Teaching and learning the Hodgkin-Huxley model based on software developed in NEURON's programming language hoc.

Science.gov (United States)

Hernández, Oscar E; Zurek, Eduardo E

2013-05-15

We present a software tool called SENB, which allows the geometric and biophysical neuronal properties in a simple computational model of a Hodgkin-Huxley (HH) axon to be changed. The aim of this work is to develop a didactic and easy-to-use computational tool in the NEURON simulation environment, which allows graphical visualization of both the passive and active conduction parameters and the geometric characteristics of a cylindrical axon with HH properties. The SENB software offers several advantages for teaching and learning electrophysiology. First, SENB offers ease and flexibility in determining the number of stimuli. Second, SENB allows immediate and simultaneous visualization, in the same window and time frame, of the evolution of the electrophysiological variables. Third, SENB calculates parameters such as time and space constants, stimuli frequency, cellular area and volume, sodium and potassium equilibrium potentials, and propagation velocity of the action potentials. Furthermore, it allows the user to see all this information immediately in the main window. Finally, with just one click SENB can save an image of the main window as evidence. The SENB software is didactic and versatile, and can be used to improve and facilitate the teaching and learning of the underlying mechanisms in the electrical activity of an axon using the biophysical properties of the squid giant axon.

Stochastic resonance on Newman-Watts networks of Hodgkin-Huxley neurons with local periodic driving

Energy Technology Data Exchange (ETDEWEB)

Ozer, Mahmut [Zonguldak Karaelmas University, Engineering Faculty, Department of Electrical and Electronics Engineering, 67100 Zonguldak (Turkey)], E-mail: mahmutozer2002@yahoo.com; Perc, Matjaz [University of Maribor, Faculty of Natural Sciences and Mathematics, Department of Physics, Koroska cesta 160, SI-2000 Maribor (Slovenia); Uzuntarla, Muhammet [Zonguldak Karaelmas University, Engineering Faculty, Department of Electrical and Electronics Engineering, 67100 Zonguldak (Turkey)

2009-03-02

We study the phenomenon of stochastic resonance on Newman-Watts small-world networks consisting of biophysically realistic Hodgkin-Huxley neurons with a tunable intensity of intrinsic noise via voltage-gated ion channels embedded in neuronal membranes. Importantly thereby, the subthreshold periodic driving is introduced to a single neuron of the network, thus acting as a pacemaker trying to impose its rhythm on the whole ensemble. We show that there exists an optimal intensity of intrinsic ion channel noise by which the outreach of the pacemaker extends optimally across the whole network. This stochastic resonance phenomenon can be further amplified via fine-tuning of the small-world network structure, and depends significantly also on the coupling strength among neurons and the driving frequency of the pacemaker. In particular, we demonstrate that the noise-induced transmission of weak localized rhythmic activity peaks when the pacemaker frequency matches the intrinsic frequency of subthreshold oscillations. The implications of our findings for weak signal detection and information propagation across neural networks are discussed.

A path integral approach to the Hodgkin-Huxley model

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Baravalle, Roman; Rosso, Osvaldo A.; Montani, Fernando

2017-11-01

To understand how single neurons process sensory information, it is necessary to develop suitable stochastic models to describe the response variability of the recorded spike trains. Spikes in a given neuron are produced by the synergistic action of sodium and potassium of the voltage-dependent channels that open or close the gates. Hodgkin and Huxley (HH) equations describe the ionic mechanisms underlying the initiation and propagation of action potentials, through a set of nonlinear ordinary differential equations that approximate the electrical characteristics of the excitable cell. Path integral provides an adequate approach to compute quantities such as transition probabilities, and any stochastic system can be expressed in terms of this methodology. We use the technique of path integrals to determine the analytical solution driven by a non-Gaussian colored noise when considering the HH equations as a stochastic system. The different neuronal dynamics are investigated by estimating the path integral solutions driven by a non-Gaussian colored noise q. More specifically we take into account the correlational structures of the complex neuronal signals not just by estimating the transition probability associated to the Gaussian approach of the stochastic HH equations, but instead considering much more subtle processes accounting for the non-Gaussian noise that could be induced by the surrounding neural network and by feedforward correlations. This allows us to investigate the underlying dynamics of the neural system when different scenarios of noise correlations are considered.

A self-organizing state-space-model approach for parameter estimation in hodgkin-huxley-type models of single neurons.

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Dimitrios V Vavoulis

Full Text Available Traditional approaches to the problem of parameter estimation in biophysical models of neurons and neural networks usually adopt a global search algorithm (for example, an evolutionary algorithm, often in combination with a local search method (such as gradient descent in order to minimize the value of a cost function, which measures the discrepancy between various features of the available experimental data and model output. In this study, we approach the problem of parameter estimation in conductance-based models of single neurons from a different perspective. By adopting a hidden-dynamical-systems formalism, we expressed parameter estimation as an inference problem in these systems, which can then be tackled using a range of well-established statistical inference methods. The particular method we used was Kitagawa's self-organizing state-space model, which was applied on a number of Hodgkin-Huxley-type models using simulated or actual electrophysiological data. We showed that the algorithm can be used to estimate a large number of parameters, including maximal conductances, reversal potentials, kinetics of ionic currents, measurement and intrinsic noise, based on low-dimensional experimental data and sufficiently informative priors in the form of pre-defined constraints imposed on model parameters. The algorithm remained operational even when very noisy experimental data were used. Importantly, by combining the self-organizing state-space model with an adaptive sampling algorithm akin to the Covariance Matrix Adaptation Evolution Strategy, we achieved a significant reduction in the variance of parameter estimates. The algorithm did not require the explicit formulation of a cost function and it was straightforward to apply on compartmental models and multiple data sets. Overall, the proposed methodology is particularly suitable for resolving high-dimensional inference problems based on noisy electrophysiological data and, therefore, a

Theoretical analysis of transcranial magneto-acoustical stimulation with Hodgkin–Huxley neuron model

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Yi eYuan

2016-04-01

Full Text Available Transcranial magneto-acoustical stimulation (TMAS is a novel stimulation technology in which an ultrasonic wave within a magnetostatic field generates an electric current in an area of interest in the brain to modulate neuronal activities. As a key part of the neural network, neurons transmit information in the nervous system. However, the effect of TMAS on the neuronal firing rhythm remains unknown. To address this problem, we investigated the stimulatory mechanism of TMAS on neurons with a Hodgkin-Huxley neuron model. The simulation results indicate that the magnetostatic field intensity and ultrasonic power can affect the amplitude and interspike interval of neuronal action potential under continuous wave ultrasound. The simulation results also show that the ultrasonic power, duty cycle and repetition frequency can alter the firing rhythm of neural action potential under pulsed ultrasound. This study can help to reveal and explain the biological mechanism of TMAS and to provide a theoretical basis for TMAS in the treatment or rehabilitation of neuropsychiatric disorders.

Anti-electromagnetic interference analysis of equivalent circuit of ion channel based on the Hodgkin-Huxley model

International Nuclear Information System (INIS)

Chu, J; Chang, X L; Zhao, M; Man, M H; Wei, M; Yuan, L

2013-01-01

With the continuous improvement of circuit integration and working clock frequency in the electronic system, it is increasingly easy for the system to be affected by electromagnetic waves, and electromagnetic susceptibility and vulnerability become more severe. However, living beings in nature have shown extraordinary compatibility, immunity and adaptability to the electromagnetism at the same time. In addition, the ion channel on the neuron cytomembrane is a typical representation of b ioelectrical immunity . So the Hodgkin-Huxley circuit model with one capacitor in parallel with some power supplies and resistors was adopted to simulate the ion channel on the neuron cytomembrane. Through analysis, the circuit model can be used to simulate some electrical characteristics of biological neuron cells, and then acquire a certain level of anti-electromagnetic interference ability. This method will be useful for improving the reliability, compatibility and anti-interference capability of the electronic system in the complicated electromagnetic environment.

The what and where of adding channel noise to the Hodgkin-Huxley equations.

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Joshua H Goldwyn

2011-11-01

Full Text Available Conductance-based equations for electrically active cells form one of the most widely studied mathematical frameworks in computational biology. This framework, as expressed through a set of differential equations by Hodgkin and Huxley, synthesizes the impact of ionic currents on a cell's voltage--and the highly nonlinear impact of that voltage back on the currents themselves--into the rapid push and pull of the action potential. Later studies confirmed that these cellular dynamics are orchestrated by individual ion channels, whose conformational changes regulate the conductance of each ionic current. Thus, kinetic equations familiar from physical chemistry are the natural setting for describing conductances; for small-to-moderate numbers of channels, these will predict fluctuations in conductances and stochasticity in the resulting action potentials. At first glance, the kinetic equations provide a far more complex (and higher-dimensional description than the original Hodgkin-Huxley equations or their counterparts. This has prompted more than a decade of efforts to capture channel fluctuations with noise terms added to the equations of Hodgkin-Huxley type. Many of these approaches, while intuitively appealing, produce quantitative errors when compared to kinetic equations; others, as only very recently demonstrated, are both accurate and relatively simple. We review what works, what doesn't, and why, seeking to build a bridge to well-established results for the deterministic equations of Hodgkin-Huxley type as well as to more modern models of ion channel dynamics. As such, we hope that this review will speed emerging studies of how channel noise modulates electrophysiological dynamics and function. We supply user-friendly MATLAB simulation code of these stochastic versions of the Hodgkin-Huxley equations on the ModelDB website (accession number 138950 and http://www.amath.washington.edu/~etsb/tutorials.html.

Crisis of interspike intervals in Hodgkin-Huxley model

International Nuclear Information System (INIS)

Jin Wuyin; Xu Jianxue; Wu Ying; Hong Ling; Wei Yaobing

2006-01-01

The bifurcations of the chaotic attractor in a Hodgkin-Huxley (H-H) model under stimulation of periodic signal is presented in this work, where the frequency of signal is taken as the controlling parameter. The chaotic behavior is realized over a wide range of frequency and is visualized by using interspike intervals (ISIs). Many kinds of abrupt undergoing changes of the ISIs are observed in different frequency regions, such as boundary crisis, interior crisis and merging crisis displaying alternately along with the changes of external signal frequency. And there are logistic-like bifurcation behaviors, e.g., periodic windows and fractal structures in ISIs dynamics. The saddle-node bifurcations resulting in collapses of chaos to period-6 orbit in dynamics of ISIs are identified

Spike neural models (part I: The Hodgkin-Huxley model

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Johnson, Melissa G.

2017-05-01

Full Text Available Artificial neural networks, or ANNs, have grown a lot since their inception back in the 1940s. But no matter the changes, one of the most important components of neural networks is still the node, which represents the neuron. Within spiking neural networks, the node is especially important because it contains the functions and properties of neurons that are necessary for their network. One important aspect of neurons is the ionic flow which produces action potentials, or spikes. Forces of diffusion and electrostatic pressure work together with the physical properties of the cell to move ions around changing the cell membrane potential which ultimately produces the action potential. This tutorial reviews the Hodkgin-Huxley model and shows how it simulates the ionic flow of the giant squid axon via four differential equations. The model is implemented in Matlab using Euler's Method to approximate the differential equations. By using Euler's method, an extra parameter is created, the time step. This new parameter needs to be carefully considered or the results of the node may be impaired.

Saddle Slow Manifolds and Canard Orbits in [Formula: see text] and Application to the Full Hodgkin-Huxley Model.

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Hasan, Cris R; Krauskopf, Bernd; Osinga, Hinke M

2018-04-19

Many physiological phenomena have the property that some variables evolve much faster than others. For example, neuron models typically involve observable differences in time scales. The Hodgkin-Huxley model is well known for explaining the ionic mechanism that generates the action potential in the squid giant axon. Rubin and Wechselberger (Biol. Cybern. 97:5-32, 2007) nondimensionalized this model and obtained a singularly perturbed system with two fast, two slow variables, and an explicit time-scale ratio ε. The dynamics of this system are complex and feature periodic orbits with a series of action potentials separated by small-amplitude oscillations (SAOs); also referred to as mixed-mode oscillations (MMOs). The slow dynamics of this system are organized by two-dimensional locally invariant manifolds called slow manifolds which can be either attracting or of saddle type.In this paper, we introduce a general approach for computing two-dimensional saddle slow manifolds and their stable and unstable fast manifolds. We also develop a technique for detecting and continuing associated canard orbits, which arise from the interaction between attracting and saddle slow manifolds, and provide a mechanism for the organization of SAOs in [Formula: see text]. We first test our approach with an extended four-dimensional normal form of a folded node. Our results demonstrate that our computations give reliable approximations of slow manifolds and canard orbits of this model. Our computational approach is then utilized to investigate the role of saddle slow manifolds and associated canard orbits of the full Hodgkin-Huxley model in organizing MMOs and determining the firing rates of action potentials. For ε sufficiently large, canard orbits are arranged in pairs of twin canard orbits with the same number of SAOs. We illustrate how twin canard orbits partition the attracting slow manifold into a number of ribbons that play the role of sectors of rotations. The upshot is that we

Spike trains in Hodgkin-Huxley model and ISIs of acupuncture manipulations

International Nuclear Information System (INIS)

Wang Jiang; Si Wenjie; Che Yanqiu; Fei Xiangyang

2008-01-01

The Hodgkin-Huxley equations (HH) are parameterized by a number of parameters and shows a variety of qualitatively different behaviors depending on the parameter values. Under stimulation of an external periodic voltage, the ISIs (interspike intervals) of a HH model are investigated in this work, while the frequency of the voltage is taken as the controlling parameter. As well-known, the science of acupuncture and moxibustion is an important component of Traditional Chinese Medicine with a long history. Although there are a number of different acupuncture manipulations, the method for distinguishing them is rarely investigated. With the idea of ISI, we study the electrical signal time series at the spinal dorsal horn produced by three different acupuncture manipulations in Zusanli point and present an effective way to distinguish them

Spike trains in Hodgkin-Huxley model and ISIs of acupuncture manipulations

Energy Technology Data Exchange (ETDEWEB)

Wang Jiang [School of Electrical and Automation Engineering, Tianjin University, Tianjin 300072 (China)], E-mail: jiangwang@tju.edu.cn; Si Wenjie; Che Yanqiu; Fei Xiangyang [School of Electrical and Automation Engineering, Tianjin University, Tianjin 300072 (China)

2008-05-15

The Hodgkin-Huxley equations (HH) are parameterized by a number of parameters and shows a variety of qualitatively different behaviors depending on the parameter values. Under stimulation of an external periodic voltage, the ISIs (interspike intervals) of a HH model are investigated in this work, while the frequency of the voltage is taken as the controlling parameter. As well-known, the science of acupuncture and moxibustion is an important component of Traditional Chinese Medicine with a long history. Although there are a number of different acupuncture manipulations, the method for distinguishing them is rarely investigated. With the idea of ISI, we study the electrical signal time series at the spinal dorsal horn produced by three different acupuncture manipulations in Zusanli point and present an effective way to distinguish them.

On non-linear dynamics and an optimal control synthesis of the action potential of membranes (ideal and non-ideal cases) of the Hodgkin-Huxley (HH) mathematical model

International Nuclear Information System (INIS)

Chavarette, Fabio Roberto; Balthazar, Jose Manoel; Rafikov, Marat; Hermini, Helder Anibal

2009-01-01

In this paper, we have studied the plasmatic membrane behavior using an electric circuit developed by Hodgkin and Huxley in 1952 and have dealt with the variation of the amount of time related to the potassium and sodium conductances in the squid axon. They developed differential equations for the propagation of electric signals; the dynamics of the Hodgkin-Huxley model have been extensively studied both from the view point of its their biological implications and as a test bed for numerical methods, which can be applied to more complex models. Recently, an irregular chaotic movement of the action potential of the membrane was observed for a number of techniques of control with the objective to stabilize the variation of this potential. This paper analyzes the non-linear dynamics of the Hodgkin-Huxley mathematical model, and we present some modifications in the governing equations of the system in order to make it a non-ideal one (taking into account that the energy source has a limited power supply). We also developed an optimal linear control design for the action potential of membranes. Here, we discuss the conditions that allow the use of control linear feedback for this kind of non-linear system.

Teaching and learning the Hodgkin-Huxley model based on software developed in NEURON’s programming language hoc

Science.gov (United States)

2013-01-01

Background We present a software tool called SENB, which allows the geometric and biophysical neuronal properties in a simple computational model of a Hodgkin-Huxley (HH) axon to be changed. The aim of this work is to develop a didactic and easy-to-use computational tool in the NEURON simulation environment, which allows graphical visualization of both the passive and active conduction parameters and the geometric characteristics of a cylindrical axon with HH properties. Results The SENB software offers several advantages for teaching and learning electrophysiology. First, SENB offers ease and flexibility in determining the number of stimuli. Second, SENB allows immediate and simultaneous visualization, in the same window and time frame, of the evolution of the electrophysiological variables. Third, SENB calculates parameters such as time and space constants, stimuli frequency, cellular area and volume, sodium and potassium equilibrium potentials, and propagation velocity of the action potentials. Furthermore, it allows the user to see all this information immediately in the main window. Finally, with just one click SENB can save an image of the main window as evidence. Conclusions The SENB software is didactic and versatile, and can be used to improve and facilitate the teaching and learning of the underlying mechanisms in the electrical activity of an axon using the biophysical properties of the squid giant axon. PMID:23675833

Identifying generalized Fitzhugh-Nagumo equation from a numerical solution of Hodgkin-Huxley model

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Nikola V. Georgiev

2003-01-01

Full Text Available An analytic time series in the form of numerical solution (in an appropriate finite time interval of the Hodgkin-Huxley current clamped (HHCC system of four differential equations, well known in the neurophysiology as an exact empirical model of excitation of a giant axon of Loligo, is presented. Then we search for a second-order differential equation of generalized Fitzhugh-Nagumo (GFN type, having as a solution the given single component (action potential of the numerical solution. The given time series is used as a basis for reconstructing orders, powers, and coefficients of the polynomial right-hand sides of GFN equation approximately governing the process of action potential. For this purpose, a new geometrical method for determining phase space dimension of the unknown dynamical system (GFN equation and a specific modification of least squares method for identifying unknown coefficients are developed and applied.

Dynamics from seconds to hours in Hodgkin-Huxley model with time-dependent ion concentrations and buffer reservoirs.

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Niklas Hübel

2014-12-01

Full Text Available The classical Hodgkin-Huxley (HH model neglects the time-dependence of ion concentrations in spiking dynamics. The dynamics is therefore limited to a time scale of milliseconds, which is determined by the membrane capacitance multiplied by the resistance of the ion channels, and by the gating time constants. We study slow dynamics in an extended HH framework that includes time-dependent ion concentrations, pumps, and buffers. Fluxes across the neuronal membrane change intra- and extracellular ion concentrations, whereby the latter can also change through contact to reservoirs in the surroundings. Ion gain and loss of the system is identified as a bifurcation parameter whose essential importance was not realized in earlier studies. Our systematic study of the bifurcation structure and thus the phase space structure helps to understand activation and inhibition of a new excitability in ion homeostasis which emerges in such extended models. Also modulatory mechanisms that regulate the spiking rate can be explained by bifurcations. The dynamics on three distinct slow times scales is determined by the cell volume-to-surface-area ratio and the membrane permeability (seconds, the buffer time constants (tens of seconds, and the slower backward buffering (minutes to hours. The modulatory dynamics and the newly emerging excitable dynamics corresponds to pathological conditions observed in epileptiform burst activity, and spreading depression in migraine aura and stroke, respectively.

Dynamics from seconds to hours in Hodgkin-Huxley model with time-dependent ion concentrations and buffer reservoirs.

Science.gov (United States)

Hübel, Niklas; Dahlem, Markus A

2014-12-01

The classical Hodgkin-Huxley (HH) model neglects the time-dependence of ion concentrations in spiking dynamics. The dynamics is therefore limited to a time scale of milliseconds, which is determined by the membrane capacitance multiplied by the resistance of the ion channels, and by the gating time constants. We study slow dynamics in an extended HH framework that includes time-dependent ion concentrations, pumps, and buffers. Fluxes across the neuronal membrane change intra- and extracellular ion concentrations, whereby the latter can also change through contact to reservoirs in the surroundings. Ion gain and loss of the system is identified as a bifurcation parameter whose essential importance was not realized in earlier studies. Our systematic study of the bifurcation structure and thus the phase space structure helps to understand activation and inhibition of a new excitability in ion homeostasis which emerges in such extended models. Also modulatory mechanisms that regulate the spiking rate can be explained by bifurcations. The dynamics on three distinct slow times scales is determined by the cell volume-to-surface-area ratio and the membrane permeability (seconds), the buffer time constants (tens of seconds), and the slower backward buffering (minutes to hours). The modulatory dynamics and the newly emerging excitable dynamics corresponds to pathological conditions observed in epileptiform burst activity, and spreading depression in migraine aura and stroke, respectively.

Results on a Binding Neuron Model and Their Implications for Modified Hourglass Model for Neuronal Network

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Viswanathan Arunachalam

2013-01-01

Full Text Available The classical models of single neuron like Hodgkin-Huxley point neuron or leaky integrate and fire neuron assume the influence of postsynaptic potentials to last till the neuron fires. Vidybida (2008 in a refreshing departure has proposed models for binding neurons in which the trace of an input is remembered only for a finite fixed period of time after which it is forgotten. The binding neurons conform to the behaviour of real neurons and are applicable in constructing fast recurrent networks for computer modeling. This paper develops explicitly several useful results for a binding neuron like the firing time distribution and other statistical characteristics. We also discuss the applicability of the developed results in constructing a modified hourglass network model in which there are interconnected neurons with excitatory as well as inhibitory inputs. Limited simulation results of the hourglass network are presented.

Impact of Bounded Noise and Rewiring on the Formation and Instability of Spiral Waves in a Small-World Network of Hodgkin-Huxley Neurons.

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Yao, Yuangen; Deng, Haiyou; Ma, Chengzhang; Yi, Ming; Ma, Jun

2017-01-01

Spiral waves are observed in the chemical, physical and biological systems, and the emergence of spiral waves in cardiac tissue is linked to some diseases such as heart ventricular fibrillation and epilepsy; thus it has importance in theoretical studies and potential medical applications. Noise is inevitable in neuronal systems and can change the electrical activities of neuron in different ways. Many previous theoretical studies about the impacts of noise on spiral waves focus an unbounded Gaussian noise and even colored noise. In this paper, the impacts of bounded noise and rewiring of network on the formation and instability of spiral waves are discussed in small-world (SW) network of Hodgkin-Huxley (HH) neurons through numerical simulations, and possible statistical analysis will be carried out. Firstly, we present SW network of HH neurons subjected to bounded noise. Then, it is numerically demonstrated that bounded noise with proper intensity σ, amplitude A, or frequency f can facilitate the formation of spiral waves when rewiring probability p is below certain thresholds. In other words, bounded noise-induced resonant behavior can occur in the SW network of neurons. In addition, rewiring probability p always impairs spiral waves, while spiral waves are confirmed to be robust for small p, thus shortcut-induced phase transition of spiral wave with the increase of p is induced. Furthermore, statistical factors of synchronization are calculated to discern the phase transition of spatial pattern, and it is confirmed that larger factor of synchronization is approached with increasing of rewiring probability p, and the stability of spiral wave is destroyed.

Resonant Activation in a Stochastic Hodgkin-Huxley Model: Interplay between noise and suprathreshold driving effect

DEFF Research Database (Denmark)

Pankratova, Evgeniya; Polovinkin, A.V.; Mosekilde, Erik

2005-01-01

The paper considers an excitable Hodgkin-Huxley system subjected to a strong periodic forcing in the presence of random noise. The influence of the forcing frequency on the response of the system is examined in the realm of suprathreshold amplitudes. Our results confirm that the presence of noise...... a minimum as functions of the forcing frequency. The destructive influence of noise on the interspike interval can also be reduced. With driving signals in a certain frequency range, the system can show stable periodic spiking even for relatively large noise intensities. Outside this frequency range, noise...... of similar intensity destroys the regularity of the spike trains by suppressing the generation of some of the spikes....

A study of quantum mechanical probabilities in the classical Hodgkin-Huxley model.

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Moradi, N; Scholkmann, F; Salari, V

2015-03-01

The Hodgkin-Huxley (HH) model is a powerful model to explain different aspects of spike generation in excitable cells. However, the HH model was proposed in 1952 when the real structure of the ion channel was unknown. It is now common knowledge that in many ion-channel proteins the flow of ions through the pore is governed by a gate, comprising a so-called "selectivity filter" inside the ion channel, which can be controlled by electrical interactions. The selectivity filter (SF) is believed to be responsible for the selection and fast conduction of particular ions across the membrane of an excitable cell. Other (generally larger) parts of the molecule such as the pore-domain gate control the access of ions to the channel protein. In fact, two types of gates are considered here for ion channels: the "external gate", which is the voltage sensitive gate, and the "internal gate" which is the selectivity filter gate (SFG). Some quantum effects are expected in the SFG due to its small dimensions, which may play an important role in the operation of an ion channel. Here, we examine parameters in a generalized model of HH to see whether any parameter affects the spike generation. Our results indicate that the previously suggested semi-quantum-classical equation proposed by Bernroider and Summhammer (BS) agrees strongly with the HH equation under different conditions and may even provide a better explanation in some cases. We conclude that the BS model can refine the classical HH model substantially.

Spiking sychronization regulated by noise in three types of Hodgkin—Huxley neuronal networks

International Nuclear Information System (INIS)

Zhang Zheng-Zhen; Zeng Shang-You; Tang Wen-Yan; Hu Jin-Lin; Zeng Shao-Wen; Ning Wei-Lian; Qiu Yi; Wu Hui-Si

2012-01-01

In this paper, we study spiking synchronization in three different types of Hodgkin—Huxley neuronal networks, which are the small-world, regular, and random neuronal networks. All the neurons are subjected to subthreshold stimulus and external noise. It is found that in each of all the neuronal networks there is an optimal strength of noise to induce the maximal spiking synchronization. We further demonstrate that in each of the neuronal networks there is a range of synaptic conductance to induce the effect that an optimal strength of noise maximizes the spiking synchronization. Only when the magnitude of the synaptic conductance is moderate, will the effect be considerable. However, if the synaptic conductance is small or large, the effect vanishes. As the connections between neurons increase, the synaptic conductance to maximize the effect decreases. Therefore, we show quantitatively that the noise-induced maximal synchronization in the Hodgkin—Huxley neuronal network is a general effect, regardless of the specific type of neuronal network

A Neuron-Based Model of Sleep-Wake Cycles

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Postnova, Svetlana; Peters, Achim; Braun, Hans

2008-03-01

In recent years it was discovered that a neuropeptide orexin/hypocretin plays a main role in sleep processes. This peptide is produced by the neurons in the lateral hypothalamus, which project to almost all brain areas. We present a computational model of sleep-wake cycles, which is based on the Hodgkin-Huxley type neurons and considers reciprocal glutaminergic projections between the lateral hypothalamus and the prefrontal cortex. Orexin is released as a neuromodulator and is required to keep the neurons firing, which corresponds to the wake state. When orexin is depleted the neurons are getting silent as observed in the sleep state. They can be reactivated by the circadian signal from the suprachiasmatic nucleus and/or external stimuli (alarm clock). Orexin projections to the thalamocortical neurons also can account for their transition from tonic firing activity during wakefulness to synchronized burst discharges during sleep.

Efficient Spike-Coding with Multiplicative Adaptation in a Spike Response Model

NARCIS (Netherlands)

S.M. Bohte (Sander)

2012-01-01

htmlabstractNeural adaptation underlies the ability of neurons to maximize encoded informa- tion over a wide dynamic range of input stimuli. While adaptation is an intrinsic feature of neuronal models like the Hodgkin-Huxley model, the challenge is to in- tegrate adaptation in models of neural

Computer Modelling of Functional Aspects of Noise in Endogenously Oscillating Neurons

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Huber, M. T.; Dewald, M.; Voigt, K.; Braun, H. A.; Moss, F.

1998-03-01

Membrane potential oscillations are a widespread feature of neuronal activity. When such oscillations operate close to the spike-triggering threshold, noise can become an essential property of spike-generation. According to that, we developed a minimal Hodgkin-Huxley-type computer model which includes a noise term. This model accounts for experimental data from quite different cells ranging from mammalian cortical neurons to fish electroreceptors. With slight modifications of the parameters, the model's behavior can be tuned to bursting activity, which additionally allows it to mimick temperature encoding in peripheral cold receptors including transitions to apparently chaotic dynamics as indicated by methods for the detection of unstable periodic orbits. Under all conditions, cooperative effects between noise and nonlinear dynamics can be shown which, beyond stochastic resonance, might be of functional significance for stimulus encoding and neuromodulation.

Numerical simulations of piecewise deterministic Markov processes with an application to the stochastic Hodgkin-Huxley model

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Ding, Shaojie; Qian, Min; Qian, Hong; Zhang, Xuejuan

2016-12-01

The stochastic Hodgkin-Huxley model is one of the best-known examples of piecewise deterministic Markov processes (PDMPs), in which the electrical potential across a cell membrane, V(t), is coupled with a mesoscopic Markov jump process representing the stochastic opening and closing of ion channels embedded in the membrane. The rates of the channel kinetics, in turn, are voltage-dependent. Due to this interdependence, an accurate and efficient sampling of the time evolution of the hybrid stochastic systems has been challenging. The current exact simulation methods require solving a voltage-dependent hitting time problem for multiple path-dependent intensity functions with random thresholds. This paper proposes a simulation algorithm that approximates an alternative representation of the exact solution by fitting the log-survival function of the inter-jump dwell time, H(t), with a piecewise linear one. The latter uses interpolation points that are chosen according to the time evolution of the H(t), as the numerical solution to the coupled ordinary differential equations of V(t) and H(t). This computational method can be applied to all PDMPs. Pathwise convergence of the approximated sample trajectories to the exact solution is proven, and error estimates are provided. Comparison with a previous algorithm that is based on piecewise constant approximation is also presented.

Neuromorphic silicon neuron circuits

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Giacomo eIndiveri

2011-05-01

Full Text Available Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance based Hodgkin-Huxley models to bi-dimensional generalized adaptive Integrate and Fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips.

Energy consumption in Hodgkin–Huxley type fast spiking neuron model exposed to an external electric field

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K. Usha

2016-09-01

Full Text Available This paper evaluates the change in metabolic energy required to maintain the signalling activity of neurons in the presence of an external electric field. We have analysed the Hodgkin–Huxley type conductance based fast spiking neuron model as electrical circuit by changing the frequency and amplitude of the applied electric field. The study has shown that, the presence of electric field increases the membrane potential, electrical energy supply and metabolic energy consumption. As the amplitude of applied electric field increases by keeping a constant frequency, the membrane potential increases and consequently the electrical energy supply and metabolic energy consumption increases. On increasing the frequency of the applied field, the peak value of membrane potential after depolarization gradually decreases as a result electrical energy supply decreases which results in a lower rate of hydrolysis of ATP molecules.

Bistability induces episodic spike communication by inhibitory neurons in neuronal networks.

Science.gov (United States)

Kazantsev, V B; Asatryan, S Yu

2011-09-01

Bistability is one of the important features of nonlinear dynamical systems. In neurodynamics, bistability has been found in basic Hodgkin-Huxley equations describing the cell membrane dynamics. When the neuron is clamped near its threshold, the stable rest potential may coexist with the stable limit cycle describing periodic spiking. However, this effect is often neglected in network computations where the neurons are typically reduced to threshold firing units (e.g., integrate-and-fire models). We found that the bistability may induce spike communication by inhibitory coupled neurons in the spiking network. The communication is realized in the form of episodic discharges with synchronous (correlated) spikes during the episodes. A spiking phase map is constructed to describe the synchronization and to estimate basic spike phase locking modes.

Biophysically realistic minimal model of dopamine neuron

Science.gov (United States)

Oprisan, Sorinel

2008-03-01

We proposed and studied a new biophysically relevant computational model of dopaminergic neurons. Midbrain dopamine neurons are involved in motivation and the control of movement, and have been implicated in various pathologies such as Parkinson's disease, schizophrenia, and drug abuse. The model we developed is a single-compartment Hodgkin-Huxley (HH)-type parallel conductance membrane model. The model captures the essential mechanisms underlying the slow oscillatory potentials and plateau potential oscillations. The main currents involved are: 1) a voltage-dependent fast calcium current, 2) a small conductance potassium current that is modulated by the cytosolic concentration of calcium, and 3) a slow voltage-activated potassium current. We developed multidimensional bifurcation diagrams and extracted the effective domains of sustained oscillations. The model includes a calcium balance due to the fundamental importance of calcium influx as proved by simultaneous electrophysiological and calcium imaging procedure. Although there are significant evidences to suggest a partially electrogenic calcium pump, all previous models considered only elecrtogenic pumps. We investigated the effect of the electrogenic calcium pump on the bifurcation diagram of the model and compared our findings against the experimental results.

Comparison of Langevin and Markov channel noise models for neuronal signal generation.

Science.gov (United States)

Sengupta, B; Laughlin, S B; Niven, J E

2010-01-01

The stochastic opening and closing of voltage-gated ion channels produce noise in neurons. The effect of this noise on the neuronal performance has been modeled using either an approximate or Langevin model based on stochastic differential equations or an exact model based on a Markov process model of channel gating. Yet whether the Langevin model accurately reproduces the channel noise produced by the Markov model remains unclear. Here we present a comparison between Langevin and Markov models of channel noise in neurons using single compartment Hodgkin-Huxley models containing either Na+ and K+, or only K+ voltage-gated ion channels. The performance of the Langevin and Markov models was quantified over a range of stimulus statistics, membrane areas, and channel numbers. We find that in comparison to the Markov model, the Langevin model underestimates the noise contributed by voltage-gated ion channels, overestimating information rates for both spiking and nonspiking membranes. Even with increasing numbers of channels, the difference between the two models persists. This suggests that the Langevin model may not be suitable for accurately simulating channel noise in neurons, even in simulations with large numbers of ion channels.

Spiking Regularity and Coherence in Complex Hodgkin–Huxley Neuron Networks

International Nuclear Information System (INIS)

Zhi-Qiang, Sun; Ping, Xie; Wei, Li; Peng-Ye, Wang

2010-01-01

We study the effects of the strength of coupling between neurons on the spiking regularity and coherence in a complex network with randomly connected Hodgkin–Huxley neurons driven by colored noise. It is found that for the given topology realization and colored noise correlation time, there exists an optimal strength of coupling, at which the spiking regularity of the network reaches the best level. Moreover, when the temporal regularity reaches the best level, the spatial coherence of the system has already increased to a relatively high level. In addition, for the given number of neurons and noise correlation time, the values of average regularity and spatial coherence at the optimal strength of coupling are nearly independent of the topology realization. Furthermore, there exists an optimal value of colored noise correlation time at which the spiking regularity can reach its best level. These results may be helpful for understanding of the real neuron world. (cross-disciplinary physics and related areas of science and technology)

Controlling Chaos in Neuron Based on Lasalle Invariance Principle

International Nuclear Information System (INIS)

Wei Duqu; Qin Yinghua

2011-01-01

A new control law is proposed to asymptotically stabilize the chaotic neuron system based on LaSalle invariant principle. The control technique does not require analytical knowledge of the system dynamics and operates without an explicit knowledge of the desired steady-state position. The well-known modified Hodgkin-Huxley (MHH) and Hindmarsh-Rose (HR) model neurons are taken as examples to verify the implementation of our method. Simulation results show the proposed control law is effective. The outcome of this study is significant since it is helpful to understand the learning process of a human brain towards the information processing, memory and abnormal discharge of the brain neurons. (general)

A chimeric path to neuronal synchronization

Science.gov (United States)

Essaki Arumugam, Easwara Moorthy; Spano, Mark L.

2015-01-01

Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an "all or none" phenomenon, but can pass through an intermediate stage (chimera).

A chimeric path to neuronal synchronization

Energy Technology Data Exchange (ETDEWEB)

Essaki Arumugam, Easwara Moorthy; Spano, Mark L. [School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287-9709 (United States)

2015-01-15

Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an “all or none” phenomenon, but can pass through an intermediate stage (chimera)

A chimeric path to neuronal synchronization

International Nuclear Information System (INIS)

Essaki Arumugam, Easwara Moorthy; Spano, Mark L.

2015-01-01

Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an “all or none” phenomenon, but can pass through an intermediate stage (chimera)

Non-linear leak currents affect mammalian neuron physiology

Directory of Open Access Journals (Sweden)

Shiwei eHuang

2015-11-01

Full Text Available In their seminal works on squid giant axons, Hodgkin and Huxley approximated the membrane leak current as Ohmic, i.e. linear, since in their preparation, sub-threshold current rectification due to the influence of ionic concentration is negligible. Most studies on mammalian neurons have made the same, largely untested, assumption. Here we show that the membrane time constant and input resistance of mammalian neurons (when other major voltage-sensitive and ligand-gated ionic currents are discounted varies non-linearly with membrane voltage, following the prediction of a Goldman-Hodgkin-Katz-based passive membrane model. The model predicts that under such conditions, the time constant/input resistance-voltage relationship will linearize if the concentration differences across the cell membrane are reduced. These properties were observed in patch-clamp recordings of cerebellar Purkinje neurons (in the presence of pharmacological blockers of other background ionic currents and were more prominent in the sub-threshold region of the membrane potential. Model simulations showed that the non-linear leak affects voltage-clamp recordings and reduces temporal summation of excitatory synaptic input. Together, our results demonstrate the importance of trans-membrane ionic concentration in defining the functional properties of the passive membrane in mammalian neurons as well as other excitable cells.

APPLICATION OF UKRAINIAN GRID INFRASTRUCTURE FOR INVESTIGATION OF NONLINEAR DYNAMICS IN LARGE NEURONAL NETWORKS

Directory of Open Access Journals (Sweden)

O. О. Sudakov

2015-12-01

Full Text Available In present work the Ukrainian National Grid (UNG infrastructure was applied for investigation of synchronization in large networks of interacting neurons. This application is important for solving of modern neuroscience problems related to mechanisms of nervous system activities (memory, cognition etc. and nervous pathologies (epilepsy, Parkinsonism, etc.. Modern non-linear dynamics theories and applications provides powerful basis for computer simulations of biological neuronal networks and investigation of phenomena which mechanisms hardly could be clarified by other approaches. Cubic millimeter of brain tissue contains about 105 neurons, so realistic (Hodgkin-Huxley model and phenomenological (Kuramoto-Sakaguchi, FitzHugh-Nagumo, etc. models simulations require consideration of large neurons numbers.

Increasing inhibitory input increases neuronal firing rate: why and when? Diffusion process cases

Energy Technology Data Exchange (ETDEWEB)

Feng Jianfeng [COGS, Sussex University (United Kingdom)]. E-mail: jf218@cam.ac.uk; Wei Gang [Department of Mathematics, Hong Kong Baptist University, Hong Kong (China)]. E-mail gwei@math.hkbu.edu.hk

2001-09-21

Increasing inhibitory input to single neuronal models, such as the FitzHugh-Nagumo model and the Hodgkin-Huxley model, can sometimes increase their firing rates, a phenomenon which we term inhibition-boosted firing (IBF). Here we consider neuronal models with diffusion approximation inputs, i.e. they share the identical first- and second-order statistics of the corresponding Poisson process inputs. Using the integrate-and-fire model and the IF-FHN model, we explore theoretically how and when IBF can happen. For both models, it is shown that there is a critical input frequency at which the efferent firing rate is identical when the neuron receives purely excitatory inputs or exactly balanced inhibitory and excitatory inputs. When the input frequency is lower than the critical frequency, IBF occurs. (author)

Mode-locking behavior of Izhikevich neurons under periodic external forcing

Science.gov (United States)

Farokhniaee, AmirAli; Large, Edward W.

2017-06-01

Many neurons in the auditory system of the brain must encode periodic signals. These neurons under periodic stimulation display rich dynamical states including mode locking and chaotic responses. Periodic stimuli such as sinusoidal waves and amplitude modulated sounds can lead to various forms of n :m mode-locked states, in which a neuron fires n action potentials per m cycles of the stimulus. Here, we study mode-locking in the Izhikevich neurons, a reduced model of the Hodgkin-Huxley neurons. The Izhikevich model is much simpler in terms of the dimension of the coupled nonlinear differential equations compared with other existing models, but excellent for generating the complex spiking patterns observed in real neurons. We obtained the regions of existence of the various mode-locked states on the frequency-amplitude plane, called Arnold tongues, for the Izhikevich neurons. Arnold tongue analysis provides useful insight into the organization of mode-locking behavior of neurons under periodic forcing. We find these tongues for both class-1 and class-2 excitable neurons in both deterministic and noisy regimes.

Colored noise and memory effects on formal spiking neuron models

Science.gov (United States)

da Silva, L. A.; Vilela, R. D.

2015-06-01

Simplified neuronal models capture the essence of the electrical activity of a generic neuron, besides being more interesting from the computational point of view when compared to higher-dimensional models such as the Hodgkin-Huxley one. In this work, we propose a generalized resonate-and-fire model described by a generalized Langevin equation that takes into account memory effects and colored noise. We perform a comprehensive numerical analysis to study the dynamics and the point process statistics of the proposed model, highlighting interesting new features such as (i) nonmonotonic behavior (emergence of peak structures, enhanced by the choice of colored noise characteristic time scale) of the coefficient of variation (CV) as a function of memory characteristic time scale, (ii) colored noise-induced shift in the CV, and (iii) emergence and suppression of multimodality in the interspike interval (ISI) distribution due to memory-induced subthreshold oscillations. Moreover, in the noise-induced spike regime, we study how memory and colored noise affect the coherence resonance (CR) phenomenon. We found that for sufficiently long memory, not only is CR suppressed but also the minimum of the CV-versus-noise intensity curve that characterizes the presence of CR may be replaced by a maximum. The aforementioned features allow to interpret the interplay between memory and colored noise as an effective control mechanism to neuronal variability. Since both variability and nontrivial temporal patterns in the ISI distribution are ubiquitous in biological cells, we hope the present model can be useful in modeling real aspects of neurons.

Multi-timescale Modeling of Activity-Dependent Metabolic Coupling in the Neuron-Glia-Vasculature Ensemble

KAUST Repository

Jolivet, Renaud

2015-02-26

Glucose is the main energy substrate in the adult brain under normal conditions. Accumulating evidence, however, indicates that lactate produced in astrocytes (a type of glial cell) can also fuel neuronal activity. The quantitative aspects of this so-called astrocyte-neuron lactate shuttle (ANLS) are still debated. To address this question, we developed a detailed biophysical model of the brain’s metabolic interactions. Our model integrates three modeling approaches, the Buxton-Wang model of vascular dynamics, the Hodgkin-Huxley formulation of neuronal membrane excitability and a biophysical model of metabolic pathways. This approach provides a template for large-scale simulations of the neuron-glia-vasculature (NGV) ensemble, and for the first time integrates the respective timescales at which energy metabolism and neuronal excitability occur. The model is constrained by relative neuronal and astrocytic oxygen and glucose utilization, by the concentration of metabolites at rest and by the temporal dynamics of NADH upon activation. These constraints produced four observations. First, a transfer of lactate from astrocytes to neurons emerged in response to activity. Second, constrained by activity-dependent NADH transients, neuronal oxidative metabolism increased first upon activation with a subsequent delayed astrocytic glycolysis increase. Third, the model correctly predicted the dynamics of extracellular lactate and oxygen as observed in vivo in rats. Fourth, the model correctly predicted the temporal dynamics of tissue lactate, of tissue glucose and oxygen consumption, and of the BOLD signal as reported in human studies. These findings not only support the ANLS hypothesis but also provide a quantitative mathematical description of the metabolic activation in neurons and glial cells, as well as of the macroscopic measurements obtained during brain imaging.

Multi-timescale Modeling of Activity-Dependent Metabolic Coupling in the Neuron-Glia-Vasculature Ensemble

Science.gov (United States)

Jolivet, Renaud; Coggan, Jay S.; Allaman, Igor; Magistretti, Pierre J.

2015-01-01

Glucose is the main energy substrate in the adult brain under normal conditions. Accumulating evidence, however, indicates that lactate produced in astrocytes (a type of glial cell) can also fuel neuronal activity. The quantitative aspects of this so-called astrocyte-neuron lactate shuttle (ANLS) are still debated. To address this question, we developed a detailed biophysical model of the brain’s metabolic interactions. Our model integrates three modeling approaches, the Buxton-Wang model of vascular dynamics, the Hodgkin-Huxley formulation of neuronal membrane excitability and a biophysical model of metabolic pathways. This approach provides a template for large-scale simulations of the neuron-glia-vasculature (NGV) ensemble, and for the first time integrates the respective timescales at which energy metabolism and neuronal excitability occur. The model is constrained by relative neuronal and astrocytic oxygen and glucose utilization, by the concentration of metabolites at rest and by the temporal dynamics of NADH upon activation. These constraints produced four observations. First, a transfer of lactate from astrocytes to neurons emerged in response to activity. Second, constrained by activity-dependent NADH transients, neuronal oxidative metabolism increased first upon activation with a subsequent delayed astrocytic glycolysis increase. Third, the model correctly predicted the dynamics of extracellular lactate and oxygen as observed in vivo in rats. Fourth, the model correctly predicted the temporal dynamics of tissue lactate, of tissue glucose and oxygen consumption, and of the BOLD signal as reported in human studies. These findings not only support the ANLS hypothesis but also provide a quantitative mathematical description of the metabolic activation in neurons and glial cells, as well as of the macroscopic measurements obtained during brain imaging. PMID:25719367

Multi-timescale modeling of activity-dependent metabolic coupling in the neuron-glia-vasculature ensemble.

Directory of Open Access Journals (Sweden)

Renaud Jolivet

2015-02-01

Full Text Available Glucose is the main energy substrate in the adult brain under normal conditions. Accumulating evidence, however, indicates that lactate produced in astrocytes (a type of glial cell can also fuel neuronal activity. The quantitative aspects of this so-called astrocyte-neuron lactate shuttle (ANLS are still debated. To address this question, we developed a detailed biophysical model of the brain's metabolic interactions. Our model integrates three modeling approaches, the Buxton-Wang model of vascular dynamics, the Hodgkin-Huxley formulation of neuronal membrane excitability and a biophysical model of metabolic pathways. This approach provides a template for large-scale simulations of the neuron-glia-vasculature (NGV ensemble, and for the first time integrates the respective timescales at which energy metabolism and neuronal excitability occur. The model is constrained by relative neuronal and astrocytic oxygen and glucose utilization, by the concentration of metabolites at rest and by the temporal dynamics of NADH upon activation. These constraints produced four observations. First, a transfer of lactate from astrocytes to neurons emerged in response to activity. Second, constrained by activity-dependent NADH transients, neuronal oxidative metabolism increased first upon activation with a subsequent delayed astrocytic glycolysis increase. Third, the model correctly predicted the dynamics of extracellular lactate and oxygen as observed in vivo in rats. Fourth, the model correctly predicted the temporal dynamics of tissue lactate, of tissue glucose and oxygen consumption, and of the BOLD signal as reported in human studies. These findings not only support the ANLS hypothesis but also provide a quantitative mathematical description of the metabolic activation in neurons and glial cells, as well as of the macroscopic measurements obtained during brain imaging.

Acceleration of spiking neural network based pattern recognition on NVIDIA graphics processors.

Science.gov (United States)

Han, Bing; Taha, Tarek M

2010-04-01

There is currently a strong push in the research community to develop biological scale implementations of neuron based vision models. Systems at this scale are computationally demanding and generally utilize more accurate neuron models, such as the Izhikevich and the Hodgkin-Huxley models, in favor of the more popular integrate and fire model. We examine the feasibility of using graphics processing units (GPUs) to accelerate a spiking neural network based character recognition network to enable such large scale systems. Two versions of the network utilizing the Izhikevich and Hodgkin-Huxley models are implemented. Three NVIDIA general-purpose (GP) GPU platforms are examined, including the GeForce 9800 GX2, the Tesla C1060, and the Tesla S1070. Our results show that the GPGPUs can provide significant speedup over conventional processors. In particular, the fastest GPGPU utilized, the Tesla S1070, provided a speedup of 5.6 and 84.4 over highly optimized implementations on the fastest central processing unit (CPU) tested, a quadcore 2.67 GHz Xeon processor, for the Izhikevich and the Hodgkin-Huxley models, respectively. The CPU implementation utilized all four cores and the vector data parallelism offered by the processor. The results indicate that GPUs are well suited for this application domain.

A multiscale approach to modelling electrochemical processes occurring across the cell membrane with application to transmission of action potentials.

Science.gov (United States)

Richardson, G

2009-09-01

By application of matched asymptotic expansions, a simplified partial differential equation (PDE) model for the dynamic electrochemical processes occurring in the vicinity of a membrane, as ions selectively permeate across it, is formally derived from the Poisson-Nernst-Planck equations of electrochemistry. It is demonstrated that this simplified model reduces itself, in the limit of a long thin axon, to the cable equation used by Hodgkin and Huxley to describe the propagation of action potentials in the unmyelinated squid giant axon. The asymptotic reduction from the simplified PDE model to the cable equation leads to insights that are not otherwise apparent; these include an explanation of why the squid giant axon attains a diameter in the region of 1 mm. The simplified PDE model has more general application than the Hodgkin-Huxley cable equation and can, e.g. be used to describe action potential propagation in myelinated axons and neuronal cell bodies.

Inverse stochastic resonance in networks of spiking neurons.

Science.gov (United States)

Uzuntarla, Muhammet; Barreto, Ernest; Torres, Joaquin J

2017-07-01

Inverse Stochastic Resonance (ISR) is a phenomenon in which the average spiking rate of a neuron exhibits a minimum with respect to noise. ISR has been studied in individual neurons, but here, we investigate ISR in scale-free networks, where the average spiking rate is calculated over the neuronal population. We use Hodgkin-Huxley model neurons with channel noise (i.e., stochastic gating variable dynamics), and the network connectivity is implemented via electrical or chemical connections (i.e., gap junctions or excitatory/inhibitory synapses). We find that the emergence of ISR depends on the interplay between each neuron's intrinsic dynamical structure, channel noise, and network inputs, where the latter in turn depend on network structure parameters. We observe that with weak gap junction or excitatory synaptic coupling, network heterogeneity and sparseness tend to favor the emergence of ISR. With inhibitory coupling, ISR is quite robust. We also identify dynamical mechanisms that underlie various features of this ISR behavior. Our results suggest possible ways of experimentally observing ISR in actual neuronal systems.

Chaos control and synchronization of two neurons exposed to ELF external electric field

International Nuclear Information System (INIS)

Wang Jiang; Zhang Ting; Che Yanqiu

2007-01-01

Chaos control and synchronization of two unidirectional coupled neurons exposed to ELF electrical field via nonlinear control technique is investigated. Based on results of space-time characteristics of trans-membrane voltage, the variation of cell trans-membrane voltage exposed to extremely low frequency (ELF) electric field is analyzed. The dynamical behaviors of the modified Hodgkin-Huxley (HH) model are identified under the periodic ELF electric field using both analytical and numerical analysis. Then, using the results of the analysis, a nonlinear feedback linearization control scheme and a modified adaptive control strategy are designed to synchronize the two unidirectional coupled neurons and stabilize the chaotic trajectory of the slave system to desired periodic orbit of the master system. The simulation results demonstrated the efficiency of the proposed algorithms

Studies of phase return map and symbolic dynamics in a periodically driven Hodgkin—Huxley neuron

International Nuclear Information System (INIS)

Ding Jiong; Zhang Hong; Tong Qin-Ye; Chen Zhuo

2014-01-01

How neuronal spike trains encode external information is a hot topic in neurodynamics studies. In this paper, we investigate the dynamical states of the Hodgkin—Huxley neuron under periodic forcing. Depending on the parameters of the stimulus, the neuron exhibits periodic, quasiperiodic and chaotic spike trains. In order to analyze these spike trains quantitatively, we use the phase return map to describe the dynamical behavior on a one-dimensional (1D) map. According to the monotonicity or discontinuous point of the 1D map, the spike trains are transformed into symbolic sequences by implementing a coarse-grained algorithm — symbolic dynamics. Based on the ordering rules of symbolic dynamics, the parameters of the external stimulus can be measured in high resolution with finite length symbolic sequences. A reasonable explanation for why the nervous system can discriminate or cognize the small change of the external signals in a short time is also presented. (general)

Weak noise in neurons may powerfully inhibit the generation of repetitive spiking but not its propagation.

Directory of Open Access Journals (Sweden)

Henry C Tuckwell

2010-05-01

Full Text Available Many neurons have epochs in which they fire action potentials in an approximately periodic fashion. To see what effects noise of relatively small amplitude has on such repetitive activity we recently examined the response of the Hodgkin-Huxley (HH space-clamped system to such noise as the mean and variance of the applied current vary, near the bifurcation to periodic firing. This article is concerned with a more realistic neuron model which includes spatial extent. Employing the Hodgkin-Huxley partial differential equation system, the deterministic component of the input current is restricted to a small segment whereas the stochastic component extends over a region which may or may not overlap the deterministic component. For mean values below, near and above the critical values for repetitive spiking, the effects of weak noise of increasing strength is ascertained by simulation. As in the point model, small amplitude noise near the critical value dampens the spiking activity and leads to a minimum as noise level increases. This was the case for both additive noise and conductance-based noise. Uniform noise along the whole neuron is only marginally more effective in silencing the cell than noise which occurs near the region of excitation. In fact it is found that if signal and noise overlap in spatial extent, then weak noise may inhibit spiking. If, however, signal and noise are applied on disjoint intervals, then the noise has no effect on the spiking activity, no matter how large its region of application, though the trajectories are naturally altered slightly by noise. Such effects could not be discerned in a point model and are important for real neuron behavior. Interference with the spike train does nevertheless occur when the noise amplitude is larger, even when noise and signal do not overlap, being due to the instigation of secondary noise-induced wave phenomena rather than switching the system from one attractor (firing regularly to

First-spike latency in Hodgkin's three classes of neurons.

Science.gov (United States)

Wang, Hengtong; Chen, Yueling; Chen, Yong

2013-07-07

We study the first-spike latency (FSL) in Hodgkin's three classes of neurons with the Morris-Lecar neuron model. It is found that all the three classes of neurons can encode an external stimulus into FSLs. With DC inputs, the FSLs of all of the neurons decrease with input intensity. With input current decreased to the threshold, class 1 neurons show an arbitrary long FSL whereas class 2 and 3 neurons exhibit the short-limit FSLs. When the input current is sinusoidal, the amplitude, frequency and initial phase can be encoded by all the three classes of neurons. The FSLs of all of the neurons decrease with the input amplitude and frequency. When the input frequency is too high, all of the neurons respond with infinite FSLs. When the initial phase increases, the FSL decreases and then jumps to a maximal value and finally decreases linearly. With changes in the input parameters, the FSLs of the class 1 and 2 neurons exhibit similar properties. However, the FSL of the class 3 neurons became slightly longer and only produces responses for a narrow range of initial phase if input frequencies are low. Moreover, our results also show that the FSL and firing rate responses are mutually independent processes and that neurons can encode an external stimulus into different FSLs and firing rates simultaneously. This finding is consistent with the current theory of dual or multiple complementary coding mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of channel noise on firing coherence of small-world Hodgkin-Huxley neuronal networks

Science.gov (United States)

Sun, X. J.; Lei, J. Z.; Perc, M.; Lu, Q. S.; Lv, S. J.

2011-01-01

We investigate the effects of channel noise on firing coherence of Watts-Strogatz small-world networks consisting of biophysically realistic HH neurons having a fraction of blocked voltage-gated sodium and potassium ion channels embedded in their neuronal membranes. The intensity of channel noise is determined by the number of non-blocked ion channels, which depends on the fraction of working ion channels and the membrane patch size with the assumption of homogeneous ion channel density. We find that firing coherence of the neuronal network can be either enhanced or reduced depending on the source of channel noise. As shown in this paper, sodium channel noise reduces firing coherence of neuronal networks; in contrast, potassium channel noise enhances it. Furthermore, compared with potassium channel noise, sodium channel noise plays a dominant role in affecting firing coherence of the neuronal network. Moreover, we declare that the observed phenomena are independent of the rewiring probability.

From Knights Corner to Landing: a Case Study Based on a Hodgkin-Huxley Neuron Simulator

OpenAIRE

George Chatzikonstantis; Diego Jiménez; Esteban Meneses; Christos Strydis; Harry Sidiropoulos; Dimitrios Soudris

2017-01-01

Brain modeling has been presenting significant challenges to the world of high-performance computing (HPC) over the years. The field of computational neuroscience has been developing a demand for physiologically plausible neuron models, that feature increased complexity and thus, require greater computational power. We explore Intel’s newest generation of Xeon Phi computing platforms, named Knights Landing (KNL), as a way to match the need for processing power and as an upgrade over the previ...

Correlated conductance parameters in leech heart motor neurons contribute to motor pattern formation.

Science.gov (United States)

Lamb, Damon G; Calabrese, Ronald L

2013-01-01

Neurons can have widely differing intrinsic membrane properties, in particular the density of specific conductances, but how these contribute to characteristic neuronal activity or pattern formation is not well understood. To explore the relationship between conductances, and in particular how they influence the activity of motor neurons in the well characterized leech heartbeat system, we developed a new multi-compartmental Hodgkin-Huxley style leech heart motor neuron model. To do so, we evolved a population of model instances, which differed in the density of specific conductances, capable of achieving specific output activity targets given an associated input pattern. We then examined the sensitivity of measures of output activity to conductances and how the model instances responded to hyperpolarizing current injections. We found that the strengths of many conductances, including those with differing dynamics, had strong partial correlations and that these relationships appeared to be linked by their influence on heart motor neuron activity. Conductances that had positive correlations opposed one another and had the opposite effects on activity metrics when perturbed whereas conductances that had negative correlations could compensate for one another and had similar effects on activity metrics.

Autaptic pacemaker mediated propagation of weak rhythmic activity across small-world neuronal networks

Science.gov (United States)

Yilmaz, Ergin; Baysal, Veli; Ozer, Mahmut; Perc, Matjaž

2016-02-01

We study the effects of an autapse, which is mathematically described as a self-feedback loop, on the propagation of weak, localized pacemaker activity across a Newman-Watts small-world network consisting of stochastic Hodgkin-Huxley neurons. We consider that only the pacemaker neuron, which is stimulated by a subthreshold periodic signal, has an electrical autapse that is characterized by a coupling strength and a delay time. We focus on the impact of the coupling strength, the network structure, the properties of the weak periodic stimulus, and the properties of the autapse on the transmission of localized pacemaker activity. Obtained results indicate the existence of optimal channel noise intensity for the propagation of the localized rhythm. Under optimal conditions, the autapse can significantly improve the propagation of pacemaker activity, but only for a specific range of the autaptic coupling strength. Moreover, the autaptic delay time has to be equal to the intrinsic oscillation period of the Hodgkin-Huxley neuron or its integer multiples. We analyze the inter-spike interval histogram and show that the autapse enhances or suppresses the propagation of the localized rhythm by increasing or decreasing the phase locking between the spiking of the pacemaker neuron and the weak periodic signal. In particular, when the autaptic delay time is equal to the intrinsic period of oscillations an optimal phase locking takes place, resulting in a dominant time scale of the spiking activity. We also investigate the effects of the network structure and the coupling strength on the propagation of pacemaker activity. We find that there exist an optimal coupling strength and an optimal network structure that together warrant an optimal propagation of the localized rhythm.

Toward Petascale Biologically Plausible Neural Networks

Science.gov (United States)

Long, Lyle

This talk will describe an approach to achieving petascale neural networks. Artificial intelligence has been oversold for many decades. Computers in the beginning could only do about 16,000 operations per second. Computer processing power, however, has been doubling every two years thanks to Moore's law, and growing even faster due to massively parallel architectures. Finally, 60 years after the first AI conference we have computers on the order of the performance of the human brain (1016 operations per second). The main issues now are algorithms, software, and learning. We have excellent models of neurons, such as the Hodgkin-Huxley model, but we do not know how the human neurons are wired together. With careful attention to efficient parallel computing, event-driven programming, table lookups, and memory minimization massive scale simulations can be performed. The code that will be described was written in C + + and uses the Message Passing Interface (MPI). It uses the full Hodgkin-Huxley neuron model, not a simplified model. It also allows arbitrary network structures (deep, recurrent, convolutional, all-to-all, etc.). The code is scalable, and has, so far, been tested on up to 2,048 processor cores using 107 neurons and 109 synapses.

Switching neuronal state: optimal stimuli revealed using a stochastically-seeded gradient algorithm.

Science.gov (United States)

Chang, Joshua; Paydarfar, David

2014-12-01

Inducing a switch in neuronal state using energy optimal stimuli is relevant to a variety of problems in neuroscience. Analytical techniques from optimal control theory can identify such stimuli; however, solutions to the optimization problem using indirect variational approaches can be elusive in models that describe neuronal behavior. Here we develop and apply a direct gradient-based optimization algorithm to find stimulus waveforms that elicit a change in neuronal state while minimizing energy usage. We analyze standard models of neuronal behavior, the Hodgkin-Huxley and FitzHugh-Nagumo models, to show that the gradient-based algorithm: (1) enables automated exploration of a wide solution space, using stochastically generated initial waveforms that converge to multiple locally optimal solutions; and (2) finds optimal stimulus waveforms that achieve a physiological outcome condition, without a priori knowledge of the optimal terminal condition of all state variables. Analysis of biological systems using stochastically-seeded gradient methods can reveal salient dynamical mechanisms underlying the optimal control of system behavior. The gradient algorithm may also have practical applications in future work, for example, finding energy optimal waveforms for therapeutic neural stimulation that minimizes power usage and diminishes off-target effects and damage to neighboring tissue.

Synaptic Plasticity and Spike Synchronisation in Neuronal Networks

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Borges, Rafael R.; Borges, Fernando S.; Lameu, Ewandson L.; Protachevicz, Paulo R.; Iarosz, Kelly C.; Caldas, Iberê L.; Viana, Ricardo L.; Macau, Elbert E. N.; Baptista, Murilo S.; Grebogi, Celso; Batista, Antonio M.

2017-12-01

Brain plasticity, also known as neuroplasticity, is a fundamental mechanism of neuronal adaptation in response to changes in the environment or due to brain injury. In this review, we show our results about the effects of synaptic plasticity on neuronal networks composed by Hodgkin-Huxley neurons. We show that the final topology of the evolved network depends crucially on the ratio between the strengths of the inhibitory and excitatory synapses. Excitation of the same order of inhibition revels an evolved network that presents the rich-club phenomenon, well known to exist in the brain. For initial networks with considerably larger inhibitory strengths, we observe the emergence of a complex evolved topology, where neurons sparsely connected to other neurons, also a typical topology of the brain. The presence of noise enhances the strength of both types of synapses, but if the initial network has synapses of both natures with similar strengths. Finally, we show how the synchronous behaviour of the evolved network will reflect its evolved topology.

Electrosensory Midbrain Neurons Display Feature Invariant Responses to Natural Communication Stimuli.

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Tristan Aumentado-Armstrong

2015-10-01

Full Text Available Neurons that respond selectively but in an invariant manner to a given feature of natural stimuli have been observed across species and systems. Such responses emerge in higher brain areas, thereby suggesting that they occur by integrating afferent input. However, the mechanisms by which such integration occurs are poorly understood. Here we show that midbrain electrosensory neurons can respond selectively and in an invariant manner to heterogeneity in behaviorally relevant stimulus waveforms. Such invariant responses were not seen in hindbrain electrosensory neurons providing afferent input to these midbrain neurons, suggesting that response invariance results from nonlinear integration of such input. To test this hypothesis, we built a model based on the Hodgkin-Huxley formalism that received realistic afferent input. We found that multiple combinations of parameter values could give rise to invariant responses matching those seen experimentally. Our model thus shows that there are multiple solutions towards achieving invariant responses and reveals how subthreshold membrane conductances help promote robust and invariant firing in response to heterogeneous stimulus waveforms associated with behaviorally relevant stimuli. We discuss the implications of our findings for the electrosensory and other systems.

Electrosensory Midbrain Neurons Display Feature Invariant Responses to Natural Communication Stimuli.

Science.gov (United States)

Aumentado-Armstrong, Tristan; Metzen, Michael G; Sproule, Michael K J; Chacron, Maurice J

2015-10-01

Neurons that respond selectively but in an invariant manner to a given feature of natural stimuli have been observed across species and systems. Such responses emerge in higher brain areas, thereby suggesting that they occur by integrating afferent input. However, the mechanisms by which such integration occurs are poorly understood. Here we show that midbrain electrosensory neurons can respond selectively and in an invariant manner to heterogeneity in behaviorally relevant stimulus waveforms. Such invariant responses were not seen in hindbrain electrosensory neurons providing afferent input to these midbrain neurons, suggesting that response invariance results from nonlinear integration of such input. To test this hypothesis, we built a model based on the Hodgkin-Huxley formalism that received realistic afferent input. We found that multiple combinations of parameter values could give rise to invariant responses matching those seen experimentally. Our model thus shows that there are multiple solutions towards achieving invariant responses and reveals how subthreshold membrane conductances help promote robust and invariant firing in response to heterogeneous stimulus waveforms associated with behaviorally relevant stimuli. We discuss the implications of our findings for the electrosensory and other systems.

Emulating the electrical activity of the neuron using a silicon oxide RRAM cell

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Adnan eMehonic

2016-02-01

Full Text Available In recent years, formidable effort has been devoted to exploring the potential of Resistive RAM (RRAM devices to model key features of biological synapses. This is done to strengthen the link between neuro-computing architectures and neuroscience, bearing in mind the extremely low power consumption and immense parallelism of biological systems. Here we demonstrate the feasibility of using the RRAM cell to go further and to model aspects of the electrical activity of the neuron. We focus on the specific operational procedures required for the generation of controlled voltage transients, which resemble spike-like responses. Further, we demonstrate that RRAM devices are capable of integrating input current pulses over time to produce thresholded voltage transients. We show that the frequency of the output transients can be controlled by the input signal, and we relate recent models of the redox-based nanoionic resistive memory cell to two common neuronal models, the Hodgkin-Huxley (HH conductance model and the leaky integrate-and-fire model. We employ a simplified circuit model to phenomenologically describe voltage transient generation.

Emulating the Electrical Activity of the Neuron Using a Silicon Oxide RRAM Cell

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Mehonic, Adnan; Kenyon, Anthony J.

2016-01-01

In recent years, formidable effort has been devoted to exploring the potential of Resistive RAM (RRAM) devices to model key features of biological synapses. This is done to strengthen the link between neuro-computing architectures and neuroscience, bearing in mind the extremely low power consumption and immense parallelism of biological systems. Here we demonstrate the feasibility of using the RRAM cell to go further and to model aspects of the electrical activity of the neuron. We focus on the specific operational procedures required for the generation of controlled voltage transients, which resemble spike-like responses. Further, we demonstrate that RRAM devices are capable of integrating input current pulses over time to produce thresholded voltage transients. We show that the frequency of the output transients can be controlled by the input signal, and we relate recent models of the redox-based nanoionic resistive memory cell to two common neuronal models, the Hodgkin-Huxley (HH) conductance model and the leaky integrate-and-fire model. We employ a simplified circuit model to phenomenologically describe voltage transient generation. PMID:26941598

Assimilation of Biophysical Neuronal Dynamics in Neuromorphic VLSI.

Science.gov (United States)

Wang, Jun; Breen, Daniel; Akinin, Abraham; Broccard, Frederic; Abarbanel, Henry D I; Cauwenberghs, Gert

2017-12-01

Representing the biophysics of neuronal dynamics and behavior offers a principled analysis-by-synthesis approach toward understanding mechanisms of nervous system functions. We report on a set of procedures assimilating and emulating neurobiological data on a neuromorphic very large scale integrated (VLSI) circuit. The analog VLSI chip, NeuroDyn, features 384 digitally programmable parameters specifying for 4 generalized Hodgkin-Huxley neurons coupled through 12 conductance-based chemical synapses. The parameters also describe reversal potentials, maximal conductances, and spline regressed kinetic functions for ion channel gating variables. In one set of experiments, we assimilated membrane potential recorded from one of the neurons on the chip to the model structure upon which NeuroDyn was designed using the known current input sequence. We arrived at the programmed parameters except for model errors due to analog imperfections in the chip fabrication. In a related set of experiments, we replicated songbird individual neuron dynamics on NeuroDyn by estimating and configuring parameters extracted using data assimilation from intracellular neural recordings. Faithful emulation of detailed biophysical neural dynamics will enable the use of NeuroDyn as a tool to probe electrical and molecular properties of functional neural circuits. Neuroscience applications include studying the relationship between molecular properties of neurons and the emergence of different spike patterns or different brain behaviors. Clinical applications include studying and predicting effects of neuromodulators or neurodegenerative diseases on ion channel kinetics.

Effects of the network structure and coupling strength on the noise-induced response delay of a neuronal network

International Nuclear Information System (INIS)

Ozer, Mahmut; Uzuntarla, Muhammet

2008-01-01

The Hodgkin-Huxley (H-H) neuron model driven by stimuli just above threshold shows a noise-induced response delay with respect to time to the first spike for a certain range of noise strengths, an effect called 'noise delayed decay' (NDD). We study the response time of a network of coupled H-H neurons, and investigate how the NDD can be affected by the connection topology of the network and the coupling strength. We show that the NDD effect exists for weak and intermediate coupling strengths, whereas it disappears for strong coupling strength regardless of the connection topology. We also show that although the network structure has very little effect on the NDD for a weak coupling strength, the network structure plays a key role for an intermediate coupling strength by decreasing the NDD effect with the increasing number of random shortcuts, and thus provides an additional operating regime, that is absent in the regular network, in which the neurons may also exploit a spike time code

Bistable dynamics underlying excitability of ion homeostasis in neuron models.

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Niklas Hübel

2014-05-01

Full Text Available When neurons fire action potentials, dissipation of free energy is usually not directly considered, because the change in free energy is often negligible compared to the immense reservoir stored in neural transmembrane ion gradients and the long-term energy requirements are met through chemical energy, i.e., metabolism. However, these gradients can temporarily nearly vanish in neurological diseases, such as migraine and stroke, and in traumatic brain injury from concussions to severe injuries. We study biophysical neuron models based on the Hodgkin-Huxley (HH formalism extended to include time-dependent ion concentrations inside and outside the cell and metabolic energy-driven pumps. We reveal the basic mechanism of a state of free energy-starvation (FES with bifurcation analyses showing that ion dynamics is for a large range of pump rates bistable without contact to an ion bath. This is interpreted as a threshold reduction of a new fundamental mechanism of ionic excitability that causes a long-lasting but transient FES as observed in pathological states. We can in particular conclude that a coupling of extracellular ion concentrations to a large glial-vascular bath can take a role as an inhibitory mechanism crucial in ion homeostasis, while the Na⁺/K⁺ pumps alone are insufficient to recover from FES. Our results provide the missing link between the HH formalism and activator-inhibitor models that have been successfully used for modeling migraine phenotypes, and therefore will allow us to validate the hypothesis that migraine symptoms are explained by disturbed function in ion channel subunits, Na⁺/K⁺ pumps, and other proteins that regulate ion homeostasis.

Optimal physiological structure of small neurons to guarantee stable information processing

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Zeng, S. Y.; Zhang, Z. Z.; Wei, D. Q.; Luo, X. S.; Tang, W. Y.; Zeng, S. W.; Wang, R. F.

2013-02-01

Spike is the basic element for neuronal information processing and the spontaneous spiking frequency should be less than 1 Hz for stable information processing. If the neuronal membrane area is small, the frequency of neuronal spontaneous spiking caused by ion channel noise may be high. Therefore, it is important to suppress the deleterious spontaneous spiking of the small neurons. We find by simulation of stochastic neurons with Hodgkin-Huxley-type channels that the leakage system is critical and extremely efficient to suppress the spontaneous spiking and guarantee stable information processing of the small neurons. However, within the physiological limit the potassium system cannot do so. The suppression effect of the leakage system is super-exponential, but that of the potassium system is quasi-linear. With the minor physiological cost and the minimal consumption of metabolic energy, a slightly lower reversal potential and a relatively larger conductance of the leakage system give the optimal physiological structure to suppress the deleterious spontaneous spiking and guarantee stable information processing of small neurons, dendrites and axons.

Top-down inputs enhance orientation selectivity in neurons of the primary visual cortex during perceptual learning.

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Samat Moldakarimov

2014-08-01

Full Text Available Perceptual learning has been used to probe the mechanisms of cortical plasticity in the adult brain. Feedback projections are ubiquitous in the cortex, but little is known about their role in cortical plasticity. Here we explore the hypothesis that learning visual orientation discrimination involves learning-dependent plasticity of top-down feedback inputs from higher cortical areas, serving a different function from plasticity due to changes in recurrent connections within a cortical area. In a Hodgkin-Huxley-based spiking neural network model of visual cortex, we show that modulation of feedback inputs to V1 from higher cortical areas results in shunting inhibition in V1 neurons, which changes the response properties of V1 neurons. The orientation selectivity of V1 neurons is enhanced without changing orientation preference, preserving the topographic organizations in V1. These results provide new insights to the mechanisms of plasticity in the adult brain, reconciling apparently inconsistent experiments and providing a new hypothesis for a functional role of the feedback connections.

Model-based analysis and control of a network of basal ganglia spiking neurons in the normal and Parkinsonian states

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Liu, Jianbo; Khalil, Hassan K.; Oweiss, Karim G.

2011-08-01

Controlling the spatiotemporal firing pattern of an intricately connected network of neurons through microstimulation is highly desirable in many applications. We investigated in this paper the feasibility of using a model-based approach to the analysis and control of a basal ganglia (BG) network model of Hodgkin-Huxley (HH) spiking neurons through microstimulation. Detailed analysis of this network model suggests that it can reproduce the experimentally observed characteristics of BG neurons under a normal and a pathological Parkinsonian state. A simplified neuronal firing rate model, identified from the detailed HH network model, is shown to capture the essential network dynamics. Mathematical analysis of the simplified model reveals the presence of a systematic relationship between the network's structure and its dynamic response to spatiotemporally patterned microstimulation. We show that both the network synaptic organization and the local mechanism of microstimulation can impose tight constraints on the possible spatiotemporal firing patterns that can be generated by the microstimulated network, which may hinder the effectiveness of microstimulation to achieve a desired objective under certain conditions. Finally, we demonstrate that the feedback control design aided by the mathematical analysis of the simplified model is indeed effective in driving the BG network in the normal and Parskinsonian states to follow a prescribed spatiotemporal firing pattern. We further show that the rhythmic/oscillatory patterns that characterize a dopamine-depleted BG network can be suppressed as a direct consequence of controlling the spatiotemporal pattern of a subpopulation of the output Globus Pallidus internalis (GPi) neurons in the network. This work may provide plausible explanations for the mechanisms underlying the therapeutic effects of deep brain stimulation (DBS) in Parkinson's disease and pave the way towards a model-based, network level analysis and closed

Bi-directional astrocytic regulation of neuronal activity within a network

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Susan Yu Gordleeva

2012-11-01

Full Text Available The concept of a tripartite synapse holds that astrocytes can affect both the pre- and postsynaptic compartments through the Ca2+-dependent release of gliotransmitters. Because astrocytic Ca2+ transients usually last for a few seconds, we assumed that astrocytic regulation of synaptic transmission may also occur on the scale of seconds. Here, we considered the basic physiological functions of tripartite synapses and investigated astrocytic regulation at the level of neural network activity. The firing dynamics of individual neurons in a spontaneous firing network was described by the Hodgkin-Huxley model. The neurons received excitatory synaptic input driven by the Poisson spike train with variable frequency. The mean field concentration of the released neurotransmitter was used to describe the presynaptic dynamics. The amplitudes of the excitatory postsynaptic currents (PSCs obeyed the gamma distribution law. In our model, astrocytes depressed the presynaptic release and enhanced the postsynaptic currents. As a result, low frequency synaptic input was suppressed while high frequency input was amplified. The analysis of the neuron spiking frequency as an indicator of network activity revealed that tripartite synaptic transmission dramatically changed the local network operation compared to bipartite synapses. Specifically, the astrocytes supported homeostatic regulation of the network activity by increasing or decreasing firing of the neurons. Thus, the astrocyte activation may modulate a transition of neural network into bistable regime of activity with two stable firing levels and spontaneous transitions between them.

Action potential energy efficiency varies among neuron types in vertebrates and invertebrates.

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Biswa Sengupta

2010-07-01

Full Text Available The initiation and propagation of action potentials (APs places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na(+ and K(+ currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin-Huxley model of the squid axon, optimizing the kinetics or number of Na(+ and K(+ channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost.

Modeling the cellular mechanisms and olfactory input underlying the triphasic response of moth pheromone-sensitive projection neurons.

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Yuqiao Gu

Full Text Available In the antennal lobe of the noctuid moth Agrotis ipsilon, most pheromone-sensitive projection neurons (PNs exhibit a triphasic firing pattern of excitation (E1-inhibition (I-excitation (E2 in response to a pulse of the sex pheromone. To understand the mechanisms underlying this stereotypical discharge, we developed a biophysical model of a PN receiving inputs from olfactory receptor neurons (ORNs via nicotinic cholinergic synapses. The ORN is modeled as an inhomogeneous Poisson process whose firing rate is a function of time and is fitted to extracellular data recorded in response to pheromone stimulations at various concentrations and durations. The PN model is based on the Hodgkin-Huxley formalism with realistic ionic currents whose parameters were derived from previous studies. Simulations revealed that the inhibitory phase I can be produced by a SK current (Ca2+-gated small conductance K+ current and that the excitatory phase E2 can result from the long-lasting response of the ORNs. Parameter analysis further revealed that the ending time of E1 depends on some parameters of SK, Ca2+, nACh and Na+ currents; I duration mainly depends on the time constant of intracellular Ca2+ dynamics, conductance of Ca2+ currents and some parameters of nACh currents; The mean firing frequency of E1 and E2 depends differentially on the interaction of various currents. Thus it is likely that the interplay between PN intrinsic currents and feedforward synaptic currents are sufficient to generate the triphasic firing patterns observed in the noctuid moth A. ipsilon.

Transition Dynamics of a Dentate Gyrus-CA3 Neuronal Network during Temporal Lobe Epilepsy.

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Zhang, Liyuan; Fan, Denggui; Wang, Qingyun

2017-01-01

In temporal lobe epilepsy (TLE), the variation of chemical receptor expression underlies the basis of neural network activity shifts, resulting in neuronal hyperexcitability and epileptiform discharges. However, dynamical mechanisms involved in the transitions of TLE are not fully understood, because of the neuronal diversity and the indeterminacy of network connection. Hence, based on Hodgkin-Huxley (HH) type neurons and Pinsky-Rinzel (PR) type neurons coupling with glutamatergic and GABAergic synaptic connections respectively, we propose a computational framework which contains dentate gyrus (DG) region and CA3 region. By regulating the concentration range of N-methyl-D-aspartate-type glutamate receptor (NMDAR), we demonstrate the pyramidal neuron can generate transitions from interictal to seizure discharges. This suggests that enhanced endogenous activity of NMDAR contributes to excitability in pyramidal neuron. Moreover, we conclude that excitatory discharges in CA3 region vary considerably on account of the excitatory currents produced by the excitatory pyramidal neuron. Interestingly, by changing the backprojection connection, we find that glutamatergic type backprojection can promote the dominant frequency of firings and further motivate excitatory counterpropagation from CA3 region to DG region. However, GABAergic type backprojection can reduce firing rate and block morbid counterpropagation, which may be factored into the terminations of TLE. In addition, neuronal diversity dominated network shows weak correlation with different backprojections. Our modeling and simulation studies provide new insights into the mechanisms of seizures generation and connectionism in local hippocampus, along with the synaptic mechanisms of this disease.

Stochastic resonance of ensemble neurons for transient spike trains: Wavelet analysis

International Nuclear Information System (INIS)

Hasegawa, Hideo

2002-01-01

By using the wavelet transformation (WT), I have analyzed the response of an ensemble of N (=1, 10, 100, and 500) Hodgkin-Huxley neurons to transient M-pulse spike trains (M=1 to 3) with independent Gaussian noises. The cross correlation between the input and output signals is expressed in terms of the WT expansion coefficients. The signal-to-noise ratio (SNR) is evaluated by using the denoising method within the WT, by which the noise contribution is extracted from the output signals. Although the response of a single (N=1) neuron to subthreshold transient signals with noises is quite unreliable, the transmission fidelity assessed by the cross correlation and SNR is shown to be much improved by increasing the value of N: a population of neurons plays an indispensable role in the stochastic resonance (SR) for transient spike inputs. It is also shown that in a large-scale ensemble, the transmission fidelity for suprathreshold transient spikes is not significantly degraded by a weak noise which is responsible to SR for subthreshold inputs

Human Brain Networks: Spiking Neuron Models, Multistability, Synchronization, Thermodynamics, Maximum Entropy Production, and Anesthetic Cascade Mechanisms

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Wassim M. Haddad

2014-07-01

Full Text Available Advances in neuroscience have been closely linked to mathematical modeling beginning with the integrate-and-fire model of Lapicque and proceeding through the modeling of the action potential by Hodgkin and Huxley to the current era. The fundamental building block of the central nervous system, the neuron, may be thought of as a dynamic element that is “excitable”, and can generate a pulse or spike whenever the electrochemical potential across the cell membrane of the neuron exceeds a threshold. A key application of nonlinear dynamical systems theory to the neurosciences is to study phenomena of the central nervous system that exhibit nearly discontinuous transitions between macroscopic states. A very challenging and clinically important problem exhibiting this phenomenon is the induction of general anesthesia. In any specific patient, the transition from consciousness to unconsciousness as the concentration of anesthetic drugs increases is very sharp, resembling a thermodynamic phase transition. This paper focuses on multistability theory for continuous and discontinuous dynamical systems having a set of multiple isolated equilibria and/or a continuum of equilibria. Multistability is the property whereby the solutions of a dynamical system can alternate between two or more mutually exclusive Lyapunov stable and convergent equilibrium states under asymptotically slowly changing inputs or system parameters. In this paper, we extend the theory of multistability to continuous, discontinuous, and stochastic nonlinear dynamical systems. In particular, Lyapunov-based tests for multistability and synchronization of dynamical systems with continuously differentiable and absolutely continuous flows are established. The results are then applied to excitatory and inhibitory biological neuronal networks to explain the underlying mechanism of action for anesthesia and consciousness from a multistable dynamical system perspective, thereby providing a

When long-range zero-lag synchronization is feasible in cortical networks

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Atthaphon eViriyopase

2012-07-01

Full Text Available Many studies have reported long-range synchronization of neuronal activity between brain areas, in particular in the gamma-band with frequencies in the range of 40-80 Hz. Several studies have reported synchrony with zero phase lag, which is remarkable considering the synaptic and conduction delays inherent in the connections between distant brain areas. This result has led to many speculations about the possible functional role of zero-lag synchrony, e.g., for neuronal communication in attention, memory and feature binding. However, recent studies using recordings of single-unit activity and local field potentials report that neuronal synchronization occurs with non-zero phase lags. This raises the questions whether zero-lag synchrony can occur in the brain and, if so, under which conditions.We used analytical methods and computer simulations to investigate which connectivity between neuronal populations allows or prohibits zero-lag synchrony. We did so for a model where two oscillators interact via a relay oscillator. Analytical results and computer simulations were obtained for both type I Mirollo-Strogatz neurons and type II Hodgkin-Huxley neurons. We have investigated the dynamics of the model for various types of synaptic coupling and importantly considered the potential impact of Spike-Timing Dependent Plasticity (STDP and its learning window. We confirm previous results that zero-lag synchrony can be achieved in this configuration. This is much easier to achieve with Hodgkin-Huxley neurons, which have a biphasic phase response curve, than for type I neurons. STDP facilitates zero-lag synchrony as it adjusts the synaptic strengths such that zero-lag synchrony is feasible for a much larger range of parameters than without STDP.

Singularly perturbed Burger-Huxley equation: Analytical solution ...

African Journals Online (AJOL)

user

solutions of singularly perturbed nonlinear differential equations. ... for solving generalized Burgers-Huxley equation but this equation is not singularly ...... Solitary waves solutions of the generalized Burger Huxley equations, Journal of.

Modelled temperature-dependent excitability behaviour of a generalised human peripheral sensory nerve fibre

CSIR Research Space (South Africa)

Smit, Jacoba E

2009-09-01

Full Text Available The objective of this study was to determine if a recently developed human Ranvier node model, which is based on a modified version of the Hodgkin-Huxley model, could predict the excitability behaviour in human peripheral sensory nerve fibres...

Memristive Systems Analysis of 3-Terminal Devices

OpenAIRE

Mouttet, Blaise

2010-01-01

Memristive systems were proposed in 1976 by Leon Chua and Sung Mo Kang as a model for 2-terminal passive nonlinear dynamical systems which exhibit memory effects. Such systems were originally shown to be relevant to the modeling of action potentials in neurons in regards to the Hodgkin-Huxley model and, more recently, to the modeling of thin film materials such as TiO2-x proposed for non-volatile resistive memory. However, over the past 50 years a variety of 3-terminal non-passive dynamical d...

Neuromorphic Silicon Neuron Circuits

Science.gov (United States)

Indiveri, Giacomo; Linares-Barranco, Bernabé; Hamilton, Tara Julia; van Schaik, André; Etienne-Cummings, Ralph; Delbruck, Tobi; Liu, Shih-Chii; Dudek, Piotr; Häfliger, Philipp; Renaud, Sylvie; Schemmel, Johannes; Cauwenberghs, Gert; Arthur, John; Hynna, Kai; Folowosele, Fopefolu; Saighi, Sylvain; Serrano-Gotarredona, Teresa; Wijekoon, Jayawan; Wang, Yingxue; Boahen, Kwabena

2011-01-01

Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain–machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance-based Hodgkin–Huxley models to bi-dimensional generalized adaptive integrate and fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips. PMID:21747754

[Effect of pulse magnetic field on distribution of neuronal action potential].

Science.gov (United States)

Zheng, Yu; Cai, Di; Wang, Jin-Hai; Li, Gang; Lin, Ling

2014-08-25

The biological effect on the organism generated by magnetic field is widely studied. The present study was aimed to observe the change of sodium channel under magnetic field in neurons. Cortical neurons of Kunming mice were isolated, subjected to 15 Hz, 1 mT pulse magnetic stimulation, and then the currents of neurons were recorded by whole-cell patch clamp. The results showed that, under magnetic stimulation, the activation process of Na(+) channel was delayed, and the inactivation process was accelerated. Given the classic three-layer model, the polarization diagram of cell membrane potential distribution under pulse magnetic field was simulated, and it was found that the membrane potential induced was associated with the frequency and intensity of magnetic field. Also the effect of magnetic field-induced current on action potential was simulated by Hodgkin-Huxley (H-H) model. The result showed that the generation of action potential was delayed, and frequency and the amplitudes were decreased when working current was between -1.32 μA and 0 μA. When the working current was higher than 0 μA, the generation frequency of action potential was increased, and the change of amplitudes was not obvious, and when the working current was lower than -1.32 μA, the time of rising edge and amplitudes of action potential were decreased drastically, and the action potential was unable to generate. These results suggest that the magnetic field simulation can affect the distribution frequency and amplitude of action potential of neuron via sodium channel mediation.

Linear stability analysis of retrieval state in associative memory neural networks of spiking neurons

International Nuclear Information System (INIS)

Yoshioka, Masahiko

2002-01-01

We study associative memory neural networks of the Hodgkin-Huxley type of spiking neurons in which multiple periodic spatiotemporal patterns of spike timing are memorized as limit-cycle-type attractors. In encoding the spatiotemporal patterns, we assume the spike-timing-dependent synaptic plasticity with the asymmetric time window. Analysis for periodic solution of retrieval state reveals that if the area of the negative part of the time window is equivalent to the positive part, then crosstalk among encoded patterns vanishes. Phase transition due to the loss of the stability of periodic solution is observed when we assume fast α function for direct interaction among neurons. In order to evaluate the critical point of this phase transition, we employ Floquet theory in which the stability problem of the infinite number of spiking neurons interacting with α function is reduced to the eigenvalue problem with the finite size of matrix. Numerical integration of the single-body dynamics yields the explicit value of the matrix, which enables us to determine the critical point of the phase transition with a high degree of precision

Memristor, Hodgkin–Huxley, and Edge of Chaos

International Nuclear Information System (INIS)

Chua, Leon

2013-01-01

From a pedagogical point of view, the memristor is defined in this tutorial as any 2-terminal device obeying a state-dependent Ohm’s law. This tutorial also shows that from an experimental point of view, the memristor can be defined as any 2-terminal device that exhibits the fingerprints of ‘pinched’ hysteresis loops in the v–i plane. It also shows that memristors endowed with a continuum of equilibrium states can be used as non-volatile analog memories. This tutorial shows that memristors span a much broader vista of complex phenomena and potential applications in many fields, including neurobiology. In particular, this tutorial presents toy memristors that can mimic the classic habituation and LTP learning phenomena. It also shows that sodium and potassium ion-channel memristors are the key to generating the action potential in the Hodgkin–Huxley equations, and that they are the key to resolving several unresolved anomalies associated with the Hodgkin–Huxley equations. This tutorial ends with an amazing new result derived from the new principle of local activity, which uncovers a minuscule life-enabling ‘Goldilocks zone’, dubbed the edge of chaos, where complex phenomena, including creativity and intelligence, may emerge. From an information processing perspective, this tutorial shows that synapses are locally-passive memristors, and that neurons are made of locally-active memristors. (tutorial)

Thomas Henry Huxley et la Bible Thomas Henry Huxley and the Bible

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Christophe Duvey

2009-10-01

Full Text Available Thomas Henry Huxley devoted several essays to the study of the Bible. This interest can only be accounted for if his ideas on history, religion as well as epistemology are examined. According to him, a struggle between free thought and supernaturalism was culminating during the Victorian era, hence the need for a “New Reformation” which was heir to the ideals of freedom defended by the humanists of the Renaissance. This movement opposed the principles of the supporters of what he called “ecclesiasticism”. The advocates of the “New Reformation” could rely on the progress of modern science, and agnosticism, which Huxley identified with scientific method, became its epistemological foundation. As a result, Huxley thought that the authority of physical science was in conflict with the infallibility of the Scriptures and with the theological arguments which rested on it, and this notably led him to the conclusion that the biblical narrative of the Flood was unhistorical. The naturalisation of the Scriptures seems then logically to follow his philosophical views based on the limits of human knowledge.It appears that it was the question of authority which underlay Huxley’s interest in the Bible. He thought that the authority of the Scriptures must be replaced by that of science.

Ordering chaos and synchronization transitions by chemical delay and coupling on scale-free neuronal networks

International Nuclear Information System (INIS)

Gong Yubing; Xie Yanhang; Lin Xiu; Hao Yinghang; Ma Xiaoguang

2010-01-01

Research highlights: → Chemical delay and chemical coupling can tame chaotic bursting. → Chemical delay-induced transitions from bursting synchronization to intermittent multiple spiking synchronizations. → Chemical coupling-induced different types of delay-dependent firing transitions. - Abstract: Chemical synaptic connections are more common than electric ones in neurons, and information transmission delay is especially significant for the synapses of chemical type. In this paper, we report a phenomenon of ordering spatiotemporal chaos and synchronization transitions by the delays and coupling through chemical synapses of modified Hodgkin-Huxley (MHH) neurons on scale-free networks. As the delay τ is increased, the neurons exhibit transitions from bursting synchronization (BS) to intermittent multiple spiking synchronizations (SS). As the coupling g syn is increased, the neurons exhibit different types of firing transitions, depending on the values of τ. For a smaller τ, there are transitions from spatiotemporal chaotic bursting (SCB) to BS or SS; while for a larger τ, there are transitions from SCB to intermittent multiple SS. These findings show that the delays and coupling through chemical synapses can tame the chaotic firings and repeatedly enhance the firing synchronization of neurons, and hence could play important roles in the firing activity of the neurons on scale-free networks.

'Great is Darwin and Bergson his poet': Julian Huxley's other evolutionary synthesis.

Science.gov (United States)

Herring, Emily

2018-01-01

In 1912, Julian Huxley published his first book The Individual in the Animal Kingdom which he dedicated to the then world-famous French philosopher Henri Bergson. Historians have generally adopted one of two attitudes towards Huxley's early encounter with Bergson. They either dismiss it entirely as unimportant or minimize it, deeming it a youthful indiscretion preceding Huxley's full conversion to Fisherian Darwinism. Close biographical study and archive materials demonstrate, however, that neither position is tenable. The study of the Bergsonian elements in play in Julian Huxley's early works fed into Huxley's first ideas about progress in evolution and even his celebrated theories of bird courtship. Furthermore, the view that Huxley rejected Bergson in his later years needs to be revised. Although Huxley ended up claiming that Bergson's theory of evolution had no explanatory power, he never repudiated the descriptive power of Bergson's controversial notion of the élan vital. Even into the Modern Synthesis period, Huxley represented his own synthesis as drawing decisively on Bergson's philosophy.

Modeling removal of accumulated potassium from T-tubules by inward rectifier potassium channels

NARCIS (Netherlands)

Wallinga, W.; Vliek, M.; Wienk, E.D.; Alberink, M.J.; Ypey, D.L.; Ypey, D.L.

1996-01-01

The membrane models of Cannon et al. (1993) and Alberink et al. (1995) for mammalian skeletal muscle fibers are based upon Hodgkin-Huxley descriptions of sodium, potassium delayed rectifier and leak conductances and the capacitive current taking into account fast inactivation of sodium channels. Now

Impact of bounded noise on the formation and instability of spiral wave in a 2D Lattice of neurons

Science.gov (United States)

Yao, Yuangen; Deng, Haiyou; Yi, Ming; Ma, Jun

2017-02-01

Spiral waves in the neocortex may provide a spatial framework to organize cortical oscillations, thus help signal communication. However, noise influences spiral wave. Many previous theoretical studies about noise mainly focus on unbounded Gaussian noise, which contradicts that a real physical quantity is always bounded. Furthermore, non-Gaussian noise is also important for dynamical behaviors of excitable media. Nevertheless, there are no results concerning the effect of bounded noise on spiral wave till now. Based on Hodgkin-Huxley neuron model subjected to bounded noise with the form of Asin[ωt + σW(t)], the influences of bounded noise on the formation and instability of spiral wave in a two-dimensional (2D) square lattice of neurons are investigated in detail by separately adjusting the intensity σ, amplitude A, and frequency f of bounded noise. It is found that the increased intensity σ can facilitate the formation of spiral wave while the increased amplitude A tends to destroy spiral wave. Furthermore, frequency of bounded noise has the effect of facilitation or inhibition on pattern synchronization. Interestingly, for the appropriate intensity, amplitude and frequency can separately induce resonance-like phenomenon.

Adaptive coupling optimized spiking coherence and synchronization in Newman-Watts neuronal networks.

Science.gov (United States)

Gong, Yubing; Xu, Bo; Wu, Ya'nan

2013-09-01

In this paper, we have numerically studied the effect of adaptive coupling on the temporal coherence and synchronization of spiking activity in Newman-Watts Hodgkin-Huxley neuronal networks. It is found that random shortcuts can enhance the spiking synchronization more rapidly when the increment speed of adaptive coupling is increased and can optimize the temporal coherence of spikes only when the increment speed of adaptive coupling is appropriate. It is also found that adaptive coupling strength can enhance the synchronization of spikes and can optimize the temporal coherence of spikes when random shortcuts are appropriate. These results show that adaptive coupling has a big influence on random shortcuts related spiking activity and can enhance and optimize the temporal coherence and synchronization of spiking activity of the network. These findings can help better understand the roles of adaptive coupling for improving the information processing and transmission in neural systems.

Single or multiple synchronization transitions in scale-free neuronal networks with electrical or chemical coupling

International Nuclear Information System (INIS)

Hao Yinghang; Gong, Yubing; Wang Li; Ma Xiaoguang; Yang Chuanlu

2011-01-01

Research highlights: → Single synchronization transition for gap-junctional coupling. → Multiple synchronization transitions for chemical synaptic coupling. → Gap junctions and chemical synapses have different impacts on synchronization transition. → Chemical synapses may play a dominant role in neurons' information processing. - Abstract: In this paper, we have studied time delay- and coupling strength-induced synchronization transitions in scale-free modified Hodgkin-Huxley (MHH) neuron networks with gap-junctions and chemical synaptic coupling. It is shown that the synchronization transitions are much different for these two coupling types. For gap-junctions, the neurons exhibit a single synchronization transition with time delay and coupling strength, while for chemical synapses, there are multiple synchronization transitions with time delay, and the synchronization transition with coupling strength is dependent on the time delay lengths. For short delays we observe a single synchronization transition, whereas for long delays the neurons exhibit multiple synchronization transitions as the coupling strength is varied. These results show that gap junctions and chemical synapses have different impacts on the pattern formation and synchronization transitions of the scale-free MHH neuronal networks, and chemical synapses, compared to gap junctions, may play a dominant and more active function in the firing activity of the networks. These findings would be helpful for further understanding the roles of gap junctions and chemical synapses in the firing dynamics of neuronal networks.

Single or multiple synchronization transitions in scale-free neuronal networks with electrical or chemical coupling

Energy Technology Data Exchange (ETDEWEB)

Hao Yinghang [School of Physics, Ludong University, Yantai 264025 (China); Gong, Yubing, E-mail: gongyubing09@hotmail.co [School of Physics, Ludong University, Yantai 264025 (China); Wang Li; Ma Xiaoguang; Yang Chuanlu [School of Physics, Ludong University, Yantai 264025 (China)

2011-04-15

Research highlights: Single synchronization transition for gap-junctional coupling. Multiple synchronization transitions for chemical synaptic coupling. Gap junctions and chemical synapses have different impacts on synchronization transition. Chemical synapses may play a dominant role in neurons' information processing. - Abstract: In this paper, we have studied time delay- and coupling strength-induced synchronization transitions in scale-free modified Hodgkin-Huxley (MHH) neuron networks with gap-junctions and chemical synaptic coupling. It is shown that the synchronization transitions are much different for these two coupling types. For gap-junctions, the neurons exhibit a single synchronization transition with time delay and coupling strength, while for chemical synapses, there are multiple synchronization transitions with time delay, and the synchronization transition with coupling strength is dependent on the time delay lengths. For short delays we observe a single synchronization transition, whereas for long delays the neurons exhibit multiple synchronization transitions as the coupling strength is varied. These results show that gap junctions and chemical synapses have different impacts on the pattern formation and synchronization transitions of the scale-free MHH neuronal networks, and chemical synapses, compared to gap junctions, may play a dominant and more active function in the firing activity of the networks. These findings would be helpful for further understanding the roles of gap junctions and chemical synapses in the firing dynamics of neuronal networks.

Modeling of action potential generation in NG108-15 cells.

Science.gov (United States)

Molnar, Peter; Hickman, James J

2014-01-01

In order to explore the possibility of identifying toxins based on their effect on the shape of action potentials, we created a computer model of the action potential generation in NG108-15 cells (a neuroblastoma/glioma hybrid cell line). To generate the experimental data for model validation, voltage-dependent sodium, potassium and high-threshold calcium currents, as well as action potentials, were recorded from NG108-15 cells with conventional whole-cell patch-clamp methods. Based on the classic Hodgkin-Huxley formalism and the linear thermodynamic description of the rate constants, ion-channel parameters were estimated using an automatic fitting method. Utilizing the established parameters, action potentials were generated using the Hodgkin-Huxley formalism and were fitted to the recorded action potentials. To demonstrate the applicability of the method for toxin detection and discrimination, the effect of tetrodotoxin (a sodium channel blocker) and tefluthrin (a pyrethroid that is a sodium channel opener) were studied. The two toxins affected the shape of the action potentials differently, and their respective effects were identified based on the predicted changes in the fitted parameters.

Dynamic transition on the seizure-like neuronal activity by astrocytic calcium channel block

International Nuclear Information System (INIS)

Li, Jiajia; Wang, Rong; Du, Mengmeng; Tang, Jun; Wu, Ying

2016-01-01

The involvement of astrocytes in neuronal firing dynamics is becoming increasingly evident. In this study, we used a classical hippocampal tripartite synapse model consisting of soma-dendrite coupled neuron models and a Hodgkin–Huxley-like astrocyte model, to investigate the seizure-like firing in the somatic neuron induced by the over-expressed neuronal N-methyl-d-aspartate (NMDA) receptors. Based on this model, we further investigated the effect of the astrocytic channel block on the neuronal firing through a bifurcation analysis. Results show that blocking inositol-1,4,5-triphosphate(IP3)-dependent calcium channel in astrocytes efficiently suppresses the astrocytic calcium oscillation, which in turn suppresses the seizure-like firing in the neuron.

Impact of adaptation currents on synchronization of coupled exponential integrate-and-fire neurons.

Directory of Open Access Journals (Sweden)

Josef Ladenbauer

Full Text Available The ability of spiking neurons to synchronize their activity in a network depends on the response behavior of these neurons as quantified by the phase response curve (PRC and on coupling properties. The PRC characterizes the effects of transient inputs on spike timing and can be measured experimentally. Here we use the adaptive exponential integrate-and-fire (aEIF neuron model to determine how subthreshold and spike-triggered slow adaptation currents shape the PRC. Based on that, we predict how synchrony and phase locked states of coupled neurons change in presence of synaptic delays and unequal coupling strengths. We find that increased subthreshold adaptation currents cause a transition of the PRC from only phase advances to phase advances and delays in response to excitatory perturbations. Increased spike-triggered adaptation currents on the other hand predominantly skew the PRC to the right. Both adaptation induced changes of the PRC are modulated by spike frequency, being more prominent at lower frequencies. Applying phase reduction theory, we show that subthreshold adaptation stabilizes synchrony for pairs of coupled excitatory neurons, while spike-triggered adaptation causes locking with a small phase difference, as long as synaptic heterogeneities are negligible. For inhibitory pairs synchrony is stable and robust against conduction delays, and adaptation can mediate bistability of in-phase and anti-phase locking. We further demonstrate that stable synchrony and bistable in/anti-phase locking of pairs carry over to synchronization and clustering of larger networks. The effects of adaptation in aEIF neurons on PRCs and network dynamics qualitatively reflect those of biophysical adaptation currents in detailed Hodgkin-Huxley-based neurons, which underscores the utility of the aEIF model for investigating the dynamical behavior of networks. Our results suggest neuronal spike frequency adaptation as a mechanism synchronizing low frequency

Calcium current activation kinetics in isolated pyramidal neurones of the Ca1 region of the mature guinea-pig hippocampus.

Science.gov (United States)

Kay, A R; Wong, R K

1987-11-01

1. Neurones were isolated from the CA1 region of the guinea-pig hippocampus and subjected to the whole-cell mode of voltage clamping, to determine the kinetics of voltage-gated Ca2+ channel activation. 2. Isolated neurones had an abbreviated morphology, having lost most of the distal dendritic tree during the isolation procedure. The electrical compactness of the cells facilitates voltage clamp analysis. 3. Block of sodium and potassium currents revealed a persistent current activated on depolarization above -40 mV, which inactivated slowly when the intracellular medium contained EGTA. The current was blocked by Co2+ and Cd2+, augmented by increases in Ca2+ and could be carried by Ba2+, suggesting that the current is borne by Ca2+. 4. Steady-state activation of the Ca2+ current was found to be well described by the Boltzman equation raised to the second power. 5. The open channel's current-voltage (I-V) relationship rectified in the inward direction and was consistent with the constant-field equation. 6. The kinetics of Ca2+ current onset followed m2 kinetics throughout the range of its activation. Tail current kinetics were in accord with this model. A detailed Hodgkin-Huxley model was derived, defining the activation of this current. 7. The kinetics of the currents observed in this regionally and morphologically defined class of neurones were consistent with the existence of a single kinetic class of channels.

Calculus for cognitive scientists partial differential equation models

CERN Document Server

Peterson, James K

2016-01-01

This book shows cognitive scientists in training how mathematics, computer science and science can be usefully and seamlessly intertwined. It is a follow-up to the first two volumes on mathematics for cognitive scientists, and includes the mathematics and computational tools needed to understand how to compute the terms in the Fourier series expansions that solve the cable equation. The latter is derived from first principles by going back to cellular biology and the relevant biophysics.  A detailed discussion of ion movement through cellular membranes, and an explanation of how the equations that govern such ion movement leading to the standard transient cable equation are included. There are also solutions for the cable model using separation of variables, as well an explanation of why Fourier series converge and a description of the implementation of MatLab tools to compute the solutions. Finally, the standard Hodgkin - Huxley model is developed for an excitable neuron and is solved using MatLab.

Study Under AC Stimulation on Excitement Properties of Weighted Small-World Biological Neural Networks with Side-Restrain Mechanism

International Nuclear Information System (INIS)

Yuan Wujie; Luo Xiaoshu; Jiang Pinqun

2007-01-01

In this paper, we propose a new model of weighted small-world biological neural networks based on biophysical Hodgkin-Huxley neurons with side-restrain mechanism. Then we study excitement properties of the model under alternating current (AC) stimulation. The study shows that the excitement properties in the networks are preferably consistent with the behavior properties of a brain nervous system under different AC stimuli, such as refractory period and the brain neural excitement response induced by different intensities of noise and coupling. The results of the study have reference worthiness for the brain nerve electrophysiology and epistemological science.

N2A: a computational tool for modeling from neurons to algorithms

Directory of Open Access Journals (Sweden)

Fredrick eRothganger

2014-01-01

Full Text Available The exponential increase in available neural data has combined with the exponential growth in computing (Moore’s law to create new opportunities to understand neural systems at large scale and high detail. The ability to produce large and sophisticated simulations has introduced unique challenges to neuroscientists. Computational models in neuroscience are increasingly broad efforts, often involving the collaboration of experts in different domains. Furthermore, the size and detail of models have grown to levels for which understanding the implications of variability and assumptions is no longer trivial. Here, we introduce the model design platform N2A which aims to facilitate the design and validation of biologically realistic models. N2A uses a hierarchical representation of neural information to enable the integration of models from different users. N2A streamlines computational validation of a model by natively implementing standard tools in sensitivity analysis and uncertainty quantification. The part-relationship representation allows both network-level analysis and dynamical simulations. We will demonstrate how N2A can be used in a range of examples, including a simple Hodgkin-Huxley cable model, basic parameter sensitivity of an 80/20 network, and the expression of the structural plasticity of a growing dendrite and stem cell proliferation and differentiation.

Spike Neural Models Part II: Abstract Neural Models

Directory of Open Access Journals (Sweden)

Johnson, Melissa G.

2018-02-01

Full Text Available Neurons are complex cells that require a lot of time and resources to model completely. In spiking neural networks (SNN though, not all that complexity is required. Therefore simple, abstract models are often used. These models save time, use less computer resources, and are easier to understand. This tutorial presents two such models: Izhikevich's model, which is biologically realistic in the resulting spike trains but not in the parameters, and the Leaky Integrate and Fire (LIF model which is not biologically realistic but does quickly and easily integrate input to produce spikes. Izhikevich's model is based on Hodgkin-Huxley's model but simplified such that it uses only two differentiation equations and four parameters to produce various realistic spike patterns. LIF is based on a standard electrical circuit and contains one equation. Either of these two models, or any of the many other models in literature can be used in a SNN. Choosing a neural model is an important task that depends on the goal of the research and the resources available. Once a model is chosen, network decisions such as connectivity, delay, and sparseness, need to be made. Understanding neural models and how they are incorporated into the network is the first step in creating a SNN.

Data assimilation using a GPU accelerated path integral Monte Carlo approach

Science.gov (United States)

Quinn, John C.; Abarbanel, Henry D. I.

2011-09-01

The answers to data assimilation questions can be expressed as path integrals over all possible state and parameter histories. We show how these path integrals can be evaluated numerically using a Markov Chain Monte Carlo method designed to run in parallel on a graphics processing unit (GPU). We demonstrate the application of the method to an example with a transmembrane voltage time series of a simulated neuron as an input, and using a Hodgkin-Huxley neuron model. By taking advantage of GPU computing, we gain a parallel speedup factor of up to about 300, compared to an equivalent serial computation on a CPU, with performance increasing as the length of the observation time used for data assimilation increases.

Dynamics of the exponential integrate-and-fire model with slow currents and adaptation.

Science.gov (United States)

Barranca, Victor J; Johnson, Daniel C; Moyher, Jennifer L; Sauppe, Joshua P; Shkarayev, Maxim S; Kovačič, Gregor; Cai, David

2014-08-01

In order to properly capture spike-frequency adaptation with a simplified point-neuron model, we study approximations of Hodgkin-Huxley (HH) models including slow currents by exponential integrate-and-fire (EIF) models that incorporate the same types of currents. We optimize the parameters of the EIF models under the external drive consisting of AMPA-type conductance pulses using the current-voltage curves and the van Rossum metric to best capture the subthreshold membrane potential, firing rate, and jump size of the slow current at the neuron's spike times. Our numerical simulations demonstrate that, in addition to these quantities, the approximate EIF-type models faithfully reproduce bifurcation properties of the HH neurons with slow currents, which include spike-frequency adaptation, phase-response curves, critical exponents at the transition between a finite and infinite number of spikes with increasing constant external drive, and bifurcation diagrams of interspike intervals in time-periodically forced models. Dynamics of networks of HH neurons with slow currents can also be approximated by corresponding EIF-type networks, with the approximation being at least statistically accurate over a broad range of Poisson rates of the external drive. For the form of external drive resembling realistic, AMPA-like synaptic conductance response to incoming action potentials, the EIF model affords great savings of computation time as compared with the corresponding HH-type model. Our work shows that the EIF model with additional slow currents is well suited for use in large-scale, point-neuron models in which spike-frequency adaptation is important.

Whistles, bells, and cogs in machines: Thomas Huxley and epiphenomenalism.

Science.gov (United States)

Greenwood, John

2010-01-01

In this paper I try to shed some historical light upon the doctrine of epiphenomenalism, by focusing on the version of epiphenomenalism championed by Thomas Huxley, which is often treated as a classic statement of the doctrine. I argue that it is doubtful if Huxley held any form of metaphysical epiphenomenalism, and that he held a more limited form of empirical epiphenomenalism with respect to consciousness but not with respect to mentality per se. Contrary to what is conventionally supposed, Huxley's empirical epiphenomenalism with respect to consciousness was not simply based upon the demonstration of the neurophysiological basis of conscious mentality, or derived from the extension of mechanistic and reflexive principles of explanation to encompass all forms of animal and human behavior, but was based upon the demonstration of purposive and coordinated animal and human behavior in the absence of consciousness. Given Huxley's own treatment of mentality, his characterization of animals and humans as "conscious automata" was not well chosen.

Author as a Corporal Subject of A. Huxley's Works

Science.gov (United States)

Falaleeva, Svetlana S.; Musaeva, Diana R.; Samoylova, Tatiana I.; Linnik, Anna M.

2016-01-01

The relevance of the problem studied in the article is conditioned by the fact that A. Huxley's works are regarded in the context of the modern theory of mimesis for the first time. The aim of the article is to analyze the author's problem as a corporal subject of Huxley's works in the context of the modern theory of mimesis. The leading method…

Physiological models of the lateral superior olive.

Directory of Open Access Journals (Sweden)

Go Ashida

2017-12-01

Full Text Available 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

Effects of dynamic synapses on noise-delayed response latency of a single neuron

Science.gov (United States)

Uzuntarla, M.; Ozer, M.; Ileri, U.; Calim, A.; Torres, J. J.

2015-12-01

The noise-delayed decay (NDD) phenomenon emerges when the first-spike latency of a periodically forced stochastic neuron exhibits a maximum for a particular range of noise intensity. Here, we investigate the latency response dynamics of a single Hodgkin-Huxley neuron that is subject to both a suprathreshold periodic stimulus and a background activity arriving through dynamic synapses. We study the first-spike latency response as a function of the presynaptic firing rate f . This constitutes a more realistic scenario than previous works, since f provides a suitable biophysically realistic parameter to control the level of activity in actual neural systems. We first report on the emergence of classical NDD behavior as a function of f for the limit of static synapses. Second, we show that when short-term depression and facilitation mechanisms are included at the synapses, different NDD features can be found due to their modulatory effect on synaptic current fluctuations. For example, an intriguing double NDD (DNDD) behavior occurs for different sets of relevant synaptic parameters. Moreover, depending on the balance between synaptic depression and synaptic facilitation, single NDD or DNDD can prevail, in such a way that synaptic facilitation favors the emergence of DNDD whereas synaptic depression favors the existence of single NDD. Here we report the existence of the DNDD effect in the response latency dynamics of a neuron.

Neuroelectronics and modeling of electrical signals for monitoring and control of Parkinson's disease

Science.gov (United States)

Chintakuntla, Ritesh R.; Abraham, Jose K.; Varadan, Vijay K.

2009-03-01

The brain and the human nervous system are perhaps the most researched but least understood components of the human body. This is so because of the complex nature of its working and the high density of functions. The monitoring of neural signals could help one better understand the working of the brain and newer recording and monitoring methods have been developed ever since it was discovered that the brain communicates internally by means of electrical pulses. Neuroelectronics is the field which deals with the interface between electronics or semiconductors to living neurons. This includes monitoring of electrical activity from the brain as well as the development of feedback devices for stimulation of parts of the brain for treatment of disorders. In this paper these electrical signals are modeled through a nano/microelectrode arrays based on the electronic equivalent model using Cadence PSD 15.0. The results were compared with those previously published models such as Kupfmuller and Jenik's model, McGrogan's Neuron Model which are based on the Hodgkin and Huxley model. We have developed and equivalent circuit model using discrete passive components to simulate the electrical activity of the neurons. The simulated circuit can be easily be modified by adding some more ionic channels and the results can be used to predict necessary external stimulus needed for stimulation of neurons affected by the Parkinson's disease (PD). Implementing such a model in PD patients could predict the necessary voltages required for the electrical stimulation of the sub-thalamus region for the control tremor motion.

Dynamic behaviors in directed networks

International Nuclear Information System (INIS)

Park, Sung Min; Kim, Beom Jun

2006-01-01

Motivated by the abundance of directed synaptic couplings in a real biological neuronal network, we investigate the synchronization behavior of the Hodgkin-Huxley model in a directed network. We start from the standard model of the Watts-Strogatz undirected network and then change undirected edges to directed arcs with a given probability, still preserving the connectivity of the network. A generalized clustering coefficient for directed networks is defined and used to investigate the interplay between the synchronization behavior and underlying structural properties of directed networks. We observe that the directedness of complex networks plays an important role in emerging dynamical behaviors, which is also confirmed by a numerical study of the sociological game theoretic voter model on directed networks

A novel electrical model of nerve and muscle using Pspice

CERN Document Server

Peasgood, W; Lam, C K; Armstrong, A G; Wood, W

2003-01-01

In this work, a model is developed to simulate the biological processes involved in nerve fibre transmission and subsequent muscle contraction. The model has been based on approximating biological structure and function to electrical circuits and as such was implemented on an electronics simulation software package called Pspice. Models of nerve, the nerve-muscle interface and muscle fibre have been implemented. The time dependent ionic properties of the nerve and muscle membranes have been simulated using the Hodgkin-Huxley equations and for the muscle fibre, the implementation of the Huxley sliding filament theory for muscular contraction. The results show that nerve may be considered as a fractal transmission line and that the amplitude of the nerve membrane depolarization is dependent on the dimensions of the fibre. Additionally, simulation of the nerve-muscle interface allows the fractal nerve model to be connected to the muscle fibre model and it is shown that a two sarcomere molecular simulation can pr...

The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization.

Directory of Open Access Journals (Sweden)

Niklas Hübel

2017-10-01

Full Text Available Simultaneous changes in ion concentrations, glutamate, and cell volume together with exchange of matter between cell network and vasculature are ubiquitous in numerous brain pathologies. A complete understanding of pathological conditions as well as normal brain function, therefore, hinges on elucidating the molecular and cellular pathways involved in these mostly interdependent variations. In this paper, we develop the first computational framework that combines the Hodgkin-Huxley type spiking dynamics, dynamic ion concentrations and glutamate homeostasis, neuronal and astroglial volume changes, and ion exchange with vasculature into a comprehensive model to elucidate the role of glutamate uptake in the dynamics of spreading depolarization (SD-the electrophysiological event underlying numerous pathologies including migraine, ischemic stroke, aneurysmal subarachnoid hemorrhage, intracerebral hematoma, and trauma. We are particularly interested in investigating the role of glutamate in the duration and termination of SD caused by K+ perfusion and oxygen-glucose deprivation. Our results demonstrate that glutamate signaling plays a key role in the dynamics of SD, and that impaired glutamate uptake leads to recovery failure of neurons from SD. We confirm predictions from our model experimentally by showing that inhibiting astrocytic glutamate uptake using TFB-TBOA nearly quadruples the duration of SD in layers 2-3 of visual cortical slices from juvenile rats. The model equations are either derived purely from first physical principles of electroneutrality, osmosis, and conservation of particles or a combination of these principles and known physiological facts. Accordingly, we claim that our approach can be used as a future guide to investigate the role of glutamate, ion concentrations, and dynamics cell volume in other brain pathologies and normal brain function.

The role of glutamate in neuronal ion homeostasis: A case study of spreading depolarization.

Science.gov (United States)

Hübel, Niklas; Hosseini-Zare, Mahshid S; Žiburkus, Jokūbas; Ullah, Ghanim

2017-10-01

Simultaneous changes in ion concentrations, glutamate, and cell volume together with exchange of matter between cell network and vasculature are ubiquitous in numerous brain pathologies. A complete understanding of pathological conditions as well as normal brain function, therefore, hinges on elucidating the molecular and cellular pathways involved in these mostly interdependent variations. In this paper, we develop the first computational framework that combines the Hodgkin-Huxley type spiking dynamics, dynamic ion concentrations and glutamate homeostasis, neuronal and astroglial volume changes, and ion exchange with vasculature into a comprehensive model to elucidate the role of glutamate uptake in the dynamics of spreading depolarization (SD)-the electrophysiological event underlying numerous pathologies including migraine, ischemic stroke, aneurysmal subarachnoid hemorrhage, intracerebral hematoma, and trauma. We are particularly interested in investigating the role of glutamate in the duration and termination of SD caused by K+ perfusion and oxygen-glucose deprivation. Our results demonstrate that glutamate signaling plays a key role in the dynamics of SD, and that impaired glutamate uptake leads to recovery failure of neurons from SD. We confirm predictions from our model experimentally by showing that inhibiting astrocytic glutamate uptake using TFB-TBOA nearly quadruples the duration of SD in layers 2-3 of visual cortical slices from juvenile rats. The model equations are either derived purely from first physical principles of electroneutrality, osmosis, and conservation of particles or a combination of these principles and known physiological facts. Accordingly, we claim that our approach can be used as a future guide to investigate the role of glutamate, ion concentrations, and dynamics cell volume in other brain pathologies and normal brain function.

Chimera States in Neural Oscillators

Science.gov (United States)

Bahar, Sonya; Glaze, Tera

2014-03-01

Chimera states have recently been explored both theoretically and experimentally, in various coupled nonlinear oscillators, ranging from phase-oscillator models to coupled chemical reactions. In a chimera state, both coherent and incoherent (or synchronized and desynchronized) states occur simultaneously in populations of identical oscillators. We investigate chimera behavior in a population of neural oscillators using the Huber-Braun model, a Hodgkin-Huxley-like model originally developed to characterize the temperature-dependent bursting behavior of mammalian cold receptors. One population of neurons is allowed to synchronize, with each neuron receiving input from all the others in its group (global within-group coupling). Subsequently, a second population of identical neurons is placed under an identical global within-group coupling, and the two populations are also coupled to each other (between-group coupling). For certain values of the coupling constants, the neurons in the two populations exhibit radically different synchronization behavior. We will discuss the range of chimera activity in the model, and discuss its implications for actual neural activity, such as unihemispheric sleep.

BrainFrame: a node-level heterogeneous accelerator platform for neuron simulations

Science.gov (United States)

Smaragdos, Georgios; Chatzikonstantis, Georgios; Kukreja, Rahul; Sidiropoulos, Harry; Rodopoulos, Dimitrios; Sourdis, Ioannis; Al-Ars, Zaid; Kachris, Christoforos; Soudris, Dimitrios; De Zeeuw, Chris I.; Strydis, Christos

2017-12-01

Objective. The advent of high-performance computing (HPC) in recent years has led to its increasing use in brain studies through computational models. The scale and complexity of such models are constantly increasing, leading to challenging computational requirements. Even though modern HPC platforms can often deal with such challenges, the vast diversity of the modeling field does not permit for a homogeneous acceleration platform to effectively address the complete array of modeling requirements. Approach. In this paper we propose and build BrainFrame, a heterogeneous acceleration platform that incorporates three distinct acceleration technologies, an Intel Xeon-Phi CPU, a NVidia GP-GPU and a Maxeler Dataflow Engine. The PyNN software framework is also integrated into the platform. As a challenging proof of concept, we analyze the performance of BrainFrame on different experiment instances of a state-of-the-art neuron model, representing the inferior-olivary nucleus using a biophysically-meaningful, extended Hodgkin-Huxley representation. The model instances take into account not only the neuronal-network dimensions but also different network-connectivity densities, which can drastically affect the workload’s performance characteristics. Main results. The combined use of different HPC technologies demonstrates that BrainFrame is better able to cope with the modeling diversity encountered in realistic experiments while at the same time running on significantly lower energy budgets. Our performance analysis clearly shows that the model directly affects performance and all three technologies are required to cope with all the model use cases. Significance. The BrainFrame framework is designed to transparently configure and select the appropriate back-end accelerator technology for use per simulation run. The PyNN integration provides a familiar bridge to the vast number of models already available. Additionally, it gives a clear roadmap for extending the platform

Multiphasic on/off pheromone signalling in moths as neural correlates of a search strategy.

Directory of Open Access Journals (Sweden)

Dominique Martinez

Full Text Available Insects and robots searching for odour sources in turbulent plumes face the same problem: the random nature of mixing causes fluctuations and intermittency in perception. Pheromone-tracking male moths appear to deal with discontinuous flows of information by surging upwind, upon sensing a pheromone patch, and casting crosswind, upon losing the plume. Using a combination of neurophysiological recordings, computational modelling and experiments with a cyborg, we propose a neuronal mechanism that promotes a behavioural switch between surge and casting. We show how multiphasic On/Off pheromone-sensitive neurons may guide action selection based on signalling presence or loss of the pheromone. A Hodgkin-Huxley-type neuron model with a small-conductance calcium-activated potassium (SK channel reproduces physiological On/Off responses. Using this model as a command neuron and the antennae of tethered moths as pheromone sensors, we demonstrate the efficiency of multiphasic patterning in driving a robotic searcher toward the source. Taken together, our results suggest that multiphasic On/Off responses may mediate olfactory navigation and that SK channels may account for these responses.

Multiphasic on/off pheromone signalling in moths as neural correlates of a search strategy.

Science.gov (United States)

Martinez, Dominique; Chaffiol, Antoine; Voges, Nicole; Gu, Yuqiao; Anton, Sylvia; Rospars, Jean-Pierre; Lucas, Philippe

2013-01-01

Insects and robots searching for odour sources in turbulent plumes face the same problem: the random nature of mixing causes fluctuations and intermittency in perception. Pheromone-tracking male moths appear to deal with discontinuous flows of information by surging upwind, upon sensing a pheromone patch, and casting crosswind, upon losing the plume. Using a combination of neurophysiological recordings, computational modelling and experiments with a cyborg, we propose a neuronal mechanism that promotes a behavioural switch between surge and casting. We show how multiphasic On/Off pheromone-sensitive neurons may guide action selection based on signalling presence or loss of the pheromone. A Hodgkin-Huxley-type neuron model with a small-conductance calcium-activated potassium (SK) channel reproduces physiological On/Off responses. Using this model as a command neuron and the antennae of tethered moths as pheromone sensors, we demonstrate the efficiency of multiphasic patterning in driving a robotic searcher toward the source. Taken together, our results suggest that multiphasic On/Off responses may mediate olfactory navigation and that SK channels may account for these responses.

A quantitative overview of biophysical forces impinging on neural function

International Nuclear Information System (INIS)

Mueller, Jerel K; Tyler, William J

2014-01-01

The fundamentals of neuronal membrane excitability are globally described using the Hodgkin-Huxley (HH) model. The HH model, however, does not account for a number of biophysical phenomena associated with action potentials or propagating nerve impulses. Physical mechanisms underlying these processes, such as reversible heat transfer and axonal swelling, have been compartmentalized and separately investigated to reveal neuronal activity is not solely influenced by electrical or biochemical factors. Instead, mechanical forces and thermodynamics also govern neuronal excitability and signaling. To advance our understanding of neuronal function and dysfunction, compartmentalized analyses of electrical, chemical, and mechanical processes need to be revaluated and integrated into more comprehensive theories. The present perspective is intended to provide a broad overview of biophysical forces that can influence neural function, but which have been traditionally underappreciated in neuroscience. Further, several examples where mechanical forces have been shown to exert their actions on nervous system development, signaling, and plasticity are highlighted to underscore their importance in sculpting neural function. By considering the collective actions of biophysical forces influencing neuronal activity, our working models can be expanded and new paradigms can be applied to the investigation and characterization of brain function and dysfunction. (topical review)

Singularly perturbed Burger-Huxley equation: Analytical solution ...

African Journals Online (AJOL)

The work presented considers the initial boundary value problem for nonlinear singularly perturbed time dependent Burger- Huxley equation. The equation contains two terms with nonlinearities, the cubic term and the advection term. Generally, the severe difficulties of two types encounter in solving this problem. The first ...

Biophysical Neural Spiking, Bursting, and Excitability Dynamics in Reconfigurable Analog VLSI.

Science.gov (United States)

Yu, T; Sejnowski, T J; Cauwenberghs, G

2011-10-01

We study a range of neural dynamics under variations in biophysical parameters underlying extended Morris-Lecar and Hodgkin-Huxley models in three gating variables. The extended models are implemented in NeuroDyn, a four neuron, twelve synapse continuous-time analog VLSI programmable neural emulation platform with generalized channel kinetics and biophysical membrane dynamics. The dynamics exhibit a wide range of time scales extending beyond 100 ms neglected in typical silicon models of tonic spiking neurons. Circuit simulations and measurements show transition from tonic spiking to tonic bursting dynamics through variation of a single conductance parameter governing calcium recovery. We similarly demonstrate transition from graded to all-or-none neural excitability in the onset of spiking dynamics through the variation of channel kinetic parameters governing the speed of potassium activation. Other combinations of variations in conductance and channel kinetic parameters give rise to phasic spiking and spike frequency adaptation dynamics. The NeuroDyn chip consumes 1.29 mW and occupies 3 mm × 3 mm in 0.5 μm CMOS, supporting emerging developments in neuromorphic silicon-neuron interfaces.

Electro-Quasistatic Simulations in Bio-Systems Engineering and Medical Engineering

Directory of Open Access Journals (Sweden)

U. van Rienen

2005-01-01

Full Text Available Slowly varying electromagnetic fields play a key role in various applications in bio-systems and medical engineering. Examples are the electric activity of neurons on neurochips used as biosensors, the stimulating electric fields of implanted electrodes used for deep brain stimulation in patients with Morbus Parkinson and the stimulation of the auditory nerves in deaf patients, respectively. In order to simulate the neuronal activity on a chip it is necessary to couple Maxwell's and Hodgkin-Huxley's equations. First numerical results for a neuron coupling to a single electrode are presented. They show a promising qualitative agreement with the experimentally recorded signals. Further, simulations are presented on electrodes for deep brain stimulation in animal experiments where the question of electrode ageing and energy deposition in the surrounding tissue are of major interest. As a last example, electric simulations for a simple cochlea model are presented comparing the field in the skull bones for different electrode types and stimulations in different positions.

expansion method for the Burgers, Burgers–Huxley and modified

Indian Academy of Sciences (India)

expansion method; Burgers equation; Burgers–Huxley equation; modified. Burgers–KdV equation .... Substituting the solution set (12) and the corresponding solutions of (4) into (8), we have ..... During the past several years, many have done.

The "History" of Victorian Scientific Naturalism: Huxley, Spencer and the "End" of natural history.

Science.gov (United States)

Lightman, Bernard

2016-08-01

As part of their defence of evolutionary theory, T. H. Huxley and Herbert Spencer argued that natural history was no longer a legitimate scientific discipline. They outlined a secularized concept of life from biology to argue for the validity of naturalism. Despite their support for naturalism, they offered two different responses to the decline of natural history. Whereas Huxley emphasized the creation of a biological discipline, and all that that entailed, Spencer was more concerned with constructing an entire intellectual system based on the idea of evolution. In effect, Spencer wanted to create a new scientific worldview based on evolutionary theory. This had consequences for their understanding of human history, especially of how science had evolved through the ages. It affected their conceptions of human agency, contingency, and directionality in history. Examining Huxley's and Spencer's responses to the "end" of natural history reveals some of the deep divisions within scientific naturalism and the inherent problems of naturalism in general. Whereas Huxley chose to separate the natural and the historical, Spencer opted to fuse them into a single system. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Las matemáticas en la transmisión del impulso nervioso

OpenAIRE

García García, Lara

2016-01-01

En este trabajo se analizan algunos de los modelos que describen la transmisión del impulso nervioso o sinapsis neuronal. Más concretamente, el modelo de Hodgkin y Huxley (por el que ganaron el premio Nobel de Fisiología en 1963) y otros modelos simplificados de FitzHugh y Nagumo y McKean. Se determinan condiciones sobre los parámetros que aparecen en los modelos para que existan soluciones del tipo observado en los experimentos originales de los fisiólogos. Grado en Matemáticas

GeNN: a code generation framework for accelerated brain simulations

Science.gov (United States)

Yavuz, Esin; Turner, James; Nowotny, Thomas

2016-01-01

Large-scale numerical simulations of detailed brain circuit models are important for identifying hypotheses on brain functions and testing their consistency and plausibility. An ongoing challenge for simulating realistic models is, however, computational speed. In this paper, we present the GeNN (GPU-enhanced Neuronal Networks) framework, which aims to facilitate the use of graphics accelerators for computational models of large-scale neuronal networks to address this challenge. GeNN is an open source library that generates code to accelerate the execution of network simulations on NVIDIA GPUs, through a flexible and extensible interface, which does not require in-depth technical knowledge from the users. We present performance benchmarks showing that 200-fold speedup compared to a single core of a CPU can be achieved for a network of one million conductance based Hodgkin-Huxley neurons but that for other models the speedup can differ. GeNN is available for Linux, Mac OS X and Windows platforms. The source code, user manual, tutorials, Wiki, in-depth example projects and all other related information can be found on the project website http://genn-team.github.io/genn/.

SpikingLab: modelling agents controlled by Spiking Neural Networks in Netlogo.

Science.gov (United States)

Jimenez-Romero, Cristian; Johnson, Jeffrey

2017-01-01

The scientific interest attracted by Spiking Neural Networks (SNN) has lead to the development of tools for the simulation and study of neuronal dynamics ranging from phenomenological models to the more sophisticated and biologically accurate Hodgkin-and-Huxley-based and multi-compartmental models. However, despite the multiple features offered by neural modelling tools, their integration with environments for the simulation of robots and agents can be challenging and time consuming. The implementation of artificial neural circuits to control robots generally involves the following tasks: (1) understanding the simulation tools, (2) creating the neural circuit in the neural simulator, (3) linking the simulated neural circuit with the environment of the agent and (4) programming the appropriate interface in the robot or agent to use the neural controller. The accomplishment of the above-mentioned tasks can be challenging, especially for undergraduate students or novice researchers. This paper presents an alternative tool which facilitates the simulation of simple SNN circuits using the multi-agent simulation and the programming environment Netlogo (educational software that simplifies the study and experimentation of complex systems). The engine proposed and implemented in Netlogo for the simulation of a functional model of SNN is a simplification of integrate and fire (I&F) models. The characteristics of the engine (including neuronal dynamics, STDP learning and synaptic delay) are demonstrated through the implementation of an agent representing an artificial insect controlled by a simple neural circuit. The setup of the experiment and its outcomes are described in this work.

Treatment of Hodgkin`s disease; Tratamento da doenca de Hodgkin

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Silva, E.M. [Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, Rio de Janeiro, RJ (Brazil). Servico de Hematologia Clinica

1993-12-31

This study consists of a revision of the treatment and prognosis of Hodgkin`s disease, comparing the chemotherapeutic and radiotherapeutic therapy and the complications both as a direct result of the disease and a result of the treatment. (author). 34 refs, 1 tab.

Past as Prediction: Newcomb, Huxley, The Eclipse of Thales, and The Power of Science

Science.gov (United States)

Stanley, Matthew

2009-12-01

The ancient eclipse of Thales was an important, if peculiar, focus of scientific attention in the 19th century. Victorian-era astronomers first used it as data with which to calibrate their lunar theories, but its status became strangely malleable as the century progressed. The American astronomer Simon Newcomb re-examined the eclipse and rejected it as the basis for lunar theory. But strangely, it was the unprecedented accuracy of Newcomb's calculations that led the British biologist T.H. Huxley to declare the eclipse to be the quintessential example of the power of science. Huxley argued that astronomy's ability to create "retrospective prophecy” showed how scientific reasoning was superior to religion (and incidentally, helped support Darwin's theories). Both Newcomb and Huxley declared that prediction (of past and future) was what gave science its persuasive power. The eclipse of Thales's strange journey through Victorian astronomy reveals how these two influential scientists made the case for the social and cultural authority of science.

Hodgkin lymphoma

Science.gov (United States)

Lymphoma - Hodgkin; Hodgkin disease; Cancer - Hodgkin lymphoma ... to 70 years old. Past infection with the Epstein-Barr virus ( EBV ) is thought to contribute to some cases. People with HIV infection are at increased risk compared to the general population.

Synchronization and Inter-Layer Interactions of Noise-Driven Neural Networks.

Science.gov (United States)

Yuniati, Anis; Mai, Te-Lun; Chen, Chi-Ming

2017-01-01

In this study, we used the Hodgkin-Huxley (HH) model of neurons to investigate the phase diagram of a developing single-layer neural network and that of a network consisting of two weakly coupled neural layers. These networks are noise driven and learn through the spike-timing-dependent plasticity (STDP) or the inverse STDP rules. We described how these networks transited from a non-synchronous background activity state (BAS) to a synchronous firing state (SFS) by varying the network connectivity and the learning efficacy. In particular, we studied the interaction between a SFS layer and a BAS layer, and investigated how synchronous firing dynamics was induced in the BAS layer. We further investigated the effect of the inter-layer interaction on a BAS to SFS repair mechanism by considering three types of neuron positioning (random, grid, and lognormal distributions) and two types of inter-layer connections (random and preferential connections). Among these scenarios, we concluded that the repair mechanism has the largest effect for a network with the lognormal neuron positioning and the preferential inter-layer connections.

On the identification of multiple space dependent ionic parameters in cardiac electrophysiology modelling

Science.gov (United States)

Abidi, Yassine; Bellassoued, Mourad; Mahjoub, Moncef; Zemzemi, Nejib

2018-03-01

In this paper, we consider the inverse problem of space dependent multiple ionic parameters identification in cardiac electrophysiology modelling from a set of observations. We use the monodomain system known as a state-of-the-art model in cardiac electrophysiology and we consider a general Hodgkin-Huxley formalism to describe the ionic exchanges at the microscopic level. This formalism covers many physiological transmembrane potential models including those in cardiac electrophysiology. Our main result is the proof of the uniqueness and a Lipschitz stability estimate of ion channels conductance parameters based on some observations on an arbitrary subdomain. The key idea is a Carleman estimate for a parabolic operator with multiple coefficients and an ordinary differential equation system.

Characterization of Different Types of Excitability in Large Somatosensory Neurons and Its Plastic Changes in Pathological Pain States

Science.gov (United States)

Xie, Rou-Gang; Chu, Wen-Guang; Hu, San-Jue; Luo, Ceng

2018-01-01

Sensory neuron types have been distinguished by distinct morphological and transcriptional characteristics. Excitability is the most fundamental functional feature of neurons. Mathematical models described by Hodgkin have revealed three types of neuronal excitability based on the relationship between firing frequency and applied current intensity. However, whether natural sensory neurons display different functional characteristics in terms of excitability and whether this excitability type undergoes plastic changes under pathological pain states have remained elusive. Here, by utilizing whole-cell patch clamp recordings, behavioral and pharmacological assays, we demonstrated that large dorsal root ganglion (DRG) neurons can be classified into three classes and four subclasses based on their excitability patterns, which is similar to mathematical models raised by Hodgkin. Analysis of hyperpolarization-activated cation current (Ih) revealed different magnitude of Ih in different excitability types of large DRG neurons, with higher Ih in Class 2-1 than that in Class 1, 2-2 and 3. This indicates a crucial role of Ih in the determination of excitability type of large DRG neurons. More importantly, this pattern of excitability displays plastic changes and transition under pathological pain states caused by peripheral nerve injury. This study sheds new light on the functional characteristics of large DRG neurons and extends functional classification of large DRG neurons by integration of transcriptomic and morphological characteristics. PMID:29303989

Characterization of Different Types of Excitability in Large Somatosensory Neurons and Its Plastic Changes in Pathological Pain States

Directory of Open Access Journals (Sweden)

Rou-Gang Xie

2018-01-01

Full Text Available Sensory neuron types have been distinguished by distinct morphological and transcriptional characteristics. Excitability is the most fundamental functional feature of neurons. Mathematical models described by Hodgkin have revealed three types of neuronal excitability based on the relationship between firing frequency and applied current intensity. However, whether natural sensory neurons display different functional characteristics in terms of excitability and whether this excitability type undergoes plastic changes under pathological pain states have remained elusive. Here, by utilizing whole-cell patch clamp recordings, behavioral and pharmacological assays, we demonstrated that large dorsal root ganglion (DRG neurons can be classified into three classes and four subclasses based on their excitability patterns, which is similar to mathematical models raised by Hodgkin. Analysis of hyperpolarization-activated cation current (Ih revealed different magnitude of Ih in different excitability types of large DRG neurons, with higher Ih in Class 2-1 than that in Class 1, 2-2 and 3. This indicates a crucial role of Ih in the determination of excitability type of large DRG neurons. More importantly, this pattern of excitability displays plastic changes and transition under pathological pain states caused by peripheral nerve injury. This study sheds new light on the functional characteristics of large DRG neurons and extends functional classification of large DRG neurons by integration of transcriptomic and morphological characteristics.

A single Markov-type kinetic model accounting for the macroscopic currents of all human voltage-gated sodium channel isoforms.

Science.gov (United States)

Balbi, Pietro; Massobrio, Paolo; Hellgren Kotaleski, Jeanette

2017-09-01

Modelling ionic channels represents a fundamental step towards developing biologically detailed neuron models. Until recently, the voltage-gated ion channels have been mainly modelled according to the formalism introduced by the seminal works of Hodgkin and Huxley (HH). However, following the continuing achievements in the biophysical and molecular comprehension of these pore-forming transmembrane proteins, the HH formalism turned out to carry limitations and inconsistencies in reproducing the ion-channels electrophysiological behaviour. At the same time, Markov-type kinetic models have been increasingly proven to successfully replicate both the electrophysiological and biophysical features of different ion channels. However, in order to model even the finest non-conducting molecular conformational change, they are often equipped with a considerable number of states and related transitions, which make them computationally heavy and less suitable for implementation in conductance-based neurons and large networks of those. In this purely modelling study we develop a Markov-type kinetic model for all human voltage-gated sodium channels (VGSCs). The model framework is detailed, unifying (i.e., it accounts for all ion-channel isoforms) and computationally efficient (i.e. with a minimal set of states and transitions). The electrophysiological data to be modelled are gathered from previously published studies on whole-cell patch-clamp experiments in mammalian cell lines heterologously expressing the human VGSC subtypes (from NaV1.1 to NaV1.9). By adopting a minimum sequence of states, and using the same state diagram for all the distinct isoforms, the model ensures the lightest computational load when used in neuron models and neural networks of increasing complexity. The transitions between the states are described by original ordinary differential equations, which represent the rate of the state transitions as a function of voltage (i.e., membrane potential). The

Understanding the Electrical Behavior of the Action Potential in Terms of Elementary Electrical Sources

Science.gov (United States)

Rodriguez-Falces, Javier

2015-01-01

A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However,…

Hodgkin lymphoma - children

Science.gov (United States)

... families share common experiences may help ease your stress. American Childhood Cancer Organization - www.acco.org Leukemia and ... Cancer - Hodgkin lymphoma - children; Childhood Hodgkin lymphoma ... Cancer Institute website. Childhood Hodgkin lymphoma treatment (PDQ) - health professional ...

Numerical investigation of action potential transmission in plants

Directory of Open Access Journals (Sweden)

Mariusz Pietruszka

2014-01-01

Full Text Available In context of a fairly concise review of recent literature and well established experimental results we reconsider the problem of action potential propagating steadily down the plant cell(s. Having adopted slightly modified Hodgkin-Huxley set of differential equations for the action potential we carried out the numerical investigation of these equations in the course of time. We argue that the Hodgkin-Huxley-Katz model for the nerve impulse can be used to describe the phenomena which take place in plants - this point of view seems to be plausible since the mechanisms involving active ionic transport across membranes from the mathematical point of view are similar. Besides, we compare in a qualitative way our theoretical outcomes with typical experimental results for the action potentials which arise as the reaction of plants to electrical, mechanical and light stimuli. Moreover, we point out the relevance of the sequence of events during the pulse with the appropriate ionic fluxes.

Hodgkin`s disease: internal mammary lymph nodes relapse diagnosed by Gallium-67 scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Ruiz Hernandez, G.; Ampudia, J.; Castillo, F.J.; Romero, C. [Hospital Clinico Univ., Valencia (Spain). Servicio de Medicina Nuclear; Pallardo, Y. [Hospital Clinico Univ., Valencia (Spain). Servicio de Radiologia; Garcia Conde, J. [Hospital Clinico Univ., Valencia (Spain). Servicio de Hematologia y Oncologia Medica; Ramos, D. [Hospital Clinico Univ., Valencia (Spain). Servicio de Anatomia Patologica

1999-04-01

This article presents the case of a 62-year-old man with treated Hodgkin`s disease who had internal mammary lymph nodes relapse after a complete initial response. These masses were gallium avid. These findings were explained by histologically documented Hodgkin`s relapse, the first such case reported in that localization without chest wall involvement. The literature on mediastinal Hodgkin`s disease and diagnostic procedures are reviewed. (orig.) [Deutsch] Beschrieben wird der Fall eines 62jaehrigen Mannes, der nach initial erfolgreicher Therapie eines Morbus Hodgkin ein Lymphknotenrezidiv im Bereich der Brust aufweist. Die Lymphknoten reicherten Gallium an. Histologisch wurde das Hodgkinrezidiv gesichert. Es handelt sich um den ersten in diesem Bereich beschriebenen Fall ohne Infiltration der Brustwand. Die Literatur ueber mediastinalen Morbus Hodgkin und diagnostisches Vorgehen wurde ueberprueft. (orig.)

Immunohistochemical Profile of Hodgkin and Non-Hodgkin Lymphoma

International Nuclear Information System (INIS)

Shahid, R.; Gulzar, R.; Avesi, L.; Hassan, S.; Danish, F.; Mirza, T.

2016-01-01

Objective: To analyze the frequencies of histological types of lymphoma, diagnosed with complete immunohistochemical profile in younger and older age group. Study Design: Cross-sectional analytical study. Place and Duration of Study: Dow Diagnostic Research and Reference Laboratory, Dow University of Health Sciences, Karachi, from January 2009 to September 2013. Methodology: Consecutive cases of lymphomas, which were diagnosed using immunohistochemistry, were analyzed according to WHO classification. Frequency and percentages for different types of lymphomas were calculated. Hodgkin and non-Hodgkin lymphomas characteristics in two age groups of less than and more than 40 years were compared, applying chi-square test. Results: Out of the 318 cases, 79 (25 percentage) were Hodgkin Lymphomas (HL) and 239 (75 percentage) were Non-Hodgkin Lymphomas (NHL). Mixed Cellularity Hodgkin Lymphoma (MCHL) was the commonest (n=48). Amongst the NHL, 215 (89.95 percentage) were B cell lymphomas and 24 (10.05percentage) were T-cell lymphomas. Diffuse Large B-Cell Lymphoma (DLBCL) was the commonest lymphoma (n=165, 69.95 percentage of NHL). Anaplastic T-Cell Lymphoma (ALCL, n=10) was the commonest T-cell lymphoma. The frequency of HL was significantly higher in the younger age group and that of NHL was higher in the older age group (p < 0.001). Primary lymph node involvement was reported in 175 (55 percentage) and cervical lymph node was the most frequent site. Extra nodal involvement was seen in 93 (29 percentage) of all cases and was reported in 87 (36.4 percentage) of NHL and 6 (7.5 percentage) of HL. The most common extra nodal site was the gastrointestinal tract. Conclusion: Hodgkin lymphoma comprises 25 percentage and non-Hodgkin lymphoma comprises 75 percentage of all lymphomas. Both occur in younger age groups than reported in the West. B-cell NHL is three times more common than T-cell lymphoma. DLBCL is the most frequent lymphoma. ALCL is the most common T-cell, and mixed

Noisy Neurons

Indian Academy of Sciences (India)

IAS Admin

Hodgkin–Huxley Model and Stochastic Variants. Shruti Paranjape ... ticellular forms, diffusion and signal transduction which suffice for ... on information from and to the brain. Nerves are .... Figure 3 (left). This is the ... Figure 4 (right). This is the.

Coexistence between silent and bursting states in a biophysical Hodgkin-Huxley-type of model

DEFF Research Database (Denmark)

Stankevich, Nataliya; Mosekilde, Erik

2017-01-01

in a slightly modified, biophysical model that describe the dynamics of pancreatic beta-cells. To realize this form of coexistence, we have introduced an additional voltage-dependent potassium current that is activated in the region around the original, unstable equilibrium point. It is interesting to note...... that this modification also leads the model to display a blue-sky catastrophe in the transition region between chaotic and bursting states....

Modelling in vivo action potential propagation along a giant axon.

Science.gov (United States)

George, Stuart; Foster, Jamie M; Richardson, Giles

2015-01-01

A partial differential equation model for the three-dimensional current flow in an excitable, unmyelinated axon is considered. Where the axon radius is significantly below a critical value R(crit) (that depends upon intra- and extra-cellular conductivity and ion channel conductance) the resistance of the intracellular space is significantly higher than that of the extracellular space, such that the potential outside the axon is uniformly small whilst the intracellular potential is approximated by the transmembrane potential. In turn, since the current flow is predominantly axial, it can be shown that the transmembrane potential is approximated by a solution to the one-dimensional cable equation. It is noted that the radius of the squid giant axon, investigated by (Hodgkin and Huxley 1952e), lies close to R(crit). This motivates us to apply the three-dimensional model to the squid giant axon and compare the results thus found to those obtained using the cable equation. In the context of the in vitro experiments conducted in (Hodgkin and Huxley 1952e) we find only a small difference between the wave profiles determined using these two different approaches and little difference between the speeds of action potential propagation predicted. This suggests that the cable equation approximation is accurate in this scenario. However when applied to the it in vivo setting, in which the conductivity of the surrounding tissue is considerably lower than that of the axoplasm, there are marked differences in both wave profile and speed of action potential propagation calculated using the two approaches. In particular, the cable equation significantly over predicts the increase in the velocity of propagation as axon radius increases. The consequences of these results are discussed in terms of the evolutionary costs associated with increasing the speed of action potential propagation by increasing axon radius.

A numerical scheme for the generalized Burgers–Huxley equation

Directory of Open Access Journals (Sweden)

Brajesh K. Singh

2016-10-01

Full Text Available In this article, a numerical solution of generalized Burgers–Huxley (gBH equation is approximated by using a new scheme: modified cubic B-spline differential quadrature method (MCB-DQM. The scheme is based on differential quadrature method in which the weighting coefficients are obtained by using modified cubic B-splines as a set of basis functions. This scheme reduces the equation into a system of first-order ordinary differential equation (ODE which is solved by adopting SSP-RK43 scheme. Further, it is shown that the proposed scheme is stable. The efficiency of the proposed method is illustrated by four numerical experiments, which confirm that obtained results are in good agreement with earlier studies. This scheme is an easy, economical and efficient technique for finding numerical solutions for various kinds of (nonlinear physical models as compared to the earlier schemes.

Feedback controlled electrical nerve stimulation: a computer simulation.

Science.gov (United States)

Doruk, R Ozgur

2010-07-01

The role of repetitive firing in neurophysiologic or neuropsychiatric disorders, such as Parkinson, epilepsy and bipolar type disorders, has always been a topic of medical research as therapies target either the cease of firing or a decrease in its frequency. In electrotherapy, one of the mechanisms to achieve the purpose in point is to apply a low density electric current to the nervous system. In this study, a computer simulation is provided of a treatment in which the stimulation current is computed by nerve fiber cell membrane potential feedback so that the level of the current is automatically instead of manually adjusted. The behavior of the nerve cell is represented by the Hodgkin-Huxley (HH) model, which is slightly modified into a linear model with state dependent coefficients. Due to this modification, the algebraic and differential Riccati equations can be applied, which allows an optimal controller minimizing a quadratic performance index given by the user. Using a controlled current injection can decrease unnecessarily long current injection times that may be harmful to the neuronal network. This study introduces a prototype for a possible future application to a network of neurons as it is more realistic than a single neuron. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Hodgkin's sygdom--et histologisk problem

DEFF Research Database (Denmark)

Lauritzen, A F; Specht, L; Nissen, N I

1989-01-01

Since the Rye classification of Hodgkin's disease, many lesions which resemble Hodgkin's disease microscopically have been described. The histological features of Hodgkin's disease, including the BNLI subclassification of nodular sclerosis, and the lesions which resemble Hodgkin's disease microsc...

A neuron-astrocyte transistor-like model for neuromorphic dressed neurons.

Science.gov (United States)

Valenza, G; Pioggia, G; Armato, A; Ferro, M; Scilingo, E P; De Rossi, D

2011-09-01

Experimental evidences on the role of the synaptic glia as an active partner together with the bold synapse in neuronal signaling and dynamics of neural tissue strongly suggest to investigate on a more realistic neuron-glia model for better understanding human brain processing. Among the glial cells, the astrocytes play a crucial role in the tripartite synapsis, i.e. the dressed neuron. A well-known two-way astrocyte-neuron interaction can be found in the literature, completely revising the purely supportive role for the glia. The aim of this study is to provide a computationally efficient model for neuron-glia interaction. The neuron-glia interactions were simulated by implementing the Li-Rinzel model for an astrocyte and the Izhikevich model for a neuron. Assuming the dressed neuron dynamics similar to the nonlinear input-output characteristics of a bipolar junction transistor, we derived our computationally efficient model. This model may represent the fundamental computational unit for the development of real-time artificial neuron-glia networks opening new perspectives in pattern recognition systems and in brain neurophysiology. Copyright © 2011 Elsevier Ltd. All rights reserved.

Stages of Childhood Hodgkin Lymphoma

Science.gov (United States)

... Version Key Points Childhood Hodgkin lymphoma is a disease in which malignant (cancer) cells form in the lymph system. There are two types of childhood Hodgkin lymphoma. Epstein-Barr virus infection increases the risk of childhood Hodgkin ...

Action Potential Energy Efficiency Varies Among Neuron Types in Vertebrates and Invertebrates

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Sengupta, Biswa; Stemmler, Martin; Laughlin, Simon B.; Niven, Jeremy E.

2010-01-01

The initiation and propagation of action potentials (APs) places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na+ and K+ currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin–Huxley model of the squid axon, optimizing the kinetics or number of Na+ and K+ channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost. PMID:20617202

Non-Hodgkin's lymphomas

International Nuclear Information System (INIS)

Glatstein, E.; Wasserman, T.H.

1987-01-01

Non-Hodgkin's lymphomas are a varied and complex group of diseases that must be distinguished from Hodgkin's disease. The latter almost always begins in lymph nodes and spreads primarily in an axial fashion; non-Hodgkin's lymphomas may begin either in lymph nodes or in extranodal tissue and can spread both in an axial fashion and centrifugally. Because of changes in pathology terminology and the introduction of a classification using cell surface markers, many prognostic groups of patients with lymphomas have evolved. Therapeutic choices and prognosis are greatly influenced by variations in anatomic sites and extent of disease. Currently, the decisions on management require a balancing of radiation therapy with systemic chemotherapy. In some cases, radiation therapy alone may be sufficient; however, because most patients with non-Hodgkins's lymphomas tend to have advanced disease, a large percentage of patients will be managed with chemotherapy alone or in combination with radiation therapy

Radiation-induced splenic atrophy in patients with Hodgkin's disease and non-Hodgkin's lymphomas

International Nuclear Information System (INIS)

Dailey, M.O.; Coleman, C.N.; Kaplan, H.S.

1980-01-01

Effective treatment of Hodgkin's disease requires the determination of the extent of the disease. This usually involves staging laparotomy, which includes splenectomy and biopsies of the para-aortic lymph nodes, liver, and bone marrow. Absence of the spleen predisposes a person to fulminant septicemia from encapsulated bacteria, a risk even greater in patients undergoing treatment for Hodgkin's disease. For this reason, some investigators have suggested that spleens not be removed for diagnosis but, rather, that they be included within the fields of radiation, which would preserve normal splenic function. We present a case of fatal spontaneous pneumococcal sepsis in a patient with splenic atrophy; the sepsis occurred 12 years after successful treatment of Hodgkin's disease by total nodal and splenic irradiation. A retrospective study of patients treated for Hodgkin's and non-Hodgkin's lymphomas indicated that atrophy and functional asplenia may be an important sequela of splenic irradiation

Pediatric Hodgkin's disease - up, up, and beyond

International Nuclear Information System (INIS)

Donaldson, Sarah S.

2002-01-01

Juan A. del Regato, 1909-1999, was a superb clinician-educator who recognized the radiocurability of Hodgkin's disease but questioned treatment without late effects, particularly in children. The remarkable progress in pediatric Hodgkin's disease today is a tribute to this influential pioneer, who served as a role model to many. Combined modality therapy using low-dose, involved-field radiation and multiagent chemotherapy today results in a 5-year relative survival rate of 94% among American children with Hodgkin's disease. However, several areas hold promise for future advances, including a new pathology classification and biology studies that distinguish classic Hodgkin's disease from other lymphomas; new noninvasive staging techniques, including 18F-fluorodeoxyglucose-positron emission tomography; the definition of risk groups to segregate low-, intermediate-, and high-risk groups on the basis of a prognostic index, facilitating risk-adapted therapy; and myeloablative therapy followed by hematopoietic stem cell transplantation. Currently used for children with relapse, it is associated with a 5-year survival of 65% and should be considered as the initial therapy for high-risk groups. Idiopathic diffuse pulmonary toxicity after autologous transplantation is high among children with an atopic history; thus, atopy should be considered when selecting children appropriate for transplantation. Finally, novel therapies, such as the anti-CD20 antibody, rituximab, may be useful for children with CD20+, lymphocyte-predominant Hodgkin's disease. The universal goal of cure without late effects is realistic for almost all children with Hodgkin's disease today

Suppression of anomalous synchronization and nonstationary behavior of neural network under small-world topology

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Boaretto, B. R. R.; Budzinski, R. C.; Prado, T. L.; Kurths, J.; Lopes, S. R.

2018-05-01

It is known that neural networks under small-world topology can present anomalous synchronization and nonstationary behavior for weak coupling regimes. Here, we propose methods to suppress the anomalous synchronization and also to diminish the nonstationary behavior occurring in weakly coupled neural network under small-world topology. We consider a network of 2000 thermally sensitive identical neurons, based on the model of Hodgkin-Huxley in a small-world topology, with the probability of adding non local connection equal to p = 0 . 001. Based on experimental protocols to suppress anomalous synchronization, as well as nonstationary behavior of the neural network dynamics, we make use of (i) external stimulus (pulsed current); (ii) biologic parameters changing (neuron membrane conductance changes); and (iii) body temperature changes. Quantification analysis to evaluate phase synchronization makes use of the Kuramoto's order parameter, while recurrence quantification analysis, particularly the determinism, computed over the easily accessible mean field of network, the local field potential (LFP), is used to evaluate nonstationary states. We show that the methods proposed can control the anomalous synchronization and nonstationarity occurring for weak coupling parameter without any effect on the individual neuron dynamics, neither in the expected asymptotic synchronized states occurring for large values of the coupling parameter.

Detection of nonstationary transition to synchronized states of a neural network using recurrence analyses

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Budzinski, R. C.; Boaretto, B. R. R.; Prado, T. L.; Lopes, S. R.

2017-07-01

We study the stability of asymptotic states displayed by a complex neural network. We focus on the loss of stability of a stationary state of networks using recurrence quantifiers as tools to diagnose local and global stabilities as well as the multistability of a coupled neural network. Numerical simulations of a neural network composed of 1024 neurons in a small-world connection scheme are performed using the model of Braun et al. [Int. J. Bifurcation Chaos 08, 881 (1998), 10.1142/S0218127498000681], which is a modified model from the Hodgkin-Huxley model [J. Phys. 117, 500 (1952)]. To validate the analyses, the results are compared with those produced by Kuramoto's order parameter [Chemical Oscillations, Waves, and Turbulence (Springer-Verlag, Berlin Heidelberg, 1984)]. We show that recurrence tools making use of just integrated signals provided by the networks, such as local field potential (LFP) (LFP signals) or mean field values bring new results on the understanding of neural behavior occurring before the synchronization states. In particular we show the occurrence of different stationary and nonstationarity asymptotic states.

Transition Dynamics of a Dentate Gyrus-CA3 Neuronal Network during Temporal Lobe Epilepsy

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Liyuan Zhang

2017-07-01

Full Text Available In temporal lobe epilepsy (TLE, the variation of chemical receptor expression underlies the basis of neural network activity shifts, resulting in neuronal hyperexcitability and epileptiform discharges. However, dynamical mechanisms involved in the transitions of TLE are not fully understood, because of the neuronal diversity and the indeterminacy of network connection. Hence, based on Hodgkin–Huxley (HH type neurons and Pinsky–Rinzel (PR type neurons coupling with glutamatergic and GABAergic synaptic connections respectively, we propose a computational framework which contains dentate gyrus (DG region and CA3 region. By regulating the concentration range of N-methyl-D-aspartate-type glutamate receptor (NMDAR, we demonstrate the pyramidal neuron can generate transitions from interictal to seizure discharges. This suggests that enhanced endogenous activity of NMDAR contributes to excitability in pyramidal neuron. Moreover, we conclude that excitatory discharges in CA3 region vary considerably on account of the excitatory currents produced by the excitatory pyramidal neuron. Interestingly, by changing the backprojection connection, we find that glutamatergic type backprojection can promote the dominant frequency of firings and further motivate excitatory counterpropagation from CA3 region to DG region. However, GABAergic type backprojection can reduce firing rate and block morbid counterpropagation, which may be factored into the terminations of TLE. In addition, neuronal diversity dominated network shows weak correlation with different backprojections. Our modeling and simulation studies provide new insights into the mechanisms of seizures generation and connectionism in local hippocampus, along with the synaptic mechanisms of this disease.

Potential benefits of therapeutic splenectomy for patients with Hodgkin's disease and non-Hodgkin's lymphomas

International Nuclear Information System (INIS)

Schreiber, D.P.; Jacobs, C.; Rosenberg, S.A.; Cox, R.S.; Hoppe, R.T.

1985-01-01

Thirty-four patients with Hodgkin's disease and non-Hodgkin's lymphoma underwent therapeutic splenectomies to improve hematologic tolerance for chemotherapy. The mean age was 40 years; there were 16 males and 18 females. Fourteen had Hodgkin's disease, 19 had non-Hodgkin's lymphoma, and 1 had malignant histocytosis. Nineteen had palpable splenomegaly, 19 had marrow involvement and 20 had splenic involvement by lymphoma. The following data were analyzed before and after splenectomy: mean white blood cell count (WBC) and platelet count on planned first day of cycle, delay ratio of chemotherapy delivery and percent maximal dose rate. Thirteen patients had non-Hodgkin's lymphoma, splenomegaly and positive bone marrow and showed significant benefit in all of the aforementioned parameters. Of the patients with prior irradiation, only those who completed their radiation greater than six months prior to splenectomy showed benefit. Ten patients had Hodgkin's disease, negative bone marrow and no splenomegaly. This group showed significant improvement in mean platelet count but more limited benefit in delay ratio and percent maximal dose rate. Thus, selected patients with lymphoma who are experiencing delays in chemotherapy because of poor count tolerance may benefit from splenectomy

The stomatogastric nervous system as a model for studying sensorimotor interactions in real-time closed-loop conditions

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Nelly eDaur

2012-03-01

Full Text Available The perception of proprioceptive signals that report the internal state of the body is one of the essential tasks of the nervous system and helps to continuously adapt body movements to changing circumstances. Despite the impact of proprioceptive feedback on motor activity it has rarely been studied in conditions in which motor output and sensory activity interact as they do in behaving animals, i.e. in closed-loop conditions. The interaction of motor and sensory activities, however, can create emergent properties that may govern the functional characteristics of the system. We here demonstrate the use of a well-characterized model system for central pattern generation, the stomatogastric nervous system, for studying these properties in vitro. We created a real-time computer model of a single-cell muscle tendon organ in the gastric mill of the crab foregut that uses intracellular current injections to control the activity of the biological proprioceptor. The resulting motor output of a gastric mill motor neuron is then recorded intracellularly and fed into a simple muscle model consisting of a series of low-pass filters. The muscle output is used to activate a one-dimensional Hodgkin-Huxley type model of the muscle tendon organ in real-time, allowing closed-loop conditions. Model properties were either hand-tuned to achieve the best match with data from semi-intact muscle preparations, or an exhaustive search was performed to determine the best set of parameters. We report the real-time capabilities of our models, its performance and its interaction with the biological motor system.

Modeling pathogenesis and treatment response in childhood absence epilepsy.

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Knox, Andrew T; Glauser, Tracy; Tenney, Jeffrey; Lytton, William W; Holland, Katherine

2018-01-01

Childhood absence epilepsy (CAE) is a genetic generalized epilepsy syndrome with polygenic inheritance, with genes for γ-aminobutyric acid (GABA) receptors and T-type calcium channels implicated in the disorder. Previous studies of T-type calcium channel electrophysiology have shown genetic changes and medications have multiple effects. The aim of this study was to use an established thalamocortical computer model to determine how T-type calcium channels work in concert with cortical excitability to contribute to pathogenesis and treatment response in CAE. The model is comprised of cortical pyramidal, cortical inhibitory, thalamocortical relay, and thalamic reticular single-compartment neurons, implemented with Hodgkin-Huxley model ion channels and connected by AMPA, GABA A , and GABA B synapses. Network behavior was simulated for different combinations of T-type calcium channel conductance, inactivation time, steady state activation/inactivation shift, and cortical GABA A conductance. Decreasing cortical GABA A conductance and increasing T-type calcium channel conductance converted spindle to spike and wave oscillations; smaller changes were required if both were changed in concert. In contrast, left shift of steady state voltage activation/inactivation did not lead to spike and wave oscillations, whereas right shift reduced network propensity for oscillations of any type. These results provide a window into mechanisms underlying polygenic inheritance in CAE, as well as a mechanism for treatment effects and failures mediated by these channels. Although the model is a simplification of the human thalamocortical network, it serves as a useful starting point for predicting the implications of ion channel electrophysiology in polygenic epilepsy such as CAE. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Hodgkin Lymphoma (For Kids)

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... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Hodgkin Lymphoma KidsHealth / For Kids / Hodgkin Lymphoma What's in this article? What Is ...

Optimal decoding and information transmission in Hodgkin–Huxley neurons under metabolic cost constraints

Czech Academy of Sciences Publication Activity Database

Košťál, Lubomír; Kobayashi, R.

2015-01-01

Roč. 136, Oct 2015 (2015), s. 3-10 ISSN 0303-2647 R&D Projects: GA ČR(CZ) GA15-08066S Institutional support: RVO:67985823 Keywords : neuronal coding * information transfer * optimal decoding Subject RIV: BD - Theory of Information Impact factor: 1.495, year: 2015

Epstein-Barr Virus in Classical Hodgkin Lymphoma

International Nuclear Information System (INIS)

Azhar, M.; Din, H. U.; Muhammad, I.; Hashmi, S. N.; Akhtar, F.

2016-01-01

Background: Epstein-Barr virus plays an important role in pathogenesis of Hodgkin lymphoma. The first patient with Epstein-Barr positive Reed Sternberg cells was described in 1985. Since then association between Epstein-Barr virus and Hodgkin lymphoma has been shown in many parts of the world and its occurrence shows significant variation from continent to continent and from country to country. Method: The study was carried out at department of histopathology, Armed Forces Institute of Pathology from 27th April 2013 to 10th March 2014. A total of 55 cases of classical Hodgkin lymphoma were included in the study. Results: Out of 55 patients, 38 (69 percent) were male and 17 (31 percent) were female. The age of the patients ranged between 4-67 years with an average age of 29.4±21.72 years. Out of these, 44 cases (80 percent) were positive for latent membrane protein-1. Among positive cases 32 (72.72 percent) were male and 12 (27.28 percent) were female. Based upon histological subtypes MCHL was the commonest as a whole accounting for 87.3 percent as well as among both genders. Out of total 55 cases, 79.16 percent (38/48) of mixed cellularity Hodgkin lymphoma cases showed positivity for latent membrane protein-1 while 83.33 percent (5/6) cases of nodular sclerosis Hodgkin lymphoma and 100 percent (1/1) cases of lymphocyte depleted Hodgkin lymphoma showed positivity. No case of lymphocyte predominant classical Hodgkin lymphoma was diagnosed during the study. 80 percent of our classical Hodgkin lymphoma cases showed association with EBV expression. A total of 79.16 percent cases of mixed cellularity Hodgkin lymphoma showed LMP1 expression while 100 percent of lymphocyte depleted Hodgkin lymphoma showed LMP1 expression. Conclusion: The highest expression seen in lymphocyte depleted Hodgkin lymphoma subtype in contrast to mixed cellularity requires to be confirmed by a larger scale study comprising of substantial number of patients of lymphocyte depleted Hodgkin lymphoma

Special issue on Computational Neuroscience - PREFACE

DEFF Research Database (Denmark)

Ditlevsen, Susanne; Lansky, Petr

2014-01-01

This Special Issue of Mathematical Biosciences and Engineering contains ten selected papers presented at the Neural Coding 2012 workshop. Neuroscience is traditionally very close to mathematics which stems from the famous theoretical work of McCulloch--Pitts and Hodgkin--Huxley in the middle...

Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

Science.gov (United States)

2017-11-15

Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

Synchronization in networks with heterogeneous coupling delays

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Otto, Andreas; Radons, Günter; Bachrathy, Dániel; Orosz, Gábor

2018-01-01

Synchronization in networks of identical oscillators with heterogeneous coupling delays is studied. A decomposition of the network dynamics is obtained by block diagonalizing a newly introduced adjacency lag operator which contains the topology of the network as well as the corresponding coupling delays. This generalizes the master stability function approach, which was developed for homogenous delays. As a result the network dynamics can be analyzed by delay differential equations with distributed delay, where different delay distributions emerge for different network modes. Frequency domain methods are used for the stability analysis of synchronized equilibria and synchronized periodic orbits. As an example, the synchronization behavior in a system of delay-coupled Hodgkin-Huxley neurons is investigated. It is shown that the parameter regions where synchronized periodic spiking is unstable expand when increasing the delay heterogeneity.

Fluid mechanics in dentinal microtubules provides mechanistic insights into the difference between hot and cold dental pain.

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Lin, Min; Luo, Zheng Yuan; Bai, Bo Feng; Xu, Feng; Lu, Tian Jian

2011-03-23

Dental thermal pain is a significant health problem in daily life and dentistry. There is a long-standing question regarding the phenomenon that cold stimulation evokes sharper and more shooting pain sensations than hot stimulation. This phenomenon, however, outlives the well-known hydrodynamic theory used to explain dental thermal pain mechanism. Here, we present a mathematical model based on the hypothesis that hot or cold stimulation-induced different directions of dentinal fluid flow and the corresponding odontoblast movements in dentinal microtubules contribute to different dental pain responses. We coupled a computational fluid dynamics model, describing the fluid mechanics in dentinal microtubules, with a modified Hodgkin-Huxley model, describing the discharge behavior of intradental neuron. The simulated results agreed well with existing experimental measurements. We thence demonstrated theoretically that intradental mechano-sensitive nociceptors are not "equally sensitive" to inward (into the pulp) and outward (away from the pulp) fluid flows, providing mechanistic insights into the difference between hot and cold dental pain. The model developed here could enable better diagnosis in endodontics which requires an understanding of pulpal histology, neurology and physiology, as well as their dynamic response to the thermal stimulation used in dental practices.

Dorothy Crowfoot Hodgkin

Science.gov (United States)

Montalvo, Jessica

2009-10-01

Born in 1910 in Cairo, Egypt, Dorothy Crowfoot Hodgkin would later be known as the third woman in history to win the Nobel Prize in Chemistry for her research on the structure of vitamin B-12. Her X-ray crystallography work also included discovering the molecular structure of penicillin and insulin. Dr. Hodgkin's work has aided in determining the structures of molecules for others to expand the technology necessary for today's medicine.

Stochastic neuron models

CERN Document Server

Greenwood, Priscilla E

2016-01-01

This book describes a large number of open problems in the theory of stochastic neural systems, with the aim of enticing probabilists to work on them. This includes problems arising from stochastic models of individual neurons as well as those arising from stochastic models of the activities of small and large networks of interconnected neurons. The necessary neuroscience background to these problems is outlined within the text, so readers can grasp the context in which they arise. This book will be useful for graduate students and instructors providing material and references for applying probability to stochastic neuron modeling. Methods and results are presented, but the emphasis is on questions where additional stochastic analysis may contribute neuroscience insight. An extensive bibliography is included. Dr. Priscilla E. Greenwood is a Professor Emerita in the Department of Mathematics at the University of British Columbia. Dr. Lawrence M. Ward is a Professor in the Department of Psychology and the Brain...

Stages of Adult Hodgkin Lymphoma

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... Lymphocyte-rich classical Hodgkin lymphoma. Age, gender, and Epstein-Barr infection can affect the risk of adult Hodgkin lymphoma. Anything that increases your risk of getting a disease is called a risk factor . Having a risk ...

Gain control network conditions in early sensory coding.

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Eduardo Serrano

Full Text Available Gain control is essential for the proper function of any sensory system. However, the precise mechanisms for achieving effective gain control in the brain are unknown. Based on our understanding of the existence and strength of connections in the insect olfactory system, we analyze the conditions that lead to controlled gain in a randomly connected network of excitatory and inhibitory neurons. We consider two scenarios for the variation of input into the system. In the first case, the intensity of the sensory input controls the input currents to a fixed proportion of neurons of the excitatory and inhibitory populations. In the second case, increasing intensity of the sensory stimulus will both, recruit an increasing number of neurons that receive input and change the input current that they receive. Using a mean field approximation for the network activity we derive relationships between the parameters of the network that ensure that the overall level of activity of the excitatory population remains unchanged for increasing intensity of the external stimulation. We find that, first, the main parameters that regulate network gain are the probabilities of connections from the inhibitory population to the excitatory population and of the connections within the inhibitory population. Second, we show that strict gain control is not achievable in a random network in the second case, when the input recruits an increasing number of neurons. Finally, we confirm that the gain control conditions derived from the mean field approximation are valid in simulations of firing rate models and Hodgkin-Huxley conductance based models.

Hodgkin's Lymphoma of the Breast

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TNHJOURNALPH

RESULT. A tissue diagnosis of Hodgkin's lymphoma with typical ... It was the first cancer to be cured ... ultrasonography showed enlarged liver. The .... McMillan A, Horning S. Non-Hodgkins lymphoma of the Breast. Cancer. 2007;110:25-30. 5.

Hodgkin's disease in pregnancy

International Nuclear Information System (INIS)

Szelc, S.; Szeliga, E.

1993-01-01

Pregnancy outcome and its influence on the effect of the MOPP chemotherapy for 30 patients with Hodgkin's disease were analyzed. During the first 6 months after completing the treatment 305 of pregnancies were interrupted. Pregnancy during complete remission of Hodgkin's disease after combined treatment does not increase the risk of relapse and is not a risk to delivery and foetus. (author)

ATR alterations in Hodgkin's lymphoma

NARCIS (Netherlands)

Liu, Angen; Takakuwa, Tetsuya; Fujita, Shigeki; Luo, Wen-Juan; Tresnasari, Kristianti; Van den Berg, Anke; Poppema, Sibrand; Aozasa, Katsuyuki

Hodgkin's lymphoma (HL) is characterized by the presence of neoplastic Hodgkin and Reed-Sternberg cells (HRSC) in a background of inflammatory cells. Free radicals and oxidative stress generated in the inflammatory lesions could cause DNA damage, thus providing a basis for lymphomagenesis.

Effects of channel blocking on information transmission and energy efficiency in squid giant axons.

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Liu, Yujiang; Yue, Yuan; Yu, Yuguo; Liu, Liwei; Yu, Lianchun

2018-04-01

Action potentials are the information carriers of neural systems. The generation of action potentials involves the cooperative opening and closing of sodium and potassium channels. This process is metabolically expensive because the ions flowing through open channels need to be restored to maintain concentration gradients of these ions. Toxins like tetraethylammonium can block working ion channels, thus affecting the function and energy cost of neurons. In this paper, by computer simulation of the Hodgkin-Huxley neuron model, we studied the effects of channel blocking with toxins on the information transmission and energy efficiency in squid giant axons. We found that gradually blocking sodium channels will sequentially maximize the information transmission and energy efficiency of the axons, whereas moderate blocking of potassium channels will have little impact on the information transmission and will decrease the energy efficiency. Heavy blocking of potassium channels will cause self-sustained oscillation of membrane potentials. Simultaneously blocking sodium and potassium channels with the same ratio increases both information transmission and energy efficiency. Our results are in line with previous studies suggesting that information processing capacity and energy efficiency can be maximized by regulating the number of active ion channels, and this indicates a viable avenue for future experimentation.

Neurite, a finite difference large scale parallel program for the simulation of electrical signal propagation in neurites under mechanical loading.

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Julián A García-Grajales

Full Text Available With the growing body of research on traumatic brain injury and spinal cord injury, computational neuroscience has recently focused its modeling efforts on neuronal functional deficits following mechanical loading. However, in most of these efforts, cell damage is generally only characterized by purely mechanistic criteria, functions of quantities such as stress, strain or their corresponding rates. The modeling of functional deficits in neurites as a consequence of macroscopic mechanical insults has been rarely explored. In particular, a quantitative mechanically based model of electrophysiological impairment in neuronal cells, Neurite, has only very recently been proposed. In this paper, we present the implementation details of this model: a finite difference parallel program for simulating electrical signal propagation along neurites under mechanical loading. Following the application of a macroscopic strain at a given strain rate produced by a mechanical insult, Neurite is able to simulate the resulting neuronal electrical signal propagation, and thus the corresponding functional deficits. The simulation of the coupled mechanical and electrophysiological behaviors requires computational expensive calculations that increase in complexity as the network of the simulated cells grows. The solvers implemented in Neurite--explicit and implicit--were therefore parallelized using graphics processing units in order to reduce the burden of the simulation costs of large scale scenarios. Cable Theory and Hodgkin-Huxley models were implemented to account for the electrophysiological passive and active regions of a neurite, respectively, whereas a coupled mechanical model accounting for the neurite mechanical behavior within its surrounding medium was adopted as a link between electrophysiology and mechanics. This paper provides the details of the parallel implementation of Neurite, along with three different application examples: a long myelinated axon

Efficient Coding and Energy Efficiency Are Promoted by Balanced Excitatory and Inhibitory Synaptic Currents in Neuronal Network.

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Yu, Lianchun; Shen, Zhou; Wang, Chen; Yu, Yuguo

2018-01-01

Selective pressure may drive neural systems to process as much information as possible with the lowest energy cost. Recent experiment evidence revealed that the ratio between synaptic excitation and inhibition (E/I) in local cortex is generally maintained at a certain value which may influence the efficiency of energy consumption and information transmission of neural networks. To understand this issue deeply, we constructed a typical recurrent Hodgkin-Huxley network model and studied the general principles that governs the relationship among the E/I synaptic current ratio, the energy cost and total amount of information transmission. We observed in such a network that there exists an optimal E/I synaptic current ratio in the network by which the information transmission achieves the maximum with relatively low energy cost. The coding energy efficiency which is defined as the mutual information divided by the energy cost, achieved the maximum with the balanced synaptic current. Although background noise degrades information transmission and imposes an additional energy cost, we find an optimal noise intensity that yields the largest information transmission and energy efficiency at this optimal E/I synaptic transmission ratio. The maximization of energy efficiency also requires a certain part of energy cost associated with spontaneous spiking and synaptic activities. We further proved this finding with analytical solution based on the response function of bistable neurons, and demonstrated that optimal net synaptic currents are capable of maximizing both the mutual information and energy efficiency. These results revealed that the development of E/I synaptic current balance could lead a cortical network to operate at a highly efficient information transmission rate at a relatively low energy cost. The generality of neuronal models and the recurrent network configuration used here suggest that the existence of an optimal E/I cell ratio for highly efficient energy

Mechanism for propagation of rate signals through a 10-layer feedforward neuronal network

International Nuclear Information System (INIS)

Jie, Li; Wan-Qing, Yu; Ding, Xu; Feng, Liu; Wei, Wang

2009-01-01

Using numerical simulations, we explore the mechanism for propagation of rate signals through a 10-layer feedforward network composed of Hodgkin–Huxley (HH) neurons with sparse connectivity. When white noise is afferent to the input layer, neuronal firing becomes progressively more synchronous in successive layers and synchrony is well developed in deeper layers owing to the feedforward connections between neighboring layers. The synchrony ensures the successful propagation of rate signals through the network when the synaptic conductance is weak. As the synaptic time constant τ syn varies, coherence resonance is observed in the network activity due to the intrinsic property of HH neurons. This makes the output firing rate single-peaked as a function of τ syn , suggesting that the signal propagation can be modulated by the synaptic time constant. These results are consistent with experimental results and advance our understanding of how information is processed in feedforward networks. (cross-disciplinary physics and related areas of science and technology)

Energy Model of Neuron Activation.

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Romanyshyn, Yuriy; Smerdov, Andriy; Petrytska, Svitlana

2017-02-01

On the basis of the neurophysiological strength-duration (amplitude-duration) curve of neuron activation (which relates the threshold amplitude of a rectangular current pulse of neuron activation to the pulse duration), as well as with the use of activation energy constraint (the threshold curve corresponds to the energy threshold of neuron activation by a rectangular current pulse), an energy model of neuron activation by a single current pulse has been constructed. The constructed model of activation, which determines its spectral properties, is a bandpass filter. Under the condition of minimum-phase feature of the neuron activation model, on the basis of Hilbert transform, the possibilities of phase-frequency response calculation from its amplitude-frequency response have been considered. Approximation to the amplitude-frequency response by the response of the Butterworth filter of the first order, as well as obtaining the pulse response corresponding to this approximation, give us the possibility of analyzing the efficiency of activating current pulses of various shapes, including analysis in accordance with the energy constraint.

Large-scale modelling of neuronal systems

International Nuclear Information System (INIS)

Castellani, G.; Verondini, E.; Giampieri, E.; Bersani, F.; Remondini, D.; Milanesi, L.; Zironi, I.

2009-01-01

The brain is, without any doubt, the most, complex system of the human body. Its complexity is also due to the extremely high number of neurons, as well as the huge number of synapses connecting them. Each neuron is capable to perform complex tasks, like learning and memorizing a large class of patterns. The simulation of large neuronal systems is challenging for both technological and computational reasons, and can open new perspectives for the comprehension of brain functioning. A well-known and widely accepted model of bidirectional synaptic plasticity, the BCM model, is stated by a differential equation approach based on bistability and selectivity properties. We have modified the BCM model extending it from a single-neuron to a whole-network model. This new model is capable to generate interesting network topologies starting from a small number of local parameters, describing the interaction between incoming and outgoing links from each neuron. We have characterized this model in terms of complex network theory, showing how this, learning rule can be a support For network generation.

Autonomic dysfunction in Hodgkin and non-Hodgkin lymphoma. A paraneoplastic syndrome?

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Franca Bilora

2010-11-01

Full Text Available We wanted to determine whether autonomic dysfunction in patients with lymphoma is related to chemotherapy or represent a paraneoplastic syndrome. 40 patients with current or cured Hodgkin or non-Hodgkin lymphoma and 40 healthy controls, matched for age, gender, hypertension and diabetes mellitus underwent autonomic evaluation (Deep Breath, Valsalva Maneuver, Hand Grip, Lying to Standing, Tilt Test. Current patients also suffering from diabetes or hypertension, or still on chemotherapy revealed autonomic changes, while cured or healthy subjects did not. Autonomic dysfunction in lymphoma is a transient manifestation of a paraneoplastic syndrome.

General Information about Adult Hodgkin Lymphoma

Science.gov (United States)

... Lymphocyte-rich classical Hodgkin lymphoma. Age, gender, and Epstein-Barr infection can affect the risk of adult Hodgkin lymphoma. Anything that increases your risk of getting a disease is called a risk factor . Having a risk ...

Fitting neuron models to spike trains

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Cyrille eRossant

2011-02-01

Full Text Available Computational modeling is increasingly used to understand the function of neural circuitsin systems neuroscience.These studies require models of individual neurons with realisticinput-output properties.Recently, it was found that spiking models can accurately predict theprecisely timed spike trains produced by cortical neurons in response tosomatically injected currents,if properly fitted. This requires fitting techniques that are efficientand flexible enough to easily test different candidate models.We present a generic solution, based on the Brian simulator(a neural network simulator in Python, which allowsthe user to define and fit arbitrary neuron models to electrophysiological recordings.It relies on vectorization and parallel computing techniques toachieve efficiency.We demonstrate its use on neural recordings in the barrel cortex andin the auditory brainstem, and confirm that simple adaptive spiking modelscan accurately predict the response of cortical neurons. Finally, we show how a complexmulticompartmental model can be reduced to a simple effective spiking model.

C. elegans model of neuronal aging

OpenAIRE

Peng, Chiu-Ying; Chen, Chun-Hao; Hsu, Jiun-Min; Pan, Chun-Liang

2011-01-01

Aging of the nervous system underlies the behavioral and cognitive decline associated with senescence. Understanding the molecular and cellular basis of neuronal aging will therefore contribute to the development of effective treatments for aging and age-associated neurodegenerative disorders. Despite this pressing need, there are surprisingly few animal models that aim at recapitulating neuronal aging in a physiological context. We recently developed a C. elegans model of neuronal aging, and...

[Predictive value of Hodgkin's lymphoma tumor burden in present].

Science.gov (United States)

Kulyova, S A; Karitsky, A P

2014-01-01

Today approximately 70% of patients with Hodgkin lymphoma can be cured with the combined-modality therapy. Tumor burden, the importance of which was demonstrated 15 years ago for the first time, is a powerful prognostic factor. Data of literature of representations on predictive value of Hodgkin's lymphoma tumor burden are shown in the article. The difficult immunological relations between tumor cells and reactive ones lead to development of the main symptoms. Nevertheless, the collective sign of tumor burden shows the greatest influence on survival and on probability of resistance, which relative risk can be predicted on this variable and treatment program. Patients with bulky disease need escalated therapy with high-dose chemotherapy. Integration into predictive models of the variable will change an expected contribution of clinical and laboratory parameters in the regression analyses constructed on patients with Hodgkin's lymphoma. Today the role of diagnostic functional methods, in particular a positron emission tomography, for metabolic active measurement is conducted which allows excluding a reactive component.

Functionalized anatomical models for EM-neuron Interaction modeling

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Neufeld, Esra; Cassará, Antonino Mario; Montanaro, Hazael; Kuster, Niels; Kainz, Wolfgang

2016-06-01

The understanding of interactions between electromagnetic (EM) fields and nerves are crucial in contexts ranging from therapeutic neurostimulation to low frequency EM exposure safety. To properly consider the impact of in vivo induced field inhomogeneity on non-linear neuronal dynamics, coupled EM-neuronal dynamics modeling is required. For that purpose, novel functionalized computable human phantoms have been developed. Their implementation and the systematic verification of the integrated anisotropic quasi-static EM solver and neuronal dynamics modeling functionality, based on the method of manufactured solutions and numerical reference data, is described. Electric and magnetic stimulation of the ulnar and sciatic nerve were modeled to help understanding a range of controversial issues related to the magnitude and optimal determination of strength-duration (SD) time constants. The results indicate the importance of considering the stimulation-specific inhomogeneous field distributions (especially at tissue interfaces), realistic models of non-linear neuronal dynamics, very short pulses, and suitable SD extrapolation models. These results and the functionalized computable phantom will influence and support the development of safe and effective neuroprosthetic devices and novel electroceuticals. Furthermore they will assist the evaluation of existing low frequency exposure standards for the entire population under all exposure conditions.

Hodgkin's disease and age

DEFF Research Database (Denmark)

Specht, L.; Nissen, N.I.

1989-01-01

506 unselected, previously untreated patients with Hodgkin's disease were treated at the Finsen Institute between 1969 and 1983. The prognostic significance of age, sex, stage, systemic symptoms, histologic subtype, number of involved nodal regions, total tumour burden (peripheral + intrathoracic...... modality, stage, and total tumour burden, whereas age had no prognostic significance. With regard to death from Hodgkin's disease only age and total tumour burden had independent significance. The significance of age would seem to stem from the fact that some older patients could not be given adequate...

Stochastic models for spike trains of single neurons

CERN Document Server

Sampath, G

1977-01-01

1 Some basic neurophysiology 4 The neuron 1. 1 4 1. 1. 1 The axon 7 1. 1. 2 The synapse 9 12 1. 1. 3 The soma 1. 1. 4 The dendrites 13 13 1. 2 Types of neurons 2 Signals in the nervous system 14 2. 1 Action potentials as point events - point processes in the nervous system 15 18 2. 2 Spontaneous activi~ in neurons 3 Stochastic modelling of single neuron spike trains 19 3. 1 Characteristics of a neuron spike train 19 3. 2 The mathematical neuron 23 4 Superposition models 26 4. 1 superposition of renewal processes 26 4. 2 Superposition of stationary point processe- limiting behaviour 34 4. 2. 1 Palm functions 35 4. 2. 2 Asymptotic behaviour of n stationary point processes superposed 36 4. 3 Superposition models of neuron spike trains 37 4. 3. 1 Model 4. 1 39 4. 3. 2 Model 4. 2 - A superposition model with 40 two input channels 40 4. 3. 3 Model 4. 3 4. 4 Discussion 41 43 5 Deletion models 5. 1 Deletion models with 1nd~endent interaction of excitatory and inhibitory sequences 44 VI 5. 1. 1 Model 5. 1 The basic de...

Hodgkin's Lymphoma

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... People who have had illnesses caused by the Epstein-Barr virus, such as infectious mononucleosis, are more likely to develop Hodgkin's lymphoma than are people who haven't had Epstein-Barr infections. By Mayo Clinic Staff . Mayo Clinic Footer ...

Intussuscepção em linfoma Não-Hodgkin Intussuception in Non-Hodgkin's lymphoma

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Alessandra O. Ehrhardt

2003-06-01

Full Text Available Intussusception in adults is a rare condition and it can occur as a gastric complication from non-Hodgkin's lymphoma. Such complications can be difficult to diagnose because of ill-defined symptoms. Methods of imaging such as abdominal X-rays, ultrasonography, tomography and colonoscopy are useful for its diagnosis. Here a female patient with non-Hodgkin's lymphoma that evolved to intussusception of bowels, the regression of which was achieved by clinical and chemotherapeutic treatment without surgical intervention.

Second cancers after treatment for Hodgkin's disease: A review

International Nuclear Information System (INIS)

Boivin, J.F.; Hutchison, G.B.

1984-01-01

The authors review several reports of series of patients with Hodgkin's disease among whom second primary cancers have been diagnosed after radiotherapy or chemotherapy or both for Hodgkin's disease. An analysis of these reports suggests that (a) chemotherapy is a strong risk factor for leukemia, and (b) in the absence of chemotherapy, leukemia shows little or no increased incidence over ''spontaneous'' rates. Seven drugs have been identified as being frequently used in treatment of Hodgkin's disease (nitrogen mustard, cyclophosphamide, chlorambucil, procarbazine, vinglastine, vincristine, and prednisone). A large proportion of the patients receiving chemotherapy for Hodgkin's disease are exposed to several drugs and quantitative estimates of the independent leukemogenic effects of these drugs have not yet been obtained. Most of the person-years' experience accrued in the published studies occurred in the first decade after treatment for Hodgkin's disease. Follow-up over longer intervals of time will be necessary before solid tumor risk after therapy for Hodgkin's disease can be evaluated

Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma

DEFF Research Database (Denmark)

Shepherd, Leah; Ryom, Lene; Law, Matthew

2018-01-01

Background: Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are increased in populations with immune dysfunction, including people living with HIV; however, there is little evidence for to what degree immunological and virological factors differently affect NHL and HL risk. Methods: Data from...... the Data Collection on Adverse events of Anti-HIV Drugs Study cohort were analyzed to identify independent risk factors for NHL and HL using hazard ratios (HRs), focusing on current and cumulative area under the curve (AUC) measures of immunological and virological status. Variables with different...

MRI assessment of bone marrow involvement in Hodgkin disease and non-Hodgkin lymphoma

International Nuclear Information System (INIS)

Tesoro Tess, J.D.; Balzarini, L.; Ceglia, E.; Petrillo, R.; Musumeci, R.

1990-01-01

In order to evaluate the possible role of MRI in detecting lymphomatous marrow involvement, a MRI examination was performed in newly diagnosed patients with Hodgkin's disease (HD) and nonHodgkin lymphoma (NHL). From this the authors concluded that MRI should not be used as a replacement for bone marrow biopsies in HD and NHL, but rather as a complementary tool utilizing the panoramic view offered by MRI which permit to disclose focal areas of bone involvement different from the sacrum, thus not valuable with routine biopsies. (author). 4 refs.; 1 tab

Characteristics of Hodgkin's lymphoma after infectious mononucleosis

DEFF Research Database (Denmark)

Hjalgrim, Henrik; Askling, Johan; Rostgaard, Klaus

2003-01-01

BACKGROUND: Infectious mononucleosis-related Epstein-Barr virus (EBV) infection has been associated with an increased risk of Hodgkin's lymphoma in young adults. Whether the association is causal remains unclear. METHODS: We compared the incidence rates of Hodgkin's lymphoma in two population...

Linfoma no-Hodgkin del sistema nervioso central

OpenAIRE

Iglesias Rozas, José Rafael, 1942-

2000-01-01

Diecisiete imágenes de un linfoma no-Hodgkin del sistema nervioso central en una paciente de 66 años. Seventeen pictures of a non-Hodgkin lymphoma of the central nervous system in a 66-year-old female patient.

A minimal model for a slow pacemaking neuron

International Nuclear Information System (INIS)

Zakharov, D.G.; Kuznetsov, A.

2012-01-01

Highlights: ► We have constructed a phenomenological model for slow pacemaking neurons. ► The model implements a nonlinearity introduced by an ion-dependent current. ► The new nonlinear dependence allows for differentiating responses to various stimuli. ► We discuss implications of our results for a broad class of neurons. - Abstract: We have constructed a phenomenological model for slow pacemaking neurons. These are neurons that generate very regular periodic oscillations of the membrane potential. Many of these neurons also differentially respond to various types of stimulation. The model is based on FitzHugh–Nagumo (FHN) oscillator and implements a nonlinearity introduced by a current that depends on an ion concentration. The comparison with the original FHN oscillator has shown that the new nonlinear dependence allows for differentiating responses to various stimuli. We discuss implications of our results for a broad class of neurons.

PET imaging in pediatric Hodgkin's lymphoma

International Nuclear Information System (INIS)

Hudson, M.M.; Krasin, M.J.; Kaste, S.C.

2004-01-01

Advances in diagnostic imaging technology, especially functional imaging modalities like positron emission tomography (PET), have significantly influenced the staging and treatment approaches used for pediatric Hodgkin's lymphoma. Today, the majority of children and adolescents diagnosed with Hodgkin's lymphoma will be cured following treatment with noncross-resistant combination chemotherapy alone or in combination with low-dose, involved-field radiation. This success produced a greater appreciation of long-term complications related to radiation, chemotherapy, and surgical staging that prompted significant changes in staging and treatment protocols for children and adolescents with Hodgkin's lymphoma. Contemporary treatment for pediatric Hodgkin's lymphoma uses a risk-adapted approach that reduces the number of combination chemotherapy cycles and radiation treatment fields and doses for patients with localized favorable disease presentation. Advances in diagnostic imaging technology have played a critical role in the development of these risk-adapted treatment regimens. The introduction of computed tomography (CT) provided an accurate and non-invasive modality to define nodal involvement below the diaphragm that motivated the change from surgical to clinical staging. The introduction of functional imaging modalities, like positron emission tomography (PET) scanning, provided the means to correlate tumor activity with anatomic features generated by CT and modify treatment based on tumor response. For centers with access to this modality, PET imaging plays an important role in staging, evaluating tumor response, planning radiation treatment fields, and monitoring after completion of therapy for pediatric Hodgkin's lymphoma. (orig.)

Targeted immunotherapy in Hodgkin lymphoma

DEFF Research Database (Denmark)

Hutchings, Martin

2015-01-01

In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13.......In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13....

Observability and synchronization of neuron models

Science.gov (United States)

Aguirre, Luis A.; Portes, Leonardo L.; Letellier, Christophe

2017-10-01

Observability is the property that enables recovering the state of a dynamical system from a reduced number of measured variables. In high-dimensional systems, it is therefore important to make sure that the variable recorded to perform the analysis conveys good observability of the system dynamics. The observability of a network of neuron models depends nontrivially on the observability of the node dynamics and on the topology of the network. The aim of this paper is twofold. First, to perform a study of observability using four well-known neuron models by computing three different observability coefficients. This not only clarifies observability properties of the models but also shows the limitations of applicability of each type of coefficients in the context of such models. Second, to study the emergence of phase synchronization in networks composed of neuron models. This is done performing multivariate singular spectrum analysis which, to the best of the authors' knowledge, has not been used in the context of networks of neuron models. It is shown that it is possible to detect phase synchronization: (i) without having to measure all the state variables, but only one (that provides greatest observability) from each node and (ii) without having to estimate the phase.

[Establishment of oxygen and glucose deprive model of in vitro cultured hippocampal neuron and effect of ligustrazine on intracellular Ca+ level in model neurons].

Science.gov (United States)

Wan, Hai-tong; Wang, Yu; Yang, Jie-hong

2007-03-01

To establish the oxygen and glucose deprive (OGD) model in cultured hippocampal neuron and study the effect of ligustrazine on intracellular Ca2+ level in the model neurons. The OGD model was established in cultured hippocampal neuron, and the intracellular Ca2+ level in it was detected by laser scanning confocal microscope (LSCM). The OGD model was successfully established in cultured hippocampal neurons; the intracellular Ca2+ level in the OGD model group was significantly higher than that in the blank control group (P neuron, which could be antagonized by ligustrazine, indicating that ligustrazine has a protective effect on hippocampal neuron from hypoxic-ischemic injury.

Mucormicosis yeyunal en paciente con linfoma de Hodgkin Jejunal mucormycosis in a patient with Hodgkin's lymphoma

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B. Madrigal

2008-08-01

Full Text Available Comunicamos un caso de mucormicosis intestinal en un hombre de 46 años de edad, diagnosticado de enfermedad de Hodgkin clásica, estadio IV-B. Durante la primera fase de la quimioterapia, sufrió una hemorragia digestiva masiva secundaria a una úlcera yeyunal por zigomicosis tipo mucor, diagnosticada por biopsia endoscópica. El paciente fue tratado con antifúngicos y resección quirúrgica del intestino afectado. En la cirugía, se apreció una doble perforación yeyunal cubierta. El estudio anatomopatológico de la pieza confirmó el diagnóstico previo. Tras un año de seguimiento, el paciente está recuperado y su linfoma de Hodgkin en remisión completa. Tras una extensa revisión de la literatura, según nuestro conocimiento, este es el segundo caso publicado en la literatura de mucormicosis intestinal en un paciente con linfoma de Hodgkin.We report a case of intestinal mucormycosis in a 46-year-old male diagnosed with classical Hodgkin's disease, IV-B stage. During the first phase of chemotherapy he had a massive digestive bleeding event secondary to a jejunal ulcer, and zygomicosis mucor-type was diagnosed by endoscopic biopsy. The patient was treated with antifungal drugs and surgical resection of the intestine involved. At surgery a double covered perforation of the jejunum was seen. Pathological examination confirmed the previous diagnosis. After one year of follow-up the patient is doing well, and his lymphoma is on remission. To our best knowledge this is the second case of intestinal mucormycosis in a patient with Hodgkin's lymphoma reported in the medical literature.

A hidden Markov model approach to neuron firing patterns.

Science.gov (United States)

Camproux, A C; Saunier, F; Chouvet, G; Thalabard, J C; Thomas, G

1996-11-01

Analysis and characterization of neuronal discharge patterns are of interest to neurophysiologists and neuropharmacologists. In this paper we present a hidden Markov model approach to modeling single neuron electrical activity. Basically the model assumes that each interspike interval corresponds to one of several possible states of the neuron. Fitting the model to experimental series of interspike intervals by maximum likelihood allows estimation of the number of possible underlying neuron states, the probability density functions of interspike intervals corresponding to each state, and the transition probabilities between states. We present an application to the analysis of recordings of a locus coeruleus neuron under three pharmacological conditions. The model distinguishes two states during halothane anesthesia and during recovery from halothane anesthesia, and four states after administration of clonidine. The transition probabilities yield additional insights into the mechanisms of neuron firing.

How neurons migrate: a dynamic in-silico model of neuronal migration in the developing cortex

LENUS (Irish Health Repository)

Setty, Yaki

2011-09-30

Abstract Background Neuronal migration, the process by which neurons migrate from their place of origin to their final position in the brain, is a central process for normal brain development and function. Advances in experimental techniques have revealed much about many of the molecular components involved in this process. Notwithstanding these advances, how the molecular machinery works together to govern the migration process has yet to be fully understood. Here we present a computational model of neuronal migration, in which four key molecular entities, Lis1, DCX, Reelin and GABA, form a molecular program that mediates the migration process. Results The model simulated the dynamic migration process, consistent with in-vivo observations of morphological, cellular and population-level phenomena. Specifically, the model reproduced migration phases, cellular dynamics and population distributions that concur with experimental observations in normal neuronal development. We tested the model under reduced activity of Lis1 and DCX and found an aberrant development similar to observations in Lis1 and DCX silencing expression experiments. Analysis of the model gave rise to unforeseen insights that could guide future experimental study. Specifically: (1) the model revealed the possibility that under conditions of Lis1 reduced expression, neurons experience an oscillatory neuron-glial association prior to the multipolar stage; and (2) we hypothesized that observed morphology variations in rats and mice may be explained by a single difference in the way that Lis1 and DCX stimulate bipolar motility. From this we make the following predictions: (1) under reduced Lis1 and enhanced DCX expression, we predict a reduced bipolar migration in rats, and (2) under enhanced DCX expression in mice we predict a normal or a higher bipolar migration. Conclusions We present here a system-wide computational model of neuronal migration that integrates theory and data within a precise

How neurons migrate: a dynamic in-silico model of neuronal migration in the developing cortex

Directory of Open Access Journals (Sweden)

Skoblov Nikita

2011-09-01

Full Text Available Abstract Background Neuronal migration, the process by which neurons migrate from their place of origin to their final position in the brain, is a central process for normal brain development and function. Advances in experimental techniques have revealed much about many of the molecular components involved in this process. Notwithstanding these advances, how the molecular machinery works together to govern the migration process has yet to be fully understood. Here we present a computational model of neuronal migration, in which four key molecular entities, Lis1, DCX, Reelin and GABA, form a molecular program that mediates the migration process. Results The model simulated the dynamic migration process, consistent with in-vivo observations of morphological, cellular and population-level phenomena. Specifically, the model reproduced migration phases, cellular dynamics and population distributions that concur with experimental observations in normal neuronal development. We tested the model under reduced activity of Lis1 and DCX and found an aberrant development similar to observations in Lis1 and DCX silencing expression experiments. Analysis of the model gave rise to unforeseen insights that could guide future experimental study. Specifically: (1 the model revealed the possibility that under conditions of Lis1 reduced expression, neurons experience an oscillatory neuron-glial association prior to the multipolar stage; and (2 we hypothesized that observed morphology variations in rats and mice may be explained by a single difference in the way that Lis1 and DCX stimulate bipolar motility. From this we make the following predictions: (1 under reduced Lis1 and enhanced DCX expression, we predict a reduced bipolar migration in rats, and (2 under enhanced DCX expression in mice we predict a normal or a higher bipolar migration. Conclusions We present here a system-wide computational model of neuronal migration that integrates theory and data within a

Pneumonitis following infradiaphragmatic irradiation in Hodgkin's disease. Pneumonitis nach infradiaphragmaler Bestrahlung bei Morbus Hodgkin

Energy Technology Data Exchange (ETDEWEB)

Zierhut, D.; Flentje, M. (Radiologische Klinik, Heidelberg Univ. (Germany)); Kalle, A. von (Medizinische Poliklinik, Heidelberg Univ. (Germany)); Moeller, P. (Pathologisches Inst., Heidelberg Univ. (Germany))

1992-12-01

A case is reported on radiation pneumonitis in the left costodiaphragmatic sinus 6 weeks following combined chemo- and radiotherapy of Hodgkin's disease. Thoracotomy was performed in order to exclude a pulmonal relapse of Hodgkin's disease. Thereby the diagnosis of radiation pneumonitis was histologically proven. The development of pneumonitis after irradiation of the spleen may occur and has to be considered in the differential diagnosis of pulmonal affections. (orig.).

Role of routine imaging in detecting recurrent lymphoma; a review of 258 patients with relapsed aggressive non-Hodgkin and Hodgkin lymphoma

DEFF Research Database (Denmark)

El-Galaly, Tarec Christoffer; Mylam, Karen Juul; Bøgsted, Martin

2014-01-01

After first-line therapy, patients with Hodgkin and aggressive non-Hodgkin lymphomas are followed closely for early signs of relapse. The current follow-up practice with frequent use of surveillance imaging is highly controversial and warrants a critical evaluation. Therefore a retrospective...... multicenter study of relapsed Hodgkin and aggressive non-Hodgkin lymphomas (nodal T-cell and diffuse large B-cell lymphomas) was conducted. All included patients had been diagnosed during the period 2002-2011 and relapsed after achieving complete remission on first-line therapy. Characteristics and outcome...... of imaging-detected relapses were compared to other relapses. A total of 258 patients with recurrent lymphoma were included in the study. Relapse investigations were initiated outside preplanned visits in 52% of the patients. Relapse detection could be attributed to patient-reported symptoms alone...

Formation and Dynamics of Waves in a Cortical Model of Cholinergic Modulation.

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James P Roach

2015-08-01

Full Text Available Acetylcholine (ACh is a regulator of neural excitability and one of the neurochemical substrates of sleep. Amongst the cellular effects induced by cholinergic modulation are a reduction in spike-frequency adaptation (SFA and a shift in the phase response curve (PRC. We demonstrate in a biophysical model how changes in neural excitability and network structure interact to create three distinct functional regimes: localized asynchronous, traveling asynchronous, and traveling synchronous. Our results qualitatively match those observed experimentally. Cortical activity during slow wave sleep (SWS differs from that during REM sleep or waking states. During SWS there are traveling patterns of activity in the cortex; in other states stationary patterns occur. Our model is a network composed of Hodgkin-Huxley type neurons with a M-current regulated by ACh. Regulation of ACh level can account for dynamical changes between functional regimes. Reduction of the magnitude of this current recreates the reduction in SFA the shift from a type 2 to a type 1 PRC observed in the presence of ACh. When SFA is minimal (in waking or REM sleep state, high ACh patterns of activity are localized and easily pinned by network inhomogeneities. When SFA is present (decreasing ACh, traveling waves of activity naturally arise. A further decrease in ACh leads to a high degree of synchrony within traveling waves. We also show that the level of ACh determines how sensitive network activity is to synaptic heterogeneity. These regimes may have a profound functional significance as stationary patterns may play a role in the proper encoding of external input as memory and traveling waves could lead to synaptic regularization, giving unique insights into the role and significance of ACh in determining patterns of cortical activity and functional differences arising from the patterns.

Anatomically detailed and large-scale simulations studying synapse loss and synchrony using NeuroBox

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Markus eBreit

2016-02-01

Full Text Available The morphology of neurons and networks plays an important role in processing electrical and biochemical signals. Based on neuronal reconstructions, which are becoming abundantly available through databases such as NeuroMorpho.org, numerical simulations of Hodgkin-Huxley-type equations, coupled to biochemical models, can be performed in order to systematically investigate the influence of cellular morphology and the connectivity pattern in networks on the underlying function. Development in the area of synthetic neural network generation and morphology reconstruction from microscopy data has brought forth the software tool NeuGen. Coupling this morphology data (either from databases, synthetic or reconstruction to the simulation platform UG 4 (which harbors a neuroscientific portfolio and VRL-Studio, has brought forth the extendible toolbox NeuroBox. NeuroBox allows users to perform numerical simulations on hybrid-dimensional morphology representations. The code basis is designed in a modular way, such that e.g. new channel or synapse types can be added to the library. Workflows can be specified through scripts or through the VRL-Studio graphical workflow representation. Third-party tools, such as ImageJ, can be added to NeuroBox workflows. In this paper, NeuroBox is used to study the electrical and biochemical effects of synapse loss vs. synchrony in neurons, to investigate large morphology data sets within detailed biophysical simulations, and used to demonstrate the capability of utilizing high-performance computing infrastructure for large scale network simulations. Using new synapse distribution methods and Finite Volume based numerical solvers for compartment-type models, our results demonstrate how an increase in synaptic synchronization can compensate synapse loss at the electrical and calcium level, and how detailed neuronal morphology can be integrated in large-scale network simulations.

From spiking neuron models to linear-nonlinear models.

Science.gov (United States)

Ostojic, Srdjan; Brunel, Nicolas

2011-01-20

Neurons transform time-varying inputs into action potentials emitted stochastically at a time dependent rate. The mapping from current input to output firing rate is often represented with the help of phenomenological models such as the linear-nonlinear (LN) cascade, in which the output firing rate is estimated by applying to the input successively a linear temporal filter and a static non-linear transformation. These simplified models leave out the biophysical details of action potential generation. It is not a priori clear to which extent the input-output mapping of biophysically more realistic, spiking neuron models can be reduced to a simple linear-nonlinear cascade. Here we investigate this question for the leaky integrate-and-fire (LIF), exponential integrate-and-fire (EIF) and conductance-based Wang-Buzsáki models in presence of background synaptic activity. We exploit available analytic results for these models to determine the corresponding linear filter and static non-linearity in a parameter-free form. We show that the obtained functions are identical to the linear filter and static non-linearity determined using standard reverse correlation analysis. We then quantitatively compare the output of the corresponding linear-nonlinear cascade with numerical simulations of spiking neurons, systematically varying the parameters of input signal and background noise. We find that the LN cascade provides accurate estimates of the firing rates of spiking neurons in most of parameter space. For the EIF and Wang-Buzsáki models, we show that the LN cascade can be reduced to a firing rate model, the timescale of which we determine analytically. Finally we introduce an adaptive timescale rate model in which the timescale of the linear filter depends on the instantaneous firing rate. This model leads to highly accurate estimates of instantaneous firing rates.

Discrete peritoneal and pericardial implants of non-Hodgkin lymphoma

International Nuclear Information System (INIS)

Eckel, C.G.; Davis, M.; Mettler, F.A. Jr.; Rosenberg, R.

1987-01-01

Peritoneal spread of non-Hodgkin lymphoma is rare: fewer than three percent of persons afflicted with this disease develop peritoneal spread. Pericardial involvement by non-Hodgkin lymphoma is equally rare. We report an instance of peritoneal and pericardial spread in a patient with non-Hodgkin lymphoma that was detected only by CT scan. The peritoneal lesions were not visible by ultrasound examination. A pertinent review of the literature is presented. (author)

Diffusion approximation-based simulation of stochastic ion channels: which method to use?

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Danilo ePezo

2014-11-01

Full Text Available To study the effects of stochastic ion channel fluctuations on neural dynamics, several numerical implementation methods have been proposed. Gillespie’s method for Markov Chains (MC simulation is highly accurate, yet it becomes computationally intensive in the regime of high channel numbers. Many recent works aim to speed simulation time using the Langevin-based Diffusion Approximation (DA. Under this common theoretical approach, each implementation differs in how it handles various numerical difficulties – such as bounding of state variables to [0,1]. Here we review and test a set of the most recently published DA implementations (Dangerfield et al., 2012; Linaro et al., 2011; Huang et al., 2013a; Orio and Soudry, 2012; Schmandt and Galán, 2012; Goldwyn et al., 2011; Güler, 2013, comparing all of them in a set of numerical simulations that asses numerical accuracy and computational efficiency on three different models: the original Hodgkin and Huxley model, a model with faster sodium channels, and a multi-compartmental model inspired in granular cells. We conclude that for low channel numbers (usually below 1000 per simulated compartment one should use MC – which is both the most accurate and fastest method. For higher channel numbers, we recommend using the method by Orio and Soudry (2012, possibly combined with the method by Schmandt and Galán (2012 for increased speed and slightly reduced accuracy. Consequently, MC modelling may be the best method for detailed multicompartment neuron models – in which a model neuron with many thousands of channels is segmented into many compartments with a few hundred channels.

Balanced plasticity and stability of the electrical properties of a molluscan modulatory interneuron after classical conditioning: a computational study

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Dimitris Vavoulis

2010-05-01

Full Text Available The Cerebral Giant Cells (CGCs are a pair of identified modulatory interneurons in the Central Nervous System of the pond snail Lymnaea stagnalis with an important role in the expression of both unconditioned and conditioned feeding behavior. Following single-trial food-reward classical conditioning, the membrane potential of the CGCs becomes persistently depolarized. This depolarization contributes to the conditioned response by facilitating sensory cell to command neuron synapses, which results in the activation of the feeding network by the conditioned stimulus. Despite the depolarization of the membrane potential, which enables the CGGs to play a key role in learning-induced network plasticity, there is no persistent change in the tonic firing rate or shape of the action potentials, allowing these neurons to retain their normal network function in feeding. In order to understand the ionic mechanisms of this novel combination of plasticity and stability of intrinsic electrical properties, we first constructed and validated a Hodgkin-Huxley-type model of the CGCs. We then used this model to elucidate how learning-induced changes in a somal persistent sodium and a delayed rectifier potassium current lead to a persistent depolarization of the CGCs whilst maintaining their firing rate. Including in the model an additional increase in the conductance of a high-voltage-activated calcium current allowed the spike amplitude and spike duration also to be maintained after conditioning. We conclude therefore that a balanced increase in three identified conductances is sufficient to explain the electrophysiological changes found in the CGCs after classical conditioning.

Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia.

Science.gov (United States)

Landgren, Ola; Engels, Eric A; Pfeiffer, Ruth M; Gridley, Gloria; Mellemkjaer, Lene; Olsen, Jørgen H; Kerstann, Kimberly F; Wheeler, William; Hemminki, Kari; Linet, Martha S; Goldin, Lynn R

2006-09-20

Personal history of autoimmune diseases is consistently associated with increased risk of non-Hodgkin lymphoma. In contrast, there are limited data on risk of Hodgkin lymphoma following autoimmune diseases and almost no data addressing whether there is a familial association between the conditions. Using population-based linked registry data from Sweden and Denmark, 32 separate autoimmune and related conditions were identified from hospital diagnoses in 7476 case subjects with Hodgkin lymphoma, 18,573 matched control subjects, and more than 86,000 first-degree relatives of case and control subjects. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risks for each condition using logistic regression and also applied multivariable hierarchical regression models. All P values are two-sided. We found statistically significantly increased risks of Hodgkin lymphoma associated with personal histories of several autoimmune conditions, including rheumatoid arthritis (OR = 2.7, 95% CI = 1.9 to 4.0), systemic lupus erythematosus (OR = 5.8, 95% CI = 2.2 to 15.1), sarcoidosis (OR = 14.1, 95% CI = 5.4 to 36.8), and immune thrombocytopenic purpura (OR = infinity, P = .002). A statistically significant increase in risk of Hodgkin lymphoma was associated with family histories of sarcoidosis (OR = 1.8, 95% CI = 1.01 to 3.1) and ulcerative colitis (OR = 1.6, 95% CI = 1.02 to 2.6). Personal or family history of certain autoimmune conditions was strongly associated with increased risk of Hodgkin lymphoma. The association between both personal and family histories of sarcoidosis and a statistically significantly increased risk of Hodgkin lymphoma suggests shared susceptibility for these conditions.

Ion transport through biological membranes an integrated theoretical approach

CERN Document Server

Mackey, Michael C

1975-01-01

This book illustrates some of the ways physics and mathematics have been, and are being, used to elucidate the underlying mechan­ isms of passive ion movement through biological membranes in general, and the membranes of excltable cells in particular. I have made no effort to be comprehensive in my introduction of biological material and the reader interested in a brief account of single cell electro­ physlology from a physically-oriented biologists viewpoint will find the chapters by Woodbury (1965) an excellent introduction. Part I is introductory in nature, exploring the basic electrical properties of inexcitable and excitable cell plasma membranes. Cable theory is utilized to illustrate the function of the non-decrementing action potential as a signaling mechanism for the long range trans­ mission of information in the nervous system, and to gain some in­ sight into the gross behaviour of neurons. The detailed analysis of Hodgkin and Huxley on the squid giant axon membrane ionic conductance properties...

Automatic fitting of spiking neuron models to electrophysiological recordings

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Cyrille Rossant

2010-03-01

Full Text Available Spiking models can accurately predict the spike trains produced by cortical neurons in response to somatically injected currents. Since the specific characteristics of the model depend on the neuron, a computational method is required to fit models to electrophysiological recordings. The fitting procedure can be very time consuming both in terms of computer simulations and in terms of code writing. We present algorithms to fit spiking models to electrophysiological data (time-varying input and spike trains that can run in parallel on graphics processing units (GPUs. The model fitting library is interfaced with Brian, a neural network simulator in Python. If a GPU is present it uses just-in-time compilation to translate model equations into optimized code. Arbitrary models can then be defined at script level and run on the graphics card. This tool can be used to obtain empirically validated spiking models of neurons in various systems. We demonstrate its use on public data from the INCF Quantitative Single-Neuron Modeling 2009 competition by comparing the performance of a number of neuron spiking models.

Diffusion approximation-based simulation of stochastic ion channels: which method to use?

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Pezo, Danilo; Soudry, Daniel; Orio, Patricio

2014-01-01

To study the effects of stochastic ion channel fluctuations on neural dynamics, several numerical implementation methods have been proposed. Gillespie's method for Markov Chains (MC) simulation is highly accurate, yet it becomes computationally intensive in the regime of a high number of channels. Many recent works aim to speed simulation time using the Langevin-based Diffusion Approximation (DA). Under this common theoretical approach, each implementation differs in how it handles various numerical difficulties—such as bounding of state variables to [0,1]. Here we review and test a set of the most recently published DA implementations (Goldwyn et al., 2011; Linaro et al., 2011; Dangerfield et al., 2012; Orio and Soudry, 2012; Schmandt and Galán, 2012; Güler, 2013; Huang et al., 2013a), comparing all of them in a set of numerical simulations that assess numerical accuracy and computational efficiency on three different models: (1) the original Hodgkin and Huxley model, (2) a model with faster sodium channels, and (3) a multi-compartmental model inspired in granular cells. We conclude that for a low number of channels (usually below 1000 per simulated compartment) one should use MC—which is the fastest and most accurate method. For a high number of channels, we recommend using the method by Orio and Soudry (2012), possibly combined with the method by Schmandt and Galán (2012) for increased speed and slightly reduced accuracy. Consequently, MC modeling may be the best method for detailed multicompartment neuron models—in which a model neuron with many thousands of channels is segmented into many compartments with a few hundred channels. PMID:25404914

Mirror neurons: functions, mechanisms and models.

Science.gov (United States)

Oztop, Erhan; Kawato, Mitsuo; Arbib, Michael A

2013-04-12

Mirror neurons for manipulation fire both when the animal manipulates an object in a specific way and when it sees another animal (or the experimenter) perform an action that is more or less similar. Such neurons were originally found in macaque monkeys, in the ventral premotor cortex, area F5 and later also in the inferior parietal lobule. Recent neuroimaging data indicate that the adult human brain is endowed with a "mirror neuron system," putatively containing mirror neurons and other neurons, for matching the observation and execution of actions. Mirror neurons may serve action recognition in monkeys as well as humans, whereas their putative role in imitation and language may be realized in human but not in monkey. This article shows the important role of computational models in providing sufficient and causal explanations for the observed phenomena involving mirror systems and the learning processes which form them, and underlines the need for additional circuitry to lift up the monkey mirror neuron circuit to sustain the posited cognitive functions attributed to the human mirror neuron system. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Optimal autaptic and synaptic delays enhanced synchronization transitions induced by each other in Newman–Watts neuronal networks

International Nuclear Information System (INIS)

Wang, Baoying; Gong, Yubing; Xie, Huijuan; Wang, Qi

2016-01-01

Highlights: • Optimal autaptic delay enhanced synchronization transitions induced by synaptic delay in neuronal networks. • Optimal synaptic delay enhanced synchronization transitions induced by autaptic delay. • Optimal coupling strength enhanced synchronization transitions induced by autaptic or synaptic delay. - Abstract: In this paper, we numerically study the effect of electrical autaptic and synaptic delays on synchronization transitions induced by each other in Newman–Watts Hodgkin–Huxley neuronal networks. It is found that the synchronization transitions induced by synaptic delay vary with varying autaptic delay and become strongest when autaptic delay is optimal. Similarly, the synchronization transitions induced by autaptic delay vary with varying synaptic delay and become strongest at optimal synaptic delay. Also, there is optimal coupling strength by which the synchronization transitions induced by either synaptic or autaptic delay become strongest. These results show that electrical autaptic and synaptic delays can enhance synchronization transitions induced by each other in the neuronal networks. This implies that electrical autaptic and synaptic delays can cooperate with each other and more efficiently regulate the synchrony state of the neuronal networks. These findings could find potential implications for the information transmission in neural systems.

A COMPUTATIONAL MODEL OF MOTOR NEURON DEGENERATION

Science.gov (United States)

Le Masson, Gwendal; Przedborski, Serge; Abbott, L.F.

2014-01-01

SUMMARY To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. PMID:25088365

A computational model of motor neuron degeneration.

Science.gov (United States)

Le Masson, Gwendal; Przedborski, Serge; Abbott, L F

2014-08-20

To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. Copyright © 2014 Elsevier Inc. All rights reserved.

Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

Science.gov (United States)

2018-04-10

Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Primary Cutaneous B-Cell Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Hodgkin's disease and age

DEFF Research Database (Denmark)

Specht, L; Nissen, N I

1989-01-01

506 unselected, previously untreated patients with Hodgkin's disease were treated at the Finsen Institute between 1969 and 1983. The prognostic significance of age, sex, stage, systemic symptoms, histologic subtype, number of involved nodal regions, total tumour burden (peripheral + intrathoracic...... nodal tumour burden, intraabdominal nodal tumour burden, and number of involved extranodal sites), pretreatment ESR, lymphocytopenia, and treatment modality were examined in multivariate analyses. The only factors of independent prognostic significance for disease-free survival proved to be treatment...... modality, stage, and total tumour burden, whereas age had no prognostic significance. With regard to death from Hodgkin's disease only age and total tumour burden had independent significance. The significance of age would seem to stem from the fact that some older patients could not be given adequate...

Doença de Hodgkin

Directory of Open Access Journals (Sweden)

Marina Pereira

1999-05-01

Full Text Available RESUMO: Os autores descrevem um caso de doença de Hodgkin, do subtipo esclerose nodular, numa mulher de 24 anos de idade. A forma de apresentação clínica, pouco habitual, é constituída por uma massa na regão esternal e parede anterior do hemitórax esquerdo, a qual adquire grande volume ao fim de 2 anos e meio de evolução natural da doença. Esta é tratada com quimioterapia (MOPP e radioterapia adjuvante, sofrendo uma reeressão total das suas manifestações clínicas.REV PORT PNEUMOL 1999; V (3: 349-355 ABSTRACT: A case of a 24 years old woman with Hodgkin’s disease, nodular sclerosis subtype, is reported. The disease present with an anterior chest wall mass, an unusual clinical presentation form. The patient receive MOPP chemotherapy and adjuvant radio-therapy with complete resolution of her clinical manifestations.REV PORT PNEUMOL 1999; V (3: 349-355 Palavras-chave: Doença de Hodgkin, Massa da parede torácica anterior, Forma de apresentação clinica, Key-words: Hodgkin’s disease, Anterior chest wall mass, Clinical presentation form

Mediastinal Hodgkin lymphomas in computertomography: exact CT-based volume assessment and approximations with simple geometric models; Mediastinale Hodgkin-Lymphone in der Computertomographie. Vergleich von exakter CT-gestuetzter Volumetrie und Volumenabschaetzung mit Hilfe einfacher geometrischer Modelle

Energy Technology Data Exchange (ETDEWEB)

Battmann, A. [Marburg Univ. (Germany). Abt. fuer Strahlendiagnostik; Dieckmann, K.; Resch, A.; Poetter, R. [Allgemeines Krankenhaus, Wien (Austria). Universitaetsklinik Strahlentherapie und Strahlenbiologie; Battmann, A. [Giessen Univ. (Germany). Zentrum fuer Pathologie

2001-03-01

Background: The importance of the size of the primary tumor in lymphomas and its size after treatment is still uncertain. Assuming a prognostic relevance, an assessment of tumor volume before and after induction of chemotherapy has been performed in the pediatric Hodgkin's disease study (HD-90). Since an exact CT-scan-based volumetric tumor assessment is time-consuming and in some centers not possible, the tumor volume is often estimated based on simple geometric approximations. Aim of this study was the development of an easy to apply and nearly exact model of volume estimation compared to CT-scan-based tumor volume measurements. Material and Methods: thirty computed tomographies (CT) of mediastinal Hodgkin lymphomas of children aged 5 to 16 years have been examined. The CT scans were digitalized using a CCD camera combined with a frame grabber. Applying the Global Lab image software, the true tumor volume was determined excluding local organs, which did not belong to the lymphoma. Subsequently, volumes were assessed using simple geometric models (block, ellipsoid, octaeder) by using the maximum diameters of the tumor. The differences between the volume of the geometric models and the true volume, based on the CT scan evaluation, were compared. Results: the maximum diameters of a tumor can be used to calculate its volume based on simple geometric models. The model 'block' overestimates the volume by 89 to 268%. The model 'ellipsoid' overestimates the volume on average by 29%. The model 'octaeder' underestimates the volume on average by 18%. A division of the block volume by 2.3 approximated the geometric closest to the true volume: the average volume was overestimated by 2% in tumors with a volume larger than 20 ml. No model was sufficient to approximate tumors with a volume of less than 20 ml. Conclusions: for the estimation of tumor volumes in mediastinal Hodgkin lumphomas exceeding 20 ml, the formula 'block /2.3&apos

Dynamical analysis of Parkinsonian state emulated by hybrid Izhikevich neuron models

Science.gov (United States)

Liu, Chen; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xile; Li, Huiyan; Loparo, Kenneth A.; Fietkiewicz, Chris

2015-11-01

Computational models play a significant role in exploring novel theories to complement the findings of physiological experiments. Various computational models have been developed to reveal the mechanisms underlying brain functions. Particularly, in the development of therapies to modulate behavioral and pathological abnormalities, computational models provide the basic foundations to exhibit transitions between physiological and pathological conditions. Considering the significant roles of the intrinsic properties of the globus pallidus and the coupling connections between neurons in determining the firing patterns and the dynamical activities of the basal ganglia neuronal network, we propose a hypothesis that pathological behaviors under the Parkinsonian state may originate from combined effects of intrinsic properties of globus pallidus neurons and synaptic conductances in the whole neuronal network. In order to establish a computational efficient network model, hybrid Izhikevich neuron model is used due to its capacity of capturing the dynamical characteristics of the biological neuronal activities. Detailed analysis of the individual Izhikevich neuron model can assist in understanding the roles of model parameters, which then facilitates the establishment of the basal ganglia-thalamic network model, and contributes to a further exploration of the underlying mechanisms of the Parkinsonian state. Simulation results show that the hybrid Izhikevich neuron model is capable of capturing many of the dynamical properties of the basal ganglia-thalamic neuronal network, such as variations of the firing rates and emergence of synchronous oscillations under the Parkinsonian condition, despite the simplicity of the two-dimensional neuronal model. It may suggest that the computational efficient hybrid Izhikevich neuron model can be used to explore basal ganglia normal and abnormal functions. Especially it provides an efficient way of emulating the large-scale neuron network

Hodgkin's disease part 1: pathology, staging, and management of early stage disease

International Nuclear Information System (INIS)

Mauch, Peter; Yahalom, Joachim

1995-01-01

Over the past 25 years there have been dramatic improvements in our understanding of the epidemiology, biology, natural history, and treatment of Hodgkins disease. Hodgkin's disease is one of the few cancers where both chemotherapy and radiation therapy have provided dramatic improvements in cure of this once uniformly fatal disease. Part 1 of the refresher course on Hodgkin's disease will include a review of: 1) New Findings in epidemiology, immunohistochemistry and molecular biology of the Reed-Sternberg cell including association with Epstein-Barr virus; 2) Review of pathology including discussions of NS 1 vs NS2, and nodular LP subclassifications; 3) Recommendations for staging including the role of staging laparotomy in Hodgkin's disease; 4) Standard techniques for commonly used radiation therapy fields for Hodgkin's disease and 5) Treatment of early stage Hodgkin's disease including an overview on recent and current clinical trials

Comparison of squamous cell carcinoma with non-Hodgkin's lymphoma of tonsillar region

International Nuclear Information System (INIS)

Tsukiyama, Iwao; Yamashita, Kohsuke; Kajiura, Yuuichi; Ogino, Takashi; Akine, Yasuyuki; Egawa, Sunao; Ono, Isamu

1987-01-01

A total of 98 patients with malignant tumors of the tonsil (Squamous cell carcinoma, 34 patients, Non-Hodgkin's lymphoma, 64 patients) werw treated with radiation therapy between 1962 and 1979 at the National Cancer Center Hospital. All were staged by the TNM system, using UICC Classification 1978. With regard to stage distribution, Stage III is most frequent (47.1 %) in squamous cell carcinoma, Stage IV is most frequent (48.4 %) in Non-Hodgkin's lymphoma. Much more advanced cases were included in Non-Hodgkin's lymphoma. Five year survival rate for patients with squamous cell carcinoma and Non-Hodgkin's lymphoma were 49 % and 62 %, respectively. 50 % survival months with squamous cell carcinoma and Non-Hodgkin's lymphoma were 58.7 months and 195.5 months, respectively. Better prognosis was observed in Non-Hodgkin's lymphoma than squamous cell cacinoma. (author)

Direct Neuronal Reprogramming for Disease Modeling Studies Using Patient-Derived Neurons: What Have We Learned?

Directory of Open Access Journals (Sweden)

Janelle Drouin-Ouellet

2017-09-01

Full Text Available Direct neuronal reprogramming, by which a neuron is formed via direct conversion from a somatic cell without going through a pluripotent intermediate stage, allows for the possibility of generating patient-derived neurons. A unique feature of these so-called induced neurons (iNs is the potential to maintain aging and epigenetic signatures of the donor, which is critical given that many diseases of the CNS are age related. Here, we review the published literature on the work that has been undertaken using iNs to model human brain disorders. Furthermore, as disease-modeling studies using this direct neuronal reprogramming approach are becoming more widely adopted, it is important to assess the criteria that are used to characterize the iNs, especially in relation to the extent to which they are mature adult neurons. In particular: i what constitutes an iN cell, ii which stages of conversion offer the earliest/optimal time to assess features that are specific to neurons and/or a disorder and iii whether generating subtype-specific iNs is critical to the disease-related features that iNs express. Finally, we discuss the range of potential biomedical applications that can be explored using patient-specific models of neurological disorders with iNs, and the challenges that will need to be overcome in order to realize these applications.

Rheumatic manifestations at presentation of Hodgkin's disease and non-Hodgkin's malignant lymphoma. A national survey of one hundred forty-six patients

International Nuclear Information System (INIS)

Gaudin, P.; Rozand, Y.; Fauconnier, J.; Phelip, X.

1995-01-01

The authors report the findings of a national survey conducted at the request for the French Society for Rheumatology to list the rheumatic manifestations that can be inaugural in Hodgkin's disease on non-Hodgkin's malignant lymphoma. This was an exploratory, retrospective, descriptive study of 146 patients from 22 rheumatology departments. A number of clinical features (young male, nocturnal sweats, generalized pruritus, protracted fever, central or peripheral lymphadenopathy) and laboratory test abnormalities (evidence of severe inflammation) considerably increased the likelihood of Hodgkin's disease rather than malignant lymphoma. The diagnosis of bony involvement requires multidisciplinary studies of tumor specimens. (authors). 4 figs., 7 tabs., 71 refs

Pneumonitis following infradiaphragmatic irradiation in Hodgkin's disease

International Nuclear Information System (INIS)

Zierhut, D.; Flentje, M.; Kalle, A. von; Moeller, P.

1992-01-01

A case is reported on radiation pneumonitis in the left costodiaphragmatic sinus 6 weeks following combined chemo- and radiotherapy of Hodgkin's disease. Thoracotomy was performed in order to exclude a pulmonal relapse of Hodgkin's disease. Thereby the diagnosis of radiation pneumonitis was histologically proven. The development of pneumonitis after irradiation of the spleen may occur and has to be considered in the differential diagnosis of pulmonal affections. (orig.) [de

Reconstruction of neuronal input through modeling single-neuron dynamics and computations

International Nuclear Information System (INIS)

Qin, Qing; Wang, Jiang; Yu, Haitao; Deng, Bin; Chan, Wai-lok

2016-01-01

Mathematical models provide a mathematical description of neuron activity, which can better understand and quantify neural computations and corresponding biophysical mechanisms evoked by stimulus. In this paper, based on the output spike train evoked by the acupuncture mechanical stimulus, we present two different levels of models to describe the input-output system to achieve the reconstruction of neuronal input. The reconstruction process is divided into two steps: First, considering the neuronal spiking event as a Gamma stochastic process. The scale parameter and the shape parameter of Gamma process are, respectively, defined as two spiking characteristics, which are estimated by a state-space method. Then, leaky integrate-and-fire (LIF) model is used to mimic the response system and the estimated spiking characteristics are transformed into two temporal input parameters of LIF model, through two conversion formulas. We test this reconstruction method by three different groups of simulation data. All three groups of estimates reconstruct input parameters with fairly high accuracy. We then use this reconstruction method to estimate the non-measurable acupuncture input parameters. Results show that under three different frequencies of acupuncture stimulus conditions, estimated input parameters have an obvious difference. The higher the frequency of the acupuncture stimulus is, the higher the accuracy of reconstruction is.

Reconstruction of neuronal input through modeling single-neuron dynamics and computations

Energy Technology Data Exchange (ETDEWEB)

Qin, Qing; Wang, Jiang; Yu, Haitao; Deng, Bin, E-mail: dengbin@tju.edu.cn; Chan, Wai-lok [School of Electrical Engineering and Automation, Tianjin University, Tianjin 300072 (China)

2016-06-15

Mathematical models provide a mathematical description of neuron activity, which can better understand and quantify neural computations and corresponding biophysical mechanisms evoked by stimulus. In this paper, based on the output spike train evoked by the acupuncture mechanical stimulus, we present two different levels of models to describe the input-output system to achieve the reconstruction of neuronal input. The reconstruction process is divided into two steps: First, considering the neuronal spiking event as a Gamma stochastic process. The scale parameter and the shape parameter of Gamma process are, respectively, defined as two spiking characteristics, which are estimated by a state-space method. Then, leaky integrate-and-fire (LIF) model is used to mimic the response system and the estimated spiking characteristics are transformed into two temporal input parameters of LIF model, through two conversion formulas. We test this reconstruction method by three different groups of simulation data. All three groups of estimates reconstruct input parameters with fairly high accuracy. We then use this reconstruction method to estimate the non-measurable acupuncture input parameters. Results show that under three different frequencies of acupuncture stimulus conditions, estimated input parameters have an obvious difference. The higher the frequency of the acupuncture stimulus is, the higher the accuracy of reconstruction is.

Hodgkin's lymphoma mimicking necrotizing pneumonia: case report

Energy Technology Data Exchange (ETDEWEB)

Park, Eun Ah; Lee, Hyun Ju; Im, Jung GI; Goo, Jin Mo; Lim, Kun Young; Lee, Chang Hyun [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

2004-11-01

This study describes a case of pulmonary Hodgkin's lymphoma of the nodular sclerosing type presenting as a large cavitary mass with air-fluid levels. We also conduct a review of the previous articles on pulmonary Hodgkin's lymphoma.

An introduction to modeling neuronal dynamics

CERN Document Server

Börgers, Christoph

2017-01-01

This book is intended as a text for a one-semester course on Mathematical and Computational Neuroscience for upper-level undergraduate and beginning graduate students of mathematics, the natural sciences, engineering, or computer science. An undergraduate introduction to differential equations is more than enough mathematical background. Only a slim, high school-level background in physics is assumed, and none in biology. Topics include models of individual nerve cells and their dynamics, models of networks of neurons coupled by synapses and gap junctions, origins and functions of population rhythms in neuronal networks, and models of synaptic plasticity. An extensive online collection of Matlab programs generating the figures accompanies the book. .

Computational model of neuron-astrocyte interactions during focal seizure generation

Directory of Open Access Journals (Sweden)

Davide eReato

2012-10-01

Full Text Available Empirical research in the last decade revealed that astrocytes can respond to neurotransmitters with Ca2+ elevations and generate feedback signals to neurons which modulate synaptic transmission and neuronal excitability. This discovery changed our basic understanding of brain function and provided new perspectives for how astrocytes can participate not only to information processing, but also to the genesis of brain disorders, such as epilepsy. Epilepsy is a neurological disorder characterized by recurrent seizures that can arise focally at restricted areas and propagate throughout the brain. Studies in brain slice models suggest that astrocytes contribute to epileptiform activity by increasing neuronal excitability through a Ca2+-dependent release of glutamate. The underlying mechanism remains, however, unclear. In this study, we implemented a parsimonious network model of neurons and astrocytes. The model consists of excitatory and inhibitory neurons described by Izhikevich's neuron dynamics. The experimentally observed Ca2+ change in astrocytes in response to neuronal activity was modeled with linear equations. We considered that glutamate is released from astrocytes above certain intracellular Ca2+ concentrations thus providing a non-linear positive feedback signal to neurons. Propagating seizure-like ictal discharges (IDs were reliably evoked in our computational model by repeatedly exciting a small area of the network, which replicates experimental results in a slice model of focal ID in entorhinal cortex. We found that the threshold of focal ID generation was lowered when an excitatory feedback-loop between astrocytes and neurons was included. Simulations show that astrocytes can contribute to ID generation by directly affecting the excitatory/inhibitory balance of the neuronal network. Our model can be used to obtain mechanistic insights into the distinct contributions of the different signaling pathways to the generation and

Multistability in a neuron model with extracellular potassium dynamics

Science.gov (United States)

Wu, Xing-Xing; Shuai, J. W.

2012-06-01

Experiments show a primary role of extracellular potassium concentrations in neuronal hyperexcitability and in the generation of epileptiform bursting and depolarization blocks without synaptic mechanisms. We adopt a physiologically relevant hippocampal CA1 neuron model in a zero-calcium condition to better understand the function of extracellular potassium in neuronal seizurelike activities. The model neuron is surrounded by interstitial space in which potassium ions are able to accumulate. Potassium currents, Na+-K+ pumps, glial buffering, and ion diffusion are regulatory mechanisms of extracellular potassium. We also consider a reduced model with a fixed potassium concentration. The bifurcation structure and spiking frequency of the two models are studied. We show that, besides hyperexcitability and bursting pattern modulation, the potassium dynamics can induce not only bistability but also tristability of different firing patterns. Our results reveal the emergence of the complex behavior of multistability due to the dynamical [K+]o modulation on neuronal activities.

Metallothionein as a useful marker in Hodgkin lymphoma subclassification

DEFF Research Database (Denmark)

Penkowa, Milena; Sørensen, Brit Ladegaard; Nielsen, Signe Lidou

2009-01-01

Metallothionein (MT) expression is considered to be a prognostic factor that promotes tumor resistance to apoptosis. In non-Hodgkin lymphomas, MT is differentially expressed and constitutes a risk factor. We have characterised MT in lymph nodes of Hodgkin lymphoma (HL) [patients with nodular...

Modelled temperature-dependent excitability behaviour of a generalised human peripheral sensory nerve fibre.

Science.gov (United States)

Smit, Jacoba E; Hanekom, Tania; Hanekom, Johan J

2009-08-01

The objective of this study was to determine if a recently developed human Ranvier node model, which is based on a modified version of the Hodgkin-Huxley model, could predict the excitability behaviour in human peripheral sensory nerve fibres with diameters ranging from 5.0 to 15.0 microm. The Ranvier node model was extended to include a persistent sodium current and was incorporated into a generalised single cable nerve fibre model. Parameter temperature dependence was included. All calculations were performed in Matlab. Sensory nerve fibre excitability behaviour characteristics predicted by the new nerve fibre model at different temperatures and fibre diameters compared well with measured data. Absolute refractory periods deviated from measured data, while relative refractory periods were similar to measured data. Conduction velocities showed both fibre diameter and temperature dependence and were underestimated in fibres thinner than 12.5 microm. Calculated strength-duration time constants ranged from 128.5 to 183.0 micros at 37 degrees C over the studied nerve fibre diameter range, with chronaxie times about 30% shorter than strength-duration time constants. Chronaxie times exhibited temperature dependence, with values overestimated by a factor 5 at temperatures lower than body temperature. Possible explanations include the deviated absolute refractory period trend and inclusion of a nodal strangulation relationship.

Bilateral breast cancer after cured Hodgkin's disease

International Nuclear Information System (INIS)

Anderson, N.; Lokich, J.

1990-01-01

Three patients developed bilateral breast cancer at 10 to 24 years after mantle irradiation for locally or systemically advanced Hodgkin's disease (HD). Four of the six cancers in the three patients were detected only by mammography. Pathologically, five of the cancers were intraductal carcinomas (four with an invasive component) with one being a lobular carcinoma. Five of the six lesions were Stage I pathologically without evidence of axillary nodal involvement. It is recommended that female patients with Hodgkin's disease who have received mantle irradiation as part of the therapy for their Hodgkin's disease and who are observed for 10 or more years after completion of mantle irradiation be considered at risk for the development of breast cancer. Such patients should be monitored appropriately by routine bilateral mammograms to increase the early detection of early stage lesions

Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

Science.gov (United States)

2015-05-06

Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I AIDS-related Lymphoma; Stage II AIDS-related Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Dorothy Reed and Hodgkin's disease: a reflection after a century

International Nuclear Information System (INIS)

Zwitter, Matjaz; Cohen, Joel R.; Barrett, Ann; Robinton, Elizabeth D.

2002-01-01

It has now been 100 years since Dorothy Reed, at the age of 28, wrote her paper on Hodgkin's disease. Her biography reveals the difficult lives of women entering the hitherto male-dominated field of medicine, let alone medical research. Her historic paper on Hodgkin's disease is remarkable for its brilliant observations and concise scientific reasoning. Nevertheless, she was told that as a woman she could not hope for a career as an academic pathologist. After marriage to Charles Elwood Mendenhall, Professor of Physics at the University of Wisconsin and after giving birth to four children, the second part of her career began. Motivated by the loss of her firstborn, she began a study of infant mortality, an interest that lasted throughout her career. In 1926, Mendenhall undertook a survey comparing infant and maternal mortality rates in Denmark and the United States. This influential study concluded that American mortality rates were higher because of unnecessary interference in the natural process of childbirth and recommended the education of midwives follow the Danish model. In 1937, her efforts were rewarded when Madison, WI received recognition for having the lowest infant mortality of any city in the United States. Reading Reed's paper on Hodgkin's disease, we see that her observations go far beyond a description of a specific cell. Her presentation of macroscopic and microscopic features is remarkable for the distinction between 'young' and 'old' growths: Reed saw Hodgkin's disease as a process, rather than the spreading of a cancer. She was the first to note that those most commonly affected are boys or young adults, especially those whose general health before the disease had been excellent. She was also the first to note anergy to tuberculin. Dorothy Reed defined Hodgkin's disease in relation to tuberculosis, described its pathologic features, and offered comments on its pathogenesis, epidemiology, and immunology that still deserve to be discussed

On the limit dynamics of systems with infinite multiple degrees of freedom

Energy Technology Data Exchange (ETDEWEB)

Braun, W A

1977-01-01

By using N/sup -2/ phi (g sub i - g sub j) regular pair interactions, it is shown that, for n approaching infinity, the Vlasovdynamics is the omega meson resonances -limit of the classical canonical N-particle-dynamics. Propagation of molecular chaos holds in this limit and the fluctuations converge to a Gaussian stochastic process, which is, however, non-Markovian. A model of a nerve membrane is studied in the limit of singular interaction with Fermion reservoirs. The resulting axon equations have the same structure as the Hodgkin Huxley equations. Recently proven theorems are used on nonlinear diffusion equations to show the existance of a propagating pulse solution.

Comparison of time stepping schemes on the cable equation

Directory of Open Access Journals (Sweden)

Chuan Li

2010-09-01

Full Text Available Electrical propagation in excitable tissue, such as nerve fibers and heart muscle, is described by a parabolic PDE for the transmembrane voltage $V(x,t$, known as the cable equation, $$ frac{1}{r_a}frac{partial^2V}{partial x^2} = C_mfrac{partial V}{partial t} + I_{m ion}(V,t + I_{m stim}(t $$ where $r_a$ and $C_m$ are the axial resistance and membrane capacitance. The source term $I_{m ion}$ represents the total ionic current across the membrane, governed by the Hodgkin-Huxley or other more complicated ionic models. $I_{m stim}(t$ is an applied stimulus current.

Hyperbolic Plykin attractor can exist in neuron models

DEFF Research Database (Denmark)

Belykh, V.; Belykh, I.; Mosekilde, Erik

2005-01-01

Strange hyperbolic attractors are hard to find in real physical systems. This paper provides the first example of a realistic system, a canonical three-dimensional (3D) model of bursting neurons, that is likely to have a strange hyperbolic attractor. Using a geometrical approach to the study...... of the neuron model, we derive a flow-defined Poincare map giving ail accurate account of the system's dynamics. In a parameter region where the neuron system undergoes bifurcations causing transitions between tonic spiking and bursting, this two-dimensional map becomes a map of a disk with several periodic...... holes. A particular case is the map of a disk with three holes, matching the Plykin example of a planar hyperbolic attractor. The corresponding attractor of the 3D neuron model appears to be hyperbolic (this property is not verified in the present paper) and arises as a result of a two-loop (secondary...

Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma

DEFF Research Database (Denmark)

Hertel, Christina B; Zhou, Xiao-ge; Hamilton-Dutoit, Stephen J

2002-01-01

In classical Hodgkin lymphoma the malignant Hodgkin/Reed-Sternberg (HRS) cells characteristically constitute only a small minority of the tumour load. Their origin has been debated for decades, but on the basis of rearrangement and somatic hypermutations of their immunoglubulin (Ig) genes, HRS ce...

Non-Hodgkin lymphoma - children

Science.gov (United States)

... families share common experiences may help ease your stress. American Childhood Cancer Organization - www.acco.org Leukemia and ... Updated: January 27, 2016. Accessed June 3, 2016. American Society of Clinical ... Institute website. Childhood non-Hodgkin lymphoma treatment (PDQ) - health ...

Stomach cancer risk after treatment for hodgkin lymphoma

DEFF Research Database (Denmark)

Morton, Lindsay M; Dores, Graça M; Curtis, Rochelle E

2013-01-01

Treatment-related stomach cancer is an important cause of morbidity and mortality among the growing number of Hodgkin lymphoma (HL) survivors, but risks associated with specific HL treatments are unclear.......Treatment-related stomach cancer is an important cause of morbidity and mortality among the growing number of Hodgkin lymphoma (HL) survivors, but risks associated with specific HL treatments are unclear....

Female reproductive potential after treatment for Hodgkin's disease

International Nuclear Information System (INIS)

Horning, S.J.; Hoppe, R.T.; Kaplan, H.S.; Rosenberg, S.A.

1981-01-01

The probability of maintaining ovarian function, becoming pregnant, and delivering a normal child is important to young women anticipating successful therapy for Hodgkin's disease. In this study, reproductive function was retrospectively examined in 103 women 40 years old or younger who had undergone treatment for Hodgkin's disease with total-lymphoid irradiation (TLI) alone, combination chemotherapy, or combined TLI and chemotherapy. Infertility was directly related to gonadal exposure to therapy and to age at treatment. Twenty women became pregnant after receiving total-nodal irradiation or combination chemotherapy or both. No fetal wastage occurred, and no birth defects were seen in the 24 infants born to these women. Even after intensive treatment programs, women successfully treated for Hodgkin's disease have become pregnant and delivered phenotypically normal children

Apoptosis and radiosensitization of Hodgkin cells by proteasome inhibition

International Nuclear Information System (INIS)

Pajonk, Frank; Pajonk, Katja; McBride, William H.

2000-01-01

Purpose: Malignant cells from Hodgkin's disease have been reported to be defective in regulation of NF-κB activity. Ionizing radiation is known to activate NF-κB, and it has been suggested that this pathway may protect cells from apoptosis following exposure to radiation and other therapeutic agents. Defective NF-κB regulation in Hodgkin cells could therefore dictate the response of this disease to therapy, as well as be responsible for maintaining the malignant phenotype. The purpose of this study was to explore whether NF-κB activity could be modulated in Hodgkin cells and whether it determines the response of these cells to treatment with ionizing radiation and/or dexamethasone. Methods and Materials: Activation of NF-κB in cells is accomplished in large part by degradation of its inhibitor IκB through the 26s proteasome. HD-My-Z Hodgkin cells were treated with the proteasome inhibitor MG-132 or transduced with a dominant negative super-repressor IκBα. Clonogenic survival, apoptosis, proteasome activity, and NF-κB binding activity were monitored in response to ionizing radiation and/or dexamethasone treatment. Results: HD-My-Z Hodgkin cells had modest NF-κB levels but, unlike other cell types, did not decrease their level of constitutively active NF-κB in response to proteasome inhibition with MG-132. In contrast, transduction with a non-phosphorable IκBα construct abolished expression. MG-132 did, however, induce apoptosis in HD-My-Z cells and sensitized them to ionizing radiation. Dexamethasone treatment had no effect on NF-κB activity or clonogenic survival of Hodgkin cells, but protected them from irradiation. Conclusion: We conclude that inhibition of 26s proteasome activity can induce apoptosis in HD-My-Z Hodgkin cells and radiosensitize them, in spite of the fact that their constitutively active NF-κB levels are unaltered. The proteasome may be a promising new therapeutic target for intervention in this disease. In contrast, the use of

Towards reproducible descriptions of neuronal network models.

Directory of Open Access Journals (Sweden)

Eilen Nordlie

2009-08-01

Full Text Available Progress in science depends on the effective exchange of ideas among scientists. New ideas can be assessed and criticized in a meaningful manner only if they are formulated precisely. This applies to simulation studies as well as to experiments and theories. But after more than 50 years of neuronal network simulations, we still lack a clear and common understanding of the role of computational models in neuroscience as well as established practices for describing network models in publications. This hinders the critical evaluation of network models as well as their re-use. We analyze here 14 research papers proposing neuronal network models of different complexity and find widely varying approaches to model descriptions, with regard to both the means of description and the ordering and placement of material. We further observe great variation in the graphical representation of networks and the notation used in equations. Based on our observations, we propose a good model description practice, composed of guidelines for the organization of publications, a checklist for model descriptions, templates for tables presenting model structure, and guidelines for diagrams of networks. The main purpose of this good practice is to trigger a debate about the communication of neuronal network models in a manner comprehensible to humans, as opposed to machine-readable model description languages. We believe that the good model description practice proposed here, together with a number of other recent initiatives on data-, model-, and software-sharing, may lead to a deeper and more fruitful exchange of ideas among computational neuroscientists in years to come. We further hope that work on standardized ways of describing--and thinking about--complex neuronal networks will lead the scientific community to a clearer understanding of high-level concepts in network dynamics, and will thus lead to deeper insights into the function of the brain.

Simple cortical and thalamic neuron models for digital arithmetic circuit implementation

Directory of Open Access Journals (Sweden)

Takuya eNanami

2016-05-01

Full Text Available Trade-off between reproducibility of neuronal activities and computational efficiency is one ofcrucial subjects in computational neuroscience and neuromorphic engineering. A wide variety ofneuronal models have been studied from different viewpoints. The digital spiking silicon neuron(DSSN model is a qualitative model that focuses on efficient implementation by digital arithmeticcircuits. We expanded the DSSN model and found appropriate parameter sets with which itreproduces the dynamical behaviors of the ionic-conductance models of four classes of corticaland thalamic neurons. We first developed a 4-variable model by reducing the number of variablesin the ionic-conductance models and elucidated its mathematical structures using bifurcationanalysis. Then, expanded DSSN models were constructed that reproduce these mathematicalstructures and capture the characteristic behavior of each neuron class. We confirmed thatstatistics of the neuronal spike sequences are similar in the DSSN and the ionic-conductancemodels. Computational cost of the DSSN model is larger than that of the recent sophisticatedIntegrate-and-Fire-based models, but smaller than the ionic-conductance models. This modelis intended to provide another meeting point for above trade-off that satisfies the demand forlarge-scale neuronal network simulation with closer-to-biology models.

John Dewey em visita ao jardim de Huxley: uma discussão sobre a teoria da evolução e as concepções éticas

Directory of Open Access Journals (Sweden)

José Cláudio Morelli Matos

2010-05-01

Full Text Available http://dx.doi.org/10.5007/1677-2954.2010v9n2p199 John Dewey escreve um de seus primeiros trabalhos sobre ética em resposta às idéias de Thomas Huxley. Huxley, em seu artigo “Evolution and Ethics” (1894, defendia uma oposição entre os processos naturais e os processos éticos. A ética, segundo ele, é contrária aos princípios que se observa na natureza. Para Dewey, por outro lado, não há dualismo entre as regularidades naturais e as regularidades sociais. Dewey pretende, em seu artigo homônimo ao de Huxley (1898, reconstruir o sentido de noções fundamentais ao pensamento evolutivo como “adaptado”, “luta pela vida” e “seleção natural”. Dando início a uma versão evolucionista da reflexão ética, Dewey supõe a continuidade entre o mundo natural e o mundo dos valores. Suas conclusões indicam não só uma abordagem evolutiva das questões éticas, mas a proposição de valores e condutas que estejam em conformidade com o crescimento e a mudança constante nos ambientes e nas funções adaptativas, tais como se observa no mundo natural.

Childhood Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

In childhood Hodgkin lymphoma, current treatment uses risk-adapted, response-based paradigms to determine the length and intensity of treatment. Get detailed information about newly diagnosed and recurrent classical and nodular lymphocyte predominant Hodgkin lymphoma, including presentation, diagnosis and staging, prognosis, and treatment in this summary for clinicians.

Checkpoint inhibitors and radiation treatment in Hodgkin's lymphoma. New study concepts of the German Hodgkin Study Group

Energy Technology Data Exchange (ETDEWEB)

Baues, C.; Semrau, R.; Marnitz, S. [University of Cologne, Medical Faculty, Department of Radiooncology, Cologne (Germany); University of Cologne, German Hodgkin Study Group (GHSG), Cologne (Germany); Gaipl, U.S. [University Hospital Erlangen, Department of Radiooncology, Erlangen (Germany); Broeckelmann, P.J.; Engert, A. [University of Cologne, German Hodgkin Study Group (GHSG), Cologne (Germany); University of Cologne, Medical Faculty, Department of Internal Medicine I, Cologne (Germany); Rosenbrock, J. [University of Cologne, Medical Faculty, Department of Radiooncology, Cologne (Germany)

2017-02-15

Patients with classical Hodgkin's lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options. A remarkable and durable response rate with a favorable toxicity profile was observed in heavily pretreated cHL patients. Planning to perform prospective randomized clinical trials in the content of radio-immune treatment in patients with Hodgkin's lymphoma (HL), we transferred the results of preliminary clinical studies and basic research in clinical relevant study concepts. Based on these promising early phase trial data, the German Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in upcoming phase II trials. The therapeutic efficacy and potential synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will be investigated in various settings of HL. (orig.) [German] Patienten mit einem klassischen Hodgkin-Lymphom (cHL) haben ueber alle Stadien hinweg eine gute Prognose. Allerdings treten unter der kombinierten Therapie mit Chemotherapie und Bestrahlung therapieabhaengige Toxizitaeten wie z. B. Organschaeden, Sekundaertumoren, Fatigue oder Langzeit-Fatigue auf. Viele Patienten leiden trotz einer Heilung an diesen Symptomen. Daher bietet die nachgewiesene Wirksamkeit der Anti-PD1/PD-L1-Antikoerper bei soliden Tumoren, aber auch beim HL neue Behandlungsoptionen. Bei intensiv vorbehandelten Patienten mit rezidiviertem cHL wurde bei guter Vertraeglichkeit eine hohe Ansprechrate mit z. T. langanhaltenden Remissionen beobachtet. Im Rahmen der Planung prospektiver randomisierter Studien im

One-dimensional map-based neuron model: A logistic modification

International Nuclear Information System (INIS)

Mesbah, Samineh; Moghtadaei, Motahareh; Hashemi Golpayegani, Mohammad Reza; Towhidkhah, Farzad

2014-01-01

A one-dimensional map is proposed for modeling some of the neuronal activities, including different spiking and bursting behaviors. The model is obtained by applying some modifications on the well-known Logistic map and is named the Modified and Confined Logistic (MCL) model. Map-based neuron models are known as phenomenological models and recently, they are widely applied in modeling tasks due to their computational efficacy. Most of discrete map-based models involve two variables representing the slow-fast prototype. There are also some one-dimensional maps, which can replicate some of the neuronal activities. However, the existence of four bifurcation parameters in the MCL model gives rise to reproduction of spiking behavior with control over the frequency of the spikes, and imitation of chaotic and regular bursting responses concurrently. It is also shown that the proposed model has the potential to reproduce more realistic bursting activity by adding a second variable. Moreover the MCL model is able to replicate considerable number of experimentally observed neuronal responses introduced in Izhikevich (2004) [23]. Some analytical and numerical analyses of the MCL model dynamics are presented to explain the emersion of complex dynamics from this one-dimensional map

Context-aware modeling of neuronal morphologies

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Benjamin eTorben-Nielsen

2014-09-01

Full Text Available Neuronal morphologies are pivotal for brain functioning: physical overlap between dendrites and axons constrain the circuit topology, and the precise shape and composition of dendrites determine the integration of inputs to produce an output signal. At the same time, morphologies are highly diverse and variant. The variance, presumably, originates from neurons developing in a densely packed brain substrate where they interact (e.g., repulsion or attraction with other actors in this substrate. However, when studying neurons their context is never part of the analysis and they are treated as if they existed in isolation.Here we argue that to fully understand neuronal morphology and its variance it is important to consider neurons in relation to each other and to other actors in the surrounding brain substrate, i.e., their context. We propose a context-aware computational framework, NeuroMaC, in which large numbers of neurons can be grown simultaneously according to growth rules expressed in terms of interactions between the developing neuron and the surrounding brain substrate.As a proof of principle, we demonstrate that by using NeuroMaC we can generate accurate virtual morphologies of distinct classes both in isolation and as part of neuronal forests. Accuracy is validated against population statistics of experimentally reconstructed morphologies. We show that context-aware generation of neurons can explain characteristics of variation. Indeed, plausible variation is an inherent property of the morphologies generated by context-aware rules. We speculate about the applicability of this framework to investigate morphologies and circuits, to classify healthy and pathological morphologies, and to generate large quantities of morphologies for large-scale modeling.

Pyrogen release in vitro by lymphoid tissues from patients with Hodgkin's disease.

Science.gov (United States)

Bodel, P

1974-01-01

The mechanism of fever in patients with Hodgkin's disease was investigated by examining endogenous pyrogen production by blood, spleen, and lymph node cells incubated in vitro. Blood leucocytes from febrile or afebrile patients with Hodgkin's disease did not produce pyrogen spontaneously. Spleen cells, however, frequently released pyrogen during initial incubations, unlike spleen cells from patients with non-malignant diseases. Pyrogen production occurred from spleens without observed pathologic infiltrates of Hodgkin's disease. Lymph nodes involved with Hodgkin's disease produced pyrogen more frequently than did nodes involved with other diseases. Pyrogen production by tissue cells was prolonged, required protein synthesis, and in some cases was due to mononuclear cells; it did not correlate with fever in the patient. These studies demonstrate spontaneous production of endogenous pyrogen in vitro by lymphoid tissue cells from patients with Hodgkin's disease.

Avascular osteonecrosis in patients treated for Hodgkin`s disease

Energy Technology Data Exchange (ETDEWEB)

Enrici, R.M.; Donato, V.; Santoro, M. [La Sapienza Univ. of Rome, Inst. of Radiology, Chair of Radiation Oncology, Rome (Italy); Tombolini, V. [Univ of L`Aquila, Hospital S. Maria di Collemaggio, Dept. of Radiation Oncology, L`Aquila (Italy); Anselmo, A.P. [La Sapienza Univ. of Rome, Dept. of Human Biopathology, Haematology Section, Rome (Italy)

1998-09-01

The aim of this study is to assess the risk of avascular osteonecrosis (AVN) of the femoral head in patients treated for Hodgkin`s disease (HD), in relation to the type of treatment they have received. For this purpose, a cohort of 1391 patients treated for HD at University of Rome between 1972 and 1996 was divided into 2 groups according to their initial treatment. The first group contained 784 patients treated, at the onset of HD, either with chemotherapy (CT) containing steroids, combined in some cases with subdiaphragmatic radiotherapy (RT), or with subdiaphragmatic RT combined with CT without steroids. The second group was made up of 607 patients who had received, initially, supradiaphragmatic RT alone or supradiaphragmatic RT combined with CT without steroids. For the purpose of this study, only the 784 patients belonging to the first group were observed for the appearance of AVN, which occurred in 9 cases. The period of time which elapsed between the end of treatment and the radiological evidence of AVN ranged from 23 to 97 months, with an average of 35 months. Because the number of cases of AVN was so small, the pathogenesis of this complication could not be identified. (au) 55 refs.

Hybrid Scheme for Modeling Local Field Potentials from Point-Neuron Networks

DEFF Research Database (Denmark)

Hagen, Espen; Dahmen, David; Stavrinou, Maria L

2016-01-01

on populations of network-equivalent multicompartment neuron models with layer-specific synaptic connectivity, can be used with an arbitrary number of point-neuron network populations, and allows for a full separation of simulated network dynamics and LFPs. We apply the scheme to a full-scale cortical network......With rapidly advancing multi-electrode recording technology, the local field potential (LFP) has again become a popular measure of neuronal activity in both research and clinical applications. Proper understanding of the LFP requires detailed mathematical modeling incorporating the anatomical...... and electrophysiological features of neurons near the recording electrode, as well as synaptic inputs from the entire network. Here we propose a hybrid modeling scheme combining efficient point-neuron network models with biophysical principles underlying LFP generation by real neurons. The LFP predictions rely...

A Neuronal Network Model for Pitch Selectivity and Representation

OpenAIRE

Huang, Chengcheng; Rinzel, John

2016-01-01

Pitch is a perceptual correlate of periodicity. Sounds with distinct spectra can elicit the same pitch. Despite the importance of pitch perception, understanding the cellular mechanism of pitch perception is still a major challenge and a mechanistic model of pitch is lacking. A multi-stage neuronal network model is developed for pitch frequency estimation using biophysically-based, high-resolution coincidence detector neurons. The neuronal units respond only to highly coincident input among c...

Digital hardware implementation of a stochastic two-dimensional neuron model.

Science.gov (United States)

Grassia, F; Kohno, T; Levi, T

2016-11-01

This study explores the feasibility of stochastic neuron simulation in digital systems (FPGA), which realizes an implementation of a two-dimensional neuron model. The stochasticity is added by a source of current noise in the silicon neuron using an Ornstein-Uhlenbeck process. This approach uses digital computation to emulate individual neuron behavior using fixed point arithmetic operation. The neuron model's computations are performed in arithmetic pipelines. It was designed in VHDL language and simulated prior to mapping in the FPGA. The experimental results confirmed the validity of the developed stochastic FPGA implementation, which makes the implementation of the silicon neuron more biologically plausible for future hybrid experiments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radiotherapy in the Hodgkin's disease

International Nuclear Information System (INIS)

Pinto, A.C.L.C.; Moura, J.E.F.M. de; Leite, M.T.T.; Santa Casa de Misericordia de Belo Horizonte

1983-01-01

An up-to-date summary of Hodgkin's disease is presented taking into account its natural history, dissemination patterns, history, staging and therapeutic sugestions, with special regard to radiotherapy. (Author) [pt

Hybrid B-Spline Collocation Method for Solving the Generalized Burgers-Fisher and Burgers-Huxley Equations

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Imtiaz Wasim

2018-01-01

Full Text Available In this study, we introduce a new numerical technique for solving nonlinear generalized Burgers-Fisher and Burgers-Huxley equations using hybrid B-spline collocation method. This technique is based on usual finite difference scheme and Crank-Nicolson method which are used to discretize the time derivative and spatial derivatives, respectively. Furthermore, hybrid B-spline function is utilized as interpolating functions in spatial dimension. The scheme is verified unconditionally stable using the Von Neumann (Fourier method. Several test problems are considered to check the accuracy of the proposed scheme. The numerical results are in good agreement with known exact solutions and the existing schemes in literature.

Risk of Hodgkin's disease and other cancers after infectious mononucleosis

DEFF Research Database (Denmark)

Hjalgrim, H; Askling, J; Sørensen, P

2000-01-01

BACKGROUND: Infectious mononucleosis, which is caused by the Epstein-Barr virus, has been associated with an increased risk for Hodgkin's disease. Little is known, however, about how infectious mononucleosis affects long-term risk of Hodgkin's disease, how this risk varies with age at infectious...... mononucleosis diagnosis, or how the risk for Hodgkin's disease varies in different age groups. In addition, the general cancer profile among patients who have had infectious mononucleosis has been sparsely studied. METHODS: Population-based cohorts of infectious mononucleosis patients in Denmark and Sweden were...... statistical tests including the trend tests were two-sided. RESULTS: A total of 1381 cancers were observed during 689 619 person-years of follow-up among 38 562 infectious mononucleosis patients (SIR = 1. 03; 95% confidence interval [CI] = 0.98-1.09). Apart from Hodgkin's disease (SIR = 2.55; 95% CI = 1...

Modeling task-specific neuronal ensembles improves decoding of grasp

Science.gov (United States)

Smith, Ryan J.; Soares, Alcimar B.; Rouse, Adam G.; Schieber, Marc H.; Thakor, Nitish V.

2018-06-01

Objective. Dexterous movement involves the activation and coordination of networks of neuronal populations across multiple cortical regions. Attempts to model firing of individual neurons commonly treat the firing rate as directly modulating with motor behavior. However, motor behavior may additionally be associated with modulations in the activity and functional connectivity of neurons in a broader ensemble. Accounting for variations in neural ensemble connectivity may provide additional information about the behavior being performed. Approach. In this study, we examined neural ensemble activity in primary motor cortex (M1) and premotor cortex (PM) of two male rhesus monkeys during performance of a center-out reach, grasp and manipulate task. We constructed point process encoding models of neuronal firing that incorporated task-specific variations in the baseline firing rate as well as variations in functional connectivity with the neural ensemble. Models were evaluated both in terms of their encoding capabilities and their ability to properly classify the grasp being performed. Main results. Task-specific ensemble models correctly predicted the performed grasp with over 95% accuracy and were shown to outperform models of neuronal activity that assume only a variable baseline firing rate. Task-specific ensemble models exhibited superior decoding performance in 82% of units in both monkeys (p  <  0.01). Inclusion of ensemble activity also broadly improved the ability of models to describe observed spiking. Encoding performance of task-specific ensemble models, measured by spike timing predictability, improved upon baseline models in 62% of units. Significance. These results suggest that additional discriminative information about motor behavior found in the variations in functional connectivity of neuronal ensembles located in motor-related cortical regions is relevant to decode complex tasks such as grasping objects, and may serve the basis for more

Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

Directory of Open Access Journals (Sweden)

Afonso José Pereira Cortez

2011-02-01

Full Text Available BACKGROUND: Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. OBJECTIVES: To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. METHODS: A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. RESULTS: The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. CONCLUSION: Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not

Hybrid Scheme for Modeling Local Field Potentials from Point-Neuron Networks.

Science.gov (United States)

Hagen, Espen; Dahmen, David; Stavrinou, Maria L; Lindén, Henrik; Tetzlaff, Tom; van Albada, Sacha J; Grün, Sonja; Diesmann, Markus; Einevoll, Gaute T

2016-12-01

With rapidly advancing multi-electrode recording technology, the local field potential (LFP) has again become a popular measure of neuronal activity in both research and clinical applications. Proper understanding of the LFP requires detailed mathematical modeling incorporating the anatomical and electrophysiological features of neurons near the recording electrode, as well as synaptic inputs from the entire network. Here we propose a hybrid modeling scheme combining efficient point-neuron network models with biophysical principles underlying LFP generation by real neurons. The LFP predictions rely on populations of network-equivalent multicompartment neuron models with layer-specific synaptic connectivity, can be used with an arbitrary number of point-neuron network populations, and allows for a full separation of simulated network dynamics and LFPs. We apply the scheme to a full-scale cortical network model for a ∼1 mm 2 patch of primary visual cortex, predict laminar LFPs for different network states, assess the relative LFP contribution from different laminar populations, and investigate effects of input correlations and neuron density on the LFP. The generic nature of the hybrid scheme and its public implementation in hybridLFPy form the basis for LFP predictions from other and larger point-neuron network models, as well as extensions of the current application with additional biological detail. © The Author 2016. Published by Oxford University Press.

Clinical aspects and therapy of non-Hodgkin lymphomas

International Nuclear Information System (INIS)

Meissner, K.; Jaenner, M.

1981-01-01

Definition, incidence and distribution of age and sex of cutaneous non-Hodgkin lymphomas are presented. Clinical appearance of cutaneous non-Hodgkin lymphomas may exhibit specific and unspecific cutaneous lesions. Histological examination is of greatest importance for subsequent diagnostic and therapeutic procedures. Topical treatment, X-ray- or photochemotherapy are performed in the early stages, in case of therapeutic resistance and in advanced disease systemical chemotherapy is indicated. (orig.) [de

Cochlear spike synchronization and neuron coincidence detection model

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Bader, Rolf

2018-02-01

Coincidence detection of a spike pattern fed from the cochlea into a single neuron is investigated using a physical Finite-Difference model of the cochlea and a physiologically motivated neuron model. Previous studies have shown experimental evidence of increased spike synchronization in the nucleus cochlearis and the trapezoid body [Joris et al., J. Neurophysiol. 71(3), 1022-1036 and 1037-1051 (1994)] and models show tone partial phase synchronization at the transition from mechanical waves on the basilar membrane into spike patterns [Ch. F. Babbs, J. Biophys. 2011, 435135]. Still the traveling speed of waves on the basilar membrane cause a frequency-dependent time delay of simultaneously incoming sound wavefronts up to 10 ms. The present model shows nearly perfect synchronization of multiple spike inputs as neuron outputs with interspike intervals (ISI) at the periodicity of the incoming sound for frequencies from about 30 to 300 Hz for two different amounts of afferent nerve fiber neuron inputs. Coincidence detection serves here as a fusion of multiple inputs into one single event enhancing pitch periodicity detection for low frequencies, impulse detection, or increased sound or speech intelligibility due to dereverberation.

Primary Refractory and Relapsed Classical Hodgkin Lymphoma - Significance of Differential CD15 Expression in Hodgkin-Reed-Sternberg Cells

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Daniel Benharroch, Shai Pilosof, Jacob Gopas, Itai Levi

2012-01-01

Full Text Available We recognized a few possible complications of classical Hodgkin lymphoma therapy in a cohort of 209 patients: 8 developed a primary refractory disease (primary progression, 36 showed an early relapse and 21 showed a late relapse. Sialyl-CD15 expression in Hodgkin-Reed-Sternberg cells was significantly more positive in primary refractory Hodgkin lymphoma, which confirms our previously published findings. Bcl-2 showed a significantly lower level of expression in primary refractory disease than in the other follow-up groups. This is in contrast with a previous finding of Bcl-2, associated with a poor prognosis in primary refractory illness. Another category of variables, old age and advanced stages, was significantly different in the various complications but this finding is probably to be expected. We could not demonstrate a difference between the sequels and the control group with regard to several clinical and immunohistochemical markers. Sialyl-CD15 and Bcl-2 expression, in contrast, were confirmed as prognostic factors, mainly of tumor progression into primary refractory disease.

Linfoma não-Hodgkin de órbita: relato de caso Non-Hodgkin orbital lymphoma: case report

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Cristiane do Prado Silva

2008-04-01

Full Text Available O objetivo é relatar manifestação incomum de linfoma não-Hodgkin de órbita. Paciente masculino, de 75 anos, se apresentou com queixa de lacrimejamento crônico bilateral. Havia feito dacriocistorrinostomia endonasal à direita e à esquerda por duas vezes, sem sucesso. Ao exame, massas de consistência fibroelástica, em topografia das "bolsas" de gordura das pálpebras inferiores e proptose axial. O paciente negava outros sintomas ou sinais sistêmicos. Hemograma sem alteração, hormônios tireoidianos normais. A tomografia computadorizada mostrava infiltrado difuso na órbita e proptose axial. Biópsia de gordura orbitária e de medula óssea diagnosticaram linfoma não-Hodgkin. O paciente foi tratado com quimioterapia, sendo em seguida submetido à cirurgia da via lacrimal bilateral, com resolução do quadro. A doença sistêmica que exigia diagnóstico e tratamento adequados para que se tivesse bom prognóstico estava mascarada pelo quadro de epífora bilateral.The purpose is to report an unusual case of orbital non-Hodgkin lymphoma. A 75-year-old man presented with bilateral chronic epiphora complaint and inferior eyelid tumors, axial proptosis, without previous systemic manifestation. The patient was submitted to bilateral endonasal dacryocystorhinostomy twice and the epiphora complaint persisted. The inferior eyelid and bone marrow biopsy revealed non-Hodgkin lymphoma. The patient was treated with systemic chemotherapy and dacryocystorhinostomy with good resolution. The precise diagnosis and the treatment were very important to reach a good resolution of the bilateral epiphora complaint.

Brentuximab Vedotin Treatment for Primary Refractory Hodgkin Lymphoma

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Hung-Bo Wu

2013-01-01

Full Text Available Up to 40% of patients with advanced Hodgkin lymphoma (HL become refractory or relapsed after current standard chemotherapy, among which primary refractory HL confers a particularly poor outcome. With intensive salvage chemotherapy and autologous stem cell transplantation, the long-term remission rate for these patients was only 30%, but more selective treatments with higher therapeutic index are needed. We report the experience of using a new anti-CD30 immunotoxin, brentuximab vedotin, in salvage treatment of a 30-year-old woman with primary refractory Hodgkin lymphoma. The patient presented with SVC syndrome due to the bulky mediastinal tumor and was confirmed to have classical Hodgkin lymphoma, nodular sclerosis type, stage IIIA. The tumor responded to induction chemotherapy transiently, but local progression was noted during subsequent cycles of treatment. Salvage radiotherapy to the mediastinal tumor, obtained no remission but was followed by rapid in-field progression and then lung metastasis. She declined stem cell transplantation and received salvage brentuximab vedotin (BV therapy, which induced dramatic shrinkage of tumor without significant side effects. Serial followup of PET/CT imaging confirmed a rapid and continuous complete remission for 12 months. Although durability of the remission needs further observation, this case illustrates the excellent efficacy of brentuximab vedotin in primary refractory Hodgkin lymphoma.

On the number of preganglionic neurones driving human postganglionic sympathetic neurones: a comparison of modelling and empirical data

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Vaughan G Macefield

2011-12-01

Full Text Available Postganglionic sympathetic axons in awake healthy human subjects, regardless of their identity as muscle vasoconstrictor, cutaneous vasoconstrictor or sudomotor neurones, discharge with a low firing probability (~30%, generate low firing rates (~0.5 Hz and typically fire only once per cardiac interval. The purpose of the present study was to use modelling of spike trains in an attempt to define the number of preganglionic neurones that drive an individual postganglionic neurone. Artificial spike trains were generated in 1-3 preganglionic neurones converging onto a single postganglionic neurone. Each preganglionic input fired with a mean interval distribution of either 1000, 1500, 2000, 2500 or 3000 ms and the standard deviation varied between 0.5, 1.0 and 2.0 x the mean interval; the discharge frequency of each preganglionic neurone exhibited positive skewness and kurtosis. Of the 45 patterns examined, the mean discharge properties of the postganglionic neurone could only be explained by it being driven by, on average, two preganglionic neurones firing with a mean interspike interval of 2500 ms and SD of 5000 ms. The mean firing rate resulting from this pattern was 0.22 Hz, comparable to that of spontaneously active muscle vasoconstrictor neurones in healthy subjects (0.40 Hz. Likewise, the distribution of the number of spikes per cardiac interval was similar between the modelled and actual data: 0 spikes (69.5 vs 66.6 %, 1 spike (25.6 vs 21.2 %, 2 spikes (4.3 vs 6.4 %, 3 spikes (0.5 vs 1.7 % and 4 spikes (0.1 vs 0.7 %. Although some features of the firing patterns could be explained by the postganglionic neurone being driven by a single preganglionic neurone, none of the emulated firing patterns generated by the firing of three preganglionic neurones matched the discharge of the real neurones. These modelling data indicate that, on average, human postganglionic sympathetic neurones are driven by two preganglionic inputs.

Management of breast cancer following Hodgkin's disease

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Wolden, Suzanne L.; Carlson, Robert W.; Jeffrey, Stefanie S.; Hancock, Steven L.

1997-01-01

Purpose: To evaluate the incidence, histology, risk factors, treatment, and prognosis of breast cancer occurring after Hodgkin's disease. Materials and Methods: Sixty-five cases of breast cancer in 61 survivors of Hodgkin's lymphoma were analyzed. The median age at treatment for Hodgkin's disease was 24.1 [range (R): 13.3 - 71.8] years. Fifty-one percent had received radiotherapy alone, 47% radiation and chemotherapy, and 2% chemotherapy only. Relative and absolute risks were calculated based on 47 invasive breast cancers in 1049 women treated for Hodgkin's disease at Stanford. Results: The median age at diagnosis of breast cancer was 41.9 (R: 23.0 - 79.1) years; 76% of women were premenopausal. The median interval between Hodgkin's disease and breast cancer was 17.6 (R: 1.5 - 32.7) years with an increasing incidence beginning eight years after radiotherapy. The current relative risk of invasive breast cancer following Hodgkin's disease is 4.7 [95% confidence interval (CI): 3.4 - 6.1] with an absolute risk of 29.5 (CI: 18.8 - 40.2) excess cases per 10,000 person-years. Eighty-seven percent of breast cancers occurred in or at the margin of a prior radiotherapy field where a mean dose of 43.5 (R: 24.0 - 51.0) Gy was delivered. There was a family history of breast cancer in 31% of women. Cancers were detected by self examination (66%), screening mammography (27%), and physician examination (7%). Many tumors (60%) were located in the upper outer quadrants, corresponding to the axillary portion of a mantle field. There were seven cases of carcinoma in situ: six DCIS and one LCIS. The histologic distribution of invasive tumors paralleled that reported in the general population: 4% pure lobular, 35% high grade ductal, 45% intermediate grade ductal, 7% low-grade ductal, 4% tubular, 2% medullary, and 2% mucinous. Estrogen receptors were positive in 59% of evaluable cases. While 90% of invasive tumors were smaller than four centimeters, 96% were managed with mastectomy

Hodgkin's disease: internal mammary lymph nodes relapse diagnosed by Gallium-67 scintigraphy

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Ruiz Hernandez, G.; Ampudia, J.; Castillo, F.J.; Romero, C.; Pallardo, Y.; Garcia Conde, J.; Ramos, D.

1999-01-01

This article presents the case of a 62-year-old man with treated Hodgkin's disease who had internal mammary lymph nodes relapse after a complete initial response. These masses were gallium avid. These findings were explained by histologically documented Hodgkin's relapse, the first such case reported in that localization without chest wall involvement. The literature on mediastinal Hodgkin's disease and diagnostic procedures are reviewed. (orig.) [de

Open questions in the management of nodular lymphocyte predominant hodgkin lymphoma.

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Tyran, Marguerite; Gonzague, Laurence; Bouabdallah, Reda; Resbeut, Michel

2014-01-01

Localized Nodular Lymphocyte Predominant Hodgkin Lymphoma is a rare disease with an overall good prognosis but frequent late relapses. Due to it's rarity there is no standard therapeutic approach and pathological diagnosis may be hard. In this paper we discuss the technical aspects of the radiation therapy and histological issues. The new fields reductions proposed for classical Hodgkin lymphoma cannot be applied to early stages Nodular Lymphocyte Predominant Hodgkin lymphomas which are usually treated with radiation therapy without systemic chemotherapy.

PA03.13. Effect of triphaladi rasayana along with yoga therapy on low grade non hodgkins lymphoma and resistant intermediate and high grade non hodgkins lymphoma

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Soumya, MS Surya; Sarasa, TP

2013-01-01

Purpose: 1. To find out the effect of Thriphaladi Rasayana along with Yoga Therapy on low grade Non Hodgkins Lymphoma and resistant intermediate and high grade NonHodgkins Lymphoma. 2. To apply a less costly, less morbid, well accepted method of treatment on NHL. 3.To find a simple method to increase the immunity. 4.To try a drug which is easy to prepare? Method: Purposive sampling technique was used for the study. Sample of 30 patients age range 25 75 years with histologicaly proven NonHodgkins lymphoma, attending the M.O.I.O.P of the regional cancer centre during a period of 18 months. Groups1) Low grade NonHodgkins Lymphoma 2) Resistant intermediate &High grade NonHodgkins lymphoma (failed chemotherapy) were taken. Procedure : 2 groups were given Triphaladhi Rasayana (15 grams of powder with ghee and honey) twice dailymorning& at bed time with milk as anupana for period of 1month along with selected yoga asanas and niyama? Result: Symptoms included were fever, night sweats, weight loss, lymph nodes enlargement, splenomegaly, and hepatomegaly. In low grade symptom relief was noted in almost all cases. Lymph node changes notedLow grade5 2% (complete remission), 38% (partial remission), 10% (no change), intermediate35% (CR), 52% (PR) & 13% (NC), High grade67% (CR), 33%(PR). Hepatomegaly changes :ve in low grade92.86%, intermediate 90.9% & high grade100%. Splenomegaly changes :ve in low grade92.86%, intermediate72.72% & high grade80% Over all remission status of 30 patientscomplete remission30%, partial remission 30% & no change30%? Conclusion: Thriphaladirasayana along with Yoga therapy is very effective in Low grade NonHodgkins lymphoma and resistant intermediate and high grade Non hodgkins Lymphoma?

Biophysics Model of Heavy-Ion Degradation of Neuron Morphology in Mouse Hippocampal Granular Cell Layer Neurons.

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Alp, Murat; Cucinotta, Francis A

2018-03-01

Exposure to heavy-ion radiation during cancer treatment or space travel may cause cognitive detriments that have been associated with changes in neuron morphology and plasticity. Observations in mice of reduced neuronal dendritic complexity have revealed a dependence on radiation quality and absorbed dose, suggesting that microscopic energy deposition plays an important role. In this work we used morphological data for mouse dentate granular cell layer (GCL) neurons and a stochastic model of particle track structure and microscopic energy deposition (ED) to develop a predictive model of high-charge and energy (HZE) particle-induced morphological changes to the complex structures of dendritic arbors. We represented dendrites as cylindrical segments of varying diameter with unit aspect ratios, and developed a fast sampling method to consider the stochastic distribution of ED by δ rays (secondary electrons) around the path of heavy ions, to reduce computational times. We introduce probabilistic models with a small number of parameters to describe the induction of precursor lesions that precede dendritic snipping, denoted as snip sites. Predictions for oxygen ( 16 O, 600 MeV/n) and titanium ( 48 Ti, 600 MeV/n) particles with LET of 16.3 and 129 keV/μm, respectively, are considered. Morphometric parameters to quantify changes in neuron morphology are described, including reduction in total dendritic length, number of branch points and branch numbers. Sholl analysis is applied for single neurons to elucidate dose-dependent reductions in dendritic complexity. We predict important differences in measurements from imaging of tissues from brain slices with single neuron cell observations due to the role of neuron death through both soma apoptosis and excessive dendritic length reduction. To further elucidate the role of track structure, random segment excision (snips) models are introduced and a sensitivity study of the effects of the modes of neuron death in predictions

Novel animal model defines genetic contributions for neuron-to-neuron transfer of α-synuclein.

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Tyson, Trevor; Senchuk, Megan; Cooper, Jason F; George, Sonia; Van Raamsdonk, Jeremy M; Brundin, Patrik

2017-08-08

Cell-to-cell spreading of misfolded α-synuclein (α-syn) is suggested to contribute to the progression of neuropathology in Parkinson's disease (PD). Compelling evidence supports the hypothesis that misfolded α-syn transmits from neuron-to-neuron and seeds aggregation of the protein in the recipient cells. Furthermore, α-syn frequently appears to propagate in the brains of PD patients following a stereotypic pattern consistent with progressive spreading along anatomical pathways. We have generated a C. elegans model that mirrors this progression and allows us to monitor α-syn neuron-to-neuron transmission in a live animal over its lifespan. We found that modulation of autophagy or exo/endocytosis, affects α-syn transfer. Furthermore, we demonstrate that silencing C. elegans orthologs of PD-related genes also increases the accumulation of α-syn. This novel worm model is ideal for screening molecules and genes to identify those that modulate prion-like spreading of α-syn in order to target novel strategies for disease modification in PD and other synucleinopathies.

Complete Neuron-Astrocyte Interaction Model: Digital Multiplierless Design and Networking Mechanism.

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Haghiri, Saeed; Ahmadi, Arash; Saif, Mehrdad

2017-02-01

Glial cells, also known as neuroglia or glia, are non-neuronal cells providing support and protection for neurons in the central nervous system (CNS). They also act as supportive cells in the brain. Among a variety of glial cells, the star-shaped glial cells, i.e., astrocytes, are the largest cell population in the brain. The important role of astrocyte such as neuronal synchronization, synaptic information regulation, feedback to neural activity and extracellular regulation make the astrocytes play a vital role in brain disease. This paper presents a modified complete neuron-astrocyte interaction model that is more suitable for efficient and large scale biological neural network realization on digital platforms. Simulation results show that the modified complete interaction model can reproduce biological-like behavior of the original neuron-astrocyte mechanism. The modified interaction model is investigated in terms of digital realization feasibility and cost targeting a low cost hardware implementation. Networking behavior of this interaction is investigated and compared between two cases: i) the neuron spiking mechanism without astrocyte effects, and ii) the effect of astrocyte in regulating the neurons behavior and synaptic transmission via controlling the LTP and LTD processes. Hardware implementation on FPGA shows that the modified model mimics the main mechanism of neuron-astrocyte communication with higher performance and considerably lower hardware overhead cost compared with the original interaction model.

Modeling the Development of Goal-Specificity in Mirror Neurons.

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Thill, Serge; Svensson, Henrik; Ziemke, Tom

2011-12-01

Neurophysiological studies have shown that parietal mirror neurons encode not only actions but also the goal of these actions. Although some mirror neurons will fire whenever a certain action is perceived (goal-independently), most will only fire if the motion is perceived as part of an action with a specific goal. This result is important for the action-understanding hypothesis as it provides a potential neurological basis for such a cognitive ability. It is also relevant for the design of artificial cognitive systems, in particular robotic systems that rely on computational models of the mirror system in their interaction with other agents. Yet, to date, no computational model has explicitly addressed the mechanisms that give rise to both goal-specific and goal-independent parietal mirror neurons. In the present paper, we present a computational model based on a self-organizing map, which receives artificial inputs representing information about both the observed or executed actions and the context in which they were executed. We show that the map develops a biologically plausible organization in which goal-specific mirror neurons emerge. We further show that the fundamental cause for both the appearance and the number of goal-specific neurons can be found in geometric relationships between the different inputs to the map. The results are important to the action-understanding hypothesis as they provide a mechanism for the emergence of goal-specific parietal mirror neurons and lead to a number of predictions: (1) Learning of new goals may mostly reassign existing goal-specific neurons rather than recruit new ones; (2) input differences between executed and observed actions can explain observed corresponding differences in the number of goal-specific neurons; and (3) the percentage of goal-specific neurons may differ between motion primitives.

Hodgkin's disease of the prostate: a detailed case report

International Nuclear Information System (INIS)

Klotz, L.H.; Herr, H.W.

1986-01-01

Malignant lymphoma of the prostate is an unusual entity, and nonHodgkin's lymphoma constitutes most reported cases. We report a well documented case of Hodgkin's lymphoma, initially involving the gastrointestinal tract and spleen, which recurred in the prostate following initial remission with chemotherapy. Treatment with external beam radiotherapy resulted in a rapid complete response that has been sustained for 18 months

Thalamic neuron models encode stimulus information by burst-size modulation

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Daniel Henry Elijah

2015-09-01

Full Text Available Thalamic neurons have been long assumed to fire in tonic mode during perceptive states, and in burst mode during sleep and unconsciousness. However, recent evidence suggests that bursts may also be relevant in the encoding of sensory information. Here we explore the neural code of such thalamic bursts. In order to assess whether the burst code is generic or whether it depends on the detailed properties of each bursting neuron, we analyzed two neuron models incorporating different levels of biological detail. One of the models contained no information of the biophysical processes entailed in spike generation, and described neuron activity at a phenomenological level. The second model represented the evolution of the individual ionic conductances involved in spiking and bursting, and required a large number of parameters. We analyzed the models' input selectivity using reverse correlation methods and information theory. We found that n-spike bursts from both models transmit information by modulating their spike count in response to changes to instantaneous input features, such as slope, phase, amplitude, etc. The stimulus feature that is most efficiently encoded by bursts, however, need not coincide with one of such classical features. We therefore searched for the optimal feature among all those that could be expressed as a linear transformation of the time-dependent input current. We found that bursting neurons transmitted 6 times more information about such more general features. The relevant events in the stimulus were located in a time window spanning ~100 ms before and ~20 ms after burst onset. Most importantly, the neural code employed by the simple and the biologically realistic models was largely the same, implying that the simple thalamic neuron model contains the essential ingredients that account for the computational properties of the thalamic burst code. Thus, our results suggest the n-spike burst code is a general property of

Thalamic neuron models encode stimulus information by burst-size modulation.

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Elijah, Daniel H; Samengo, Inés; Montemurro, Marcelo A

2015-01-01

Thalamic neurons have been long assumed to fire in tonic mode during perceptive states, and in burst mode during sleep and unconsciousness. However, recent evidence suggests that bursts may also be relevant in the encoding of sensory information. Here, we explore the neural code of such thalamic bursts. In order to assess whether the burst code is generic or whether it depends on the detailed properties of each bursting neuron, we analyzed two neuron models incorporating different levels of biological detail. One of the models contained no information of the biophysical processes entailed in spike generation, and described neuron activity at a phenomenological level. The second model represented the evolution of the individual ionic conductances involved in spiking and bursting, and required a large number of parameters. We analyzed the models' input selectivity using reverse correlation methods and information theory. We found that n-spike bursts from both models transmit information by modulating their spike count in response to changes to instantaneous input features, such as slope, phase, amplitude, etc. The stimulus feature that is most efficiently encoded by bursts, however, need not coincide with one of such classical features. We therefore searched for the optimal feature among all those that could be expressed as a linear transformation of the time-dependent input current. We found that bursting neurons transmitted 6 times more information about such more general features. The relevant events in the stimulus were located in a time window spanning ~100 ms before and ~20 ms after burst onset. Most importantly, the neural code employed by the simple and the biologically realistic models was largely the same, implying that the simple thalamic neuron model contains the essential ingredients that account for the computational properties of the thalamic burst code. Thus, our results suggest the n-spike burst code is a general property of thalamic neurons.

Neurons other than motor neurons in motor neuron disease.

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Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

2017-11-01

Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

Interictal to Ictal Phase Transition in a Small-World Network

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Nemzer, Louis; Cravens, Gary; Worth, Robert

Real-time detection and prediction of seizures in patients with epilepsy is essential for rapid intervention. Here, we perform a full Hodgkin-Huxley calculation using n 50 in silico neurons configured in a small-world network topology to generate simulated EEG signals. The connectivity matrix, constructed using a Watts-Strogatz algorithm, admits randomized or deterministic entries. We find that situations corresponding to interictal (non-seizure) and ictal (seizure) states are separated by a phase transition that can be influenced by congenital channelopathies, anticonvulsant drugs, and connectome plasticity. The interictal phase exhibits scale-free phenomena, as characterized by a power law form of the spectral power density, while the ictal state suffers from pathological synchronization. We compare the results with intracranial EEG data and show how these findings may be used to detect or even predict seizure onset. Along with the balance of excitatory and inhibitory factors, the network topology plays a large role in determining the overall characteristics of brain activity. We have developed a new platform for testing the conditions that contribute to the phase transition between non-seizure and seizure states.

A distance constrained synaptic plasticity model of C. elegans neuronal network

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Badhwar, Rahul; Bagler, Ganesh

2017-03-01

Brain research has been driven by enquiry for principles of brain structure organization and its control mechanisms. The neuronal wiring map of C. elegans, the only complete connectome available till date, presents an incredible opportunity to learn basic governing principles that drive structure and function of its neuronal architecture. Despite its apparently simple nervous system, C. elegans is known to possess complex functions. The nervous system forms an important underlying framework which specifies phenotypic features associated to sensation, movement, conditioning and memory. In this study, with the help of graph theoretical models, we investigated the C. elegans neuronal network to identify network features that are critical for its control. The 'driver neurons' are associated with important biological functions such as reproduction, signalling processes and anatomical structural development. We created 1D and 2D network models of C. elegans neuronal system to probe the role of features that confer controllability and small world nature. The simple 1D ring model is critically poised for the number of feed forward motifs, neuronal clustering and characteristic path-length in response to synaptic rewiring, indicating optimal rewiring. Using empirically observed distance constraint in the neuronal network as a guiding principle, we created a distance constrained synaptic plasticity model that simultaneously explains small world nature, saturation of feed forward motifs as well as observed number of driver neurons. The distance constrained model suggests optimum long distance synaptic connections as a key feature specifying control of the network.

Environmental risk factors related to the development of canine non-Hodgkin's lymphoma Fatores de risco ambientais relacionados ao desenvolvimento do linfoma não Hodgkin canino

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Danielle Almeida Zanini

2013-01-01

Full Text Available This research aimed to investigate the possible risk factors associated with the development of canine non-Hodgkin's lymphoma. Owners of 83 dogs with non-Hodgkin's lymphoma and of 84 healthy dogs answered an epidemiological questionnaire. Dogs who lived outside of the house and within 100 meters of busy streets or avenues (defined as more than 50 vehicles per minute had a higher risk for developing the disease (OR: 3.1, 95% CI: 1.4-6.9, P=0.005. These results suggest that air pollution derived from vehicle traffic may be associated with the development of canine non-Hodgkin's lymphoma.Este trabalho teve como objetivo investigar os possíveis fatores de risco ambientais, associados com o desenvolvimento de linfoma não-Hodgkin nos cães. Um questionário epidemiológico foi aplicado aos proprietários de 83 cães com linfoma não-Hodgkin e 84 proprietários de cães saudáveis. Os cães que viviam permanentemente no lado de fora da casa e em torno de 100 metros de ruas movimentadas ou avenidas (mais de 50 veículos por minuto tiveram um maior risco de desenvolvimento da doença (OR: 3,1, IC 95%: 1,4-6,9, P=0,005. Esses resultados sugerem que a poluição do ar oriunda do tráfego veicular pode estar associada com o desenvolvimento de linfomas não-Hodgkin canino.

Association between simian virus 40 and non-Hodgkin lymphoma

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Vilchez, Regis A.; Madden, Charles R.; Kozinetz, Claudia A.; Halvorson, Steven J.; White, Zoe S.; Jorgensen, Jeffrey L.; Finch, Chris J.; Butel, Janet S.

2002-01-01

BACKGROUND: Non-Hodgkin lymphoma has increased in frequency over the past 30 years, and is a common cancer in HIV-1-infected patients. Although no definite risk factors have emerged, a viral cause has been postulated. Polyomaviruses are known to infect human beings and to induce tumours in laboratory animals. We aimed to identify which one of the three polyomaviruses able to infect human beings (simian virus 40 [SV40], JC virus, and BK virus) was associated with non-Hodgkin lymphoma. METHODS: We analysed systemic non-Hodgkin lymphoma from 76 HIV-1-infected and 78 HIV-1-uninfected patients, and non-malignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumours; 54 colon and breast carcinoma samples served as cancer controls. We used PCR followed by Southern blot hybridisation and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. FINDINGS: Polyomavirus T antigen sequences, all of which were SV40-specific, were detected in 64 (42%) of 154 non-Hodgkin lymphomas, none of 186 non-malignant lymphoid samples, and none of 54 control cancers. This difference was similar for HIV-1-infected patients and HIV-1-uninfected patients alike. Few tumours were positive for both SV40 and Epstein-Barr virus. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B-cell and follicular-type lymphomas. INTERPRETATION: SV40 is significantly associated with some types of non-Hodgkin lymphoma. These results add lymphomas to the types of human cancers associated with SV40.

From in silico astrocyte cell models to neuron-astrocyte network models: A review.

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Oschmann, Franziska; Berry, Hugues; Obermayer, Klaus; Lenk, Kerstin

2018-01-01

The idea that astrocytes may be active partners in synaptic information processing has recently emerged from abundant experimental reports. Because of their spatial proximity to neurons and their bidirectional communication with them, astrocytes are now considered as an important third element of the synapse. Astrocytes integrate and process synaptic information and by doing so generate cytosolic calcium signals that are believed to reflect neuronal transmitter release. Moreover, they regulate neuronal information transmission by releasing gliotransmitters into the synaptic cleft affecting both pre- and postsynaptic receptors. Concurrent with the first experimental reports of the astrocytic impact on neural network dynamics, computational models describing astrocytic functions have been developed. In this review, we give an overview over the published computational models of astrocytic functions, from single-cell dynamics to the tripartite synapse level and network models of astrocytes and neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

Lymphocyte-predominant Hodgkin disease: a comprehensive overview.

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Bose, Sumit; Ganesan, Chitra; Pant, Manish; Lai, Catherine; Tabbara, Imad A

2013-02-01

Lymphocyte-predominant Hodgkin disease is a rare form of Hodgkin lymphoma that is recognized as a separate histopathological entity. This disease tends to have multiple relapses, but has an overall good prognosis. Owing to its rarity, and the prolonged time period between recurrence and transformation events, there is no consensus regarding optimal management. However, the National Comprehensive Cancer Network guidelines indicate that for early stages, appropriate treatment is radiotherapy. Several management options have been reported including observation, radiation, chemotherapy, combined chemoradiotherapy, and anti-CD20 antibody therapy. Salvage therapy remains effective in inducing prolonged remission in patients with relapsed/refractory disease.

Breast Cancer After Treatment of Hodgkin's Lymphoma: General Review

International Nuclear Information System (INIS)

Alm El-Din, Mohamed A.; El-Badawy, Samy A.; Taghian, Alphonse G.

2008-01-01

The improved survival rates among patients with Hodgkin's lymphoma over the past few decades have come with increased incidence of second malignancies. One of the major concerns among female survivors is the significantly elevated risk of breast cancer that appears with extended follow-up. In this review, we include the published literature regarding the risk of breast cancer after irradiation for Hodgkin's lymphoma. We also present the possible long-term surveillance strategies and the optimal time to start screening these women. This could potentially help in early detection of secondary breast cancers and consequently improve outcomes. Furthermore, because of prior radiotherapy, the management of the breast cancer among this unique population has been controversial. We discuss the characteristics of breast cancer that occurs after Hodgkin's lymphoma and also treatment options that could be implemented

Functional hyposplenia after splenic irradiation for Hodgkin's disease

International Nuclear Information System (INIS)

Coleman, C.N.; McDougall, I.R.; Dailey, M.O.; Ager, P.; Bush, S.; Kaplan, H.S.

1982-01-01

We previously reported a patients who developed fulminant pneumococcal sepsis 12 years after successful treatment for Hodgkin's disease, which included splenic irradiation. We have since evaluated splenic size and function in 25 patients who had received splenic irradiation 5 to 16 years previously either for Hodgkin's disease (n . 19) or non-Hodgkin's lymphoma (n . 6). Mean maximum splenic diameter as measured on a 99mTc-sulfur colloid liver-spleen scan was 6.2 cm in the irradiated group and 9.7 cm in a control group (p less than 0.001). The mean percentage of erythrocytes containing pits when observed with interference phase microscopy was 13.0% in the irradiated group, which was significantly different (p less than 0.001) from the levels found in each of the control groups: normal subjects, 0.9%; unstaged and untreated lymphoma patients, 0.6%; and patients after splenectomy, 33.7%. Patients who have had splenic irradiation should be considered at risk of developing overwhelming pneumococcal sepsis

Hodgkin's lymphoma arising in a case of mycosis fungoides: An unusual association

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Preeti Sharma

2018-01-01

Full Text Available Mycosis fungoides is a cutaneous T-cell lymphoma with a high risk for developing secondary malignancies, especially B-cell lymphoproliferative disorders. About 40 cases of Hodgkin's lymphoma associated with mycosis fungoides have been reported in literature till date. We report a case of a 35-year-old gentleman who presented with intensely itchy reddish lesions all over the body. Multiple skin biopsies taken from the lesions on scalp and back confirmed the clinical diagnosis of mycosis fungoides. While on treatment, he presented with multiple bilateral cervical, axillary and inguinal lymphadenopathy 9 years after the primary diagnosis of mycosis fungoides. Excision biopsy of a cervical lymph node revealed partial effacement of architecture by a tumor comprising polymorphous background. Histopathology and immunohistochemistry revealed a diagnosis of Hodgkin's lymphoma - nodular sclerosis subtype. The patient was started on chemotherapy for stage IV Hodgkin's lymphoma. Our case emphasizes the importance of keeping secondary Hodgkin's lymphoma in mind while dealing with a patient of mycosis fungoides. Our case immunohistochemically supports the distinct etiopathogenesis of Epstein–Barr virus-negative Hodgkin's lymphoma vis-à-vis cutaneous mycosis fungoides.

Nodal involvement in Hodgkin disease and non-Hodgkin lymphoma assessed by magnetic resonance

International Nuclear Information System (INIS)

Tesoro Tess, J.D.; Balzarini, L.; Ceglia, E.; Petrillo, R.; Musumeci, R.

1990-01-01

Magnetic Resonance Imaging (MRI) demonstrates a good capability in distinguishing nodal involvement in hodgkin disease and nonhodgkin lymphoma both in the chest and in the retroperitoneal areas the initial presentation of the disease. However CT and lymphangiography demonstrated comparable or superior values of accuracy and sensitivity. (H.W.) 4 refs.; 2 tabs

Expression of Epstein-Barr virus in Hodgkin lymphoma Specimens in IRAN.

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Laila Mozafari

2013-09-01

Full Text Available  Background &Objectives: The Epstein-Barr Virus (EBV( is related with various diseases including infectious mononucleosis, Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma and post-transplant lymphoprolifrative disorders. The aim of this study was to characterize the association between EBV and Hodgkin's lymphoma through EBERs in situ hybridization (EBER-ISH in Iranian patients.    Materials &Methods: In this study, 43 Hodgkin's lymphoma tissue samples were selected from formalin-fixed paraffin embedded blocks and analyzed by EBERs in situ hybridization. Data analyzed by SPSS16 statistical software, Fisher's exact test and Mantel-Haensel significant level 0.05.   Results: 43 Hodgkin's lymphoma patients were 29 (67% male samples and 14 (33% female samples. In 20 (47% samples Epstein-Barr virus was present. The positive cases included 13 samples  male and 7 samples female. Fisher's exact test showed statistically no significant difference between sex and subtypes. Age distribution of relation of Hodgkin's lymphoma and EBV virus were 75% (12 of 16 in the age group of 1-14 years,  22% (5 of 23 in the age group 15-49 years and 75% (3 of 4 in the age group over 49 years, respectively. Fisher's exact test showed statistically significant difference between 1-14 and 15-49 age group years (p-value: 0.003.   Conclusion: Results shown higher presence rate of Epstein-Barr virus in Hodgkin's lymphoma specimens  of children and older adult. This pattern is similar to other developing countries. 

Drugs Approved for Hodgkin Lymphoma

Science.gov (United States)

This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Hodgkin lymphoma. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

Thyroid dysfunction after mantle irradiation of Hodgkin`s disease patients

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Khoo, V.S.; Liew, K.H.; Crennan, E.C.; D`Costa, I.M. [Peter MacCallum Caner Institute, East Melbourne, VIC (Australia). Department of Radiation Oncology; Quong, G. [Austin and Repatriation Medical Centre, West Heidelberg, VIC (Australia). Department of Radiation Oncology

1998-02-01

Thyroid dysfunction can develop in patients with Hodgkin`s disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, Iymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated. Copyright (1998) Blackwell Science Pty Ltd 32 refs., 3 tabs.

Bifurcation software in Matlab with applications in neuronal modeling.

Science.gov (United States)

Govaerts, Willy; Sautois, Bart

2005-02-01

Many biological phenomena, notably in neuroscience, can be modeled by dynamical systems. We describe a recent improvement of a Matlab software package for dynamical systems with applications to modeling single neurons and all-to-all connected networks of neurons. The new software features consist of an object-oriented approach to bifurcation computations and the partial inclusion of C-code to speed up the computation. As an application, we study the origin of the spiking behaviour of neurons when the equilibrium state is destabilized by an incoming current. We show that Class II behaviour, i.e. firing with a finite frequency, is possible even if the destabilization occurs through a saddle-node bifurcation. Furthermore, we show that synchronization of an all-to-all connected network of such neurons with only excitatory connections is also possible in this case.

A Neuron Model Based Ultralow Current Sensor System for Bioapplications

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A. K. M. Arifuzzman

2016-01-01

Full Text Available An ultralow current sensor system based on the Izhikevich neuron model is presented in this paper. The Izhikevich neuron model has been used for its superior computational efficiency and greater biological plausibility over other well-known neuron spiking models. Of the many biological neuron spiking features, regular spiking, chattering, and neostriatal spiny projection spiking have been reproduced by adjusting the parameters associated with the model at hand. This paper also presents a modified interpretation of the regular spiking feature in which the firing pattern is similar to that of the regular spiking but with improved dynamic range offering. The sensor current ranges between 2 pA and 8 nA and exhibits linearity in the range of 0.9665 to 0.9989 for different spiking features. The efficacy of the sensor system in detecting low amount of current along with its high linearity attribute makes it very suitable for biomedical applications.

Bilateral breast cancer after cured Hodgkin's disease

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Anderson, N.; Lokich, J. (New England Baptist Hospital, Boston, MA (USA))

1990-01-15

Three patients developed bilateral breast cancer at 10 to 24 years after mantle irradiation for locally or systemically advanced Hodgkin's disease (HD). Four of the six cancers in the three patients were detected only by mammography. Pathologically, five of the cancers were intraductal carcinomas (four with an invasive component) with one being a lobular carcinoma. Five of the six lesions were Stage I pathologically without evidence of axillary nodal involvement. It is recommended that female patients with Hodgkin's disease who have received mantle irradiation as part of the therapy for their Hodgkin's disease and who are observed for 10 or more years after completion of mantle irradiation be considered at risk for the development of breast cancer. Such patients should be monitored appropriately by routine bilateral mammograms to increase the early detection of early stage lesions.

Acute myelomonocytic leukemia following splenectomy in a patient with long-standing Hodgkin disease

International Nuclear Information System (INIS)

Rosenbloom, B.E.; Klein, E.J.; Uszler, J.M.; Ellis, R.; Block, J.B.; Tanaka, K.R.

1978-01-01

The association of acute nonlymphocytic leukemia with Hodgkin disease has been recorded in more than 100 instances. In most of these cases the patient has had long-standing Hodgkin disease and radiotherapy has been carried out. The combination of previous radiotherapy and chemotherapy appears to further increase the risk of leukemia developing. In a patient under our care with Hodgkin disease acute myelomonocytic leukemia developed following splenectomy for hypersplenism. The onset of acute leukemia immediately following splenectomy in a patient with Hodgkin disease has not previously been noted. In addition, because the patient's usual bone marrow sampling sites were hypoplastic, we utilized an 111 In-chloride bone marrow scan to find a site that was accessible for aspiration

Probing the dynamics of identified neurons with a data-driven modeling approach.

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Thomas Nowotny

2008-07-01

Full Text Available In controlling animal behavior the nervous system has to perform within the operational limits set by the requirements of each specific behavior. The implications for the corresponding range of suitable network, single neuron, and ion channel properties have remained elusive. In this article we approach the question of how well-constrained properties of neuronal systems may be on the neuronal level. We used large data sets of the activity of isolated invertebrate identified cells and built an accurate conductance-based model for this cell type using customized automated parameter estimation techniques. By direct inspection of the data we found that the variability of the neurons is larger when they are isolated from the circuit than when in the intact system. Furthermore, the responses of the neurons to perturbations appear to be more consistent than their autonomous behavior under stationary conditions. In the developed model, the constraints on different parameters that enforce appropriate model dynamics vary widely from some very tightly controlled parameters to others that are almost arbitrary. The model also allows predictions for the effect of blocking selected ionic currents and to prove that the origin of irregular dynamics in the neuron model is proper chaoticity and that this chaoticity is typical in an appropriate sense. Our results indicate that data driven models are useful tools for the in-depth analysis of neuronal dynamics. The better consistency of responses to perturbations, in the real neurons as well as in the model, suggests a paradigm shift away from measuring autonomous dynamics alone towards protocols of controlled perturbations. Our predictions for the impact of channel blockers on the neuronal dynamics and the proof of chaoticity underscore the wide scope of our approach.

Fertility and sexual function in female Hodgkin lymphoma survivors of reproductive age.

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Eeltink, Corien M; Incrocci, Luca; Witte, Birgit I; Meurs, Saskia; Visser, Otto; Huijgens, Peter; Verdonck-de Leeuw, Irma M

2013-12-01

To assess the perceived fertility status and to determine the association between perceived fertility status and sexual function, as reported by young female Hodgkin lymphoma survivors. Young female Hodgkin lymphoma survivors are at risk of infertility and impaired sexual function. However, little is known about their awareness of infertility and its association with sexual functioning. A descriptive questionnaire survey. In this cross-sectional study, a survey was completed by female Hodgkin lymphoma survivors (40 years). Outcome measures included self-reported fertility status and sexual problems and the internationally validated Female Sexual Function Index. In total, 36 survivors were included (mean age 32 years, SD 4). Eighteen women (50%) thought themselves fertile. Eight survivors (22%) who perceived themselves as being infertile were more often treated with alkylator-based chemotherapy, and 63% reported sexual dysfunction. Ten survivors (28%) were not aware as to whether they were fertile or not; seven of these would like to have children. The reported fertility status was related to age and chemotherapy regimen. Regarding sexuality, 14 (39%) of the female Hodgkin lymphoma survivors reported one or more sexual problem and none reported recovery. Female sexual dysfunction according to the Female Sexual Function Index was reported by 11 (31%) survivors. Almost 30% of Hodgkin lymphoma survivors do not know whether they are fertile or not. Overall sexual dysfunction is common in Hodgkin lymphoma survivors and comparable to the general population. However, a lack of desire was significantly more often reported in female Hodgkin lymphoma survivors. To prevent assumed infertility and unintended childlessness by postponing parenthood in young female survivors, awareness of fertility status is needed. There is also a need to routinely assess sexual function and provide adequate interventions to improve arousal and lubrication problems. © 2013 John Wiley & Sons Ltd.

General Information about Childhood Hodgkin Lymphoma

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... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Resources for ... memory. Second cancers (new types of cancer). For female survivors of Hodgkin lymphoma, there is an increased ...

Mathematical and numerical study of nonlinear boundary problems related to plasma physics

International Nuclear Information System (INIS)

Sermange, M.

1982-06-01

After the study of some equations based on the Hodgkin-Huxley model, the work presented here is concerned with nonlinear boundary problems in MHD. They are gathered in two subjects: equilibrium equations and stability equations. The axisymmetric MHD equilibrium equations with free boundary have been studied by different authors, particularly the existence, regularity, unicity and non-unicity. Here, bifurcation, convergence of calculation methods existence of solutions in a discontinuous frame are studied. MHD stability can be determined by the principle of Bernstein et al; the mathematical work concerned here bears on the equivalence, in the case of two-dimensional or axisymmetric stability, between this model and a scalar eigenvalue problem which is introduced. At last, modules for computing MHD equilibrium for the simulation of plasma confinement in a tokamak are described [fr

Complex Behavior in a Selective Aging Neuron Model Based on Small World Networks

International Nuclear Information System (INIS)

Zhang Guiqing; Chen Tianlun

2008-01-01

Complex behavior in a selective aging simple neuron model based on small world networks is investigated. The basic elements of the model are endowed with the main features of a neuron function. The structure of the selective aging neuron model is discussed. We also give some properties of the new network and find that the neuron model displays a power-law behavior. If the brain network is small world-like network, the mean avalanche size is almost the same unless the aging parameter is big enough.

Electrical Activity in a Time-Delay Four-Variable Neuron Model under Electromagnetic Induction

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Keming Tang

2017-11-01

Full Text Available To investigate the effect of electromagnetic induction on the electrical activity of neuron, the variable for magnetic flow is used to improve Hindmarsh–Rose neuron model. Simultaneously, due to the existence of time-delay when signals are propagated between neurons or even in one neuron, it is important to study the role of time-delay in regulating the electrical activity of the neuron. For this end, a four-variable neuron model is proposed to investigate the effects of electromagnetic induction and time-delay. Simulation results suggest that the proposed neuron model can show multiple modes of electrical activity, which is dependent on the time-delay and external forcing current. It means that suitable discharge mode can be obtained by selecting the time-delay or external forcing current, which could be helpful for further investigation of electromagnetic radiation on biological neuronal system.

Lifetime physical inactivity is associated with increased risk for Hodgkin and non-Hodgkin lymphoma: A case-control study.

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Etter, John Lewis; Cannioto, Rikki; Soh, Kah Teong; Alquassim, Emad; Almohanna, Hani; Dunbar, Zachary; Joseph, Janine M; Balderman, Sophia; Hernandez-Ilizaliturri, Francisco; Moysich, Kirsten B

2018-03-27

Although physical activity is a well-established risk factor for several cancer types, studies evaluating its association with lymphoma have yielded inconclusive results. In such cases where physical activity is not clearly associated with cancer risk in a dose-dependent manner, investigators have begun examining physical inactivity as an independent exposure of interest. Associations of self-reported, lifetime physical inactivity with risk of developing Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) were evaluated in a hospital-based case control study using data from the Patient Epidemiology Data System at Roswell Park Comprehensive Cancer Center. Participants included 87 patients with HL and 236 patients with NHL as well as 348 and 952 cancer-free controls, respectively. Multivariable-adjusted logistic regression models were fit to calculate odds ratios (OR) and 95% confidence intervals (CI) estimating the association between physical inactivity and lymphoma risk. We observed significant, positive associations between lifetime recreational physical inactivity and risk of both HL (OR = 1.90, 95% CI: 1.15-3.15) and NHL (OR = 1.35, 95% CI: 1.01-1.82). The current analysis provides evidence for a positive association between physical inactivity and risk of both HL and NHL. These results add to a growing body of research suggesting that lifetime physical inactivity may be an important independent, modifiable behavioral risk factor for cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fertility and sexual function in female Hodgkin lymphoma survivors of reproductive age

NARCIS (Netherlands)

Eeltink, C.M.; Incrocci, L.; Witte, B.I.; Meurs, S.; Visser, O.; Huijgens, P.C.; de Leeuw, I.M.

2013-01-01

Aims and objectives: To assess the perceived fertility status and to determine the association between perceived fertility status and sexual function, as reported by young female Hodgkin lymphoma survivors. Background: Young female Hodgkin lymphoma survivors are at risk of infertility and impaired

ONC201 induces cell death in pediatric non-Hodgkin's lymphoma cells

OpenAIRE

Talekar, Mala K; Allen, Joshua E; Dicker, David T; El-Deiry, Wafik S

2015-01-01

ONC201/TIC10 is a small molecule initially discovered by its ability to coordinately induce and activate the TRAIL pathway selectively in tumor cells and has recently entered clinical trials in adult advanced cancers. The anti-tumor activity of ONC201 has previously been demonstrated in several preclinical models of cancer, including refractory solid tumors and a transgenic lymphoma mouse model. Based on the need for new safe and effective therapies in pediatric non-Hodgkin's lymphoma (NHL) a...

Characteristics of lymphographic semiotics in children with Hodgkin's disease

International Nuclear Information System (INIS)

Baryshnikov, V.L.; Krivenko, Eh.V.; Minkh, N.V.

1984-01-01

Direct low lymphography was performed in 140 children aged 2.5 to 16 wheh Hodgkin's disease. Typical changes in the lymph nodes were found in 45 (32.14%) patient;. Symptoms of disordered drainage function of the nodes in children occur more frequently than in adults (in 71% of the cases observed). X.ray signs of the morphological changes in the lymph nodes that in combination with functional symptoms give 4 main symptomocomplexes which are characteristic of Hodgkin's disease in children are singled out

Non-Hodgkin's lymphoma - the role of radiation therapy

International Nuclear Information System (INIS)

Gospodarowicz, Mary K.

1995-01-01

Objective: To review the approach to the diagnosis, assessment, treatment and continuing management of patients with Non-Hodgkin's lymphoma with the emphasis on the role of radiation therapy in this group of diseases. The entity of 'Non-Hodgkin's Lymphoma' encompasses a diverse group of disorders involving almost any part of the body. This diversity bedevils any attempt to unify the approach to this disease on a rational basis. Nevertheless, some broad principles can be applied to almost any presentation of Non-Hodgkin's lymphoma. The approach to the management of Non-Hodgkin's lymphoma is based on the histologic type, localization and extent of disease and other disease and patient related prognostic factors. The accurate pathologic diagnosis of lymphoma has been greatly facilitated by availability of markers, molecular and genetic techniques. The newly proposed revised classification of lymphomas and its impact on these of RT will be discussed. Although the Ann Arbor staging classification has been shown to provide important prognostic information, other factors have equivalent, if not greater, influence on outcome in patients with Non-Hodgkin's lymphomas. The management of lymphomas is based primarily on the histologic type and extent of the disease including stage, tumour bulk, number of sites involved and location of the disease. The success of curative radiation therapy is contingent upon the presence of localized disease, normal tissue tolerance allowing the delivery of RT curative dose (30-35 Gy) and the tumour bulk. The current evidence suggests that locoregional RT for stage I and II low grade lymphoma results in approximately 50% prolonged (10-15 years) failure free rate and possible cure. Radiation alone is no longer used for intermediate and high grade lymphomas. The standard management of stage I and II intermediate grade large cell and mixed lymphomas is with doxorubicin based chemotherapy (e.g. CHOP) followed by involved field radiation. The

Non-Hodgkin's lymphoma presenting as a single liver mass; Linfoma nao-Hodgkin apresentando-se como massa hepatica unica

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Peixoto, Mila Correia Gois; Peixoto Filho, Anibal Araujo Alves; D' Ippolito, Giuseppe [Hospital Sao Luiz, Sao Paulo, SP (Brazil). Setor de US/TC/RM]. E-mail: scoposl@uol.com.br; Ribeiro, Alessandra Caivano Rodrigues [Hospital Sao Luiz, Sao Paulo, SP (Brazil). Setor de Diagnostico por Imagem

2009-01-15

Objective: to describe the main imaging findings of non-Hodgkin's lymphoma presenting as a single liver mass. Materials and methods: a retrospective study was developed with analysis of cases where a single liver mass was observed at ultrasonography, computed tomography and magnetic resonance imaging, and histologically diagnosed as non-Hodgkin's lymphoma. The studies were reviewed by two observers in consensus. Results: three male patients in the fifth decade of life, with non-specific clinical manifestations and single liver mass diagnosed as non-Hodgkin's lymphoma were identified. A hepatic lesion with target sign was observed at ultrasonography in all of the cases. At computed tomography, all the patients presented a heterogeneous, hypodense mass with a ring enhancement. At magnetic resonance imaging, the lesions were heterogeneous and hypointense on T1-weighted and hyperintense on T2-weighted images. Additionally, a ring enhancement was observed in all of the cases after contrast injection. At the moment of the diagnosis, none of the patients presented lymphadenomegaly or involvement of other solid viscera. Conclusion: the diagnosis of hepatic lymphoma should be considered in the presence of a ring-enhanced single liver mass. (author)

Novel insights in the pathogenesis of Hodgkin lymphoma : microenvironment, genetic landscape and regulation of HLA expression

NARCIS (Netherlands)

Liu, Yuxuan

2013-01-01

Gemuteerde genen spelen belangrijke rol in ontstaan Hodgkin lymfoom Het klassieke Hodgkin lymfoom (eerder bekend als ‘de ziekte van Hodgkin’) bestaat voor slechts een zeer klein deel uit tumorcellen en voor het overgrote deel uit normale immuuncellen. Die samenstelling maakt het Hodgkin lymfoom

Effects of radiochemotherapy and splenectomy on cellular immunity in long-term survivors of Hodgkin's disease and non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Steele, R.; Han, T.

1978-01-01

Thirty-six patients treated for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) who had been in complete remission and off all therapy for greater than two years were examined for evidence of immunosuppression. All patients were found to have marked depression of their lymphocyte blastogenic response to phytohemagglutinin (PHA) and of their skin test responses. No abnormalities of serum protein or immunoglobulins were found. T cells were significantly lower than normal in patients who had had Hodgkin's disease, but not in those who had had NHL. B cells, on the other hand, were significantly elevated in both groups. Splenectomy elevated the total lymphocyte count, while those who had not had a splenectomy had lower than normal lymphocyte counts. B cells were elevated while T cells tended to be lower in both splenectomy and nonsplenectomy groups, though only in the nonsplenectomized patients did this reach statistical significance. The PHA response tended to be higher in patients with less advanced disease and less extensive treatment than in those with more advanced disease and more extensive treatment, although there was no statistically significant difference. Skin test response though, was shown to correlate well with both stage of disease at diagnosis and extent of treatment

An experimental electronic model for a neuronal cell

International Nuclear Information System (INIS)

Campos-Cantón, I; Martel-Gallegos, G; Rangel-López, A; Vertiz-Hérnandez, A; Zarazúa, S

2014-01-01

Over the last two decades, the study of information transmission in living beings has acquired great relevance, because it regulates and conducts the functioning of all of the organs in the body. In information transmission pathways, the neuron plays an important role in that it receives, transmits, and processes electrical signals from different parts of the human body; these signals are transmitted as electrical impulses called action potentials, and they transmit information from one neuron to another. In this work, and with the aim of developing experiments for teaching biological processes, we implemented an electronic circuit of the neuron cell device and its mathematical model based on piecewise linear functions. (paper)

Noise-Induced Transition in a Voltage-Controlled Oscillator Neuron Model

International Nuclear Information System (INIS)

Xie Huizhang; Liu Xuemei; Li Zhibing; Ai Baoquan; Liu Lianggang

2008-01-01

In the presence of Gaussian white noise, we study the properties of voltage-controlled oscillator neuron model and discuss the effects of the additive and multiplicative noise. It is found that the additive noise can accelerate and counterwork the firing of neuron, which depends on the value of central frequency of neuron itself, while multiplicative noise can induce the continuous change or mutation of membrane potential

A Neuronal Network Model for Pitch Selectivity and Representation.

Science.gov (United States)

Huang, Chengcheng; Rinzel, John

2016-01-01

Pitch is a perceptual correlate of periodicity. Sounds with distinct spectra can elicit the same pitch. Despite the importance of pitch perception, understanding the cellular mechanism of pitch perception is still a major challenge and a mechanistic model of pitch is lacking. A multi-stage neuronal network model is developed for pitch frequency estimation using biophysically-based, high-resolution coincidence detector neurons. The neuronal units respond only to highly coincident input among convergent auditory nerve fibers across frequency channels. Their selectivity for only very fast rising slopes of convergent input enables these slope-detectors to distinguish the most prominent coincidences in multi-peaked input time courses. Pitch can then be estimated from the first-order interspike intervals of the slope-detectors. The regular firing pattern of the slope-detector neurons are similar for sounds sharing the same pitch despite the distinct timbres. The decoded pitch strengths also correlate well with the salience of pitch perception as reported by human listeners. Therefore, our model can serve as a neural representation for pitch. Our model performs successfully in estimating the pitch of missing fundamental complexes and reproducing the pitch variation with respect to the frequency shift of inharmonic complexes. It also accounts for the phase sensitivity of pitch perception in the cases of Schroeder phase, alternating phase and random phase relationships. Moreover, our model can also be applied to stochastic sound stimuli, iterated-ripple-noise, and account for their multiple pitch perceptions.

A metabolomic comparison of mouse models of the Neuronal Ceroid Lipofuscinoses

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Salek, Reza M.; Pears, Michael R. [University of Cambridge, Department of Biochemistry and Cambridge Systems Biology Centre (United Kingdom); Cooper, Jonathan D. [King' s College London, Pediatric Storage Disorders Laboratory, Department of Neuroscience, Institute of Psychiatry (United Kingdom); Mitchison, Hannah M. [Royal Free and University College Medical School, Department of Paediatrics and Child Health (United Kingdom); Pearce, David A. [Sanford School of Medicine of the University of South Dakota, Department of Pediatrics (United States); Mortishire-Smith, Russell J. [Johnson and Johnson PR and D (Belgium); Griffin, Julian L., E-mail: jlg40@mole.bio.cam.ac.uk [University of Cambridge, Department of Biochemistry and the Cambridge Systems Biology Centre (United Kingdom)

2011-04-15

The Neuronal Ceroid Lipofuscinoses (NCL) are a group of fatal inherited neurodegenerative diseases in humans distinguished by a common clinical pathology, characterized by the accumulation of storage body material in cells and gross brain atrophy. In this study, metabolic changes in three NCL mouse models were examined looking for pathways correlated with neurodegeneration. Two mouse models; motor neuron degeneration (mnd) mouse and a variant model of late infantile NCL, termed the neuronal ceroid lipofuscinosis (nclf) mouse were investigated experimentally. Both models exhibit a characteristic accumulation of autofluorescent lipopigment in neuronal and non neuronal cells. The NMR profiles derived from extracts of the cortex and cerebellum from mnd and nclf mice were distinguished according to disease/wildtype status. In particular, a perturbation in glutamine and glutamate metabolism, and a decrease in {gamma}-amino butyric acid (GABA) in the cerebellum and cortices of mnd (adolescent mice) and nclf mice relative to wildtype at all ages were detected. Our results were compared to the Cln3 mouse model of NCL. The metabolism of mnd mice resembled older (6 month) Cln3 mice, where the disease is relatively advanced, while the metabolism of nclf mice was more akin to younger (1-2 months) Cln3 mice, where the disease is in its early stages of progression. Overall, our results allowed the identification of metabolic traits common to all NCL subtypes for the three animal models.

A metabolomic comparison of mouse models of the Neuronal Ceroid Lipofuscinoses

International Nuclear Information System (INIS)

Salek, Reza M.; Pears, Michael R.; Cooper, Jonathan D.; Mitchison, Hannah M.; Pearce, David A.; Mortishire-Smith, Russell J.; Griffin, Julian L.

2011-01-01

The Neuronal Ceroid Lipofuscinoses (NCL) are a group of fatal inherited neurodegenerative diseases in humans distinguished by a common clinical pathology, characterized by the accumulation of storage body material in cells and gross brain atrophy. In this study, metabolic changes in three NCL mouse models were examined looking for pathways correlated with neurodegeneration. Two mouse models; motor neuron degeneration (mnd) mouse and a variant model of late infantile NCL, termed the neuronal ceroid lipofuscinosis (nclf) mouse were investigated experimentally. Both models exhibit a characteristic accumulation of autofluorescent lipopigment in neuronal and non neuronal cells. The NMR profiles derived from extracts of the cortex and cerebellum from mnd and nclf mice were distinguished according to disease/wildtype status. In particular, a perturbation in glutamine and glutamate metabolism, and a decrease in γ-amino butyric acid (GABA) in the cerebellum and cortices of mnd (adolescent mice) and nclf mice relative to wildtype at all ages were detected. Our results were compared to the Cln3 mouse model of NCL. The metabolism of mnd mice resembled older (6 month) Cln3 mice, where the disease is relatively advanced, while the metabolism of nclf mice was more akin to younger (1-2 months) Cln3 mice, where the disease is in its early stages of progression. Overall, our results allowed the identification of metabolic traits common to all NCL subtypes for the three animal models.

[Hodgkin and non-Hodgkin lymphoma of adolescents and young adults].

Science.gov (United States)

Garciaz, Sylvain; Coso, Diane; Brice, Pauline; Bouabdallah, Réda

2016-12-01

Lymphoma is one of the most frequent cancers in adolescent and young adults. Hodgkin Lymphoma is curable in more than 90% of cases. Recent pediatric and adults protocols aimed to decrease long term toxicities (mostly gonadic and cardiovascular) and secondary malignancies, reducing the use of alkylating agents and limiting radiation fields. Risk-adapted strategies, using positron emission tomography staging, are about to become a standard, both in adult and pediatric protocols. These approaches allow obtaining excellent results in adolescents with Hodgkin lymphoma. On the other hand, treatment of adolescents with diffuse large B-cell lymphoma raises some questions. Even through children have good outcomes when treated with risk-adapted strategies, adolescents who are between 15 and 18 years old seem to experience poorer survivals, whereas patients older than 18 years old have globally the same outcome than older adults. This category of patient needs a particular care, based on a tight coordination between adults and pediatric oncologists. Primary mediastinal lymphomas, a subtype of BLDCL frequent in young adult population, exhibits poorer outcomes in children or young adolescent population than in older ones. Taking together, B-cell lymphoma benefited from recent advances in immunotherapy (in particular with the extended utilization of rituximab) and metabolic response-adapted strategies. In conclusion, adolescent and young adult's lymphomas are very curable diseases but require a personalized management in onco-hematological units. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Association of Hodgkin's lymphoma with Epstein Barr virus infection

Directory of Open Access Journals (Sweden)

Elmir Čičkušić

2007-02-01

Full Text Available The role of Epstein Barr virus (EBV in the onset of Hodgkin's lymphoma has been a subject of ongoing research. However, confirmation of EBV oncogenic involvement was not possible due to the small number of neoplastic cells characteristic for this type of tumor. Presence of EBV infection in neoplastic and non-neoplastic cells was analyzed in 81 cases of Hodgkin's lymphoma. In neoplastic cells, using an immunohistochemical method, latent membrane protein 1 (LMP1 was found in 33,3% of cases, while in situ hybridization results demonstrated the presence of EBER RNA in 48,1% of the cases. EBER RNA was found in non-neoplastic lymphocytes in 38,3% of cases. EBV is most frequently associated with Hodgkin's lymphoma in the first and seventh decade of life, specifically the nodular sclerosis subtype. No apparent difference was observed in the association of Hodgkin's lymphoma with EBV between genders, or in relation to clinical stage of the disease and average age of the patient. However, association with childhood age is significantly greater in comparison to adults. EBV associated disease shows a significantly greater prevalence in T lymphocytes. Slightly more abundant are cytotoxic T lymphocytes, which are also more frequently in contact with Reed-Sternberg cells, although there is no difference in number and positioning of histiocytes. Variations between the data on the association of EBV with Hodgkin's lymphoma among studies from different parts of the world suggest that factors of age, gender, ethnic background and social status might present biological modifiers of EBV influence on the pathogenesis of this neoplasm. The differences in non-neoplastic infiltrate EBV+ and EBV- lymphoma indicate the effect of the virus on the immune interaction of tumor and host in this disease.

A flexible, interactive software tool for fitting the parameters of neuronal models.

Science.gov (United States)

Friedrich, Péter; Vella, Michael; Gulyás, Attila I; Freund, Tamás F; Káli, Szabolcs

2014-01-01

The construction of biologically relevant neuronal models as well as model-based analysis of experimental data often requires the simultaneous fitting of multiple model parameters, so that the behavior of the model in a certain paradigm matches (as closely as possible) the corresponding output of a real neuron according to some predefined criterion. Although the task of model optimization is often computationally hard, and the quality of the results depends heavily on technical issues such as the appropriate choice (and implementation) of cost functions and optimization algorithms, no existing program provides access to the best available methods while also guiding the user through the process effectively. Our software, called Optimizer, implements a modular and extensible framework for the optimization of neuronal models, and also features a graphical interface which makes it easy for even non-expert users to handle many commonly occurring scenarios. Meanwhile, educated users can extend the capabilities of the program and customize it according to their needs with relatively little effort. Optimizer has been developed in Python, takes advantage of open-source Python modules for nonlinear optimization, and interfaces directly with the NEURON simulator to run the models. Other simulators are supported through an external interface. We have tested the program on several different types of problems of varying complexity, using different model classes. As targets, we used simulated traces from the same or a more complex model class, as well as experimental data. We successfully used Optimizer to determine passive parameters and conductance densities in compartmental models, and to fit simple (adaptive exponential integrate-and-fire) neuronal models to complex biological data. Our detailed comparisons show that Optimizer can handle a wider range of problems, and delivers equally good or better performance than any other existing neuronal model fitting tool.

A flexible, interactive software tool for fitting the parameters of neuronal models

Directory of Open Access Journals (Sweden)

Péter eFriedrich

2014-07-01

Full Text Available The construction of biologically relevant neuronal models as well as model-based analysis of experimental data often requires the simultaneous fitting of multiple model parameters, so that the behavior of the model in a certain paradigm matches (as closely as possible the corresponding output of a real neuron according to some predefined criterion. Although the task of model optimization is often computationally hard, and the quality of the results depends heavily on technical issues such as the appropriate choice (and implementation of cost functions and optimization algorithms, no existing program provides access to the best available methods while also guiding the user through the process effectively. Our software, called Optimizer, implements a modular and extensible framework for the optimization of neuronal models, and also features a graphical interface which makes it easy for even non-expert users to handle many commonly occurring scenarios. Meanwhile, educated users can extend the capabilities of the program and customize it according to their needs with relatively little effort. Optimizer has been developed in Python, takes advantage of open-source Python modules for nonlinear optimization, and interfaces directly with the NEURON simulator to run the models. Other simulators are supported through an external interface. We have tested the program on several different types of problem of varying complexity, using different model classes. As targets, we used simulated traces from the same or a more complex model class, as well as experimental data. We successfully used Optimizer to determine passive parameters and conductance densities in compartmental models, and to fit simple (adaptive exponential integrate-and-fire neuronal models to complex biological data. Our detailed comparisons show that Optimizer can handle a wider range of problems, and delivers equally good or better performance than any other existing neuronal model fitting

Immuno phenotype of blood lymphocytes in radiation-associated Hodgkin's disease

International Nuclear Information System (INIS)

Butenko, A.K.

2000-01-01

Immuno phenotype of peripheral blood lymphocytes has been studied in Hodgkin's disease including patients exposed to radionuclides of the characteristic Chernobyl pattern. The group of patients under study has been characterized by decreasing T- and NK-cell immunity, such a decrease being more pronounced in radiation-associated Hodgkin's lymphoma. The data obtained as well as the evidence of Epstein-Barr virus activation could explain the aggressiveness of the disease in such patients and the difficulties in their treatment

Novel treatment concepts in Hodgkin lymphoma

NARCIS (Netherlands)

Glimelius, I.; Diepstra, A.

Treatment of classical Hodgkin's lymphoma (HL) has been a success story, with cure of localized disease with radiotherapy in the 1930s, cure of advanced stages with combination chemotherapy with/without radiotherapy in the mid-1960s and continuous improvements since then. Nonetheless, at present

The fractional-order modeling and synchronization of electrically coupled neuron systems

KAUST Repository

Moaddy, K.

2012-11-01

In this paper, we generalize the integer-order cable model of the neuron system into the fractional-order domain, where the long memory dependence of the fractional derivative can be a better fit for the neuron response. Furthermore, the chaotic synchronization with a gap junction of two or multi-coupled-neurons of fractional-order are discussed. The circuit model, fractional-order state equations and the numerical technique are introduced in this paper for individual and multiple coupled neuron systems with different fractional-orders. Various examples are introduced with different fractional orders using the non-standard finite difference scheme together with the Grünwald-Letnikov discretization process which is easily implemented and reliably accurate. © 2011 Elsevier Ltd. All rights reserved.

The fractional-order modeling and synchronization of electrically coupled neuron systems

KAUST Repository

Moaddy, K.; Radwan, Ahmed G.; Salama, Khaled N.; Momani, Shaher M.; Hashim, Ishak

2012-01-01

In this paper, we generalize the integer-order cable model of the neuron system into the fractional-order domain, where the long memory dependence of the fractional derivative can be a better fit for the neuron response. Furthermore, the chaotic synchronization with a gap junction of two or multi-coupled-neurons of fractional-order are discussed. The circuit model, fractional-order state equations and the numerical technique are introduced in this paper for individual and multiple coupled neuron systems with different fractional-orders. Various examples are introduced with different fractional orders using the non-standard finite difference scheme together with the Grünwald-Letnikov discretization process which is easily implemented and reliably accurate. © 2011 Elsevier Ltd. All rights reserved.

Computerised tomography in the staging of Hodgkin's disease and non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Vinnicombe, Sarah J.; Reznek, Rodney H.

2003-01-01

The last 25 years have seen major changes in the imaging investigation and subsequent management of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL); accurate staging is vital for prognostication and treatment in both, and particularly in HD. The choice of imaging modality for staging depends on its accuracy, impact on clinical decision-making, and availability. Modern CT scanners fulfil most of the desired criteria. The advent of CT scanning, along with the development of ever more effective chemotherapeutic regimens, has resulted in the virtual demise of bipedal lymphangiography (LAG) as a staging tool in patients with lymphoma. It has rendered superfluous a battery of other tests that were in routine use. This contribution reviews the evidence for the use of CT in preference to LAG. CT accurately depicts nodal enlargement above and below the diaphragm, has variable sensitivity for intra-abdominal visceral involvement and is generally outstanding in depicting the extent of disease, especially extranodal extension. Despite the advances in CT technology, there are still areas where CT performs less well (e.g. disease in normal-sized lymph nodes, splenic and bone marrow infiltration). The influence of technical factors, such as the use of intravenous contrast medium, is discussed. In some instances, CT is not the imaging modality of choice and the place of newer techniques such as MRI and endoscopic ultrasound will be reviewed. (orig.)

Nab-paclitaxel/Rituximab-coated Nanoparticle AR160 in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Science.gov (United States)

2018-04-17

Aggressive Non-Hodgkin Lymphoma; CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

Assessment of multiple frequency ELF electric and magnetic field exposure

International Nuclear Information System (INIS)

Leitgeb, N

2008-01-01

Electromagnetic fields both in daily life and at workplaces exhibit increasingly complex frequency spectra. Present spectral assessment rules proved to be too conservative for health risk assessment. This is because they are based on the assumption that cells would react like linear systems in terms of responding to a sum of frequencies by a sum of independent responses to each individual frequency. Based on numerical investigations with the Hodgkin-Huxley and the Frankenhaeuser-Huxley nerve cell models, it could be shown that accounting for the nonlinear behaviour of cellular excitation processes avoids considerable overestimation of simultaneous exposures to multiple frequency ELF electric and magnetic fields. Besides this, it could be shown that the role of phase relationships is less important than that assumed so far. The present assessment rules lead to non-compliances of marketed electric appliances. For general application, a nonlinear biology-based assessment (NBBA) rule has been proposed, validated and proven advantageous compared with ICNIRP's rule. While staying conservative it avoids unnecessary overestimation and demonstrates compliance even in cases of suspected non-conformities. It is up to responsible bodies to decide upon the adoption of this proposal and the potential need for implementing additional or reducing the already incorporated safety factors

Bone marrow in pediatric patients with Hodgkin's disease.

Science.gov (United States)

Khan, Fauzia Shafi; Hasan, Rabiya Fayyaz

2012-01-01

Hodgkin's disease is a malignant process of lymphoreticular system that constitutes 6% of childhood cancers Accurate staging of lymphoma is the basis for rational therapeutic planning and assessment of the presence or absence of marrow involvement is a basic part of the staging evaluation. The objective of this study was to determine the incidence of marrow infiltration in paediatric patients with Hodgkin's disease and to ascertain its morphological spectrum in the marrow. The study included 85 paediatric patients with diagnosed Hodgkin's disease seen at The Children's Hospital/Institute of Child Health, Lahore, from January 2010 to December 2011, referred to haematology department for bone marrow biopsies. Ages ranged between two years to fourteen years with an average age of seven years, the male female ratio being 13:1. Mixed cellularity was the commonest histological type present in 66 (78%) cases. The presenting feature common in all cases was superficial lymphadenopathy followed by hepatomegaly in 17 (20%) cases and splenomegaly in 16 (19%). All the marrow aspirates were negative for infiltration. Trephine biopsies revealed marrow infiltration in 9 (10.5%). Five (56%) cases had bilateral while 4 (44%) had unilateral involvement. Pattern of infiltration was diffuse in 8 (89%) and focal in one (11%) trephines. Increased marrow fibrosis was present in eight (89%) cases. Diagnostic Reed Sternberg cells were identified in only one case and the mononuclear variants were present in six cases and atypical cells were present in two cases in these immunohistochemistry for CD15 and CD30 was performed which was positive. Granulomas in one and lymphoid aggregates were present in two trephine biopsies otherwise negative for Hodgkin's infiltration. Bone marrow infiltration was present in 10.5% cases, immunohistochemistry was used to confirm infiltration in two cases, the pattern of infiltration being diffuse in majority (89%).

Second cancers following non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Travis, L.B.; Curtis, R.E.; Boice, J.D. Jr.; Hankey, B.F.; Fraumeni, J.F. Jr.

1991-01-01

The risk of second malignancies following non-Hodgkin's lymphoma (NHL) was estimated in 29,153 patients diagnosed with NHL between 1973 and 1987 in one of nine areas participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Compared with the general population, NHL patients were at a significantly increased risk of developing second cancers (observed/expected [O/E] = 1.18; O = 1231). The O/E ratio increased significantly with time to reach 1.77 in 10-year survivors. Significant excesses were noted for acute nonlymphocytic leukemia (O/E = 2.88), cancers of the bladder (O/E = 1.30), kidney (O/E = 1.47), and lung (O/E = 1.57), malignant melanoma (O/E = 2.44), and Hodgkin's disease (O/E = 4.16). Chemotherapy appeared related to subsequent acute nonlymphocytic leukemia (ANLL) and bladder cancer. Radiation therapy was associated with ANLL and possibly cancers of the lung, bladder, and bone. Malignant melanoma was not clearly related to initial NHL treatment

Non-Coding RNAs in Hodgkin Lymphoma

Directory of Open Access Journals (Sweden)

Anna Cordeiro

2017-05-01

Full Text Available MicroRNAs (miRNAs, small non-coding RNAs that regulate gene expression by binding to the 3’-UTR of their target genes, can act as oncogenes or tumor suppressors. Recently, other types of non-coding RNAs—piwiRNAs and long non-coding RNAs—have also been identified. Hodgkin lymphoma (HL is a B cell origin disease characterized by the presence of only 1% of tumor cells, known as Hodgkin and Reed-Stenberg (HRS cells, which interact with the microenvironment to evade apoptosis. Several studies have reported specific miRNA signatures that can differentiate HL lymph nodes from reactive lymph nodes, identify histologic groups within classical HL, and distinguish HRS cells from germinal center B cells. Moreover, some signatures are associated with survival or response to chemotherapy. Most of the miRNAs in the signatures regulate genes related to apoptosis, cell cycle arrest, or signaling pathways. Here we review findings on miRNAs in HL, as well as on other non-coding RNAs.

Effects of inhibitory neurons on the quorum percolation model and dynamical extension with the Brette-Gerstner model

Science.gov (United States)

Fardet, Tanguy; Bottani, Samuel; Métens, Stéphane; Monceau, Pascal

2018-06-01

The Quorum Percolation model (QP) has been designed in the context of neurobiology to describe the initiation of activity bursts occurring in neuronal cultures from the point of view of statistical physics rather than from a dynamical synchronization approach. This paper aims at investigating an extension of the original QP model by taking into account the presence of inhibitory neurons in the cultures (IQP model). The first part of this paper is focused on an equivalence between the presence of inhibitory neurons and a reduction of the network connectivity. By relying on a simple topological argument, we show that the mean activation behavior of networks containing a fraction η of inhibitory neurons can be mapped onto purely excitatory networks with an appropriately modified wiring, provided that η remains in the range usually observed in neuronal cultures, namely η ⪅ 20%. As a striking result, we show that such a mapping enables to predict the evolution of the critical point of the IQP model with the fraction of inhibitory neurons. In a second part, we bridge the gap between the description of bursts in the framework of percolation and the temporal description of neural networks activity by showing how dynamical simulations of bursts with an adaptive exponential integrate-and-fire model lead to a mean description of bursts activation which is captured by Quorum Percolation.

ALTERNATIVE EQUATIONS FOR DYNAMIC BEHAVIOR OF IONIC CHANNEL ACTIVATION AND INACTIVATION GATES

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Mahmut ÖZER

2003-03-01

Full Text Available In this paper, alternative equations for dynamics of ionic channel activation and inactivation gates are proposed based on the path probability method. Dynamic behavior of a voltage-gated ionic channel is modeled by the conventional Hodgkin-Huxley (H-H mathematical formalism. In that model, conductance of the channel is defined in terms of activation and inactivation gates. Dynamics of the activation and inactivation gates is modeled by first-order differential equations dependent on the gate variable and the membrane potential. In the new approach proposed in this study, dynamic behavior of activation and inactivation gates is modeled by a firstorder differential equation dependent on internal energy and membrane potential by using the path probability method which is widely used in statistical physics. The new model doesn't require the time constant and steadystate values which are used explicitly in the H-H model. The numerical results show validity of the proposed method.

A Challenging Case of Primary Breast Hodgkin's Lymphoma.

Science.gov (United States)

Zarnescu, Narcis Octavian; Iliesiu, Andreea; Procop, Alexandru; Tampa, Mircea; Matei, Clara; Sajin, Maria; Costache, Mariana; Dumitru, Adrian; Lazaroiu, Anca Mihaela

2015-03-01

Primary breast lymphoma (PBL) is a rare entity accounting for less than 1% of all breast malignancies. Diagnostic criteria for primary Hodgkin's lymphoma of the breast are: the presence of sufficient tissue for diagnosis, close interaction between mammary tissue and lymphomatous infiltrate and no evidence or prior diagnosis of widespread lymphoma. Our case illustrates an unusual presentation of Hodgkin's lymphoma of the breast: clinically as inflammatory breast cancer and core biopsy as granulomatous mastitis, the final diagnosis requiring surgical biopsy. Current information regarding this entity is scant, mainly build upon its rarity. In this paper we assess the clinical presentation, the step-by-step diagnosis, the treatment and the importance of immunohistochemistry in this uncommon condition.

MiR-17/106b seed family regulates p21 in Hodgkin's lymphoma

NARCIS (Netherlands)

Gibcus, Johan H.; Kroesen, Bart-Jan; Koster, Roelof; Halsema, Nancy; de Jong, Debora; de Jong, Steven; Poppema, Sibrand; Kluiver, Joost; Diepstra, Arjan; van den Berg, Anke

2011-01-01

Hodgkin's lymphoma (HL) is a B cell-derived lymphoma characterized by a minority of malignant Hodgkin Reed-Sternberg (HRS) cells that have lost their normal B cell phenotype. Alterations in the cell cycle and apoptosis pathways might contribute to their resistance to apoptosis and sustained cell

Is the Langevin phase equation an efficient model for oscillating neurons?

Science.gov (United States)

Ota, Keisuke; Tsunoda, Takamasa; Omori, Toshiaki; Watanabe, Shigeo; Miyakawa, Hiroyoshi; Okada, Masato; Aonishi, Toru

2009-12-01

The Langevin phase model is an important canonical model for capturing coherent oscillations of neural populations. However, little attention has been given to verifying its applicability. In this paper, we demonstrate that the Langevin phase equation is an efficient model for neural oscillators by using the machine learning method in two steps: (a) Learning of the Langevin phase model. We estimated the parameters of the Langevin phase equation, i.e., a phase response curve and the intensity of white noise from physiological data measured in the hippocampal CA1 pyramidal neurons. (b) Test of the estimated model. We verified whether a Fokker-Planck equation derived from the Langevin phase equation with the estimated parameters could capture the stochastic oscillatory behavior of the same neurons disturbed by periodic perturbations. The estimated model could predict the neural behavior, so we can say that the Langevin phase equation is an efficient model for oscillating neurons.

Is the Langevin phase equation an efficient model for oscillating neurons?

International Nuclear Information System (INIS)

Ota, Keisuke; Tsunoda, Takamasa; Aonishi, Toru; Omori, Toshiaki; Okada, Masato; Watanabe, Shigeo; Miyakawa, Hiroyoshi

2009-01-01

The Langevin phase model is an important canonical model for capturing coherent oscillations of neural populations. However, little attention has been given to verifying its applicability. In this paper, we demonstrate that the Langevin phase equation is an efficient model for neural oscillators by using the machine learning method in two steps: (a) Learning of the Langevin phase model. We estimated the parameters of the Langevin phase equation, i.e., a phase response curve and the intensity of white noise from physiological data measured in the hippocampal CA1 pyramidal neurons. (b) Test of the estimated model. We verified whether a Fokker-Planck equation derived from the Langevin phase equation with the estimated parameters could capture the stochastic oscillatory behavior of the same neurons disturbed by periodic perturbations. The estimated model could predict the neural behavior, so we can say that the Langevin phase equation is an efficient model for oscillating neurons.

[No Hodgkin Linfoma diagnosis with intra-atrial infiltration].

Science.gov (United States)

Alcocer Gamba, Marco Antonio; León González, Salvador; Castro Montes, Eliodoro; Loarca Piña, Luis Martín; Lugo Gavidia, Leslie Marisol; García Hernández, Enrique; González Galindo, Ulises; Paredes Serrano, Miguel Isaías

2012-09-01

Cardiac tumors are rare entities in clinical practice, with an incidence of 0.05%. Approximately 75% are benign and 25% malignant. Among these, Lymphomas are uncommon, representing about 0.25%. The non-Hodgkin lymphomas can occur in extranodal tissues in 20% of the cases and 80% of these non-Hodgkin lymphomas are composed of diffuse B cells. The extranodal presentation is most frequent in young adults, with a high degree of malignancy and rapid growth. It can present with primary infiltration of various organs; cardiac involvement occurs in 20 to 28% of cases, usually located in the right chambers and with nonspecific symptoms, depending on the location and extent of the tumor. The diagnostic test in these cases is undoubtedly the biopsy of the lymph node or the affected tissue. We present the case of non-Hodgkin disease of diffuse large cells, with right intra-atrial involvement in a 23-year-old-female patient, who presented with progressive dyspnea. A transesophageal echocardiography was performed and an intra-atrial tumor mass was detected. A biopsy was performed, by femoral venous catheterization, allowing the establishment of the histopathological diagnosis and treatment. At a one year follow up, the patient shows complete remission.

Chronic Prurigo: An Unusual Presentation of Hodgkin Lymphoma

Directory of Open Access Journals (Sweden)

Shireen Dumont

2018-05-01

Full Text Available Background: Prurigo nodularis is a condition of unknown origin defined by papulonodular eruption and intense pruritus. Hodgkin lymphoma often presents nonspecific initial symptoms. An association between systemic malignancy and cutaneous manifestations has long been documented. We report a case of prurigo nodularis as a first presentation of Hodgkin lymphoma. Case: A 35-year-old woman presented with a 2-year history of pruritus. Previously diagnosed with bedbugs, the pruritus persisted even after insect eradication, with the appearance of papulonodular lesions consistent with chronic prurigo. The pruritus and the pain were refractory to all treatments. She had no past medical history or clinical, radiological, or laboratory findings. A lymphadenopathy was revealed 2 years after onset of the symptoms. Lymph node biopsy showed a nodular sclerosis Hodgkin lymphoma. The patient was initiated on chemotherapy and the skin lesions decreased. Conclusion: This case report of chronic prurigo as the first manifestation of a systemic malignancy reminds us of the importance of a systematic diagnostic approach to this kind of patients initially and throughout time, especially if the symptoms do not respond to treatment. Our case may question the role of imaging examinations in the management and follow-up of a persistent prurigo nodularis.

Model-Based Design of Stimulus Trains for Selective Microstimulation of Targeted Neuronal Populations

National Research Council Canada - National Science Library

McIntyre, Cameron

2001-01-01

... that accurately reproduced the dynamic firing properties of mammalian neurons, The neuron models were coupled to a three-dimensional finite element model of the spinal cord that solved for the potentials...

Fertility preservation after chemotherapy for Hodgkin lymphoma

NARCIS (Netherlands)

van der Kaaij, Marleen A. E.; van Echten-Arends, Jannie; Simons, Arnold H. M.; Kluin-Nelemans, Hanneke C.

2010-01-01

Treatment for Hodgkin lymphoma can negatively affect fertility. This review summarizes data on fertility after chemotherapy in adult patients. Alkylating chemotherapy, especially if containing procarbazine and/or cyclophosphamide, is most harmful to gonadal functioning. Alkylating regimens cause

Hodgkin's disease in childhood

International Nuclear Information System (INIS)

Misol Perez, A.; Dabezies Antia, A.

1994-01-01

Actually, the majority of the children that suffer from Hodgkin illness can have long period of survive. The cures are related with the continuous achievements in biology molecular; techniques of different state, radiotherapy, chemotherapy, imagenology, proceedings and to the multidisciplinary handling. This article summarizes those aspects related with the illness and its treatment, taking in count the biggest impact of the secondary effects on children and adolescents that are in growth and active development. (Au) [es

Population density models of integrate-and-fire neurons with jumps: well-posedness.

Science.gov (United States)

Dumont, Grégory; Henry, Jacques

2013-09-01

In this paper we study the well-posedness of different models of population of leaky integrate-and-fire neurons with a population density approach. The synaptic interaction between neurons is modeled by a potential jump at the reception of a spike. We study populations that are self excitatory or self inhibitory. We distinguish the cases where this interaction is instantaneous from the one where there is a repartition of conduction delays. In the case of a bounded density of delays both excitatory and inhibitory population models are shown to be well-posed. But without conduction delay the solution of the model of self excitatory neurons may blow up. We analyze the different behaviours of the model with jumps compared to its diffusion approximation.

Mirror Neurons Modeled Through Spike-Timing-Dependent Plasticity are Affected by Channelopathies Associated with Autism Spectrum Disorder.

Science.gov (United States)

Antunes, Gabriela; Faria da Silva, Samuel F; Simoes de Souza, Fabio M

2018-06-01

Mirror neurons fire action potentials both when the agent performs a certain behavior and watches someone performing a similar action. Here, we present an original mirror neuron model based on the spike-timing-dependent plasticity (STDP) between two morpho-electrical models of neocortical pyramidal neurons. Both neurons fired spontaneously with basal firing rate that follows a Poisson distribution, and the STDP between them was modeled by the triplet algorithm. Our simulation results demonstrated that STDP is sufficient for the rise of mirror neuron function between the pairs of neocortical neurons. This is a proof of concept that pairs of neocortical neurons associating sensory inputs to motor outputs could operate like mirror neurons. In addition, we used the mirror neuron model to investigate whether channelopathies associated with autism spectrum disorder could impair the modeled mirror function. Our simulation results showed that impaired hyperpolarization-activated cationic currents (Ih) affected the mirror function between the pairs of neocortical neurons coupled by STDP.

A Dynamic Bayesian Model for Characterizing Cross-Neuronal Interactions During Decision-Making.

Science.gov (United States)

Zhou, Bo; Moorman, David E; Behseta, Sam; Ombao, Hernando; Shahbaba, Babak

2016-01-01

The goal of this paper is to develop a novel statistical model for studying cross-neuronal spike train interactions during decision making. For an individual to successfully complete the task of decision-making, a number of temporally-organized events must occur: stimuli must be detected, potential outcomes must be evaluated, behaviors must be executed or inhibited, and outcomes (such as reward or no-reward) must be experienced. Due to the complexity of this process, it is likely the case that decision-making is encoded by the temporally-precise interactions between large populations of neurons. Most existing statistical models, however, are inadequate for analyzing such a phenomenon because they provide only an aggregated measure of interactions over time. To address this considerable limitation, we propose a dynamic Bayesian model which captures the time-varying nature of neuronal activity (such as the time-varying strength of the interactions between neurons). The proposed method yielded results that reveal new insight into the dynamic nature of population coding in the prefrontal cortex during decision making. In our analysis, we note that while some neurons in the prefrontal cortex do not synchronize their firing activity until the presence of a reward, a different set of neurons synchronize their activity shortly after stimulus onset. These differentially synchronizing sub-populations of neurons suggests a continuum of population representation of the reward-seeking task. Secondly, our analyses also suggest that the degree of synchronization differs between the rewarded and non-rewarded conditions. Moreover, the proposed model is scalable to handle data on many simultaneously-recorded neurons and is applicable to analyzing other types of multivariate time series data with latent structure. Supplementary materials (including computer codes) for our paper are available online.

Automatic parameter estimation of multicompartmental neuron models via minimization of trace error with control adjustment.

Science.gov (United States)

Brookings, Ted; Goeritz, Marie L; Marder, Eve

2014-11-01

We describe a new technique to fit conductance-based neuron models to intracellular voltage traces from isolated biological neurons. The biological neurons are recorded in current-clamp with pink (1/f) noise injected to perturb the activity of the neuron. The new algorithm finds a set of parameters that allows a multicompartmental model neuron to match the recorded voltage trace. Attempting to match a recorded voltage trace directly has a well-known problem: mismatch in the timing of action potentials between biological and model neuron is inevitable and results in poor phenomenological match between the model and data. Our approach avoids this by applying a weak control adjustment to the model to promote alignment during the fitting procedure. This approach is closely related to the control theoretic concept of a Luenberger observer. We tested this approach on synthetic data and on data recorded from an anterior gastric receptor neuron from the stomatogastric ganglion of the crab Cancer borealis. To test the flexibility of this approach, the synthetic data were constructed with conductance models that were different from the ones used in the fitting model. For both synthetic and biological data, the resultant models had good spike-timing accuracy. Copyright © 2014 the American Physiological Society.

SEPTIN2 and STATHMIN Regulate CD99-Mediated Cellular Differentiation in Hodgkin's Lymphoma.

Directory of Open Access Journals (Sweden)

Wenjing Jian

Full Text Available Hodgkin's lymphoma (HL is a lymphoid neoplasm characterized by Hodgkin's and Reed-Sternberg (H/RS cells, which is regulated by CD99. We previously reported that CD99 downregulation led to the transformation of murine B lymphoma cells (A20 into cells with an H/RS phenotype, while CD99 upregulation induced differentiation of classical Hodgkin's lymphoma (cHL cells (L428 into terminal B-cells. However, the molecular mechanism remains unclear. In this study, using fluorescence two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS, we have analyzed the alteration of protein expression following CD99 upregulation in L428 cells as well as downregulation of mouse CD99 antigen-like 2 (mCD99L2 in A20 cells. Bioinformatics analysis showed that SEPTIN2 and STATHMIN, which are cytoskeleton proteins, were significantly differentially expressed, and chosen for further validation and functional analysis. Differential expression of SEPTIN2 was found in both models and was inversely correlated with CD99 expression. STATHMIN was identified in the A20 cell line model and its expression was positively correlated with that of CD99. Importantly, silencing of SEPTIN2 with siRNA substantially altered the cellular cytoskeleton in L428 cells. The downregulation of STATHMIN by siRNA promoted the differentiation of H/RS cells toward terminal B-cells. These results suggest that SEPTIN2-mediated cytoskeletal rearrangement and STATHMIN-mediated differentiation may contribute to changes in cell morphology and differentiation of H/RS cells with CD99 upregulation in HL.

Linfoma não-Hodgkin apresentando-se como massa hepática única Non-Hodgkin's lymphoma presenting as a single liver mass

Directory of Open Access Journals (Sweden)

Mila Correia Góis Peixoto

2009-02-01

Full Text Available OBJETIVO: Descrever as principais características de imagem do linfoma não-Hodgkin apresentando-se como massa hepática única. MATERIAIS E MÉTODOS: Realizamos estudo retrospectivo mediante análise de casos de pacientes com massa hepática única aos exames de ultrassonografia, tomografia computadorizada e ressonância magnética, com diagnóstico histológico de linfoma não-Hodgkin. Esses exames foram analisados por dois examinadores em consenso. RESULTADOS: Identificamos três pacientes, todos do sexo masculino, na quinta década de vida, com quadro clínico inespecífico e que apresentavam massa hepática única e com diagnóstico de linfoma não-Hodgkin. Na ultrassonografia a lesão hepática apresentava-se como massa com aspecto "em alvo" nos três casos estudados. Na tomografia computadorizada observou-se massa hipodensa e heterogênea, com realce anelar em todos os casos. Na ressonância magnética as lesões apresentavam-se heterogêneas, hipointensas em T1 e hiperintensas em T2, e também com realce anelar após a injeção do contraste. Nenhum paciente apresentava linfonodomegalia ou comprometimento de outras vísceras sólidas no momento do diagnóstico. CONCLUSÃO: Na presença de massa hepática solitária e com aspecto "em alvo" deve-se considerar, entre as hipóteses, o diagnóstico de linfoma.OBJECTIVE: To describe the main imaging findings of non-Hodgkin's lymphoma presenting as a single liver mass. MATERIALS AND METHODS: A retrospective study was developed with analysis of cases where a single liver mass was observed at ultrasonography, computed tomography and magnetic resonance imaging, and histologically diagnosed as non-Hodgkin's lymphoma. The studies were reviewed by two observers in consensus. RESULTS: Three male patients in the fifth decade of life, with non-specific clinical manifestations and single liver mass diagnosed as non-Hodgkin's lymphoma were identified. A hepatic lesion with target sign was observed at

Studies of stimulus parameters for seizure disruption using neural network simulations.

Science.gov (United States)

Anderson, William S; Kudela, Pawel; Cho, Jounhong; Bergey, Gregory K; Franaszczuk, Piotr J

2007-08-01

A large scale neural network simulation with realistic cortical architecture has been undertaken to investigate the effects of external electrical stimulation on the propagation and evolution of ongoing seizure activity. This is an effort to explore the parameter space of stimulation variables to uncover promising avenues of research for this therapeutic modality. The model consists of an approximately 800 mum x 800 mum region of simulated cortex, and includes seven neuron classes organized by cortical layer, inhibitory or excitatory properties, and electrophysiological characteristics. The cell dynamics are governed by a modified version of the Hodgkin-Huxley equations in single compartment format. Axonal connections are patterned after histological data and published models of local cortical wiring. Stimulation induced action potentials take place at the axon initial segments, according to threshold requirements on the applied electric field distribution. Stimulation induced action potentials in horizontal axonal branches are also separately simulated. The calculations are performed on a 16 node distributed 32-bit processor system. Clear differences in seizure evolution are presented for stimulated versus the undisturbed rhythmic activity. Data is provided for frequency dependent stimulation effects demonstrating a plateau effect of stimulation efficacy as the applied frequency is increased from 60 to 200 Hz. Timing of the stimulation with respect to the underlying rhythmic activity demonstrates a phase dependent sensitivity. Electrode height and position effects are also presented. Using a dipole stimulation electrode arrangement, clear orientation effects of the dipole with respect to the model connectivity is also demonstrated. A sensitivity analysis of these results as a function of the stimulation threshold is also provided.

Minimal time spiking in various ChR2-controlled neuron models.

Science.gov (United States)

Renault, Vincent; Thieullen, Michèle; Trélat, Emmanuel

2018-02-01

We use conductance based neuron models, and the mathematical modeling of optogenetics to define controlled neuron models and we address the minimal time control of these affine systems for the first spike from equilibrium. We apply tools of geometric optimal control theory to study singular extremals, and we implement a direct method to compute optimal controls. When the system is too large to theoretically investigate the existence of singular optimal controls, we observe numerically the optimal bang-bang controls.

Studying the Behaviour of Model of Mirror Neuron System in Case of Autism

Directory of Open Access Journals (Sweden)

Shikha Anirban

2012-04-01

Full Text Available Several experiment done by the researchers conducted that autism is caused by the dysfunctional mirror neuron system and the dysfunctions of mirror neuron system is proportional to the symptom severity of autism. In the present work those experiments were studied as well as studying a model of mirror neuron system called MNS2 developed by a research group. This research examined the behavior of the model in case of autism and compared the result with those studies conducting dysfunctions of mirror neuron system in autism. To perform this, a neural network employing the model was developed which recognized the three types of grasping (faster, normal and slower. The network was implemented with back propagation through time learning algorithm. The whole grasping process was divided into 30 time steps and different hand and object states at each time step was used as the input of the network. Normally the network successfully recognized all of the three types of grasps. The network required more times as the number of inactive neurons increased. And in case of maximum inactive neurons of the mirror neuron system the network became unable to recognize the types of grasp. As the time to recognize the types of grasp is proportional to the number of inactive neurons, the experiment result supports the hypothesis that dysfunctions of MNS is proportional to the symptom severity of autism. Keywords— Autism, MNS, mirror neuron, neural network, BPTT

Codimension-two bifurcation analysis on firing activities in Chay neuron model

International Nuclear Information System (INIS)

Duan Lixia; Lu Qishao

2006-01-01

Using codimension-two bifurcation analysis in the Chay neuron model, the relationship between the electric activities and the parameters of neurons is revealed. The whole parameter space is divided into two parts, that is, the firing and silence regions of neurons. It is found that the transition sets between firing and silence regions are composed of the Hopf bifurcation curves of equilibrium states and the saddle-node bifurcation curves of limit cycles, with some codimension-two bifurcation points. The transitions from silence to firing in neurons are due to the Hopf bifurcation or the fold limit cycle bifurcation, but the codimension-two singularities lead to complexity in dynamical behaviour of neuronal firing

Codimension-two bifurcation analysis on firing activities in Chay neuron model

Energy Technology Data Exchange (ETDEWEB)

Duan Lixia [School of Science, Beijing University of Aeronautics and Astronautics, Beijing 100083 (China); Lu Qishao [School of Science, Beijing University of Aeronautics and Astronautics, Beijing 100083 (China)]. E-mail: qishaolu@hotmail.com

2006-12-15

Using codimension-two bifurcation analysis in the Chay neuron model, the relationship between the electric activities and the parameters of neurons is revealed. The whole parameter space is divided into two parts, that is, the firing and silence regions of neurons. It is found that the transition sets between firing and silence regions are composed of the Hopf bifurcation curves of equilibrium states and the saddle-node bifurcation curves of limit cycles, with some codimension-two bifurcation points. The transitions from silence to firing in neurons are due to the Hopf bifurcation or the fold limit cycle bifurcation, but the codimension-two singularities lead to complexity in dynamical behaviour of neuronal firing.

Radiotherapy in non-Hodgkin lymphomas

International Nuclear Information System (INIS)

Faria, S.L.

1992-01-01

The treatment of non-Hodgkin lymphomas (NHL) is discussed. The use of radiotherapy, chemotherapy or both in a combined therapy is studied considering several aspects as age of the patients (adults vs children), size and extension of the lymphoma, stage of the disease. It is mentioned that more advanced cases and those with more aggressive histology need combined modality treatments or even just chemotherapy. (M.A.C.)

Orbital involvement by non-Hodgkin lymphoma NK T cells.

Science.gov (United States)

Hervás-Ontiveros, A; España-Gregori, E; Hernández-Martínez, P; Vera-Sempere, F J; Díaz-Llopis, M

2014-11-01

The case is presented of 37 year-old male with a history of nasal obstruction with right rhinorrhea, headache, hearing loss and right exophthalmos of 4 months progression. The MRI revealed that the ethmoidal and maxillary sinuses contained inflammatory tissue extending into the orbital region. The biopsy confirmed a non-Hodgkin lymphoma of natural killer (NK) T cells. Non-Hodgkin's T NK lymphoma is a rare tumor in the orbital area that requires an early detection and multi-disciplinary care to ensure appropriate monitoring and treatment. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Noise and Synchronization Analysis of the Cold-Receptor Neuronal Network Model

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Ying Du

2014-01-01

Full Text Available This paper analyzes the dynamics of the cold receptor neural network model. First, it examines noise effects on neuronal stimulus in the model. From ISI plots, it is shown that there are considerable differences between purely deterministic simulations and noisy ones. The ISI-distance is used to measure the noise effects on spike trains quantitatively. It is found that spike trains observed in neural models can be more strongly affected by noise for different temperatures in some aspects; meanwhile, spike train has greater variability with the noise intensity increasing. The synchronization of neuronal network with different connectivity patterns is also studied. It is shown that chaotic and high period patterns are more difficult to get complete synchronization than the situation in single spike and low period patterns. The neuronal network will exhibit various patterns of firing synchronization by varying some key parameters such as the coupling strength. Different types of firing synchronization are diagnosed by a correlation coefficient and the ISI-distance method. The simulations show that the synchronization status of neurons is related to the network connectivity patterns.

Generalized rate-code model for neuron ensembles with finite populations

International Nuclear Information System (INIS)

Hasegawa, Hideo

2007-01-01

We have proposed a generalized Langevin-type rate-code model subjected to multiplicative noise, in order to study stationary and dynamical properties of an ensemble containing a finite number N of neurons. Calculations using the Fokker-Planck equation have shown that, owing to the multiplicative noise, our rate model yields various kinds of stationary non-Gaussian distributions such as Γ, inverse-Gaussian-like, and log-normal-like distributions, which have been experimentally observed. The dynamical properties of the rate model have been studied with the use of the augmented moment method (AMM), which was previously proposed by the author from a macroscopic point of view for finite-unit stochastic systems. In the AMM, the original N-dimensional stochastic differential equations (DEs) are transformed into three-dimensional deterministic DEs for the means and fluctuations of local and global variables. The dynamical responses of the neuron ensemble to pulse and sinusoidal inputs calculated by the AMM are in good agreement with those obtained by direct simulation. The synchronization in the neuronal ensemble is discussed. The variabilities of the firing rate and of the interspike interval are shown to increase with increasing magnitude of multiplicative noise, which may be a conceivable origin of the observed large variability in cortical neurons

Spider Silk as Guiding Biomaterial for Human Model Neurons

Directory of Open Access Journals (Sweden)

Frank Roloff

2014-01-01

Full Text Available Over the last years, a number of therapeutic strategies have emerged to promote axonal regeneration. An attractive strategy is the implantation of biodegradable and nonimmunogenic artificial scaffolds into injured peripheral nerves. In previous studies, transplantation of decellularized veins filled with spider silk for bridging critical size nerve defects resulted in axonal regeneration and remyelination by invading endogenous Schwann cells. Detailed interaction of elongating neurons and the spider silk as guidance material is unknown. To visualize direct cellular interactions between spider silk and neurons in vitro, we developed an in vitro crossed silk fiber array. Here, we describe in detail for the first time that human (NT2 model neurons attach to silk scaffolds. Extending neurites can bridge gaps between single silk fibers and elongate afterwards on the neighboring fiber. Culturing human neurons on the silk arrays led to an increasing migration and adhesion of neuronal cell bodies to the spider silk fibers. Within three to four weeks, clustered somata and extending neurites formed ganglion-like cell structures. Microscopic imaging of human neurons on the crossed fiber arrays in vitro will allow for a more efficient development of methods to maximize cell adhesion and neurite growth on spider silk prior to transplantation studies.

Long-term pruritus as the initial and sole clinical manifestation of occult Hodgkin's disease.

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Omidvari, Shapour H; Khojasteh, Habib Noorani; Mohammadianpanah, Mohammad; Monabati, Ahmad; Mosalaei, Ahmad; Ahmadloo, Niloofar

2004-06-01

Pruritus or itch is a frequent symptom of patients with Hodgkin's disease. It often occurs during the clinical course of the disease and rarely may precede the diagnosis of underlying disease. In this report, we present a 16-year-old patient who had history of generalized pruritus without any skin rash for 4 years before the diagnosis of Hodgkin's disease. Within that period, she had received symptom-oriented medications, with no significant effect. After the first cycle of chemotherapy, her pruritus resolved completely. This case suggests that long-term generalized pruritus may be indicative of a significant underlying problem like Hodgkin's disease.

Collective firing regularity of a scale-free Hodgkin–Huxley neuronal network in response to a subthreshold signal

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Yilmaz, Ergin, E-mail: erginyilmaz@yahoo.com [Department of Biomedical Engineering, Engineering Faculty, Bülent Ecevit University, 67100 Zonguldak (Turkey); Ozer, Mahmut [Department of Electrical and Electronics Engineering, Engineering Faculty, Bülent Ecevit University, 67100 Zonguldak (Turkey)

2013-08-01

We consider a scale-free network of stochastic HH neurons driven by a subthreshold periodic stimulus and investigate how the collective spiking regularity or the collective temporal coherence changes with the stimulus frequency, the intrinsic noise (or the cell size), the network average degree and the coupling strength. We show that the best temporal coherence is obtained for a certain level of the intrinsic noise when the frequencies of the external stimulus and the subthreshold oscillations of the network elements match. We also find that the collective regularity exhibits a resonance-like behavior depending on both the coupling strength and the network average degree at the optimal values of the stimulus frequency and the cell size, indicating that the best temporal coherence also requires an optimal coupling strength and an optimal average degree of the connectivity.

Diffusion approximation of neuronal models revisited

Czech Academy of Sciences Publication Activity Database

Čupera, Jakub

2014-01-01

Roč. 11, č. 1 (2014), s. 11-25 ISSN 1547-1063. [International Workshop on Neural Coding (NC) /10./. Praha, 02.09.2012-07.09.2012] R&D Projects: GA ČR(CZ) GAP103/11/0282 Institutional support: RVO:67985823 Keywords : stochastic model * neuronal activity * first-passage time Subject RIV: JD - Computer Applications, Robotics Impact factor: 0.840, year: 2014

Utility of LRF/Pokemon and NOTCH1 protein expression in the distinction between nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma.

Science.gov (United States)

Bohn, Olga; Maeda, Takahiro; Filatov, Alexander; Lunardi, Andrea; Pandolfi, Pier Paolo; Teruya-Feldstein, Julie

2014-02-01

Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are considered separate entities with different prognosis and treatment. However, morphologic features can be similar and immunohistochemical studies are essential in the distinction; thus, determination of additional biomarkers is of utmost importance. LRF/Pokemon is a proto-oncogene, an interacting partner co-expressed with BCL6 in germinal centers and highly expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely, loss of the LRF gene in mouse hematopoietic stem cells results in complete block of early B cell development with concomitant Notch de-repression, indicating its critical role in B versus T cell fate decision at the hematopoietic stem cell stage. For the first time, we show that LRF/Pokemon is predominantly expressed in NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon expression with higher NOTCH1 expression. We illustrate a potential functional interaction between LRF and BCL6 in NLPHL pathogenesis, and differential expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential expression, making for an additional diagnostic marker and therapeutic target.

Utility of LRF/Pokemon and NOTCH1 Protein Expression in the Distinction of Nodular Lymphocyte-Predominant Hodgkin Lymphoma and Classical Hodgkin Lymphoma

Science.gov (United States)

Bohn, Olga; Maeda, Takahiro; Filatov, Alexander; Lunardi, Andrea; Pandolfi, Pier Paolo; Teruya-Feldstein, Julie

2014-01-01

Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are considered separate entities with different prognosis and treatment. However, morphologic features can be similar and immunohistochemical studies are essential in the distinction; thus, determination of additional biomarkers is of utmost importance. LRF/Pokemon is a protooncogene, an interacting partner co-expressed with BCL6 in germinal centers and highly expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely, loss of the LRF gene in mouse hematopoietic stem cells results in complete block of early B cell development with concomitant Notch derepression, indicating its critical role in B versus T cell fate decision at the hematopoietic stem cell stage. For the first time, we show that LRF/Pokemon is predominantly expressed in NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon expression with higher NOTCH1 expression. We illustrate a potential functional interaction between LRF and BCL6 in NLPHL pathogenesis, and differential expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential expression, making for an additional diagnostic marker and therapeutic target. PMID:24326827

A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma

NARCIS (Netherlands)

E. van den Neste (Eric); J.-L. André (Jean-Luc); Gastinne, T. (Thomas); A. Stamatoullas (Aspasia); C. Haioun (Corinne); Belhabri, A. (Amine); O. Reman (Oumédaly); O. Casasnovas (O.); H. Ghesquieres; G.E.G. Verhoef (Gregor); Claessen, M.-J. (Marie-José); H.A. Poirel (Hélène A); M.-C. Copin; Dubois, R. (Romain); P. Vandenberghe (Peter); Stoian, I.-A. (Ioanna-Andrea); Cottereau, A.S. (Anne S.); Bailly, S. (Sarah); L. Knoops (Laurent); F. Morschhauser (Frank)

2018-01-01

textabstractJAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in Hodgkin lymphoma. In this phase II study we

Stochastic biomathematical models with applications to neuronal modeling

CERN Document Server

Batzel, Jerry; Ditlevsen, Susanne

2013-01-01

Stochastic biomathematical models are becoming increasingly important as new light is shed on the role of noise in living systems. In certain biological systems, stochastic effects may even enhance a signal, thus providing a biological motivation for the noise observed in living systems. Recent advances in stochastic analysis and increasing computing power facilitate the analysis of more biophysically realistic models, and this book provides researchers in computational neuroscience and stochastic systems with an overview of recent developments. Key concepts are developed in chapters written by experts in their respective fields. Topics include: one-dimensional homogeneous diffusions and their boundary behavior, large deviation theory and its application in stochastic neurobiological models, a review of mathematical methods for stochastic neuronal integrate-and-fire models, stochastic partial differential equation models in neurobiology, and stochastic modeling of spreading cortical depression.

Electroneutral models for dynamic Poisson-Nernst-Planck systems

Science.gov (United States)

Song, Zilong; Cao, Xiulei; Huang, Huaxiong

2018-01-01

The Poisson-Nernst-Planck (PNP) system is a standard model for describing ion transport. In many applications, e.g., ions in biological tissues, the presence of thin boundary layers poses both modeling and computational challenges. In this paper, we derive simplified electroneutral (EN) models where the thin boundary layers are replaced by effective boundary conditions. There are two major advantages of EN models. First, it is much cheaper to solve them numerically. Second, EN models are easier to deal with compared to the original PNP system; therefore, it would also be easier to derive macroscopic models for cellular structures using EN models. Even though the approach used here is applicable to higher-dimensional cases, this paper mainly focuses on the one-dimensional system, including the general multi-ion case. Using systematic asymptotic analysis, we derive a variety of effective boundary conditions directly applicable to the EN system for the bulk region. This EN system can be solved directly and efficiently without computing the solution in the boundary layer. The derivation is based on matched asymptotics, and the key idea is to bring back higher-order contributions into the effective boundary conditions. For Dirichlet boundary conditions, the higher-order terms can be neglected and the classical results (continuity of electrochemical potential) are recovered. For flux boundary conditions, higher-order terms account for the accumulation of ions in boundary layer and neglecting them leads to physically incorrect solutions. To validate the EN model, numerical computations are carried out for several examples. Our results show that solving the EN model is much more efficient than the original PNP system. Implemented with the Hodgkin-Huxley model, the computational time for solving the EN model is significantly reduced without sacrificing the accuracy of the solution due to the fact that it allows for relatively large mesh and time-step sizes.

Hodgkin Lymphomas epidemiology

International Nuclear Information System (INIS)

Diaz, Carlos; Barroso, Maria; Alvarez, Julio; Sarmiento, Sofia; Diaz, Jose

2003-01-01

The interest of this study has been to learn the bio demographic characteristics of the Hodgkin lymphoma in our surrounding in accord with different clinical statistics that are considered of interest taken as references the results obtained in each on them. The clinical histories of the patients were evaluated retrospectively with diagnosis of Hodgkin, and registered in the national Institute of Oncology in Havana during the years 1980-1985 (group1) and the 1990-1995 (group 2). The sample was constituted by 242 patients (156 group 1, 86 group 2). The disease was slightly more frequent in males (1.3:1) in both groups. The biggest incidence fell upon the patients under 30 year of age with 74 (31%) in the group 1, and 41 (17%) group 2; followed by the group of patients between 30 and 49 years old with 24% in group 1 and 12 in group 2. The histological subtype most frequently found was the mixed cellularity 55% of the patients followed by nodular sclerosis in 32% clinical stage III was the most frequent with 138 patients (55%) the cervical adenopathy was the most consulted symptom referred by 199 (82%) of the patients. The ionizing radiation as only treatment were used in 115 patients (48%) while 80 (33%) were treated in conjunction with polychemotherapy, and in 40 (17%) polychemotherapy was used alone. A total of 204 (84%) patients showed complete remission when ended the initial treatment while 96 (40.9%) showed a relapse and 55 (62%) of them obtained a second CR. Until the last news, there are 196 (81%) alive patients and 43 (18%) dead. (The author)

Growth of cortical neuronal network in vitro: Modeling and analysis

International Nuclear Information System (INIS)

Lai, P.-Y.; Jia, L. C.; Chan, C. K.

2006-01-01

We present a detailed analysis and theoretical growth models to account for recent experimental data on the growth of cortical neuronal networks in vitro [Phys. Rev. Lett. 93, 088101 (2004)]. The experimentally observed synchronized firing frequency of a well-connected neuronal network is shown to be proportional to the mean network connectivity. The growth of the network is consistent with the model of an early enhanced growth of connection, but followed by a retarded growth once the synchronized cluster is formed. Microscopic models with dominant excluded volume interactions are consistent with the observed exponential decay of the mean connection probability as a function of the mean network connectivity. The biological implications of the growth model are also discussed

Dynamic chromosomal rearrangements in Hodgkin's lymphoma are due to ongoing three-dimensional nuclear remodeling and breakage-bridge-fusion cycles.

Science.gov (United States)

Guffei, Amanda; Sarkar, Rahul; Klewes, Ludger; Righolt, Christiaan; Knecht, Hans; Mai, Sabine

2010-12-01

Hodgkin's lymphoma is characterized by the presence of mono-nucleated Hodgkin cells and bi- to multi-nucleated Reed-Sternberg cells. We have recently shown telomere dysfunction and aberrant synchronous/asynchronous cell divisions during the transition of Hodgkin cells to Reed-Sternberg cells.1 To determine whether overall changes in nuclear architecture affect genomic instability during the transition of Hodgkin cells to Reed-Sternberg cells, we investigated the nuclear organization of chromosomes in these cells. Three-dimensional fluorescent in situ hybridization revealed irregular nuclear positioning of individual chromosomes in Hodgkin cells and, more so, in Reed-Sternberg cells. We characterized an increasingly unequal distribution of chromosomes as mono-nucleated cells became multi-nucleated cells, some of which also contained chromosome-poor 'ghost' cell nuclei. Measurements of nuclear chromosome positions suggested chromosome overlaps in both types of cells. Spectral karyotyping then revealed both aneuploidy and complex chromosomal rearrangements: multiple breakage-bridge-fusion cycles were at the origin of the multiple rearranged chromosomes. This conclusion was challenged by super resolution three-dimensional structured illumination imaging of Hodgkin and Reed-Sternberg nuclei. Three-dimensional super resolution microscopy data documented inter-nuclear DNA bridges in multi-nucleated cells but not in mono-nucleated cells. These bridges consisted of chromatids and chromosomes shared by two Reed-Sternberg nuclei. The complexity of chromosomal rearrangements increased as Hodgkin cells developed into multi-nucleated cells, thus indicating tumor progression and evolution in Hodgkin's lymphoma, with Reed-Sternberg cells representing the highest complexity in chromosomal rearrangements in this disease. This is the first study to demonstrate nuclear remodeling and associated genomic instability leading to the generation of Reed-Sternberg cells of Hodgkin's lymphoma

Recurrence of non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Watanabe, Toshikazu; Kiyono, Kunihiro; Niibe, Hideo; Horiuchi, Junichi; Kaneta, Koichi; Morita, Kozo; Masaki, Norie; Hayabuchi, Naofumi.

1988-01-01

563 patients with Stage I and II non-Hodgkin's lymphoma were treated by radiotherapy. 34 recurrences that occured after 3 years from initial treatment were seen in those patients. 15 (44 %) of 34 recurrences occured after 5 years. 20 patients (59 %) had remission by re-treatment, and 13 (38 %) survived more than 2 years. 20 (59 %) of recurrences were seen on head and neck lesions and superficial lymph nodes. (author)

Recurrence of non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Watanabe, Toshikazu; Oguchi, Masahiko; Niibe, Hideo; Horiuchi, Junichi; Kaneta, Koichi; Morita, Kozo; Masaki, Norie; Hayabuchi, Naofumi.

1988-01-01

From 1972 to 1982, 563 patients with Stage I and II non-Hodgkin's lymphoma received radiation therapy in the department of radiology which belongs to the JLRTS group. Local control failures were seen in only 5 cases (0.9 %). The regional recurrences were found in 30 cases (5 %). 17 of recurrences occured during the first 5 years. 17 cases had remissions again, and 5 cases had 5 year survivals. (author)

Mucosal bridges of the upper esophagus after radiotherapy for Hodgkin's disease

International Nuclear Information System (INIS)

Papazian, A.; Capron, J.P.; Ducroix, J.P.; Dupas, J.L.; Quenum, C.; Besson, P.

1983-01-01

A 47-yr-old man developed dysphagia 4 yr after mediastinal radiotherapy for Hodgkin's disease. X-ray series, fiberoptic endoscopy, and computerized transverse tomography showed mucosal bridges in the upper esophagus. Histologically, these bridges were constituted from normal epithelium overlying a chronic inflammatory lamina propria, without evidence of Hodgkin's disease recurrence or of squamous cell carcinoma. Swallowing was improved by endoscopic electrocoagulation and Eder-Puestow dilatations. Several arguments favor the hypothesis that these mucosal bridges were the late sequelae of radiation esophagitis

Late effects after treatment for Hodgkin lymphoma

NARCIS (Netherlands)

Daniëls, Laurien Aletta

2014-01-01

Although modern treatment strategies have made Hodgkin Lymphoma (HL) a highly curable disease, there is a life-long increased risk of morbidity and mortality due to treatment. Over time it has become increasingly evident that the historically used extensive treatment fields can potentially lead to

Building functional networks of spiking model neurons.

Science.gov (United States)

Abbott, L F; DePasquale, Brian; Memmesheimer, Raoul-Martin

2016-03-01

Most of the networks used by computer scientists and many of those studied by modelers in neuroscience represent unit activities as continuous variables. Neurons, however, communicate primarily through discontinuous spiking. We review methods for transferring our ability to construct interesting networks that perform relevant tasks from the artificial continuous domain to more realistic spiking network models. These methods raise a number of issues that warrant further theoretical and experimental study.

Gallium scan in recurrent Hodgkin's disease in children

International Nuclear Information System (INIS)

Yeh, S.D.; Benua, R.S.; Tan, C.T.

1979-01-01

In 18 of 88 children with biopsy proven and previously untreated Hodgkin's disease, recurrence developed during a period from four to 53 months after therapy (median period, 22 months). In 16 patients in whom gallium scans were performed, 21 positive gallium scans were obtained during 26 episodes of recurrence. Abnormalities were noted in half of them during a period from one to 10 months prior to physical, laboratory, radiographic or histologic confirmation of recurrence (median period about 5 months). We have concluded that the gallium scan is very useful in initial workup and is sensitive in detecting early recurrence in children with Hodgkin's disease. Such scans are indicated when there is clinical suspicion of recurrence, when other modalities are unavailable or when the results of other studies are equivocal

Predicting the past: ancient eclipses and Airy, Newcomb, and Huxley on the authority of science.

Science.gov (United States)

Stanley, Matthew

2012-06-01

Greek historical accounts of ancient eclipses were an important, if peculiar, focus of scientific attention in the nineteenth century. Victorian-era astronomers tried to correct the classical histories using scientific methods, then used those histories as data with which to calibrate their lunar theories, then rejected the histories as having any relevance at all. The specific dating of these eclipses--apparently a simple exercise in celestial mechanics--became bound up with tensions between scientific and humanistic approaches to the past as well as with wider social debates over the power and authority of science in general. The major figures discussed here, including G. B. Airy, Simon Newcomb, and T. H. Huxley, argued that the critical question was whether science could speak authoritatively about the past. To them, the ability of science to talk about the past indicated its power to talk about the future; it was also the fulcrum of fierce boundary disputes among science, history, and religion.

Hodgkin's disease following thorium dioxide angiography

Energy Technology Data Exchange (ETDEWEB)

Gotlieb, A I; Kirk, M E [McGill Univ., Montreal, Quebec (Canada). Dept. of Pathology; Hutchison, J L [Montreal General Hospital, Quebec (Canada)

1976-09-04

Hodgkin's disease occurred in a 53-year-old man who, 25 years previously, had undergone cerebral angiography, for which thorium dioxide suspension (Thorotrast) was used. Deposits of thorium dioxide were noted in reticuloendothelial cells in various locations. An association between thorium dioxide administration and the subsequent development of malignant tumours and neoplastic hematologic disorders has previously been reported.

Modeling chemotherapeutic neurotoxicity with human induced pluripotent stem cell-derived neuronal cells.

Directory of Open Access Journals (Sweden)

Heather E Wheeler

Full Text Available There are no effective agents to prevent or treat chemotherapy-induced peripheral neuropathy (CIPN, the most common non-hematologic toxicity of chemotherapy. Therefore, we sought to evaluate the utility of human neuron-like cells derived from induced pluripotent stem cells (iPSCs as a means to study CIPN. We used high content imaging measurements of neurite outgrowth phenotypes to compare the changes that occur to iPSC-derived neuronal cells among drugs and among individuals in response to several classes of chemotherapeutics. Upon treatment of these neuronal cells with the neurotoxic drug paclitaxel, vincristine or cisplatin, we identified significant differences in five morphological phenotypes among drugs, including total outgrowth, mean/median/maximum process length, and mean outgrowth intensity (P < 0.05. The differences in damage among drugs reflect differences in their mechanisms of action and clinical CIPN manifestations. We show the potential of the model for gene perturbation studies by demonstrating decreased expression of TUBB2A results in significantly increased sensitivity of neurons to paclitaxel (0.23 ± 0.06 decrease in total neurite outgrowth, P = 0.011. The variance in several neurite outgrowth and apoptotic phenotypes upon treatment with one of the neurotoxic drugs is significantly greater between than within neurons derived from four different individuals (P < 0.05, demonstrating the potential of iPSC-derived neurons as a genetically diverse model for CIPN. The human neuron model will allow both for mechanistic studies of specific genes and genetic variants discovered in clinical studies and for screening of new drugs to prevent or treat CIPN.

Imaging of supradiaphragmatic manifestations of extranodal nonHodgkin's lymphoma

International Nuclear Information System (INIS)

Cohnen, M.; Saleh, A.; Engelbrecht, V.; Moedder, U.; Germing, U.

2002-01-01

Malignant lymphomas are differentiated into Hodgkin's and non-Hodgkin's-lymphoma (NHL). The following article discusses the imaging of extranodal NHL in supradiaphragmatic localizations. Lymphoma can affect nearly all tissues, and represent a rare entity as primary extranodal NHL. A secondary involvement of non-nodal tissue as consequence of a generalized lymphoproliferative disease is more common,and may be seen as well in HIV-positive patients defining AIDS. As extranodal lymphoma mimick the radiologic appearance of other malignant tumors, direct diagnosis without histologic analysis is often impossible. The article describes typical manifestations of lymphoma of the lungs, the head and neck area including the large glands, and rare localizations as the heart or the breast. (orig.) [de

Frequent alteration of MDM2 and p53 in the molecular progression of recurring non-Hodgkin's lymphoma

DEFF Research Database (Denmark)

Møller, Michael Boe; Nielsen, O; Pedersen, Niels Tinggaard

2002-01-01

-Hodgkin's lymphoma. METHODS AND RESULTS: We have analysed sequential biopsies from 42 non-Hodgkin's lymphoma patients immunohistochemically for p53 alterations (based on p53 and p21Waf1 expression), as well as for expression of MDM2, p27Kip1 and cyclin D3. Relapse of follicle centre lymphoma was associated with p53...... alterations as 5/6 (83%) follicle centre lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. Of these cases, three showed transformation to diffuse large B-cell lymphoma. p53 alteration was also associated with relapse of de novo diffuse large B-cell lymphoma and T-cell non......-Hodgkin's lymphoma, as 2/5 (40%) diffuse large B-cell lymphomas and 3/9 (33%) T-cell non-Hodgkin's lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. No indolent non-Hodgkin's lymphoma case showed MDM2 over-expression at diagnosis, whereas 4/5 (80%) transformed diffuse large B-cell lymphomas...

Late cardiotoxicity after treatment for Hodgkin lymphoma

DEFF Research Database (Denmark)

Aleman, Berthe M P; van den Belt-Dusebout, Alexandra W; De Bruin, Marie L

2007-01-01

We assessed cardiovascular disease (CVD) incidence in 1474 survivors of Hodgkin lymphoma (HL) younger than 41 years at treatment (1965-1995). Multivariable Cox regression and competing risk analyses were used to quantify treatment effects on CVD risk. After a median follow-up of 18.7 years, risks...

Studying the Behaviour of Model of Mirror Neuron System in Case of Autism

OpenAIRE

Anirban, Shikha; Hanif Ali, Mohammad

2012-01-01

Several experiment done by the researchers conducted that autism is caused by the dysfunctional mirror neuron system and the dysfunctions of mirror neuron system is proportional to the symptom severity of autism. In the present work those experiments were studied as well as studying a model of mirror neuron system called MNS2 developed by a research group. This research examined the behavior of the model in case of autism and compared the result with those studies conducting dysfunctions of m...

Composite Lymphoma : EBV-positive Classic Hodgkin Lymphoma and Peripheral T-cell Lymphoma A Case Report

NARCIS (Netherlands)

Gualco, Gabriela; Chioato, Lucimara; Van Den Berg, Anke; Weiss, Lawrence M.; Bacchi, Carlos E.

Composite lymphomas are rare and defined as hematopoietic neoplasms with more than I malignant lymphomatous clone showing different phenotypic features. Of all possible combinations between non-Hodgkin lymphomas, B cell or T cell, and Hodgkin lymphoma, the least frequent are the ones combining

Treatment of Hodgkin's lymphoma

International Nuclear Information System (INIS)

Petrov, M.

1986-01-01

The data pertinent to 101 patients with Hodgkin's disease who had been subjected to splenectomy and combined radiation therapy and chemotherapy are analyzed. The efficacy of the treatment was relatively dependent on the initial localization and the degree of the generalization and appresiveness of the disease. Acceleration of the disease gene realization stemmed from totally deranged antitumor immunity. The modern therapeutic remedies have reached the peak of their potentialities. This prompt the necessity of the search for new, still unknown biological methods, permitting the attainment of a more complete demalignancy

Multiple coherence resonances and synchronization transitions by time delay in adaptive scale-free neuronal networks with spike-timing-dependent plasticity

International Nuclear Information System (INIS)

Xie, Huijuan; Gong, Yubing

2017-01-01

In this paper, we numerically study the effect of spike-timing-dependent plasticity (STDP) on multiple coherence resonances (MCR) and synchronization transitions (ST) induced by time delay in adaptive scale-free Hodgkin–Huxley neuronal networks. It is found that STDP has a big influence on MCR and ST induced by time delay and on the effect of network average degree on the MCR and ST. MCR is enhanced or suppressed as the adjusting rate A p of STDP decreases or increases, and there is optimal A p by which ST becomes strongest. As network average degree 〈k〉 increases, ST is enhanced and there is optimal 〈k〉 at which MCR becomes strongest. Moreover, for a larger A p value, ST is enhanced more rapidly with increasing 〈k〉 and the optimal 〈k〉 for MCR increases. These results show that STDP can either enhance or suppress MCR, and there is optimal STDP that can most strongly enhance ST induced by time delay in the adaptive neuronal networks. These findings could find potential implication for the information processing and transmission in neural systems.

A model explaining synchronization of neuron bioelectric frequency under weak alternating low frequency magnetic field

Energy Technology Data Exchange (ETDEWEB)

Moral, A. del, E-mail: delmoral@unizar.es [Laboratorio de Magnetismo, Departamento de Física de Materia Condensada and Instituto de Ciencia de Materiales, Universidad de Zaragoza and Consejo Superior de Investigaciones Científicas, 50009 Zaragoza (Spain); Laboratorio de Magnetobiología, Departamento de Anatomía e Histología, Facultad de Medicina, Universidad de Zaragoza, 50009 Zaragoza (Spain); Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, 28223 Madrid (Spain); Azanza, María J., E-mail: mjazanza@unizar.es [Laboratorio de Magnetobiología, Departamento de Anatomía e Histología, Facultad de Medicina, Universidad de Zaragoza, 50009 Zaragoza (Spain); Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, 28223 Madrid (Spain)

2015-03-01

A biomagnetic-electrical model is presented that explains rather well the experimentally observed synchronization of the bioelectric potential firing rate (“frequency”), f, of single unit neurons of Helix aspersa mollusc under the application of extremely low frequency (ELF) weak alternating (AC) magnetic fields (MF). The proposed model incorporates to our widely experimentally tested model of superdiamagnetism (SD) and Ca{sup 2+} Coulomb explosion (CE) from lipid (LP) bilayer membrane (SD–CE model), the electrical quadrupolar long range interaction between the bilayer LP membranes of synchronized neuron pairs, not considered before. The quadrupolar interaction is capable of explaining well the observed synchronization. Actual extension of our SD–CE-model shows that the neuron firing frequency field, B, dependence becomes not modified, but the bioelectric frequency is decreased and its spontaneous temperature, T, dependence is modified. A comparison of the model with synchronization experimental results of pair of neurons under weak (B{sub 0}≅0.2–15 mT) AC-MF of frequency f{sub M}=50 Hz is reported. From the deduced size of synchronized LP clusters under B, is suggested the formation of small neuron networks via the membrane lipid correlation. - Highlights: • Neuron pair synchronization under low frequency alternating (AC) magnetic field (MF). • Superdiamagnetism and Ca{sup 2+} Coulomb explosion for AC MF effect in synchronized frequency. • Membrane lipid electrical quadrupolar pair interaction as synchronization mechamism. • Good agreement of model with electrophysiological experiments on mollusc Helix neurons.

A model explaining synchronization of neuron bioelectric frequency under weak alternating low frequency magnetic field

International Nuclear Information System (INIS)

Moral, A. del; Azanza, María J.

2015-01-01

A biomagnetic-electrical model is presented that explains rather well the experimentally observed synchronization of the bioelectric potential firing rate (“frequency”), f, of single unit neurons of Helix aspersa mollusc under the application of extremely low frequency (ELF) weak alternating (AC) magnetic fields (MF). The proposed model incorporates to our widely experimentally tested model of superdiamagnetism (SD) and Ca 2+ Coulomb explosion (CE) from lipid (LP) bilayer membrane (SD–CE model), the electrical quadrupolar long range interaction between the bilayer LP membranes of synchronized neuron pairs, not considered before. The quadrupolar interaction is capable of explaining well the observed synchronization. Actual extension of our SD–CE-model shows that the neuron firing frequency field, B, dependence becomes not modified, but the bioelectric frequency is decreased and its spontaneous temperature, T, dependence is modified. A comparison of the model with synchronization experimental results of pair of neurons under weak (B 0 ≅0.2–15 mT) AC-MF of frequency f M =50 Hz is reported. From the deduced size of synchronized LP clusters under B, is suggested the formation of small neuron networks via the membrane lipid correlation. - Highlights: • Neuron pair synchronization under low frequency alternating (AC) magnetic field (MF). • Superdiamagnetism and Ca 2+ Coulomb explosion for AC MF effect in synchronized frequency. • Membrane lipid electrical quadrupolar pair interaction as synchronization mechamism. • Good agreement of model with electrophysiological experiments on mollusc Helix neurons

Economic evaluations in aggressive non-Hodgkin's lymphoma

NARCIS (Netherlands)

M. van Agthoven (Michel)

2004-01-01

textabstractNon-Hodgkin's lymphoma (NHL) has the highest incidence rate of all haematological malignancies in the Western world 1 • In the USA, the number of deaths attributable to NHL currently ranks in the top five of cancer related deaths2 In the Netherlands, haematological malignancies rank 8 in

Linfoma no Hodgkin primario de mama, revisión de la literatura y presentación de un caso Primary non-Hodgkin breast lymphoma, literature review and a case a presentation

Directory of Open Access Journals (Sweden)

Caridad Verdecia Cañizares

2011-06-01

Full Text Available El linfoma no Hodgkin primario de la mama es una entidad poco frecuente en pediatría y representa el 0,4 al 0,5 % de todos los tumores mamarios malignos. Debido a que carecen de características propias, tanto clínicas, citológicas como ecográficas, resulta muy difícil establecer el diagnóstico preoperatorio. Se presenta el caso de un linfoma no Hodgkin primario de la mama en una paciente de 3 años que llegó en estadio avanzado de la enfermedad, y se subraya la importancia del tratamiento en un equipo multidisciplinario.The primary non-Hodgkin breast lymphoma is a not frequent entity in children and account for the 0,4 to 0,5% of the malignant breast tumors. Due to they lack of own clinical, cytological and echography features, it is very difficult to made the preoperative diagnosis. This is the case of a primary non-Hodgkin breast lymphoma in a patient aged 3 with an advanced stage of disease, emphasizing the significance of treatment in a multidisciplinary staff.

Prognostic factors in Hodgkin's disease stage III with special reference to tumour burden

DEFF Research Database (Denmark)

Specht, L; Nissen, N I

1988-01-01

143 patients with Hodgkin's disease stage III (65 PS III, 78 CS III) were treated with radiotherapy alone (33 patients), combination chemotherapy alone (56 patients), or radiotherapy plus combination chemotherapy (54 patients). They were followed till death or from 7 to 191 months. Prognostic fac...... regarding early stage disease to the effect that tumour burden is the single most important prognostic factor in Hodgkin's disease....

Challenging normative orthodoxies in depression: Huxley's Utopia or Dante's Inferno?

Science.gov (United States)

Cutcliffe, John R; Lakeman, Richard

2010-04-01

Although there appears to be a widespread consensus that depression is a ubiquitous human experience, definitions of depression, its prevalence, and how mental health services respond to it have changed significantly over time, particularly during recent decades. Epistemological limitations notwithstanding, it is now estimated that approximately 121 million people experience depression. At the same time, it should be acknowledged that the last two decades have seen the widespread acceptance of depression as a chemical imbalance and a massive corresponding increase in the prescription of antidepressants, most notably of selective serotonin reuptake inhibitors (SSRIs). However, questions have been raised about the effectiveness and iatrogenic side effects of antidepressants; related questions have also been asked about whose interests are served by the marketing and sales of these drugs. Accordingly, this article attempts to problematize the normative orthodoxy concerning depression and creates a "space" in which an alternative can be articulated and enacted. In so doing, the article finds that the search for a world where the automatic response to depression is a pharmacological intervention not only ignores the use of alternative efficacious treatment options but may also inhibit the persons' chance to explore the meaning of their experience and thus prevent people from individual growth and personal development. Interestingly, in worlds analogous to this pharmacologically induced depression-free state, such as utopias like that in Huxley's Brave New World, no "properly conditioned citizen" is depressed or suicidal. Yet, in the same Brave New World, no one is free to suffer, to be different, or crucially, to be independent. Copyright 2010 Elsevier Inc. All rights reserved.

Multivariate Normal Tissue Complication Probability Modeling of Heart Valve Dysfunction in Hodgkin Lymphoma Survivors

International Nuclear Information System (INIS)

Cella, Laura; Liuzzi, Raffaele; Conson, Manuel; D’Avino, Vittoria; Salvatore, Marco; Pacelli, Roberto

2013-01-01

Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced asymptomatic heart valvular defects (RVD). Methods and Materials: Fifty-six patients treated with sequential chemoradiation therapy for Hodgkin lymphoma (HL) were retrospectively reviewed for RVD events. Clinical information along with whole heart, cardiac chambers, and lung dose distribution parameters was collected, and the correlations to RVD were analyzed by means of Spearman's rank correlation coefficient (Rs). For the selection of the model order and parameters for NTCP modeling, a multivariate logistic regression method using resampling techniques (bootstrapping) was applied. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: When we analyzed the whole heart, a 3-variable NTCP model including the maximum dose, whole heart volume, and lung volume was shown to be the optimal predictive model for RVD (Rs = 0.573, P<.001, AUC = 0.83). When we analyzed the cardiac chambers individually, for the left atrium and for the left ventricle, an NTCP model based on 3 variables including the percentage volume exceeding 30 Gy (V30), cardiac chamber volume, and lung volume was selected as the most predictive model (Rs = 0.539, P<.001, AUC = 0.83; and Rs = 0.557, P<.001, AUC = 0.82, respectively). The NTCP values increase as heart maximum dose or cardiac chambers V30 increase. They also increase with larger volumes of the heart or cardiac chambers and decrease when lung volume is larger. Conclusions: We propose logistic NTCP models for RVD considering not only heart irradiation dose but also the combined effects of lung and heart volumes. Our study establishes the statistical evidence of the indirect effect of lung size on radio-induced heart toxicity

Localization of Hodgkin's disease and lymphomas by 67-gallium substraction scanning

Energy Technology Data Exchange (ETDEWEB)

Krolikiewicz, H; Maruyama, Y; Deland, F H; Beihn, R M; Hafner, T; Utley, J F

1977-01-01

/sup 67/Ga-subtraction scan was found to be useful and a promising new method for the pre-treatment evaluation of the patient with Hodgkin's disease or non-Hodgkin's lymphoma. The scan appeared to be most accurate in the neck, chest, and axillary regions. It appears to offer a means of increasing the accuracy of evaluating the abdomen, the para-aortic and pelvic regions. It may be a useful method for the follow-up to detect recurrences. It was an easily performed, safe, non-invasive test, well tolerated and accepted by patients.

NON-HODGKIN'S LYMPHOMAS OF FEMALE REPRODUCTIVE SYSTEM

Directory of Open Access Journals (Sweden)

A. V. Babkina

2008-01-01

Full Text Available Non-Hodgkin's lymphomas are extremely rare among all tumors of female reproductive system. Diagnostic mistakes and inadequate therapeu- tic tactics in these diseases are results of usual absence of alertness of gynecologists. The aims are to analyze reasons of diagnostic mistakes in patients with non-Hodgkin's lymphomas of female reproductive system and to discover definitive clinical and morphological characteristics of female reproductive system lymphoid tumors. During the period between 1989 and 2006, 305 cases of primary extranodal non-Hodgkin's lym- phomas were detected; female reproductive system was affected in 7% of patients (totally 40 patients, which were included in investigated group. In the whole analyzed group of women (n=40, median age 43 yrs, range 17-84 yrs, patients with primary lesion of female reproductive system had median age of 40 yrs and with secondary involvement - 46 yrs. Most of patients were fertile (60%, n=24. Such tumors was localized in breast in 40% of cases (n=16, in ovaries - 20% (n=8, in uterine corpus - 12,5% (n=5, in uterine cervix - 15% (n=6, and in vagina - remaining 12,5% (n=5. Average time from diagnosis to beginning of the treatment was 7,5 months. As a result, the onset of specific therapy was delayed in 65% cases (n=26 and 50% (n=20 underwent unneeded surgery. Diagnostic mistakes lead to inadequate treatment. Extranodal non-Hodgkin’s lymphomas of female reproductive system, both primary and secondary, are rare pathology. Primary lesion is more typical for older women, sec- ondary is mainly affecting younger women (in reproductive period. Chemotherapy response and prognosis are better in primary cases.

Bidirectional coupling between astrocytes and neurons mediates learning and dynamic coordination in the brain: a multiple modeling approach.

Directory of Open Access Journals (Sweden)

John J Wade

Full Text Available In recent years research suggests that astrocyte networks, in addition to nutrient and waste processing functions, regulate both structural and synaptic plasticity. To understand the biological mechanisms that underpin such plasticity requires the development of cell level models that capture the mutual interaction between astrocytes and neurons. This paper presents a detailed model of bidirectional signaling between astrocytes and neurons (the astrocyte-neuron model or AN model which yields new insights into the computational role of astrocyte-neuronal coupling. From a set of modeling studies we demonstrate two significant findings. Firstly, that spatial signaling via astrocytes can relay a "learning signal" to remote synaptic sites. Results show that slow inward currents cause synchronized postsynaptic activity in remote neurons and subsequently allow Spike-Timing-Dependent Plasticity based learning to occur at the associated synapses. Secondly, that bidirectional communication between neurons and astrocytes underpins dynamic coordination between neuron clusters. Although our composite AN model is presently applied to simplified neural structures and limited to coordination between localized neurons, the principle (which embodies structural, functional and dynamic complexity, and the modeling strategy may be extended to coordination among remote neuron clusters.

Thyroid neoplasia following radiation therapy for Hodgkin's lymphoma

International Nuclear Information System (INIS)

McHenry, C.; Jarosz, H.; Calandra, D.; McCall, A.; Lawrence, A.M.; Paloyan, E.

1987-01-01

The question of thyroid neoplasia following high-dose radiation treatment to the neck and mediastinum for malignant neoplasms such as Hodgkin's lymphoma in children and young adults has been raised recently. Five patients, 19 to 39 years old, were operated on for thyroid neoplasms that developed following cervical and mediastinal radiation therapy for Hodgkin's lymphoma. Three patients had papillary carcinomas and two had follicular adenomas. The latency period between radiation exposure and the diagnosis of thyroid neoplasm ranged from eight to 16 years. This limited series provided strong support for the recommendation that children and young adults who are to receive high-dose radiation therapy to the head, neck, and mediastinum should receive suppressive doses of thyroxine prior to radiation therapy in order to suppress thyrotropin (thyroid-stimulating hormone) and then be maintained on a regimen of suppression permanently

Renal and perirenal non-Hodgkin's lymphoma: CT findings

International Nuclear Information System (INIS)

Lee, Seon Kyu; Kim, Seung Hyup; Lee, Goo; Choi, Byeung In; Han, Man Chung

1992-01-01

CT findings of 19 kidneys in 12 patients with renal and perirenal non-Hodgkin's lymphoma were retrospectively reviewed to determine distinguishing characteristic and specific findings. CT manifestation of the renal and perirenal lymphoma included multiple nodules in five kidneys(26.3%), trans-capsular infiltration in three kidneys(15.8%), trans-sinus infiltration in nine kidneys(47.4%) and diffuse infiltration in two kidneys(10.5%). Perirenal changes were thickening of the renal fascia in ten kidneys(52.6%) and crescent lesion of low attenuation in the subcapsular area in five kidneys(26.3%) Retroperitoneal lymphadenopathy was evident in eleven patient(57.9%). Renal calyceal dilatation without renal pelvic dilatation(selective calycelal dilatation) was noted in three kidneys. Familiarity with these CT findings of renal and perirenal lymphoma may be helpful in the diagnosis and management of patient with non-Hodgkin's lymphoma

Restoring neuronal progranulin reverses deficits in a mouse model of frontotemporal dementia.

Science.gov (United States)

Arrant, Andrew E; Filiano, Anthony J; Unger, Daniel E; Young, Allen H; Roberson, Erik D

2017-05-01

Loss-of-function mutations in progranulin (GRN), a secreted glycoprotein expressed by neurons and microglia, are a common autosomal dominant cause of frontotemporal dementia, a neurodegenerative disease commonly characterized by disrupted social and emotional behaviour. GRN mutations are thought to cause frontotemporal dementia through progranulin haploinsufficiency, therefore, boosting progranulin expression from the intact allele is a rational treatment strategy. However, this approach has not been tested in an animal model of frontotemporal dementia and it is unclear if boosting progranulin could correct pre-existing deficits. Here, we show that adeno-associated virus-driven expression of progranulin in the medial prefrontal cortex reverses social dominance deficits in Grn+/- mice, an animal model of frontotemporal dementia due to GRN mutations. Adeno-associated virus-progranulin also corrected lysosomal abnormalities in Grn+/- mice. The adeno-associated virus-progranulin vector only transduced neurons, suggesting that restoring neuronal progranulin is sufficient to correct deficits in Grn+/- mice. To further test the role of neuronal progranulin in the development of frontotemporal dementia-related deficits, we generated two neuronal progranulin-deficient mouse lines using CaMKII-Cre and Nestin-Cre. Measuring progranulin levels in these lines indicated that most brain progranulin is derived from neurons. Both neuronal progranulin-deficient lines developed social dominance deficits similar to those in global Grn+/- mice, showing that neuronal progranulin deficiency is sufficient to disrupt social behaviour. These data support the concept of progranulin-boosting therapies for frontotemporal dementia and highlight an important role for neuron-derived progranulin in maintaining normal social function. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Central nervous system complications in non-Hodgkin-lymphomas and radiotherapy

International Nuclear Information System (INIS)

Liffers, R.

1981-01-01

261 case historys of malignant non-Hodgkin-lymphomas were analysed in the years from 1969 until 1978 in the 'Radiologische Universitaetsklinik Kiel'/West-Germany. 18 Patients got a central nervous complication of Non Hodgkin-Lymphoma earlier or later, a percentage of about 7. There were 7 cases of lymphoblastic lymphoma (LB), a percentage of 10 for this entity. In the group of immunoblastic lymphoma (IB) 6 cases of central nervous infiltration were detected, that is a ratio of 7.7 percent. 4 case histories M. Brill-Symmers (CC/CB) were complicated by central nervous dissemination, a percentage of 5.3. Patients with lymphoblastic lymphoma have the highest risk of central nervous complication. The beginning of central nervous dissemination in the single case histories is very different between the histological groups. Patients with lymphoblastic lymphoma suffered from central nervous complication in an early phase of history, in cases of M. Brill-Symmers central nervous infiltration can occur also in a late phase. The results may determine the discussion about stratifying of radiotherapy. Early radiotherapy including central nervous system may be discussed and investigated in special histological entities of malignant non-Hodgkin-lymphoma. (orig.) [de

Establishment of mouse neuron and microglial cell co-cultured models and its action mechanism.

Science.gov (United States)

Zhang, Bo; Yang, Yunfeng; Tang, Jun; Tao, Yihao; Jiang, Bing; Chen, Zhi; Feng, Hua; Yang, Liming; Zhu, Gang

2017-06-27

The objective of this study is to establish a co-culture model of mouse neurons and microglial cells, and to analyze the mechanism of action of oxygen glucose deprivation (OGD) and transient oxygen glucose deprivation (tOGD) preconditioning cell models. Mouse primary neurons and BV2 microglial cells were successfully cultured, and the OGD and tOGD models were also established. In the co-culture of mouse primary neurons and microglial cells, the cell number of tOGD mouse neurons and microglial cells was larger than the OGD cell number, observed by a microscope. CCK-8 assay result showed that at 1h after treatment, the OD value in the control group is lower compared to all the other three groups (P control group compared to other three groups (P neurons cells were cultured. In the meantime mouse BV2 microglia cells were cultured. Two types of cells were co-cultured, and OGD and tOGD cell models were established. There were four groups in the experiment: control group (OGD), treatment group (tOGD+OGD), placebo group (tOGD+OGD+saline) and minocycline intervention group (tOGD+OGD+minocycline). CCK-8 kit was used to detect cell viability and flow cytometry was used to detect apoptosis. In this study, mouse primary neurons and microglial cells were co-cultured. The OGD and tOGD models were established successfully. tOGD was able to effectively protect neurons and microglial cells from damage, and inhibit the apoptosis caused by oxygen glucose deprivation.

Incidence of subclinical hypothyroidism in patients with Hodgkin lymphoma and non-Hodgkin requiring neck irradiation and/or mediastinum in the Hospital Mexico in the year 2009

International Nuclear Information System (INIS)

Monestel Umana, Rigoberto

2010-01-01

The treatment of lymphoma, both Hodgkin as non-Hodgkin, has had irradiation as part of management. The neck and/or mediastinum is irradiated and occurs, inevitably, partial or total irradiation of the thyroid gland. The evaluation that the effect may have on the function of the gland has been the purpose of this study. The risk of hypothyroidism in patients with Hodgkin lymphoma and non-Hodgkin should receive radiation therapy to the head, neck and/or mediastinum was studied. This has represented a first report of a follow-up study, of 2 years, analytical, longitudinal, observational, prospective. This is a first report of a follow-up study, of 2 years, analytical, longitudinal, observational, prospective. Design of cases, controls and a sample of 32 patients were studied; of these 31.25% have developed subclinical hypothyroidism. The subgroup with hypothyroidism was studied and an association was found between thyroid failure and dose, including the possibility of reversion of disorders. Association with the type of lymphoma and received chemotherapy was found, while with age, sex, lymphoma staging and dose received by the lymphoma is found without association. The onset of subclinical hypothyroidism generated by irradiation of the neck and/or mediastinum is associated with the radiation dose received by the thyroid. A relationship, unclear, has existed between the type of lymphoma and chemotherapy indicated as a treatment and should be explored further, a routine basis indicating the evaluation of the thyroid function in all these patients to avoid the development of unmonitored disorders. (author) [es

Modeling of Auditory Neuron Response Thresholds with Cochlear Implants

Directory of Open Access Journals (Sweden)

Frederic Venail

2015-01-01

Full Text Available The quality of the prosthetic-neural interface is a critical point for cochlear implant efficiency. It depends not only on technical and anatomical factors such as electrode position into the cochlea (depth and scalar placement, electrode impedance, and distance between the electrode and the stimulated auditory neurons, but also on the number of functional auditory neurons. The efficiency of electrical stimulation can be assessed by the measurement of e-CAP in cochlear implant users. In the present study, we modeled the activation of auditory neurons in cochlear implant recipients (nucleus device. The electrical response, measured using auto-NRT (neural responses telemetry algorithm, has been analyzed using multivariate regression with cubic splines in order to take into account the variations of insertion depth of electrodes amongst subjects as well as the other technical and anatomical factors listed above. NRT thresholds depend on the electrode squared impedance (β = −0.11 ± 0.02, P<0.01, the scalar placement of the electrodes (β = −8.50 ± 1.97, P<0.01, and the depth of insertion calculated as the characteristic frequency of auditory neurons (CNF. Distribution of NRT residues according to CNF could provide a proxy of auditory neurons functioning in implanted cochleas.

Chimera-like states in a neuronal network model of the cat brain

Science.gov (United States)

Santos, M. S.; Szezech, J. D.; Borges, F. S.; Iarosz, K. C.; Caldas, I. L.; Batista, A. M.; Viana, R. L.; Kurths, J.

2017-08-01

Neuronal systems have been modeled by complex networks in different description levels. Recently, it has been verified that networks can simultaneously exhibit one coherent and other incoherent domain, known as chimera states. In this work, we study the existence of chimera states in a network considering the connectivity matrix based on the cat cerebral cortex. The cerebral cortex of the cat can be separated in 65 cortical areas organised into the four cognitive regions: visual, auditory, somatosensory-motor and frontolimbic. We consider a network where the local dynamics is given by the Hindmarsh-Rose model. The Hindmarsh-Rose equations are a well known model of neuronal activity that has been considered to simulate membrane potential in neuron. Here, we analyse under which conditions chimera states are present, as well as the affects induced by intensity of coupling on them. We observe the existence of chimera states in that incoherent structure can be composed of desynchronised spikes or desynchronised bursts. Moreover, we find that chimera states with desynchronised bursts are more robust to neuronal noise than with desynchronised spikes.

Synaptic potentiation onto habenula neurons in learned helplessness model of depression

Science.gov (United States)

Li, Bo; Piriz, Joaquin; Mirrione, Martine; Chung, ChiHye; Proulx, Christophe D.; Schulz, Daniela; Henn, Fritz; Malinow, Roberto

2010-01-01

The cellular basis of depressive disorders is poorly understood1. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (i.e. disappointment or anticipation of a negative outcome)2, 3, 4. LHb neurons project to and modulate dopamine-rich regions such as the ventral-tegmental area (VTA)2, 5 that control reward-seeking behavior6 and participate in depressive disorders7. Here we show in two learned helplessness models of depression that excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal’s helplessness behavior and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective on depressed patients8, 9, dramatically suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behavior in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression. PMID:21350486

Recapitulation of spinal motor neuron-specific disease phenotypes in a human cell model of spinal muscular atrophy

Institute of Scientific and Technical Information of China (English)

Zhi-Bo Wang; Xiaoqing Zhang; Xue-Jun Li

2013-01-01

Establishing human cell models of spinal muscular atrophy (SMA) to mimic motor neuron-specific phenotypes holds the key to understanding the pathogenesis of this devastating disease.Here,we developed a closely representative cell model of SMA by knocking down the disease-determining gene,survival motor neuron (SMN),in human embryonic stem cells (hESCs).Our study with this cell model demonstrated that knocking down of SMN does not interfere with neural induction or the initial specification of spinal motor neurons.Notably,the axonal outgrowth of spinal motor neurons was significantly impaired and these disease-mimicking neurons subsequently degenerated.Furthermore,these disease phenotypes were caused by SMN-full length (SMN-FL) but not SMN-A7 (lacking exon 7)knockdown,and were specific to spinal motor neurons.Restoring the expression of SMN-FL completely ameliorated all of the disease phenotypes,including specific axonal defects and motor neuron loss.Finally,knockdown of SMNFL led to excessive mitochondrial oxidative stress in human motor neuron progenitors.The involvement of oxidative stress in the degeneration of spinal motor neurons in the SMA cell model was further confirmed by the administration of N-acetylcysteine,a potent antioxidant,which prevented disease-related apoptosis and subsequent motor neuron death.Thus,we report here the successful establishment of an hESC-based SMA model,which exhibits disease gene isoform specificity,cell type specificity,and phenotype reversibility.Our model provides a unique paradigm for studying how motor neurons specifically degenerate and highlights the potential importance of antioxidants for the treatment of SMA.

Parametric Modeling of Nerve Cell under the Sinusoidal Environmental 50 Hz Extremely Low Frequency Magnetic Fields

Directory of Open Access Journals (Sweden)

Homayoun Ebrahimian

2013-06-01

Full Text Available Background & Objectives: The development of technology has naturally given rise to an increase in environmental low-frequency electromagnetic fields and consequently has attracted scholars' attention. Most of the studies have focused on transmission lines and power system distribution with 50 Hz. This research is an attempt to show the effect of 50 Hz magnetic fields on bioelectric parameters and indicates the possible influence of this change in F1 cells of Helix aspersa .   Methods: The present research used Helix aspersa neuron F1 to identify the location of magnetic fields as well as the rate of effects of environmental magnetic fields on nervous system. Control group was used to study the effect of elapsed time, electrode entering and the cell membrane rupture. Intuition group and environmental group were considered in order to study the potential impact of interfering environmental factors and identify the effectiveness rate of magnetic fields, respectively. For the purpose of producing uniform magnetic field Helmholtz coil was used. Electrophysiological recording was realized under the requirements of current clamp. And, in order to show the impacts from magnetic fields on ion channels Hodgkin-Huxley cell model was applied. All data were analyzed taking the advantage of SPSS 16 software and two-way ANOVA statistical test. P < 0.05 was considered as significance level. And MATLAB software environment and PSO were used in order for applying the algorithm and estimating the parameters.   Result: No statistically significant difference was found between control and sham groups in different time intervals. Once the 45.87 microtesla was applied significant differences were observed 12 minutes after the application. The highest amount of change happened 14 minutes after the application of more fields. With the application of the field, the amplitude of the sodium action potential shows decreasing trend . No significant changes were observed in

Serotonin Neuron Abnormalities in the BTBR Mouse Model of Autism

Science.gov (United States)

Guo, Yue-Ping; Commons, Kathryn G.

2017-01-01

The inbred mouse strain BTBR T+ Itpr3tf/J (BTBR) i studied as a model of idiopathic autism because they are less social and more resistant to change than other strains. Forebrain serotonin receptors and the response to serotonin drugs are altered in BTBR mice, yet it remains unknown if serotonin neurons themselves are abnormal. In this study, we found that serotonin tissue content and the density of serotonin axons is reduced in the hippocampus of BTBR mice in comparison to C57BL/6J (C57) mice. This was accompanied by possible compensatory changes in serotonin neurons that were most pronounced in regions known to provide innervation to the hippocampus: the caudal dorsal raphe (B6) and the median raphe. These changes included increased numbers of serotonin neurons and hyperactivation of Fos expression. Metrics of serotonin neurons in the rostral 2/3 of the dorsal raphe and serotonin content of the prefrontal cortex were less impacted. Thus, serotonin neurons exhibit region-dependent abnormalities in the BTBR mouse that may contribute to their altered behavioral profile. PMID:27478061

Radioimmunotherapy of non-Hodgkin lymphoma

International Nuclear Information System (INIS)

Batista Cuellar, Juan F.

2016-01-01

Non-Hodgkin lymphoma have a worse prognosis compared with other varieties of lymphoma and conventional therapy has specific onco higher incidence of unsatisfactory answers becoming more frequent recurrences of the disease. Radioimmunotherapy has proven to be an effective adjuvant therapy often in cases where conventional therapy this not proving effective. In this paper an exhibition of the current international state of the therapeutic and experiences and possibilities that exist in our environment to develop their use is done. (author)

Computational modeling of seizure dynamics using coupled neuronal networks: factors shaping epileptiform activity.

Directory of Open Access Journals (Sweden)

Sebastien Naze

2015-05-01

Full Text Available Epileptic seizure dynamics span multiple scales in space and time. Understanding seizure mechanisms requires identifying the relations between seizure components within and across these scales, together with the analysis of their dynamical repertoire. Mathematical models have been developed to reproduce seizure dynamics across scales ranging from the single neuron to the neural population. In this study, we develop a network model of spiking neurons and systematically investigate the conditions, under which the network displays the emergent dynamic behaviors known from the Epileptor, which is a well-investigated abstract model of epileptic neural activity. This approach allows us to study the biophysical parameters and variables leading to epileptiform discharges at cellular and network levels. Our network model is composed of two neuronal populations, characterized by fast excitatory bursting neurons and regular spiking inhibitory neurons, embedded in a common extracellular environment represented by a slow variable. By systematically analyzing the parameter landscape offered by the simulation framework, we reproduce typical sequences of neural activity observed during status epilepticus. We find that exogenous fluctuations from extracellular environment and electro-tonic couplings play a major role in the progression of the seizure, which supports previous studies and further validates our model. We also investigate the influence of chemical synaptic coupling in the generation of spontaneous seizure-like events. Our results argue towards a temporal shift of typical spike waves with fast discharges as synaptic strengths are varied. We demonstrate that spike waves, including interictal spikes, are generated primarily by inhibitory neurons, whereas fast discharges during the wave part are due to excitatory neurons. Simulated traces are compared with in vivo experimental data from rodents at different stages of the disorder. We draw the conclusion

Self-Organized Criticality in a Simple Neuron Model Based on Scale-Free Networks

International Nuclear Information System (INIS)

Lin Min; Wang Gang; Chen Tianlun

2006-01-01

A simple model for a set of interacting idealized neurons in scale-free networks is introduced. The basic elements of the model are endowed with the main features of a neuron function. We find that our model displays power-law behavior of avalanche sizes and generates long-range temporal correlation. More importantly, we find different dynamical behavior for nodes with different connectivity in the scale-free networks.

Therapy for stage I aggressive non-Hodgkin's lymphoma

NARCIS (Netherlands)

Kluin-Nelemans, Hanneke

2002-01-01

Although radiotherapy was considered sufficient for stage I and limited stage II aggressive non-Hodgkin's lymphoma in the past, new data from randomized studies have shown that intensified chemotherapy or combined modality therapy (multiagent chemotherapy followed by involved field radiotherapy) can