Ontology and medical terminology: Why description logics are not enough

Ontology is currently perceived as the solution of first resort for all problems related to biomedical terminology, and the use of description logics is seen as a minimal requirement on adequate ontology-based systems. Contrary to common conceptions, however, description logics alone are not able to prevent incorrect representations; this is because they do not come with a theory indicating what is computed by using them, just as classical arithmetic does not tell us anything about the entities that are added or subtracted. In this paper we shall show that ontology is indeed an essential part of any solution to the problems of medical terminology – but only if it is understood in the right sort of way. Ontological engineering, we shall argue, should in every case go hand in hand with a sound ontological theory

A computational study of astrocytic glutamate influence on post-synaptic neuronal excitability

<p><b>Postsynaptic activity due to synaptic and intrinsic currents</b>, triggered by (a) synaptic glutamate [Glu]_syn (b-d) simulation with [Glu]_ast,eq = 1.5mM, 5mM, and 10mM respectively, synaptic currents (I_syn) combined AMPA- and NMDA-mediated currents in response to synaptic glutamate, membrane potential (V_m) of postsynaptic neuron resulting from combination of I_syn and voltage-gated currents (Na⁺, K⁺ and leak). Prolonged time course of synaptic glutamate leads to enhanced synaptic currents (I_syn) and higher frequency postsynaptic firing response (V_m depolarisations) as [Glu]_ast,eq increases.</p

A Computational Study of Astrocytic GABA Release at the Glutamatergic Synapse: EAAT-2 and GAT-3 Coupled Dynamics

Neurotransmitter dynamics within neuronal synapses can be controlled by astrocytes and reflect key contributors to neuronal activity. In particular, Glutamate (Glu) released by activated neurons is predominantly removed from the synaptic space by perisynaptic astrocytic transporters EAAT-2 (GLT-1). In previous work, we showed that the time course of Glu transport is affected by ionic concentration gradients either side of the astrocytic membrane and has the propensity for influencing postsynaptic neuronal excitability. Experimental findings co-localize GABA transporters GAT-3 with EAAT-2 on the perisynaptic astrocytic membrane. While these transporters are unlikely to facilitate the uptake of synaptic GABA, this paper presents simulation results which demonstrate the coupling of EAAT-2 and GAT-3, giving rise to the ionic-dependent reversed transport of GAT-3. The resulting efflux of GABA from the astrocyte to the synaptic space reflects an important astrocytic mechanism for modulation of hyperexcitability. Key results also illustrate an astrocytic-mediated modulation of synaptic neuronal excitation by released GABA at the glutamatergic synapse

Tidal Excitation of Oscillation Modes in Compact White Dwarf Binaries: I. Linear Theory

We study the tidal excitation of gravity modes (g-modes) in compact white dwarf binary systems with periods ranging from minutes to hours. As the orbit of the system decays via gravitational radiation, the orbital frequency increases and sweeps through a series of resonances with the g-modes of the white dwarf. At each resonance, the tidal force excites the g-mode to a relatively large amplitude, transferring the orbital energy to the stellar oscillation. We calculate the eigenfrequencies of g-modes and their coupling coefficients with the tidal field for realistic non-rotating white dwarf models. Using these mode properties, we numerically compute the excited mode amplitude in the linear approximation as the orbit passes though the resonance, including the backreaction of the mode on the orbit. We also derive analytical estimates for the mode amplitude and the duration of the resonance, which accurately reproduce our numerical results for most binary parameters. We find that the g-modes can be excited to a dimensionless (mass-weighted) amplitude up to 0.1, with the mode energy approaching $10^{-3}$ of the gravitational binding energy of the star. This suggests that thousands of years prior to the binary merger, the white dwarf may be heated up significantly by tidal interactions. However, more study is needed since the physical amplitudes of the excited oscillation modes become highly nonlinear in the outer layer of the star, which can reduce the mode amplitude attained by tidal excitation.Comment: 10 pages, 8 figure

Potassium and sodium microdomains in thin astroglial processes: A computational model study

A biophysical model that captures molecular homeostatic control of ions at the perisynaptic cradle (PsC) is of fundamental importance for understanding the interplay between astroglial and neuronal compartments. In this paper, we develop a multi-compartmental mathematical model which proposes a novel mechanism whereby the flow of cations in thin processes is restricted due to negatively charged membrane lipids which result in the formation of deep potential wells near the dipole heads. These wells restrict the flow of cations to “hopping” between adjacent wells as they transverse the process, and this surface retention of cations will be shown to give rise to the formation of potassium (K+) and sodium (Na+) microdomains at the PsC. We further propose that a K+ microdomain formed at the PsC, provides the driving force for the return of K+ to the extracellular space for uptake by the neurone, thereby preventing K+ undershoot. A slow decay of Na+ was also observed in our simulation after a period of glutamate stimulation which is in strong agreement with experimental observations. The pathological implications of microdomain formation during neuronal excitation are also discussed

Dynamical Tides in Compact White Dwarf Binaries: Tidal Synchronization and Dissipation

In compact white dwarf (WD) binary systems (with periods ranging from minutes to hours), dynamical tides involving the excitation and dissipation of gravity waves play a dominant role in determining the physical conditions of the WDs prior to mass transfer or binary merger. We calculate the amplitude of the tidally excited gravity waves as a function of the tidal forcing frequency \omega=2(\Omega-\Omega_s) (where \Omega is the orbital frequency and \Omega_s is the spin frequency) for several realistic carbon-oxygen WD models, assuming that the waves are efficiently dissipated in the outer layer of the star by nonlinear effects or radiative damping. The mechanism of wave excitation in WDs is complex due to the sharp features associated with composition changes inside the WD, and in our WD models gravity waves are launched just below the helium-carbon boundary. We find that the tidal torque on the WD and the related tidal energy transfer rate, \dot E_{\rm tide}, depend on \omega in an erratic way. On average, \dot E_{\rm tide} scales approximately as \Omega^5\omega^5 for a large range of tidal frequencies. We also study the effects of dynamical tides on the long-term evolution of WD binaries. Above a critical orbital frequency \Omega_c, corresponding to an orbital period of order one hour (depending on WD models), dynamical tides efficiently drive \Omega_s toward \Omega, although a small, almost constant degree of asynchronization (\Omega-\Omega_s\sim {\rm constant}) is maintained even at the smallest binary periods. While the orbital decay is always dominated by gravitational radiation, the tidal energy transfer can induce significant phase error in the low-frequency gravitational waveforms, detectable by the planned LISA project. Tidal dissipation may also lead to significant heating of the WD envelope and brightening of the system long before binary merger.Comment: 24 pages, 17 figures, published in MNRA