text:
abductor pollicis brevis
contingent negative variation
common peroneal nerve
holding phase
long-term potentiation
motor cortex
movement execution phase
movement-related cortical potential
paired associative stimulation
- PMd
premotor cortex
peak negativity
stimulator output
- Sol
- RTh
resting threshold
tibialis anterior
Precise temporal association between cortical potentials evoked by motor imagination and afference induces cortical plasticity
S. R. Kristensen and I. K. Niazi contributed equally to this work.
N. Mrachacz-Kersting: Centre for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Aalborg University Fredrik Bajers Vej 7 D3, 9220 Aalborg Ø, Denmark. Email: firstname.lastname@example.com
Key points
- • Here we use the naturally generated brain activation when a person imagines a simple movement and combine this with the afferent inflow that would be generated had the movement been performed rather than imagined.
- • We show that the excitability of the neural projections connecting the relevant brain areas to the target muscle is increased only when the afferent inflow arrives during the highest activation phase.
- • Furthermore, the changes are specific to the task and the neural connections between the brain and muscle involved in the task.
- • This novel intervention will open up the possibilities to alter afferent-generated feedback depending on the demands of the movement to be performed.
Abstract In monkeys, the repeated activation of somatosensory afferents projecting onto the motor cortex (M1) has a pivotal role in motor skill learning. Here we investigate if sensory feedback that is artificially generated at specific times during imagination of a dorsiflexion task leads to reorganization of the human M1. The common peroneal nerve was stimulated to generate an afferent volley timed to arrive during specific phases of the cortical potential generated when a movement was imagined (50 repetitions). The change in the output of M1 was quantified by applying single transcranial magnetic stimuli to the area of M1 controlling the tibialis anterior muscle. The results demonstrated that the concomitance between the cognitive process of movement (motor imagination) and the ascending volley due to the peripheral nerve stimulation can lead to significant increases in cortical excitability. These increases were critically dependent on the timing between the peripherally generated afferent volley and the cortical potential generated during the imagined movement. Only if the afferent volley arrived during the peak negative deflection of the potential, were significant alterations in motor cortical output attained. These results demonstrate that an artificially generated signal (the peripheral afferent volley) can interact with a physiologically generated signal in humans leading to plastic changes within the M1, the final output stage for movement generation within the human brain. The results presented may have implications in systems for artificially inducing cortical plasticity in patients with motor impairments (neuromodulation).
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Long-term potentiation (LTP) is one proposed mechanism for inducing synaptic plasticity thought to underlie processes of memory and learning (Bliss & Collingridge, 1993; Cooke & Bliss, 2006; Letzkus et al. 2007). One form of LTP, associative LTP, is based on Hebbian theory, according to which synapses that experience correlated activation of two converging inputs are strengthened whereas those weakened by uncorrelated activity are lost (Hebb, 1949).
Animal experiments demonstrated that induction of LTP is enhanced in regions of increased excitability following lesions (Hagemann et al. 1998). In humans, several techniques have been proposed to induce associative LTP within the motor cortex (M1; for review see Ziemann et al. 2008). During the execution of a movement, the excitability of M1 is increased (Lazzaro et al. 1998). Evidence supports the notion that associative LTP can be more readily induced when M1 is transiently disinhibited as during a voluntary muscle contraction (Kujirai et al. 2006; Mrachacz-Kersting et al. 2007; Thabit et al. 2010).
Voluntary movements are associated to slow negative cortical potentials, the movement-related cortical potentials (MRCPs). If a warning stimulus is provided followed by a cue to start the movement the MRCP is generally termed the contingent negative variation (CNV). The CNV, first described by Walter et al. (1964), is comprised of several well-defined parts, which are known to be linked to specific neurophysiological mechanisms. The first deflection, the early CNV, typically commences immediately following the warning stimulus (Hamano et al. 1997). The late CNV appears 1 to 0.5 s prior to the cue to perform the movement (Hamano et al. 1997). It is associated with the planning of voluntary movements and is altered in neurological disease (Ikeda et al. 1997). During the movement execution and after the cue, a more complex waveform may be observed, thought to be related to somatosensory feedback or alternatively to the attention level during task execution (Hamano et al. 1997). Although the exact generators of the CNVs are not known, these potentials are modulated by the way a task is executed since their characteristics change with variations in the force and speed of the executed or imagined movement (do Nascimento et al. 2005a,b, 2006; do Nascimento & Farina, 2008; Gu et al. 2009).
Since the CNVs contain information on movement planning and execution, they may be used to trigger the artificial activation of somatosensory afferents projecting onto M1. Repetitive electrical stimulation leads to increases in excitability of the cortical projections to the target muscle that are accompanied by significant functional improvements (e.g. walking speed in stroke patients) (Everaert et al. 2010). The repeated activation of somatosensory afferents projecting onto M1 has a pivotal role in motor skill learning in monkeys (Pavlides et al. 1993). Here we describe a conditioning protocol that uses the CNV generated by a cue-driven imagined movement and a single peripheral electrical stimulus timed to arrive at specific components of the CNV to induce associative LTP. LTP induction is assessed by exploring changes in the excitability of the cortical projections to the target muscle using single-pulse transcranial magnetic stimulation.
Ethical approval
Six experiments (one reliability experiment, one main experiment and four control experiments) were con-ducted in a total of 24 subjects (15 male, 9 female; age: 24.9 ± 4.9 years) with no prior history of neurological conditions. All procedures were in accordance with the Declaration of Helsinki and approved by the Scientific Ethics Committee of Northern Jutland (reference number: VN-20100067). Subjects gave their written consent prior to participation.
Contingent negative variation (CNV)
Monopolar EEG signals were recorded by an EEG amplifier (EEG100c, Biopac system, USA) and acquired by an acquisition card (National Instruments, NI6122) at 1024 Hz (0.1–100 Hz). Ag–AgCl scalp electrodes were placed according to the International 10–20 system in the positions C1, Cz, C2 and CPz. The right ear lobe was used as a reference and the ground electrode was placed at the nasion.
To investigate the reliability of the recorded CNVs over time, 10 subjects (5 male, 5 female; age: 25.3 ± 2.4 years) attended three separate sessions on day 1, 7 and 21, respectively ('CNV reliability experiment'). In a separate set of experiments ('Intervention experiment'), 9 subjects (5 male, 4 female; age: 27 ± 6.9 years) participated in one baseline session (determining the peak negativity of the CNVs) before proceeding to three intervention sessions separated by at least 2 days (range 2–9 days), as described under the section 'Interventions'. For each subject, the CNV was recorded during the imagination of a right ankle dorsiflexion. A custom-made Matlab script provided visual information via a screen positioned 2 m in front of the subject on when to mentally prepare, execute and release the movement. Each trial consisted of five time periods, namely focus, preparation, execution, hold and rest period (Fig. 1). When the cursor reached the ramp (task period), the subjects had to imagine the kinaesthetics of a ballistic (as fast as possible) dorsiflexion and hold this for 2 s before resting prior to the subsequent trial. The time period of the focus phase was randomized between 2–3 s for each trial, while the preparation phase remained fixed at 2 s. The holding phase was set to 2 s and the inter-trial rest time was randomized between 4 to 5 s. The timing of these phases was chosen empirically. A total of 50 imaginary dorsiflexion movements were recorded in two 25-trial sets, with a 1–2 min rest period between each set.
Prior to the CNV recording, every subject was instructed to perform 25 ballistic dorsiflexion movements with the right foot following the same procedure as above. The reason of this was to train the subjects in performing ballistic dorsiflexion movements uniformly in relation to the visual cue and build up their strategy for the motor imagery task.
Feature extraction from CNV
The EEG data containing the CNVs were divided into epochs of 4.5 s (from 2 s before to 2.5 s after the visual cue) for each imaginary movement. The root-mean-square (RMS) values for all epochs were calculated. Any epoch containing activation of the tibialis anterior (TA) muscles (more than 3× the resting RMS value) were discarded, as were all epochs containing eye-movement artifacts. EEG signals were band-pass filtered from 0.05 Hz to 10 Hz, and subsequently wavelet denoising was applied (wavelet: 'db4') to smooth the CNV in each epoch. Next a window of 500 ms on either side of task onset was chosen. If any epoch's peak negativity was outside the selected window it was discarded. The time of occurrence for the minimum values of the remaining epochs were subsequently plotted in a histogram. Based on these remaining epochs the mean peak negativity (PN) was defined as the time of occurrence for the minimum value of the averaged CNV in relation to the visual cue. The mean PN and standard deviation (SD) were used to calculate the points in time for when to apply the peripheral stimulation in the intervention sessions described below.
Recording and stimulation
Surface electrodes (20 mm Blue Sensor Ag–AgCl, AMBU A/S, Denmark) were used to record the electromyographic (EMG) activity of the TA muscle of the right leg for all aspects of the experiments. The electrodes were placed in accordance with the recommendations of Garland et al. (1994). All data were sampled at a frequency of 4 kHz. The EMG signals were amplified and band-pass filtered at 20 Hz–2 kHz.
A Magstim 200 (Magstim Company, Dyfed, UK) with a focal figure-of-eight double-cone coil (110 mm diameter) was used to apply single pulses to elicit a motor-evoked potential (MEP) in the TA. The direction of the current was directed from posterior to anterior.
Peripheral nerve stimulation was performed during the interventions. Stimulation of the common peroneal nerve (CPN) was applied using a NoxiTest isolated peripheral stimulator (IES 230). Stimulating electrodes (32 mm, PALS Platinum, Patented Conductive Neurostimulation Electrodes, Axelgaard Manufacturing Co., Ltd, USA) were placed on the skin overlying the deep branch of the right common peroneal nerve (CPN – L4 and L5) with the cathode proximal. A suitable position for stimulation, defined as the site where a maximal M-wave was produced in the TA with no activity from the synergistic peroneal muscles and no activity from the antagonist soleus (Sol), was identified. Palpation of Sol and peroneal muscles was performed during stimulation trials to ensure that this was occurring. The stimulation site corresponded to a point just anterior to the level of the caput fibulae. The pulse width was 1 ms and the intensity 1 × motor threshold.
Experimental procedures
During all experiments described below, subjects were seated in a chair (hip 90 deg, knee 130 deg) with their right and left foot resting on separate footplates. Initially the intensity for the magnetic stimulation was set at approximately 50% of the stimulator output (SO) to find the optimal site for evoking a MEP in the TA. The best spot for stimulation (also termed the hot-spot) was defined as the coordinate where the peak-to-peak amplitudes of the MEPs were greater in the target muscle than the amplitudes of adjacent coordinates for a given stimulus intensity. For all subjects, this site was approximately 2–3 cm anterior to the vertex and a stimulation applied to this area also evoked a response in the Sol. Once the hot-spot was identified, it was marked to ensure that the coil position was maintained so that the stimulation was always applied over the same area of M1.
Subsequently, the resting threshold (RTh), defined as the highest stimulus intensity that produced no more than 5 of 10 consecutive TA MEPs with a peak-to-peak amplitude of ∼50 μV while the muscle was at rest, was identified. Next, 12 MEPs were elicited in the resting TA at five TMS intensities; 90, 100, 110, 120 and 130% of RTh. The TMS stimuli were delivered randomly every 5–7 s in a randomized order.
The intervention protocols consisted of a single electrical stimulation of the common peroneal nerve de-livered at motor threshold (MT) timed to arrive during (a) the late CNV (CPN+lateCNV), (b) the movement execution phase (CPN+ME) or (c) the holding phase (CPN+HP) (Fig. 2). The timing was calculated according to the following formulae: mean peak negativity – 50 ms (CPN+ME); mean peak negativity – 50 ms – SD (CPN+lateCNV); mean peak negativity – 50 ms + SD (CPN+HP). The 50 ms represent the average latency for the peripheral stimulus to reach the somatosensory cortex plus a cortical processing delay and is based on previous work (Mrachacz-Kersting et al. 2007). The resulting timing was subsequently rounded up/down to the nearest 50 ms due to a limitation of the computer algorithm.
A total of 50 pairings (every 10–12 s) were applied in two sets of 25 trials in nine subjects. The mean peak-to-peak TA MEP amplitude measured prior to and following each intervention was plotted against TMS intensity. This relation was fitted with the Boltzmann sigmoidal function by the Levenberg–Marquard non-linear, least-mean-squares fit, as previously described (Devanne et al. 1997).
Control experiment 1–3: imagery alone, specificity and effects of the visual input
Three control experiments were performed. In eight subjects (3 male, 5 female; age: 23.3 ± 3.5 years), the intervention performed consisted of only the imagined movement (every 10–12 s) to quantify the effects of imagination alone ('Control experiment 1'). In nine subjects (7 male, 2 female; age: 24.2 ± 2.4 years), the tibial nerve was stimulated at MT, timed so that the afferent volley generated arrived during the movement execution phase (as for the CPN+ME intervention; 50 pairs, 10–12 s apart) ('Control experiment 2'). This was to establish the specificity of the protocol. In the third control experiment ('Control experiment 3'), four subjects (2 male, 2 female; age: 22 ± 2.7 years) were asked to simply look at the screen, which contained the same display of information as for the main interventions. The electrical stimulus was applied to the CPN at the same time as during the CPN+ME intervention. The purpose of this last control experiment was to exclude the effect of the visual cue as possibly altering the excitability of the cortical projections to the TA. In all the control experiment the subjects were naïve to the protocol.
Control experiment 4: stretch reflex recording
It is not possible to differentiate if alterations in the MEP are due to changes in spinal or cortical circuitry. For this purpose, TA stretch reflexes were elicited prior to and following the CPN+ME intervention in four subjects (1 male, 3 females; age: 22.5 ± 2.5 years). The right leg was affixed to a servo-controlled hydraulic actuator (MTS-systems Corporation, 215.35; Voigt et al. 1999), such that the anatomical ankle axis of rotation was aligned with the fulcrum of the actuator. The foot segment of the right leg of the subject was firmly strapped to a custom-made plate that extended from the actuator, thus producing a tight interface between the arm of the motor and the foot of the subject, ensuring that the movement of the actuator was transmitted solely to the ankle joint. The angular position of the actuator was monitored by an angular displacement transducer (Transtek, DC ADT series 600). The subjects were asked to produce three maximum voluntary contractions (MVC) of the TA, separated by 3 min of rest. The greatest of the three MVC forces was used as the reference MVC. The root mean square value of the rectified TA EMG for the MVC over a 1 s period was calculated. Subsequently, the subjects were provided with visual feedback via a computer screen displaying horizontal markings set at 5% MVC and a vertical bar displaying the subject's current level of TA activation. Subjects were asked to maintain the bar between the horizontal markings while the perturbations were applied without interfering with the imposed plantarflexion perturbations.
Thirty stretches were randomly applied at intervals ranging from 5 to 7 s (velocity: 100–200 deg s−1; amplitude: 4–6 deg; hold-time: 460 ms). The angular velocity and the amplitude of the imposed perturbations were adjusted for each subject prior to the intervention so that the amplitude of the three response peaks observed in the TA EMG trace were approximately the same and also similar to the amplitude of the TA MEP prior to the intervention. The latency of the first response peak (termed M1 or alternatively short latency reflex (SLR) in the literature) were extracted from the data both prior to and immediately following the intervention. The root mean square (RMS) value of a window extending 10 ms on either side of the SLR was calculated and used as an indication of the size of this component of the TA stretch reflex.
Since it is possible that the motor units targeted by an imposed stimulus (mechanically or electrically) differ when a muscle is relaxed compared with when it is contracted, it was necessary to record the TA MEP during a contraction of the TA. For this, the active threshold (ATh) was identified as the highest stimulus intensity that produced no more than 5 out of 10 consecutive TA MEPs with an amplitude of ∼100 μV while the muscle was contracting at 5% of its maximum voluntary contraction. Prior to and following the CPN+ME intervention, 12 MEPs were recorded during a 5% MVC contraction of the TA. The TMS intensity was chosen based on the amplitude of the rectified MEP being matched to the amplitude of the M1 component of the stretch reflex prior to the intervention.
Statistical procedures
A one-way repeated-measures ANOVA with the factor 'day' (1, 1; 2, 7; 3, 21) was used to establish the repeatability of the onset and occurrence of peak negativity of the MRCP. A three-way repeated-measures ANOVA with factors 'time' (1, pre; 2, post), 'intervention' (1, CPN+lateCNV; 2, CPN+ME; 3, CPN+HP) and 'stimulus intensity' (1, 90%; 2, 100%; 3, 110%; 4, 120%; and 5, 130% RTh) was used to investigate the effects of the three main interventions (CPN+lateCNV, CP+ME and CP+HP) on the changes in the MEP amplitude. Paired t tests with Bonferroni correction were used to assess changes in the parameters of the input–output curve (the stimulus intensity required to obtain a response that is 50% of the maximum (S50), the slope and the r2 value). A two-way repeated-measures ANOVA with factors 'time' (1, pre; 2, post) and 'stimulus intensity' (1, 90%; 2, 100%; 3, 110%; 4, 120%; and 5, 130% RTh) was used to assess the changes in MEP amplitude for the three control experiments. Each analysis was performed separately for each control experiment. The Student's t test was used to investigate possible difference in the pre- and post-stretch reflex data. For all experiments, statistical significance was set to P < 0·05.
Reliability of CNV measures
As CNVs were used to identify the instant of time to trigger peripheral stimulation, it was essential to analyse the reliability of their features when measured over different days. Figure 3 shows the average CNV for all subjects on day 1, 7 and 21. Across all subjects the average onset was −1630 ± 309 ms and the PN occurred at −15 ± 217 ms. On average seven trials were rejected for all the subjects. There was no significant difference in the onset (F(2,27)= 0.31; P = 0.60) or the time of PN (F(2,27)= 0.52; P= 0.74) of the CNV.
Interventions: dependence on timing of peripheral stimulus
The effectiveness of the intervention protocols was quantified by assessing changes in the input–output properties of the TA MEP prior to and following each intervention in a total of nine subjects. The TA MEP was elicited at five intensities of TMS, ranging from 90% to 130% of RTh. A Boltzmann fit was applied to the extracted peak-to-peak TA MEP curve. Figure 4A shows the averaged raw data as well as the fitted data for one subject prior to and following each intervention. For this subject, the peak negativity of the CNV occurred at 119 ± 229 ms (Fig. 4B). In the figure, the onset of the imagined task is also indicated (vertical dashed line) and assumed as time zero by convention. The arrows in the figure indicate when the signal from the peripheral nerve stimulation arrives in relation to the CNV based on our assumptions (see Methods). For this subject, the timing is 200 ms prior to the start of the imagined movement (CPN+lateCNV) in the first intervention, 50 ms after the start of the imagined task (CPN+ME), and 300 ms after the start of the imagined movement (CPN+HP) for the other two interventions.
Across all subjects the afferent volley from the common peroneal nerve stimulation was elicited 101 ± 110 ms prior to the start of the imagined movement (CPN+lateCNV), 134 ± 115 ms after the start of the imagined task (CPN+ME), and 368 ± 196 ms after the start of the imagined movement (CPN+HP). Figure 5 shows the averaged TA MEP size prior to and following the three interventions for all subjects. Data are expressed as a fraction of the maximum TA MEP prior to the intervention. Across all subjects, the Boltzmann fit accounted for more than 80% of the total variance in the data (r2≥ 0.8). Three variables were extracted from the fitted data: the maximum value (TA MEPmax), the slope of the steepest part of the curve (k) and S50. However, the maximum MEP varies widely across individuals due to the TA representation on M1 being buried deep in the interhemispheric fissures. We thus normalized the peak-to-peak TA MEP for each subject and all stimulation intensities to the maximum TA MEP recorded in the pre-intervention. A three-way repeated-measures ANOVA with factors 'time' (1, pre; 2, post), 'intervention' (1, CPN+lateCNV; 2, CPN+ME; 3, CPN+HP) and 'stimulus intensity' (1, 90%; 2, 100%; 3, 110%; 4, 120%; and 5, 130% RTh) revealed a significant effect of time (F(1,8)= 22.65; P = 0.001) and a significant time × intervention interaction (F(2,16)= 4.83; P = 0.02). Post hoc analysis of the latter interaction using paired t tests with Bonferroni correction revealed significantly greater TA MEPs following the CPN+ME intervention (P = 0.02) but not after the CPN+lateCNV (P = 0.92) or following the CPN + HP (P = 0.19) interventions.
The size of the TA MEPs in the pre-test were not significantly different across the three main interventions (F(2,16)= 0.14; P = 0.39; two-way repeated-measures ANOVA with factors 'intervention' (1, CPN+lateCNV; 2, CPN+ME; 3, CPN+HP) and 'stimulus intensity' (1, 90%; 2, 100%; 3, 110%; 4, 120%; and 5, 130% RTh).
The changes in the TA MEP sizes may be explained by alterations in the slope of the input–output relation (k), the threshold for eliciting a response or both. Paired t tests with Bonferroni correction revealed that the S50 variable of the Boltzmannn fitted data was significantly different before and after the CPN+ME intervention (P = 0.003). Across all subjects, the S50 had a value of 49.6 ± 5.1% RTh prior to and 47.8 ± 4.4% RTh post-intervention. The S50 parameter is not a direct measure of threshold, and thus it does not indicate the effectiveness of the TMS onto M1 representation of the TA. Rather, it represents the stimulation intensity required to elicit a response 50% of the maximum TA MEP. In our case, this intensity was significantly lower following the CPN+ME intervention while the slope parameter k remained unchanged (P = 0.16).
Control experiment 1: CNV – effect of imagination only
As the changes observed in cortical excitability could have been elicited by imagination only, as a control in eight subjects we recorded the TA MEP recruitment curve prior to and following an intervention where subjects were asked to only imagine the task following the same cue as for the previous interventions but without receiving any peripheral stimulation. A two-way repeated-measures ANOVA with factors 'time' (1, pre; 2, post) and 'stimulus intensity' (1, 90%; 2, 100%; 3, 110%; 4, 120%; and 5, 130% RTh) revealed a significant effect of stimulus intensity (F(4,28)= 11.36; P < 0.001). However, there was no significant effect of time (F(1,7)= 0.25; P = 0.63). This control measure indicates that imagination only was not effective in increasing cortical excitability.
Control experiment 2: specificity – effect of peripheral tibial nerve stimulation
To ensure that the effects from the main intervention were due to specific afferent inflow from the muscle involved in the imagined movement, this intervention tested if stimulation of a nerve not involved in the imagined movement would alter the TA MEP amplitude. Nine subjects received tibial nerve stimulation at motor threshold that was timed to arrive during the movement execution phase of the MRCP. A two-way repeated-measures ANOVA with factors 'time' (1, pre; 2, post) and 'stimulus intensity' (1, 90%; 2, 100%; 3, 110%; 4, 120%; and
5, 130% RTh) revealed a significant effect of stimulus intensity (F(4,32)= 19.84; P < 0.001); however, there was no significant effect of time (F(1,8)= 3.53; P = 0.097), nor significant interactions (F(4,32)= 0.68; P = 0.61). This control measure indicates that stimulation of the antagonistic nerve was not effective in increasing cortical excitability.
Control experiment 3: vision – effect of attention on the visual display combined with peripheral nerve stimulation
In an additional control experiment, we asked four subjects to simply view the visual cue and at the time where the cursor indicates the movement onset, we applied the peripheral nerve stimulus. During this control experiment the subjects were unaware of the meaning of the visual cue. The only instructions to the subjects were to pay attention to the display screen in front of them. A two-way repeated-measures ANOVA with factors 'time' (1, pre; 2, post) and 'stimulus intensity' (1, 90%; 2, 100%; 3, 110%; 4, 120%; and 5, 130% RTh) revealed a significant effect of stimulus intensity (F(4,12)= 8.44; P = 0.002); however, there was no significant effect of time (F(1,3)= 0.05; P = 0.84), nor significant interactions (F(4,12)= 0.34; P = 0.85). This control measure indicates that the visual input from seeing the cursor moving upwards combined with the peripheral stimulus was not effective in increasing cortical excitability.
CPN+ME intervention versus control experiments 1–3
In an additional test, we compared the specificity of the main finding, namely that the excitability of the cortical projections to the target muscle is only increased when the peripheral afferent volley was timed to arrive at the peak negativity of the CNV. An ANOVA with factors 'intervention' (1, CPN+ME; 2, TN+ME; 3, imagination only; and 4, watching only), 'stimulus intensity' (1, 90%; 2, 100%; 3, 110%; 4, 120%; and 5, 130% RTh) and time (1, pre and 2, post) revealed a significant effect of intervention (F(3,260)= 3.44; P = 0,02), stimulus intensity (F(4,260)= 24,14; P = <0.001) and a significant interaction between these two factors (F(12, 260)= 4.30; P < 0.001). Post hoc analysis using paired t tests with Bonferroni correction revealed significantly greater TA MEPs following the CPN+ME intervention (P < 0.001) but not after imagination only (P = 885), TN+ME (P = 0.11) or watching only (P = 86) control experiments. Figure 6 displays the changes in the TA MEPmax for all conditions across all subjects. Changes are expressed as a percentage of pre-intervention values.
Control experiment 4: spinal excitability
To identify potential changes in spinal excitability, reflex responses in the TA to sudden plantarflexion rotations were investigated prior to and following the CPN+ME intervention in four subjects. These imposed rotations had an amplitude of 4–6 deg and a velocity of 100–200 deg s−1. The changes in ankle angle as well as the EMG recording of the TA both prior to and following the CPN+ME intervention are shown for one subject in Fig. 7A and B, respectively. Each trace is the average of 30 imposed rotations. The TA responds with three discernible peaks (Fig. 7B), of which the SLR is generated exclusively through spinal circuitries. Across all subjects, the SLR component of the TA stretch reflex did not significantly change in amplitude (t= 2.9821, P = 0.06; pre: 21 ± 10 μV, post: 25 ± 13 μV). The background level of activation during the imposed plantarflexion perturbations did not differ significantly pre and post the intervention (t= 0.45, P = 0.06; pre: 17 ± 3 μV, post: 17 ± 3 μV). Figure 7C shows the average size of the SLR, MLR and LLR prior to and following the CPN+ME intervention for all four subjects.
The active MEP was also recorded prior to and following the intervention. Across all subjects, the rectified and averaged active MEP did not change significantly in amplitude (t= 1.13, P= 0.13; pre: 53 ± 16 μV, post: 46 ± 22 μV).
We presented a new conditioning technique for inducing changes in the excitability of cortical projections to the TA muscle. The pivotal proof of principle in our study is that only the CPN+ME intervention led to significant excitability changes that outlasted the stimulation period while other interventions did not have significant effects. The results thus indicate the crucial importance of the timing of peripheral stimulation in relation to the CNV components and therefore the timing between motor planning and the afferent volley to induce associative LTP. Invasive animal and human experiments employing either single-cell or subdural recordings suggest that neural elements within M1, the prefrontal area as well as the supplementary sensorimotor area contribute to the late CNV and ME phase during cued movements (Okano & Tanji, 1987; Kurata & Wise, 1988; Hamano et al. 1997).
The results also showed that afferent feedback from the periphery is necessary to induce the observed plastic changes as a disinhibition of M1 by imagery alone did not lead to a significant change in excitability. We did not assess the effects from peripheral nerve stimulation alone; however, past studies have demonstrated that any changes in MEP size from peripheral nerve stimulation alone require higher stimulation frequencies than those used in the current study (Khaslavskaia & Sinkjaer, 2005) or, alternatively, a longer period of stimulation (2 h) at lower frequencies (Kaelin-Lang et al. 2002). Further, the results demonstrate the specificity of the observed effect as the afferent volley generated by the stimulation of a nerve supplying the antagonist did not lead to any significant changes.
The proposed approach is based on the assumption that CNVs are stable over different recording sessions. In past studies it has been possible to extract parameters of the intended movement from the recorded CNV (do Nascimento et al. 2005a,b, 2006; do Nascimento & Farina, 2008; Gu et al. 2009). This implies that the CNV is stable within one recording session. Here we provide further evidence of this as well as of the CNV stability over days. In the current protocol we used the peak negativity rather than the cue provided to the subject to establish the timing of the afferent generated signal. Indeed, the cue and the peak negativity do not necessarily occur at the same time. In investigating the repeatability of the peak negativity, although we found it to be repeatable within one subject between days, the variability across subjects is in the order of a few hundred milliseconds. This is probably due to the fact that some individuals are better able to react to a cue than others, thus by timing the arrival of the afferent volley at peak negativity we were ensuring that it arrived during the subjects' imagination of the task execution.
Jackson et al. (2006) used cortically implanted electronic circuits in freely behaving primates to record the activity from one cortical site to subsequently stimulate a different site, creating a causal relation between the neural activity at the two sites. Over a number of days the output of the stimulated site resembled that of the recorded site and this effect, which was specific to the stimulated circuitry, persisted over weeks. This elegant study demonstrated that a physiologically generated signal may be used to drive stimulation at a remote site leading to associative LTP. In the current study we used a physiological signal and paired this with an artificially generated signal to induce associative LTP at the cortical level in humans. Although we did not assess how long this effect lasted, the duration of the post-MEP measures was approximately 10 min after the cessation of each intervention. In addition, the effect was not only timing dependent but also specific since electrical stimulation of the nerve supplying the antagonist muscle did not lead to significant changes in the size of the MEPs. These effects taken together strongly suggest that the changes evoked from the CPN+ME intervention resembled associative LTP. There are several recent studies which have combined a peripheral nerve stimulation with a direct stimulation of M1 using TMS. This protocol, termed paired associative stimulation (PAS), was initially developed to target hand muscles by Stefan et al. (2000) and has since been developed to target lower limb muscles (Mrachacz-Kersting et al. 2007; Poon et al. 2008). There are several differences of the current intervention over PAS. The number of pairings required in the current study is only 50 to produce the desired changes in MEP amplitude. This is far less than those used for the conventional PAS protocols. Perhaps more importantly, here we use a physiologically generated signal within the human brain and pair it with a peripheral electrical nerve stimulation. This opens the possibility to investigate non-invasively those areas of the brain that may be involved in PAS protocols. TMS at the intensities used in PAS protocols (usually 120% RTh) will stimulate a wide area over M1. In particular for lower limb muscles, it is thus not possible to differentially affect the left leg muscles versus the right leg muscles due to the location of the representation of the leg muscles within M1. This may be one reason why the interstimulus interval for PAS when targeting lower limb muscles differs so widely across studies and subjects.
Thabit et al. (2010) modified the PAS protocols described above by using a simple reaction time task and imposed a single magnetic stimulus over M1 timed either 50 ms prior or 100 ms following movement onset. The protocol of their study may not be directly comparable to that implemented here as the TMS current will probably spread to areas other than the M1 representation of the target muscle. However, it is striking that unlike in the present study, they reported significant increases in the TMS-induced MEP of the target muscle (abductor pollicis brevis, APB) only when the TMS stimulus arrived 50 ms prior to movement onset. Several reasons may explain the discrepancy between the results in the current study and those of Thabit et al. (2010). The effects of TMS have been shown to interact with the peripheral nerve stimulus even if TMS is delivered up to 90 ms prior to the peripheral nerve stimulus (Roy et al. 2007). Further, it is specifically the later-occurring I3 waves that interact with the afferent signal from the peripheral nerve stimulation to induce the LTP-like effects following PAS (Kujirai et al. 2006). It can thus not be excluded that the summation of the two stimuli in their study occurred during the movement execution rather than prior to it.
Since there were no alterations to the spinally mediated TA stretch reflex, it is unlikely that subcortical sites contributed to the observed effects. In past studies, the H-reflex has been assessed as an indicator of spinal excitability (Mrachacz-Kersting et al. 2007). The H-reflex probes only that pathway arising from muscle spindle Ia afferents as opposed to the stretch reflex that has various components which are believed to arise from different muscle afferents (Kearney & Hunter, 1984; Petersen et al. 1998). However, it is not possible to probe the entire network of spinal pathways even with the stretch reflex and thus it cannot be excluded that some of the changes may have occurred at subcortical or spinal sites.
In the current study the subjects were presented with a warning signal prior to the presentation of the cue to imagine the movement. The subjects consequently acted on a sensory signal from the outside world and it is generally accepted that in this situation the cortical potential up to 500 ms prior to movement initiation is generated in the contralateral premotor cortex (PMd) (Jenkins et al. 2000). The PMd receives afferent input from several parietal areas and connects with several motor areas (Rizzolatti et al. 1998). Although it is part of a complex neural network involved in selecting, planning and executing of voluntary movements, the intervention CPN+RP did not result in a significant change in the excitability of the cortical projections to the TA. Using a repetitive transcranial magnetic stimulation (rTMS) protocol over the contralateral PMd to increase excitability, Lu et al. (2011) failed to demonstrate a significant change in MEP size while Rizzo et al. (2004) reported significant increases. Similar to the protocol implemented in this study, rTMS as used in the latter studies is thought to induce LTP-like effects. One important difference with respect to our protocol is that we combined peripheral afferent feedback with the natural activation of PMd. As the intensity of the CPN stimulation was at motor threshold it would have activated the lowest threshold afferents, which are those originating in receptors of the target muscle. It may be speculated that if the intensity had been elevated to also recruit pain receptors or conversely if the receptors located in the antagonist muscle had also been activated, this would have resulted in significant MEP changes following the CPN+lateCNV.
The generator of the cortical potential during movement execution is most probably the primary motor cortex (M1; Hamano et al. 1997). This region connects to and receives input from somatosensory and other non-primary cortices (Rizzolatti et al. 1998). In the CPN+ME intervention, cells within M1 are activated simultaneously via commands from other brain regions as well as from the peripherally generated sensory feedback from the target muscle. Together, this produced a significant increase in our outcome measure (the TA MEP). While data presented here do not provide direct evidence as to the locus of this modification, the lack of changes in the stretch reflex renders this to a cortical site and probably M1. As mentioned in the previous section, the intensity of the peripheral stimulus was at motor threshold. It is widely accepted that at this intensity only the low-threshold afferents originating in muscle receptors are recruited. While it is not the aim of this study to investigate the role of muscle afferents in movement generation, several studies have reported these to contribute by up to 50% to the muscle activation during normal walking (Sinkjaer et al. 2000; Nielsen & Sinkjaer, 2002). It may therefore not be surprising that the control experiment where subjects only imagined the task without any input from the periphery did not produce any change in MEP size.
The results presented may have implications in systems for artificially inducing cortical plasticity in patients (neuromodulation). In these applications, the intention to move can be detected without a cue directly from the EEG traces. By identifying the late CNV, there would be sufficient time for triggering the electrical stimulator. It is well known that the early components of the MRCP are prone to alterations in onset in various neurological conditions (Dick et al. 1989; Filipoviçet al. 2001; Bai et al. 2006). In stroke patients, the onset of the MRCP does not change; however, the size of the waveform is decreased over time (Jankelowitz & Colebatch, 2005). In the current study this has little implication; however, if movement characteristics are to be derived from the changes in the shape of the MRCPs, then this factor has to be addressed.
In conclusion, we have developed a novel intervention using self-generated physiological signals for inducing plastic changes within the intact M1. The significant coincident summation effect when the peripheral stimulus was timed to arrive during the peak negativity of the MRCP has wide implications. On the one hand, as it is believed that during cue-driven movements M1 is the generator of the cortical potential during movement execution, our study demonstrates that this activation is sufficient when combined with peripheral afferent feedback for the state of excitability in M1 to be altered beyond the intervention. It also further supports the importance of peripherally generated muscle feedback in the generation of normal ongoing movement. In this case, muscle receptors probably have a greater role beyond their involvement in the stretch reflex. It remains to be investigated how these changes in excitability are reflected in alterations of functional parameters.
Author contributions
All authors contributed to the concept and design of the experiments as well as to the collection, analysis and interpretation of the data. The work was performed at the Centre for Sensory–Motor Interaction, Aalborg University. N.M.-K. and D.F. drafted the manuscript and all authors approved the final version for publication.
This work was supported by the Danish Agency for Science and Technology and Innovation, by the European project BETTER (contract no. 247935) and by the Bernstein Focus Neurotechnology Göttingen.


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Beringer St. Helena Home Vineyard Cabernet Sauvignon 2010
Member Reviews for Beringer St. Helena Home Vineyard Cabernet SauvignonAdd your review
Big, bold, smokey cab. Very nice balance, with a great nose.
Had it with capellini con funghi - nothing fancy, and for just a simple glass with a simple homemade dinner? Why not? Mouthfeel adds a touch of elegance and brightness. Medium-ish body, surprisingly complex, deep cherry-sh flavors. Silky tannin, just enough of a hint (as of yet, I don't like chewy wines).
For me the Knight's Valley is a dark ruby red, with moderate aroma, earthy, sticky, blackberry jam. It had a dry, medium body ,and the flavors we're amazing with a long finish. It was fantastic with a bolognese pulled from the freezer.
My 5-wine rating only applies to wines priced below $25. In that price range...this cab is awesome. A bit softer than some of the Cabs that come from the main Napa Valley further south of Knights Valley. Very lush and plush. Full bodied but a "velvety smoothness" that's quite unique. Might have to do with the slight bit of Merlot/Cab Franc/Syrah that tyically makes up about 5-8% of the blend. If you prefer Meritage over Cab...then this is your Cab. Not in the same class as Dominus or Opus, but better than many Cabs in the $35-$50 range. I can regularly find it for 16-19 dollars with shopping card discounts. Haven't tried the 2007 yet...but the 1998-2006 have never dissapointed me.
Nice plummy nose. Great mineral undertones. Despite the fruit its a very woody wine in which drying tannins dominate. Long finish and secondary flavors like tobacco come through.
Crisp, cabernet franc-like nose. Ripe, lush, dark berry compote. Anise hints throughout. - Tasted at Beringer Private Reserve Tasting at the Mandarin Oriental Las Vegas 4/5/10
AWESOME! Dark crimson in the glass. Super concentrated nose. Lush and beautiful fruit. Wonderfully integrated tannin. The fruit is lush and ripe and lingers long and pure. Very floral on the back end. Pleasant hints of spice on the finish. Some slight mint. - Tasted at Beringer Private Reserve Tasting at the Mandarin Oriental Las Vegas 4/5/10
External Reviews for Beringer St. Helena Home Vineyard Cabernet Sauvignon
Rich, with loamy earth, currant, sage, dill and dried berry fruit that's very tight, tannic and compact. Should benefit from short-term cellaring. Best from 2010 through 2015.
RP: 87 Points
Beringer Founder's Estate Cabernet Sauvignon 2006: Dekantier-Empfehlung (1 Std. vorher belüften), empf. Trinktemperatur 16-18°C, in Barriques gereift (12 Monate), lagerfähig 3 - 5 Jahre ab Jahrgang,,Jahrgang: 2006Inhalt: 0,75 LRegion: KalifornienWeingut: Beringer VineyardsRebsorte: Cabernet SauvignonRestzucker: Restsäure: Alkoholgehalt: 0.14 Rotwein
Beringer's Private Reserve Cabernet is always one of Napa Valley's best becuase Beringer has access to such a wide array of prime vineyard sites throughout the Valley. Cabernet Sauvignon grapes are sourced from Bancroft Ranch and Steinhauer Ranch on Howell Mountain as well as St. Helena Home Ranch, Marston and Chabot Ranches.
Good deep, bright ruby. Black cherry, licorice and fresh herbs on the slightly medicinal nose. At once dense and juicy, with lively acidity and a firm tannic spine keeping the bright dark berry and licorice flavors under wraps today. This has good weight and balance and finishes with broad, serious, building tannins that call for a year or two of patience. Already showing a bit of flesh, but give this another year or two to round out in bottle.
Granatrote Farbe, Aromen von Holz, schwarzem Pfeffer und Lebkuchengwürz. Am Gaumen gut strukturiert, reich, Aromen von Heidelbeeren, mit einer leichten Tabaknote.
Beringer Founders' Estate Cabernet Sauvignon 2006 750ML
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High-temperature operation of 1.3-μm wavelength multiquantum-well (MQW) lasers with an active stripe horizontally tapered over whole cavity, for direct coupling to single-mode fibers (SMFs), are reported. The lasers have reduced the output-beam divergence in a simple structure which does not contain an additional spot-size transformer. To improve high-temperature characteristics, we have investigated the influence of the thickness of separate-confinement-heterostructure layers and the number of quantum wells (QWs) on the threshold current and the output-beam divergence at high temperature. As a result, the fabricated lasers show low-threshold current (∼18 mA) and high-slope efficiency (∼0.4 mW/mA) with narrow output-beam divergence (∼12°) at 85°C. Moreover, we have obtained maximum coupling efficiency of -4.7 dB in a direct coupling to a SMF, and the reliability of longer than 10 5 h (MTTF) by a lifetime test of over 2000 h at 85°C.


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- Taught intensive and regular Mandarin-Chinese language classes at many big ...
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...Mandarin Chinese is my first language and I enjoy sharing it with others. I believe in order to successfully learn a language one must have fun while learning and practicing. I have worked in China as a Chinese teacher to non-native speakers for several schools, but recently I moved to Colorado as my husband relocated for work.
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Don't Waste Your Sports Unabridged Audiobook on CD
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Product Description
Unabridged audio CD; approximately 1 hour; 1 CD; read by Sean Runnette.
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|Format: Compact disc
Vendor: christianaudio
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Publisher's Description
A concise audio encouraging Christian athletes to see sports as a true gift from God, created for his glory.
"Why is it that sports seem to bring out the best and the worst in us?" asks author C. J. Mahaney. "Sports are a gift from God. But as soon as you introduce the human heart, things get complicated." For the Christian athlete, sports are one of the key battlegrounds in which pride and self-glory are regular temptations. If sports are indeed a gift from God, why are playing fields and courts so often arenas for our egos? How are we to enjoy sports in a godly way?
Self-described "pastor athlete" C. J. Mahaney looks to Scripture for principles that speak to the role of sports in our lives. This booklet outlines how Christian athletes are to play for the glory of God and model gratitude, humility, and service. With candor and humor, Mahaney recounts his own story with sports and through illustrations and practical applications exhorts athletes not to waste their sports.


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- Individual hostels may have special booking conditions relating to group stays, please read the hostel booking conditions carefully before making your reservation.
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Welcome CBS listeners
Just a quick note to welcome CBS listeners who have tracked me down here after the interview with Frank and the mention on Market Watch in the past few hours. If you're looking for more information on the six figure blogging course – head here to get the free preview ...moreProBlogger Site News
Signatures in Blog Comments
Has anyone else noticed recently that a lot of people leaving genuine comments on blogs have also started leaving 'signature like' links to their own blogs at the bottom of their comments? (NB: I'm not talking about links within comments that are relevant to the conversation happening in the comment ...moreMiscellaneous Blog Tips
Google Adsense Change Log
A few weeks ago I was chatting to a Google Adsense consultant who was asking me for my opinion on how to improve Adsense. One of my suggestions was that they should add some sort of a 'Change Log' system which would help publishers to track changes that they make ...moreAdsense
14 Instant Messaging Etiquette Tips for Bloggers
One of the best parts about this blog is that it puts me into direct contact with hundreds of bloggers from around the world every week. This happens on a variety of levels – comments, email and increasingly Instant Messaging. I have my IM details on my about pages which ...moreMiscellaneous Blog Tips
Introducing a Shoddy Blogger
Want to see a slimey blog? A blog that tries to pass off content of other people as it's own? Have a look at Blogger Tips (no follow tag used) – a blog that is filled with either posts that are 'free articles' or other people's content. In both types ...morePro Blogging News
Online communities and integrating blogs into mainstream marketing campaigns
If you've got a spare 10 minutes can I recommend heading to Rachel's blog and downloading a PDF that she's posted that is the verbatim of a talk that she and her partner (that's blog partner and life partner) Regan did to the New Zealand Marketing Association on the topic ...moreBusiness Blogging
Gawker Announces the 'Deadspin' Sports Blog
Gawker have gone live with their latest new sports blog – Deadspin. If you want to know the power of having a successful blog network – check out their stats. At the time of writing this – the blog went live about 10 hours ago and has already had 7000 ...moreBlog Networks
Understanding Google Updates
Matt Cutts (from Google) has an enlightening post on his blog titled – What's an update? which quite simply lays out information on the topic of their updating system. I'm sure it's more complicated than he's outlined here but the information resonates with my experience of Google's updating system as ...moreSearch Engine Optimization
Preview Call Available for Download
Andy and I did the preview call yesterday for the six figure blogging course and it was really fun. It was great to hear some of the voices of some regular readers of ProBlogger.net during the Question and Answer time. Thanks for those who called in – especially those who ...moreProBlogger Site News


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Model :HT-SL-09-250
Power :250W
Input Voltage :AC85~265V 50/60Hz or DC12V
Power factor :>0.9
Nominal luminous flux :20500LM
Emitting angle :60°* 130°
Protection level :IP65
Lamp size :868*280*105mm
G.W(kg/pc) :14kg
Nominal working life :35000h
Material :Die casting aluminum body
Warranty :3 years
Detail display:
Product features:
1. Using super bright import Cree LED chip and Meanwell power supply.
2. LED street light waterproof protection grade is IP65.
3. LED street lamp is no UV or IR radiation, no mercury pollution.
4. Easy installation or replacement.
Light Distribution Curve:
Package Pictures:
LED street light appliations:
Widely used in main roads, high ways ,viaducts, urban streets, overpasses, sidewalks, public, squares ,schools, residential areas ,industrial districts, parks etc outdoor lighting


text:
During his brief remarks, Mr. O'Connell talked about the need for stability and long-term planning that was necessary for the the community. He congratulated the Community for the continued improvement in test scores which the Board also reported out in its' latest dispatch. But, what he also noted was that the turmoil at the highest echelon of the Board would eventually catch up. As such, he reinforced how things had to change and change now.
Orange County - Local
California Democrats Announce Confirmed Speakers at Daily Delegation Breakfasts for National Convention


text:
Receive Breaking News updates as they occur
Rory McIlroy, Dustin Johnson and Phil Mickelson were among the stars humbled by Baltusrol in Thursday's opening round of the PGA Championship, leaving unheralded Jimmy Walker to seize the lead. Walker, a 37-year-old American who missed the cut in three of his past four majors, fired a five-under-par 65 for a one-stroke lead over Britain's Ross Fisher, two-time major winner Martin Kaymer of Germany and Argentina's Emiliano Grillo. "All in all it was a great day," Walker said.
SOMERVILLE, Mass. (AP) — About 50 police officers and their supporters upset about a Black Lives Matter banner that has been hanging outside City Hall for nearly a year rallied on Thursday to try to pressure the mayor to remove it.


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I'm staying in Franschhoek for 2 nights at the end of the year and was wondering if all the wineries in that area are within walking distance. My husband and I are in our twenties so we don't mind walking/climbing.
Also, I've seen a couple of posts about a woman named Jaci that offers transfers/tours in the area, however, the e-mail address for her is no longer valid. Has anyone used her recently and/or have updated contact information for her?


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Item #
Northwood Blue Opalescent Tree Trunk Vase
This lovely form was produced by Northwood circa 1907-08. Popularly known as the tree trunk style, this gorgeous piece features beautiful opalescence on a stunning shade of blue.The vase measures 11" high, 2" wide at the base and 4" wide at the mouth. In excellent condition, the vase is free of any chips, cracks or discolorations.
Circa: 1907
Manufacturer: Northwood Glass Co.
Northwood Blue Opalescent Leaf Chalice Novelty Vase
This interesting vase in a pattern called Leaf Chalice was considered a novelty piece and made by Northwood about 1903. Very pretty blue opalescent, the vase measures 5 3/4" high and 4" wide. There is a flake on the base of one of the feet, otherwise free of any cracks or discolorations.
Circa: 1903
Manufacturer: Northwood Glass Co.
Fenton Deilbiss Blue Opalescent Spiral Sides Perfume
The Fenton Art Glass Co. produced glass perfume bottles for the DeVilbiss Co. beginning in the 1940's. DeVilbiss manufactured the atomizers but no glass so they looked to glass manufacturers of the day to produce the bottles. This gorgeous example was made in the 1940's and features fabulous opalescence, a ribbed body with rows of spirals on either side. There would have been a metal fitting and attached rubber and thread atomizer. Due to age, many of the metal fittings and atomizers disintegrated and were not replaced. Replacement atomizers are still available today. This beautiful perfume bottle measures 5 1/2" high, 1 1/2" wide on the body and 2 3/8" wide including the spiral sides.The bottle is in excellent condition, free of any chips, cracks or discolorations.
Circa: 1941
Manufacturer: Fenton Art Glass Co.
Fenton Blue Opalescent Hobnail Round Wine Goblets - Pr.
Fenton produced the round wine goblet in blue opalescent hobnail from 1940 to 1955.Each of these pretty wine goblets measure 4" high and 2 1/2" wide at the top of the mouth.Both goblets are free of any chips, cracks or discolorations.
Circa: 1940
Manufacturer: Fenton Art Glass Co.
Vintage Fostoria Blue Opalescent Heirloom Square Bowl
Fostoria made the lovely opalescent Heirloom pattern glass from 1959 to 1970. This is a large square shaped centerpiece or fruit bowl. The bowl measures 9" wide and 6" high. It is free of any chips, cracks or discolorations.
Circa: 1959
Manufacturer: Fostoria Glass Co.
Duncan & Miller Blue Opalescent Canterbury Candlesticks
The Duncan & Miller Glass Co. produced the Canterbury pattern from 1937 to the 1950's. These candlesticks are blue opalescent and have the most beautiful color and fire. Each candlestick measures 3 1/4" high and 4 1/4" wide on the base. Both candlesticks are free of any chips, cracks or discolorations.
Circa: 1937 - 1950's
Manufacturer: Duncan & Miller Glass Co.
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I would take my review with a grain of salt. I have never had a memory foam anything before, and was used to much lower quality box springs and futon beds. I did my research however and this bed met the specifications I wanted. Low cost, light weight, good user rating, and I did want to try out memory foam.-----Since the mattress is not 100% memory foam it will only contour so far against your body. If you stand on it, it will contour almost to the ground with about 2 inches of thickness between you and the base support. I still cannot feel the base support though so that is great. If laying on it, it feels very firm. I liked this because even though it feels firm it still contours to your body. Laying on my back I feel like I am laying on a very firm level board without the worry of certain 'parts' of my body raising my spine up in unusual ways.-----I do however sleep on my side and can notice it feel more resistant to the extra weight, which leaves me feeling uneven. I find myself actually sleeping on my side/stomach and sleeping peacefully. I believe if it was closer to 60% memory foam instead of the 1.5-2 inches of memory foam topper I would be sleeping on my side a lot easier. But those get real high in price based on what I can see, so this is very forgivable in my eyes.-----In short, great value for a firm mattress for a back sleeper. If your like me and plan to put this on top of a loft bed one day, I think you would be hard pressed to find another mattress with such a great value, quality, and low weight. I am glad I got the 8 inch mattress versus the 6 inch.-----P.S. it took my mattress 12 hours to go from 6 inches to closer to 7, and after the full 72 hours it's closer to 8 inches (or rather it probably is, but it is hard to measure from dead center above and below at the same time.) I think the review that says it's a light 6 inch mattress did not give it any time to expand beyond it's initial form. Also there was no smell with mine.
I purchased this after realizing how poor my granddaughters bed was. This was a steal! It is so so comfortable for me. I have had guests - adults and they have commented on how well they slept. For the price the quality is outstanding. I would recommend this purchase to anyone. When you get the bed it is rolled up so initially you have doubts, but unroll it and sleep on it one night. I have had it for several months and it has not changed in quality. What a great buy.
- Please tell us about the quality of the product. What a steal. This bed is so comfortable it is unbelievable. My granddaughter has slept much better since we purchased this mattress.
- How accurate was the on site description of the product? very accurate
This is our second memory foam mattress from overstock. The first we ordered was a 10 inch mattress for the top of a daybed. This 8 inch mattress we purchased for the pop up trundle that goes under the day bed. This mattress works well for that purpose. It fits the trundle perfectly and still slides under the bed. However, this is a very soft mattress. The other bed we had ordered was much more firm and had that true memory foam feel. This mattress is more like regular foam. It doesn't really form to your body and give you that weightless feeling that true memory foam does. It took no time at all to pop into its correct shape after opening. The smell wasn't too bad, but did take a good day or so to dissapate. I would reccomend this mattress for bunk beds or trundle beds. I would not reccomend it if you are looking for a high quality memory foam mattress for everyday use.
Love these! Ordered for vacation house, now ordering for home too.
The quality is good and no strong odor after open it, is not like the one that was made in China. To me, it is medium firm. I prefer softer mattress like Ikea's *%$^&$# (&^%, which I bought for my son.
This foam mattress is SOOOOO comfortable. We purchased 2 of overstock's 8" Comfort Dreams Memory foam mattresses last year for our college age boys & they love the mattresses. Since then we purchased a summer cottage and are replacing old mattresses there with the same. Last weekend I slept on one & it really is so incredibly comfortable. A better than excellent nights sleep! People ask "doesn't foam get hot?" A mattress pad, like one you would want to use on any mattress, takes care of that & we have not had that problem at all.
This mattress is amazing. It is soft yet firm and your body just melts into it. I had never slept on a memory foam mattress before however I have used and liked a memory foam mattress topper. If you have ever tried and liked a topper than you will love this mattress. The mattress was packed and shipped with great care and Overstock has never let me down on the quality of their shipping. The mattress is solid but I was able to move and lift it on the bed by myself. I am thrilled with my purchase and would highly recommend it and purchasing it from Overstock.
Since "soft" and "medium" appear to be fairly subjective terms, I'll just say this is VERY comfortable. bought the twin size for a guest bed. If I stand on it, I sink right down, and would think it's WAY too soft. But when my body weight is distributed more evenly, it conforms around me just enough (I do like my beds soft, though), but still provides support -- I don't feel like I'm sinking into the mattress.
This was good quality but not firm enough, I was using it as a 'sitting cushion' for a daybed that is being used as a sofa. I gave it to a single working mother who could use it for her son. I bought a 'regular' twin mattress locally to replace it.. Even though it didn't fit my need, I would still recommend it for a childs bed.
My kids loved this mattress. It's not soft & not too hard. I would buy again. Also the mattress didn't have a scent when I unrolled it.
This mattress is great!! Very, very comfortable - I highly recommend it!
Firm yet not too hard, affordable and resistant
Purchased one for our vacation home and it was so comfortable we ordered 2 more. Perfect night sleep.
Bought it for my 4 year old niece's bed. Great quality, I see this lasting a long time.
well worth getting. You will sleep well.
This comes in a tiny roll! But don't be worried, it puffs right up. It is SO comfortable! My child LOVES it!
Love this mattress, just the right firmness and paid a reasonable price
Once you have slept on a memory foam mattress you will never sleep on anything else. When you lie down your whole body goes aaaaaaaah! This is a good quality mattress at a reasonable cost. I bought it specifically for an antique, single, 4 poster bed. Fits beautifully.
I think this is a medium as described - not too firm and not plush. I think it's great for side sleepers and it expanded to size as described. We've had it for 2 weeks now and it seems it will last.
My daughter needed a new mattress for her daybed so we took her to a mattress store to try out mattress. She loved a $900 tempurpedic, but there was no way we could spend that amount of money on a twin mattress. A friend suggested this mattress and my daughter loves it. She no longer gets up in the morning talking about a bad night's sleep and now my son wants one. It is the perfect firmness for her and it doesn't get hot like some memory foam mattresses. It was a great purchase.


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|"Ian Hunter" <ihun...@hunterweb.net>
|Object with links to objects from a different database
|Tue, 03 Aug 2004 15:27:17 GMT
I have a system that uses one database for storing 95% of it's data, but 5% of it lives in a separate ERP that I'm linking to. OJB is talking to both databases just fine, but when I try to load an object that has auto-retrieve turned on that also happens to reference an object in a different database, OJB can't figure out that the "subobject" lives elsewhere and tries to access its table in the current database. Help?!?! --- Aoccdrnig to a rscheearch at Cmabrigde Uinervtisy, it deosn't mttaer in waht oredr the ltteers in a wrod are, the olny iprmoetnt tihng is taht the frist and lsat ltteer be at the rghit pclae. The rset can be a total mses and you can sitll raed it wouthit porbelm. Tihs is bcuseae the huamn mnid deos not raed ervey lteter by istlef, but the wrod as a wlohe. --------------------------------------------------------------------- To unsubscribe, e-mail: firstname.lastname@example.com For additional commands, e-mail: firstname.lastname@example.com
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text:
Judith A Naumann
Shawano, WI
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* Failure would be biggest bank failure this year
* Deal approved by FDIC on Thursday, report says (Adds background)
By Anurag Kotoky and Sweta Singh
BANGALORE, Aug 14 U.S. Southeast regional bank BB&T Corp (BBT.N) will buy deposits and branches of Colonial BancGroup Inc CNB.N following a move by regulators to take the struggling lender into receivership, media reports said, citing people familiar with the matter.
The deal was approved by the Federal Deposit Insurance Corp (FDIC) on Thursday night and is expected to be announced later on Friday, Dow Jones news agency reported.
BB&T shares soared as much as 10 percent on the New York Stock Exchange, while trading in Colonial shares was halted.
"BBT is trading up on the news as they would likely be able to assume the deposits at an attractive price," analyst Paul Miller of FBR Capital Markets wrote in a note to clients. "Given Colonial's risky loan portfolio, we would expect significant FDIC loss-sharing to be involved."
Colonial officials did not respond to repeated calls seeking confirmation. The FDIC said it does not comment on open and operating institutions. A BB&T spokesman declined to comment.
Colonial, based in Montgomery, Alabama, operates 355 branches in Florida, Alabama, Georgia, Nevada and Texas and has more than $25 billion in assets.
Its failure would be the largest bank failure since Wachovia's near collapse last September. Last year Wells Fargo & Co (WFC.N) won an FDIC-brokered deal to buy Wachovia after a brief but acrimonious battle with rival bidder Citigroup Inc (C.N), which initially had agreed to buy Wachovia's banking assets with government assistance.
Colonial was organized as a bank-holding company in 1981 with $166 million in assets. It website says it provides "the strength and stability of a Top 30 commercial bank."
BB&T ended June with $152.4 billion of assets. It operates 1,505 branches in 11 states and Washington, D.C.
In June, BB&T repaid the U.S. government the $3.1 billion it received under the Troubled Asset Relief Program after regulators determined the bank was well capitalized.
"We would view the transaction as a big positive for BBT," Miller said. "It would be very accretive to net interest margin."
Earlier this week, the Alabama State Banking Department had said it might appoint the FDIC as receiver or conservator for its banking unit after Aug. 12.
On Wednesday, however, Alabama banking regulators canceled a scheduled meeting with Colonial to discuss the bank's fate, without giving a reason. [ID:nN8C121593] Colonial has been battered by the credit crisis and faces a U.S. Justice Department criminal probe into alleged accounting irregularities at its mortgage lending unit.
At one of Colonial Bank's main branches in downtown Montgomery, Alabama, business appeared to continue as normal but there was no immediate sign of panic from customers.
"As long as it doesn't mess with my money, I'm fine," said Dawn Williams, a 24-year-old mother of two.
But another customer told Reuters she was worried and wanted to withdraw her money.
"I am freaking out. It doesn't makes sense to play with people's money. They work hard for it," said retired nurse Deborah Burney, 53, who has an account with husband at the branch.
"I had asked my husband to take the money out of this bank when I heard something on the TV the other night," she said. "I have been married 35 years, and that hardhead can take the money out or say goodbye."
In July, Colonial posted a $606 million second-quarter loss, its fifth loss in a row, as higher charge-offs and rising foreclosures in the bank's Florida construction-loan portfolio continue to strain its balance sheet.
BB&T shares were 7 percent higher at $27.58 by midafternoon after trading as high as $28.41, while Colonial shares remained halted. (Additional reporting by Verna Gates in Montgomery, Alabama, and Karey Wutkowski in Washington; Editing by Anil D'Silva and Mike Miller; Reuters messaging: email@example.com; within U.S. +1 646 223 8780; outside U.S. +91 80 4135 5800))
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Article List
What's in a name? Looks like rejection to me
TTAB jilts surname mark application by Ayoub, opposed by Ayoub.
Generic terms: Less than zero?
Soft drink makers tangle over trademark for zero. "That ain't nuthin,'" says TTAB.
Getting defensive: A fresh take at the TTAB?
Ruling on prior registration defense presents a new wrinkle in clothing case.
Jaws ruling gives pause
Citing mark's fame, TTAB affirms a refusal on Jaws for cooking show
Window into a foreign language? The answer's hidden
In trademark law, the doctrine of foreign equivalents is intended to protect consumers from confusion or deception caused by the use of terms in different languages.
Caution flag on stock-car legend's name, race goes on
The dispute over Earnhardt trademark introduces a wrinkle in opposing surname use
"Consent" presents a heady brew at TTAB
"Gentlemen prefer blondes," goes the phrase—though the title of Howard Hawks' 1953 reminds us of a different (and thankfully now distant) era.
Extended Argument Comes to Naught: Opposer Loses Claim of Fraud on USPTO in TTAB's First Precedential Ruling This Year
Often, when filing a questionable specimen in connection with a statement of use, applicants for a trademark at the U.S. Patent and Trademark Office will at the same time file a request for an extension of time to file that statement of use. They do so to keep the window...
Cadbury typo tests TTAB's patience
How many times might a young associate have pulled up a previously served set of document requests, performed a search for one party's name, replaced it with another's—and missed one? Probably an incalculable number of times, and if you've worked in a larger law firm, you've surely seen it happen....
Sixth Circuit says yes to the dress
A divided panel ruling in a ccopyright case suggests that there could be new protections for unique clothing.


text:
- Esteban Vicente Turégano, Segovia, Spain, 1903 - Bridgehampton, New York, USA, 2001
- Date:1959
- Technique:Oil on canvas
- Dimensions:177,8 x 200 cm
- Category: Painting
- Entry date:1999
- Register number:DO00522
- Long-term loan of Harriet and Esteban Vicente, 1999 (Promised gift)
- On display in:
Esteban Vicente moved to the United States in 1936. There he participated in two of the foundational exhibitions of American Abstract Expressionism: New Talents 1950 and 9th Street. His name is thus attached to the first generation of the New York School, and he was the only Spaniard to belong to it. Esteban Vicente contributes a very personal diction to the new treatment of abstraction, as he moves away from the action painting of the American artists and instead paints in a way marked by the structure of the composition and by chromatic work. Vicente brings a measure of intimacy that seeks clarity and simplicity, giving less importance to drama and gesture than his contemporaries did. To do so, he makes use of collage work as preparatory pieces for his paintings. Through collage, he experiments with how to modify the pictorial plane using rhythm, vibration and the interaction of colour fields created by pieces of cut-out or torn paper. No. 3 shows the characteristics of his mature language, which over his long trajectory displays interest in progressively simpler compositions, the essence of which refers to both the Baroque painting of Zurbarán and the Cubism of Juan Gris.
In the library
Esteban Vicente : pinturas, dibujos y collages, 1925-1999 : del 7 de julio al 16 de septiembre de 2007, Museo del Patrimonio Municipal / [textos, Enrique Castaños Alés, Jose María Parreño].Vicente, Esteban ( 1903-2001)[Málaga] : Ayuntamiento de Málaga, Área de Cultura, [2007]
Blanco y negro : 17 marzo-14 abril, 2000, Galería Elvira González / Esteban Vicente.Vicente, Esteban ( 1903-2001)[Madrid] : Galería Elvira González, [2000]
Esteban Vicente : pinturas y "collages" 1925-1985 : Fundación Banco Exterior, Madrid, 24 de abril al 15 de junio de 1987 / [comisarios, Vicente Todolí, Natacha Seseña].Vicente, Esteban ( 1903-2001)Madrid : Fundación Banco Exterior, [1987]
Esteban Vicente : Pinturas 1951 - 1998 / Esteban Vicente Turégano.Vicente, Esteban ( 1903-2001)Madrid : Galería Elvira González, 1998.
Esteban Vicente : recent Works. / Esteban Vicente.Vicente, Esteban ( 1903-2001)New York : Berry-Hill Galleries, 1989.


text:
Definition of bidon in English:
A container for water or other liquids, particularly as used by cyclists: never ride with an empty bidon or a full bladder
More example sentences
- After crossing the line, he talked of the hard time he had on the ascent, as he couldn't drink after he lost his bidon after 8-9 km.
- Thankfully for him, he got a huge help from Panaria's Paolo Tiralongo, who gave him his bidon as Ivan passed the Sicilian on the false-flat section.
- I believe that the tiny Tour de France winner Jean Robic - almost sixty years ago, mind - used to take bidons of lead on descents to weigh him down.
Mid 19th century: French.
For editors and proofreaders
Line breaks: bidon
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text: When I try to go to other devices, such as network drive, other computers, I click on "browse network" then "Windows Network" comes up, I double click on it, then the name of my work group "Starband" comes up. Then after about a 30 second period a message comes up "Unable to mount location, Failed to retrieve share list from server". I used to be able to connect to other devices on the network OK and can still do so under Win 7. Something has changed but being an absolute beginner I do know what. I am running 12.04. My wireless network is working as I can surf the net, just cannot connect to other devices other than the wireless router (Buffalo technologies, running DD-WRT firmware) and my DSL modem. How can I diagnose and fix this problem?


text:
Download or print the 2016/17 Academic Calendar.
Berlin Area School District's online registration is now open. All students attending school for the 2016-17 school year must be registered prior to September 1st.
Please see the attached Clay Lamberton supply lists by class for the 2016-17 school year.
Attention BHS Senior Parent/Guardian. We've come to the senior photo time of year! Now is the time to have your student's senior photos taken for the 2017 Yearbook. Click here for all of the information
Berlin summer swim lesson schedules will be posted soon. Please stay tuned here for updated lesson schedules.


text:
opacitynoun [ U ]uk /əʊˈpæs.ə.ti/ us /oʊˈpæs.ə.t̬i/ formal
Thesaurus: synonyms and related words
(Definition of "opacity" from the Cambridge Advanced Learner's Dictionary & Thesaurus © Cambridge University Press)
(Definition of "opacity" from the Cambridge Business English Dictionary © Cambridge University Press)
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Palabra del día
water, especially from a river or stream, dropping from a higher to a lower point, sometimes from a great height
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