Computational and Mathematical Modelling of the EGF Receptor System

This chapter gives an overview of computational and mathematical modelling of the EGF receptor system. It begins with a survey of motivations for producing such models, then describes the main approaches that are taken to carrying out such modelling, viz. differential equations and individual-based modelling. Finally, a number of projects that applying modelling and simulation techniques to various aspects of the EGF receptor system are described

Pattern Recognition in a Bimodal Aquifer Using the Normal-Score Ensemble Kalman Filter

The ensemble Kalman filter (EnKF) is now widely used in diverse disciplines to estimate model parameters and update model states by integrating observed data. The EnKF is known to perform optimally only for multi-Gaussian distributed states and parameters. A new approach, the normal-score EnKF (NS-EnKF), has been recently proposed to handle complex aquifers with non-Gaussian distributed parameters. In this work, we aim at investigating the capacity of the NS-EnKF to identify patterns in the spatial distribution of the model parameters (hydraulic conductivities) by assimilating dynamic observations in the absence of direct measurements of the parameters themselves. In some situations, hydraulic conductivity measurements (hard data) may not be available, which requires the estimation of conductivities from indirect observations, such as piezometric heads. We show how the NS-EnKF is capable of retrieving the bimodal nature of a synthetic aquifer solely from piezometric head data. By comparison with a more standard implementation of the EnKF, the NS-EnKF gives better results with regard to histogram preservation, uncertainty assessment, and transport predictions. © 2011 International Association for Mathematical Geosciences.The authors gratefully acknowledge the financial support by the Spanish Ministry of Science and Innovation through project CGL2011-23295. The first author appreciates the financial aid from China Scholarship Council (CSC No. [2007]3020).Zhou, H.; Li, L.; Hendricks Franssen, H.; Gómez-Hernández, JJ. (2012). Pattern Recognition in a Bimodal Aquifer Using the Normal-Score Ensemble Kalman Filter. Mathematical Geosciences. 44(2):169-185. https://doi.org/10.1007/s11004-011-9372-3S169185442Arulampalam MS, Maskell S, Gordon N, Clapp T (2002) A tutorial on particle filters for online nonlinear/non-Gaussian Bayesian tracking. IEEE Trans Signal Process 50(2):174–188Bertino L, Evensen G, Wackernagel H (2003) Sequential data assimilation techniques in oceanography. Int Stat Rev 71(2):223–241Burgers G, Jan van Leeuwen P, Evensen G (1998) Analysis scheme in the ensemble Kalman filter. Mon Weather Rev 126(6):1719–1724Carrera J, Neuman SP (1986b) Estimation of aquifer parameters under transient and steady state conditions: 2. Uniqueness, stability, and solution algorithms. Water Resour Res 22(2):211–227Chen Y, Zhang D (2006) Data assimilation for transient flow in geologic formations via ensemble Kalman filter. Adv Water Resour 29:1107–1122Delhomme JP (1979) Spatial variability and uncertainty in groundwater flow parameters: a geostatistical approach. Water Resour Res 15(2):269–280Evensen G (1994) Sequential data assimilation with a nonlinear quasi-geostrophic model using Monte Carlo methods to forecast error statistics. J Geophys Res 99(C5):10143–10162Evensen G (2007) Data assimilation: the ensemble Kalman filter. Springer, Berlin, 279 ppFernàndez-Garcia D, Illangasekare T, Rajaram H (2005) Differences in the scale dependence of dispersivity and retardation factors estimated from forced-gradient and uniform flow tracer tests in three-dimensional physically and chemically heterogeneous porous media. Water Resour Res 41(3):W03012Gómez-Hernández JJ, Journel AG (1993) Joint sequential simulation of multi-Gaussian fields. In: Soares A (ed) Geostatistics Tróia ’92, vol 1. Kluwer Academic, Dordrecht, pp 85–94Gómez-Hernández JJ, Wen XH (1998) To be or not to be multi-Gaussian? A reflection on stochastic hydrogeology. Adv Water Resour 21(1):47–61Gu Y, Oliver DS (2006) The ensemble Kalman filter for continuous updating of reservoir simulation models. J Energy Resour Technol 128:79–87Harbaugh AW, Banta ER, Hill MC, McDonald MG (2000) MODFLOW-2000, the U.S. geological survey modular ground-water model—user guide to modularization concepts and the ground-water flow process. Tech rep. Open-File Report 00-92, U.S. Department of the Interior, U.S. Geological Survey. Reston, Virginia, 121 ppHendricks Franssen HJ, Kinzelbach W (2008) Real-time groundwater flow modeling with the Ensemble Kalman Filter: joint estimation for states and parameters and the filter inbreeding problem. Water Resour Res 44:W09408Hendricks Franssen HJ, Kinzelbach W (2009) Ensemble Kalman filtering versus sequential self-calibration for inverse modelling of dynamic groundwater flow systems. J Hydrol 365(3–4):261–274Houtekamer PL, Mitchell HL (2001) A sequential ensemble Kalman filter for atmospheric data assimilation. Mon Weather Rev 129:123–137Journel AG, Deutsch CV (1993) Entropy and spatial disorder. Math Geol 25(3):329–355Li L, Zhou H, Gómez-Hernández JJ (2011a) A comparative study of three-dimensional hydraulic conductivity upscaling at the macrodispersion experiment (MADE) site, Columbus air force base, Mississippi (USA). J Hydrol 404(3–4):278–293Li L, Zhou H, Gómez-Hernández JJ (2011b) Transport upscaling using multi-rate mass transfer in three-dimensional highly heterogeneous porous media. Adv Water Resour 34(4):478–489Moradkhani H, Sorooshian S, Gupta HV, Houser PR (2005) Dual state-parameter estimation of hydrological models using ensemble Kalman filter. Adv Water Resour 28:135–147Naevdal G, Johnsen L, Aanonsen S, Vefring E (Mar. 2005) Reservoir monitoring and continuous model updating using ensemble Kalman filter. SPE J 10(1):66–74Pardo-Igúzquiza E, Dowd PA (2003) CONNEC3D: a computer program for connectivity analysis of 3D random set models. Comput Geosci 29:775–785Schöniger A, Nowak W, Hendricks Franssen HJ (2011) Parameter estimation by ensemble Kalman filters with transformed data: approach and application to hydraulic tomography. Water Resour Res (submitted)Simon E, Bertino L (2009) Application of the Gaussian anamorphosis to assimilation in a 3-D coupled physical-ecosystem model of the North Atlantic with the EnKF: a twin experiment. Ocean Sci 5:495–510Stauffer D, Aharony A (1994) Introduction to percolation theory. Taylor and Francis, London. 181 ppStrébelle S 2000. Sequential simulation drawing structures from training images. PhD thesis, Stanford University. 187 ppStrebelle S (2002) Conditional simulation of complex geological structures using multiple-point statistics. Math Geol 34(1):1–21Wen X, Chen W (2006) Real-time reservoir model updating using ensemble Kalman filter: the confirming approach. SPE J 11(4):431–442Wen X, Chen W (2007) Some practical issues on real time reservoir updating using ensemble Kalman filter. SPE J 12(2):156–166Zhou H, Gómez-Hernández JJ, Hendricks Franssen H-J, Li L (2011) An approach to handling non-gaussianity of parameters and state variables in ensemble Kalman filtering. Adv Water Resour 34(7):844–864Zinn B, Harvey C (2003) When good statistical models of aquifer heterogeneity go bad: a comparison of flow, dispersion, and mass transfer in connected and multivariate Gaussian hydraulic conductivity fields. Water Resour Res 39(3):105

Training, Match and Non-Rugby Activities in Elite Male Youth Rugby Union Players in England

Rugby union is a late specialisation sport. As a consequence, youth players may still be engaged in other activities and sports throughout the year as they transition to rugby specialisation. Limited research exists quantifying rugby union training and matches as well as engagement in other activities and sports. Therefore, the aim of this study was to quantify and compare rugby union training, matches and other activities of elite youth U15 and U16 rugby union players at different stages of the season

Efferent Control of the Electrical and Mechanical Properties of Hair Cells in the Bullfrog's Sacculus

Background: Hair cells in the auditory, vestibular, and lateral-line systems respond to mechanical stimulation and transmit information to afferent nerve fibers. The sensitivity of mechanoelectrical transduction is modulated by the efferent pathway, whose activity usually reduces the responsiveness of hair cells. The basis of this effect remains unknown. Methodology and Principal Findings: We employed immunocytological, electrophysiological, and micromechanical approaches to characterize the anatomy of efferent innervation and the effect of efferent activity on the electrical and mechanical properties of hair cells in the bullfrog’s sacculus. We found that efferent fibers form extensive synaptic terminals on all macular and extramacular hair cells. Macular hair cells expressing the Ca 2+-buffering protein calretinin contain half as many synaptic ribbons and are innervated by twice as many efferent terminals as calretinin-negative hair cells. Efferent activity elicits inhibitory postsynaptic potentials in hair cells and thus inhibits their electrical resonance. In hair cells that exhibit spiking activity, efferent stimulation suppresses the generation of action potentials. Finally, efferent activity triggers a displacement of the hair bundle’s resting position. Conclusions and Significance: The hair cells of the bullfrog’s sacculus receive a rich efferent innervation with the heaviest projection to calretinin-containing cells. Stimulation of efferent axons desensitizes the hair cells and suppresses their spiking activity. Although efferent activation influences mechanoelectrical transduction, the mechanical effects on hair bundles ar

Rhizome Severing Increases Root Lifespan of Leymus chinensis in a Typical Steppe of Inner Mongolia

Root lifespan is an important trait that determines plants' ability to acquire and conserve soil resources. There have been several studies investigating characteristics of root lifespan of both woody and herbaceous species. However, most of the studies have focused on non-clonal plants, and there have been little data on root lifespan for clonal plants that occur widely in temperate grasslands.We investigated the effects of rhizome severing on overall root lifespan of Leymus chinensis, a clonal, dominant grass species in the temperate steppe in northern China, in a 2-year field study using modified rhizotron technique. More specifically, we investigated the effects of rhizome severing on root lifespan of roots born in different seasons and distributed at different soil depths. Rhizome severing led to an increase in the overall root lifespan from 81 to 103 days. The increase in root lifespan exhibited spatial and temporal characteristics such that it increased lifespan for roots distributed in the top two soil layers and for roots born in summer and spring, but it had no effect on lifespan of roots in the deep soil layer and born in autumn. We also examined the effect of rhizome severing on carbohydrate and N contents in roots, and found that root carbohydrate and N contents were not affected by rhizome severing. Further, we found that root lifespan of Stipa krylovii and Artemisia frigida, two dominant, non-clonal species in the temperate steppe, was significantly longer (118 d) than that of L. chinensis (81 d), and this value became comparable to that of L. chinensis under rhizome severing (103 d).We found that root lifespan in dominant, clonal L. chinensis was shorter than for the dominant, non-clonal species of S. krylovii and A. frigida. There was a substantial increase in the root lifespan of L. chinensis in response to severing their rhizomes, and this increase in root lifespan exhibited temporal and spatial characteristics. These findings suggest that the presence of rhizomes is likely to account for the observed short lifespan of clonal plant species in the temperate steppe

A neural tracking and motor control approach to improve rehabilitation of upper limb movements

<p>Abstract</p> <p>Background</p> <p>Restoration of upper limb movements in subjects recovering from stroke is an essential keystone in rehabilitative practices. Rehabilitation of arm movements, in fact, is usually a far more difficult one as compared to that of lower extremities. For these reasons, researchers are developing new methods and technologies so that the rehabilitative process could be more accurate, rapid and easily accepted by the patient. This paper introduces the proof of concept for a new non-invasive FES-assisted rehabilitation system for the upper limb, called smartFES (sFES), where the electrical stimulation is controlled by a biologically inspired neural inverse dynamics model, fed by the kinematic information associated with the execution of a planar goal-oriented movement. More specifically, this work details two steps of the proposed system: an <it>ad hoc </it>markerless motion analysis algorithm for the estimation of kinematics, and a neural controller that drives a synthetic arm. The vision of the entire system is to acquire kinematics from the analysis of video sequences during planar arm movements and to use it together with a neural inverse dynamics model able to provide the patient with the electrical stimulation patterns needed to perform the movement with the assisted limb.</p> <p>Methods</p> <p>The markerless motion tracking system aims at localizing and monitoring the arm movement by tracking its silhouette. It uses a specifically designed motion estimation method, that we named Neural Snakes, which predicts the arm contour deformation as a first step for a silhouette extraction algorithm. The starting and ending points of the arm movement feed an Artificial Neural Controller, enclosing the muscular Hill's model, which solves the inverse dynamics to obtain the FES patterns needed to move a simulated arm from the starting point to the desired point. Both position error with respect to the requested arm trajectory and comparison between curvature factors have been calculated in order to determine the accuracy of the system.</p> <p>Results</p> <p>The proposed method has been tested on real data acquired during the execution of planar goal-oriented arm movements. Main results concern the capability of the system to accurately recreate the movement task by providing a synthetic arm model with the stimulation patterns estimated by the inverse dynamics model. In the simulation of movements with a length of ± 20 cm, the model has shown an unbiased angular error, and a mean (absolute) position error of about 1.5 cm, thus confirming the ability of the system to reliably drive the model to the desired targets. Moreover, the curvature factors of the factual human movements and of the reconstructed ones are similar, thus encouraging future developments of the system in terms of reproducibility of the desired movements.</p> <p>Conclusion</p> <p>A novel FES-assisted rehabilitation system for the upper limb is presented and two parts of it have been designed and tested. The system includes a markerless motion estimation algorithm, and a biologically inspired neural controller that drives a biomechanical arm model and provides the stimulation patterns that, in a future development, could be used to drive a smart Functional Electrical Stimulation system (sFES). The system is envisioned to help in the rehabilitation of post stroke hemiparetic patients, by assisting the movement of the paretic upper limb, once trained with a set of movements performed by the therapist or in virtual reality. Future work will include the application and testing of the stimulation patterns in real conditions.</p

Nociceptive Afferents to the Premotor Neurons That Send Axons Simultaneously to the Facial and Hypoglossal Motoneurons by Means of Axon Collaterals

It is well known that the brainstem premotor neurons of the facial nucleus and hypoglossal nucleus coordinate orofacial nociceptive reflex (ONR) responses. However, whether the brainstem PNs receive the nociceptive projection directly from the caudal spinal trigeminal nucleus is still kept unclear. Our present study focuses on the distribution of premotor neurons in the ONR pathways of rats and the collateral projection of the premotor neurons which are involved in the brainstem local pathways of the orofacial nociceptive reflexes of rat. Retrograde tracer Fluoro-gold (FG) or FG/tetramethylrhodamine-dextran amine (TMR-DA) were injected into the VII or/and XII, and anterograde tracer biotinylated dextran amine (BDA) was injected into the caudal spinal trigeminal nucleus (Vc). The tracing studies indicated that FG-labeled neurons receiving BDA-labeled fibers from the Vc were mainly distributed bilaterally in the parvicellular reticular formation (PCRt), dorsal and ventral medullary reticular formation (MdD, MdV), supratrigeminal nucleus (Vsup) and parabrachial nucleus (PBN) with an ipsilateral dominance. Some FG/TMR-DA double-labeled premotor neurons, which were observed bilaterally in the PCRt, MdD, dorsal part of the MdV, peri-motor nucleus regions, contacted with BDA-labeled axonal terminals and expressed c-fos protein-like immunoreactivity which induced by subcutaneous injection of formalin into the lip. After retrograde tracer wheat germ agglutinated horseradish peroxidase (WGA-HRP) was injected into VII or XII and BDA into Vc, electron microscopic study revealed that some BDA-labeled axonal terminals made mainly asymmetric synapses on the dendritic and somatic profiles of WGA-HRP-labeled premotor neurons. These data indicate that some premotor neurons could integrate the orofacial nociceptive input from the Vc and transfer these signals simultaneously to different brainstem motonuclei by axonal collaterals

Inducible Ablation of Melanopsin-Expressing Retinal Ganglion Cells Reveals Their Central Role in Non-Image Forming Visual Responses

Rod/cone photoreceptors of the outer retina and the melanopsin-expressing retinal ganglion cells (mRGCs) of the inner retina mediate non-image forming visual responses including entrainment of the circadian clock to the ambient light, the pupillary light reflex (PLR), and light modulation of activity. Targeted deletion of the melanopsin gene attenuates these adaptive responses with no apparent change in the development and morphology of the mRGCs. Comprehensive identification of mRGCs and knowledge of their specific roles in image-forming and non-image forming photoresponses are currently lacking. We used a Cre-dependent GFP expression strategy in mice to genetically label the mRGCs. This revealed that only a subset of mRGCs express enough immunocytochemically detectable levels of melanopsin. We also used a Cre-inducible diphtheria toxin receptor (iDTR) expression approach to express the DTR in mRGCs. mRGCs develop normally, but can be acutely ablated upon diphtheria toxin administration. The mRGC-ablated mice exhibited normal outer retinal function. However, they completely lacked non-image forming visual responses such as circadian photoentrainment, light modulation of activity, and PLR. These results point to the mRGCs as the site of functional integration of the rod/cone and melanopsin phototransduction pathways and as the primary anatomical site for the divergence of image-forming and non-image forming photoresponses in mammals

A xandarellid artiopodan from Morocco – a middle Cambrian link between soft-bodied euarthropod communities in North Africa and South China

NB. A corrigendum [correction] for this article was published online on 09 May 2017; this has been attached to this article as an additional file. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ © The Author(s) 2017. The attached file is the published version of the article