text:
In slow neocortical paroxysmal oscillations, the de- and hyperpolarizing envelopes in neocortical neurons are large compared with slow sleep oscillations. Increased local synchrony of membrane potential oscillations during seizure is reflected in larger electroencephalographic oscillations and the appearance of spike- or polyspike-wave complex recruitment at 2- to 3-Hz frequencies. The oscillatory mechanisms underlying this paroxysmal activity were investigated in computational models of cortical networks. The extracellular K+ concentration ([K+]o) was continuously computed based on neuronal K+ currents and K+ pumps as well as glial buffering. An increase of [K+]o triggered a transition from normal awake-like oscillations to 2- to 3-Hz seizure-like activity. In this mode, the cells fired periodic bursts and nearby neurons oscillated highly synchronously; in some cells depolarization led to spike inactivation lasting 50–100 ms. A [K+]o increase, sufficient to produce oscillations could result from excessive firing (e.g., induced by external stimulation) or inability of K+ regulatory system (e.g., when glial buffering was blocked). A combination of currents including high-threshold Ca2+, persistent Na+ and hyperpolarization-activated depolarizing (Ih) currents was sufficient to maintain 2- to 3-Hz activity. In a network model that included lateral K+ diffusion between cells, increase of [K+]o in a small region was generally sufficient to maintain paroxysmal oscillations in the whole network. Slow changes of [K+]o modulated the frequency of bursting and, in some case, led to fast oscillations in the 10- to 15-Hz frequency range, similar to the fast runs observed during seizures in vivo. These results suggest that modifications of the intrinsic currents mediated by increase of [K+]o can explain the range of neocortical paroxysmal oscillations in vivo.
Although it is well established that the extracellular potassium concentration ([K+]o) increases during epileptogenesis (Moody et al. 1974), whether this is the primary seizure-eliciting factor, or the increased firing causes the [K+]o elevation, remains unknown. According to the Grafstein potassium hypothesis, K+ released during intense neuron firing can accumulate in the interstitial space, thus depolarizing neurons and leading to spike inactivation. Slow diffusion of K+ into surrounding areas could then depolarize neurons and create slowly propagating waves of spreading depression (SD) (Grafstein 1957). Delayed increase of [K+]o compared with membrane potential depolarization measured during SD propagation (Herreras and Somjen 1993) suggests, however, that K+ diffusion may not be the primary mechanism maintaining SD waves, but it might still trigger SD phenomena (Kager et al. 2000).
Modulation of [K+]o has a profound impact on the excitability of neurons and neuronal networks. Increase of [K+]o depolarizes the K+ currents reversal potential and can affect the maximal conductances of some depolarizing currents such as the hyperpolarization-activated depolarizing current (Ih) (Spain et al. 1987) and the persistent sodium current (INa(p)) (Somjen and Muller 2000), increasing excitability. A recent study showed that K+-mediated increase of Ih may lead to periodic bursting in a cortical network model (Timofeev et al. 2002a). Periodic bursting was found in vitro after increasing [K+]o (Jensen and Yaari 1997; Leschinger et al. 1993; Pan and Stringer 1997). Traumatic brain injury leading to loss of K+ conductance in hippocampal glia can result in the failure of glial K+ homeostasis and abnormal neuronal function including seizures (D'Ambrosio et al. 1999).
The Lennox-Gastaut syndrome is one of the most severe and difficult epileptic conditions (Niedermeyer 2002). The electroencephalographic (EEG) pattern for this type of seizure consists of slow spike-wave (SW) or polyspike-wave (PSW) complexes and runs of rapid EEG "spikes" (10–25/s). This pattern closely resembles paroxysmal oscillations observed in experiments with anesthetized and chronic animals, consisting of SW/PSW complexes recurring at 2–3 Hz, often interrupted by fast runs at 10–15 Hz (Steriade et al. 1998a). The thalamic or cortical origin of these seizures is still actively debated. The occurrence of SW complexes in the depths of monkey cortex without a reflection at the cortical surface (Steriade 1974) and observation of seizures with SW/PSW complexes in completely isolated cortical slabs in vivo (Timofeev et al. 1998) suggest that focal SW seizure are initiated within the cortex. Multi-site recordings show that SW/PSW seizures may be initiated in cortex and then spread to the thalamus after a few-second delay (Neckelmann et al. 1998). Dual recordings from cortex and thalamus indicate that thalamic reticular neurons faithfully follow each cortical EEG "spike," whereas target thalamocortical (TC) neurons are relatively hyperpolarized during seizure episodes with SW/PSW complexes and thus cannot enhance paroxysmal bursting (Neckelmann et al. 1998; Steriade and Contreras 1995, 1998; Steriade et al. 1998a; Timofeev et al. 1998). Intracellular recordings from TC neurons during SW discharges in genetic models of absence epilepsy in rats also demonstrated that a majority of TC cells (>90%) were tonically hyperpolarized (Pinault et al. 1998).
This paper is a computational study of intracortical mechanisms for generating paroxysmal oscillations. We demonstrate an increased neuronal firing prior to seizure in vivo and we study with a computational network model whether local increases of [K+]o, either after intensive neuronal firing or when K+ regulatory system fail to maintain [K+]o level, can explain the observed transition to 2- to 3-Hz paroxysmal bursting in the cortical network.
In vivo recordings
Intracellular recordings from neocortical neurons were performed in 16 cats anesthetized with ketamine-xylazine (10–15 and 2–3 mg/kg im). After ketamine-xylazine anesthesia, ∼30% of cats (n = 6) displayed spontaneous electrographic seizures consisting of SW/PSW complexes at 1.5–3 Hz, often associated with fast runs at ∼10–15 Hz. Details of surgery are described in the companion paper (Timofeev et al. 2004).
Focal field potentials and multiunit recordings were obtained by means of an array of six equally spaced tungsten electrodes inserted in the cortex with an angle 45° arranged in the way that tips of all electrodes were aligned perpendicular to cortical surface and that the most superficial electrode was at depth ∼100 μm and the deepest electrode was at depth ∼1.6 mm. Intracellular recordings from cortical neurons were obtained with sharp glass micropipettes having resistance of 30–80 MΩ. The intracellular pipette was lowered in the cortical depth at distances <500 μm from the tips of tungsten electrodes composing the array. All experimental procedures were performed according to national guidelines and were approved by the committee for animal care of Laval University.
Computational model
Models of cortical pyramidal (PY) cells and interneurons (INs) had two compartments with channels governed by Hodgkin-Huxley kinetics (Mainen and Sejnowski 1996): (1) where Cm, gL are the membrane capacitance and the leakage conductance of the dendritic compartment, EL is the reversal potential, VD and VS are the membrane potentials of dendritic and axo-somatic compartments, IDint and ISint are the sums of active intrinsic currents in axo-somatic and dendritic compartments, Isyn is a sum of synaptic currents, and g is the conductance between axo-somatic and dendritic compartments. In this model, the axo-somatic compartment had no capacitance, which sped up the simulations but had little effect on the spike firing patterns (Mainen and Sejnowski 1996).
The model included fast Na+ channels, INa, with a high density in the axo-somatic compartment and a low density in the dendritic compartment. A fast delayed rectifier potassium K+ current, IK, was present in the axo-somatic compartment. A persistent sodium current, INa(p), was included in the axo-somatic and dendritic compartments (Alzheimer et al. 1993; Kay et al. 1998). A slow voltage-dependent noninactivating K+ current, IKm, a slow Ca2+-dependent K+ current, IK(Ca), a high-threshold Ca2+ current, ICa, hyperpolarization-activated depolarizing current Ih were included in the dendritic compartment. A potassium leak current, IKL = gKL(V − EK), was included in the dendritic and axo-somatic compartments. For INa(P), INa(p) = gNa(p) m(V − 50), dm/dt = (m∞ − m)/0.2, m∞ = 1/{1 + exp[−(V + 42)/5]} (Alzheimer et al. 1993). For Ih, Ih = gh (0.8m1+ 0.2m2)(V + 40), dmi/dt = −(m∞ − mi)/τi, m∞ = 1/{1 + exp[(V + 82)/7]}, τ1 = 38 ms, τ2 = 319 ms (Spain et al. 1987). The slow Ih component (τ2) was found to have little effect on the firing patterns and was omitted in these simulations. The expressions for the voltage- and Ca2+-dependent transition rates for all other currents are given in (Timofeev et al. 2000). In most of the simulations, the maximal conductances and passive properties were Ssoma = 1.0·10−6 cm2 (Mainen and Sejnowski 1996), gNa = 3,000 mS/cm2 (Mainen and Sejnowski 1996), gK = 200 mS/cm2 (Mainen and Sejnowski 1996), gKL = 0.1 mS/cm2, gNa(p) = 0.07 mS/cm2 (Kay et al. 1998) for axo-somatic compartment and Cm = 0.75 μF/cm2 (Mainen and Sejnowski 1996), gL = 0.033 mS/cm2 (Mainen and Sejnowski 1996), gKL = 0.01 mS/cm2, Sdend = Ssoma r, gCa = 0.022 mS/cm2 (Reuveni et al. 1993), gNa = 1 mS/cm2 (Mainen and Sejnowski 1996), gK(Ca) = 2.5 mS/cm2, gKm = 0.01 mS/cm2 (Gutfreund et al. 1995), gNa(p) = 0.07 mS/cm2 (Kay et al. 1998), gh = 0.01–0.02 mS/cm2 (Alzheimer et al. 1993) for dendritic compartment. gK(Ca) was chosen to prevent membrane potential "lock" in the depolarized state after [K+]o increase. Many of these conductances were systematically varied to find the range for the observed phenomena. INa(p) was not included in IN cells. The resistance between compartments was R = 10 MΩ.
Reversal potentials for all K+-mediated currents were calculated using Nernst equation EK = 26.64 ln ([K+]o/[K+]i), where [K+]o is extra- and [K+]i is intracellular K+ concentrations, EK is reversal potential in millivolts. [K+]i was held constant at 130 mM through most of the simulations. Reversal potentials for Ih and leak currents were calculated as where [Na+]o = 130 mM, [Na+]i = 20 mM, [Cl−]i = 8 mM, [Cl−]o = 130 mM. In some simulations, [K+]i, [Na+]o, and [Na+]i were continuously updated to examine whether they had any effect on the results.
The extracellular K+ concentration was continuously updated based on K+ currents, K+ pumps, K+ buffering simulating the glial K+ uptake system (Kager et al. 2000) and lateral K+ diffusion (2) where F = 96,489 C/mol is the Faraday constant, d = 0.15 μM is the ratio of extracellular volume (per cell compartment) to the surface area, k = 10 is the unit conversion constant for currents, IKΣ (in μA/cm2) in is a sum of all K+ currents including an inward K+ current produced by active K+ pumps (Kager et al. 2000) [K+]o(eq) = 3.5 mM is an equilibrium [K+]o concentration, Imax is the maximal flux generated by the pump (to compensate K+ leak at resting conditions we selected Imax = 5 μA/cm2 for dendritic and Imax = 40 μA/cm2 for somatic compartments), D = 4 10−6 cm2/s is diffusion coefficient [D = 2.5–3.3 10−6 cm2/s was estimated for cat neocortex (Fisher et al. 1976)]. In the model, we assumed that each cell compartment had an associated extracellular volume and [K+]o indicates the average concentration within this volume, [K+]o(+) and [K+]o(−) are K+ concentrations in the adjacent volumes (corresponding to the neighboring cells), [K+]o(sd) is K+ concentrations in the adjacent compartment (soma or dendrites), G is a variable describing the effect of the glial buffering system. In the one-dimensional approximation to diffusion along the x axis, the distance between volume centers was estimated as Δx = 100 μm based on the assumption that one synaptic footprint (10 cells in the model) corresponded to ∼1 mm in the cortex. In most single cell simulations (except Figs. 3E and Fig. 4), the diffusion between somatic and dendritic compartments was set to zero to explore effects of difference in [K+]o between compartments. In the network simulations (Figs. 8–11), the diffusion between compartments was always present and nearly identical levels of [K+]o were maintained in all compartments.
The glial buffering was modeled by first-order kinetics (3) where [B] is a free buffer concentration, [B]max = 500 mM is total buffer, [KB] = [B]max − [B] is K+ bound to the buffer, k1 = 0.0008 and k2 = k1/{1+exp[([K+]o − [K+]o(th))/(−1.15)]} are rate constants, k1N = 1.1, [K+]o(th) = 15 mM for soma and [K+]o(th) = 9 mM for dendritic compartment (Kager et al. 2000). The threshold [K+]o concentrations,[K+]o(th), were systematically varied and final values were chosen to achieve steady state levels of [K+]o for two different modes of behavior: silent and tonic firing (see Fig. 2).
The firing properties of the two compartment model in Eq. 1 depend on the coupling conductance between compartments (g = 1/R, where R is resistance between compartments) and the ratio of dendritic area to axo-somatic area. The ratio, r, controls the firing patterns in the model (Mainen and Sejnowski 1996). We used a model of a regular-spiking neuron for PY cells (r = 165) and a model of a fast spiking neuron for IN cells (r = 50).
Synaptic currents
All synaptic currents were calculated according to (4) where gsyn is the maximal conductivity, [O](t) is the fraction of open channels, Esyn is the reversal potential. EAMPAsyn = 0 mV for AMPA and N-methyl-d-aspartate (NMDA) receptors, EGABAAsyn = −80 mV for GABAA receptors. A simple phenomenological model was used to describe short-term depression of intracortical excitatory connections (Abbott et al. 1997; Galarreta and Hestrin 1998; Timofeev et al. 2000; Tsodyks and Markram 1997). According to this a maximal synaptic conductance was multiplied to depression variable, D ≤ 1, representing the amount of available "synaptic resources" where U = 0.07 is the fraction of resources used per action potential, τ = 700 ms the time constant of recovery of the synaptic resources, Di the value of D immediately before the ith event, and (t − ti) the time after ith event.
GABAA, NMDA, and AMPA synaptic currents were modeled by first-order activation schemes (Destexhe et al. 1994). Dependence on postsynaptic voltage for NMDA receptors was 1/{1+exp[−(Vpost − Vth)/σ]}, where Vth = −25 mV, σ = 12.5 mV (Destexhe et al. 1994; Golomb and Amitai 1997; Traub et al. 1991). The equations for all synaptic currents are given in (Timofeev et al. 2000). The maximal conductances (for each synapse) were gAMPA(PY-PY) = 0.08–0.15 μS, gNMDA(PY-PY) = 0.01 μS, gAMPA(PY-IN) = 0.05 μS, gNMDA(PY-IN) = 0.008 μS, gGABAA(IN-PY) = 0.05 μS.
Network geometry and stimulation
The cortical model consisted of a one-dimensional two-layer array of 100 PY and 25 IN cells. This is the simplest possible network geometry capable of displaying a spatial expansion of the bursting activity initiated in a localized focus. Network models including 300 PY and 74 IN neurons were also tested. Varying the size of the inhibitory population versus excitatory one had minimal effect on the network dynamics: other PY to IN ratios (such as equal number of PY and IN neurons) produced similar network dynamics as long as the total inhibitory drive to a given PY cell was strong enough to compensate for excitatory inputs. In most of the simulations, the connection fan out was ±5 cells for AMPA and NMDA mediated PY-PY synapses; ±1 cell for AMPA and NMDA mediated PY-IN synapses; ±5 cells for GABAA mediated IN-PY synapses. Other radii of synaptic interconnections were used to test the sensitivity of the results. The model geometry is based on assumption that the network size, N, is much larger than the number of neurons, M, within a synaptic footprint. Some of the intrinsic parameters of the neurons in the network were initialized with random variability (Gaussian distribution with σ = 5–10%) to ensure the robustness of the results (Bazhenov et al. 1998). In simulations with external input, all the cells in the network were stimulated by Poisson distributed spike trains with an average rate of 10 Hz.
Neuronal firing associated with seizures
In the six experiments in which an array of microelectrodes was inserted in the neocortex and in which simultaneous intracellular recordings were obtained, we recorded extra- and intracellular activities during >100 seizures. Of these, in three experiments (56 seizures), we observed an increased frequency of spontaneous neuronal firing prior to the seizure and a progressive decrease in the mean firing frequency toward the end of the seizure (Fig. 1). The progressive increase in the neuronal firing prior to seizure was often associated with progressive depolarization of the membrane potential of simultaneously recorded neuron that eventually led to a firing (Fig. 1). The decrease in firing rate during the seizure was related to the presence of prolonged hyperpolarizing, silent periods, which corresponded to the EEG "wave" components of seizures and to a strong depolarization to the level of spike inactivation, associated with paroxysmal depolarizing shifts (PDSs). In the focus of seizure, the high-frequency firing during the PDSs was recorded only in fast-spiking inhibitory interneurons (Timofeev et al. 2002b) and in some fast-rhythmic-bursting neurons (not shown). The increased firing in a large population of neurons recorded at different depths within one cortical column will likely lead to increased [K+]o that should depolarize neighboring neurons due to depolarizing shift in the reversal potential for K+ conductances, thus further increasing their firing and leading to the generation of seizures.
Extracellular K+ concentration in silent and active states
We further investigated seizure generation due to increased [K+]o with computational models, starting with the periodic bursting in a single (isolated) PY cells. Based on these results we then study network dynamics.
In normal conditions, random Poisson-distributed input spike trains applied to an isolated PY cell induced asynchronous firing in the 30- to 40-Hz frequency range. K+ was released into the extracellular space with each spike and was largely taken up by the glial buffering system. The K+ pump also prevented [K+]o from growing. It took ∼50 s to reach steady state, where [K+]o in the soma and dendrites were stabilized at ∼3–3.5 mM and the concentration of somatic buffered K+, [KB], reached 20–25 mM (Fig. 2). When the external input was removed, the cell remained silent. The release of K+ to the extracellular space through K+ leak channels was reduced and the steady-state value of [KB], the potassium bound to the buffer, was much lower (∼10 mM); [K+]o in soma and dendrites were slightly lower than in the active state (see Fig. 2, right).
These results show that the glial buffering system implemented in the model can control [K+]o in different neuron states. Because the total capacity of the K+ buffer was set to have a concentration of 500 mM, it would require a significantly higher frequency of firing before the buffer was saturated.
Effect of external stimulation on extracellular K+ concentration
When a long (10 s) DC pulse was applied to the cell, it fired at high frequency and led to a gradual increase in [K+]o (Fig. 3). [KB] reached ∼80 mM. After the DC stimulus was removed, the cell did not stop firing immediately but displayed 2.5- to 3.5-Hz oscillations lasting ∼10 s, followed by a shorter (∼5 s) period of 10- to 15-Hz activity and then by silence. Both [KB] and [K+]o decayed during the oscillatory state. This decay was mainly due to the K+ pump: when the K+ pump was blocked just before removing the DC pulse, [K+]o kept growing and the oscillations never stopped (not shown). Reducing the DC pulse amplitude reduced the frequency of firing, the [K+]o was less elevated at the end of stimulation and the duration of the bursting phase was reduced. The minimal frequency of stimulus-induced firing to produce periodic bursting was ∼65 Hz. For lower frequencies of firing (induced by stimulations of lower amplitude), the glial buffering and K+ pump were sufficient to restrict the [K+]o increase and prevent oscillations. Note, however, that in this single-cell model [K+]o increased faster during cell firing than it would normally in cortex because K+ was confined to the region surrounding a neuron and could not diffuse away.
During the initial phase of oscillations, each burst started with a few Na+ spikes followed by spike inactivation and a depolarizing plateau that lasted 50–100 ms (see Fig. 3A, left). Activation of the high-threshold Ca2+ channels increased the intracellular Ca2+ concentration and increased IK(Ca), which eventually triggered a switch to the hyperpolarized state (Fig. 3B, top). During elevated [K+]o, the reversal potentials for all K+ currents [including Ih (Spain et al. 1987)] were depolarized (Fig. 3A, bottom). The slow membrane potential depolarization after the burst termination eventually activated the persistent sodium current (Fig. 3B, bottom) and led to a new burst. The frequency of bursting was determined by Ih and IK(Ca), which were the only two currents active during hyperpolarized state (Fig. 3B). Such bursting with spike inactivation is frequently observed during 2- to 3-Hz SW seizures (Neckelmann et al. 1998; Steriade and Contreras 1995, 1998; Steriade et al. 1998a; Timofeev et al. 1998). When [K+]o was partially reduced 5–6 s later, the high-frequency bursts occurred without spike inactivation and the frequency of bursting was increased to 3–4 Hz (see Fig. 3A, right). During the last phase of oscillation, the bursting was replaced by single spikes or spike doublets occurred at 10–15 Hz. This later form of oscillation resembled "fast-runs" recorded during spike-wave seizures (Steriade et al. 1998a). The transition from low-frequency bursting with many spikes per burst to fast bursting with only few spikes was a result of progressive decrease of [K+]o. In the next section, we will show that changing [K+]o from 4 to 5 mM leads to a sequence of bifurcations when the spikes count per burst progressively changes (see Fig. 4).
To determine whether simultaneous depolarization of the K+ reversal potentials in the soma and dendrites was required for oscillations, [K+]o was held constant during stimulation either around the dendritic compartment (Fig. 3B, left) or around the soma (Fig. 3B, right). In both cases the slow 2- to 3-Hz paroxysmal oscillations were not observed. Brief (∼2 s duration) 10-Hz activity occurred in the latter case. This suggests that although elevation of [K+]o in soma and dendrites can affect different conductances, both phenomena are required to initiate and maintain slow periodic oscillations (see following text). We also tested whether the difference in [K+]o between soma and dendrites is critical for the results presented here. Figure 3E presents results of simulations identical to Fig. 3A except that K+ diffusion between dendrites and soma was included. It provided nearly identical levels of [K+]o between compartments (see Fig. 3E, bottom) but results (neuron response patterns) stayed the same except that duration of poststimulus oscillations was increased slightly.
When the same DC stimulus was applied to an isolated IN, periodic oscillation was not found after stimulus termination (Fig. 3D). This is explained by absence of INa(p) and reduced IK(Ca) (gK(Ca) = 0.3 mS/cm2), ICa (gCa = 10 μS/cm2), and Ih (gh = 0.05 mS/cm2) conductances in the IN model. Direct increase of the [K+]o led to IN tonic firing (not shown) but bursting was never observed in this model.
Effect of [K+]o increase on neuron oscillations
To better explore the effect of [K+]o on neuron oscillations, we blocked the subsystem updating [K+]o in the model and then increased [K+]o gradually from its baseline level [K+]o = 3 mM, keeping [K+]o identical around soma and dendrites. Figure 4A shows steady-state voltage for nonoscillatory regime ([K+]o < 4.3 mM) and the maximum and minimal voltage for periodic solutions ([K+]o > 4.3 mM). Figure 4B displays [Ca2+]i versus [K+]o on the secant Vm = 0. The first bifurcation occurs at [K+]o ∼4.3 mM where steady-state regime (Fig. 4C, top left) is replaced by periodic firing (Fig. 4C, top right). Near this point each burst was relatively short and included two to three spikes, which was not sufficient to activate IK(Ca). The inset (Fig. 4B) shows a blow-up of the region where a few bifurcations were found that corresponded to changes in the spike count. In a narrow region 4.85 mM < [K+]o < 4.95 mM long bursts with more than four spikes were observed (Fig. 4C, middle left). Starting from [K+]o ∼4.95 mM, periodic bursting was followed by spike inactivation (Fig. 4C, middle right). In Fig. 4B, the last oscillatory mode was characterized by the appearance of the upper branch corresponding to the burst termination after a depolarizing plateau. This regime was observed over a large range of [K+]o; longer intervals of spike inactivation were observed for higher levels of [K+]o (Fig. 4C, bottom left). Finally, when [K+]o exceeded ∼13.5 mM, the membrane potential became permanently locked in the depolarized state (Fig. 4C, bottom right). Projections of the phase space to the plane Vm([Ca2+]i) for some of these regimes are shown in Fig. 4D.
Oscillations induced by K+ injection
To study the relative importance of the [K+]o increase around the soma and dendrites, a fixed amount of K+ was directly injected into the extracellular space during the silent state of the neuron (Fig. 5). Increase of [K+]o alone around the soma was not sufficient to induce oscillations (Fig. 5A). Note that [K+]o at first increased significantly but then rapidly decayed to a lower steady-state level. This decay was due to the K+ glial buffering and occurred simultaneously with increase in [KB]. When [K+]o was elevated both around the soma and dendrites (Fig. 5B), the previously described low-frequency bursting with spike inactivation occurred. Further increase of [K+]o around dendrites led to bursting without spikes inactivation (Fig. 5C) and finally to fast 10- to 15-Hz oscillations (Fig. 5D). When [K+]o was increased around dendrites to the same level as in Fig. 5B but with a less significant increase in soma, only fast 10- to 15-Hz oscillations were observed (Fig. 5E). These results are summarized at Fig. 5F where regions of different behavior are shown. Slow (<4 Hz) bursting with spike inactivation was observed over a wide range of [K+]o including the line [K+]o(soma = [K+]o(dend). Note that the region of bursting without spike inactivation, which was relatively small in the model with identical levels of [K+]o around soma and dendrites (4.3 mM < [K+]o < 4.95 mM; see, Fig. 4), was now extended to much larger values of [K+]o; however, [K+]o(soma) had to be less than [K+]o(dend) for this to occur.
Effects of intrinsic conductances on K+-induced oscillations
High-threshold Ca2+ and persistent Na+ currents were important in creating periodic bursting after a [K+]o increase (Fig. 6). After oscillations were induced by long DC stimulation, as described in the preceding text, a sufficiently high maximal conductances for INa(p) and ICa were required to maintain periodic bursting. On the gCa(gNa(p)) plane (see Fig. 6A, left), the region for bursting was bounded by two curves. Below the bottom curve no oscillations were observed. Above the top curve strong ICa and/or INa(p) induced a transient "lock" of the membrane potential in a depolarized state (spike inactivation). All these regimes are illustrated in Fig. 6C, where the maximal change of [Ca2+]i during a burst duration is plotted for a cell held at a constant elevated level of [K+]o = 5.5 mM (note that Fig. 4B shows [Ca2+]i change as a function of [K+]o). Increase of INa(p) and/or ICa led to bursts with more spikes producing higher [Ca2+]i increase. A transient region B between lower plateau A and upper plateau C in Fig. 6C corresponds to the area between two curves in the Fig. 6A (left) where the number of spikes progressively increases as gCa and/or gNa(p) changes; region C corresponds to long bursts with spike inactivation. Finally, in region D, the membrane potential was permanently "locked" in a depolarized state (see Fig. 4C, bottom right), which occurred for high gNa(p) and relatively low gCa. The latter condition ensured weak IK(Ca) activation. Examples of different firing patterns are shown in Fig. 6B.
The conductance for IK(Ca) significantly affected both the frequency and duration of poststimulus oscillations (Fig. 6A, right). When gK(Ca) was below ∼2 mS/cm2 only fast long-lasting oscillations were observed. For higher conductances 2- to 3-Hz periodic bursting was found. The frequency increased slightly for gK(Ca) >5 mS/cm2, which was primary the result of a reduced burst duration. Stronger IK(Ca) was more effective in terminating the depolarized plateau, so less Ca2+ entered during the depolarized state and repolarization from a hyperpolarized state was also faster.
Among all the currents, Ih was most effective in controlling the frequency of oscillations. Reduction of the gh reduced the frequency to ∼1 Hz and then eliminated bursting (Fig. 6D, left). This is consistent with the importance of Ih in maintaining paroxysmal oscillations as proposed previously (Timofeev et al. 2002a). Increase of the maximal conductances for INa(p) and IKm had the opposite effect on frequency (Fig. 6D, middle and right). Changing maximal conductance for ICa had a relatively weak effect on the frequency, although it had to be above certain limit to maintain bursting. This limit depended on the maximal conductance for INa(p), as shown in the Fig. 6A, left.
Role of K+ pump and glial buffering
Results with single-cell simulations suggest that elevated [K+]o might also be important for network oscillations. When [K+]o was sufficiently elevated, periodic bursting was found, which resembled oscillations observed during SW seizure in vivo. Two different mechanisms—K+ pump and glial buffering—controlled [K+]o in our model. We tested them by separately blocking each system. Figure 7A shows cell activity when glial buffering was blocked. Immediately following the block of the glial buffer (Fig. 7A), the asynchronous firing maintained by random input (see Fig. 2, left) was replaced by periodic ∼2.5-Hz bursting with spike inactivation. [K+]o continued to increase slowly during the oscillatory phase and after ∼15 s the oscillations disappeared with the membrane potential permanently "locked" at a depolarized level. The K+ reversal potential increased to a point that IK(Ca) became ineffective in terminating the depolarized state.
Blocking the K+ pump in a single cell had a less dramatic effect but eventually led to bursting (Fig. 7B). In the presence of random input, this bursting was irregular and occurred in a broad 4- to 20-Hz range. Periods of faster oscillations were interrupted by slower rhythms in the 4- to 7-Hz range. [K+]o was increased both around the dendrites and in the soma; however, [K+]o(soma) was saturated at a noticeably lower level. Based on the diagram shown in Fig. 5F, we expected that the [K+]o(soma) increase was insufficient by itself to induce low-frequency oscillations with spike inactivation. When external input was removed at t = 30 s, the oscillation continued and become more regular (not shown). Later we will show that in a network of PY cells, blocking K+ pump can induce paroxysmal low-frequency bursting.
Stimulus-induced paroxysmal oscillations in the cortical network
To study the properties of [K+]o-dependent oscillations in a population of cortical cells, a two-layer network model including 100 PY cells and 25 inhibitory interneurons (INs) was simulated without lateral diffusion of K+ (Fig. 8A). All cells were identical except that Ih was included only in a small (10%) randomly selected group of PY neurons (Timofeev et al. 2002a). Without random excitatory stimulation the background state was silent. A DC pulse applied to cells 30–50 induced high-frequency firing leading to the elevation of [K+]o. When the DC stimulation was removed after 30 s, the network continued to oscillate at ∼3 Hz. This low-frequency bursting had the same nature as oscillations previously described in an isolated PY cell. Starting ∼10 s after the beginning of stimulation, the neurons outside the region of high [K+]o also displayed periodic bursting. Their activity was mediated by synaptic input from the overexcited region.
When the same simulation was repeated including lateral diffusion of K+ (between PY cells), the results were different (Fig. 8B). Increase of [K+]o within the region of DC stimulation created diffusion of K+ to the neighboring regions, so almost all PY cells in the network oscillated starting from ∼2 s after DC stimulation. One hundred percent of the cells displayed bursting after the stimulus was removed at t = 38 s; these oscillations were well synchronized across population. PY cells inside region of DC stimulation typically showed bursts with spike inactivation. The cells outside this region displayed high-frequency bursts without spike inactivation (see Fig, 8B, bottom). Each cycle of poststimulus oscillations was started in a small group of cells (numbers 50–60). These cells were located near the region of DC stimulation where [K+]o was significantly increased; a few of these cells included Ih (these cells were slightly depolarized and could be identified at the graph by darker traces). In contrast to the model without diffusion, the oscillations lasted only ∼15 s after removing DC stimulation. In the model with diffusion, a larger subpopulation of "glial cells" was effectively involved in accommodation of excessive [K+]o; its level progressively reduced both in the soma and dendrites until the oscillations could no longer be sustained (see Fig. 8B, middle). Thus lateral K+ diffusion may reduce the duration of paroxysmal bursting. K+ diffusion between compartments maintained identical levels of [K+]o around soma and dendrites.
Once started the oscillation propagated in both directions with a velocity of ∼300 cells/s. We studied the effect of K+ diffusion on the velocity of burst propagation but could not find any significant velocity changes in a range of D = 0 to D = 1.2 10−5 cm2/s. Lateral K+ diffusion promoted bursting by depolarizing neurons located outside the area of direct stimulation; however, this had only minimal effect of the burst velocity. Parameters controlling burst velocity in the model were maximal conductances for excitatory and inhibitory synapses. In agreement with previous works, an increase of lateral excitation between PY neurons increased velocity while increase of inhibitory feedback through IN slowed down propagation (see, e.g., Bazhenov et al. 2002; Compte et al. 2003; Golomb and Ermentrout 2001) .
To test effect of NMDA currents, we repeated simulations without NMDA conductances. In all cases, after blocking NMDA currents network bursting persisted with only minor changes in shape or duration as long as [K+]o was elevated to the same level. Because the presence on NMDA receptors increased the frequency of firing during high-frequency stimulations, longer stimulation times were required to reach the same level of [K+]o. Thus to obtain (after NMDA blocking), a response identical to the one shown in the Fig. 8, the duration of DC stimulation had to be increased from 20 to 40 s.
We compared responses found in the 100-PY-25-IN cell network with the larger networks and networks with different synaptic footprints. Our simulations show that doubling or halving the number of neurons in our model network while keeping the same number of synaptic neighbors did not change results. Effect of the footprint change in shown in the Fig. 8C presenting results of 300-PY-75-IN network simulations. In those cells (numbers 160–220) where external stimulation was applied, the oscillations were determined primarily by their intrinsic properties and by the level of [K+]o and therefore were identical to activity in the equivalent group of cells in the smaller network (Fig. 8B). Neurons in the rest of the network were driven by synaptic inputs and K+ diffusion; all neurons in the network became involved in periodic bursting which continued for ∼10 s after stimulus termination.
Effect of inhibition on network oscillations
In the simulations shown in Fig. 9, random network activity was induced by Poisson-distributed spike trains delivered to all PY cells as in the experiments with isolated PY neuron. To compensate for the external stimulation, the strength of synaptic coupling between PY neurons was reduced from 0.15 to 0.115 μS. In control conditions, the network displayed random firing with the level of [K+]o oscillating around 3 mM, which was identical outside the soma and dendrites (see Fig. 9A). When all GABAergic synapses were blocked at t = 5 s, increase of firing in many PY neurons led to the gradual increase of [K+]o (Fig. 9B). After ∼20 s, the system started to display spontaneous bursting at progressively increasing frequency, which stabilized at 2–3 Hz after ∼45 s. The periodic bursting was typically initiated in a group of cells with Ih (cells 55–60).
We also tested networks where inhibition was removed in only a small group of neurons (cells 30–50). In simulations with lateral PY-PY diffusion, localized disinhibition produced no noticeable effect (data not shown). Excessive firing in a small group of PY cells increased K+ concentration in adjacent extracellular space; however, most of K+ ions then diffused away so the total increase in [K+]o was not sufficient to induce paroxysmal oscillations. This suggests that diffusion can control the "normal" level of network activity.
Effect of K+ pump on network oscillations
K+ pumps were blocked at t = 5 s in a group of cells (numbers 30–50) in the network (Fig. 10). Initially random firing that was maintained by random excitatory input as described in the previous section. Elevation of [K+]o after pump blocking progressively depolarized PY neurons thus increasing their frequency of firing, which led to the release of additional K+ into the extracellular space. Starting at about t = 12 s, many cells in the network showed bursting, which continued even after random external input was removed at t = 50 s. Under these conditions, the neurons were locally synchronized similar to that observed after DC stimulation in the model with lateral diffusion (Fig. 8B). During first 15–20 s after K+ pumps were blocked in a group of cells, only neurons inside and near this group displayed oscillations. The size of bursting cluster of neurons increased progressively and a whole network started oscillating after ∼25 s after K+ pumps blocking.
Effect of glial buffering on network oscillations
When glial buffering was blocked in a group of cells (numbers 30–50) from the same network as studies in the preceding text, slow 2-Hz bursting with spike inactivation immediately started (Fig. 11A). Without lateral K+ diffusion, this bursting in a group of cells did not have significant effect on the rest of the PY population (see Fig. 11A). As [K+]o increased, the frequency of oscillations also increased, and ∼15 s later the oscillations stopped with the PY cells' membrane potential permanently "locked" into the depolarized state. When random external stimulation was removed at t =50 s, all the cells became silent.
Including lateral PY-PY K+ diffusion to the model dramatically changed the firing patterns of all neurons (Fig. 11B). The flow of K+ out of the region where glial buffering was blocked prevented permanent depolarization, so the cells kept oscillating at ∼3 Hz. It also increased [K+]o in the surrounding region; the cells there fired at a higher frequency and eventually started to burst (see Fig. 11B). This bursting continued after removing external stimulation at t = 50 s. Similar to the results discussed in the previous sections, the bursts started in the middle of the network in the region where a few closely located PY neurons with Ih were found. Figure 11 also illustrates the [K+]o dynamics near two different PY cells, one belonging to the region where glial buffering was blocked (cell 35) and another outside this region (cell 0). In the first cell, [K+]o increased immediately after removal of the glial buffering. In the remote neuron, [K+]o increase was much more gradual and the K+ concentration stabilized at lower level.
In vivo recordings from intact cat neocortex and cortical slab preparations suggest a cortical origin for SW and PSW electrographic seizures (Neckelmann et al. 1998; Steriade and Contreras 1995, 1998; Steriade et al. 1998a; Timofeev et al. 1998). These studies showed that although thalamic reticular GABAergic neurons faithfully display spike-burst after each synchronous firing of cortical neurons (EEG "spike"), target thalamocortical neurons are hyperpolarized during seizure episodes with SW/PSW complexes and cannot fire paroxysmal bursting. Sufficiency of intracortical mechanisms for generating paroxysmal activity is also supported by data from cortical slice preparations (Gutnick et al. 1982; Schwartzkroin and Prince 1978).
Different protocols are known to induce paroxysmal activity in vivo, including electrical stimulation and bicuculline infusion (Neckelmann et al. 1998; Steriade and Contreras 1998; Steriade et al. 1998b; Timofeev et al. 1998). These all lead to the excessive firing in large cell populations that can affect the extracellular K+ concentration. In vivo paroxysmal activity is frequently observed in acute (Topolnik et al. 2003) and chronic (Echlin and Battista 1963; Grafstein and Sastry 1957; Sharpless and Halpern 1962) cortical slab preparations. Although pathological development of paroxysmal activities in chronic slabs is likely to be due to homeostatic plasticity mechanisms (Turrigiano 1999), the increased likelihood of spontaneous seizures in acute preparations may be a partial result of [K+]o increase after cells damage.
In this study, we tested the hypothesis that a combination of intrinsic conductances and elevated [K+]o can be sufficient to initiate 2- to 3-Hz SW/PSW oscillations. Increased [K+]o may occur due to spontaneous increase in local neuronal firing (see Fig. 1). In the model, the extracellular K+ concentration was continuously computed based on K+ currents and K+ pumps; extracellular K+ also depended on glial buffering. Increase in [K+]o affected the reversal potentials for K+-mediated currents, such as IKm, IK(Ca), IK(leak), and Ih. Previously we showed with a simplified model of the cortical network that K+-dependent enhancement of Ih, including Ih reversal potential depolarization and increase of the maximal conductance (Spain et al. 1987), is sufficient to produce 2- to 3-Hz bursting (Timofeev et al. 2002a). Here the elevation of [K+]o was modeled with different protocols, including intensive stimulation leading to high-frequency firing, direct K+ injection to the extracellular space, blocking the K+ pump, and blocking the glial buffering system. In a single PY neuron when [K]o increased sufficiently, slow 2- to 3-Hz bursting was often accompanied by spike inactivation. Typically, after one to two spikes the cell membrane potential became "locked" into the depolarized state maintained by the effects of INa and IK. An increase of the intracellular Ca2+ mediated by a high-threshold Ca2+ current eventually increased IK(Ca) to the level where the depolarized state became unstable and the membrane potential rapidly hyperpolarized. This hyperpolarization led to Ih activation and slow repolarization to the level where INa(p) became activated and initiated the next burst. The frequency of this bursting depended on many intrinsic conductances, especially gK(Ca) and gh. We also tested the model where both K+ and Na+ ionic concentrations were updated based on the currents flow and Na+/K+ pump and found that [K+]o had a major effect on cell dynamics.
The role of elevated [K+]o in producing synchronized neuronal bursts through the shift of the K+ reversal potential was previously studied in hippocampal slice models (Traub and Dingledine 1990). In Kager et al. (2000), periodic bursting after [K+]o increase was described in a single cell; however, in this model, bursts occurred at very low frequency (1 every 10–15 s) that might be attributed to the lack of IK(Ca). In recordings from granule cells of the dentate gyrus of the hippocampus at different levels of ionic concentrations in vitro, a simultaneous increase in [K+]o and decrease in [Ca2+]o caused cellular bursts to appear at K+/Ca2+ concentrations that were previously recorded in vivo before the onset of synchronized reverberatory seizure activity (Pan and Stringer 1997).
The firing patterns found in our model had close similarities with those observed in vivo. The progressive increase in the firing rate preceding periodic bursting in our model (see, e.g., Figs. 3 and 8–11) was similar to the increase in frequency of spontaneous neuronal firing prior to the seizure found in vivo (see Fig. 1). High-frequency bursting with or without spike inactivation in the different model neurons (see, e.g., Figs. 3 and 8) was also observed in vivo (see e.g., Figs. 1 and 2 in Timofeev et al. 2004). The "lock" of the membrane potential in the depolarized state found in the model for very high levels of [K+]o (Fig. 4C) has also been observed in vivo (see Fig. 2 in Timofeev et al. 2004). Fast 10- to 15-Hz oscillations found in the model for particular region of [K+]o values (see Figs. 3–5), were similar to fast runs in vivo (see e.g., Fig. 2, middle, in Timofeev et al. 2004).
In exploring the effects of different intrinsic currents, we found that a combination of a few conductances such as gCa, gNa(p), gh, and gK(Ca) was sufficient to produce periodic bursting. When maximal conductances for ICa, INa(p), or Ih were reduced below a certain level no bursting occurred after [K+]o elevation. Eliminating IK(Ca) could produce a permanent "lock" of the membrane potential in the depolarized state. The importance of cooperative effects of several conductances for generating spreading depression has been previously shown in a computational study (Kager et al. 2000). In our model, paroxysmal oscillations were obtained without including a low-threshold Ca2+ (T-type) current, which was important in some other modeling studies (Destexhe et al. 2001). Synaptic conductances also were not required. These results are consistent with data from hippocampal slices where increasing neuronal excitability (by removing extracellular Mg2+ and increasing extracellular K+) in the presence of Cd2+, a nonselective Ca2+ channel antagonist, or veratridine, a persistent sodium conductance enhancer, induced spontaneous nonsynaptic epileptiform activity (Bikson et al. 2002). In recordings from rat hippocampal slices with high [K+]o, the local generation of population bursts in CA1 was caused by intrinsically bursting pyramidal cells, which recruit and synchronize other neurons (Jensen and Yaari 1997).
In the network model that included layers of PY cells, IN cells, and lateral K+ diffusion between PY cells, an increase of [K+]o in a small region was generally sufficient to maintain paroxysmal oscillations in the whole network. This local [K+]o increase could be induced by intense stimulation or by disrupting homeostatic [K+]o mechanisms; K+ diffusion increased the excitability of the neighboring cells so the whole network became oscillatory. The cells inside the region of high [K+]o usually oscillated with spike inactivation while remote cells displayed high-frequency bursts. Paroxysmal discharges propagated from the single most active network focus. This focus typically included cells with the highest Ih. The threshold for initiating paroxysmal oscillations was lower in the network model compared with isolated PY cell. AMPA- and NMDA-mediated synaptic currents enhanced oscillations especially in the region surrounding paroxysmal foci where neurons fired high-frequency bursts without spike inactivation. However, NMDA currents were not necessary to maintain network bursting as long as [K+]o was sufficiently elevated. This result is an agreement with data obtained in a companion paper where paroxysmal oscillations were found under ketamine anesthesia that blocks NMDA synaptic transmission (Timofeev et al. 2004). The role of long-range spatial buffering of K+ operated by glia in synchronizing and/or spreading of paroxysmal oscillations has been recently studied in vivo (Amzica et al. 2002).
The level of [K+]o in the model was determined by K+-mediated currents, the K+ pump, and glial buffering. When either the K+ pump or glial buffering failed to perform normally, the [K+]o increase led to paroxysmal bursting. Recent studies of physiological properties of glial cells from acute slices of biopsies from patients operated for intractable mesio-temporal lobe epilepsy indicate that glial K+ buffering could be impaired at the seizure focus, thus contributing to the pathophysiology of seizures (Bordey and Sontheimer 1998). In the model, excessive firing induced by external stimulation could produce K+ outward flow exceeding the capacity of the K+ pump and glial buffering system and could result in periodic bursting. Cell swelling during seizures (Jing et al. 1994; Perez-Pinzon et al. 1995) would restrict interstitial space and further amplify increase of [K+]o. If all the cells in the model displayed bursts with spike inactivation, the lack of spiking reduced the outward flow of K+ and normal level of [K+]o could be restored after a certain period of time, which eventually terminated the oscillations. The oscillations could last longer in a heterogeneous network when bursting with spike inactivation in a small group of cells maintained firing in the neighbor cortical population through synaptic coupling. In return, high-frequency bursts in this surrounding region helped to maintain a high level of [K+]o inside the central focus.
Changes in [K+]o could explain transitions between slow 2- to 3-Hz bursting and fast runs as observed in vivo (Timofeev et al. 1998). In the model, the oscillatory pattern (slow bursting or fast run) depended on the absolute level of [K+]o and also on the relative levels of [K+]o around soma and dendrites (Fig. 5). In particular, slow bursting could be replaced by fast ∼10-Hz oscillations when the level of [K+]o was reduced because of spike inactivation (see e.g., Fig. 3).
Our model suggests that increase of [K+]o can transform random awake-like activity into paroxysmal oscillations reminiscent of electrographic SW/PSW seizures. This model predicts that paroxysmal bursting after [K+]o increase depends on the balance of a few intrinsic conductances, can be generated in the isolated cortical network, and does not rely exclusively on any synaptic conductances. In acute conditions, brain lesions produce an immediate increase in [K+]o from intracellular pools that may trigger paroxysmal activity (Topolnik et al. 2003). Data from patients with severe brain injury indicate that posttraumatic neuronal excitation by excitatory amino acids leads to an increase in [K+]o, probably due to ion channel activation (Reinert et al. 2000). Thus increased risk for early epileptogenesis after brain trauma may be attributed to the increase of [K+]o.
This research was supported by National Institutes of Neurological Disorders and Stroke Grant NS-40522, Human Frontier Science Program and the Canadian Institutes of Health Research (grants MT-3689 and MOP-37862). I. Timofeev is scholar of Fonds de la Recherch en Santé du Québec.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Copyright © 2004 by the American Physiological Society


text:
Tom Joyner Kicks Foxy Brown Off His Cruise, Foxy Responds
Recently, Tom Joyner called out Foxy Brown, saying she had to be kicked off his annual Fantastic Voyage cruise this year.
On Friday, Joyner called out Foxy during his radio stating that he and his staff had to really put in some work to get Foxy to vacate the ship.
"We put Foxy off the cruise. Let's just say she got put off," Joyner said. "You had to really act a fool to get put off."
However upon hearing about Joyner's on-air comments, Foxy made sure to express her feelings of the situation and added that she was going somewhere where she'd be more appreciated—Belize with her "pumpkin" Shyne.

subset: commoncrawl


text:
I leave you this fine evening with a column by Susan Estrich. According to Estrich, if Barack Obama loses to John McCain, then many people who told pollsters that they intended to vote for Obama did not, in fact, intend to vote for Obama. Logically, there are at least two reasons to lie in this way:
1. The liars are racists and don't want the pollsters to know it.
2. The liars are not racists, but are afraid the pollsters will think they are if they say they're not going to vote for Obama.
Estrich doesn't even mention the second reason, which strikes me as far more plausible than the first, given the racially charged atmosphere created by progressives in recent years. Either she's stupid or she's intellectually dishonest, and she's not stupid.


text:
Discussion in 'Android Devices' started by vide infra, Jun 25, 2010.
http://www.aww-kittah-aww.com/up/files/3379/My Documents/evo pic.jpg
for the pictures with frames/effects those come from vignette
Very nice pictures! May I ask what kind of settings you use? I have no clue how the camera settings work, so it would be a big boost to know if you just used auto settings
iso - 100 (when possible never on auto)
Sharpness - -1 (Negative 1)
white balance on auto (or try switching it for the situation, but i almost always leave it auto)
I shoot between 3 and 5 megapixels. 8 is a bigger number but more megapixels does not equal better image quality
flash off unless needed
I dont understand how shooting 3-5 MP is better than 8...
Shooting at higher megapixels without proper lighting can lead to more noise in the pic making a picture appear blurry or less sharp and clear.
Yeah I have to say this camera in certain lighting conditions is just plain amazing!
I just took pictures of magazine articles rich in colors (venues for my upcoming wedding) and WOW ... the clarity and colors are incredible, its literally like your reading the article and looking at the pictures straight out of the magazine ....
Its funny some pictures come out weird looking and others you become speechless, so when everyone out there is comparing the EVO to this phone or that phone i bet given the right conditions and settings the EVO holds its own!
Nice pics. I will try those settings. Mine usually come out grainy or blurry


text:
The airline association has been conducting a campaign to fight President Obama's proposal to decrease the federal deficit by increasing taxes on flights. The campaign, dubbed Stop Air Tax Now, is trying to convince airline passengers to oppose the president's call for an increase in the per-takeoff fee on flights that could run as high as $100.
The president's plan also includes an $7.50 increase in the security taxes on passengers each way of their trips. The suggestions were originally included in the deficit-reduction suggestions he made to the supercommittee, which unsuccessfully attempted to cut $1.2 trillion or more from the federal deficit.
The airline association said the proposals would cost airlines and their passengers up to $3.5 billion.


text:
Stone Kiss Paperback
by Faye Kellerman
'It was the stunned, pale look of bad news'The call is brief. There's been a murder in the family of Lieutenant Decker's half brother, Rabbi Jonathan Levine. Ephraim Lieber, a Hassidic Jew with a catalogue of problems in his past, was found dead in a seedy Manhattan hotel, a single gunshot wound to his head. And his niece, fifteen-year-old Shaynda, is missing.In a desperate bid to track down the missing girl, Decker finds himself in an alien city and a maze of deceit and danger, on a twisted journey that takes him from the darkened slums of New Jersey and the deserted industrial streets of New York, to the hidden meeting places of Hassidic outcasts...
- Format: Paperback
- Pages: 512 pages
- Publisher: Headline Publishing Group
- Publication Date: 01/02/2003
- Category: Crime & mystery
Free Home Delivery
on all orders
Pick up orders
from local bookshops
Showing 1 - 1 of 1 reviews.
Review by mazda502001
This is the 14th in the Decker/Lazarus series and I really enjoyed this one. Having read the whole series I have found some of the series a bit lacking but overall I have enjoyed them. This was one of the better ones.Back Cover Blurb:The call is brief, but to the point. There has been a murder in the family of Lieutenant Decker's half brother, Rabbi Jonathan Levine. His brother-in-law, Ephraim Lieber, a Hassidic Jew and former drug addict, was found naked in a seedy Manhattan hotel, a single gunshot wound to his head. And his niece, fifteen year old Shaynda, is missing.Jonathan pleads with his policeman brother to come to New York to help the family.Reluctantly, Decker agrees, taking his wife, Rina, and their youngest daughter with him for company. But soon after arriving on the East Coast Decker is infuriated to discover that Shaynda's parents have changed their minds about involving him in the case. Faced with a hostile family, a city in which he's a stranger and a local police force mired in international problems, Decker is on his own. Moving from the darkened slums of New Jersey to the deserted industrial streets of New York, he is thrust into a world divided mercilessly into killers and victims.And Decker must decide which he wants to be....
Also by Faye Kellerman | View all


text:
A look at what's ahead for security operations at Los Angeles International Airport after Friday's fatal shooting involving a lone gunman who targeted TSA agents. Toni Guinyard reports for the NBC4 News at Noon.
Published at 1:00 PM PST on Nov 4, 2013 | Updated at 2:00 PM PST on Nov 4, 2013


text: I love puzzles! It's one of my favorite ways to spend time with my family during the colder seasons. :o) Look at the cool feature I found at Jigzone! You can upload your photos and turn them into online puzzles. It even has an option to send them as a postcard. Enjoy! :o)


text: Lawns are growing well this time of year, back to weekly cutting. Our questions is how long after a lawn is reseeded can you mow it. A lot of our customers are having their lawns reseeded now and we are not sure how long to wait before mowing again. It does create a problem to wait too long as then it is extremely high. Would appreciate any advice as to how long to wait after the reseeding. Thanks


text:
We recommend upgrading to the latest Internet Explorer, Google Chrome, or Firefox.
If you are using IE 9 or later, make sure you turn off "Compatibility View".
Handpicked brands for you
What a weekend! Special thanks to our northwest partners for making programs happen despite the low snowfall! So many happy faces. @mtbachelor @mthoodmeadows @skibluewood @missionridge


text:
Why the Atlanta Braves Should Trade for Justin UptonDecember 3, 2012
Why the Atlanta Braves Should Trade for Justin Upton
After signing BJ Upton last week, attention now turns to his brother. Justin Upton has been on the trade block for a few months, and now that his brother plays for the Atlanta Braves there are going to be rumors that the Braves could be trying to acquire him as well.
This article takes a look at a couple reasons why the Braves need to go out and get a deal for Justin Upton done at the winter meetings.
A Huge Hole
The addition of BJ Upton fills one of the two holes in the Braves' lineup; the other is either in left field or third base depending on where Fredi Gonzalez decides to play Martin Prado in 2013, but either way there aren't any good in-house options.
If the Braves wanted to look from within at third base they would really only have slugging reserve Juan Francisco, who is very strikeout prone and is below-average defensively. If the Braves went from within in left field, the top options are the light-hitting duo of Jose Constanza and Jordan Schafer, unless they re-sign platoon outfielder Reed Johnson.
Either of these options would leave a huge hole in the lineup, and with a team like the Washington Nationals in the NL East, the Braves need to put the best possible team on the field.
Available Money
The Braves had an estimated $12 million available for their 2013 payroll after signing BJ Upton, which would do a good job of covering Justin Upton's contract. Upton has a very team-friendly contract which will give him less than $10 million this season and $28.5 million over the following two seasons.
Atlanta also saves a few million dollars in arbitration after dealing Tommy Hanson to the Angels for Jordan Walden. While the move may not have been entirely about cost, the savings were a major benefit.
Trade Pieces
The Braves have the pieces to make a trade for Justin Upton happen. To start a deal the Diamondbacks could be looking for a shortstop in return, and although the Braves aren't likely to deal Andrelton Simmons they also have Nick Ahmed as a trade piece in the minors.
The Diamondbacks have also been rumored to be looking for a top-tier arm, and the Braves would have top prospects Julio Teheran and Randall Delgado available. They could also potentially deal a younger pitcher like Kris Medlen, though the front office may not want to deal a guy who has drawn comparisons to Greg Maddux.
The Braves also have a deep crop of relievers to deal from. In addition to Craig Kimbrel and recent acquisition Jordan Walden, the Braves have top setup men Jonny Venters and Eric O'Flaherty. This doesn't even mention 2012 rookie Luis Avilan, who had plenty of success in his debut.
Upton Is Elite
Perhaps the biggest reason why the Braves need to go out and trade for Justin Upton is the fact that the younger Upton brother has established himself among the top outfielders in the game. It may be hard to believe since he has been around for a few years, but Upton will be playing the bulk of the 2013 season at the age of 25.
Justin Upton is the type of player that could compete for MVP Awards every year. In 2011 at the age of 23, he finished fourth in voting as he hit .289 with 39 doubles, 31 homers, 88 RBI and 21 steals. That monster season helped lead his team to a playoff berth and earned him his second career All-Star selection.
Justin Upton is not yet in his prime, and he should only continue to improve upon his numbers as he gets closer to that stage of his career. Sure he struggled a bit in 2012, but he was slowed down by a thumb injury and still managed to hit .280 with 17 homers.


text:
Rep. Ehrlich Still Deciding on a Race
By Daniel LeDuc, Robert E. Pierre and Charles Babington
A flurry of stories the last couple of weeks that said U.S. Sen. Paul S. Sarbanes (D-Md.) probably will be running for a fifth term in 2000 quoted sources close to Ehrlich--who represents parts of Baltimore and Harford counties--as saying Sarbanes is "impossible" to beat.
The young Republican is intensely ambitious and has said himself that his party took a drubbing in Maryland in November. But his political director, Paul Schurick, insisted this week that Ehrlich has not made a decision about challenging Sarbanes.
"We have not decided not to run," he said. Under the right conditions, "we could be in that race tomorrow." For now the right conditions mean telling potential donors that the future is wide open.
Ehrlich is hoping to raise $500,000 at a March 22 fund-raiser, to be held at the Marriott Hotel at Baltimore-Washington International Airport--a spot, Schurick pointed out, that is not in his congressional district, the 2nd District. "The purpose is to keep that option [of challenging Sarbanes] and other options alive," Schurick said. "We're going to run for something in 2000" even if it's only reelection to the House.
In the meantime, Ehrlich is continuing the rubber chicken circuit from Montgomery County to the Eastern Shore--all places, like his fund-raiser, outside the 2nd District.
Valderrama Has Not Had Enough
For the second time in months, President Clinton's troubles have seeped into Maryland politics.
This summer, Gov. Parris N. Glendening (D) caused a stir when he chastised the president for his relationship with a White House intern and then refused to appear with the president. Glendening switched gears a short time later, realizing that many of his constituents--especially African Americans--were not pleased with his decision. That furor has died down, but Del. David M. Valderrama (D-Prince George's) doesn't think enough has been said about the president's impeachment.
Valderrama has asked his colleagues in the Maryland General Assembly to adopt a proposed resolution urging the U.S. Senate to consider a "dismissal" or "censure" option. He also has written the National Conference of State Legislatures to disseminate copies of the resolution to all state legislatures and the District.
"People from all walks of life, from Reverend Jesse Jackson to Jay Leno, have weighed in on the national debate generated by the impeachment trial of the president," Valderrama said in a news release. "All politics being local, state legislators should jump into the fray before it's too late."
By the end of this week, it may be a moot point.
Stadiums Need More Support
For years, supporters of Baltimore's publicly financed baseball and football stadiums have argued that Marylanders voluntarily paid for the structures by buying lottery tickets dedicated specifically for the Stadium Authority.
No longer. The Maryland Lottery now says that sales of the sports-related games have sagged so much that it needs permission to use proceeds from other lottery games to pay for the stadiums for baseball's Orioles and football's Ravens. Sen. Thomas L. Bromwell (D-Baltimore County), chairman of the Senate Finance Committee, has obliged the agency by introducing a bill to that effect.
The measure, Senate Bill 104, is scheduled for a hearing in his committee today.
Critics of the publicly financed stadiums are finding little comfort in saying "I told you so." They had argued throughout the 1990s that state-paid arenas weren't widely popular. Powerful political leaders--primarily Glendening and his predecessor, William Donald Schaefer, both Democrats--championed the financing plans, always contending that no Marylanders would have to pay for the stadiums against their will.
It began in 1987, when Schaefer and other stadium supporters struggled to find politically acceptable means of financing a new home for the Orioles and a new football arena in hopes of attracting a team to replace the departed Colts. They settled on a plan to designate the profits from some games of the well-established state lottery system for the newly created Stadium Authority.
The games, primarily instant scratch-off tickets, were to be clearly marked for the Stadium Authority. They also were to have sports-related themes.
The funding plan worked for a while, but it's insufficient now that the lottery must generate $32 million this year for the Stadium Authority.
"Sports tickets are generally our poorest selling scratch-offs," Lottery Director Buddy Roogow told Finance Committee members last month, according to the Annapolis Capital. "People don't like them."
Over the years, he said, lottery officials have struggled to think of new ideas for sports-related games. "We have cows playing tennis," Roogow said.
Under Bromwell's proposal, which legislators say is likely to be enacted, Roogow's agency will be free to use proceeds from any lottery games to fulfill its obligations to the Stadium Authority. Critics say it amounts to a governmental bait-and-switch, but it's too late to do anything about it, now that both stadiums are built.
"The Stadium Authority said this was going to be funded through a special sports lottery and it would rise or fall based on whether there was enough support from the public," said Sen. Christopher Van Hollen Jr. (D-Montgomery), who opposed the 1996 financing plan for the Ravens stadium. "Well, the public has spoken."
The proposed lottery plan isn't as offensive, Van Hollen said, as the state's decision to let Ravens owner Art Modell sell the stadium's naming rights to PSINet for about $10 million over 20 years.
He and other legislators tried to outlaw such an arrangement in the 1996 General Assembly, but stadium supporters insisted on keeping the option open.
Columbia Pollster Reorganizing
Mason-Dixon Political/Media Research, the Columbia-based pollster for many media organizations across the country, is undergoing a reorganization that has seen most of its employees leave.
President Brad Coker said, "I'm changing personnel" as he takes the business in a "change in direction."
He said the company is still in business but that a sister company, Mason-Dixon Campaign Polling & Strategy Inc., has folded. That company advised candidates and campaigns.
Two former Mason-Dixonites are now out on their own. Patrick E. Gonzales and Carol A. Arscott have formed Gonzales-Arscott Research & Communications Inc.
They're seeking clients and plan to provide consulting help to businesses, associations and educational institutions with interests in public policy. They'll also pursue campaign work during election years, Arscott said.
Arscott is the former chairman of the Howard County Republican Party. Gonzales is a Democrat who has advised Anne Arundel County Executive Janet S. Owens (D).
© Copyright 1999 The Washington Post Company


text:
Shopping Cart $0.00 (0 Items)
Cart Summary
- There was an error
- It was successful
- retailerId
- 1f939b58
- view
- productId
- prod71905
- category
- Knives & Tools > Axes, Saws & Shears > Pack Axes
Gerber Axe Combos
$39.99 - $46.99
Gerber Axe Combos - Axes have been around for ages. And even our award-winning axes are hardly new. But the Gator Axe is a wood-bustin' breakthrough.
You must be 18 or older to purchase ammunition and other restricted items. For safety reasons, many of these items cannot be returned and may only be shipped via ground to the 48 contiguous states. If purchasing ammunition, ensure you use the correct caliber and/or gauge in your firearm. Many states and/or municipalities have certain restrictions in place which may prevent shipment/ordering of various items. Check your local laws and regulations before ordering.
Gerber Axe Combos - Axes have been around for ages. And even our award-winning axes are hardly new. But the Gator Axe is a wood-bustin' breakthrough. Because we applied our proprietary Gator textured rubber to the grip for an unprecedented level of comfort and control. Beneath that tactile rubber surface is a virtually indestructible glass-filled nylon handle. And inside that handle is a hollow area containing a magnet that can hold a knife or saw. The axe head is engineered from forged steel, which does an outstanding job of keeping its edge.
- Forged steel head
- Gator grip handle
- Glass-filled nylon handle
Reviewed by 1 customer
Have used this many times to set up tree stands. Great use of axe and the saw is very handy. resharpens very quickly
- headerText
- Others Who Bought This Item Also Viewed
- numRecs
- 3
- -inc-price
- true
- -rec-builder
- My_Custom_Builder
- dataItems
- listPrice
- salePrice
Customer Support
We are here to help if you need us, please contact Customer Support at:


text:
Dallas, TX (PressExposure) April 29, 2013 -- The "Endoscopy Devices Market by Product, Application & Technology (2011- 2016)" analyzes and studies the major market drivers, restraints, and opportunities in Americas, Europe, Asia, Japan and Rest of the World.
Browse market data tables and in-depth TOC of "Global Endoscopy Market by Product, Application & Technology (2011- 2016)".
Early buyers will receive 10% customization on reports.
This report studies "the Global Endoscopy Market By Application, Product & Technology over the forecast period 2011-2016".
The global healthcare industry has seen a shift in paradigm and is now skewed toward less-invasive therapies that not only cures serious illnesses, but also have fewer serious side effects. Demand for endoscopy has increased manifolds over the past decade owing to patient preference for minimally invasive surgeries.
The global endoscopy market was valued at $6.1 billion in the year 2011 and is expected to be $9.7 billion in the year 2016. North America was the largest endoscopy market, followed by Europe and Japan (2011). In the next five years, Asian countries are slated to register a maximum CAGR of 14.42% owing to increased healthcare spending by the government, healthcare reforms and increased patient awareness about minimally invasive surgeries (MIS).
Global endoscopy market is broadly segmented into the following product categories; rigid endoscopes, flexible endoscopes, endoscopy visualization systems, endoscopic ultrasounds, endoscopy fluid management systems, and endoscope accessories. Introduction of new, but expensive technologies such as HD cameras, 3DHD systems, HDTV three-chip systems, Narrow Band Imaging, Capsule Endoscopy, Natural Orifice Transluminal Endoscopic Surgery (NOTES), Picture Archiving and Communication Systems (PACS), Mucosal Ablation Therapy, Robotic Endoscopes etc. are expected to drive the global endoscopy market for the coming five years.
The global endoscopy market witnesses high competitive intensity as there are many big as well small firms with similar product offerings. The market is dominated by Olympus Corporation with 70% market share, in 2011. Hoya Corporation (Pentax Medical System), Fujifilm Holding Corporation, Karl Storz, Boston Scientific, Stryker, Richard Wolf, Smith and Nephew Inc., Johnson and Johnson-Ethicon Endo Surgery (EES), Given Imaging Ltd., ConMed etc. are some of the prominent players in the global endoscopy market.


text:
We've run, jumped, and stomped all over the world of Super Mario, but, where in the universe is Super Mario EXACTLY? It's virtual so it obviously DOESN'T exist but if it did, could Super Mario world be in our solar system? And what do the planet's dynamics reveal about Mario's crazy jumping ability?
© 2017 PBS & WGBH Educational Foundation. All rights reserved.
You must be logged in to use this featureLog In Enter Code Need an account?


text:
Filter by Activity:
Filter by Activity:
The Black Diamond Experience
Welcome to the Black Diamond Experience, an organic presentation of inspirational stories, photos and videos from our athletes, employees and partners. The Black Diamond Experience is where we showcase climbing, skiing and hiking adventures from around the world, plus event news, advocacy efforts and product and technology highlights—all in one dynamic smorgasbord of stoke. Enjoy.
Luka Kranjc: Memories of The Memory—Climbing Croatia's New 5
BD Ambassador and Slovenian badass Luka Kranjc remembers an old friend during the first free ascent of Croatia's nails-hard multi-pitch.Read Full Story »
The Exum Files—Part 1: The Extended Column Test
In the first installment of the Exum Files, Senior Exum Guide Bill Anderson discusses how extended column test results affect in-the-field choices.Read Full Story »
Wasatch Classics: Noah Howell on The South Ridge of Superior
BD Athlete Noah Howell gives the low-down on his favorite mountain ridge scramble—the iconic South Ridge of Superior.Read Full Story »
Rolo Hemetzberger: Sending WOGÜ—Europe's Hardest Multi-Pitch
With a little motivation from Grandma, BD Athlete and employee Rolo Hemetzberger was able to send Europe's hardest multi-pitch. This is his story.Read Full Story »
BD Athlete Joe Grant searches for rhythm while running in the heart of the Alps.Read Full Story »
Nalle Hukkataival: Squamish Sending Spree
BD Athlete Nalle Hukkataival recently touched down in Squamish, B.C. to sample the goods. As usual, he left a slew of cutting-edge ascents in his wake. Check out this video documenting two of his hardest sends, including the coveted second ascent of the Singularity (V14/15).Read Full Story »
Joe Grant's Trailhead Tunes
BD Athlete Joe Grant shares the songs he listens to while driving to the trailhead.Read Full Story »
Gear Myths: Gates In, Or Gates Out?
In the first installment of Gear Myths, we examine the age-old question: Should you rack gates in, or gates out?Read Full Story »
Hang Right—Part 3: Healing Nagging Finger Injuries
The hangboard is often thought of as an apparatus that can strain the tendons in your fingers. But in this installment of the Hang Right series, Physical Therapist Esther Smith explains how the hangboard is actually the perfect rehabilitation tool to heal nagging finger injuries.Read Full Story »
Chris Schulte: FA's Off the Beaten Path In Switzerland
Watch BD Ambassador Chris Schulte establish beautiful lines in the less traveled reaches of Switzerland.Read Full Story »
Colette McInerney's Training Playlist
BD Athlete Colette McInerney shares the tracks that get her amped for training.Read Full Story »
Daila Ojeda: Into the Alpine to Send Digital Crack
After pushing her boundaries last spring and climbing her first multi-pitch, BD Athlete Daila Ojeda decided that she wanted to experience the mountains of Chamonix. Check out this film of Daila climbing the classic Digital Crack—a beautiful 8a at 12,500 feet in the Alps.Read Full Story »
Nalle Hukkataival: The Finnish Line (V16)—Rocklands' Hardest
This summer, BD Athlete Nalle Hukkataival journeyed to South Africa's famed Rocklands in search of first ascents. What he found was a problem every boulderer dreams of …Read Full Story »
Watch Carlo Traversi Take On The Triple 14 Challenge
In the late summer of 2016, BD Athlete Carlo Traversi set out to climb a V14, 5.14, and 14er … all in a day. Luckily, the experience was documented in this exclusive BD film.Read Full Story »
Joe Grant's Short Shorts: The True Hard Roch
In the first of his quarterly column, BD Athlete Joe Grant reflects on a true unsung hero of the Hardrock 100—Black Diamond's very own Roch Horton.Read Full Story »
QC Lab: Old vs. New Gear Testing
KP and the QC Lab crew answer four consumer questions about the strength of old, new, and old-new (yeah that's a thing) gear.Read Full Story »
Mason Earle: Battling the Cobra—King of The Cracks
BD Ambassador Mason Earle had come as close as you can get to sending the famed Cobra Crack, but sealing the deal had eluded him. This summer, however, the crack-master returned with a vengeance.Read Full Story »
Babsi and Jacopo's Epic Send of Zodiac (5.13d) on El Cap
Check out this film documenting Babsi Zangerl and Jacopo Larcher's historic third free ascent of El Cap's formidable Zodiac (5.13d).Read Full Story »
Tim Kemple: A Towering Obsession
BD Ambassador Tim Kemple takes us on a photographic journey to his top 5 summits around the globe.Read Full Story »
Team BD Sends It in Wales
BD athletes Babsi Zangerl, Jacopo Larcher and Roland Hemetzberger recently journeyed to the mythical sea cliffs of Wales to test their mettle (and metal) on the area's stout trad lines.Read Full Story »
Alex Honnold's Freerider Hangboard Workout
BD Athlete Alex Honnold dives into his training routine and why hangboarding was crucial for soloing El Cap.Read Full Story »
The Brazil Project
Last December, four BD Athletes traveled to Brazil, where they combined forces with Centro Urbana Escalada to help local kids in need by taking them climbing.Read Full Story »
Watch Joe Kinder Send Bone Tomahawk
Check out this film documenting the first ascent of BD Athlete Joe Kinder's hardest route—Bone Tomahawk.Read Full Story »
Mental Training: Skills For A Stronger Mind
BD Athlete Hazel Findlay shares her top 11 tips for building a stronger mindset at the crag.Read Full Story »
Adam Ondra and Patxi Usobiaga Attempt The Project
A very fun, inspiring and hectic weekend with two of climbing's true legends, Adam Ondra and Patxi Usobiaga, is over. That's four workshops, two slideshows, one morning show and five live streamed attempts on The Project squeezed into 35 hours.Read Full Story »
QC Lab Playlist
Pushing gear to the ultimate breaking point requires a rocking soundtrack.Read Full Story »
Watch Nalle Hukkataival Send Burden of Dreams (V17)
BD Athlete Nalle Hukkataival established Burden of Dreams (V17) after seven seasons of attempts. Luckily, the process was documented in this great new feature film, The Lappnor Project.Read Full Story »
Andrew McLean: Skiing Through Kashmir
BD Ambassador Andrew McLean finds a Shangri-La of powder in South Asia.Read Full Story »
Joe Kinder's BD Stoke Playlist
BD Athlete Joe Kinder shares the jams that get him to go a muerte on the rock.Read Full Story »
BD Athletes Tear It Up In Spain
The BD crew has been ripping it up in Spain recently, and fellow teammate Joe Kinder dropped in to document the action.Read Full Story »
Colette McInerney: Finding Like-Minded Souls at the Women's
BD Athlete Colette McInerney shares her photos and experience from the second annual Women's Climbing Festival.Read Full Story »
Alex Honnold's Moonlight Buttress Playlist
In 2008, BD Athlete Alex Honnold free soloed the iconic, 9-pitch Moonlight Buttress (V 5.12+) in Zion National Park. Honnold danced up the crack climb in 83 minutes while rocking his top tunes on his ipod. We've recreated Honnold's Moonlight playlist here. So boot up and press play!Read Full Story »
The Turns I Earned: Noah Howell and the Line He'll Never For
BD Athlete Noah Howell remembers the backcountry ski run that stands out among the rest.Read Full Story »
Daila Ojeda: Her First Multi-Pitch Experience
Daila Ojeda has travelled the world for sport climbing Yet, until recently, she had never been more than two pitches off the ground … until she journeyed to Montserrat, Spain.Read Full Story »
Will Gadd: Adventures at the Michigan Ice Fest
When BD Athlete Will Gadd says there's more high quality, natural ice in Michigan's wild Upper Peninsula than any other state he's ever visited … it's time to take notice.Read Full Story »


text:
Detalii loc de munca - London
Descrierea jobului - U.K.
Must be responsible for keeping guest rooms clean. - Responsible for providing clean linen and bedding, vacuuming and removing trash. - In addition to cleaning, provide extra linen by request. - Thorough cleaning after guests have checked out of the hotel. - Run errands, such as taking laundry to the cleaners. - Must be reliable and in good health.
Housekeepers have a formal education, at least a high school education. If desire or has expectations of becoming a supervisor, must posses a college degree. International Executive Housekeepers Association certification is an asset.


text:
Mumbai, May 4: Buyers returned to stock exchanges today, snapping one of the longest losing streaks on projections of robust gains for the ruling coalition in areas ready to cast the die in the final poll rounds.
The forecasts perked up Dalal Street, which has been plagued by poll pangs since the first round of exit polls suggested the NDA numbers would fall short of a majority.
The BSE sensex closed at 5647.15 in a leap of 62 points, or 1.11 per cent, after opening at 5616.41 and scaling a high of 5677.11. Mondays losses were wiped out.
Opinion and exit polls released after the earlier rounds of polls had spooked markets by showing the BJP-led alliance would find it difficult to secure a good lead.
Public sector companies and banks, clobbered by fears of divestment stalling and reforms slowing, were among the best performers on the trading floor this afternoon.
The return of the NDA government is seen as the best bet for the strategic divestment in some PSUs to continue. State-run banks emerged as the top draw, scooped up by those who hope the Vajpayee government would bring down the Centres stake to 33 per cent. The announcement by some banks about lower non-performing assets (NPAs) also buoyed investors. Lower NPAs make dividend declarations easier.
The BSE-PSU index moved up 111.98 points or 2.84 per cent to 4050.97; the Bankex rose 37.36 points or 1.19 per cent to 3173.69.
Technology shares advanced as investors bought them in anticipation of a profit-boost from a hardening dollar. Cement stocks firmed up on higher April shipments.
Even commodity stocks, hammered in recent times on concerns of weak Chinese demand, bounced back. Hindalco firmed up by Rs 36.50 to Rs 1102.95 while Tisco ended Rs 7.40 higher than its previous close at Rs 349.90.
Crash alert
Sebi is on high alert after the market crash last week following exit polls predicting a hung Parliament. Sebi remains on high alert. Action will be taken if anything unusual is noticed, chairman G. N. Bajpai said at a function during his visit to Calcutta.


text:
1402 Justin Rd
Lewisville, TX 75077
320 Magnolia St Stamps, AR
1216 Antigo Street Stamps, AR
My colleagues and I visited this location last week. The service was great and the burger was excellant!! I would recommend this place to everyone.4
Not a bad place to stop for a burger and brew after a round of golf. Moderalty price and good food...The service was great and they had great places to watch your favorite game.3


text:
INSERT INTO sites(host) VALUES('ignitionshop.com') 1045: Access denied for user 'www-data'@'localhost' (using password: NO)
|Meta Description:
|Meta Keywords:
|sponsored links:
|sponsored links:
|Alexa Rank:
|Google Page Rank:
|Sogou Rank:
|Baidu Cache:
|Search Engine
|Web Server:
|IP address:
|ICANN Registrar:
|Name Server:
|Whois Server:
|One Week Avg.
|Three Mon. Avg.
|Unique IP:
|Alexa Reach and Rank
|Who is ignitionshop.com at whois.PublicDomainRegistry.com
Domain Name: IGNITIONSHOP.COM
Registry Domain ID: 2016572386_DOMAIN_COM-VRSN
Registrar WHOIS Server: whois.publicdomainregistry.com
Registrar URL: www.publicdomainregistry.com
Updated Date: 2016-07-24T14:54:29Z
Creation Date: 2016-03-28T18:03:42Z
Registrar Registration Expiration Date: 2018-03-28T18:03:42Z
Registrar: PDR Ltd. d/b/a PublicDomainRegistry.com
Registrar IANA ID: 303
Domain Status: OK https://icann.org/epp#OK
Registry Registrant ID:
Registrant Name: Netcorp, LLC
Registrant Organization: Inquire about this domain via contact email address
Registrant Street: P.O. Box 251506
Registrant City: Glendale
Registrant State/Province: California
Registrant Postal Code: 91225
Registrant Country: US
Registrant Phone: +1.8185499839
Registrant Phone Ext:
Registrant Fax: +1.8185499839
Registrant Fax Ext:
Registrant Email: email816
Registry Admin ID:
Admin Name: Netcorp, LLC
Admin Organization: Inquire about this domain via contact email address
Admin Street: P.O. Box 251506
Admin City: Glendale
Admin State/Province: California
Admin Postal Code: 91225
Admin Country: US
Admin Phone: +1.8185499839
Admin Phone Ext:
Admin Fax: +1.8185499839
Admin Fax Ext:
Admin Email: email816
Registry Tech ID:
Tech Name: Netcorp, LLC
Tech Organization: Inquire about this domain via contact email address
Tech Street: P.O. Box 251506
Tech City: Glendale
Tech State/Province: California
Tech Postal Code: 91225
Tech Country: US
Tech Phone: +1.8185499839
Tech Phone Ext:
Tech Fax: +1.8185499839
Tech Fax Ext:
Tech Email: email816
Name Server: ns1.above.com
Name Server: ns2.above.com
Registrar Abuse Contact Email: email@example.com
Registrar Abuse Contact Phone: +1-2013775952
URL of the ICANN WHOIS Data Problem Reporting System: http://wdprs.internic.net/
>>> Last update of WHOIS database: 2016-08-08T03:05:36Z <<<
For more information on Whois status codes, please visit https://icann.org/epp
Registration Service Provided By: VIP.DOMAIN.COM
The data in this whois database is provided to you for information purposes
only, that is, to assist you in obtaining information about or related to a
domain name registration record. We make this information available "as is",
and do not guarantee its accuracy. By submitting a whois query, you agree
that you will use this data only for lawful purposes and that, under no
circumstances will you use this data to:
(1) enable high volume, automated, electronic processes that stress or load
this whois database system providing you this information; or
(2) allow, enable, or otherwise support the transmission of mass unsolicited,
commercial advertising or solicitations via direct mail, electronic mail, or
by telephone.
The compilation, repackaging, dissemination or other use of this data is
expressly prohibited without prior written consent from us. The Registrar of
record is PDR Ltd. d/b/a PublicDomainRegistry.com.
We reserve the right to modify these terms at any time.
By submitting this query, you agree to abide by these terms.
Description:position: absolute; clip: rect(1px 1px 1px 1px); * IE7 * clip: rect(1px, 1px, 1px, 1px); }
Keywords:commend then beware, they really know absolutely nothing about search engine optimization. Seo is a sluggish, time consuming marketing method which demands tons of persistence.


text:
• Home • All Products
Author: Denise HunterRetail Price: $14.99
Our Price: $7.99
Save: 7.00 (46.70%)Availability: In Stock
Seth has secretly loved Layla for years, even when she was dating his best friend. Maybe she'll never forgive him for the way he hurt her back then, but he has to try. And Layla is willing to keep up their engagement farce until she's landed her client. For Layla, it's the chance to save her career, but for Seth, it's his last chance to win her heart.
Unabridged audio CD; approximately 2 hours 18 minutes; 2 CDs; performed by Julie Carr.
More From ChristiansUnite...
About Us |
Privacy Policy |
ChristiansUnite.com Site Map |
Statement of Beliefs


text:
Day off. What do I do?
...go grocery shopping. For some reason, if I get bored, I'll just go to Price Chopper. I'm lucky enough to have one 5 minutes away, even though I do live in the middle of nowhere! It's no Trader Joe's or Whole Foods, though :(
Among that, of course, I've been messing around on my Flickr and Etsy all morning. Other than that, I've done laundry and that's about all. hah!
What are your favorite boredom-breakers??
I woke up ravenous this morning! I think it had a lot to do with that fact that I slept til 8:30. That is super late for me. I'm usually up by 7 even if I'm not working. I enjoy it! I stayed up much later than usual though, playing on Flickr. These challenge games are addictive!
Made myself my new fave:
Shocker! Brown Cow Greek Yogurt, Blueberries, half a large banana, Kashi H2H, raisins (these really made it complete, I think!), maple syrup, and pumpkin pie spice. Oh, and half a spelt scone! It's hiding.
Coffee this morn=Gloria Jean's Cappuccino. Not my fave, but not terrible. I save the "mediocre" flavors for days I don't have work.
Enjoyed while surfing Etsy! P.S. - check out my shop! please?
Insert random kitchen cleaning, laundry-doing, face-powdering, and grazing here, until I decided to steal Henry's jeep and run to el banko and aforementioned grocery store. Grazing = remainder of the banana and a Kashi TLC Pumpkin Pie granola bar. I can't decide if I love these bars, or if they have too much of the sweet coating "stuff" on top. But I think I'm leaning toward love.
Currently grazing on:
sugar snap peas con garlic, chili powder, and salt and a blood orange.
I was really excited to try my first blood orange but was a little let down :( They're not bad, but for some reason I was thinking they'd be like n out-of-this-world orange or something. Not really :\
I've got some "overnight oats" (that I prepared this morning, hah) waiting jusssst a little bit longer for me in the fridge. Gonna be grrrrr-ate. heh...
A random photo of the morning:
Taken October 2009 with my Nikon N90s and Nikkor 50mm f/1.8 lens on Ektar 100 film.
Catch ya lata, kids. I'm cookin' dinner tonight!


text:
Ernakulam, India (PressExposure) April 27, 2009 -- WorkMoment Software Solutions, a leading Network Security & Surveillance software development company, today announced the release of RemoteSysInfo, a special tool designed to gather all the network computer information for system auditing, inventory & diagnostic purposes.
RemoteSysInfo is a cute little tool which is designed to gather the comprehensive hardware and software information from a network computer. It works with all versions of Windows including the 32-bit and 64-bit versions. RemoteSysInfo is a must tool for network and system administrators. It helps hardware engineers understand the internals of the computer in a quicker way.
The hardware information report categories include Input Devices, Mass Storage Devices, Motherboard, Controllers, Ports, Networking Devices, Power Devices, Printing Devices, Telephony, Video & Monitor, Cooling Devices etc.
Software information include the Drivers, COM, Desktop Information, File System Information, Memory and Page Files, Multimedia Related Information, Network Drivers, Detailed Operating System Settings Information, Processes, Threads, Registry, Services, Shares, Start Menu, Event Log, Windows Product Information, Installed Software Product information etc.
With its location independent feature, it can work through LAN, WAN & Internet. It works in WorkStations, Standalone Servers, Domain Servers & Terminal Servers. It works behind NAT and Firewalls. All information of a computer can be saved to a file on a single click.
The main features include,
* Gathers information of a remote computer. * Comprehensive hardware & software information. * Processor, BIOS, Memory Information. * Complete system information on a single click. * Quick Report & Full Report selection. * Computer auditing & diagnostics. * Works through LAN, WAN, Internet, NAT & Firewalls. * Supports all versions of Windows. * Supports 32-bit & 64-bit operating systems. * Supports IP version 6.
Other benefits include,
* Life time free email support. * One year free upgrade & maintenance. * Secure online purchase. * No need to install client software on individual PCs.
A fully functional 15-day evaluation copy of RemoteSysInfo is available for download at http://www.workmoment.com
For pricing details, please visit http://www.workmoment.com/rsi/rsipricing.html
RemoteSysInfo can be downloaded at http://www.workmoment.com/rsi/rsidownload.html
For support queries, please email to email@example.com
For sales related queries, please email to firstname.lastname@example.com


text:
Quick Details
- Type: Headlight
- Voltage: 12V
- Lamp Type: LED
- Certification: Coming
- Car Make: General
- Place of Origin: Guangdong, China (Mainland)
- Brand Name: Deliang
- Model Number: WL-24001
- Warranty: 12 Months
- Color: black,white
- LED Power: 240w
- LED Bead: 80pcsx3w
- IP Rating: IP65
- Lumin: 15600lum
- Color temperature: 6000k
- Material: Diecast aluminum housing
- Lens: PMMA
- Lift time: above 30000hours
Packaging & Delivery
|Packaging Details
|Normal Eaport Carton
|Delivery Time
China 4x4 High Power 240w Car Led Light Bar For Auto
Product Details
|China 4x4 High Power 240w Car Led Light Bar For Auto
|Item NO.
|Packing Size
|1200*180*150 mm
|Ctn size
|1240*370*330 mm
. LED Power: 240W
. Optional Color: Black,White
. pattern(60degree) . Spot beam pattern(30 degree)
Sufficient Capacity Supply and strong packing to protect the customer's goods.
Shipping Way:
BY air (3-5days, more expensive)
BY Express: (5-7 days, most expensive)
BY sea (15-28days cheapest)
Payment terms:
T/T (Directly)
PayPal (small order,convenient)
Western union ( convenient )
Money gram ( convenient )
Our Company:
We are manufacturer of 4×4 accessories with high quality and pretty price many years.
Main products:Auto snorkel,air compressor,air locker,high-lift jacker,wheel spacer,wheel hub,wheel arch flares,roof tent,roof rack,electric winch,trailer ball,tow hook,auto lamp,auto seat,etc.


text:
Our Hotel
Timeless Midtown Moments at Park Hyatt New York
With an ideal location in Midtown, Park Hyatt New York promotes a curated journey through one of the world's most coveted destinations. Unwind in your spacious guestroom or suite, featuring elegant artwork, designer furnishings, and modern features. When you're seeking relaxation, take a swim in the indoor pool or exercise in the state-of-the-art fitness center. Take advantage of iPads and laptops in the hotel study to quickly cover of any work commitments. Bevy, our signature restaurant features innovative American cuisine, while The Living Room offers creative cocktails coupled with views of Carnegie Hall. When you're looking to discover the city, many of the top sights from Central Park to the Museum of Modern Art are located just a short distance from our hotel.
Made your reservation? Now, personalize your stay - from scheduling transportation to requesting extra pillows - with Hyatt E-Concierge.
Check-in Time: 3:00 P.M.
Check-out Time: 12:00 P.M.
Are you sure you want to leave the chat?


text:
Celebrate the Season: Main Line Holiday Events
No matter which holidays you celebrate, there's lots of fun...Happy Holidays!
High Five! Main Line Events for November 11-13
1. Milk & Cookies Pajama Party November 11, 6:15 pm...Enjoy the Weekend!
Feel Good Forum Offers Support for Food Allergies
If you have a child with food sensitivities and allergies,...Feel Good!
High Five! Main Line Family Events for November 5 & 6
1. Chrysanthemum Festival November 5 and 6, 9 am —...Happy Weekend!
Election Day at the National Constitution Center
With the presidential election around the corner, there's no better...experience democracy!
Playgroups and Meetups on the Main Line
Whether you're new to the area or just interested in...get out and play!
High Five! Main Line Family Events for October 28 – 30
It's all about Halloween this weekend! 1. Hayrides to the...It's Halloween Weekend!
The Trick-or-Treating Guide to the Main Line 2016
Halloween is here, and your kids are begging you to...It's Candy Time!
High Five! Main Line Family Events for October 22 & 23
Need plans? Start here. 1. Play Cafe Fall Festival October...Fall Fun All Around!
Things To Do


text:
Newman's Own Coupon (Expired)
CouponSurfer Reviews for Newman's Own: Add Your Review
Newman's products are soooo good. They don't taste like chemicals like so many other brands. They are full of flavor and healthy. I never have to worry with his products.
Newman's own products taste very good. Prices are usually reasonable.


text:
The Asskickers
Friday, September 23, 2011 No Comments
The Asskickers is a lovingly hand-drawn side-scrolling beat 'em up title that brings to mind classics like the Ninja Turtles arcade game, Double Dragon and, to some extent, Golden Axe, only better looking versions thereof. Unfortunately, that's basically where its positives end. The environment refresh rates are slow, the character animation is highly lacking and […]
Tags: arcade, classic, double dragon, golden axe, lazy, mac, ninja turtles, PC, review, the asskickers