text:
Overexpression of steroidogenic acute regulatory protein increases macrophage cholesterol efflux to apolipoprotein AI
Aims In this study, we investigated the impact of enhancing cholesterol delivery to mitochondrial sterol 27-hydroxylase, via steroidogenic acute regulatory protein (StAR), on the expression of genes involved in macrophage cholesterol homeostasis and efflux of cholesterol to apolipoprotein (apo) AI.
Methods and results Stably transfected, murine (RAW 264.7) macrophages were used to investigate the role of StAR in cholesterol homeostasis. Cellular responses were analysed using quantitative PCR, immunoblotting, and an LXRE reporter plasmid; [3H]cholesterol efflux was measured in the presence or absence of apoAI. Macrophage overexpression of mitochondrial cholesterol trafficking protein, StAR, activates and induces expression of liver X receptors (LXRs), and significantly alters expression of genes involved in cholesterol homeostasis, decreasing Fdps, Hmgcr, Mvk, Ldlr, and Scap, and markedly increasing Abca1 mRNA and protein. Overexpression of StAR, but not mutated 'loss-of-function' (R181L) StAR, enhanced efflux of [3H]cholesterol to apoAI, and this effect was maintained in macrophages pretreated with LDL or acetylated LDL. The effect of StAR overexpression on apoAI-dependent [3H]cholesterol efflux was mimicked by non-sterol agonist, T901317, and 27-hydroxycholesterol, and blocked by LXR inhibitor, geranylgeranyl pyrophosphate, sterol 27-hydroxylase inhibitor, GW273297x, and probucol, inhibitor of ATP binding cassette transporter A1 (ABCA1). Importantly, all observed effects of StAR overexpression were dependent upon cyclic AMP (cAMP analogue, dibutyryl cAMP), which is required for the full activity of the StAR protein to be manifested.
Conclusion Macrophage overexpression of StAR significantly enhances LXR-dependent apoAI- and ABCA1-dependent cholesterol efflux, by which disposal of excess arterial cholesterol deposits and atheroma regression can be achieved.
- Atherosclerosis
- Liver X receptor
- Sterol 27-hydroxylase
- Cholesterol efflux
- Apolipoprotein
- apoAI
1. Introduction
Macrophage 'foam cells', laden with cholesterol and cholesteryl esters, are a hallmark of early and developing atherosclerotic lesions, influencing both plaque progression and stability.1 Reversal of macrophage lipid accumulation, by cholesterol efflux and the reverse cholesterol transport pathway mediated by high-density lipoprotein (HDL), remains a key anti-atherogenic strategy.2 Cholesterol efflux to acceptors, such as apolipoprotein (apo) AI, apoE, and HDL, is orchestrated by ATP binding cassette transporters A1, G1, and G4.2–4 Expression of these proteins is controlled, at least in part, by liver X nuclear receptors (LXRα/β),5 which heterodimerize with 9-cis retinoid X receptors (RXRs), and bind endogenous oxysterols, including 27-hydroxycholesterol,6 generated by the mitochondrial sterol 27-hydroxylase encoded by CYP27A1.7 Up-regulation of macrophage CYP27A1 expression, by ligands for the peroxisomal proliferator-activator receptor-γ and RXRs,8,9 results in increased levels of 27-hydroxycholesterol, upregulation of LXR-mediated processes and in elimination of CYP27 metabolites as an alternative means of cholesterol efflux.10,11 High levels of sterol 27-hydroxylase are found in vascular endothelium,12 CYP27A1 is colocalizes with macrophages, in human atherosclerotic lesions,13,14 and 27-hydroxycholesterol is a major oxysterol in human atheroma.15 The importance of CYP27A1 in regulating macrophage cholesterol homeostasis is highlighted by the rare genetic disorder cerebrotendinous xanthomatosis, associated with macrophage 'foam cell' formation and increased risk of premature atherosclerosis, despite normal concentrations of cholesterol in the circulation.16 Importantly, the rate-limiting step controlling the activity of sterol 27-hydroxylase is the supply of cholesterol to the enzyme, located on the matrix side of the inner mitochondrial membrane,7 which can be mediated by steroidogenic acute regulatory protein (StAR).17–25
In steroidogenic tissues, StAR is a critical regulator of the synthesis of adrenal and gonadal steroids, delivering cholesterol to the P450 side-chain cleavage enzyme resident on the matrix side of the inner mitochondrial membrane, which converts cholesterol to pregnenolone.19–22 StAR is a nuclear encoded, mitochondrially targeted protein, expressed in cytoplasm as a 37 kDa protein, imported into mitochondria and inactivated by cleavage to a 30 kDa protein.19–22 Phosphorylation of human StAR on Ser195 by protein kinase A (PKA), combined with rapid induction of StAR biosynthesis, explains the acute regulation of steroidogenesis in response to trophic hormones.23 Mutated StAR is responsible for abrogated steroidogenesis and abnormalities associated with lipoid congenital adrenal hyperplasia;24 the same phenotype is reproduced after targeted disruption of the Star gene in mice.25
Steroidogenic acute regulatory protein has also been found in the liver, where it increases the activity of CYP27A1, production of oxysterols, and synthesis of bile acids by the 'alternative' pathway.17,18,26,27 Ma et al.28 recently provided evidence for the expression of StAR mRNA and protein in murine macrophages, and aortae of apoE−/− mice; our own work found expression of StAR in human monocytes, THP-1 macrophages, and human aortic tissue.29 Here, we considered the functional role of StAR in cholesterol homeostasis, demonstrating increases in LXR activity and LXRα gene expression, transient induction of expression of ATP binding cassette transporter A1 (ABCA1) mRNA and protein, and enhanced cholesterol efflux to apoAI, in murine macrophages overexpressing StAR protein.
2. Methods
2.1 Materials
Tissue culture reagents were purchased from Lonza (Wokingham, UK); other sources include: mammalian expression vector, pTK-Hyg (BD Biosciences, Oxford, UK), FuGene6 transfection reagent (Roche), NuPAGE gels, and buffers (InVitrogen), antibodies (AbCAM, Cambridge, UK), T901317 (Tocris), geranylgeranyl pyrophosphate (GGPP) (Sigma), primers/probes (Eurogentec, Belgium). Low-density lipoprotein (LDL) was from Athens Research (USA) and acetylated according to Brown et al.30 We are deeply indebted to the following for their very kind gifts: Prof. D. Stocco, University of Texas (murine Stard1 clone), Prof. J. Orly, Hebrew University of Israel (pCMV.5 vector), Prof. D.J. Mangelsdorf, South Western Medical Center (LXRE reporter plasmid), Prof. D. Russell, South Western Medical Center (rabbit polyclonal antibody to sterol 27-hydroxylase), Prof. W. Jessup and Dr C. Quinn, University of New South Wales, kindly facilitated by Prof. S.J. Yeaman, University of Newcastle-upon-Tyne (sterol 27-hydroxylase inhibitor, GW2739297x).
2.2 Macrophage cell lines
Murine macrophage cell line, RAW 264.7 (ECACC 91062702), was maintained in DMEM containing UltraGlutamine, supplemented with foetal bovine serum (FBS; 10%, v/v), HEPES (10 mmol L−1), sodium bicarbonate (0.075%, w/v), and penicillin/streptomycin (50 U mL−1; 50 µg mL−1). Subconfluent macrophages (3 × 105) were co-transfected (48 h) with pTK-Hyg (0.5 µg) and pCMV.5 (0.5 µg), the latter containing full-length murine Stard1, or mutated Stard1 (CGA→CTA; Arg181Leu) [site-directed mutagenesis (BioS&T, USA)]. Empty vector (pCMV.5) was used as the 'control', so that all stably transfected cells were subject to the same procedure. Cells were transfected with pTK-Hyg (0.5 µg) and pCMV.5 (0.5 µg) using Fugene6 (6 µL: 1 µg DNA); stably transfected populations were selected and maintained using hygromycin (200 µg mL−1). Transient expression of pCMX.LXRE (0.5 µg) in the same way, and luciferase activity (Britelite Plus, Perkin Elmer) assessed 24 h later. Lipids were extracted from media31 and 27-hydroxycholesterol and free cholesterol identified by co-migration with authentic standards by t.l.c. using petroleum ether:diethyl ether:glacial acetic acid (90:30:1, v/v/v) as the mobile phase. Efflux of 27-oxygenated sterol was expressed as percentage of dpm in the cholesterol pool (media + cells).
2.3 Analysis of gene and protein expression
Total RNA was isolated (TriZol) from stably transfected macrophages, reverse transcribed to cDNA (BioLine), and polymerase chain reactions (PCR) using primers designed to generate a 355 bp amplicon from StarD1 (forward: 5′-GTTCCTCGCTACGTTCAAGC-3′; reverse: 5′-GAAACACCTTGCCCACATCT-3′). Levels of mRNA encoding 84 genes implicated in lipoprotein signalling and cholesterol metabolism (SABiosciences) were measured relative to five housekeeping genes, GusB, Hprt1, Hspcb, Gapdh, and Actb. Quantitative PCR (Q-PCR) determined expression levels of Abca1, Abcg1, Abcg4, Lxr, Ldlr, Hmgcr, Scap, Mvk, Fdps, Srebf1, Srebf2, Stard3, Olr1, and Soat1 mRNA, and internal 'housekeeping' gene, Gapdh; reactions were performed as previously described29 with specific sequences reported in Table 1.
|GenBank reference
|Forward (5′–3′)
|Reverse (5′–3′)
|Probe (5′–3′)
Macrophage cell lysates, prepared in RIPA buffer plus Complete™ protease inhibitor cocktail, were separated using NuPAGE gels (10%), transferred to PDVF membrane and probed using rabbit polyclonal anti-StAR antibodies (1:1500); mouse monoclonal antibody to ABCA1 (1:1000), rabbit polyclonal antibody to sterol 27-hydroxylase (1:2000), and monoclonal antibody (1:20 000) to the loading control, GAPDH. Detection was achieved using secondary antibodies and ECL detection system.31
2.4 Macrophage lipid mass and cholesterol efflux
Incorporation of [14C]acetic acid (1 µCi mL−1) into fatty acid, phospholipid, cholesterol, cholesteryl ester, and triacylglycerol pools were measured after incubation for 24 h in the presence of cAMP (0.3 mM), in empty vector and StAR-overexpressing macrophages, as previously described.29 Macrophage lipids were extracted using hexane: isopropanol (3:2, v/v) and dried under N2, before separation by t.l.c., using chloroform, methanol, and water (60:30:5, v/v/v) as the first mobile phase and hexane, diethyl ether, and acetic acid (80:20:1.5, v/v/v) in the second phase of development; lipids were identified by co-migration with standards.29,31 Triacylglycerol mass were determined in lipid extracts, as previously.29,31
Macrophage efflux of [3H]cholesterol to apoAI was determined as previously.29,31 Efflux was initiated by the addition of serum-free DMEM containing human apoAI (20 µg mL−1) and in the presence or absence of dibutyryl cAMP (0.3 mM), and terminated after 24 h; addition of cAMP is required both to stimulate PKA-dependent StAR phosphorylation and activity,23 and to induce maximal cholesterol efflux in murine RAW 264.7 macrophages.32,33 Addition of sterol 27-hydroxylase inhibitor, GW2739297x, LXR agonist, T01317, probucol, N-acetyl-Leu-Leu-norleucinal (ALLN), and leupeptin were made using DMSO (<0.01%; v/v) as vehicle; addition of LXR antagonist, geranylgeranyl ammonium pyrophosphate ammonium salt (GGPP), was made in methanol (0.01%; v/v). Results are expressed as % cholesterol efflux, calculated as [dpm(media)/dpm(media + cells)] × 100%.
All values indicate mean ± SEM, with numbers of independent experiments denoted by n. Significant (P < 0.05) differences were determined using repeated measures analysis of variance and Tukey–Kramer post t-tests. *P < 0.05; **P < 0.01, ***P < 0.001 as indicated.
3. Results
Overall, the strategy was to demonstrate that overexpression, and cAMP-dependent activation, of StAR in macrophages increases oxysterol generation (via Cyp27A1), resulting in agonism of liver X receptors and induction of genes involved in cholesterol efflux, such as ABC transporters, enhancing cholesterol efflux to apoAI. Data on gene and protein expression derived from stably transfected murine macrophages, either expressing StAR or the empty vector, were supplemented with studies utilizing an LXRE reporter plasmid, and pharmacological agents: 27-hydroxycholesterol, LXR agonist (T0901317), and antagonist (GGPP), sterol 27-hydroxylase inhibitor (GW293927x), and inhibitor of ABCA1 function (probucol).
3.1 Overexpression and LXR activating function of StAR in murine macrophages
Expression of StAR mRNA and protein in RAW 264.7 macrophages was increased, as judged by qualitative (Supplementary material online, Figure S1A) and Q-PCR, by 5.2 ± 0.3-fold (P < 0.001) and 2.5 ± 0.66-fold (P < 0.05), respectively, following stable transfection with pCMV.Stard1, compared with empty vector control (Supplementary material online, Figure S1A and B). Moreover, only mature StAR protein (30 kDa) was detected in cell lysates and mitochondria isolated from cells overexpressing StAR, indicating normal mitochondrial processing of this protein19–22 (Supplementary material online, Figure S1B). Increased mitochondrial trafficking of cholesterol to sterol 27-hydroxylase, mediated by overexpression of StAR,17,18,26 resulted in a 45.8% (n = 9; P < 0.05) increase in the flux of [3H]27-oxygenated sterol into the medium, in the presence of cAMP (0.3 mM) and apoAI (20 µg mL−1) (% oxysterol efflux: control macrophages 0.30 ± 0.04% vs. StAR macrophages 0.49 ± 0.06%). No changes in oxysterol secretion were noted under basal conditions.
StAR overexpression was associated with increased activation of an LXRE reporter (luciferase) plasmid (Figure 1A). Importantly, this effect of StAR proved significant only in the presence of a cell permeant cAMP analogue [dibutyryl cAMP (0.3 mM), used throughout, hereafter abbreviated to cAMP]. Cyclic AMP is required to activate the StAR protein,23 indicating normal regulation of the activity of this overexpressed protein (Figure 1A). Addition of LXR agonist, T01317 (10 µM), generated the same degree of LXR activation in both control and StAR-overexpressing macrophages, confirming equivalent transfection efficiencies. Addition of cAMP and T01317 together did not induce any further significant increase in LXR activation in macrophages overexpressing StAR, beyond that seen in the presence of cAMP alone. Activation of LXRE reporter plasmid was attenuated by LXRα antagonist, GGPP (10 µM), although the impact of this inhibitor was reduced in the presence of both T01317 and cAMP in StAR-expressing cells. It is relevant to note that GGPP, a branch point intermediate of isoprenoid biosynthesis, is also involved in post-translational prenylation of several proteins (Ras, Rho, Rac) that modulate a variety of cellular processes including cell signalling, differentiation, and proliferation.
Sterol 27-hydroxylase inhibitor,34 GW2739297x (1 µM), blocked LXR activation in StAR-overexpressing, but not control macrophages (Figure 1B). As LXRα itself possesses an LXRE, steady-state levels of mRNA encoding LXRα were measured 12 and 24 h, after the addition of cAMP in both cell lines (Figure 1C). A significant increase (5.1-fold; P < 0.001) in LXRα gene expression was observed in StAR-overexpressing macrophages treated with cAMP compared with controls.
3.2 Changes in gene expression induced by StAR overexpression in murine macrophages
Overexpression, and activation (cAMP; 0.3 mM), of StAR induced (>2-fold) changes in the expression of 27 of the 84 genes tested using RT2 SuperArray ('Cholesterol and Lipoprotein Signalling') relative to mRNA levels of housekeeping genes which did not change (Table 2). StAR overexpression increased mRNA levels of Abca1, Cxcl16, and Nsdhl, and decreased the expression of Abca2, Abcg1, Fdps, Hdlbp, Hmgcr, Ldlr, Mvk, Osbp1, NrOb2, Scap, Stard3, and Srebf1 compared with controls (Table 2). Findings derived from this array were studied further in three independent experiments, using Q-PCR primers and fluorescent probes to amplify 11 genes, selected on the basis of their established roles in cholesterol synthesis, uptake and esterification: Abca1, Fdps, Hmgcr, Ldlr, Mvk, Olr, Scap, Stard3, Srebf1 and Srebf2, and Soat1. This study confirmed significant down-regulation of the expression of genes involved in cholesterol biosynthesis, Fdps, Hmgcr, Mvk, in cholesterol uptake (Ldlr), in regulation of gene transcription (Scap) and a trend towards down-regulation of expression of Srebf1 and Srebf2 transcription factors, and of the gene encoding the endosomal cholesterol trafficking protein, Stard3 (Table 2). Soat1 and the oxidized LDL receptor (Olr) were confirmed as unaltered by overexpression of StAR protein. The most strongly marked alteration in gene expression associated with StAR overexpression was up-regulation of Abca1 (17-fold; P < 0.05), consistent with the observed activation of LXRE in these cells (Figure 2), strongly suggesting a role for StAR in the regulation of cholesterol efflux to apoAI.2,4
|Gene symbol
|RT2 SuperArray profile
|Q-PCR (mean ± SEM; n = 3)
|1.06 ± 0.44
|1.18 ± 0.25
|0.54 ± 0.20
|0.55 ± 0.20
|0.57 ± 0.25
Values quoted are the fold difference in gene expression, where >2-fold changes in mRNA expression are reported; data for Olr1, Soat1, and Srebf2, which changed by <2-fold in the array, are included as references.
3.3 Overexpression of StAR increases macrophage [3H]cholesterol efflux to apoAI
Efflux of [3H]cholesterol from murine RAW 264.7 macrophages (Figure 2A) is dependent upon the presence of both an acceptor, apoAI, and cAMP analogue:31,32 addition of both apoAI (20 µg mL−1) and cAMP (0.3 mM) significantly (P < 0.001) enhanced [3H]cholesterol efflux by 2.28-fold in control macrophages. More notably, under the same conditions, % [3H]cholesterol efflux was significantly (P < 0.001) higher in StAR-overexpressing (3.78-fold) than in control macrophages. Efflux of [3H]cholesterol to apoAI (in the presence of cAMP) was inhibited by probucol35 in both control (P < 0.05) and StAR-overexpressing (P < 0.001) macrophages (Figure 2B), confirming dependence of efflux upon the ABCA1 transporter. Introduction of mutated 'loss of function' StAR (Arg181Leu)24 into murine RAW 264.7 macrophages, at equivalent levels to wild-type StAR, did not induce increases in macrophage [3H]cholesterol efflux to apoAI, when compared with control macrophages (Figure 2C). Importantly, the effect of overexpression of StAR was mimicked in control cells by the addition of exogenous 27-hydroxycholesterol (5 µM), in the presence of both cAMP and apoAI (Figure 2D). Finally, the stimulatory effect of StAR overexpression on % [3H]cholesterol efflux to apoAI was sustained, following cholesterol loading: percent cholesterol efflux increased from 2.85 ± 0.17% (basal) to 12.55 ± 1.88% (cAMP + apoAI) in control cells and from 2.90 ± 0.08% (basal) to 23.81 ± 3.64% (cAMP + apoAI) (P < 0.001) in StAR-overexpressing cells, previously treated with acetylated LDL (mean ± SEM; n = 4).
3.4 Overexpression of StAR in murine macrophages increases expression of Abca1 mRNA and protein during [3H]cholesterol efflux to apoAI
Cyclic AMP (0.3 mM) increased the expression of Abca1 by 16.6-fold (12 h, P < 0.001; n = 3) in StAR-overexpressing macrophages, whereas only non-significant increases were noted in control macrophages (Figure 3A and B). In the presence of both cAMP and apoAI, levels of Abca1 mRNA were induced by 32.5-fold and 26.1-fold (P < 0.001; n = 3) after 12 h, compared with control incubations, in StAR-overexpressing and control macrophages, respectively. This finding is consistent with the previous observations that the promoter region of murine (but not human) Abca1 contains a cAMP response element and that apoAI is required for stabilization of Abca1 mRNA. Protein levels of ABCA1 were substantially increased in StAR-overexpressing macrophages, compared with controls, after 12 h in the presence of cAMP and apoAI together, relative to the GAPDH loading control (Figure 3B). In contrast, after 24 h, protein levels of ABCA1 were significantly lower in StAR-overexpressing macrophages, compared with control macrophages (Figure 3B), and relative to GAPDH, possibly reflecting the higher rate of cholesterol efflux in these cells (Figure 2). As similar levels of ABCA1 mRNA (Figure 3A) were associated with differing levels of ABCA1 protein (Figure 3B), and when compared with cholesterol efflux (Figure 2A), it seemed likely that levels of ABCA1 protein were subject to significant, rapid post-translational regulation.35,36 Addition of apoAI appeared to stabilize ABCA1 protein expression, and increase cholesterol efflux, in both control and StAR-overexpressing cells, in good agreement with Arakawa and Yokoyama;36 however, levels of ABCA1 protein (12 h) were higher in StAR-overexpressing cells than in empty vector controls or in macrophages expressing mutated StAR (R181L) which cannot promote cholesterol efflux (Figure 3C). We also examined levels of ABCA1 protein after treatment with probucol (10 µM) or with thiol protease inhibitors (ALLN 50 µM and leupeptin 100 µM). Probucol inactivates ABCA1 in the plasma membrane and prevents apoAI binding35 (Figure 2B) but also inhibits ABCA1 digestion by calpain.35 Levels of ABCA1 protein (12 h) increased in the presence of probucol, in both empty vector controls and StAR-overexpressing cells, in the presence of cAMP and apoAI (Figure 3C, middle panel). Notably, levels of ABCA1 protein remained markedly higher in StAR-overexpressing cells, compared with controls. The same effect was observed following inhibition of thiol proteases using ALLN or leupeptin:36 ABCA1 protein levels increased in both cell types, but again the stimulatory impact of StAR overexpression on ABCA1 protein was clearly observable (Figure 3C, lowest panel).
3.5 Increases in cholesterol efflux caused by StAR overexpression are dependent upon LXR and sterol 27-hydroxylase activities
Expression of CYP27A1 protein did not vary substantively between control or StAR-overexpressing macrophage cell lines (data not shown). Addition of T01317 (10 µM) alone significantly increased apoAI-dependent efflux, in the absence of cAMP, and to a similar degree in both control and StAR-overexpressing macrophages (Figure 4A), consistent with the LXRE activation data (Figure 1A). Addition of cAMP further enhanced apoAI-dependent [3H]cholesterol efflux, and a significantly higher level of efflux in StAR-expressing cells was noted compared with control macrophages (Figure 4A). Notably, the LXR agonist induced a relatively greater increase in [3H]cholesterol efflux (62.6%; P < 0.001) in control macrophages, compared with StAR-expressing macrophages (24.5%; P < 0.05). In contrast, addition of LXR antagonist, GGPP (10 µM), did not significantly affect [3H]cholesterol efflux in control macrophages in the presence of apoAI and cAMP (Figure 4B). However, in StAR-expressing macrophages, the marked increase in cholesterol efflux seen under 'optimal' efflux conditions (1.74-fold compared with control macrophages; P < 0.05) was effectively negated in the presence of GGPP (P < 0.05).
Equally, the specific contribution of CYP27A1 activity to the observed increases in cholesterol efflux was determined using a selective inhibitor of this enzyme, GW2739297x,34 which blocks StAR-dependent activation of LXRE (Figure 1B). GW2739297x did not alter [3H]cholesterol efflux under basal conditions (Figure 4C); however, under optimal efflux conditions, GW2739297x significantly reduced (P < 0.001) apoAI-dependent [3H]cholesterol efflux by 34.2% in control cells and by 43.8% (P < 0.001) in StAR-overexpressing macrophages, effectively negating the impact of StAR in these cells.
3.6 Overexpression of StAR: impact on macrophage triacylglycerol mass
One negative aspect of non-sterol LXRα agonists is the induction of lipogenesis and accumulation of triacylglycerol, mediated by increased expression of SREBP-1c.29,37 Macrophage triacylglycerol mass (measured in the presence or absence of cAMP, 0.3 mM; 24 h) did not change in StAR-overexpressing cells compared with controls (control 21.6 ± 2.03 µg mg−1 protein vs. cAMP 22.2 ± 1.83 µg mg−1 vs. StAR overexpression 16.9 ± 0.83 µg mg−1 vs. StAR overexpression plus cAMP 24.4 ± 2.52 µg mg−1 protein; mean ± SEM; n = 3–4). However, measurement of incorporation of [14C]acetate into cellular lipid pools revealed a 2.4-fold increase in cellular lipid biosynthesis, with significant increases in [14C]-phospholipid (2.59-fold; P < 0.01), [14C]-triacylglycerol (4.2-fold; P < 0.01), and free [14C]cholesterol pools (1.7-fold; P < 0.05); no significant changes in [14C]-labelled non-esterified fatty acid or cholesteryl ester pools were noted (Figure 5). Clearly, these data reflect one potential 'downside' to the enhanced presence of StAR in vascular cells, an issue which needs to be considered carefully when studying the anti-atherogenic impact of StAR in vivo.
4. Discussion
Dysregulated macrophage cholesterol homeostasis lies at the heart of developing atherosclerotic lesions, influencing plaque progression and stability.1 Evidence is emerging that StAR may play a hitherto unsuspected role in vascular tissues. Our data confirm that StAR is expressed in human monocyte macrophages,29 and human heart aortae, Ma et al.28 report the presence of StAR in murine macrophages and in aortae of apoE−/− mice, and Ning et al.38 found StAR protein in murine b.End3 endothelioma cells. Recently, Ning et al.39 showed that overexpression of StAR in human THP-1 macrophages decreases intracellular lipids and limits secretion of inflammatory factors by these cells. Here, we provide insight into the mechanism(s) by which StAR impacts positively on macrophage lipid phenotype: overexpression of StAR in murine RAW 264.7 macrophages activates and induces LXR, via a pathway which involves sterol 27-hydroxylase (Figure 1). StAR overexpression represses a number of genes involved in cholesterol biosynthesis (Fdps, Hmgcr, Mvk) and uptake (Ldlr) and markedly increases the expression of Abca1 (Table 2), strongly suggesting that StAR increases sterol efflux to apoAI, an effect dependent upon LXR activation, sterol 27-hydroxylase, and ABCA1 activity. Importantly, cAMP was required for the full activity of the StAR protein to be manifested23 and could not be reproduced using a mutated 'loss-of-function' StAR protein (R181L).24
It is established that StAR can enhance generation of oxysterols by CYP27A1: overexpression of StAR enhances CYP27A1 activity in transfected COS cells, and in hepatocytes, producing nuclear oxysterols which potently regulate intracellular lipid homeostasis.17,18,26 Here, activation of the LXRE reporter plasmid was enhanced in macrophages overexpressing StAR, but only when StAR was activated by the addition of exogenous cAMP23 and could be blocked by the selective sterol 27-hydroxylase inhibitor, GW2739297x.34 Induction of LXRα mRNA was also observed after cAMP-dependent activation of the StAR protein, in StAR-overexpressing cells, but not in control macrophages (Figure 1C).
Activation of LXR appears to be a major factor inducing the expression of Abca1 in macrophages overexpressing StAR; [3H]cholesterol efflux to apoAI was effectively mimicked by an LXR agonist, and blocked by the inhibition of sterol 27-hydroxylase, and antagonism of LXR (Figure 4). Cyclic AMP up-regulates Abca1 expression in murine macrophages, at the transcriptional level,32,33 via a cAMP response element which acts in conjunction with a nearby STAT3/4 element:33 in both control and StAR-overexpressing macrophages the presence of both apoAI and cAMP significantly induced the expression of Abca1 mRNA and protein (Figure 3). However, in macrophages overexpressing StAR, it appears that a sterol 27-hydroxylase-dependent activation of LXR (Figure 2) induces a further up-regulation of Abca1 mRNA and protein (Figure 3), thereby enhancing [3H]cholesterol to apoAI (Figure 4).
The factor which induces StAR activity in macrophages, via increases in cAMP and activation of PKA, is not known. One hypothesis is that apoAI itself contributes to this process, as the addition of both cAMP and apoAI together enhanced the expression of ABCA1 compared with cAMP alone (Figure 3). ApoAI can activate cellular cAMP signalling through the ABCA1 transporter, triggering serine phosphorylation of ABCA1, and this effect of apoAI is particularly evident in cells expressing high levels of ABCA1.40
Finally, overexpression of StAR alters the expression of other genes implicated in cholesterol metabolism and lipoprotein signalling (Table 2). This profile should be studied more closely as, for example, expression of the pro-atherogenic gene, Cxcl16, appears induced by StAR overexpression. However, the handful of genes investigated here reveals a predominantly anti-atherogenic profile, where StAR overexpression represses transcription of genes implicated in cholesterol biosynthesis (Fdps, Hmgcr, Mvk), and LDL uptake (Ldlr), probably via enhanced oxysterol production, which can suppress SREBP processing by binding to Insig, expression of which declined in this study (Table 2).41,42
In conclusion, StAR appears to regulate macrophage cholesterol homeostasis, highlighting the importance of mitochondrial cholesterol trafficking in regulating LXR activation, downstream regulation of ABCA1 expression and efflux of cholesterol to apoAI.
Supplementary material
Supplementary material is available at Cardiovascular Research online.
Conflict of interest: none declared.
This study was supported by British Heart Foundation project grant 2006 PG/04/063/17186.
- Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2010. For permissions please email: firstname.lastname@example.com.


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Google's holiday success was first hinted at by a blurb on its own Chromebook "Buy Now" product page:
Due to the busy holiday season, some online retailers may be temporarily out of stock. If you can't find the model you're looking for, please try a different site.
And, true to its word, at the time of writing, the Acer AC700-1099 Chromebook (Wi-Fi only) and a few others have sold out from Amazon.com, with similar results on fellow electronics retailers TigerDirect and NewEgg. It's worth noting that it's mostly the midrange models that sell out: the priciest model, the Samsung Series 5 3G model (MSRP $459.99) appears to be in stock at all three retailers.
They're expected back in stock soon, and it's not as though the Christmas rush made Chromebooks into a Tickle Me Elmo-style prize. But with doubts cast on the future of the very concept of a cloud-only netbook, and with Google Chromebooks soon to be available to the search giant's reseller channel, it's an important validation of the product line's future.

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Android devices do a lot of neat stuff out of the box, but you can always load it up with new apps to make if do more stuff. And maybe some games for good measure. This is the Google Play App Roundup where we tell you what's new on Android. Just hit the links to head to the Play Store.
Your phone rides around in your pocket all day most likely, so it's an ideal vehicle for personal reminders. There are tons of apps that offer this functionality, and even Google Now offers a reminder feature. ClickMe doesn't have as many features as most reminder apps, but it lets you set reminders insanely fast.
There are several ways to access the reminder features of ClickMe, the most obvious being to simply open the app. There isn't much to get the hang of in ClickMe. The app defaults to listing your last phone call as the "subject" of the reminder, but you can also tap the new reminder or contact button to remove the phone number. Simply fill in a subject and tap the button below with the desired time until you'll be reminded. That can be as little as 10 minutes or as long as a week in a single tap. There's a calendar button if you want to do a different amount of time. If you use one of the default buttons, that's it -- the reminder is set.
I think what makes ClickMe interesting is the way it inserts itself into the user experience when you're doing other things. For example, when you finish on a call, ClickMe pops up a small bar at the bottom of the screen that allows you to set a reminder to call the person back in a single tap. This bar times out in a few seconds, and you can disable it completely if you want. The other optional integration is with screenshots. Whenever you take a screenshot, ClickMe pops up (in full screen this time) so you can set a reminder with the screenshot attached. This might be handy if you want to remind yourself to deal with an email or text message. Just take a screenshot and tap a single button in ClickMe to set a reminder.
In the app, you've got a section where all your active and completed reminders can be found. The app also contains a voice input button if you want to speak instead of type. Next to that is the camera button if you want to attach a photo to the reminder. Whenever you set a reminder (however you do it) ClickMe closes immediately afterward. It's designed to get out of your way as much as possible.
The reminders pop up with a UI that lets you quickly mark as complete, or place a call/send a message if there's a contact or phone number attached. I only wish the visual style was a little more consistent with Android. ClickMe is also free and has no in-app purchases.


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After strolling past a copse of evergreens we climbed a gentle rise and then followed the trail to the edge of a sparkling pond. Nearby a waterfall tumbled over mossy rocks, while an osprey's shrill cry pierced the air.
This was Morgan Pond Reservoir in Ledyard, a pristine expanse of clear water surrounded by dense woodlands more reminiscent of northern Vermont than southeastern Connecticut.
I was on a 3-mile group hike last week sponsored by the Ledyard Library Friends and led by Karl Acimovic, an engineer with the City of Groton Utilities, which owns the property. Such organized outings are for the time being the only way the public can legally walk on these reservoir trails, since the department tightly controls access to a water source that serves some 6,800 customers.
"The beauty of the area is absolutely breathtaking," Paul Yatcko, director of utilities, told me the other day, but added, "Job number one is the safety and security of the water system."
At issue is a longstanding debate over whether the city ever will allow hikers unsupervised access to the property, especially considering the reservoir section is a critical link in a proposed 14-mile Tri-Town Trail that would extend from Bluff Point Coastal Reserve in Groton to the Preston Community Park. We were on the section north of Sandy Hollow Road near Rosemond Pond, a small portion of the department's 300-acre reservoir holdings in both Groton and Ledyard that contain about a billion gallons of water.
David Holdridge, a former Ledyard Town Councilor who heads a committee that for years has been promoting the trail (www.tritowntrail.com), told me his group has learned it soon will receive a $160,000 grant from the state Department of Energy and Environmental Protection, in part to help secure easements and rights of way from property owners.
Though Holdridge has made his pitch numerous times to Groton officials and has been repeatedly rebuffed, he remains cautiously confident city officials eventually will relent.
I hope so.
Though I fully agree with Yatcko's point that the utilities department's first priority is to safeguard its water supply, I believe allowing responsible hikers to pass through the reservoir property will minimize rather than contribute to such problems as littering. Open-space advocates have reported such findings in numerous surveys across the country.
Acimovic, who led last week's hike, said utility workers routinely find litter and other debris on the trail – as if to prove his point, I spotted a floating beer can – but in my view this supports the case for allowing more people on the trail rather than the present system of futilely trying to bar everybody.
Obviously, anybody determined to stray onto the property can easily bypass gates, and short of installing a Berlin Wall with armed guards and patrol dogs people will continue to trespass.
Most of the hikers I know routinely pick up coffee cups, cigarette butts and other trash they encounter. For decades I've been hiking the trails at Bluff Point, among the most popular paths in the region, and almost never see so much as a candy wrapper on the ground for more than 10 seconds.
Yatcko said littering is only one concern. The department also must be wary of pollution – either accidental or deliberate.
Again, these are reasonable fears, yet a no-trespassing sign and flimsy gate would not deter anyone intent on deliberately contaminating a public water supply.
He also mentioned problems of liability, but new state laws indemnify public landowners who allow public access to their property.
There are a host of other issues – should the trail be open to equestrians, dog-walkers and bicyclists? Who should pay for trail maintenance? For rescues if hikers are lost or injured?
Holdridge and others, including mayors and state representatives who support the Tri-Town Trail, have been trying to counter these arguments and answer these questions for years, and I hope having the $160,000 in hand will help advance their cause.
Acimovic told me that at one point the city considered opening the trails using a permit system, but for one reason or other that idea was dropped.
I'm not sure why this plan never advanced, but think it is an excellent idea: Limit access only to those who have registered in advance. Why not try the proposal for a short period, say a month, and see how it works out?
In the unlikely event the city found more litter or evidence the water supply was in any way threatened, then go back to locking the gates.
I'm certain members of the committee would volunteer to patrol the area, and the magnificent trails would be safer, cleaner and better protected than they are now.
Here's another idea: Get the Groton Open Space Association (gosaonline.org) involved. This incredible organization has one of the best track records in the state for land preservation, trail creation and simply getting the job done.
Without GOSA such treasured parcels as Bluff Point and Haley Farm State Park would be paved over or dotted with housing subdivisions.
I've known Sidney Van Zandt of Noank, one of GOSA's founders and current vice presidents, for years, and trust me, if you ever want to create a park, build a trail or raise money for a worthy project, call her first.
Anyway, I hope one day we'll all be able to travel on foot from Preston to Groton without dodging too many cars or trucks, or making a sharp detour around the reservoir property.
After tramping more than a month some 700 miles along the fabled Continental Divide Trail, Mystic native Hilary Sueoka and her boyfriend, Dan Stedman, who started hiking April 22 at the U.S.-Mexican border, finally rambled from the...
By the time Phil Warner and I hit the water in his lightning-fast tandem kayak last Sunday for our team's leg in the Josh Billings Runaground Triathlon in Lenox, Mass., we had already spent a good part of the morning lugging gear...
En route to a hiking expedition in Nepal's Himalayas a number of years ago, my wife and I took a detour to India and spent a day bouncing along on a bus from New Delhi to Agra to tour the Taj Mahal.
Whoosh! ... Whoosh! … Whoosh! …
Three cheers for the Obama Administration's decision this week to officially restore the name of North America's tallest mountain to Denali, which is what early inhabitants called the 20,310-foot peak in the Alaska Range.
Remember when you were a kid how your mom wouldn't let you have ice cream every day even though nothing in the world tasted better on a hot day than a double scoop of butter crunch?
Paddling like the dickens last Sunday on Maine's Rangeley Lake, we competitors had two choices: steer clockwise or counter-clockwise around Maneskootuk Island.
More than 40 years ago, Dave Wordell of Salem took his then-10-year-old son, Dave Junior, on a boat ride up Selden Creek, a narrow, secluded tributary of the Connecticut River in Lyme.
I can never remember – do you apply facial cleanser before or after the exfoliating scrub, and then finish up with healing balm and moisturizer, or should you start with the scrub, work your way through the cleanser and then top...
The international outrage sparked by an American trophy hunter's killing of Cecil, Zimbabwe's beloved lion, justifiably vilifies the despicable practice of slaughtering wildlife for sport – but it also exposes the human...
"Head for that tree stump," I instructed authoritatively one afternoon earlier this week, as if I knew for sure where we should be heading. I have learned to exude confidence when giving directions on any expedition, even...
When internationally celebrated speedster Scott Jurek scrambled last Sunday to the 5,269-foot summit of Mount Katahdin, the northern terminus of the Appalachian Trail, he broke the record for the fastest assisted hike of the 2,189-mile...
UConn student sorry for mac and cheese meltdown, says he's ashamed
Massachusetts man sentenced for selling counterfeit electronics for use in U.S. submarines
Police find 8 grams of crack in New London apartment, arrest city man
CGA professor talks about 3-D printing on board the Cutter Healy
Groton to seek $53 million more in state school construction funding to solve racial imbalance
Armed man dies after standoff with police at Old Saybrook motel


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The Fortas Chamber Music Series at the Kennedy Center is featuring three concerts this week emphasizing ensembles who collaborate. The Emerson String Quartet and Kalichstein-Laredo-Robinson Trio perform on Tuesday the 15th. On Wednesday the 16th, it's the Orion String Quartet and Windscape. And on Thursday the 17th, the Juilliard String Quartet joins their protégés, the Afiara String Quartet. Classical WETA's Marilyn Cooley had a chat with the Juilliard Quartet's second violinist, Ronald Copes.
The longest-running news and public affairs program on public television, Washington Week has been a broadcast journalism mainstay for more than four decades.Learn more →
Classical WETA 90.9 FM showcases notable new (or newly reissued) CDs each week. Hear selections from the CD on-air throughout the week, and check online to learn more about the artist and the music.Learn more →
Historian Garrett Peck discusses the history of brewing in the nation's capital. D.C.'s beer heritage dates back to 1770 and claims some very innovative brewers.Watch now →
Sesame Street, the recipient of 85 Emmys, helps children learn and grow with its unique blend of excitement, humor, and compassion.When to watch on WETA Television →
On a snowy night in 1965, Hyattsville, Maryland's DeMatha Catholic High School defeated Lew Alcindor's Power Memorial Academy in what many call the greatest high school hoops game ever played.Learn more →
WETA's mission is to produce and broadcast programs of intellectual integrity and cultural merit that recognize viewers' and listeners' intelligence, curiosity and interest in the world around them.Learn more →


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Best of News
People pay tribute to the late wife of Batasuna's imprisoned member... News PhotoAdult,Batasuna,Death,ETA,Horizontal,Organized Group,People,Politics,Prisoner,Respect,Spain,Village,Wife,WomenPhotographer RAFA RIVASCollection: AFP 2013 AFPPeople pay tribute to the late wife of Batasuna's imprisoned member Pablo Gorostiaga, Judith Uriarte, who died on September 2, during a demonstration in favour of ETA imprisoned members in the Northern Spanish Basque village of Llodio on September 6, 2013. Hundreds of ETA members are in prison in Spain and France, including many of its leaders who have been arrested over recent years. ETA demands that its imprisoned members be moved to prisons closer to home. AFP PHOTO / RAFA RIVAS (Photo credit should read RAFA RIVAS/AFP/Getty Images)


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Obsessed with Radiohead? Play Nirvana on repeat? Alternative rock music is awesome. Check out more.
About StumbleDNA StumbleDNA
Emma's Interests
From baby animals to wild creatures to exotic pets, discover cute pictures and more about animals.
Like an online museum of the visual arts, from cave paintings to Rodin sculptures to Warhol prints.
Flex your creativity by exploring performing arts, literature, music, visual arts and more.
No telescope? No problem. Explore astronomy, from the Big Bang to the mission to Mars.
We all need a little pampering sometimes. Explore makeup trends, hairstyles, skincare and more.
Quench your thirst by Stumbling through the best recipes for refreshing drinks and beverages.
Think ordinary is boring? Explore the weird, the strange, the obscure, and the downright freaky.
Are you a bookworm? Do you dream of a Pulitzer? Explore the literature of your favorite authors.
Miss Saturday morning cartoons? Get your dose of cartoons - funny, political and more - here.
Discover funny pictures and more about cats, from cute kittens to fat cats. We promise you'll smile.
Fascinated by the lives of the rich and famous? Don't miss the latest celebrity news and gossip.
With order comes disorder. Learn about chaos theory, controlled chaos and the butterfly effect.
What's your style? From your shoes to your accessories, make a statement with your clothing.
Whether you like romantic comedies or black comedies, have a laugh by Stumbling through funny films.
Get ideas for fun and easy DIY arts and crafts perfect for kids, holidays and more. Do it yourself!
Culture means something different to everyone. Learn about ethnicity, race, nationality and more.
Ready to get your groove on? Explore the best dance music, songs, videos, lyrics, bands and more.
Explore dancing, from ballroom to salsa, and soon you'll be wow-ing everyone with your moves.
From online dating to speed dating, we can all use some advice to calm those first date jitters.


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First United Methodist Church
Friday, October 09, 2015
Skip Navigation
Sermon Archives
Bible Study
Christian Education
Sunday School Curriculum
Members & Guest Information
Pledge Form
New Members Page
Music Ministry at FUMC
Circuit Ringers (Hand-bell)
Musical Instruments of FUMC
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Pastor's Page
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Thank you for your Prayer Request.
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Contact Us
Just for You...
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About our Church Family. The First United Methodist Church is a family oriented Church with a dynamic worship service that is open to persons of any religious background or to folks who are looking for a faith that tackles the hard questions of life with a timeless commitment to Christ. We are a Church that takes the Bible seriously. We are about making disciples. If this sounds interesting to you give us a try. For the early birds we have an 8:30 a.m. service in the Chapel. At the 10:00 a.m. service we fill the sanctuary friendly faces and great music, we can also provide a nursery .
We are a Church where 'the lights are on every day and night.
It won't take long to discover that this is truly a family, rich in the relationships that matter most. When we are together on Sunday or throughout the week, we worship, we serve, we laugh, we cry, we learn, and we reach out to the world with the life transforming message of Jesus Christ.
For more information on upcoming events visit our Bulletin & announcements page. Click this link:
or click on the announcement page directly to to see our upcoming events.
putting our faith into motion
by feeding the body, mind and soul...
We are a loving church family with a shared purpose to grow more Christ-like and to keep hope alive in our community and beyond.
First United Methodist Church
34 S. Main Street
Rochester, NH 03867
Choosing the Best
Chart how you've spent your time in the last week. What priorities does your chart reveal?
Powered by United Methodist Communications
Church Website by E-zekiel


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ScriptSpot is a diverse online community of artists and developers who come together to find and share scripts that empower their creativity with 3ds Max. Our users come from all parts of the world and work in everything from visual effects to gaming, architecture, students or hobbyists.
Register for free and be part of the community!
Script for 3dsMax 2009+ that changes the default Transform Type-In dialog to mini TTI. The miniTTI is placed over the title bar of the default TTI. The script file can be placed in maxroot/scripts/startup folder so when you run 3dsMax the default TTI will be automatically transformed to mini TTI and will be placed at the last used position of the TTI(default and mini).
In the video you can see how to use the script.
Special thanks to Denis Trofimov for his help.
This tool will help you visualize distance between two points, it's very handy for people working in architecture. It's not a pure script only Text and tape stretching reflects the distance through a float script controler.
new version v0.54- fexed find / replace in rename files window- few fixes- automatic relink assets in multiple .max and .mat (material library) files
Library Track / Relink... works with Multiple .MAX .MAT files without opening them.
Dedicated to organize, collect or relink whole new model library or all projects after moving them to new location. Just few clicks and they ready to merge / open !
2.08 Changelog:
2.07 Changelog:
Relink Bitmaps is a script to easily relink all missing files (Bitmaps, VRayMeshes, Mental Ray Proxies, VRayHDRI, IES, etc) when they change directories or when you move computers, check out the short video tutorial below for more detailed information.
Unlike some other scripts of its kind, this is free! There is a small donation link within the script if you choose to donate, I will remove the nag. It is a simple licensing system, that does not force you to transfer network cards or be connected to the internet and will work with all versions of Max that are supported by the script. If you choose to donate I'll be more than happy to license multiple computers as well.
very useful to have an animation relative to a selected point (pivot) without using constraints.
Tool for fast control standard spring controller.
- set-up several spring controllers in one menu
- set-up everyone separately
- controls the value of spring
- temporarily disabling springs
- copy settings from early created springs
- saving presets
Bake animation transform keys to chosen object with specified interval and sample frame step.
Plus reduce keys for chosen object with specified interval, sample frame step and threshold.
Matlib Render is a simple Script which allows you to Render a Matlib (each Material that the lib contains) into a small HTML Gallery (Thumbs).
It is configurable (a little bit) and has some nice features (own Renderpreset, user sized Image Output .... )
Test it and see for yourself.
This is my first Max Script ....... :)
Hi, hope you like my SkinHelper.
I tried to add a bunch of selection helping tools to the skinning process, so I replaced the hole UI of the 'Weight Tool' copied the default functions and added some more functionalities like, ...
Select by Weight; Save & Load Selection; Mirror Selection; Shrink, Grow, Loop, Ring addition; Set Weight Slider
I would like to read your feature ideas for this kind of tool.
Developed in 3dsMax2013.
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So where are we? I guess we are trying all sorts of things, and perhaps we should try even more things. I find it very difficult to choose the more promising ideas, directions and comments as Tim Gowers and Terry Tao did so effectively in Polymath 1,4 and 5. Maybe this part of the moderator duty can also be outsourced. If you want to point out an idea that you find promising, even if it is your own idea, please, please do.
This post has three parts. 1) Around Nicolai's conjecture; 1) Improving the upper bounds based on the original method; 3) How to find super-polynomial constructions? Continue reading


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|Since I've gotten a couple requests for a tutorial I'm gonna direct you to a tutorial that I read before I started areaorion.blogspot.com/p/tutor…
Life Begins At DigestionA request for :iconkotovdisease:
Karrie seemed like a normal enough woman. Every day, she would wake up, brush her teeth, have herself some breakfast, go to work, and then return home by the end of the day. To anyone who passed her on the street, or gave her a polite "Hello" on the subway, she would have seemed just like any other working woman. Even her appearance was standard, dressing modestly, her red hair in a bun, wearing a pair of glasses, making herself appear much older than she actually was. Of course, as all of this buildup would indicate, she was in fact, very strange. If a strange woman had ever existed, it was her.
At the top of the list of her unusual traits was a particular fetish she had. For whatever reason, she was incredibly aroused by the thought of pregnancy, and everything about it. The kicking? A turn-on. The swollen, milk-filled breasts?? Incredibly hot. Feeling her belly bloat out, into a tight, perfectly round sphere? Arousing as all hell. She couldn't stop t
A very close family haha, VoreHi! I'm Amy, I'm nine years old, and have a twin brother named Jeff! He never really follows the rules, and always gets me dragged along with him when he does something stupid. But I still love my brother, hes so sweet and nice to me! I love him!
"Hey Amy!" Jeff called
"Yeah?" I yelled back
"We're going to the store, come on! Lets go!"
"Okay, be right there!"
It seems our story has begun!
"I'm Here" amy said as she ran to my side in the kitchen, waiting for mom to get read to go
"Took ya long enough!" I said at her
"Ready kids?" Mom asked, smiling that usual I'm happy, don't screw it up smile
"Yeah!" me and my sister screamed together
"Great, now lets get in the car!" mom said with fake enthusiasm
We ran outside into the blue Dodge minivan parked out front of our mid-sized two story house. We got into the middle back seats right inside of the sliding doors, bucked ourselves up, and prepared to leave to go to Jewel-Osco for some groceries.
~At Jewel~
We finally got there afte
Swimmers delight -VORE-"Now class, its time to settle down." I said as I swam over to my students. My name is Patty Redbox and I teach a swimming class for kids grades 6-10. For the most part is kids who are already really good, but on occasion we have students like Greg Pepper. Hes annoying, obnoxious, rebellious, and claims to be a dedicated hard working pupil who just got over his fear of water.
"Nice suit Ms. Red!" I heard come from my group. Everyone was giggling except for Greg, who had just a tiny smile on his face. He was the only 10th grader, the rest were all 6th-8th and the kids looked up to him like a god. He had a missing tooth, he claimed to have lost it in a bum fight, and every time he smiles and I see his one front tooth missing, I have no idea why, but I want to punch him in the face soo bad.
"Alright now, lets get started, I want you all to do a lap from this end to the next" everyone set off and made it to the otherside quick as a fish. With the exception of Greg who slowly doggie paddled
People Eating Contest -Vore-"Welcome to the 3rd annual People eating contest!" The announcer called as everyone started to cheer
"Lets meet our competitors!" He said as he walked over to three women. He stoped at the first one, a busty blonde whom was the deffination of fitness "First off we have Amanda! A 26 year old woman, works at Best Buy, lives in the house her boyfriend had before last years Contest, any word of the audiance?"
"YEAH!" Amanda said "I'm here and I'm starting! Bring on the guys!"
"thats very nice" The announcer chuckeled
"Next we have Jean, a 34 year old mother of two, no husband after today. She's been voring profetionally for about 10 years now and learned when she was a child with her sisters"
"Ronald hunny, this victory will be for you!" The short brunette called out as she winked at a man and then rubbed her gut.
"And finally we have Danielle! The proud mother of five children! This is her first time in a vore compition, however she was the unbirthing contest winner two years running!"
Post Breakup Depression -Vore-Today was just terrible, day six after the break up. I looked around my apartment. Nothing special, nothing fun, nothing cool.
I went into my kitchen and got a bag of chips, sat on my one lonely couch, and started eating them. I turned on my radio and tried to relax.
My phone rang, I looked at it; Ashley.
"Hello?" I said tiredly
"Hey Ho! Whats up?" She yelled
"What do ya want?" I asked, trying to get this over with
"Party tonight! Come on, whole bunch of cute guys! its what you need!"
"No, I'm..."
"My place! Now!"
She hung up.
I sat with my Chips, you know, a party's just what I need. A couple of cute guys, some friends, some beer, just what I need. I convinced myself I would go.
I got in my car and left.
I pulled up and it was in full swing, 9 cars there already, sure to be more soon, i walked inside and immediately felt self conscience. I walked around awkwardly and found Ashley, I started to turn around, but she spotted me.
"Kayla! Come here doll!" she yelled
"Oh hey! haha"
Fun in the Pool by ElPortero"Beth! Please, come inside. I'm so glad you were free to watch Emma for us. You know how hard it is to get a babysitter on such short notice."
"Yes, Mrs. Jensen. I'm glad to help. All of my friends are away at summer camps so I really don't have much to do. Besides, I always have so much fun playing with Emma."
Beth had just finished the sixth grade and so far this summer had been very boring with all her friends gone. And she really did enjoy playing with Emma. She was such a sweet little girl.
"Well, Emma was thrilled to hear that you were the one watching her today. She's out in the backyard, playing in her wading pool."
Mrs. Jensen led Beth through the house to the backyard. As they stepped outside Beth saw Emma playing with her father. The six-year-old brunette girl was wearing a white one piece bathing suit with red polka dots and was swimming around the edge o
Lois Griffin VoreLOIS GRIFFIN VORE
Character(s) created by: Seth MacFarlane
Story created by: DeidaraFan02351
It was a cloudy day in the city of Quahog. There were predictions of a possible hurricane in due time, so everyone stayed indoors for their own safety. Lois was finishing washing the dishes when Meg walked in.
"Mom! Why can't I ask him out?!" She hollared at her mother.
"Because I don't lik him," Lois replied, turning back to her daughter. "He looks like a thug..."
"But that's what I like about him!!"
"Meg, for the last time: NO!!!"
Meg squeeled off, cursing softly, but not soft enough for Lois to hear. Angered by Meg's language, Lois placed the dishes she was washing on the counter and stormed off after Meg into her room.
"Young lady, I will not have that kind of language in my house." She said, as calmly as she could.


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Thanks to a $12,000,000 budget increase from Mayor de Blasio and the City Council, all 60 Brooklyn Public Library branches will begin staying open at least six days a week. (more…)
Thanks to a $12,000,000 budget increase from Mayor de Blasio and the City Council, all 60 Brooklyn Public Library branches will begin staying open at least six days a week. (more…)
Crown Heights' Weeksville Heritage Center is holding a jazz-themed Weeksville Weekend event on Saturday, October 10. (more…)
A look at Brooklyn, then and now.
The pink house on Bergen Street was still standing when I moved to Crown Heights North in 2000. Only two blocks from my house, I saw it often. It was in rough shape then, but hadn't been boarded up yet.
According to a 1976 survey of Crown Heights North by the LPC, this house, at 1183 Bergen Street, between New York and Brooklyn avenues, was the second oldest house in the neighborhood.
It was built, they figured, somewhere between 1860 and 1865.
The oldest house in Crown Heights North is the George and Susan Elkins House, at 1375 Dean Street, a couple of blocks away. The Elkins house is only 10 years older, built around 1853.
Both houses were the last remnants of this neighborhood's suburban past, the two oldest surviving houses in Crown Heights North.
The Bedford branch of the Lefferts family owned most of the land making up Crown Heights North. They stopped farming and began selling it off in the late 1840s and '50s. The street grid had been marked out in the 1830s, and this land was advertised as a great place for a suburban villa community. (more…)
Today's condo is a three-plus bedroom unit with 2,400 square feet and a loft-like, high-ceilinged living space that's large and attractive. It's in the Westcott, a former cheese factory at 25 Bergen Street in Cobble Hill. (more…)
BRIC TV is rolling out three new shows this week. If you're interested in the borough's shifting cultural landscape, make sure to tune in to On the Grid with Zephyr Teachout—a new series exploring the real maps of a rapidly changing Brooklyn.
Hosted by Zephyr Teachout, a 2014 Democratic gubernatorial candidate, the show uses data from CUNY's Center for Urban Research to redraw traditional neighborhood boundaries. (more…)
Cities are profoundly shaped by their transportation.
As Uber fought against a City Council bill that would have limited its number of new drivers, it touted the benefits of its service to those in the outer boroughs where yellow cabs and transit lines don't always reach. But that hasn't exactly played out. (more…)
Brownsville's P.S. 150, where average school community income is just $16,440
Qualification for free or reduced-price lunch has, for decades, been the prime quantifier of students' socioeconomic status in New York City public schools. Not any more.
It's like the NFL draft for architecture lovers: Open House New York just released the listings for its annual weekend of events, lectures and behind-the-scenes tours at the city's remarkable landmarks. (more…)
Renderings were just released for a new Bushwick nightclub planned for 599 Johnson Avenue — the latest in a spurt of creative and cultural businesses in the area.
Crown Heights Residents Beat Eviction, But Worry About the Consequences [Crain's]
New York Landmark Panel Acts to Clear Backlog [WSJ]
Residents: Kensington Building Super's Body Cam Is an Invasion of Privacy [CBS]
Why Are French Guys Dressing Like They're From Brooklyn? [Vogue]
Permits Filed: 88 Linden Boulevard in Flatbush [NYY]
City Backtracks on Vow to Open a New Middle School in Dumbo, Parents Say [DNA]
[Washington Avenue in Clinton Hill | Photo: Cate Corcoran]
Investigators in Borough Park have found the remains of the second victim of this weekend's fatal gas explosion. (more…)
Beloved Owner of Tom's Diner Gets Street Co-Naming [BK Reader]
Welcome to The Hole, John Gotti's Rustic Body-Dumping Ground [Gothamist]
Brooklyn Pour Brought Local and Far-Flung Brews to Greenpoint [Greenpointers]
City Fixing Bay Ridge Intersection Decades After High-Profile Traffic Deaths [BK Paper]
District Manager Unearths List of Demolitions [Q at Parkside]
[Verrazano Bridge | Photo: Mitzgami via Flickr]


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For urgent online help with computer security problems, small companies in Plano, TX, have access to world-class support from Progent's security engineers. Progent's remote support staff is available to provide efficient and economical assistance with security crises that are impacting the productivity of your network. Progent's accredited security consultants are qualified to provide help for systems powered by Microsoft, Linux, Macintosh, Solaris, and popular versions of UNIX. Progent's broad range of services covers firewall technology, messaging systems, protected system architecture, and data restoration. Progent's support staff has earned the industry's most advanced security accreditations including CISA and Information System Security Architecture Professional (ISSAP).
Progent offers remote security assistance on a per-minute model without minimum call duration and without extra fees for setup or off-hour support. By billing by the minute and by delivering world-class support, Progent's billing model keeps expenses low and eliminates situations where simple solutions entail major charges.
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For businesses that have planned beforehand for an attack, the step-by-step incident response model promoted by Global Information Assurance Certification is Progent's approved method of reacting to a major security incident.
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Progent has skill in restoring systems and devices that have been compromised, are quarantined, or have stopped working because of a security penetration. Progent can help determine the losses caused by the attack, restore ordinary functions, and retrieve information lost as a result of the attack. Progent's security specialists can also perform a comprehensive forensic analysis by going over event logs and utilizing a variety of advanced forensics tools. Progent's experience with security problems minimizes your downtime and allows Progent to recommend effective strategies to avoid or mitigate future assaults.
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Microsoft Data Protection Manager is a ground breaking backup and recovery solution utilizing fast disk systems to increase reliability, speed, and manageability. Progent's certified Microsoft DPM engineers can assist you to develop a practical disaster recovery strategy, implement an affordable high-availability IT architecture, configure a Data Protection Manager-powered backup and recovery system, thoroughly validate your system, train your administrative personnel or local service providers how to manage Microsoft DPM, or provide extensive information technology outsourcing including off-site hosting of Microsoft DPM servers in Progent's data center. For details, go to System Center Data Protection Manager Consulting Services.
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Security Vulnerability Evaluation and Security Compliance Assessment
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MS ISA Server 2006 and its current version, Forefront Threat Management Gateway 2010, offers policy-based protection, improved performance, and centralized administration of complex networks by providing both a firewall and a Web acceleration mechanism integrated with Microsoft's Microsoft Windows Server operating system. The Microsoft Forefront TMG and MS ISA Server 2006 firewalls provide comprehensive data filtering, management of access policy, and traffic routing. The cache improves system performance by storing frequently requested Web data. Progent's Microsoft Forefront TMG 2010 engineers and MS ISA Server 2006 experts know how to plan and implement an Internet security gateway solution that matches your security requirements while avoiding restricting network efficiency.
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Progent can offer the services of a Cisco Certified Internetwork Expert (CCIE) or Cisco Certified Network Professional (CCNP) to help you to select, deploy, and support Cisco PIX and ASA Firewalls. Learn the details concerning Cisco PIX Firewall and ASA Firewall Consulting.
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Progent's Cisco CCIE engineers and Cisco CCNP experts can provide world-class consulting expertise for Cisco's entire family of security and VPN products such as PIX 500 Firewalls and ASA Series Firewalls, the Catalyst Firewall Services Module, secure broadband and IS routers, Aironet wireless access points, and Catalyst switches. Find out more details concerning Cisco Security, Virtual Private Network and Aironet Wireless Expertise.
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As well as supporting a broad array of protection technologies from Microsoft and Cisco Systems, Progent can provide small and mid-size organizations expert engineering services for solutions from other important firewall and Virtual Private Network suppliers. Progent's engineers offer:
Unannounced Intrusion Testing Consulting
Stealth penetration testing is a key method for allowing businesses to determine how vulnerable their networks are to real-world threats by showing how effectively corporate protection processes and mechanisms hold up against authorized but unpublicized intrusion attempts launched by veteran security engineers using the latest intrusion techniques. Find out additional details concerning Progent's Penetration Testing Services.
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Certified Information Security Manager (CISM) identifies the fundamental competencies and international benchmarks of service that computer security professionals are expected to master. It offers business management the assurance that those who have earned their CISM have the experience and skill to offer efficient security management and consulting services. Progent can offer a CISM-certified consultant to help your enterprise in vital security areas including data security governance, risk assessment, data protection process control, and crisis response support.
Get more details about Progent's CISM Security Consulting Expertise.
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Progent's CISSP consultants are security specialists who have earned CISSP status as a result of verified professional work, extensive study, and exhaustive examination. CISSP qualification indicates mastery of an international standard for IT security. American National Standards Institute has granted the CISSP credential accreditation in the area of IT security under ISO/IEC 17024. Areas of knowledge covered within CISSP include security administration procedures, security design and test systems, access permission methodology, applications development security, operations security, physical security, encryption, telecommunications, Internet security, and disaster recovery planning.
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ISSAP-Qualified Consultants for Secure Network Architecture
Progent's ISSAP certified security consultants are experts who have been awarded ISSAP status after thorough examination and substantial hands-on work with network security design. ISSAP security experts have acquired comprehensive understanding of access management mechanisms and methodologies, phone system and network protection, cryptography, needs evaluation, business continuity planning (BCP) and DRP, and physical security integration. Progent's ISSAP-qualified security experts can assist your business with all phases of architecture security.
Get more details concerning Progent's ISSAP Certified Secure System Architecture Engineering Services.
Certified Information Systems Auditor (CISA) Consulting Expertise
The Certified Information Systems Auditor credential is a globally recognized achievement that represents mastery in information system security audit and control. Accredited by ANSI, the CISA credential has consultants pass an extensive test administered by the ISACA international professional group. Progent offers the services of a CISA-qualified security engineer trained to help businesses in the fields of IS audit process, information technology administration, network assets and infrastructure lifecycle, information technology support, safeguarding information resources, and business continuity planning.
Get additional details concerning Progent's CISA Consulting Services.
CRISC-certified Network Risk Management Experts
The Certified in Risk and Information Systems Control (CRISC) certification program was established by ISACA to verify a consultant's ability to design, implement, and support IS control mechanisms to mitigate risk. Progent can provide the expertise of a CRISC-certified consultant to help you to develop and carry out a business continuity or disaster recovery strategy based on leading practices promoted by CRISC and crafted to match your company's risk tolerance, business goals, and IT budget. Progent's risk management services are a good fit the support provided by Progent's CISA-certified security engineers for impartially evaluating your IT management mechanisms and also with the expertise of Progent's CISM-certified support professionals for designing security policies.
Get the details about Progent's CRISC Risk Mitigation Support.
GIAC (Global Information Assurance Certification) Support Services
GIAC (Global Information Assurance Certification) was founded in 1999 to validate the knowledge of computer security experts. GIAC's goal is to verify that a certified professional possesses the skills needed to provide support in vital areas of system, information, and software security. GIAC accreditations are recognized by companies and government organizations around the world including and the United States NSA. Progent offers the help of GIAC certified security engineers for all of the network security disciplines covered under GIAC accreditation topics including auditing networks, incident response, intrusion detection, and web-based services security.
Learn additional information about Progent's GIAC Support Expertise.
Contact Progent for Computer Security Support
If your company is located in Plano or anywhere in Texas and you need computer security engineering help, telephone Progent at 800-993-9400 or send email to firstname.lastname@example.com.


text:
Advanced Remodeling Of
Serving Melville
3790 Merrick Rd Ste A
Seaford, NY 11783
Main (516) 781-7300
Latest Reviews of Advanced Remodeling Of
#1 Nov 26, 2012
Liar. Thief. Scam Artist. Cheat. Incompetent. Lowlife. I am in agreement with ALL of the other bad reviews I have encountered posted about this dirtbag and his company, as I have experienced the same. He took full payment for all jobs open and left every job unfinished. What little work he did complete was sloppy and unsafe. He doesn't even pay his own vendors. If you are contemplating using this dirtbag, I have only one word for you: DON'T. I only wish I had checked more thoroughly before we went ahead. If you are doubtful, I invite you to email me at [email protected] I will be happy to have you come to my home and see for yourself.
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United Center
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Content count3,324
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About mikemodeler
MCM Ohana
- Birthday 12/28/1963
Profile Information
- Location NASCAR Country!
- Full Name Classified
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mikemodeler's Activity
mikemodeler added a post in a topic 69 GTOMonogram had a '68 and Revell had a '69. Both were recently re-issued, should be able to find them easy enough.
mikemodeler added a post in a topic Moebius 67-72 Ford Pick-up newsNothing on the Moebius website nor Tower Hobbies, but considering the only changes (based on box art) appear to be the grille, I would think it could be here by the first of the year.
Hopefully Dave Metzner from Moebius will chime in with an expected date.
mikemodeler added a post in a topic Revell 49 MercuryMe too! I had it for years and never got around to building it.
mikemodeler added a post in a topic Real or Model #235I went with Real, cuz if it is a model, it is a very well executed one with great details.
mikemodeler added a post in a topic AMT 51 Chevy Bel-AirPM sent
mikemodeler added a post in a topic Starsky&HutchThere is an extensive review of the kit on here and it points out a lot about the kit, especially it being molded in red.
mikemodeler added a post in a topic What Irked You Today?Had a meeting with one of my customers and my boss.
Sure wish some people lived in the real world and understood how the sales process worked.
Thank goodness for a rainy weekend and adult beverages.............
mikemodeler added a post in a topic $7.99 models back at Ollies!Probably not much I need or want, but a Corvette or two might be nice.
mikemodeler added a post in a topic 9th Annual Hope it Don't Snow Show and ContestThere is the January show in Spartanburg and the May show in Simpsonville. Both great shows to see some nice models and the swap meet area usually has some great deals.
mikemodeler added a post in a topic Buying kits at swap meetsI have never bought a kit at a 1:1 show for the very reasons stated here- too dang high! The guys selling at swap meets are hoping that the people walking the meet aren't aware of Hobby Lobby or our model car swap meets where that same kit could be half as much!
When I go a model swap meet to sell, I am the guy that usually walks out with a pocket full of money because I am there to thin the stash and will make deals. Sometimes I regret selling some models so cheaply, but then I remember that the kits have sat in my garage for 10 years and I need to get my stash to a more manageable level.
If I go to a swap meet to buy, I will circle the room and look for the guy who isn't a "professional seller" as he can probably make deals. I see some of the same guys and kits at shows around the area and wonder why someone is stuck on a high price for a kit that has been at swap meets for years? I have yet to find a kit I had to have that I was willing to pay a premium for, and if they insist on a premium price, they should try their luck on eBay.
mikemodeler added a post in a topic Where did you start building model car kits?I have always been fascinated about cars and machinery. I grew up at a great time as my oldest brother is 17 years older and he would buy me Hot Wheels and Matchbox cars every week. I would circle the Sears Toy Book every year and Santa brought me lots of cars and trucks. I have the distinction of being born right after Christmas (12/28) and my birthdays were usually pretty good as I got a lot of car stuff as it went on sale after Christmas!
Some neighbor friends were given some models by their uncle in the early 70's and I got hooked on them at the same time. Been building on and off for over 40 years, have tried to find some of the kits I destroyed in my youth.
mikemodeler added a post in a topic 56' NomadWOW! Very nice and clean, shiny paint and detailed!
mikemodeler added a post in a topic Truckin for Kids 2015 picsNice pictures, looks like it was a nice show.
mikemodeler added a post in a topic Great Traders ListBack at ya! Happy with what I received and wouldn't hesitate to trade again.
mikemodeler added a post in a topic AMT 72 Chevrolet FleetsideIf you can find the GMC stepside kit from the same era, it will have the shortbed frame in it.
I may have an extra '72 C10 kit for trade, I will get back to you later once I get a chance to check the stash.


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StartUpHire is the place to find Algorithm Development Engineer jobs. Review the list of Algorithm Development Engineer career opportunities to the left. These Algorithm Development Engineer jobs represent some of the most rewarding careers available.
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Job Summary This position offers an experienced engineer the opportunity to make major contributions in developing algorithms for our software defined radio and positioning and navigation projects. This position requires strong independent and team research abilities. Flexibility9/12/2015 Colorado Springs, CO Save This Job
Research, design and develop advanced clock tree synthesis technologies, including clock tree synthesis engine design, and optimization of design performance for advanced node processing. Research and design algorithms for timing optimization, including gate level power9/6/2015 Santa Clara, CA Save This Job
Engineering Sunnyvale Sunnyvale, CA, United States Company Overview Ruckus Wireless is a pioneer in the wireless infrastructure market, enabling carriers and enterprises to stay ahead of the exploding demand for high-bandwidth applications and services. The Ruckus Smart10/8/2015 Sunnyvale, CA Save This Job
ESSENTIAL DUTIES AND RESPONSIBILITIES include the following (other duties may be assigned as necessary): Lead design and development of DSP Firmware used across the EarLens product portfolio Develop Matlab simulation models, theory of operation and implementation of DSP10/1/2015 Menlo Park, CA Save This Job
GENERAL PURPOSE OF THE POSITION: Responsible for transforming market requirements into detailed product requirements, developing system architecture, defining interfaces, generating test plan, developing system controls, generate test report. DUTIES AND RESPONSIBILITIES:8/25/2015 Ft. Collins, CO Save This Job
Job Description: Audyssey Laboratories is seeking a Research and Development Engineer to join its research and technology group. As an integral part of the R&D team, the engineer will create modular, well-organized code, produce documentation and test procedures, and assist in8/30/2015 Los Angeles, CA Save This Job
Space Exploration Technologies Work to advance the course of human history and pave the way to Mars. SpaceX is a US based advanced technology company founded by residing CEO and CTO, Elon Musk. SpaceX builds rockets and spacecraft from the ground up including cutting edge9/18/2015 Hawthorne, CA Save This Job
Location:Golden, CO Listing Date:2015-06-19 Position:Software Engineer / Senior Software Engineer Job Type:Full-Time Education Level:Bachelor's Degree Experience Level:Experienced (Non-Manager) Overview Veran?s software engineers pioneer medical solutions that positively impact8/26/2015 Golden, CO Save This Job
at Sumo Logic (View all jobs) Redwood City, CA We are Sumo Logic, and we are building the Next Generation Log Management and Analytics solution --- delivered as a cloud-based service. We have 500+ enterprise customers with $160.5M in funding from the world's leading investors9/7/2015 Redwood City, CA Save This Job
Senior SW Engineer, OpenDSP Developer Support Job Description OpenDSP is Audience?s development platform/framework that allows third party DSP developers to develop DSP solutions for Audience processors. Audience is looking for an experienced SW engineer to create and enhance10/1/2015 Mountain View, CA Save This Job
Mountain View, CA As a part of the Infra team, you would help to design and build tools, technologies and processes that allow other teams to achieve their goals more efficiently. They create leading edge technologies that are critical to our business and that are so awesome that9/9/2015 Mountain View, CA Save This Job
iOS Engineer We?re changing the way business does social media, and are fanatical about creating a product that?s elegant, useful, and ultimately makes our customers very happy. We?re a small company in that great stage of gaining massive momentum, and are looking for a8/9/2015 San Francisco, CA Save This Job
RockYou, a leading social gaming company, is seeking a Principal Software Engineer to be part of the engineering team and lead the migration of acquired games. Responsibilities: Manage the migration of games acquired from other companies to RockYou Investigate the tech stack9/16/2015 San Francisco, CA Save This Job
RockYou, a leading social gaming company is seeking a Staff Software Engineer to be part of the engineering team and help design and build technology to be used across the organization. Responsibilities: Develop centralized technologies and tools for games and other9/16/2015 San Francisco, CA Save This Job
RockYou, a leading social gaming company, is seeking a Principal Software Engineer to be part of the engineering team and help design and build technology to be used across the organization. Responsibilities: Help develop the vision for all of the shared tech across the9/16/2015 San Francisco, CA Save This Job
Job Number:003782 Job Title:Development Systems Engineer Number of Openings:1 Job Type (Employment Type):Direct Hire Country:United States State/Province:Illinois City:Chicago Job Schedule:Full Time Level of Education:Four-Year Degree Years of Experience:5 Position8/17/2015 Chicago, IL Save This Job
Mountain View, CA As a Full Stack Software Engineer on the team responsible for building the next generation of IMVU, you will collaborate with engineers, product, and design to deliver immersive and distinctive 3D content in a web browser. On any given day you may be writing a8/10/2015 Mountain View, CA Save This Job
Vormetric is looking for an experienced Windows kernel software engineer to work on challenging problems in Vormetric Data Security product. The ideal candidate has already worked on Windows File System Filter drivers, NTFS file system and understands the difficulty of building8/23/2015 San Jose, CA Save This Job
ID# 2016-13 Date: June 15, 2015 Vormetric is looking for an experienced Windows kernel software engineer to work on technical enhancement for Vormetric Data Security products. The ideal candidate has already worked on Windows File System Filter drivers, NTFS file system and8/23/2015 San Jose, CA Save This Job
RockYou, a leading social gaming company is seeking a Server Engineer to be part of the engineering team and help design and build the next generation features for social and mobile games. Responsibilities: Be capable of working independently, designing and delivering8/17/2015 Eugene, OR Save This Job


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Yamaha aims for electric scooter dominance: Starting with the EC-03
Yamaha has some bold aims when it comes to electronic transportation.
According to Motorcycle.com, the Japanese company aims to have three or four electronic scooters on the road by 2015 and then wants to be the leader in the field by 2020.
And it is kicking off its comeback into the electronic scooter market (remember the glow-in-the dark EC-02 in 2007?) with the Japanese launch of the EC-03.
The EC-03 will be classed as a 50cc scooter and is powered by a 50V lithium-ion Sanyo battery. It runs on the Yamaha Integrated Power Unit (YIPU), which has compactness at the forefront of its objectives.
It comes with a brushless DC motor, a control unit, planetary gear transmission and a drum brake all integrated within the 12-inch rear wheel.
The Yamaha EC-03 has an aluminium-alloy frame so it only weighs 56kg, which is 30 per cent less than a petrol-powered 50cc scooter.
It will cost you about £1820 (which is a bit cheaper than the Yogo) and it's capable of travelling for 26.6 miles on a single 6-hour charge.
The EC-03 is launching in Tokyo on 1 September and then the rest of Japan a month after that. No word yet as to whether we'll see it in this green and pleasant land, but here's hoping.
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