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Glutathione (GSH) dysregulation at the gene, protein, and functional levels has been observed in schizophrenia patients. Together with disease-like anomalies in GSH deficit experimental models, it suggests that such redox dysregulation can play a critical role in altering neural connectivity and synchronization, and thus possibly causing schizophrenia symptoms. To determine whether increased GSH levels would modulate EEG synchronization, N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients in a randomized, double-blind, crossover protocol for 60 days, followed by placebo for another 60 days (or vice versa). We analyzed whole-head topography of the multivariate phase synchronization (MPS) for 128-channel resting-state EEGs that were recorded at the onset, at the point of crossover, and at the end of the protocol. In this proof of concept study, the treatment with NAC significantly increased MPS compared to placebo over the left parieto-temporal, the right temporal, and the bilateral prefrontal regions. These changes were robust both at the group and at the individual level. Although MPS increase was observed in the absence of clinical improvement at a group level, it correlated with individual change estimated by Liddle's disorganization scale. Therefore, significant changes in EEG synchronization induced by NAC administration may precede clinically detectable improvement, highlighting its possible utility as a biomarker of treatment efficacy.
Citation: Carmeli C, Knyazeva MG, Cuénod M, Do KQ (2012) Glutathione Precursor N-Acetyl-Cysteine Modulates EEG Synchronization in Schizophrenia Patients: A Double-Blind, Randomized, Placebo-Controlled Trial. PLoS ONE 7(2): e29341. https://doi.org/10.1371/journal.pone.0029341
Editor: Thomas Burne, University of Queensland, Australia
Received: August 8, 2011; Accepted: November 25, 2011; Published: February 22, 2012
Copyright: © 2012 Carmeli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the Loterie Romande (http://www.loro.ch/FR/1/homepage). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Evidence increasingly points to the involvement of oxidative stress in schizophrenia pathophysiology . In the last few years, we have shown that a redox dysregulation due to a glutathione (GSH) synthesis deficit of genetic origin represents one of the major risk factors for schizophrenia . Indeed, patients suffering from schizophrenia manifest genetically determined deficits in the GSH system. Specifically, (i) GSH levels in the brain and cerebrospinal fluid of patients are decreased –; (ii) under oxidative stress conditions, activity of the key GSH synthesizing enzyme, glutamate cysteine ligase (GCL), and the GSH levels in patients' fibroblasts are diminished , and (iii) allelic variants of the GCL modulatory subunit (gclm)  and catalytic subunit (gclc)  genes are associated with the disease.
In particular, in two case-control studies, a GAG trinucleotide with 7, 8, or 9 repeats polymorphism in the gclc gene showed an association with schizophrenia . This polymorphism has functional consequences: subjects with the ‘high risk’ genotypes (8/7, 8/8, 8/9, and 9/9) showed lower GCL activity, gclc protein expression, and GSH content than subjects with ‘low risk’ genotypes (7/7 and 7/9). Moreover, in pharmacological and knock-out models, developmental GSH deficit induces morphological, neurophysiological, and behavioral anomalies analogous to those reported in schizophrenia patients –.
A developmental dysregulation of GSH synthesis of genetic origin, when combined with environmental risk factors, which generate oxidative stress at specific developmental stages, may affect functional connectivity – in particular, neural synchronization (, see also the Discussion). This is likely mediated by hypoactive N-methyl-D-aspartate (NMDA) receptors, impairment of parvalbumin immunoreactive fast-spiking GABA interneurons, imbalance between excitatory and inhibitory activity in temporal and prefrontal cortices, and damage to myelination, resulting in altered local oscillations and long-range neural synchronization .
The fact that schizophrenia is associated with abnormalities in neural synchrony is well documented. Abnormal oscillations and/or distance synchronization are manifested in the resting state –, perceptual grouping , attention , , working memory –, consciousness , and other cognitive/behavioral responses (for review see ). Therefore, the abnormalities of synchronization might represent a core pathophysiological mechanism for psychotic and cognitive disturbances.
In a recent double-blind, randomized, placebo-controlled multicenter clinical trial, the supplementation of N-acetyl-cysteine (NAC), a GSH precursor and an antioxidant, led to the improvement of the negative symptoms and reduced side effects of antipsychotics in a cohort of 140 schizophrenia patients . Based on this promising result and on the assumption that abnormal neural synchronization in schizophrenia is related to redox dysregulation/oxidative stress, we proposed that NAC may have a potential effect on EEG synchronization. To support this hypothesis, we examine in the present proof of concept study the effects of NAC treatment on the whole-head topography of multivariate EEG synchronization in a small subgroup of schizophrenia patients from the Swiss sample of the above described NAC clinical trial.
Materials and Methods
Clinical Trial Protocol
The supporting CONSORT checklist is available as supporting information; see Checklist S1. NAC (2 g daily) and placebo were administered to schizophrenia patients in a double-blind crossover design. The clinical trial was conducted from November 2003 to November 2005. One group received NAC for the first 2 months and then placebo for another period of 2 months, and the other group received placebo first and then NAC. NAC was purchased from Zambon (Italy). NAC and placebo capsules were manufactured by DFC Thompson (Sydney, Australia) and re-conditioned by a pharmacist of the Department of Psychiatry of the Centre Hospitalier Universitaire Vaudois and University of Lausanne. EEG recordings were performed at the onset of the protocol (baseline measurements), at the point of crossover, and at the end of the study. In keeping with the main trial protocol , psychopathological scales including the Positive and Negative Symptoms Scale (PANSS) were evaluated every 2 weeks. The three syndromes including a negative, a positive, and a disorganization factor have been computed according to Liddle's model . A copy of the trial protocol is included in the Supporting Information; see Protocol S1.
The CONSORT  flowchart of the trial is reported in Fig. 1. Eleven patients (nine men; two women; aged 31.9±3.4 years; mean±standard error) meeting DSM-IV criteria for schizophrenia were recruited from the ambulatory Schizophrenia Service of the Department of Psychiatry of the Centre Hospitalier Universitaire Vaudois by an experienced psychiatrist and a psychologist well trained in Diagnostic Interview for Genetic Studies. The mean duration of illness was 9.4±2.5 years. All patients received atypical antipsychotics except one who was drug-naïve. The complete demographic and clinical characteristics of participants were described in . Among the 11 patients, 9 participated in the clinical trial and 8 completed the entire study, including EEG recordings at crossover and at the end of the study. The two patients who withdrew from the study reported that it was too demanding for them. Of the eight patients who completed the entire study, six were in the group that first received NAC and then placebo; the remaining two received placebo first and then NAC. As reported in , no side-effects due to NAC have been observed. Both patients and investigators were blinded until the time of analysis, when data pooling necessitated unblinding. Recruited patients gave fully informed written consent, and the Ethics Committee of the Faculty of Biology and Medicine of the University of Lausanne approved all procedures. All 11 patients underwent the Diagnostic Interview for Genetic Studies, developed by the NIMH , , and remained on their usual antipsychotic medication for the duration of the trial both in terms of type and dose of medication. Recently the effects of NAC on auditory sensory processing as manifested by mismatch negativity, a component of auditory evoked potential related to NMDA receptor function, were studied in this group of patients .
EEG recording and pre-processing.
The resting EEGs were recorded with the 128-channel Geodesic Sensor Net in a semi-dark room with a low level of environmental noise. To control the quality of recordings the EEG tracings were constantly monitored online. The subjects were seated in a comfortable chair and instructed to stay relaxed and motionless with eyes closed for 3–4 min. All the electrode impedances were kept under 30 kΩ . The recordings of vertex-reference EEG were made using a 12-bit analog-to-digital converter, a digitization rate of 1000 samples/s, and a low-pass filter set to 100 Hz. They were further filtered (FIR, band-pass of 1–70 Hz, notch at 50 Hz) and segmented into non-overlapping 1 s epochs using NS 4.2 software (EGI Inc., Eugene, OR, USA). Finally, two separate data sets were obtained for further analysis: one by re-referencing the data against the common average reference (CAR), and one by transforming the data into a two-dimensional surface Laplacian computed via the Current Source Density toolbox . Those two data sets were the input for two separate synchronization analyzes, described further.
Artifacts in all channels were edited offline: first, automatically, based on an absolute voltage threshold (100 µV) and on a transition threshold of 50 µV (sample to sample), and then on the basis of a thorough visual inspection. The sensors that recorded artifactual EEG (>20% of the recording time) were corrected using the bad channel replacement tool (NS 4.2 EGI, USA). Furthermore, we excluded the outer-ring sensors because of their well-known instability. The number of artifact-free epochs entered into the analysis was 171±39 for the NAC condition and 168±62 for Placebo condition.
The data were filtered into four EEG frequency bands: theta (3–7 Hz), alpha (7–13 Hz), beta (13–30 Hz), and gamma (30–48 Hz). To this end, we applied an FIR filter with no phase-shift .
Multivariate phase synchronization.
To assess the interactions among the recorded neuronal pools, we computed a Multivariate Phase Synchronization (MPS) index, that is, the modulus of an order parameter of a population of oscillators . MPS is a measure sensitive only to coherence in the phase of oscillations and not to their amplitude. Specifically, MPS measures the amount of phase similarity within a population of oscillators. Consequently, the MPS may be interpreted as the collective rhythm produced by the population under study. For instance, if all oscillators move in a single tight clump, MPS is approximately 1 and the population acts like one giant oscillator. If the oscillations occur incoherently and no macroscopic rhythm is produced, MPS is approximately 0.
Let be the sampled phase of oscillator (i) at time t, L the number of available samples, and N the number of systems under study. The MPS among the N oscillators is given by the formulawhere j is the imaginary unit. The first sum provides an instantaneous estimate of the degree of phase similarity. The second sum averages that over time, thus providing an estimate of the synchronization during the observed time period. The MPS was calculated from the pre-processed epoched EEG signals in the four conventional frequency bands (see previous sub-section). The signal phase was estimated by means of the Hilbert transform . To assess the whole-head synchronization topography, we computed the MPS sensor-wise over the cluster of locations defined by the sensor itself and the surrounding sensors belonging to its second-order neighborhood . Such a cluster (on average about 12 cm wide) is shown in Fig. S1 and spans typical distances of cortico-cortical connectivity . This approach has been numerically validated and proved to be a robust and easily scalable multivariate approach, highly sensitive even with a reasonably small amount of data .
The interpretation of surface EEG synchronization is limited because of its contamination by volume conduction and reference electrode effects . These unwanted effects can be minimized with a high-resolution Laplacian, which isolates the source activity under each sensor . Yet along with volume conduction, a Laplacian removes genuine synchronization of widely distributed source regions, which can be captured by CAR EEG. Here we examined the topography of synchronization based on a combination of Laplacian and CAR EEG, thus encompassing both smaller and intermediate spatial scales of EEG dynamics.
To minimize the effects of signal-to-noise ratio variations on synchronization results, we performed a supplementary analysis of EEG power and removed from the MPS maps those sensors for which such effects could be significant (see Text S1).
Statistical assessment was performed using the repeated measures one-way ANOVA with two levels (NAC and Placebo). Statistical inference was performed independently for each frequency band of interest. The MPS and Power/Energy estimations that entered into the statistical analysis were computed for each patient by using a summary statistic (the median) over values obtained for all epochs belonging to the same condition. Considering that synchronization and power/energy values vary over a finite interval and thus cannot have a Gaussian distribution, we applied a non-parametric permutation approach. The permutation procedure was refined according to a repeated measure design .
A P-value for each sensor was obtained by performing 5000 permutations, which were identical for each sensor in order to retain the spatial covariance structure of the data. To get a statistical significance for the whole map, we controlled for multiple hypothesis testing by computing false discovery rates (FDRs) with the BH linear step-up method . As the computation of each MPS value involved its neighbors, the FDR at each sensor was estimated from the P-values of the neighboring sensors. All the reported effects correspond to FDR values less than 0.05. To highlight the most pronounced effects, we computed a Cohen index for the size of the effects. Following a conservative statistical approach, we report only sensors with effect size bigger than 1 (i.e. the standard deviation of the effect is bigger than its average value) for CAR EEG, and 0.7 for Laplacian. Finally, we report only clusters composed of at least three neighboring sensors.
To minimize the losses due to a high dropout rate characteristic for a crossover design, we tuned our analysis to a small sample size not only by using extremely rigorous and conservative group statistical analysis, but also by applying an individual level statistics. For each patient, the distribution of the MPS values upon the available epochs was compared between the two conditions, NAC and Placebo. To test the null hypothesis of equal medians, we applied a Wilkoxon rank-sum test. The BH-based FDR values were verified to be at least <0.05, and only sensors significant at population level were kept. Considering that the clinical effects of NAC were already established in a large-sample double-blind, randomized, placebo-controlled trial with 140 patients , our approach seems to be sufficient for a neuroimaging description of the probable mechanisms of clinical improvement in at least a subsample of Schizophrenia patients.
To assess whether the synchronization changes in the patients are related to psychopathological scores, we analyzed the correlation topography between MPS and PANSS as well as between MPS and Liddle's factors . The correlation maps were computed by estimating the Pearson correlation coefficient sensor-wise between the MPS contrast and the corresponding contrast for PANSS and for Liddle's score. To determine whether the correlation values were significantly non-zero, we applied a permutation-based test . The P-values obtained after performing 5000 permutations were corrected for multiple comparisons by means of the BH method and considered significant at FDR<0.05.
The NAC treatment significantly affected EEG synchronization (Fig. 2). As the head diagrams show, in the CAR EEG, it induced MPS increase between the sensors clustered over three locations – namely, the left parieto-temporal (the neighborhood of T5 and P3 locations), the right temporal (the neighborhood of T4), and the right prefrontal (the neighborhood of Fp2). The left parieto-temporal cluster was significant across all frequencies, the right temporal cluster appeared at the theta and beta-gamma frequencies, while the prefrontal cluster was limited to the alpha band. For Laplacian, we found MPS increases in these three locations only for the higher (beta-gamma) EEG frequencies.
The whole-head maps for the MPS show the surface topography of the NAC vs. Placebo effect. The maps are presented for CAR EEG data (top) and Laplacian data (bottom) for the theta (θ), alpha (α), beta (β), and gamma (γ) frequency bands. They are superimposed on the diagrams of the Geodesic 128-channel Sensor Net. The sensors corresponding to the International 10–20 System are shown with black circles. They are labeled in the upper left diagram. The large circles (irrespective of color) designate significant effect. The red sensors correspond to NAC>Placebo. All the effects are shown at FDR<0.05 and the sizes of effects are thresholded at 1 for CAR EEG and 0.7 for Laplacian. The colored surface (obtained by a trilinear interpolation from the three nearest electrodes) represents the effect size (see Materials and Methods for details).
Being limited to a small sample, we secured our group-level findings by considering the individual NAC-induced changes of EEG synchronization (Fig. 3). As can be seen from this figure, the MPS increases in the CAR EEG were robust across all the patients in all the frequency bands, except the theta band in patient P4. In the Laplacian, the results were more variable; yet, for each frequency band, the group-significant effects could be tracked at least in six out of eight patients. It should be noted that a supplementary analysis of EEG energy showed no significant effects of the NAC treatment and that the sensors for which the changes in EEG energy correlated with MPS were outside the clusters shown in Fig. 2. Furthermore, Fig. 3 shows that the imbalance in the number of patients receiving Placebo or NAC first did not affect our findings. Indeed, patients P2 and P5, which received Placebo earlier than NAC, demonstrate responses similar to the average one (Fig. 2). Furthermore, since the majority of the patients received NAC treatment prior to Placebo, any carryover effects would have reduced the difference in synchronization between the two treatment types. The fact that the effect of NAC nonetheless withstands this sequence argues against a strong influence of treatment order.
The whole-head maps for the MPS show the surface topography of the NAC vs. Placebo effect for individual patients. The reported significant changes are restricted to the sensors and frequency bands that demonstrate a significant effect at the population level (Fig. 1), including four frequency bands for CAR EEG (θ, α, β, γ) and two frequency bands for Laplacian (β, γ). Patients are labeled as P2, P3, P4, P5, P6, P7, P9 and P13. Other designations are as in Figs. 2 and S1.
A correlation analysis allowed us to look at the relationship between EEG synchronization and the psychopathological scores of the patients. No correlations were found between MPS and PANSS scores for the contrast NAC vs. Placebo. Since various factor analytic studies point to the fact that three syndromes (negative, positive, and disorganization) may underlie schizophrenia symptomatology , , and that the disorganization syndrome is associated with executive functions and attention , , we also explored the relationship between EEG synchronization and Liddle's scores . We found significant inverse correlations between Liddle's factor of disorganization and MPS changes in the NAC vs. Placebo contrast for the left parieto-temporal cluster at beta and gamma frequencies (Fig. 4). These correlations show that the greater the MPS increase, the greater the clinical improvement. The average value of the coefficient of determination (R2) was 0.39 for CAR EEG and 0.31 for Laplacian, which means that synchronization variation can predict or explain 39% and 31% of Liddle's score variation, respectively.
Significant Pearson correlations at FDR<0.05 are shown in the alpha (α) and beta (β) frequency bands for CAR EEG and Laplacian data. Blue circles designate the sensors with inverse correlations. The size of the correlations is reported as the coefficient of determination defined as the square of the Pearson correlation value (R2).
Our study, through whole-head EEG imaging of multivariate EEG synchronization, revealed for the first time that NAC, a GSH precursor, significantly affects EEG synchronization in schizophrenia patients. In so doing, it increases synchronization for three clusters located over the left parieto-temporal, the right temporal, and the bilateral prefrontal regions. These changes are manifested across theta-gamma frequency bands in the CAR EEG but limited to beta-gamma frequencies in Laplacian, suggesting involvement of deep sources at slow frequencies and both deep and superficial sources at fast frequencies , which fits current models of EEG rhythm generation –.
The synchronization changes are robust not only at a group, but also at an individual level, which, at least partially, compensates for the limitation imposed by the small size of the sample under analysis. In other words, the significant individual synchronization changes confirm the presence of a subgroup of schizophrenia patients that respond to NAC by changing the landscape of functional connectivity. Correlations between the treatment-related dynamics of Liddle's score for the factor of disorganization and the synchronization changes in the NAC vs. Placebo contrast for the left posterior and the bilateral prefrontal clusters further validate these data. These results are also consistent with reports on association between the syndrome of disorganization and defective performance in tasks involving executive functions and attention as well as language and, possibly, body representation , .
In the context of a specific pattern of synchronization changes, it is important to consider that the participants of this study were among the patients involved in a randomized, double-blind, placebo controlled, add-on clinical trial, in which the GSH precursor NAC significantly improved the negative symptoms and reduced side-effects of antipsychotics . Furthermore, in roughly the same group of patients (7 out of the 8 analyzed here), NAC improved the auditory evoked potential by increasing the NMDA-dependent mismatch negativity , which is typically reduced in schizophrenia –. On the whole, the EEG/MEG studies suggest that the temporal and frontal cortices contribute to generation of mismatch negativity (for recent review see ), which was the case for this group as well . The remarkable agreement between the topography of mismatch negativity generators, as shown by the source analysis in the latter study, and the clusters of NAC-related changes in multivariate synchronization, revealed here, suggests that functional connectivity plays a role in the central auditory and cognitive dysfunction underlying the schizophrenia symptoms.
Our findings are in agreement with previous research emphasizing abnormal functional connectivity in schizophrenia including resting and task related changes (for review see ). The report of Jalili and collaborators  is of special interest here, since it provides the whole-head landscape of multivariate synchronization in schizophrenia patients in comparison with normal subjects. Although that study applied a different measure of multivariate synchronization, namely the S-estimator , experimental data show similarity in results obtained with different estimators of multivariate EEG synchronization (e.g., ), and, thus, allow a qualitative analysis of the NAC-related changes in the context of the resting pattern of synchronization in schizophrenia.
Resting EEG in patients was characterized by bilateral hyper-synchronized clusters over the temporal lobes and by a hypo-synchronized cluster over the midline postcentral region . The individual scores from all the PANSS scales correlated with these abnormalities such that the greater synchronization changes (including increase in synchronization) in all the clusters were linked to the aggravation of pathological symptoms. Furthermore, their topography was similar to the structural maps of cortical damage in schizophrenia . Considering the fact that there is only a partial overlap between the hyper-synchronized temporal clusters in untreated patients  and the regions of increased synchronization in the NAC-treated patients (here), we can suggest that NAC is involved in a compensatory response within the networks with relatively preserved connectivity.
As mentioned in the Introduction, our experimental model has shown that abnormal connectivity can result from a redox dysregulation induced by a compromised GSH synthesis. Indeed, in the hippocampus, GSH deficit results in the alterations of NMDA-dependent synaptic plasticity through interaction with the NMDA redox site . Under an oxidative stress, GSH deficit induces a reduction in beta/gamma-oscillations in the ventral hippocampus, associated with social and emotional behavioral anomalies . In the anterior cingulate cortex, transitory GSH deficit during development leads to decreased spine density , . Similar findings were reported in schizophrenia patients , .
These abnormalities in anatomical and functional connectivity are associated with changes in the GABA-ergic fast spiking parvalbumine interneurons. For example, a reduction in beta/gamma-oscillations in ventral hippocampus was associated with a decrease in the number of parvalbumine-immunoreactive GABA interneurons . In the anterior cingulate of gclm−/− mice, a decrease in the power of beta and gamma oscillations was accompanied by the delayed maturation of parvalbumine interneurons . This is consistent with the critical role of the GABA-ergic fast spiking parvalbumine interneurons in the mechanism of network synchronization –.
A large body of evidence consistently supports the claim that parvalbumine-immunoreactive GABA interneurons are altered in schizophrenia . Moreover, converging facts link this alteration to the hypofunction of NMDA-receptors . Specifically, the hypofunction of NMDA-receptors leads to the over-production of free radicals, which can induce the impairment of parvalbumine interneurons , . Considering the association between NMDA-receptors' hypofunction and GSH deficit, these results suggest that the GSH precursor NAC can improve synchronization dynamics in schizophrenia through interaction with parvalbumine GABA-ergic connectivity .
Indeed, here we observed such effects of NAC on synchronization after 2 months of treatment, at a time when no significant amelioration of schizophrenia symptoms was yet detected at a group level. However, (i) in this group, the Liddle disorganization factor scores correlated with the individual parieto-temporal synchronization responses to NAC, which survived rigorous statistical testing, and (ii) the clinical picture improved in a larger sample within the frame of a six-month clinical study . In the case that the results observed in the present proof of concept study can be reproduced within a larger clinical sample, we conclude that synchronization dynamics can be more sensitive to the treatment effects than conventional symptomatology scales and that it has potential as an early biomarker for treatment efficacy.
Example of spatial localization of MPS estimator. The sensor locations in red exemplify the second neighborhood for sensor in green (sensor 76) that is the territory considered in the calculation of a single value of MPS.
Placebo vs. Baseline changes in population multivariate EEG synchronization. The whole-head maps for the MPS show the surface topography of the Placebo vs. Baseline effect in the whole group of schizophrenia patients. The significant effects were obtained for CAR EEG (top) and Laplacian (bottom) for the theta (θ), alpha (α) and beta (β) frequency bands. They are superimposed on the diagrams of the Geodesic 128-channel Sensor Net. The sensors corresponding to the International 10–20 System are shown with black circles. They are labeled in the upper left diagram. The large circles (irrespective of color) designate significant effect. The red sensors correspond to Placebo>Baseline, while the blue sensors correspond to Placebo<Baseline. All the effects are shown at FDR<0.05. The colored surface (obtained by a trilinear interpolation from the three nearest electrodes) represents the effect size (see Materials and Methods for details). The significant effects are thresholded at an effect size of value equal to 1.
Placebo vs. Baseline changes in individual multivariate EEG synchronization. The whole-head maps for the MPS show the surface topography of the Placebo vs. Baseline effect for individual patients. The reported significant changes are restricted to the sensors and frequency bands that demonstrate a significant effect at the population level (Fig. S1), including three frequency bands for CAR EEG (θ, α, β) and two frequency bands for Laplacian (θ, β). Patients are labeled as P2, P4, P5, P6, P7, P9 and P13. P3 is missing here since baseline recording was of insufficient quality. Other designations are as in Figs. 2 and S1.
Surface topography of correlations between MPS and Liddle's factor of disorganization for Placebo vs. Baseline contrast. Significant Pearson correlations at FDR<0.05 obtained in the theta (θ) and beta (β) frequency bands for CAR EEG are shown with large red (for positive correlations) circles. The size of correlations is reported with the coefficient of determination (R2).
Analysis of EEG energy and effects of placebo on EEG synchronization.
Trial protocol 106-03 CE_18-8-03.
We thank Suzie Lavoie for EEG data collection and participation in coordinating the project. We thank Ms. D. Polzik for assistance in the preparation of the manuscript. Finally, we would also like to acknowledge all the patients who kindly agreed to participate in the study.
Conceived and designed the experiments: MC KD. Performed the experiments: MK. Analyzed the data: CC MK. Contributed reagents/materials/analysis tools: KD CC. Wrote the paper: CC MK KD.
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ZTE has unveiled a new Blade-series phone, the Blade A2, in China. Priced at CNY 699 (about Rs. 7,000), the new ZTE Blade A2 will be available to shop for in China through e-commerce website, JD.com, starting June 15.
The successor to the ZTE Blade A1 comes with loads of enhancements which includes an all-metal frame and 4G VoLTE support. The Blade A2 sports activities a 360-degree wi-fingerprint scanner that the organization claims can unlock the tool in just zero.3 seconds. The smartphone packs a hybrid SIM slot this means that that it may assist either dual-SIM playing cards or one SIM and another slot for microSD card. The Blade A2 comes with 4G LTE and supports VoLTE (voice over LTE) with HD voice name compatibility. The chinese employer touts that the cellphone can help down load speeds of up to 300Mbps on 4G networks.
For wireless, ZTE Blade A2 functions a wiwireless-inch HD (720×1280 pixels) IPS 2.5D show. it’s miles powered by means of an octa-core MediaTek MT6750 clocked at 1.5GHz coupled with 2GB of RAM. there is 16GB garage on board and it helps expandable garage via microSD card (as much as 128GB).
The Android wiwireless.1 Lollipop-primarily based ZTE Blade A2 sports activities a thirteen-megapixel rear digital camera with LED flash and section detection autofocus (PDAF). The cellphone additionally homes a wi-five-megapixel front camera with LED flash. The handset measures 143.8×70.2×7.9mm and weighs 135 grams.
apart from 4G LTE, the Blade A2 supports 802.11 b/g/n, Bluetooth, GPS/ A-GPS, and Micro-USB connectivity alternatives. The handset is sponsored via a 2500mAh battery.


Eximpo Cool Chains (Pvt.) Limited a leading cold storage division of Star Textile Mills is seeking a dedicated “Ammonia Refrigeration Operator” for its cold storage (Ammonia Operated Units) based at Karachi.
- Proficient knowledge regarding Operation of ammonia refrigeration plant operations, diagnosis electrical and mechanical problems.
- Work experience on piston and screw compressor and their controls.
- Complete work orders, records, logs and other written or computer based documents.
- Diagnose machinery and equipment to detect and investigate for irregularities and malfunctions.
Qualification: Minimum DAE In mechanical, electrical or refrigeration
Experience: 3 years of relevant experience in ammonia operated units.
Interested candidates can apply with confidence at [email protected] by mentioning position title “Ammonia Refrigeration Operator” in the subject line.


text:
Ambassador: Turkey’s disturbances will have no lasting damage
Azerbaijan, Baku, June 3 / Trend A. Akhundov /
The recent events in Turkey will have no serious impact on the economic development of the country and its tourism potential, Turkish Ambassador to Azerbaijan Alper Coshkun said today.
"It is necessary to understand that Turkey's economy is built on a healthy and a strong foundation," the ambassador told media today. "The development of the Turkish economy is not accidental. It is the result of considered and long term reforms.
"The recent events must not form the thoughts that they will stop the trend of economic development, "he said. "Of course the current situation in Turkey will have an impact on the intention of tourists who want to visit the country. However one must not forget that the tourism industry in Turkey is developed and reliable. I do not think this will have a major impact on the tourist flow to the country."
The most important thing is that the Turkish people demonstrate their will, but this must be accompanied by compliance with the rules of public order.
Rallies are being held in various Turkish towns to support the protesters in Gezi Park at Taksim Square in Istanbul. The protesters oppose the destruction of the park. Police used tear gas and water cannons to disperse the protesters..
According to the Turkish Interior Ministry, some 58 people were injured and over 730 people detained.
The 6th Istanbul Administrative Court decided to suspend the construction of the Topcu Kıslası shopping centre on Taksim Square.

domain: economics


The Financial Intelligence Unit (FIU) is a national central agency that receives financial information from accountable
institution analyses such information and where a money laundering or terrorist financing offence is suspected to have
taken place disseminates the disclosure of information to law enforcement agencies and supervisory authorities, for investigation and possible prosecution.
It is also mandated to coordinate Anti-Money Laundering and Combating the Financing of Terrorism (AML/CFT) activities in the Country. The Unit is also going to assist
in informing policy direction by conducting research on trends of money laundering and terrorist financing and educate and inform the public about trends in money laundering and related crimes.
The FIU further exchanges and shares information with its foreign counter parts and undertakes typology studies on money laundering and terrorist financing techniques.


text:
Latest news & views
2019 European SportsTech Report features ThinkSport and THE SPOT
The 2019 version of the European SportsTech Report was published this week by SportsTechX, a company that provides data and insights about SportsTech start-ups and their surrounding ecosystem. The comprehensive report claims that there are more than 1.500 active SportsTech companies in Europe and the invested capital reached a new all time-high with about €364 mn in 2018, four times as much than in 2014. Leading European countries with regard to the amount of start-up companies are the UK, France, Germany and Spain.
The report also features an interview with ThinkSport Director Anna Hellman and puts ThinkSport’s thrilling sport and innovation event THE SPOT on the SportTech events map.
The report comes as mix of data driven insights and more than 60 interviews with people at the core of a fast moving and thrilling ecosystem, including experts, 25 start-ups, investors and deal flow, accelerator and incubator programmes as well as events and other initiatives.
Get the report for free at www.sportstechx.com/estr and meet Benjamin Penkert, founder of SportsTechX at THE SPOT from 28 to 29 May in Lausanne, where he will present details of the findings.
Asked about the motivation to compile the report he said: “Whilst the European SportsTech scene is getting more and more mature, it needs a reliable, fact-based view of the market, to grasp its actual size and development. The same is true for an overview of the involved people and projects, to showcase opportunities and success stories. Our report aims to raise transparency and awareness in order to contribute to the further growth of the community.”
First published in 2018, the report will be released annually, in order to provide a continuous view on the market.


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- United States
Ireland is offering immigration to wealthy investors from non-European Union countries though two initiatives entitled as The Immigrant Investor Programme and The Start-up Entrepreneur Programme in a bid to attract overseas investors to help improve its economy.
The target of these two immigration packages will mainly be non-Europeans who, the Irish economists think, can bring abundant of revenue to their nation.
Under the revised visa laws, the businessmen and their families will be issued multi-entry visas initially for a period of five years. However, this period will be extended on grounds of the nature of business ventures.
The minimum rang of investment that a business visa applicant will be required to ensure is EUR400,000 (USD520,000) for endowment-related investments. However this range for the new Immigrant Investor visa will be EUR2M.
Ireland’s minister for Justice, Equality and Defence, Alan Shatter, said, “We need to do more to tap into the entrepreneurial potential that exists among migrants”.
Under Start-up Entrepreneur Programme, the migrants with innovative and feasible business ideas and revenue of EUR70,000 will be granted residency in Ireland so that they can executive their ventures.
The investors will be given proper time to set up and run their businesses without setting any job creation target in the beginning. They will also be given enough relaxation in terms of taxes and other payable dues.
An Evaluation Committee will be formed to gauge the progress of business projects regularly and report to the ministry of Justice, Equality and Defence.
The new policy has been well-debated and finalised. It is likely to be unearthed by March 2012.
Badly dogged by the recent global economic recession and the resultant unemployment, Ireland needs foreign investment to recover its economy and create jobs for a large number of the youth. The Immigrant Investor Programme and The Start-up Entrepreneur Programme will prove to be greatly helpful in this regard.
Tags: Business immigration, Business Visa, Immigrant Investor Program, Immigration, Ireland, The Start-up Entrepreneur Programme


text:
But each time he reached out to hold it or kiss it, it slipped away from him. How often are longed-for arms thrust into the middle of water! Her body is gone but her bones became rocks and her voice remains and can be heard in mountain valleys and in caves. What you love—turn away from your ruin. This makes their relationship work … in the beginning. A size prodigious, his enormous bulk, if seen extended where was naught to hide, would rival in its length the Serpent's folds, involved betwixt the planes of the Twin Bears. Pausanias even stated that he believed the flower existed long before Narcissus.
Attempts to kiss and hold the reflection are in vain, and Narcissus is only frustrated by the teasing reactions of the image. Then did I climb a promontory's height, to learn from there the promise of the winds; which having done, I called the men and sought once more my ship. Whenever calamity befell the race of Cadmus she rejoiced, in secret, for she visited her rage on all Europa's kindred. However, Pausanias expresses his disbelief of how a young man old enough to fall in love could be so ridiculously naive as to not know the difference between a real man and his own reflection. Because she can't initiate conversation, she has to wait for him to make the first move.
And I alone, of twenty mariners that manned that ship, remained. Tiresias told her that her son, , would live a long and happy life as long as he did not know himself. This opposes most of the erotic myths in the Metamorphoses where the pursued is the victim. Her nature fought against it, nor did it allow her to initiate. Pausanias summarized Ovid's story, but also had his own version: The spring of Narcissus is located on a mountain top at the river Lamus in a place called Donacon.
The second major difference between the stories is in how Narcissus dies. They attempt to eliminate these uncomfortable feelings by demonstrating independence, courage, and strength — ideals with which they identify. They must contend with demands, judgments, and self-centeredness. They will do what it takes to prop up their image and block negative feedback. Then, after he had been received into the Underworld, he even began to gaze into the Stygian pool; planxere sorores naides et sectos fratri posuere capillos, planxerunt dryades; His Naead sisters began to lament, and his brothers combed his parted hair; the Dryads began to grieve; iamque rogum quassasque faces feretrumque parabant: nusquam corpus erat; croceum pro corpore florem inveniunt foliis medium cingentibus albis. Finally, he goes in search of them. Another five-years, and the lad might seem a young man or a boy.
Going through the different ways it has been interpreted, it is impossible to formulate a clear consensus. Lycaon met Jove in a mortal form but didn't believe that he was actually a god. But now an unarmed boy will conquer Thebes: a lad whom neither weapons, wars nor steeds delight; whose ringlets reek with myrrh; adorned with chaplets, purple and embroidered robes of interwoven gold. Here is a quote regarding the entirely different version of the Narcissus myth from the translation of Descriptions of Greece, book 9, chapter 31: The story goes on that Narcissus fell in love with his sister, and when the girl died, would go to the spring, knowing that it was his reflection that he saw, but in spite of this knowledge finding some relief for his love in imagining that he saw, not his own reflection, but the likeness of his sister. And, O young men, of active prime whose vigor equals mine! Cerulean Liriope first exacted an attempt, with faith, on his authenticated voice. Their criticisms escalate, and they may act distant and dismissive.
O, how often she wished to approach him with honeyed words, and to summon him with soft pleas. To plead in soft entreaty! This conflict is usually a matter of one language having a single word or succinct phrase for a concept which another language might need an entire sentence to capture. Then, Diana splashes water on Actaeon. These conflicting feelings build a sense of confusion and anxiety about the unfolding plot. When he had vainly wandered over the earth for who can fathom the deceits of Jove? Last updated 24 October 05. The poet warns men and women alike not to disdain suitors lest they suffer a similar fate.
Many youths and girls desired him, but the hubris was so great in his unfeeling frame: he touched no youths, no girls. Through the painting all he can see and hear is the reflection of him. By Bacchus do I swear to you and naught celestial is more potent all the things I tell you are as true as they surpass the limit of belief. Later, he revisits the incestuous love theme with the story of Myrrha who develops a non-filial love for her father, Cinyras. The Biblical account in Genesis, probably written by Moses around 1500 B.
In this cave, there is a spring, where Diana and her nymphs like to bathe. The unfortunate girl is already sporting a baby-bump. All that is lovely in himself he loves, and in his witless way he wants himself:—he who approves is equally approved; he seeks, is sought, he burns and he is burnt. That of yours has nothing for you. Acoetes now tells his own story. He is instructed to call the region Boeotia.
Translations of the documents have been underway since 1898, and in 2005, what appears to be remnants of a papyrus containing mythological stories was published. The Mystical Hymns of Orpheus. Therefore, it is possible that the Narcissus myth existed in the Greek oral tradition well before poets took to pen. Yet there is too much bread, too much wheat and corn, meat and oil and almost every other commodity required by man for his subsistence and material happiness. There is no lengthy appositive mourning her folly. The American dream according to americanradioworks.

domain: artistic


Onward Christmas Warriors …
It’s beginning to feel a lot like the War on Christmas, at least for culture warriors alert to any signs of an anti-Santa strain. Lucky for them, Donald Trump is around.
In the latest example of pollsters having fun, the folks at Public Policy Polling have surveyed the land and, after checking it twice, found out that among voters who believe there is an assault on yuletide cheer, the billionaire developer is the 2016 presidential candidate they most trust to protect America from the War on Christmas. “I think that those people who are inclined to believe there is a War on Christmas, that they think their country is turning away from them, or is muffling them, then Donald Trump has put himself forth as their champion, and will call out what they think is going on,” said Jim Williams, a PPP polling analyst.
Twenty-nine percent of those surveyed said Trump was the man to beat back Scrooge’s forces, beating out the 16 percent who thought retired neurosurgeon Ben Carson was their Christmas warrior. Hillary Clinton had 15 percent think she could lead the holiday cheer, followed by Sen. Ted Cruz, R-Texas, at 14 percent, former Florida Gov. Jeb Bush at 9 percent, and Sens. Marco Rubio, R-Fla., and Bernard Sanders, I-Vt., at 6 percent each.
Might there be some irony that two of Trump’s more avowedly religiously opponents, Carson and Cruz, were far behind? Williams thinks that while Trump enjoys the reputation for speaking up to purported political correctness, Cruz might be gaining.
“I think we’re in a transition time, where Carson is heading down and Cruz is heading up. If we had done this three months ago, you’d probably see Cruz ahead of Carson,” Williams said.
But there’s a rub. The number of voters who even think there is a War on Christmas is declining, according to PPP’s polling.
In 2012, when the firm left its first Christmas poll in our stockings, 47 percent of voters believed in a Kris-Kringle-centered conflict, compared to 40 percent who didn’t. Three years later, the most wonderful poll of the year found only 37 percent believing in the WOC, compared with 42 percent saying there was no such thing.
There is also a party divide, with 56 percent of Republicans saying the War on Christmas was real, compared to 26 percent who didn’t — the statistical inverse of Democrats, 26 percent of whom believed in the WOC to 55 percent who doubted it existed.
One Christmas figure not too entangled in the partisan divide is Santa Claus himself. In the 2012 holiday poll, PPP found that 44 percent of voters thought Santa was a Democrat and 28 percent thought he was in the GOP, a survey taken after President Barack Obama had been re-elected.
Fast forward three years, though, and it appears fewer boys and girls think Santa has a party preference. Twenty-eight percent thought he was a Democrat, while 22 percent thought he was a Republican, with half not sure.
Santa, it seems, might be the ultimate general election candidate.
And what was the biggest surprise PPP unwrapped?
“I think it’s kind of funny that Republicans preferred fruitcake over Democrats,” Williams said. Among all voters, 38 percent said they thought the alleged treat was good, while 52 percent opted for “nah.” But 50 percent of Republicans and 58 percent of seniors liked fruitcake, compared to only 39 percent of Democrats and 27 percent of young voters.
“Old people and Republicans are on board with fruitcake. You wouldn’t think anyone would be,” Williams said.
And then there was this shocking finding: Only 13 percent of voters thought “Die Hard” was a Christmas movie, compared to the 62 percent who said the Bruce Willis action-comedy was not, despite its Christmas-in-Los Angeles setting. Maybe those surveyed missed Willis’ gift-wrapped message to the terrorists he is battling in the movie: “Now I have a machine gun. Ho ho ho.”
The survey of 1,267 registered voters via phone and internet was conducted Dec. 16-17 and has a 3-point error margin.


text:
I had loop diathermy on the 27th March, had heavy bleeding and ended up in a&e on the same day.
after that I was having watery pinky discharge but the last day or so I've had more red blood. I had a big clot come out today and now seem to be bleeding a lot again, not sure if it's my period or not.
Has anyone had this ? I know it's normal to bleed up to 4 weeks or so after treatment but wasn't sure how much is normal??

domain: medical


text:
By Greg Evans, Digital Arts Editor
It’s a familiar feeling for many queer students in Bristol, heading out for the night, not knowing how freely you’ll be able to express yourself. It’s a likely narrative across the UK, but seems surprising in a city so often cited for its liberal atmosphere.
Enter George Buckthought, a 19-year-old creative carving out exciting new queer spaces in Bristol. Heading up their own management company, George centres the intersections of music, art and queer identity. Chatting on Zoom ahead of their most recent event, CLIMAXED at Strange Brew, we pored over our experiences of the Bristol queer scene.
The Bristol Quality of Life Survey 2020/2021 reported that 9.1 per cent of Bristol’s population identify with a sexuality other than heterosexual. Despite comprising such a significant minority, opportunities for queer students to build community in the city often don’t extend further than the Students Union.
With an ‘everyone’s welcome’ approach, CLIMAXED seeks to extend the arm of alternative nightlife into the existing queer scene in the city. Creating space for all forms of queer expression, where students and locals alike can enjoy queer art and music in a safe space, free from convention.
I ask what goes into planning such an ambitious night from scratch, ‘how much time do you have’, George quips. Running from 8pm to 2am, this multi-form and multi-genre event toes the line between art show and club in a way that pushes the boundaries of what night life can be.
The night itself opens with Benson Streaker, a Bristol based DJ spinning groove and minimal house music. Skaters and ravers alike take to the floor as a video of a baby’s baptism from the 90s is projected onto the wall, filtered heavily with neon colours and glitches. It feels subversive, and the crowd love it.
Next up are INTERVENTION, a DJ collective running free workshops and live music events that strive for accessibility and representation in the electronic scene. On the night they create an immaculate vibe on the dance floor, where strangers dance with each other like old friends. From the get-go the atmosphere is one of complete non-judgement, where everyone can unite behind their love of music and art.
In the smokers a person sits cross-legged on the pavement having their portrait drawn by the hand of a friend – I feel like I’ve stumbled upon something incredibly intimate. The neon glare of William Hill and the echoing of sirens bring me back down to earth; it’s paint me like on of your French girls, Bristol style.
The room feels disruptive, subversive, and this is echoed behind the decks. A side room is transformed into an art gallery, with an eclectic mix of Bristol-based queer artists showing their work. As people meander through the space, drink in hand, you’re struck by how sincerely people are enjoying themselves. This is a feeling that gets to the core of George's vision for CLIMAXED as a ‘fun double meaning of fun and pleasure.’
The night climaxes (appropriately) with TAAHLIAH, a Glasgow based DJ and producer who established her reputation in the underground queer clubs of Berlin. Flipping between the glaring sheen of hyperpop and the glitchy intensity of hard-dance, TAAHLIAH creates a stunning current of energy in the room that summates the night itself.
People are wearing what the hell they want, dancing how they want, talking to each other, supporting each other's work, all with a genuine sense of joy. It’s a safe place, with genre-bending music and great art, offering an alternative space for queer people across the city. A night to be celebrated: more of this please!
Featured Image: Epigram
What's your experience of nightlife in Bristol?


I made a headphone holder that I talked about in my Mark’s Learning Projects thread. I wasn’t completely happy with it, but didn’t want to waste material making another one. Then my order of Draftboard arrived and everything changed.
I took this as another opportunity to improve my Fusion 360 skills and I was very pleased with the progress I made. All of the key measurements were parameterized. I also applied some lessons I learned recently doing some test cuts and dialing in on kerf to make the slots that connect the pieces nice and tight.
My workflow evolved a bunch here. I was doing things the hard way before, making sketches of each piece individually and extruding them out. That is very much a case of “fighting the tool” and slowed me down. This time, my workflow looked more like this:
- Sketch out main body of the hook.
- Extrude one hook.
- Copy the hook and move it 0.5" to the left of the existing hook.
- Create a new component, select one of the faces from the rear slot in the hook, and extrude a material-thickness box as the beginning of the rear clip.
- Continue to sculpt the box by extruding faces, adding fillets, and so on until the shape is correct.
- Use the Cut flavor of the Combine operation with the Hook bodies as the tool to cut the notches out of the Rear Clip.
- Repeat steps 4-6 for the front clip.
- Select one of the Hook bodies and create a NEW sketch from it. Yes, I already had a sketch but this gives me a completely clean one that I can use to export a DXF from. This generated sketch will have all the paths closed, which may not be the case if you export your source sketch. This was a huge learning.
- Create new sketches for the front and rear clip and generate DXF files.
Next, I import the DXF files into Inkscape, arrange them into the orientation that I want to cut, set stroke width/color as desired (I always use 0.001" stroke width) and save as an SVG.
From there, it’s a simple matter of uploading the SVG into the GFUI, dragging it onto my material, and pressing print.
Remove the masking and assemble.
And take it for a spin!
If you’re like me the first few creations go quickly but as soon as you graduate beyond a basic coaster or sign it starts to slow down some since the designing complexity increases dramatically. The most important thing is to fully understand what happened when things don’t go as you expect while building small experiments to test your hypotheses.
For example, I spent some time last night making a few different sizes of rectangles and slots and really trying to understand kerf and how Inkscape interacts with it. As a result, my clips and slots fit perfectly on the first try. I had struggled with this previously, but the small focused experiments really helped me understand where I was going wrong.
I learned a lot in the process of making these, and I’m getting faster and faster each time I make something new. This project only took me about an hour from start to finish. I still have a long way to go, but I’m having a blast learning and even getting some useful and beautiful things occasionally along the way. Seeing the finished result look just like the model I started with in Fusion 360 is incredibly satisfying.


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Across the bridge, there is total darkness but it's in the light where you could see a community demolished by Sandy.
"This is going to be a couple of years clean up now and hopefully they can rebuild," said Kathy Kemble.
Video showed the Seaside Heights boardwalk gone, part of the amusement pier underwater and houses severely damaged.
Many in the area haven't seen the devastation because of widespread power outages.
Typically, there are three ways to get on the Barrier Island. Travelers can go by boat, which is not allowed now, through Mantoloking on Route 35, which has been destroyed or also through Route 37, which survived Sandy.
It has become the lifeline for clean up and rescue efforts. 300 people have been pulled from the area including Roberta Fourness and her pets.
"There's damage to my home. It's a mess. I'm going to have to do a major rehab and I made it through this but I won't stay for the next one," said Fourness.
On Route 37, residents and business owners were awaiting word on when they'll be able to return.
"It's eerie, it's very eerie and it's frightening. You have no control over it," said Delores Lobbato.
The only entry point into Seaside Heights was hit by a floating house during the storm but the roadway wasn't damaged.
Officials say crews are working hard to restore power, stop gas leaks and remove debris off roads so people will be able to access the Barrier Island by the weekend.

domain: news


Finger Lakes Rieslings win gold
Many people believe that Finger Lakes wineries make world-class Riesling. Anthony Road Wine Co. and two other Seneca Lake wineries proved the point in France earlier this month.
Competing at the Riesling du monde in Strasbourg, Anthony Road’s 2009 Dry Riesling captured a gold medal.The other gold medal winners from the Finger Lakes were Fox Run Vineyards for its 2008 Reserve Riesling, and Belhurst Estate Winery’s 2009 Semi-Dry Riesling. All three winning wineries are on the west side of Seneca Lake, south of Geneva.
At the same competition, silver medals were awarded to two other Finger Lakes wineries: Keuka Lake Vineyards’ 2009 Dry Riesling and Red Tail Ridge Winery’s 2009 Semi-Dry Riesling.


South Bend Clutch Dodge Clutch Kits 2005.5 and Up Dodge Cummins with G56 6 Speed Transmission
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South Bend Clutch is an American Clutch Manufacturer!
If you need replacement clutch parts only, to replace single parts from your existing South Bend Clutch Kit, those can be found here.


text:
This hair-do might just amp up your style!
This B-town beauty has won the hearts of Sonam Kapoor and Parineeti Chopra!
Sonam Kapoor and Hrithik Roshan weave magic in this romantic video!
Time to bring out the bobby pins!
Let's bring out the designer labels...
Last night, ABCD 2‘s success bash was held at Olive,...
Hey, you! My funny bone needs a stimulator!

domain: celebrity


text:
The latest Wednesday update is this converted 40mm Female Officer for my Flash Gordon collection.
Photo Two - Shows the finished figure from the back.
Photo Three - The base model is a Female officer from the Graven Images/Cliff Hanger range that was once available from Monolith Designs. I have modified the figure by removing 5mm from the middle section of the legs and filling the join with Milliput. The head is from another Jim Bowen 40mm figure - a resistance fighter and once again the join filled with Milliput.
I have used Green Stuff to add detail to the uniform and build up the tiara. The base is my usual 40mm round, lipped base with the groundwork built up from broken cork and Milliput.
Photo Four -The converted figure is given a Black undercoat.
Photo Five - The finished conversion alongside a Graven Images Trooper. The uniform is painted in a dark Crimson colour, with Cream trousers and lots of Gold detail.
Photo Six - I have used a new Gloss Varnish for this model, my trusty Ronseal Toughcoat having finally given up the ghost. The new varnish is from Wilkinsons and is waterbased. I have Matt Varnished over the top with Galleria Matt Varnish prior to adding static grass.

domain: design


text:
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domain: finance


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Mercedes Maxi CabMaxi Mercedes Cabin
Now if you think that using a Singapore saloon car servicing with a Mercedes E200 will be breaking your budgeting, then you are in for a big shock just because the prices are exceedingly reasonable. That means you will never think twice when you make this choice to hire a luxurious saloon.
Even if you only need one trip to go to a get-together for a single night, you can still hire one by selecting the full service pack. So, when you are booking a luxurious limousine or a coupé, you need to make sure that the following information is ready: One-way - that would work if you only need one trip going somewhere, and you won't need a pickup afterwards.
They may also have the opportunity to truly appreciate the beautiness and comfort of the Mercedes E200. Apart from looking like a work of artwork, this limousine is roomy and very cozy. Booking this luxurious limousine for your next meeting with your loved ones and your relatives.
C-Class & S-Class Mercedes also available.
Mercedes-Benz Sedan - 4-seater
When you are a shopkeeper, an events manager, or simply responsible for administering your company's events, you know there is a great deal to do to make them work. Providing a comfortable and dependable transport for your visitors is the first stage of a successfull organization. Singapur is one of the big towns of the whole wide range of Asiatic and Europe culture.
Award-winning as Asia's leading designer hotel and one of Singapore's most trendy hotel, Grand Park Orchard is situated in the centre of Singapore's prime retail and leisure area. Grand Park Orchard, with its unmistakable fishbone façade and modern spaces, takes its distinctive aesthetics to Singapore's city centre and is a south-east Asia land that occupies parts of the Malay Peninsula and Borneo Isle.
It is known for its beautiful sandy shores, rain forests and a mixture of Malaysia, China, India and Europe culture. Kuala Lumpur, the capitol, is home to a number of major landmarks including historic houses, bustling retail areas such as Bukit Bintang, and the legendary 451m high Petronas Twin Tower.

domain: geography


text:
Sausage gravy is one of those things I love but never made at home. I would only have it on the rare occasion when we would go to a local diner, and that hasn't happened at all in a few years. So, I was browsing Pinterest one night and I saw a recipe for it from my friend Donna at The Slow Roasted Italian called Sausage Gravy and Biscuit Skillet and I knew I had to try making it at home!
Problem, I couldn't find bulk breakfast sausage! I'm sure it exists, just not in the grocery store I usually go to. If this happens to you just break up breakfast sausage links into little pieces (the uncooked kind, not precooked!).
I decided to use aged Gouda cheese in the biscuits, because I love it, but Parmesan or Asiago would be good, too. The gravy is so easy to make, and the whole dish is ready in about 30 minutes, in one pan! I love that since I have a never-ending pile of dishes to wash. I used my cast-iron skillet, but any oven-proof skillet would do.
By the way, if any food writers are reading this, you should NEVER try writing a recipe when you haven't eaten and your starving! I'm seriously drooling looking at my pictures. Just some food for thought. Get it? Sorry, worst joke ever....just give the recipe, Bernadette!
Sausage Gravy and Biscuits
- 1 pound breakfast sausage (bulk or uncooked links broken into little pieces)
- 1 teaspoon ground sage
- 3 cups whole milk
- 4 tablespoons unsalted butter
- 4 tablespoons all-purpose flour
- 2 teaspoons fresh ground black pepper
- For the biscuits:
- 2 cups all-purpose flour
- 1 cup whole milk
- ½ cup shredded aged Gouda cheese
- 1 tablespoon baking powder
- 1 tablespoon granulated sugar
- 1 /2 teaspoon kosher salt
- Preheat oven to 450 degrees F.
- Heat a large (10 inch) well seasoned cast-iron skillet over medium-high heat, add the sausage and the ground sage, stir to combine and break up the sausage. Cook and stir until browned.
- Add the butter to the pan and stir. Once the butter is melted, sprinkle 4 tablespoons flour over the sausage and stir until no white specks of flour remain. Add the milk and pepper, stir to combine, scraping the bottom of the pan to release the tiny sausage pieces,let come to a simmer, then reduce the heat to low while you make the biscuits.
- In a mixing bowl combine the flour, cheese, baking powder, sugar, and salt. Mix well, then add the milk and stir with a fork until a solid dough forms.
- Turn off the stove then drop the biscuit mixture by the spoonful onto the gravy. Place the pan on a large metal cookie sheet, then bake in the preheated oven for 10-12 minutes, or until the biscuits are cooked through and lightly browned.

domain: food


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• to view the rest of this the code of hammurabi versus the ten commandments free essay you must submit one complete, good quality essay or term paper of your own. Compare and contrast the 10 commandments to hammurabi's code. Compare and contrast the code of hammurabi and the ten commandments essays and research papers. Hammurabi's code of laws hammurabi's code of laws vs the ten commandments 10/01/14 king of babylon king of lakeview middle school rules protected ancient babylonians.
You may have known that the 10 commandment are based on the codes of hammurabi dated to near 1750 bc however, did you know that the codes of hammurabi are based on. A topic that was discussed among peers was that the ten commandments of christian and jewish faith were based off the code of hammurabi i looked into the wikipedia. Compare and contrast the ten commandments with the code of hammurabi how are they the same and how are they different - 199193. The ten commandments and the code of hammurabi are similar in quite a few ways and they are also different in various ways in the whole they are both.
Did moses copy the law from the code of hammurabi are the ten commandments taken from the forty-two precepts of ma'at return to: miscellaneous bible questions. Hammurabi's code simply destroys any argument about the 10 commandments being (1) original (2) the first written laws (3) the origin of our laws, etc but. There are some similarities between the code of hammurabi and the ten commandments the coming years will be a constant battle to maintain church-state separation. Free essay on the hammurabi code available totally free at echeatcom, the largest free essay community.
Did moses steal the ten commandments shushan, which lies 200 miles east of babylon furthermore, mosaic law moved beyond the code of hammurabi. The ten commandments and the code of hammurabi are similar in quite a few ways and they are also different in various ways in the whole they are both based on the. History about (the code of hammurabi and the ten commandments from exodus ch 20) exodus ch 20) paper instructions: instructions: in each essay assignment, please. Code of hammurabi essays: $ 1000 common topics in hammurabi's code hammurabi’s code the code of hammurabi code of hammurabi code of hammurabi crime. Code of hammurabi and the 10 commandments origination and purpose of the code of hammurabi the code of hammurabi was designed to prevent people from doing wrong and.
Hammurabi code vs ten comandments ten commandments religious laws instead of all laws hammurabi code contained 100's of laws. Essays & papers hammurabi’s code and the ten commandments comparison - paper example hammurabi’s code and the ten commandments comparison - part 2. 1 compare and contrast the 10 commandments to hammurabi's code 2 bible as literature 3 one hour lesson 4 text and questions provided. Compare the hammurabi code and the ten commandments compare the hammurabi code and the moses took his 10 commandments from the hammurabi code. Compare and contrast the code of hammurabi and the ten commandments helped in shaping the western heritage some of these documents that capture the characteristic.

domain: law


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Type 1 diabetes can damage the vasculature and inner structure of the ear, according to a new report.
Previous research suggests that diabetes can cause hearing loss, the authors explain in the journal Otolaryngology-Head and Neck Surgery, but no previous study has measured and documented changes in the anatomy of the cochlea – the deep-seated spiral structure where sound is turned into nerve impulses – in patients with type 1 diabetes.
Dr. Hisaki Fukushima from the International Hearing Foundation in Minneapolis, Minnesota, and colleagues examined skull bones obtained at autopsy from patients with juvenile onset diabetes and compared them with similar bones obtained from normal “controls.”
Diabetics had significant thickening of the walls of blood vessels supplying the cochlear region, the team reports, as well as a significantly greater loss of outer “hair cells,” which pick up sound waves. Other structures were more shrunken.
“The findings in our study suggest that the (microvessel damage) associated with diabetes affects the inner ear vasculature and causes degeneration of inner ear structures,” Fukushima and colleagues write.
Type 1 diabetes “results in changes of the cochlea…that are likely to result in hearing loss,” they conclude.
SOURCE: Otolaryngology-Head and Neck Surgery, July 2005.

domain: biology


No baskets or containers or flowers may be placed on top of headstone or monument
1. Monuments may be erected subject to the approval of the Trustees. No objectionable design will be permitted and only granite and bronze will be allowed. The Board of Trustees will decide what monuments are “objectionable.”
2. The Cemetery Department will not be responsible for marble statues, monuments, or marble fixtures.
3a. A permit with a sketch and the size of the monument must be submitted to the Board of Trustees for approval. Lot and grave numbers and letters must appear on all bases.
3b. Monuments are restricted to the following limits:
One Grave: 2’2”x1’2”x3’0” high
Two Graves: 3’0”x1’2”x3’0” high
Three Graves: 4’0”x1’2”x3’0” high
Four Graves: 5’0”x1’6”x4’0” high
Six Graves: 6’0”x1’6”x4’0” high
Eight Graves: 8’0”x1’6”x4’0” high
3c. Corner lots having larger square footage may apply to the Board of Trustees for a larger monument. No monument will exceed ten (10) feet overall length under any circumstances.
4. Only one monument will be allowed on a grave or lot.
1. Foot Markers are allowed on 4 grave lots (8 interments) or larger.
2. Veterans Markers are permitted on any grave where a United States Veteran is interred.
3. All building foundations must be done by the Cemetery Department.
4. All work of setting and handling of monuments will be under the supervision of the Superintendent or his/her foreman. The inscribing and setting of monuments will be permitted only during regular hours of 8:00a.m. to 11:30 a.m. and 1:00 p.m. to 3:00 p.m. (Monday through Friday).
5. Orders for foundations for Memorial Day will not be accepted after May 10th. No orders for foundations will be accepted after November 1st until the frost is out of the ground in the spring. No setting of monuments when ground is covered with ice and snow.
6. The minimum charge for a foundation (graves or lots) is $200.00 for each grave, and all additional “Foot Markers” is $200.00 ($100.00 SF+).
7. Payment for foundations must be made before monument is set.
8. All work in the cemetery must be done during working hours.
9. No setting of monuments on Saturday or holidays.
10. Eternal flames, candles or solar lanterns will not be allowed in any part of the Cemetery.
Any aggrieved person may petition the Board of Trustees if he or she believes and exception to the within described rules is warranted.


Good question (thanks me), the answer to that really depends on how you feel about driving at night and how much night driving you do. While some drivers don’t have much of an issue with driving at night, at least half of drivers do feel anxious or nervous when it comes to driving on unfamiliar roads at night, or on unlit roads in general, based on a British survey. Ford’s new GPS-based headlights are one potential solution to easing that anxiety and providing drivers with better visibility at night.
And let’s be honest: that’s the whole point of having headlights in the first place. Well, they’re there to help you be more visible to other drivers at night, of course, but largely their purpose is to let you see the road and area ahead of your vehicle while driving. The more powerful headlights that we have today compared to several decades ago certainly help with that, but there are still some inherent limitations in what throwing more light at the problem can do. The GPS-based headlights being developed at Ford seek to surpass those limitations by letting your vehicle be smarter about how the road is actually lit up.
The Idea Behind It
Sometimes new inventions and innovations come to light (wordplay!) because of a “eureka” moment or a sudden instant of inspiration. More often, however, the inventions and new devices we use every day come to exist as a solution to a problem. In this case, the problem is the inherent flaw in most headlight systems on vehicles.
Your headlights are positioned on the front-end of your car, obviously, and they shine light out ahead of you to give you a better look at the road and surroundings in front of your vehicle. But when you’re driving during the day, with good weather, you’re not just looking at a small cone right in front of your vehicle (or at least you shouldn’t be). Your eyes are looking right in front of you, of course, but you’re also scanning your surroundings: glancing in your rearview and side mirrors to see what’s going on behind you, watching cars up ahead that are in other lanes, and looking at what the road is doing.
This last point is really the problem that Ford’s new GPS-based headlights seek to solve. When you’re driving at night, especially on unlit roads with only your headlights to provide illumination, you can’t see much beyond that bit of light directly in front of you. As you approach a turn in the road, for example, your lights are only illuminating a small area directly in front of you, giving you very little visibility for the shoulders and what’s coming up as the road bends. But not anymore.
How Ford’s GPS-Based Headlights Work
In the past, Ford has worked on headlights that use road signs and lane markings to adjust your headlights to illuminate the road better. They’ve gone beyond simply having your headlights react to these kinds of markers, however, and their new GPS-based headlights are able to adjust in a proactive or predictive way based on known road information. That’s where the “GPS” comes into play.
Basically, your vehicle will use GPS to keep track of your location, along with navigational information like you’d use to get directions. With this data, plus various calculations and simulation information, your vehicle will essentially know what the road is going to do up ahead, even if you can’t see it. So while you’re driving along, looking at the road as best you can, your vehicle would know that there’s a turn coming up ahead.
With this information, your car would automatically adjust your headlights to illuminate the area better when you approach a turn, curve, or similar change in the road. In one example that was shown based on the system they’re working on, extra illumination was provided for a turn so the driver could see what the road was doing and have a much better view of where they were heading. This would, in theory, alleviate stress and anxiety about night driving because you’d have a clearer view of the road ahead and not be surprised by anything in the darkness.
Is This Actually Helpful?
So far, based on the testing and the demonstrations that Ford has shown, I’d say this is definitely a concept that could help a lot of people. All else being equal, the primary difference between driving during the day and driving at night is visibility – you can see so much less at night, especially on a road without street lights, that the lack of visibility can be shocking. For a lot of people, the fear of the unknown is a huge source of anxiety and worry – and if you can’t clearly see where the two-ton machine you’re in control of is going, the unknown is definitely disconcerting.
Ford’s new GPS-based headlights look like a really interesting solution to the problem of night-driving visibility, and I think they could work incredibly well. To me, however, the solution is ultimately going to be a combination of things. For example, I’ve seen some auto companies start to utilize night vision and thermal imaging technology with their cameras. This way, when you’re driving at night, you can look at one of the displays in the car to see the road ahead using night vision, with sources of heat, like pedestrians or animals, highlighted on the screen.
I think combining these different technologies, with some improvements, will really change the way people drive at night and make a lot of us more comfortable getting behind the wheel after the sun has gone down. Imagine driving on an unlit road, knowing that your headlights will adjust automatically when you approach a curve to give you a better view of your surroundings. Now imagine adding a head-up display that uses augmented reality and night vision information to highlight sources of heat on your windshield in real-time. So as you’re driving, you’ll see a box or outline in color on your windshield warning you that a large deer is approaching the side of the road.
What Do You Need to Know as a Car Buyer?
Sounds pretty good, right? Unfortunately, the situation I just described is not something you’re going to find in a vehicle just yet. These separate systems are all being worked on and getting really close to being ready, but I don’t know of a company combining all of them into a single system for a vehicle. I wouldn’t be surprised to see it happen in the not-too-distant future, but it’s not something you’ll find right now.
So if you’re shopping for a vehicle in the next month or so, something like Ford’s new GPS-based headlight system really isn’t something you need to have in mind. This is still in testing and development, with no word on when it will be available on any of their vehicles. But in the years ahead, this is something you’ll probably find at Ford dealerships – likely on their high-end trims at first – and that will eventually become more common, perhaps even standard. It helps to know about these systems and keep them in mind so that when you go shopping for a car a decade from now, you’ll know what to expect.