condition for the engine system. This report discusses the development of the data sets and uncertainty estimates to be used in the development of the new model. It also presents the application of uncertainty analysis to analytical models and the uncertainty analysis for the conservation of mass and energy balance relations is presented. A new methodology for the assessment of the uncertainty associated with linear regressions is presented.

Patch Size, Functional Isolation, Visibility and Matrix Permeability Influences Neotropical Primate Occurrence within Highly Fragmented Landscapes

PubMed Central

da Silva, Lucas Goulart; Ribeiro, Milton Cezar; Hasui, Érica; da Costa, Carla Aparecida; da Cunha, Rogério Grassetto Teixeira

2015-01-01

Forest fragmentation and habitat loss are among the major current extinction causes. Remaining fragments are mostly small, isolated and showing poor quality. Being primarily arboreal, Neotropical primates are generally sensitive to fragmentation effects. Furthermore, primates are involved in complex ecological process. Thus, landscape changes that negatively interfere with primate population dynamic affect the structure, composition, and ultimately the viability of the whole community. We evaluated if fragment size, isolation and visibility and matrix permeability are important for explaining the occurrence of three Neotropical primate species. Employing playback, we verified the presence of Callicebus nigrifrons, Callithrix aurita and Sapajus nigritus at 45 forest fragments around the municipality of Alfenas, Brazil. We classified the landscape and evaluated the metrics through predictive models of occurrence. We selected the best models through Akaike Selection Criterion. Aiming at validating our results, we applied the plausible models to another region (20 fragments at the neighboring municipality of Poço Fundo, Brazil). Twelve models were plausible, and three were validated, two for Sapajus nigritus (Area and Area+Visibility) and one for Callicebus nigrifrons (Area+Matrix). Our results reinforce the contribution of fragment size to maintain biodiversity within highly degraded habitats. At the same time, they stress the importance of including novel, biologically relevant metrics in landscape studies, such as visibility and matrix permeability, which can provide invaluable help for similar studies in the future and on conservation practices in the long run. PMID:25658108

Model-based recovery of histological parameters from multispectral images of the colon

NASA Astrophysics Data System (ADS)

Hidovic-Rowe, Dzena; Claridge, Ela

2005-04-01

Colon cancer alters the macroarchitecture of the colon tissue. Common changes include angiogenesis and the distortion of the tissue collagen matrix. Such changes affect the colon colouration. This paper presents the principles of a novel optical imaging method capable of extracting parameters depicting histological quantities of the colon. The method is based on a computational, physics-based model of light interaction with tissue. The colon structure is represented by three layers: mucosa, submucosa and muscle layer. Optical properties of the layers are defined by molar concentration and absorption coefficients of haemoglobins; the size and density of collagen fibres; the thickness of the layer and the refractive indexes of collagen and the medium. Using the entire histologically plausible ranges for these parameters, a cross-reference is created computationally between the histological quantities and the associated spectra. The output of the model was compared to experimental data acquired in vivo from 57 histologically confirmed normal and abnormal tissue samples and histological parameters were extracted. The model produced spectra which match well the measured data, with the corresponding spectral parameters being well within histologically plausible ranges. Parameters extracted for the abnormal spectra showed the increase in blood volume fraction and changes in collagen pattern characteristic of the colon cancer. The spectra extracted from multi-spectral images of ex-vivo colon including adenocarcinoma show the characteristic features associated with normal and abnormal colon tissue. These findings suggest that it should be possible to compute histological quantities for the colon from the multi-spectral images.

Modular neuron-based body estimation: maintaining consistency over different limbs, modalities, and frames of reference

PubMed Central

Ehrenfeld, Stephan; Herbort, Oliver; Butz, Martin V.

2013-01-01

This paper addresses the question of how the brain maintains a probabilistic body state estimate over time from a modeling perspective. The neural Modular Modality Frame (nMMF) model simulates such a body state estimation process by continuously integrating redundant, multimodal body state information sources. The body state estimate itself is distributed over separate, but bidirectionally interacting modules. nMMF compares the incoming sensory and present body state information across the interacting modules and fuses the information sources accordingly. At the same time, nMMF enforces body state estimation consistency across the modules. nMMF is able to detect conflicting sensory information and to consequently decrease the influence of implausible sensor sources on the fly. In contrast to the previously published Modular Modality Frame (MMF) model, nMMF offers a biologically plausible neural implementation based on distributed, probabilistic population codes. Besides its neural plausibility, the neural encoding has the advantage of enabling (a) additional probabilistic information flow across the separate body state estimation modules and (b) the representation of arbitrary probability distributions of a body state. The results show that the neural estimates can detect and decrease the impact of false sensory information, can propagate conflicting information across modules, and can improve overall estimation accuracy due to additional module interactions. Even bodily illusions, such as the rubber hand illusion, can be simulated with nMMF. We conclude with an outlook on the potential of modeling human data and of invoking goal-directed behavioral control. PMID:24191151

Predicting Age-appropriate Pharmacokinetics of Six Volatile Organic Compounds in the Rat Utilizing Physiologically-based Pharmacokinetic Modeling (T)

EPA Science Inventory

The capability of physiologically-based pharmacokinetic (PBPK) models to incorporate ageappropriate physiological and chemical-specific parameters was utilized in this study to predict changes in internal dosimetry for six volatile organic compounds (VOCs) across different ages o...

Predicting musically induced emotions from physiological inputs: linear and neural network models.

PubMed

Russo, Frank A; Vempala, Naresh N; Sandstrom, Gillian M

2013-01-01

Listening to music often leads to physiological responses. Do these physiological responses contain sufficient information to infer emotion induced in the listener? The current study explores this question by attempting to predict judgments of "felt" emotion from physiological responses alone using linear and neural network models. We measured five channels of peripheral physiology from 20 participants-heart rate (HR), respiration, galvanic skin response, and activity in corrugator supercilii and zygomaticus major facial muscles. Using valence and arousal (VA) dimensions, participants rated their felt emotion after listening to each of 12 classical music excerpts. After extracting features from the five channels, we examined their correlation with VA ratings, and then performed multiple linear regression to see if a linear relationship between the physiological responses could account for the ratings. Although linear models predicted a significant amount of variance in arousal ratings, they were unable to do so with valence ratings. We then used a neural network to provide a non-linear account of the ratings. The network was trained on the mean ratings of eight of the 12 excerpts and tested on the remainder. Performance of the neural network confirms that physiological responses alone can be used to predict musically induced emotion. The non-linear model derived from the neural network was more accurate than linear models derived from multiple linear regression, particularly along the valence dimension. A secondary analysis allowed us to quantify the relative contributions of inputs to the non-linear model. The study represents a novel approach to understanding the complex relationship between physiological responses and musically induced emotion.

Assessing uncertainty in SRTM elevations for global flood modelling

NASA Astrophysics Data System (ADS)

Hawker, L. P.; Rougier, J.; Neal, J. C.; Bates, P. D.

2017-12-01

The SRTM DEM is widely used as the topography input to flood models in data-sparse locations. Understanding spatial error in the SRTM product is crucial in constraining uncertainty about elevations and assessing the impact of these upon flood prediction. Assessment of SRTM error was carried out by Rodriguez et al (2006), but this did not explicitly quantify the spatial structure of vertical errors in the DEM, and nor did it distinguish between errors over different types of landscape. As a result, there is a lack of information about spatial structure of vertical errors of the SRTM in the landscape that matters most to flood models - the floodplain. Therefore, this study attempts this task by comparing SRTM, an error corrected SRTM product (The MERIT DEM of Yamazaki et al., 2017) and near truth LIDAR elevations for 3 deltaic floodplains (Mississippi, Po, Wax Lake) and a large lowland region (the Fens, UK). Using the error covariance function, calculated by comparing SRTM elevations to the near truth LIDAR, perturbations of the 90m SRTM DEM were generated, producing a catalogue of plausible DEMs. This allows modellers to simulate a suite of plausible DEMs at any aggregated block size above native SRTM resolution. Finally, the generated DEM's were input into a hydrodynamic model of the Mekong Delta, built using the LISFLOOD-FP hydrodynamic model, to assess how DEM error affects the hydrodynamics and inundation extent across the domain. The end product of this is an inundation map with the probability of each pixel being flooded based on the catalogue of DEMs. In a world of increasing computer power, but a lack of detailed datasets, this powerful approach can be used throughout natural hazard modelling to understand how errors in the SRTM DEM can impact the hazard assessment.

Predictive Inference Using Latent Variables with Covariates*

PubMed Central

Schofield, Lynne Steuerle; Junker, Brian; Taylor, Lowell J.; Black, Dan A.

2014-01-01

Plausible Values (PVs) are a standard multiple imputation tool for analysis of large education survey data that measures latent proficiency variables. When latent proficiency is the dependent variable, we reconsider the standard institutionally-generated PV methodology and find it applies with greater generality than shown previously. When latent proficiency is an independent variable, we show that the standard institutional PV methodology produces biased inference because the institutional conditioning model places restrictions on the form of the secondary analysts’ model. We offer an alternative approach that avoids these biases based on the mixed effects structural equations (MESE) model of Schofield (2008). PMID:25231627

Aggregate age-at-marriage patterns from individual mate-search heuristics.

PubMed

Todd, Peter M; Billari, Francesco C; Simão, Jorge

2005-08-01

The distribution of age at first marriage shows well-known strong regularities across many countries and recent historical periods. We accounted for these patterns by developing agent-based models that simulate the aggregate behavior of individuals who are searching for marriage partners. Past models assumed fully rational agents with complete knowledge of the marriage market; our simulated agents used psychologically plausible simple heuristic mate search rules that adjust aspiration levels on the basis of a sequence of encounters with potential partners. Substantial individual variation must be included in the models to account for the demographically observed age-at-marriage patterns.

An integrated physiology model to study regional lung damage effects and the physiologic response

PubMed Central

2014-01-01

Background This work expands upon a previously developed exercise dynamic physiology model (DPM) with the addition of an anatomic pulmonary system in order to quantify the impact of lung damage on oxygen transport and physical performance decrement. Methods A pulmonary model is derived with an anatomic structure based on morphometric measurements, accounting for heterogeneous ventilation and perfusion observed experimentally. The model is incorporated into an existing exercise physiology model; the combined system is validated using human exercise data. Pulmonary damage from blast, blunt trauma, and chemical injury is quantified in the model based on lung fluid infiltration (edema) which reduces oxygen delivery to the blood. The pulmonary damage component is derived and calibrated based on published animal experiments; scaling laws are used to predict the human response to lung injury in terms of physical performance decrement. Results The augmented dynamic physiology model (DPM) accurately predicted the human response to hypoxia, altitude, and exercise observed experimentally. The pulmonary damage parameters (shunt and diffusing capacity reduction) were fit to experimental animal data obtained in blast, blunt trauma, and chemical damage studies which link lung damage to lung weight change; the model is able to predict the reduced oxygen delivery in damage conditions. The model accurately estimates physical performance reduction with pulmonary damage. Conclusions We have developed a physiologically-based mathematical model to predict performance decrement endpoints in the presence of thoracic damage; simulations can be extended to estimate human performance and escape in extreme situations. PMID:25044032

Droplet size and velocity distributions for spray modelling

NASA Astrophysics Data System (ADS)

Jones, D. P.; Watkins, A. P.

2012-01-01

Methods for constructing droplet size distributions and droplet velocity profiles are examined as a basis for the Eulerian spray model proposed in Beck and Watkins (2002,2003) [5,6]. Within the spray model, both distributions must be calculated at every control volume at every time-step where the spray is present and valid distributions must be guaranteed. Results show that the Maximum Entropy formalism combined with the Gamma distribution satisfy these conditions for the droplet size distributions. Approximating the droplet velocity profile is shown to be considerably more difficult due to the fact that it does not have compact support. An exponential model with a constrained exponent offers plausible profiles.

Impact of Missing Physiologic Data on Performance of the Simplified Acute Physiology Score 3 Risk-Prediction Model.

PubMed

Engerström, Lars; Nolin, Thomas; Mårdh, Caroline; Sjöberg, Folke; Karlström, Göran; Fredrikson, Mats; Walther, Sten M

2017-12-01

The Simplified Acute Physiology 3 outcome prediction model has a narrow time window for recording physiologic measurements. Our objective was to examine the prevalence and impact of missing physiologic data on the Simplified Acute Physiology 3 model's performance. Retrospective analysis of prospectively collected data. Sixty-three ICUs in the Swedish Intensive Care Registry. Patients admitted during 2011-2014 (n = 107,310). None. Model performance was analyzed using the area under the receiver operating curve, scaled Brier's score, and standardized mortality rate. We used a recalibrated Simplified Acute Physiology 3 model and examined model performance in the original dataset and in a dataset of complete records where missing data were generated (simulated dataset). One or more data were missing in 40.9% of the admissions, more common in survivors and low-risk admissions than in nonsurvivors and high-risk admissions. Discrimination did not decrease with one to two missing variables, but accuracy was highest with no missing data. Calibration was best in the original dataset with a mix of full records and records with some missing values (area under the receiver operating curve was 0.85, scaled Brier 27%, and standardized mortality rate 0.99). With zero, one, and two data missing, the scaled Brier was 31%, 26%, and 21%; area under the receiver operating curve was 0.84, 0.87, and 0.89; and standardized mortality rate was 0.92, 1.05 and 1.10, respectively. Datasets where the missing data were simulated for oxygenation or oxygenation and hydrogen ion concentration together performed worse than datasets with these data originally missing. There is a coupling between missing physiologic data, admission type, low risk, and survival. Increased loss of physiologic data reduced model performance and will deflate mortality risk, resulting in falsely high standardized mortality rates.

Is knowing believing? The role of event plausibility and background knowledge in planting false beliefs about the personal past.

PubMed

Pezdek, Kathy; Blandon-Gitlin, Iris; Lam, Shirley; Hart, Rhiannon Ellis; Schooler, Jonathan W

2006-12-01

False memories are more likely to be planted for plausible than for implausible events, but does just knowing about an implausible event make individuals more likely to think that the event happened to them? Two experiments assessed the independent contributions o f plausibility a nd background knowledge to planting false beliefs. In Experiment 1, subjects rated 20 childhood events as to the likelihood of each event having happened to them. The list included the implausible target event "received an enema," a critical target event of Pezdek, Finger, and Hodge (1997). Two weeks later, subjects were presented with (1) information regarding the high prevalence rate of enemas; (2) background information on how to administer an enema; (3) neither type of information; or (4) both. Immediately or 2 weeks later, they rated the 20 childhood events again. Only plausibility significantly increased occurrence ratings. In Experiment 2, the target event was changed from "barium enema administered in a hospital" to "home enema for constipation"; significant effects of both plausibility and background knowledge resulted. The results suggest that providing background knowledge can increase beliefs about personal events, but that its impact is limited by the extent of the individual's familiarity with the context of the suggested target event.

Contrast normalization contributes to a biologically-plausible model of receptive-field development in primary visual cortex (V1)

PubMed Central

Willmore, Ben D.B.; Bulstrode, Harry; Tolhurst, David J.

2012-01-01

Neuronal populations in the primary visual cortex (V1) of mammals exhibit contrast normalization. Neurons that respond strongly to simple visual stimuli – such as sinusoidal gratings – respond less well to the same stimuli when they are presented as part of a more complex stimulus which also excites other, neighboring neurons. This phenomenon is generally attributed to generalized patterns of inhibitory connections between nearby V1 neurons. The Bienenstock, Cooper and Munro (BCM) rule is a neural network learning rule that, when trained on natural images, produces model neurons which, individually, have many tuning properties in common with real V1 neurons. However, when viewed as a population, a BCM network is very different from V1 – each member of the BCM population tends to respond to the same dominant features of visual input, producing an incomplete, highly redundant code for visual information. Here, we demonstrate that, by adding contrast normalization into the BCM rule, we arrive at a neurally-plausible Hebbian learning rule that can learn an efficient sparse, overcomplete representation that is a better model for stimulus selectivity in V1. This suggests that one role of contrast normalization in V1 is to guide the neonatal development of receptive fields, so that neurons respond to different features of visual input. PMID:22230381

Folk-Psychological Interpretation of Human vs. Humanoid Robot Behavior: Exploring the Intentional Stance toward Robots

PubMed Central

Thellman, Sam; Silvervarg, Annika; Ziemke, Tom

2017-01-01

People rely on shared folk-psychological theories when judging behavior. These theories guide people’s social interactions and therefore need to be taken into consideration in the design of robots and other autonomous systems expected to interact socially with people. It is, however, not yet clear to what degree the mechanisms that underlie people’s judgments of robot behavior overlap or differ from the case of human or animal behavior. To explore this issue, participants (N = 90) were exposed to images and verbal descriptions of eight different behaviors exhibited either by a person or a humanoid robot. Participants were asked to rate the intentionality, controllability and desirability of the behaviors, and to judge the plausibility of seven different types of explanations derived from a recently proposed psychological model of lay causal explanation of human behavior. Results indicate: substantially similar judgments of human and robot behavior, both in terms of (1a) ascriptions of intentionality/controllability/desirability and in terms of (1b) plausibility judgments of behavior explanations; (2a) high level of agreement in judgments of robot behavior – (2b) slightly lower but still largely similar to agreement over human behaviors; (3) systematic differences in judgments concerning the plausibility of goals and dispositions as explanations of human vs. humanoid behavior. Taken together, these results suggest that people’s intentional stance toward the robot was in this case very similar to their stance toward the human. PMID:29184519

Physiologically relevant organs on chips

PubMed Central

Yum, Kyungsuk; Hong, Soon Gweon; Lee, Luke P.

2015-01-01

Recent advances in integrating microengineering and tissue engineering have generated promising microengineered physiological models for experimental medicine and pharmaceutical research. Here we review the recent development of microengineered physiological systems, or organs on chips, that reconstitute the physiologically critical features of specific human tissues and organs and their interactions. This technology uses microengineering approaches to construct organ-specific microenvironments, reconstituting tissue structures, tissue–tissue interactions and interfaces, and dynamic mechanical and biochemical stimuli found in specific organs, to direct cells to assemble into functional tissues. We first discuss microengineering approaches to reproduce the key elements of physiologically important, dynamic mechanical microenvironments, biochemical microenvironments, and microarchitectures of specific tissues and organs in microfluidic cell culture systems. This is followed by examples of microengineered individual organ models that incorporate the key elements of physiological microenvironments into single microfluidic cell culture systems to reproduce organ-level functions. Finally, microengineered multiple organ systems that simulate multiple organ interactions to better represent human physiology, including human responses to drugs, is covered in this review. This emerging organs-on-chips technology has the potential to become an alternative to 2D and 3D cell culture and animal models for experimental medicine, human disease modeling, drug development, and toxicology. PMID:24357624

Natural language acquisition in large scale neural semantic networks

NASA Astrophysics Data System (ADS)

Ealey, Douglas

This thesis puts forward the view that a purely signal- based approach to natural language processing is both plausible and desirable. By questioning the veracity of symbolic representations of meaning, it argues for a unified, non-symbolic model of knowledge representation that is both biologically plausible and, potentially, highly efficient. Processes to generate a grounded, neural form of this model-dubbed the semantic filter-are discussed. The combined effects of local neural organisation, coincident with perceptual maturation, are used to hypothesise its nature. This theoretical model is then validated in light of a number of fundamental neurological constraints and milestones. The mechanisms of semantic and episodic development that the model predicts are then used to explain linguistic properties, such as propositions and verbs, syntax and scripting. To mimic the growth of locally densely connected structures upon an unbounded neural substrate, a system is developed that can grow arbitrarily large, data- dependant structures composed of individual self- organising neural networks. The maturational nature of the data used results in a structure in which the perception of concepts is refined by the networks, but demarcated by subsequent structure. As a consequence, the overall structure shows significant memory and computational benefits, as predicted by the cognitive and neural models. Furthermore, the localised nature of the neural architecture also avoids the increasing error sensitivity and redundancy of traditional systems as the training domain grows. The semantic and episodic filters have been demonstrated to perform as well, or better, than more specialist networks, whilst using significantly larger vocabularies, more complex sentence forms and more natural corpora.

A Cost-Effectiveness Analysis of Nasal Surgery to Increase Continuous Positive Airway Pressure Adherence in Sleep Apnea Patients With Nasal Obstruction

PubMed Central

Kempfle, Judith S.; BuSaba, Nicholas Y.; Dobrowski, John M.; Westover, Michael B.; Bianchi, Matt T.

2017-01-01

Objectives/Hypothesis Nasal surgery has been implicated to improve continuous positive airway pressure (CPAP) compliance in patients with obstructive sleep apnea (OSA) and nasal obstruction. However, the cost-effectiveness of nasal surgery to improve CPAP compliance is not known. We modeled the cost-effectiveness of two types of nasal surgery versus no surgery in patients with OSA and nasal obstruction undergoing CPAP therapy. Study Design Cost-effectiveness decision tree model. Methods We built a decision tree model to identify conditions under which nasal surgery would be cost-effective to improve CPAP adherence over the standard of care. We compared turbinate reduction and septoplasty to nonsurgical treatment over varied time horizons from a third-party payer perspective. We included variables for cost of untreated OSA, surgical cost and complications, improved compliance postoperatively, and quality of life. Results Our study identified nasal surgery as a cost-effective strategy to improve compliance of OSA patients using CPAP across a range of plausible model assumptions regarding the cost of untreated OSA, the probability of adherence improvement, and a chronic time horizon. The relatively lower surgical cost of turbinate reduction made it more cost-effective at earlier time horizons, whereas septoplasty became cost-effective after a longer timespan. Conclusions Across a range of plausible values in a clinically relevant decision model, nasal surgery is a cost-effective strategy to improve CPAP compliance in OSA patients with nasal obstruction. Our results suggest that OSA patients with nasal obstruction who struggle with CPAP therapy compliance should undergo evaluation for nasal surgery. PMID:27653626

Categorization and decision-making in a neurobiologically plausible spiking network using a STDP-like learning rule.

PubMed

Beyeler, Michael; Dutt, Nikil D; Krichmar, Jeffrey L

2013-12-01

Understanding how the human brain is able to efficiently perceive and understand a visual scene is still a field of ongoing research. Although many studies have focused on the design and optimization of neural networks to solve visual recognition tasks, most of them either lack neurobiologically plausible learning rules or decision-making processes. Here we present a large-scale model of a hierarchical spiking neural network (SNN) that integrates a low-level memory encoding mechanism with a higher-level decision process to perform a visual classification task in real-time. The model consists of Izhikevich neurons and conductance-based synapses for realistic approximation of neuronal dynamics, a spike-timing-dependent plasticity (STDP) synaptic learning rule with additional synaptic dynamics for memory encoding, and an accumulator model for memory retrieval and categorization. The full network, which comprised 71,026 neurons and approximately 133 million synapses, ran in real-time on a single off-the-shelf graphics processing unit (GPU). The network was constructed on a publicly available SNN simulator that supports general-purpose neuromorphic computer chips. The network achieved 92% correct classifications on MNIST in 100 rounds of random sub-sampling, which is comparable to other SNN approaches and provides a conservative and reliable performance metric. Additionally, the model correctly predicted reaction times from psychophysical experiments. Because of the scalability of the approach and its neurobiological fidelity, the current model can be extended to an efficient neuromorphic implementation that supports more generalized object recognition and decision-making architectures found in the brain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Discrete Regularization for Calibration of Geologic Facies Against Dynamic Flow Data

NASA Astrophysics Data System (ADS)

Khaninezhad, Mohammad-Reza; Golmohammadi, Azarang; Jafarpour, Behnam

2018-04-01

Subsurface flow model calibration involves many more unknowns than measurements, leading to ill-posed problems with nonunique solutions. To alleviate nonuniqueness, the problem is regularized by constraining the solution space using prior knowledge. In certain sedimentary environments, such as fluvial systems, the contrast in hydraulic properties of different facies types tends to dominate the flow and transport behavior, making the effect of within facies heterogeneity less significant. Hence, flow model calibration in those formations reduces to delineating the spatial structure and connectivity of different lithofacies types and their boundaries. A major difficulty in calibrating such models is honoring the discrete, or piecewise constant, nature of facies distribution. The problem becomes more challenging when complex spatial connectivity patterns with higher-order statistics are involved. This paper introduces a novel formulation for calibration of complex geologic facies by imposing appropriate constraints to recover plausible solutions that honor the spatial connectivity and discreteness of facies models. To incorporate prior connectivity patterns, plausible geologic features are learned from available training models. This is achieved by learning spatial patterns from training data, e.g., k-SVD sparse learning or the traditional Principal Component Analysis. Discrete regularization is introduced as a penalty functions to impose solution discreteness while minimizing the mismatch between observed and predicted data. An efficient gradient-based alternating directions algorithm is combined with variable splitting to minimize the resulting regularized nonlinear least squares objective function. Numerical results show that imposing learned facies connectivity and discreteness as regularization functions leads to geologically consistent solutions that improve facies calibration quality.

Modelling the Preferences of Students for Alternative Assignment Designs Using the Discrete Choice Experiment Methodology

ERIC Educational Resources Information Center

Kennelly, Brendan; Flannery, Darragh; Considine, John; Doherty, Edel; Hynes, Stephen

2014-01-01

This paper outlines how a discrete choice experiment (DCE) can be used to learn more about how students are willing to trade off various features of assignments such as the nature and timing of feedback and the method used to submit assignments. A DCE identifies plausible levels of the key attributes of a good or service and then presents the…

White dwarf models for type 1 supernovae and quiet supernovae, and presupernova evolution

NASA Technical Reports Server (NTRS)

Nomoto, K.

1980-01-01

Supernova mechanisms in accreting white dwarfs are considered with emphasis on deflagration as a plausible mechanism for producing Type I supernovae and electron captures to form quiet supernovae leaving neutron stars. These outcomes depend on accretion rate of helium, initial mass and composition of the white dwarf. The various types of hydrogen shell burning in the presupernova stage are also discussed.

The Instability of Instability

DTIC Science & Technology

1991-05-01

thermodynamic principles, changes cannot be effected without some cost. The decision - making associated with Model I can be viewed as rational behavior. Consider...number Democratic simple majority voting is perhaps the most widely used method of group decision making i;i our time. Current theory, based on...incorporate any of several plausible characteristics of decision - making , then the instability theorems do not hold and in fact the probability of

The Gastrointestinal Microbiome and Musculoskeletal Diseases: A Beneficial Role for Probiotics and Prebiotics

PubMed Central

Vitetta, Luis; Coulson, Samantha; Linnane, Anthony W.; Butt, Henry

2013-01-01

Natural medicines are an attractive option for patients diagnosed with common and debilitating musculoskeletal diseases such as Osteoarthritis (OA) or Rheumatoid Arthritis (RA). The high rate of self-medication with natural products is due to (1) lack of an available cure and (2) serious adverse events associated with chronic use of pharmaceutical medications in particular non-steroidal anti-inflammatory drugs (NSAIDs) and high dose paracetamol. Pharmaceuticals to treat pain may disrupt gastrointestinal (GIT) barrier integrity inducing GIT inflammation and a state of and hyper-permeability. Probiotics and prebiotics may comprise plausible therapeutic options that can restore GIT barrier functionality and down regulate pro-inflammatory mediators by modulating the activity of, for example, Clostridia species known to induce pro-inflammatory mediators. The effect may comprise the rescue of gut barrier physiological function. A postulated requirement has been the abrogation of free radical formation by numerous natural antioxidant molecules in order to improve musculoskeletal health outcomes, this notion in our view, is in error. The production of reactive oxygen species (ROS) in different anatomical environments including the GIT by the epithelial lining and the commensal microbe cohort is a regulated process, leading to the formation of hydrogen peroxide which is now well recognized as an essential second messenger required for normal cellular homeostasis and physiological function. The GIT commensal profile that tolerates the host does so by regulating pro-inflammatory and anti-inflammatory GIT mucosal actions through the activity of ROS signaling thereby controlling the activity of pathogenic bacterial species. PMID:25437335

Developing a Nationwide K-12 Outreach Model: Physiology Understanding (PhUn) Week 10 Years Later

ERIC Educational Resources Information Center

Stieben, Margaret; Halpin, Patricia A.; Matyas, Marsha Lakes

2017-01-01

Since 2005, nearly 600 Physiology Understanding Week (PhUn Week) events have taken place across the U.S., involving American Physiological Society (APS) members in K-12 outreach. The program seeks to build student understanding of physiology and physiology careers, assist teachers in recognizing physiology in their standards-based curriculum, and…

A Physiologically-based Model for Methylmercury Uptake and Accumulation in Female American Kestrels

EPA Science Inventory

A physiologically-based model was developed to describe the uptake, distribution, and elimination of methylmercury in female American Kestrels (Falco sparverius). The model was adapted from established models for methylmercury in rodents. Features unique to the model include meth...

Modeling Physiological Systems in the Human Body as Networks of Quasi-1D Fluid Flows

NASA Astrophysics Data System (ADS)

Staples, Anne

2008-11-01

Extensive research has been done on modeling human physiology. Most of this work has been aimed at developing detailed, three-dimensional models of specific components of physiological systems, such as a cell, a vein, a molecule, or a heart valve. While efforts such as these are invaluable to our understanding of human biology, if we were to construct a global model of human physiology with this level of detail, computing even a nanosecond in this computational being's life would certainly be prohibitively expensive. With this in mind, we derive the Pulsed Flow Equations, a set of coupled one-dimensional partial differential equations, specifically designed to capture two-dimensional viscous, transport, and other effects, and aimed at providing accurate and fast-to-compute global models for physiological systems represented as networks of quasi one-dimensional fluid flows. Our goal is to be able to perform faster-than-real time simulations of global processes in the human body on desktop computers.

Hooke's law: applications of a recurring principle.

PubMed

Giuliodori, Mauricio J; Lujan, Heidi L; Briggs, Whitney S; Palani, Gurunanthan; DiCarlo, Stephen E

2009-12-01

Students generally approach topics in physiology as a series of unrelated phenomena that share few underlying principles. However, if students recognized that the same underlying principles can be used to explain many physiological phenomena, they may gain a more unified understanding of physiological systems. To address this concern, we developed a simple, inexpensive, and easy to build model to demonstrate the underlying principles regarding Starling's Law of the Heart as well as lung and arterial elastic recoil. A model was chosen because models significantly enhance student understanding. Working with models also encourages research-oriented learning and helps our students understand complex ideas. Students are drawn into discussion by the power of learning that is associated with manipulating and thinking about objects. Recognizing that the same underlying principles can be used to explain many physiological phenomena may help students gain a more complete understanding of physiological systems.

Investigation of an alternative generic model for predicting pharmacokinetic changes during physiological stress.

PubMed

Peng, Henry T; Edginton, Andrea N; Cheung, Bob

2013-10-01

Physiologically based pharmacokinetic models were developed using MATLAB Simulink® and PK-Sim®. We compared the capability and usefulness of these two models by simulating pharmacokinetic changes of midazolam under exercise and heat stress to verify the usefulness of MATLAB Simulink® as a generic PBPK modeling software. Although both models show good agreement with experimental data obtained under resting condition, their predictions of pharmacokinetics changes are less accurate in the stressful conditions. However, MATLAB Simulink® may be more flexible to include physiologically based processes such as oral absorption and simulate various stress parameters such as stress intensity, duration and timing of drug administration to improve model performance. Further work will be conducted to modify algorithms in our generic model developed using MATLAB Simulink® and to investigate pharmacokinetics under other physiological stress such as trauma. © The Author(s) 2013.

Self-focused and other-focused resiliency: Plausible mechanisms linking early family adversity to health problems in college women.

PubMed

Coleman, Sulamunn R M; Zawadzki, Matthew J; Heron, Kristin E; Vartanian, Lenny R; Smyth, Joshua M

2016-01-01

This study examined whether self-focused and other-focused resiliency help explain how early family adversity relates to perceived stress, subjective health, and health behaviors in college women. Female students (N = 795) participated between October 2009 and May 2010. Participants completed self-report measures of early family adversity, self-focused (self-esteem, personal growth initiative) and other-focused (perceived social support, gratitude) resiliency, stress, subjective health, and health behaviors. Using structural equation modeling, self-focused resiliency associated with less stress, better subjective health, more sleep, less smoking, and less weekend alcohol consumption. Other-focused resiliency associated with more exercise, greater stress, and more weekend alcohol consumption. Early family adversity was indirectly related to all health outcomes, except smoking, via self-focused and other-focused resiliency. Self-focused and other-focused resiliency represent plausible mechanisms through which early family adversity relates to stress and health in college women. This highlights areas for future research in disease prevention and management.

Proceedings of the 2006 Toxicology and Risk Assessment Conference: Applying Mode of Action in Risk Assessment

DTIC Science & Technology

2006-07-01

physiologically-based pharmacokinetic modeling of interactions and multiple route exposure assessment; and integrating relative potency factors with response...defaults, while at the other end is the use of extensive chemical-specific data in physiologically based pharmacokinetic (PBPK) modeling or even...for internal dosimetry as well as an in depth prospective on the use and limitations of physiologically based pharmacokinetic (PBPK) models in

Creating Simulated Microgravity Patient Models

NASA Technical Reports Server (NTRS)

Hurst, Victor; Doerr, Harold K.; Bacal, Kira

2004-01-01

The Medical Operational Support Team (MOST) has been tasked by the Space and Life Sciences Directorate (SLSD) at the NASA Johnson Space Center (JSC) to integrate medical simulation into 1) medical training for ground and flight crews and into 2) evaluations of medical procedures and equipment for the International Space Station (ISS). To do this, the MOST requires patient models that represent the physiological changes observed during spaceflight. Despite the presence of physiological data collected during spaceflight, there is no defined set of parameters that illustrate or mimic a 'space normal' patient. Methods: The MOST culled space-relevant medical literature and data from clinical studies performed in microgravity environments. The areas of focus for data collection were in the fields of cardiovascular, respiratory and renal physiology. Results: The MOST developed evidence-based patient models that mimic the physiology believed to be induced by human exposure to a microgravity environment. These models have been integrated into space-relevant scenarios using a human patient simulator and ISS medical resources. Discussion: Despite the lack of a set of physiological parameters representing 'space normal,' the MOST developed space-relevant patient models that mimic microgravity-induced changes in terrestrial physiology. These models are used in clinical scenarios that will medically train flight surgeons, biomedical flight controllers (biomedical engineers; BME) and, eventually, astronaut-crew medical officers (CMO).

Europa's Crust and Ocean: Origin, Composition, and the Prospects for Life

USGS Publications Warehouse

Kargel, J.S.; Kaye, J.Z.; Head, J. W.; Marion, G.M.; Sassen, R.; Crowley, J.K.; Ballesteros, O.P.; Grant, S.A.; Hogenboom, D.L.

2000-01-01

We have considered a wide array of scenarios for Europa's chemical evolution in an attempt to explain the presence of ice and hydrated materials on its surface and to understand the physical and chemical nature of any ocean that may lie below. We postulate that, following formation of the jovian system, the europan evolutionary sequence has as its major links: (a) initial carbonaceous chondrite rock, (b) global primordial aqueous differentiation and formation of an impure primordial hydrous crust, (c) brine evolution and intracrustal differentiation, (d) degassing of Europa's mantle and gas venting, (e) hydrothermal processes, and (f) chemical surface alteration. Our models were developed in the context of constraints provided by Galileo imaging, near infrared reflectance spectroscopy, and gravity and magnetometer data. Low-temperature aqueous differentiation from a carbonaceous CI or CM chondrite precursor, without further chemical processing, would result in a crust/ocean enriched in magnesium sulfate and sodium sulfate, consistent with Galileo spectroscopy. Within the bounds of this simple model, a wide range of possible layered structures may result; the final state depends on the details of intracrustal differentiation. Devolatilization of the rocky mantle and hydrothermal brine reactions could have produced very different ocean/crust compositions, e.g., an ocean/crust of sodium carbonate or sulfuric acid, or a crust containing abundant clathrate hydrates. Realistic chemical-physical evolution scenarios differ greatly in detailed predictions, but they generally call for a highly impure and chemically layered crust. Some of these models could lead also to lateral chemical heterogeneities by diapiric upwellings and/or cryovolcanism. We describe some plausible geological consequences of the physical-chemical structures predicted from these scenarios. These predicted consequences and observed aspects of Europa's geology may serve as a basis for further analys is and discrimination among several alternative scenarios. Most chemical pathways could support viable ecosystems based on analogy with the metabolic and physiological versatility of terrestrial microorganisms. ?? 2000 Academic Press.

Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction

EPA Science Inventory

Developing physiologically-based pharmacokinetic (PBPK) models for chemicals can be resource-intensive, as neither chemical-specific parameters nor in vivo pharmacokinetic data are easily available for model construction. Previously developed, well-parameterized, and thoroughly-v...

Virtual Patients and Sensitivity Analysis of the Guyton Model of Blood Pressure Regulation: Towards Individualized Models of Whole-Body Physiology

PubMed Central

Moss, Robert; Grosse, Thibault; Marchant, Ivanny; Lassau, Nathalie; Gueyffier, François; Thomas, S. Randall

2012-01-01

Mathematical models that integrate multi-scale physiological data can offer insight into physiological and pathophysiological function, and may eventually assist in individualized predictive medicine. We present a methodology for performing systematic analyses of multi-parameter interactions in such complex, multi-scale models. Human physiology models are often based on or inspired by Arthur Guyton's whole-body circulatory regulation model. Despite the significance of this model, it has not been the subject of a systematic and comprehensive sensitivity study. Therefore, we use this model as a case study for our methodology. Our analysis of the Guyton model reveals how the multitude of model parameters combine to affect the model dynamics, and how interesting combinations of parameters may be identified. It also includes a “virtual population” from which “virtual individuals” can be chosen, on the basis of exhibiting conditions similar to those of a real-world patient. This lays the groundwork for using the Guyton model for in silico exploration of pathophysiological states and treatment strategies. The results presented here illustrate several potential uses for the entire dataset of sensitivity results and the “virtual individuals” that we have generated, which are included in the supplementary material. More generally, the presented methodology is applicable to modern, more complex multi-scale physiological models. PMID:22761561

The cost-effectiveness of dulaglutide versus liraglutide for the treatment of type 2 diabetes mellitus in Spain in patients with BMI ≥30 kg/m2.

PubMed

Dilla, Tatiana; Alexiou, Dimitra; Chatzitheofilou, Ismini; Ayyub, Ruba; Lowin, Julia; Norrbacka, Kirsi

2017-05-01

Dulaglutide 1.5 mg once weekly is a novel glucagon-like peptide 1 (GLP-1) receptor agonist, for the treatment of type two diabetes mellitus (T2DM). The objective was to estimate the cost-effectiveness of dulaglutide once weekly vs liraglutide 1.8 mg once daily for the treatment of T2DM in Spain in patients with a BMI ≥30 kg/m 2 . The IMS CORE Diabetes Model (CDM) was used to estimate costs and outcomes from the perspective of Spanish National Health System, capturing relevant direct medical costs over a lifetime time horizon. Comparative safety and efficacy data were derived from direct comparison of dulaglutide 1.5 mg vs liraglutide 1.8 mg from the AWARD-6 trial in patients with a body mass index (BMI) ≥30 kg/m 2 . All patients were assumed to remain on treatment for 2 years before switching treatment to basal insulin at a daily dose of 40 IU. One-way sensitivity analyses (OWSA) and probabilistic sensitivity analyses (PSA) were conducted to explore the sensitivity of the model to plausible variations in key parameters and uncertainty of model inputs. Under base case assumptions, dulaglutide 1.5 mg was less costly and more effective vs liraglutide 1.8 mg (total lifetime costs €108,489 vs €109,653; total QALYS 10.281 vs 10.259). OWSA demonstrated that dulaglutide 1.5 mg remained dominant given plausible variations in key input parameters. Results of the PSA were consistent with base case results. Primary limitations of the analysis are common to other cost-effectiveness analyses of chronic diseases like T2DM and include the extrapolation of short-term clinical data to the lifetime time horizon and uncertainty around optimum treatment durations. The model found that dulaglutide 1.5 mg was more effective and less costly than liraglutide 1.8 mg for the treatment of T2DM in Spain. Findings were robust to plausible variations in inputs. Based on these results, dulaglutide may result in cost savings to the Spanish National Health System.

Evaluating the risk of patient re-identification from adverse drug event reports

PubMed Central

2013-01-01

Background Our objective was to develop a model for measuring re-identification risk that more closely mimics the behaviour of an adversary by accounting for repeated attempts at matching and verification of matches, and apply it to evaluate the risk of re-identification for Canada’s post-marketing adverse drug event database (ADE).Re-identification is only demonstrably plausible for deaths in ADE. A matching experiment between ADE records and virtual obituaries constructed from Statistics Canada vital statistics was simulated. A new re-identification risk is considered, it assumes that after gathering all the potential matches for a patient record (all records in the obituaries that are potential matches for an ADE record), an adversary tries to verify these potential matches. Two adversary scenarios were considered: (a) a mildly motivated adversary who will stop after one verification attempt, and (b) a highly motivated adversary who will attempt to verify all the potential matches and is only limited by practical or financial considerations. Methods The mean percentage of records in ADE that had a high probability of being re-identified was computed. Results Under scenario (a), the risk of re-identification from disclosing the province, age at death, gender, and exact date of the report is quite high, but the removal of province brings down the risk significantly. By only generalizing the date of reporting to month and year and including all other variables, the risk is always low. All ADE records have a high risk of re-identification under scenario (b), but the plausibility of that scenario is limited because of the financial and practical deterrent even for highly motivated adversaries. Conclusions It is possible to disclose Canada’s adverse drug event database while ensuring that plausible re-identification risks are acceptably low. Our new re-identification risk model is suitable for such risk assessments. PMID:24094134

Changes in physiological attributes of ponderosa pine from seedling to mature tree

Treesearch

Nancy E. Grulke; William A. Retzlaff

2001-01-01

Plant physiological models are generally parameterized from many different sources of data, including chamber experiments and plantations, from seedlings to mature trees. We obtained a comprehensive data set for a natural stand of ponderosa pine (Pinus ponderosa Laws.) and used these data to parameterize the physiologically based model, TREGRO....

Generalized Information Theory Meets Human Cognition: Introducing a Unified Framework to Model Uncertainty and Information Search.

PubMed

Crupi, Vincenzo; Nelson, Jonathan D; Meder, Björn; Cevolani, Gustavo; Tentori, Katya

2018-06-17

Searching for information is critical in many situations. In medicine, for instance, careful choice of a diagnostic test can help narrow down the range of plausible diseases that the patient might have. In a probabilistic framework, test selection is often modeled by assuming that people's goal is to reduce uncertainty about possible states of the world. In cognitive science, psychology, and medical decision making, Shannon entropy is the most prominent and most widely used model to formalize probabilistic uncertainty and the reduction thereof. However, a variety of alternative entropy metrics (Hartley, Quadratic, Tsallis, Rényi, and more) are popular in the social and the natural sciences, computer science, and philosophy of science. Particular entropy measures have been predominant in particular research areas, and it is often an open issue whether these divergences emerge from different theoretical and practical goals or are merely due to historical accident. Cutting across disciplinary boundaries, we show that several entropy and entropy reduction measures arise as special cases in a unified formalism, the Sharma-Mittal framework. Using mathematical results, computer simulations, and analyses of published behavioral data, we discuss four key questions: How do various entropy models relate to each other? What insights can be obtained by considering diverse entropy models within a unified framework? What is the psychological plausibility of different entropy models? What new questions and insights for research on human information acquisition follow? Our work provides several new pathways for theoretical and empirical research, reconciling apparently conflicting approaches and empirical findings within a comprehensive and unified information-theoretic formalism. Copyright © 2018 Cognitive Science Society, Inc.

Exploring the dynamics of balance data — movement variability in terms of drift and diffusion

NASA Astrophysics Data System (ADS)

Gottschall, Julia; Peinke, Joachim; Lippens, Volker; Nagel, Volker

2009-02-01

We introduce a method to analyze postural control on a balance board by reconstructing the underlying dynamics in terms of a Langevin model. Drift and diffusion coefficients are directly estimated from the data and fitted by a suitable parametrization. The governing parameters are utilized to evaluate balance performance and the impact of supra-postural tasks on it. We show that the proposed method of analysis gives not only self-consistent results but also provides a plausible model for the reconstruction of balance dynamics.

Concepts in solid tumor evolution.

PubMed

Sidow, Arend; Spies, Noah

2015-04-01

Evolutionary mechanisms in cancer progression give tumors their individuality. Cancer evolution is different from organismal evolution, however, and we discuss where concepts from evolutionary genetics are useful or limited in facilitating an understanding of cancer. Based on these concepts we construct and apply the simplest plausible model of tumor growth and progression. Simulations using this simple model illustrate the importance of stochastic events early in tumorigenesis, highlight the dominance of exponential growth over linear growth and differentiation, and explain the clonal substructure of tumors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Encouraging moderation: clues from a simple model of ideological conflict.

PubMed

Marvel, Seth A; Hong, Hyunsuk; Papush, Anna; Strogatz, Steven H

2012-09-14

Some of the most pivotal moments in intellectual history occur when a new ideology sweeps through a society, supplanting an established system of beliefs in a rapid revolution of thought. Yet in many cases the new ideology is as extreme as the old. Why is it then that moderate positions so rarely prevail? Here, in the context of a simple model of opinion spreading, we test seven plausible strategies for deradicalizing a society and find that only one of them significantly expands the moderate subpopulation without risking its extinction in the process.

Encouraging Moderation: Clues from a Simple Model of Ideological Conflict

NASA Astrophysics Data System (ADS)

Marvel, Seth A.; Hong, Hyunsuk; Papush, Anna; Strogatz, Steven H.

2012-09-01

Some of the most pivotal moments in intellectual history occur when a new ideology sweeps through a society, supplanting an established system of beliefs in a rapid revolution of thought. Yet in many cases the new ideology is as extreme as the old. Why is it then that moderate positions so rarely prevail? Here, in the context of a simple model of opinion spreading, we test seven plausible strategies for deradicalizing a society and find that only one of them significantly expands the moderate subpopulation without risking its extinction in the process.

On the applicability of STDP-based learning mechanisms to spiking neuron network models

NASA Astrophysics Data System (ADS)

Sboev, A.; Vlasov, D.; Serenko, A.; Rybka, R.; Moloshnikov, I.

2016-11-01

The ways to creating practically effective method for spiking neuron networks learning, that would be appropriate for implementing in neuromorphic hardware and at the same time based on the biologically plausible plasticity rules, namely, on STDP, are discussed. The influence of the amount of correlation between input and output spike trains on the learnability by different STDP rules is evaluated. A usability of alternative combined learning schemes, involving artificial and spiking neuron models is demonstrated on the iris benchmark task and on the practical task of gender recognition.

(−) Arctigenin and (+) Pinoresinol Are Antagonists of the Human Thyroid Hormone Receptor β

PubMed Central

2015-01-01

Lignans are important biologically active dietary polyphenolic compounds. Consumption of foods that are rich in lignans is associated with positive health effects. Using modeling tools to probe the ligand-binding pockets of molecular receptors, we found that lignans have high docking affinity for the human thyroid hormone receptor β. Follow-up experimental results show that lignans (−) arctigenin and (+) pinoresinol are antagonists of the human thyroid hormone receptor β. The modeled complexes show key plausible interactions between the two ligands and important amino acid residues of the receptor. PMID:25383984

Are there interactive effects of physiological and radiative forcing produced by increased CO2 concentration on changes of land hydrological cycle?

NASA Astrophysics Data System (ADS)

Peng, Jing; Dan, Li; Dong, Wenjie

2014-01-01

Three coupled climate-carbon cycle models including CESM (Community Earth System Model), CanEsm (the Canadian Centre for Climate Modelling and Analysis Earth System Model) and BCC (Beijing Climate Center Climate System Model) were used to estimate whether changes in land hydrological cycle responded to the interactive effects of CO2-physiological forcing and CO2-radiative forcing. No signs could be indicated that the interactive effects of CO2-physiological forcing and CO2-radiative forcing on the hydrological variables (e.g. precipitation, evapotranspiration and runoff) were detected at global and regional scales. For each model, increases in precipitation, evapotranspiration and runoff (e.g. 0.37, 0.18 and 0.25 mm/year2) were simulated in response to CO2-radiative forcing (experiment M3). Decreases in precipitation and evapotranspiration (about - 0.02 and - 0.09 mm/year2) were captured if the CO2 physiological effect was only accounted for (experiment M2). In this experiment, a reverse sign in runoff (the increase of 0.08 mm/year2) in contrast to M3 is presented. All models simulated the same signs across Eastern Asia in response to the CO2 physiological forcing and radiative forcing: increases in precipitation and evapotranspiration only considering greenhouse effect; reductions in precipitation and evapotranspiration in response to CO2-physiological effect; and enhanced trends in runoff from all experiments. However, there was still a large uncertainty on the magnitude of the effect of transpiration on runoff (decreased transpiration accounting for 8% to 250% of the increased runoff) from the three models. Two models (CanEsm and BCC) attributed most of the increase in runoff to the decrease in transpiration if the CO2-physiological effect was only accounted for, whereas CESM exhibited that the decrease in transpiration could not totally explain the increase in runoff. The attribution of the CO2-physiological forcing to changes in stomatal conductance versus changes in vegetation structure (e.g. increased Leaf Area Index) is an issue to discuss, and among the three models, no agreement appeared.

Severity scores in trauma patients admitted to ICU. Physiological and anatomic models.

PubMed

Serviá, L; Badia, M; Montserrat, N; Trujillano, J

2018-02-02

The goals of this project were to compare both the anatomic and physiologic severity scores in trauma patients admitted to intensive care unit (ICU), and to elaborate mixed statistical models to improve the precision of the scores. A prospective study of cohorts. The combined medical/surgical ICU in a secondary university hospital. Seven hundred and eighty trauma patients admitted to ICU older than 16 years of age. Anatomic models (ISS and NISS) were compared and combined with physiological models (T-RTS, APACHE II [APII], and MPM II). The probability of death was calculated following the TRISS method. The discrimination was assessed using ROC curves (ABC [CI 95%]), and the calibration using the Hosmer-Lemeshoẃs H test. The mixed models were elaborated with the tree classification method type Chi Square Automatic Interaction Detection. A 14% global mortality was recorded. The physiological models presented the best discrimination values (APII of 0.87 [0.84-0.90]). All models were affected by bad calibration (P<.01). The best mixed model resulted from the combination of APII and ISS (0.88 [0.83-0.90]). This model was able to differentiate between a 7.5% mortality for elderly patients with pathological antecedents and a 25% mortality in patients presenting traumatic brain injury, from a pool of patients with APII values ranging from 10 to 17 and an ISS threshold of 22. The physiological models perform better than the anatomical models in traumatic patients admitted to the ICU. Patients with low scores in the physiological models require an anatomic analysis of the injuries to determine their severity. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

A Physiological Signal Transmission Model to be Used for Specific Diagnosis of Cochlear Impairments

NASA Astrophysics Data System (ADS)

Saremi, Amin; Stenfelt, Stefan

2011-11-01

Many of the sophisticated characteristics of human auditory system are attributed to cochlea. Also, most of patients with a hearing loss suffer from impairments that originate from cochlea (sensorineural). Despite this, today's clinical diagnosis methods do not probe the specific origins of such cochlear lesions. The aim of this research is to introduce a physiological signal transmission model to be clinically used as a tool for diagnosis of cochlear losses. This model enables simulation of different bio-mechano-electrical processes which occur in the auditory organ of Corti inside the cochlea. What makes this model different from many available computational models is its loyalty to physiology since the ultimate goal is to model each single physiological phenomenon. This includes passive BM vibration, outer hair cells' performances such as nonlinear mechanoelectrical transduction (MET), active amplifications by somatic motor, as well as vibration to neural conversion at the inner hair cells.

Heuristic Elements of Plausible Reasoning.

ERIC Educational Resources Information Center

Dudczak, Craig A.

At least some of the reasoning processes involved in argumentation rely on inferences which do not fit within the traditional categories of inductive or deductive reasoning. The reasoning processes involved in plausibility judgments have neither the formal certainty of deduction nor the imputed statistical probability of induction. When utilizing…

Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction - poster

EPA Science Inventory

Building new physiologically based pharmacokinetic (PBPK) models requires a lot data, such as the chemical-specific parameters and in vivo pharmacokinetic data. Previously-developed, well-parameterized, and thoroughly-vetted models can be great resource for supporting the constr...