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N-acyl phosphatidylethanolamines (NAPEs) are synthesized in response to stress in a variety of organisms from bacteria to man. More recently, non-enzymatic modification of the ethanolamine headgroup of PE by various aldehydes including levuglandin/isoketals, which are γ-ketoaldehydes (γKAs) derived from arachidonic acid, has also been demonstrated. The levels of these various N-modified PEs formed during stress and their biological significance remain to be fully characterized. Such studies require an accurate, facile, and cost-effective method for quantifying N-modified PEs. Previously, NAPE and some of the non-enzymatically N-modified PE species have been quantified by mass spectrometry after hydrolysis to their constituent N-acylethanolamine by enzymatic hydrolysis, most typically with S. chromofuscus phospholipase D (PLD). However, enzymatic hydrolysis is not cost-effective for routine analysis of large number of samples and hydrolytic efficiency may vary for different N-modified PEs, making quantitation more difficult. We therefore sought a robust and inexpensive chemical hydrolysis approach. Methylamine (CH3NH2) mediated deacylation has previously been used in headgroup analysis of phosphatidylinositol phosphates. We therefore developed an accurate assay for NAPEs and γKA-PEs using CH3NH2 mediated deacylation and quantitation of the resulting glycerophospho-N-modified ethanolamines by LC/MS/MS.
Biosynthesis of N-acyl phosphatidylethanolamines (NAPEs) in response to stressors has been reported in a wide variety of organisms including bacteria [1; 2], yeast [3], plants [4; 5; 6; 7], and mammals [8; 9; 10; 11] (Fig 1). NAPEs are well-established precursors of biologically active N-acylethanolamides (NAEs), including C20:4NAE (anandamide) and C18:1NAE (oleoylethanolamine). Recent work has also raised the possibility that NAPEs are themselves biologically active mediators of protective responses to stressors [12; 13]. Increased levels of NAPEs or their metabolites reduce glutamate excitotoxicity, ischemic damage, inflammation, hunger and food intake [12; 14].
In addition to enzymatic N-acyl modification of PEs, non-enzymatic N-modification of PE can occur by lipid aldehydes generated during lipid peroxidation. These lipid aldehydes include γ-ketoaldehydes derived from arachidonic acid (γKAs) [15; 16; 17] (Figure 1), as well as α,β-unsaturated carbonyls such as 4-hydroxynonenal and acrolein [18; 19; 20]. The γKAs form as non-enzymatic rearrangement products of bicyclic endoperoxides generated from arachidonic acid (AA) either by the action of cyclooxygenases (levuglandins) [21] or non-enzymatically via free radical mediated mechanisms (isoketals)[22; 23]. Free radical mediated peroxidation of phospholipid-esterified arachidonic acid generates γKA adducted to adjacent amines while still esterified [24]. The initial stable reaction product of γKAs with amines are pyrrole adducts [25]; however, in the presence of molecular oxygen and oxidizing conditions, the pyrrole adducts mature into lactam and hydroxylactam adducts[23] (Fig 1). Although very little is known about the non-enzymatically N-modified PEs, elevated levels of γKA modified PE (γKA-PE), particularly the hydroxylactam adducts, were recently found in plasma of patients with age-related macular degeneration as well as in the liver of ethanol-fed mice [16]. Furthermore, exposure of cultured endothelial cells to γKA-PE induced cell death, suggesting that γKA-PEs are biologically active [17]. Thus, the effects of γKA-PE appear to oppose those of NAPEs, so that the relative balance of these two classes of N-modified PEs may be important determinants of health and disease. To study the roles of N-modified PE in stress responses, an accurate, facile, and cost-effective method to measure both NAPEs and γKA-PEs simultaneously is needed.
NAPEs have been previously directly measured by two methods: TLC [26] and mass spectrometry [2; 26; 27; 28; 29]. While TLC is readily available and inexpensive, it lacks specificity for individual N-acyl chains and is less sensitive and more difficult to accurately quantify than mass spectrometry methods. Mass spectrometry, particularly LC/MS/MS, has several advantages. Not only can internal standards be added to ensure that variations in extraction efficiency do not affect measured levels, but chromatography can be used to separate NAPE from other phospholipids and the exact species of NAPE can be identified by its measured mass. However, accurate quantitation of NAPEs by LC/MS/MS requires measurement of more than 50 individual masses because each NAPE contains two O-acyl chains in addition to its N-acyl chain, each of which can potentially differ in chain length and unsaturation,. Hydrolysis of NAPE to their constituent NAE using either S. chromofuscus PLD or mammalian NAPE-PLD has been employed as an alternative to measuring each individual NAPE because this procedure removes the differences in mass related to the O-acyl chains [3; 10; 12]. These methods still allow differentiation between the various species of N-acyl chains, but greatly simplify the number of total masses that must be quantified. Monitoring of N-acyl chain species is important because C20:4NAE, clearly differs in biological activity from C18:1NAE, so that relative levels of the individual precursors may be important. We have also employed hydrolysis by S. chromofuscus PLD to measure γKA-PE [17]. Unfortunately, S. chromofuscus PLD is expensive to use because relatively large amounts are required to ensure complete hydrolysis of all NAPE and γKA-PE in the sample. Whether S. chromofuscus PLD can hydrolyze other non-enzymatically N-modified PEs such as HNE-PE is also unknown. Although NAPE-PLD is an efficient lipase of NAPEs, NAPE-PLD is not commercially available and whether it can utilize γKA-PEs as a substrate is unknown. Therefore, alternative strategies are needed for a facile and inexpensive method to quantify N-modified PEs.
One potential low cost alternative to phospholipases is chemical deacylation. A four hour incubation with sodium hydroxide has been used to convert NAPEs to their constituent glycerophosphate-N-acylethanolamines (GP-NAEs)[30]. This method hydrolyzes O-acyl chains but not N-acyl chains. However, sodium hydroxide mediated deacylation requires significant additional sample clean-up to remove the excess sodium salt prior to LC/MS/MS analysis. Furthermore, we have observed that γKA adducts appear to be somewhat labile during incubation with strong acids and bases for extended periods, so we sought a milder deacylation reagent that would also be sufficiently volatile to use directly in LC/MS/MS. Deacylation mediated by methylamine (CH3NH2) has been employed for headgroup analysis of phosphatidyl inositols [31]. CH3NH2 serves as both the base and the acyl acceptor, preventing secondary reactions other than deacylation [32]. Furthermore, CH3NH2 is volatile, so that hydrolyzed samples can potentially be directly injected into LC/MS/MS without further preparation. Finally, because CH3NH2 mediates deacylation via transesterification, the deacylation product of esterified γKA adducts is expected to be a methylamide with a mass 13 amu greater than the deacylation product of non-esterified γKA adducts, making it possible to distinguish the two γKA-PE products in the mass spectrometer. Therefore, we tested whether CH3NH2 mediated deacylation could be used for quantitation of both NAPEs and γKA-PEs. We found that deacylation of NAPEs and γKA-PEs with CH3NH2 and subsequent measurement of the resulting glycerophosphates (GPs) by LC/MS/MS was a facile and cost-effective method to accurately quantify NAPE and γKA-PE levels in biological samples.
1,2 dioleoyl-sn-glycero-3-phosphoethanolamine-N-arachidonoyl ammonium salt (C20:4NAPE), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (C32:0PE), and porcine brain PE were purchased from Avanti Polar Lipids, Inc. (Alabaster, AL). Palmitoyl chloride, heptadecanoyl chloride, stearoyl chloride, and CH3NH2 (40 wt. % in water) were purchased from Sigma-Aldrich (St. Louis, MO). Organic solvents including methanol, chloroform, dichloromethane and acetonitrile were HPLC grade. All other chemicals were purchased from Sigma-Aldrich (St. Louis, MO) unless otherwise specified. E. coli C41 cells transformed with either empty vector (C41-Vec) or with the expression vector for Arabidopsis thaliana NAPE N-acyltransferase, (C41pDEST), were a kind gift from Denis Coulon and Lionel Faure from Université Victor Segalen Bordeaux 2. Sep-Pak silica cartridges was purchased from the Waters Corporation (Milford, MA)
The synthesis of NAPEs was adapted from [12] with a modified purification method. In summary, to a 50 ml flask cooled in an ice-water bath, 0.208 gram (0.3 mmol) of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) was suspended in 20 ml chloroform containing 0.1 g triethylamine with a magnetic stirring bar. An appropriate acyl chloride (1.1 mmol) in 7 ml chloroform was added in a dropwise fashion. After the addition was complete, the reaction mixture was heated to 40°C for 2 h and allowed to stir overnight at room temperature. The reaction was quenched by adding saturated NaHCO3 solution (10 mL) and the organic layer was collected and washed with 30 mL of 0.01 M HCl and 30 mL of brine. After dehydrated over anhydrous Na2SO4, the product was dried with a rotary evaporator and purified using silica gel chromatography (methanol/ethyl acetate/ ammonium hydroxide 20:80:2). The purified NAPE was weighed and the reaction yields 65-80%. The purified NAPE was analyzed by TLC using silica plates and chloroform/methanol/ethanol/ethyl acetate/0.25% KCl (10:4:10:10:3.6) as solvent. Plates were visualized with phosphomolybdic acid.
γKA (15-E2-isoketal, MW 352) and methyl ester γKA (methyl ester 15-E2-isoketal, MW 366) were prepared as previously described by organic synthesis [33]. The structure of 15-E2-isoketal is shown in Figure 1. The synthesis of γKA-PE (or esterified γKA-PE) was performed with slight modification from our previously described procedure [17]. DPPE and γKA (or methyl ester of γKA) were suspended in a mixture of 1 M triethylammonium acetate/chloroform/ethanol (1:1:3) with a final concentration of 0.25 mM and 0.083 mM for DPPE and γKA, respectively. After incubation at 37°C overnight, the pyrrole formation of the product was identified by LC-MS analysis and quantified by Ehrlich's reagent with the absorbance at 580 nm measured by spectrometer.
C41-Vec and C41pDEST were cultured according to [4] with the following modifications to produce optimal amount of NAPEs. After overnight growth in LB medium with 0.1 mg/mL ampicillin at 37 °C at 250 rpm, cultures were diluted (1:50) and continued at 37 °C at 250 rpm until they reached an optical density (A600) of 0.5-0.6. Then isopropyl β-D-thiogalactoside (1 mM) was added to induce the expression and the culture was allowed to grow overnight at 30 °C at 200 rpm. After measurement of the optical density, the cells were harvested by centrifugation at 5000 g for 15 min and the pellet was resuspended in 500 uL of water.
Human umbilical vein endothelial cells (HUVEC; passage 6) were cultured in 100 mm dishes coated with 0.2% gelatin for 4 to 6 days, allowing to grow to >90% confluence. Plates were washed three times with HBSS and then duplicate plates were incubated with 5mL of vehicle (0.1% DMSO in HBSS), synthetic γKA (1 μM in HBSS with 0.1% DMSO), or arachidonic acid (AA, 1 mM in HBSS with 0.1% DMSO) at 37 °C for 4 h. The treatment medium was carefully removed after incubation and 2 mL HBSS was added to the cells on ice. Cells were scraped and collected with the wash media into clean centrifuge tubes.
The overall work flow for analysis of N-modified PE is shown in Figure 2. The bacterial pellet from a 25 ml culture of bacterial cells or human plasma (200 uL) were mixed with 3 mL pre-chilled Folch solution (chloroform/methanol, 2:1 containing 0.01% BHT), followed with addition of 1 nmol C17:0 NAPE (10uL in CHCl3) and 1 mL of water. For HUVEC cells, 6 ml of Folch solution and 1 nmol C17:0 NAPE were added to the 2 ml of cell solution. The mixture was vortexed for 5 min and centrifuged at 4000 g for 5 min. The resulting lower (chloroform) layer was carefully collected and dried under nitrogen. The extracted lipids were reconstituted in 1 mL chloroform and loaded onto a Sep-Pak silica cartridge preequilibrated with chloroform. The cartridge was washed with 8 mL chloroform and N-modified PEs were eluted by 8 mL 50% methanol/chloroform. The lipids were dried under N2 and saved at −20 °C before methylamine hydrolysis.
Methylamine hydrolysis was adapted from those previously described for phosphoinositides [31]. Dried lipid extracts were dissolved in 200 μL methylamine reagent (CH3NH2 (40 wt.%)/CH3OH/1-butanol (4:4:1)) and mixed well. In the initial experiments, the reaction was incubated at 53°C for 0-2 h and aliquots removed at appropriate time points for TLC analysis and mass spectrometry. TLC was performed using silica plates and chloroform/methanol/ethanol/ethyl acetate/0.25% KCl (10:4:10:10:3.6) as solvent. Subsequently, all reactions were incubated at 53°C for 1 h and the resulting solution was injected for MS analysis.
Samples were analyzed on a ThermoFinnigan Quantum electrospay ionization triple quadrapole mass spectrometer operating in negative ion mode, equipped with Surveyor autosampler. Volume of injection was 5 uL. The mobile phase consisted of solvent A, 10mM t-butyl ammonium acetate in water/acetonitrile (96:4), and solvent B, 10mM t-butyl ammonium acetate in water/acetonitrile (6:94). The lipids were chromatographed on a Kinetex C18 column (50 mm × 2.10 mm, 2.6 um, 100 Å; Phenomenex, Torrance, CA) with a constant flow rate of 250 uL/min. After 0.5min hold at 1% solvent B, the solvent was gradient ramped to 99% B over 4 minutes, held at 99% B for 1.5 min and return to 1%B over 1 min and held for 2 min before the next injection. The electrospray needle was maintained at −3300 V. The ion-transfer tube was operated at −35 V and 270 °C. The tube lens voltage was set to −180 V. Product ion spectra were generated by collision-induced decomposition of the precursor ion (m/z 500.3 for C20:4 GP-NAE, m/z 530.3 for GP-γKA-Etn and m/z 543.3 for GP-γKA- MA). Only the precursor ion was allowed to pass through the first quadrupole; the ion was activated by collision with argon in the second quadrupole (10 eV; argon 1.5 mTorr). Product ion spectra were recorded for m/z 50 to 500 over 1 s. The mass spectral resolution of both quadrapoles was set to a peak width of 0.7 μm (full width at half maximum).
When the mass spectrometer was operated in the multiple reaction monitoring (MRM) mode, mass transitions with the product ion of m/z 79.1 at the specified parent ion (Table 1) at a collision energy of 50 eV were monitored. The chromatographic results were processed in Xcaliber software (ThermoFinnigan) using 11-point Gaussian smoothing. Linear regression and correlation analysis was performed using GraphPad Prism version 4.00 for Windows (GraphPad Software, San Diego, CA).
Various amount (0.2 pmol to 20 nmol) of the synthetic N-modified PE (C20:4NAPE, γKA-PE or methyl ester γKA-PE) were added to 200 μl PBS. C17:0NAPE (1 nmol) was added as the internal standard. After methylamine treatment, the samples were analyzed by LC/MS/MS using the appropriate MRM transitions. The amount of the synthetic compound was quantified as the ratio of peak height with the C17:0NAPE internal standard and plotted against the actual amount added.
The efficacy of CH3NH2 mediated deacylation was analyzed using synthetic 2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-arachidonoyl (C20:4NAPE) which was expected to produce acyl methylamides and glycerol-phospho- N-C20:4 ethanolamine (Figure 3A). CH3NH2 mediated deacylation of 1-palmitoyl-2-oleoyl-sn-glycero-3-PE (PE) was as used a control. The reaction was monitored by TLC. C20:4NAPE and C34:1PE each migrated as a single spot (Rf 0.64 and 0.49, respectively) prior to CH3NH2 treatment. After 1 h incubation at 53 °C with CH3NH2, the starting NAPE was no longer visible and two new spots appeared with Rf 0.38 and 0.78 (Fig 3B). CH3NH2 treated PE also produced a new spot with Rf 0.78, consistent with this being the expected acyl methylamide products. Negative ion LC/MS analysis of the lower spot (Rf 0.38) primarily showed a peak at m/z 500.3, which is consistent with the expected glycerolphosphate C20:4N-acyl ethanolamine (C20:4GP-NAE) product (Fig 3C). The collision induced dissociation (CID) produced ions with m/z 79, 97, 153, and 171 (Figure 3D), which are consistent with a lipid phosphate compound (Figure 3E).
The time course for CH3NH2 deacylation of C20:4NAPE was further investigated. Plasma was used as a source of additional phospholipids that might compete for hydrolysis with C20:4NAPE. C20:4NAPE was spiked into buffer (PBS) or human plasma and the phospholipids extracted by chloroform/methanol (2:1) and then further isolated by a solid phase exchange (SPE) silica cartridge. After treating the lipids with CH3NH2 at 53 °C for 0-2 h, the amount of C20:4GP-NAE was monitored by LC/MS/MS using the MRM transition m/z 500.to 79.1. The C20:4GP-NAE signal maximized by 1 h, indicating the reaction had reached completion (Figure 4).
To determine if other NAPE species could be assayed in a similar manner, we synthesized C16:0, C17:0 and C18:0 NAPEs from their respective acyl chloride and DPPE. CH3NH2 treatment of C16:0, C17:0, and C18:0NAPEs gave products with ions with m/z 452, 466, and 480, respectively. CID spectrum of these products were very similar to that of C20:4 GP-NAE with the major product ion of m/z 79 (data not shown). C17:0NAPE has been previously used as an internal standard for measurement of endogenous NAPEs based on its similar ionization as endogenous NAPE species and its absence in most biological samples. To test whether deacylation and ionization efficiency was similar for all GP-NAEs, we deacylated and analyzed a solution containing equimolar concentration of each of the four NAPEs. Analysis of the solution by MRM using the m/z 79.1 product ion for each GP-NAE produced peaks with similar peak heights and areas (Figure 5A). The individual GP-NAE eluted separately, with increasing chain length correlating with increasing retention times for the saturated GP-NAEs. Because CH3NH2 hydrolysis could potentially generate isobaric species from some ether linked PEs (i.e. hydrolysis of C18:0 alkylacyl PE would form a lyso-alkylPE (m/z 466) that is isobaric to C17:0 GP-NAE,) we hydrolyzed a commercial preparation of brain PE containing ether linked PEs (alkenylacyl and alkylacyl PE) and analyzed them using our LC/MS/MS system. We found that lyso ether PEs eluted with retention times of 6.7-7.5 minutes, so that they do not interfere with the analysis of GP-NAEs (data not shown).
To determine the linearity and sensitivity of the assay, we analyzed 200 μl PBS solutions containing 0-20 nmol C20:4NAPE and 1 nmol C17:0NAPE as internal standard. The ratio of the resulting peak heights in the LC/MS/MS analysis were used to calculate the measured amount of C20:4NAPE. There was a highly linear correlation between the amount of C20:4NAPE added and the C20:4GP-NAE measured (Figure 5B). The limit of detection was 0.2 pmol in the sample.
After confirming that C17:0NAPE was not present in common biological samples and could therefore be used as an internal standard, we analyzed NAPE in several biological samples. The Arabidopsis thaliana NAPE N-acyl transferase (NAPE-AT) was recently cloned and heterologously expressed in E. coli C41 cells resulting in the substantial levels of C16:0NAPE, C16:1NAPE, and C18:1NAPE. We therefore analyzed levels of NAPE in C41 cells transformed either with empty vector or with the expression vector for NAPE-AT. LC/MS/MS analysis of bacterial pellets from cells expressing NAPE-AT produced MRM chromatographs essentially identical to those produced from the analysis of synthetic NAPEs (Figure 6A). Monitoring of MRM for the predicted precursor ions for C16:1GP-NAE, C18:1GP-NAE, and C18:2GP-NAE also produced peaks with retention times consistent with what would be expected for unsaturated GP-NAEs. The two monounsaturated NAPEs were the most abundant NAPE in the NAPE-AT cells, followed by C16:0NAPE (Figure 6B). In contrast, E. coli C41 transformed with empty vector expressed very little NAPE and this was primarily C16:0NAPE.
Circulating levels of NAPE change very modestly (~60%) in response to stimuli such as fat feeding[12], but even these modest changes may be biological significant. Therefore accurate detection of biologically significant variations in NAPE levels requires method with low intra-assay variability. To determine the intra-assay variability of our analysis method, we measured NAPE levels in five identical aliquots of human plasma. In human plasma, C16:0NAPE and C18:0NAPE were the most abundant NAPEs and were present at nanomolar concentrations (Figure 6C). The coefficient of variation for these two NAPEs were 4.9% and 6.9%, respectively, so that changes in NAPE levels in response to stressors should be readily detectable by our methods.
A major impetus in developing these methodologies was to enable the simultaneous measurement of both NAPE and non-enzymatically N-modified PEs including γKA-PE. We therefore synthesized γKA-PE and performed a similar analysis as with NAPEs. Deacylation by CH3NH2 of a preparation of γKA-PE containing primarily γKA-PE pyrrole adducts generated products ions with m/z 530.3, 546.3, and 562.3 when analyzed by negative ion mass spectrometry (Figure 7A). These ions are consistent with the formation glycerophospho-N-γKA-ethanolamines (GP-γKA-Etn) pyrrole, lactam and hydroxylactam (lactam-OH) species. The CID spectrum of the putative pyrrole product (m/z 530) showed a similar fragmentation pattern as those for GP-NAEs with a most dominant product ion of m/z 79 (Figure 7B). The similarity in fragmentation patterns suggests that most N-modified glycerophosphate ethanolamine could be monitored by use of the m/z 79 product ion (Figure 7C). CID spectrum of the lactam and lactam-OH adducts (m/z 546 and m/z 562, respectively) gave similar results (data not shown). When these samples were analyzed by the same LC/MS/MS system as for NAPEs and using MRM with transition from the appropriate precursor ion and the m/z 79 product ion, the GP-γKA-Etn adducts eluted substantially earlier than C17:0GP-NAE (Figure 7D). This is consistent with the greater polarity of GP-γKA-Etn compared to GP-NAEs. To determine the sensitivity of the assay for measurement of γKA-PE, we analyzed 200 μl PBS solutions containing 0-20 nmol γKA-PE and 1 nmol C17:0NAPE as internal standard. The ratio of the resulting peak heights for all three adducts and C17:0NAPE in the LC/MS/MS analysis were used to calculate the measured amount of total GP-γKA-Etn adduct. There was a highly linear correlation between the amount of γKA-PE added and the GP-γKA-Etn measured (Figure 7E). The limit of detection was 2 pmol in the sample.
One potential advantage of CH3NH2 deacylation compared to standard base hydrolysis is that deacylation products of γKA-PE and esterified γKA-PE are predicted to differ by 13 amu, due to methyl amide formation at the γKA phospholipid ester. Thus the contribution of esterified γKA-PE versus non-esterified γKA-PE could be analyzed simultaneously. While the cyclooxygenase mediated pathway of γKA formation (i.e. levuglandins) occurs exclusively using non-esterified arachidonic acid, free radical mediated formation of γKA can occur while arachidonic acid is still esterified to phospholipids[24]. Therefore the formation of glycerophospho-N- γKA-ethanolamine methylamide (GP-γKA-MA) after CH3NH2 mediated deacylation should be a clear indicator of non-cyclooxygenase mediated γKA formation. To test whether CH3NH2 mediated deacylation results in formation of GP-γKA-MA, we reacted PE with the methyl ester γKA and then subjected the resulting product to CH3NH2 treatment. Mass spectrum from negative ion scan of CH3NH2 treated methyl ester γKA-PE resulted in ions with m/z 543.3, 559.3 and m/z 575.3, consistent with the pyrrole, lactam, and hydroxylactam species of GP-γKA-MA (Fig 8A). As with other GP species, CID generated primarily a product ion with m/z 79.1 (Fig 8B), as would be anticipated from the structure of this compound (Figure 8C). When analyzed by LC/MS/MS, the GP-γKA-MA eluted with similar retention times as GP-γKA-Etn (Figure 8D). When we analyzed solution containing 0-20 nmol methyl ester γKA-PE and 1 nmol C17:0NAPE as internal standard, we found a highly linear correlation between the amount of methyl ester γKA-PE added and the GP-γKA-MA measured (Figure 8E). However, the ionization efficiency of GP-γKA-MA appeared to be significantly less than that of NAPE because the x- and y-intercept deviate significantly from zero. Therefore, the ratio of GP-γKA-MA to C17:0GP-NAE must be corrected by a factor of 8.1 to accurately calculate actual esterified γKA-PE in the sample. The limit of detection for esterified γKA-PE was 2 pmol in the sample.
Oxidative injury to endothelial cells has been postulated to be an important component of cardiovascular disease. High levels of plasma free fatty acids, as occurs in metabolic syndrome and diabetes, induces oxidative stress in endothelial cells [34] and may therefore lead to formation of γKAs. NAPE is present in cultured endothelial cells, suggesting that they have the capacity to synthesize NAPE in response to stress. We therefore measured levels of N-modified PE in HUVEC generated in response to 1 mM arachidonic acid. As a positive control, we also measured the levels of N-modified PEs formed in response to 1 μM γKA. Consistent with our previous reports, treatment with 1 μM γKA resulted in significantly increased levels γKA-PE adducts compared to vehicle treated cells (Figure 9). The γKA-PE adducts were primarily pyrrole adducts. No significant changes in NAPE levels were detected. Treatment with 1 mM arachidonic acid also significantly increased levels of γKA-PE adducts, but in this case the adducts were primarily lactam and hydroxylactam adducts. No esterified γKA-PE was detected. While levels of most NAPEs did not change significantly, levels of C20:4NAPE increased about three-fold.
Our studies show that deacylation with CH3NH2 and subsequent analysis by LC/MS/MS is an accurate, facile, and cost-effective method to measure NAPEs and various species of γKA-PE. The same methods are likely to be adaptable to a broad-range of non-enzymatically N-modified PE that have previously been described including those formed by hydroxyalkenals [18; 19; 35; 36], acrolein [20], malondialdehyde[37; 38], oxysterols[39], and advanced glycation end products [40; 41]. Simultaneous measurement of the various N-modified PEs should facilitate studies to understand the relative rates of formation under various conditions and how these various biologically active lipids control cell fate during stress.
Our results with HUVEC illustrate the value of simultaneous measurement of both enzymatically and non-enzymatically N-modified PEs in understanding these processes. First, they demonstrate that γKA-PE forms endogenously under conditions of oxidative stress. Interestingly, the species of γKA-PE formed under these conditions are primarily lactam and hydroxylactam adduct, while direct addition of γKA produces primarily pyrrole adducts. Second, our results suggest that formation of γKA-PE is by itself insufficient to trigger synthesis of NAPE as we saw no increase in NAPE concentrations in response to γKA treatment. Third, our results show that while oxidative stress induced by high levels of arachidonate lead to formation of both types of N-modified PEs, it substantially favored formation of γKA-PE over NAPE. Because of the cytotoxicity of γKA-PE, such imbalances are likely to result in endothelial dysfunction. While the implications of these results require further investigation beyond the scope of these current studies, they do confirm the potential value of simultaneously measuring multiple N-modified PEs in gaining a greater understanding of the role of these bioactive lipids in the response to stress.
In summary, we have developed an accurate, facile, and relatively inexpensive assay to simultaneously measure both enzymatically and non-enzymatically N-modified PEs. Because of the potential biological importance of these N-modified PEs, the ability to simultaneously measure their levels in biological tissues is a critical tool that will facilitate studies to unravel their contributions to health and disease.
We are grateful for financial support from the National Institutes of Health (OD003137) and Vanderbilt University Department of Pharmacology. We thank Denis Coulon and Lionel Faure for their generous gift of the C41DEST expressing the A. thaliana NAPE N-acyltransferase, and Zhongyi Chen and Xavier Stien for their excellent technical support.
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"Mexico differs from other economies because it has macroeconomic stability and a robust banking system": EPN
President Enrique Peña Nieto inaugurated the
79th National Banking Convention "Mexico and Banking: Protagonists
in the New International Economic Order" in the state of Guerrero.
"Banks and the government are united by a shared commitment. We are
clear that the top priority is stability. Stability is
the basis of sustained growth and sustainable development."
Integration, stability and reforms position Mexico as one of the most
attractive economies in the world for investing and growing in the coming
Financial Reform positively impacts the growth of the economy, supports
the domestic market and improves the everyday life of Mexican families.
Financial reform: Progress 2014-2015
- There is now more, cheaper credit and in better
conditions in Mexico. Credit has grown several times more than the
national economy.
- Domestic
financial savings increased from 55.8% of GDP in 2012 to 69.3% in
2015, an increase of 13.5 percentage points.
- Private
sector financing increased from 25.7% of GDP in 2012 to 30.9% in
2015, an increase of 5.2 percentage points.
- From December 2014 to December 2015, credit
for companies grew 15.6%; with credit for micro enterprises increasing by 17.6%.
- Personal
loans rose by19.4% over the same period with mortgage loans
increasing by 9%.
- Interest rates are declining, particularly in the case of personal loans, whose rates
have been reduced by up to 8.6 percentage points.
- Credit supply has been accompanied by greater soundness of the banking system. In December 2015, its Capitalization Ratio was 14.96%, similar to the average of the G-20 countries of 15.1%.
- Also in December 2015, the Default
Rate of Commercial Banks was just 2.6%, down from 3.4% in January 2014. This translates into a
well capitalized bank with a healthy credit portfolio level.
"Today, financial reform, in addition to
transforming the financial system itself, is contributing to the transformation
of other areas of national life."
La legalidad, veracidad y la calidad de la información es estricta responsabilidad de la dependencia, entidad o empresa productiva del Estado que la proporcionó en virtud de sus atribuciones y/o facultades normativas.

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Can You Not Raw Cut Hoodie
Stop right there and think about what you've done. This terry knit hoodie features the screen print "Can You Not?" printed done the left sleeve. Complete with a raw cut hemline.
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- Model wears size Small
- Imported


text: hugo vanwoerkom <email@example.com> writes: > There was a post on this list a while ago on g++-3.3. I find that if I > use *that* on rolling Qt, things fall apart. I now use 3.2 for > everything. There was a new g++-3.3 last week in testing. I haven't seen any problems with that one (although, haven't really tested much) -- John L. Fjellstad web: http://www.fjellstad.org/ Quis custodiet ipsos custodes


text:
Financing: $105,000.00 Down and
Reason for Selling:Selling would like to retire from the business.
Well established downtown sandwich shop for over 20 years that help built up a diversified and loyal customer base. If a company has it's physical location downtown then it's employees have more than likely eaten at this establishment. It only uses the freshest of fruits, vegetables, meats, cheeses, breads, and pastas for a very unique menu offering. This cafe offers a selection of choices that no other restaurant in town offers. The seller is very motivated to sell this turn-key operation to a qualified buyer. Seller assistance is available for a smooth purchase transition. Please call 1-877-735-5224 for further information. Attention Business Owners: We are always in search of quality businesses to list, so if you are thinking of selling your business or would like to acquire another business, please email us at email@example.com or call us at 1-877-735-5224 to discover the difference that is Vested Business Brokers.
Disclaimer: The information in these listings have been provided by the Seller and Vested Business Brokers, Ltd. has not independently verified this information and has no responsibility for its accuracy or completeness. Vested recommends that you consult with an accountant, attorney and other professionals to represent and assist you in any transaction. Vested's associate brokers will arrange a meeting between you, your representatives and the Seller, but is not authorized to make any representations or warranties. You agree to hold Vested and its associated brokers harmless of any misrepresentations made by seller.
1(877) 735-5224 | 50 Karl Ave Smithtown, NY 11787 | vestedbb.com


text:
Table of Content
JCECE 2017 – The JCECE (Jharkhand Common Entrance Competitive Exam) is a state level examination managed by Jharkhand Combined Entrance Competitive Examination Board. It is organised to screen candidates for admissions in the first year of degree level professional courses in the field of agriculture, forestry and medical (BHMS). For admission into BE/B.Tech courses, the JCECE Board will be organising JEECE 2017 examination. Through this article, students can check detailed information regarding JCECE 2017
Candidate's score and the merit would be displayed in the result. The counselling of JCECE 2017 would start from 2nd week of June 2017.
JCECE 2017 Exam Dates
All the important dates of JCECE 2017 are as below:
|Online application form Availability
|3rd April 2017
|Last date to submit the online application form
|30th April 2017
|Admit Card release
|1 or 2 weeks before exam
|Exam Date
|14th May 2017
|Result Declaration
|29th May 2017
|1st Counselling begins
|2nd week of June 2017
|2nd Counselling begins
|1st week of July 2017
JCECE 2017 Eligibility Criteria
I. Residential Criteria:
- Candidates need to be a citizen of India and local or permanent resident of Jharkhand.
- They are required to submit a local or permanent resident certificate in the proper format at the time of counselling.
- It is necessary that the certificate have to be issued by the competent authority or else the same would not be accepted.
II. Educational Criteria:
Engineering courses
- Those candidates who have cleared 12th class examination with Physics and Mathematics as the compulsory subjects are eligible to apply for JCECE 2017.
- It is important to note that those belonging to reserved category need to have secured a minimum of 40% marks while the general category needs to have gained a minimum of 45% marks in the subjects taken together.
III. Age Limit:
The age limit to apply for Jharkhand CET 2017 varies for different courses:
- For engineering courses, there would be no age limit to apply.
IV. Physical Criteria:
- Medical checkup of all the individuals, for the entire course, would be done by the Board and only you fit you would be termed eligible for the admissions.
JCECE 2017 Application Form
- Candidates can apply for JCECE 2017 either online, through ICR Application Form or by purchasing OMR (Optical mark recognition) Application form from Post Office.
- Applicants can apply for JCECE 2017 exam online by visiting the official website and clicking on the apply online option.
- They need to fill the application form by providing the required information and making a payment of INR 550 ( INR 275 for Schedule Caste/Schedule Tribe) for Physics, Chemistry and Mathematics & Physics, Chemistry and Biology and INR 600 (INR 325 for Schedule Tribe/Schedule Caste) for Physics, Chemistry, Mathematics and Biology.
- The payment can be made either online via debit card/credit card or through e-challan.
- The last date of submission of online application form is May 2017.
The step-wise application process is explained below-
Step-1 Registration-
- They need to visit the official website.
- Then open the Online Application form link.
- Read the instructions carefully and fill the application form.
- Finally, you would get a registration number along with password on your mobile phone and E-mail Id.
- After Registration, you need to click on login button.
- Candidates need to enter the sent registration number and password and submit.
Step-2 Uploading the Signature, Photograph and Left Hand's Thumb Impression-
- They need to upload your scanned copy of Latest and identical passport size photograph and signature (Use JPG format only) along with Left Hand's Thumb Impression.
Step-3 Fee Payment-
- After they complete their 3rd step the next step is payment of the fee.
Candidates can pay your application fee through following a mode of payment:
- Online- Using a Debit card or Credit card.
- Offline- Download the format of E-challan from the official website and pay the application fee from any Bank after depositing the fee, wait for 2 hours for reconcile than after that again login to the official website for completing the steps of the Application form.
JCECE 2017 Admit Card
- The JCECE 2017 admit card have been announced.
- It is available in the online mode from 8th June 2017.
- To download the admit card of JCECE, you can access the link given and download the hall ticket.
- Submission of credentials such as Security Code, Registration Number and Password would allow you to download the admit card.
JCECE 2017 Exam Pattern
Exam Mode–
- The JCECE 2017 would be held offline where candidates have to fill their answers by darkening the rings against their answer in the given OMR answer sheets.
Exam Structure –
- The questions would only be asked in English language and would be of objective type only.
- The JCECE constitutes of 3 sections, namely, Chemistry, Physics and Mathematics and each section has 50 questions to its credit.
Marks Scheme –
- They would be given 1 mark for each question attempted correctly while ¼ mark would be subtracted for every incorrect answer.
- However, if any question is marked more than one time then it would not be considered for evaluation and if the question is left then it would not be assessed.
JCECE 2017 Result
- The result of JCECE 2017 has been declared online.
- Students can check it from the link above.
- To know the score and the merit, you would have to enter the JCECE 2017 roll number in the given space.
- It must be noted that the announced result cannot be challenged and on the basis of the results seat would be allocated in counselling.
JCECE 2017 Counselling
- The JCECE 2017 counselling would start from the 2nd week of June 2017 and only the successful individuals of JCECE written exam would be called for the same and such individuals need to pay the JCECE 2017 counselling fee.
- The fee submitted by the General and Backward Class categories would be Rs. 300 while the reserved categories need to remit Rs. 250.
- The whole process of counselling would be carried out using Computerized Distributed Parallel procedure.
- The allocation of the seats would be done to you through the different rounds of counselling and once you accepts the seat, he or she is supposed to pay Rs. 1000, as seat acceptance fee through Demand Draft, drawn in the name of "Controller of Examination, JCECEB" which is payable at Ranchi.
The list of the necessary documents that they have to carry at the time of counselling is as follows:
- JCECE 2017 Admit Card or the F.I.R copy (in the case of loss of admit card).
- 1 postcard and 6 passport size photographs.
- The Discharge Certificate (if applicable) I Pension Book (only applicable to those who wish to claim seat under SMQ Quota).
- Class X and XII mark sheet and admit card along with Passing Certificate.
- The Dependency certificate issued by the competent Army Officer.
- Caste certificate, Counselling letter & Income Certificate issued by the competent authority.


text:
A Bridge Too Far: The United Kingdom and the Transatlantic Relationship
For the past fifty years, British foreign policy has attempted to act as a 'bridge' between the continental European governments and US administrators. The end of the Cold War did not change this stance. First by John Major and more significantly by Tony Blair, British Prime Ministers continued to declare Britain's intent to remain 'at the heart of Europe' while also maintaining its 'special relationship' with the US. The period from September 11th 2001 to the invasion of Iraq, however, has severely shaken this concept as the British government has given its strong support to American policy. The argument of this chapter is that Prime Minister Blair's firm support came more from his personal conviction that Saddam Hussein's regime was a threat to global security than from his commitment to transatlantic cooperation under all circumstances. His support also resulted from the British preference for seeking influence within Washington through offering public support while moderating the direction of American policy through private criticism. Blair's double commitment to Europe and America, however, has created a diplomatic dilemma by deepening the level of distrust among its European partners about Britain's real intentions in the EU while also leaving its foreign policy success dependent on Washington's willingness to work with its NATO partners.
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|Date of creation:
|15 Oct 2004
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text:
|09 Apr 2014
Windows 7 Pro 64 bit
Cannot download via IE or Firefox
I have a gateway netbook that I freshly installed Windows 7 Starter. When I try to download say malwarebytes or CCleaner in IE I get
"the file was blocked because it does not have a valid digital signature"
I tried this--->the file was blocked because it does not have a valid digital - Microsoft Community
Did not fix it. I then installed a fresh copy of 7 Home Premium and the same result.
Firefox also cannot download files. I was able to get Firefox installed via a usb thumb drive.
When downloading malwarebytes via Firefox I get:
"the source file corrupted"
So I'm stumped.
|My System Specs
|09 Apr 2014
Win-7-Pro64bit 7-H-Prem-64bit
Hi and welcome to SevenForums,
Please do more to add to your system spec's page,
Post which Security exists on the machine as well,
Set clock with internet time also male sure daylight savings box is checked,
Was this fresh install from a manufactures restore partition ?
Does sound like it,
You can try,
Clean boot,
And or Safe mode with networking,
Shut down your machine, Unplug-Hold the power button down for 30/45 seconds (Power Drain)
Power up and Tap the F8 key continuously until you see a black page with white text,
Use the down arrow key to toggle to safe mode with networking/ hit the enter key.
Login as usual
Other advanced methods,
|My System Specs
|Thread Tools
|Similar help and support threads
Two Different Firefox Download Windows
I am using Version 32.0.3. Reference the attached image. The window on the left I can activate via the down arrow on the browser's toolbar. The window on the right appears when I clik on a temporary 'download complete' message display that appears near the sys tray once a download finishes. I would...
|Browsers & Mail
Download Firefox 6 Final
Source A Guy
|Browsers & Mail
Download Firefox 3.0.9 and Firefox 3.0.19.
Source - Download Firefox 3.0.9 and Firefox 3.0.19 - Available right here - Softpedia
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Firefox 3.6 RC2 for download
Build 1 is on the ftp site. Here's the link to the US English 32 bit Windows version: Index of /pub/mozilla.org/firefox/nightly/3.6rc2-candidates/build1/win32/en-US
|Browsers & Mail
Firefox 3.6 RC1 Available for Download
The first Release Candidate Build of Firefox 3.6, codenamed Namoroka, is just around the corner, literally. If all goes according to plans, Mozilla will make available for download the fully-fledged Firefox 3.6 RC 1 tomorrow, January 8th, 2010. On a delivery meeting on January 6th, the developers...
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text:
Monday, November 26, 2007
Yes I Am Complaining
Now I'm angry. Now I'm really angry. (What I'm hearing in my head is the sound of an ineffectual comic anger, so don't take the anger too seriously.)
Some posts ago (like here) I wrote a very minor post on the LNR and the policy of requiring everyone who makes money to buy advertising before getting anything published. I questioned the policy, and mentioned that I thought it made more enemies than friends.
Now I'm angry.
I wrote, and Bethany's publications person sent, a press release on "A Christmas Carol," our new production for the Christmas season. There are lots of important things to say about the production, not the least of which is that this is the largest cast we've had on the stage in many moons. I've got folks from McPherson calling for reservations. We're bringing business to town and enhancing the theatre program at Bethany.
So what's the LNR's response - you have to buy an ad because you're selling tickets. Not only that - if we just meet the technical requirements that LNR has set - say by buying a classified ad - we get a minor two line announcement in News Briefs.
In order to get the LNR to publish what we wrote for them (i.e., what they didn't bother to report on), we have to buy a display ad. The smallest display ad is $64.
This is extortion! It is legal, I suppose, but it is a clear violation of journalistic ethics. The more you pay, the more coverage you get, and John Marshall doesn't have to actually hire anyone to report the news, it's all done for him by people to pay to play.
Good Grief! This is shoddy on so many levels.
Dan Carr took umbrage at an earlier post in which I pointed out the advantages of online reporting versus what the LNR does. I hope he reads this and writes a defense of a policy that can't be defended.
A Christmas Carol, by the way, is December 7 & 8, 7:30 pm, in the Burnett Center.
The young man at the top of this post plays Jacob Marley. It's going to be an unusual production. The Lindsborg Youth Choir will perform between the staves. Ya'll come.
For more details call the Bethany Theatre Hotline - 227-3311, ext. 7910.
3 comments:
- izu said...
Question: is the performance sold out, or expected to be sold out?
- November 26, 2007 at 5:29 PM
- Kalle Lilla said...
Not sold out, but wouldn't it be nice! Tickets at the door. We'll get everyone in!
- November 26, 2007 at 10:43 PM
- Julie-Ann said...
I so agree with you. I have talked with quite a few others about this just in conversation. I have yet to talk to anyone who thinks what the LNR is doing is honourable. It is a shame. A newspaper prints the news. Period. And in a small town we should all support each other for the good of the town. How stupid not to. Just a sad commentary on what is going on.
- November 29, 2007 at 12:11 AM
Subscribe to: Post Comments (Atom)


text:
Frequently Asked Questions
Helping patients feel at ease about the many aspects of Home Infusion treatment is important. We hope that providing answers to some of these questions will help.
Home Delivery of Medication Supplies
Q: How do I store my medication?
A: Please check the medication's label and contact us if you have any questions. Be careful! Most medications should not be stored in the freezer.
Q: When will my medications be delivered?
A: A patient care coordinator will schedule each delivery with the patient. Generally, medications are delivered to the patient's home a few days prior to the date of the infusion. In some cases, home infusion medications can be delivered on the same day when you are discharged from the hospital.
Q: What happens if my shipment of medication is damaged when it arrives at my home?
A: Please contact us right away so that we can ensure that you have everything that you need for your upcoming infusion.
Q: What happens if I accidentally break a bottle of my medication?
A: Please contact us right away so that we can ensure that you have everything that you need for your upcoming infusion.
Q: What do I do with extras that are not used during the infusion?
A: This depends on whether the extras are supplies or medications. Many times, extras are kept for future infusions. Please contact us with your specific questions.
Q: What if I have questions about the contents of my medication shipment?
A: Please compare the contents of your shipment to the contents listed on your delivery ticket. If you see a discrepancy, please contact us right away so that we can ensure that you have everything that you need for your upcoming infusion.
Q: Can I request special delivery instructions?
A: We will give your special delivery instructions to our shipping partners. You do not have to be there or sign for the deliveries in most circumstances.
Q: How long is the medication good for once it arrives at my home?
A: Every box of medication has an expiration date. Your medication will be used before the medication's expiration date. You will be contacted in the event that your medication needs to be used prior to an upcoming expiration date.
Q: What if my contact information changes?
A: Please contact us right away; we want to make sure that there is no delay in your prescribed therapy.
Q: Should I be worried if my medication has been sitting outside, on my doorstep, during hot or cold weather?
A: All medications are shipped appropriately to account for extreme hot or cold weather. If you have concerns about the condition of your medication, please contact us.
Home Infusion
Q: Can a relative do my nursing?
A: Usually not, but contact BriovaRx Infusion Services because many times the answer is dependent on insurance requirements.
Q: Why was I prescribed Home Infusion Therapy?
A: Home Infusion Therapy was prescribed by your doctor. Often times, Home Infusion Therapy is more cost effective than receiving the same therapy in a hospital setting.
Q: How does Home Infusion Therapy work?
A: The first step involves your doctor prescribing Home Infusion Therapy. From there, the BriovaRx Infusion Services team will walk you through the enrollment and benefits verification process. A BriovaRx Infusion Services pharmacist will then ship your medication to your home. In the final step, a licensed BriovaRx Infusion Services nurse will be scheduled to infuse your medication in the comfort of your own home.
Q: What is Home Infusion Therapy?
A: Home Infusion Therapy means that a patient receives nursing services and intravenous (through a vein, usually in the patient's arm) medications at home. Many of the medications and treatments available in the hospital setting are able to be delivered in the comfort of your own home.
Insurance Coverage
Q: Will Medicare cover my infusion?
A: In many cases yes, please contact us for details.
Q: Can you help me understand Insurance or Medicare coverage for home infusions?
A: Yes, we have insurance and Medicare experts who can help you evaluate your coverage options.
Q: What if my insurance changes?
A: Please contact us as soon as possible to avoid interruptions in therapy or unanticipated changes in cost.
Q: Will my insurance cover my infusion?
A: BriovaRx Infusion Services works with you and your insurance to ensure the best possible coverage. You will be given your options before you authorize us to provide you with therapy.
Q: What if I can't afford my infusion?
A: Please call us if you have financial concerns. You may qualify for other assistance programs.
Scheduling Home Infusion Therapy
Q: Can my nurse infuse my medications over the weekend?
A: Generally the answer is yes. We do our best to accommodate your schedule; however the timing of your infusion may be based on the availability of our local nursing staff.
Q: Can I have the same nurse at each infusion?
A: BriovaRx Infusion Services makes every effort to schedule you the same nurse at each infusion.
Q: What happens if I get sick before my scheduled infusion?
A: Please contact your doctor or BriovaRx Infusion Services clinical coordinator so we can assess whether your infusion can be performed as scheduled. If you are feeling sick and this is an emergency, please call 911.
Q: What if I have an unexpected schedule change or need to reschedule an infusion?
A: Please contact your BriovaRx Infusion Services nurse or clinical coordinator to reschedule.
What to Expect
Q: Will I be able to move around my house during the infusion?
A: Your mobility may be limited, but a large number of regular activities are possible. Please discuss your options with your nurse.
Q: What do I need to do before my infusion?
A: It is recommended that you drink plenty of water the day before, day of and after your infusion.
Q: Where can my infusion be performed?
A: Your infusion can be performed wherever you are most comfortable, for example, your favorite chair, bed, sofa, etc.
Q: How long will the infusion take?
A: The infusion time will vary based on the therapy as well as the amount of medication prescribed. Some infusions can take an hour, and others can be as long as 6-8 hours.
Q: Why am I not scheduled for another dose?
A: Some doctors prescribe one or more doses then wait to see the patient or see test results prior to continuing therapy. Ask your doctor if you have questions related to your therapy schedule.
Q: How long before I start feeling better?
A: Some infusion therapies have immediate benefits, and some may take longer, in some cases even months. This can vary depending on your condition and the amount of medication prescribed. Contact your doctor to get a better understanding of what to expect.
Q: What happens if I have a reaction or side effect to my infusion?
A: Your BriovaRx Infusion Services nurse will tell you about common side effects. If you have any concerns after your infusion and your nurse is not present, please contact your nurse, clinical coordinator or doctor. For any unexpected reactions contact your doctor. If this is an emergency, please call 911.
Q: What if I have a general problem or concern?
A: Call us! We will do whatever we need to do to effectively answer your questions and address your concerns.


text:
Blue Sapphire Puffed Heart Shape Pendant in 18k Yellow Gold
About This pendant :
Polished sweetheart 18k yellow gold heart shape pendant with six (1.6mm each) sparkling round burnish set Blue Sapphire gemstones. The perfect gift for any occasion. Presented on a beautiful cable weave chain. Blue Sapphire is the traditional birthstone for September. Sapphire is from the Corundum mineral and can come in a variety of colors but is best known for its deep blue hue. *Semi-precious and precious stones are enhanced as part of their normal processing. Gemstone carat weight is approximate. DiamondWave offers the highest quality diamonds and gemstones at the lowest possible prices. Every stone is hand-picked to ensure exceptional quality and craftsmanship. Settings are Made in the USA.
- 100% Satisfaction Guarantee
- Free Insured Shipping in USA
- Insured International Shipping
- 45 Day No Questions Asked Money Back Guarantee
- Comes in a Beautiful Jewelry Box
- Retail Replacement Appraisal Provided with all diamond products.
Must Know
Stunning Blue Sapphire is the traditional birthstone for September. While Sapphire and Ruby are both corundum, they are distinguished by color. All red corundum is Ruby. Everything else is Sapphire. Sapphires possess the deepest blue color that comes in so many different shades and tones, such as yellow, pink, orange and purple. The most noted for the color blue, "cornflower blue" in particular. Sapphires have long been a favorite among priests and kings, who considered them symbolic of wisdom and purity. The sapphire is a 9 on Mohs scale of gemstone hardness; Sapphires are second only to diamonds in hardness. Sapphires are only found in a handful of places throughout the world, such as India, Burma, Ceylon, Thailand, Vietnam, Australia, Brazil and Africa. A Sapphire's value depends of the size, color and transparency of the stone.
Setting Information
|Total Number of Stones
|18k Yellow Gold
|Length (mm)
|Width mm
|Chain Type
|Cable Weave
|Chain Length
|Clasp Type
|Lobster clasp
Gemstones 1
|Number of Gemstones
|Stone Type
|Blue Sapphire
|Stone Shape
|Prong Metal
|18k Yellow Gold
|Eye Clean
|Medium Blue
|Stone Size (mm)
|Setting Type
Shipping and Insurance
Expected Delivery
This jewelry requires an Based on Product 5-8 business days to prepare prior to shipping.
This item ships fully insured via Free FedEx Ground® Shipping within the continental U.S. You will
receive a notice when your order ships with a tracking number.
An adult signature is required for delivery.
Can't wait? We've got you covered!
FedEx 2nd Day® Shipping: Available for $15.00 at checkout.
FedEx Priority Overnight® Shipping: Available for $25.00 at checkout.
Our Promise
We offer a 100% satisfaction guarantee on all our jewelry. You have 45 days from date of shipment, to inspect the jewelry and make your final decision. If for any reason you decide not to keep the jewelry, DiamondWave will accept it back in its original condition, for a refund or an exchange. It's that simple.
View more information about our guarantee
Why DiamondWave?
45 Day
10 Year
Trade Up
Layaway Plans
100% Satisfaction
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text:
MyEssayWriting.com - Essay Writing Services.
Ready To Order is for vocational students training to become chefs, bartenders and waiters. It is also suitable for professionals who wish to brush up their English. It caters for students from elementary to pre-intermediate level by providing activities for mixed ability groups.
READY TO ORDER consists of :
All of them are already on Ets. Workbook and Teacher's book is on ET thanks to emilio.


text:
Title: Easy
Author: Girl Who Writes
Feedback: If you feel so moved.
Character: Usagi (NQS)
Prompt: Ordinary
Word Count: 371
Rating: PG
Genre: Angst
Summary: It would be so easy, she knew, to hold the crystal tight and replace her worries, her sadness, with easy happiness.
Notes: This is very different to the first part, but I do love dark Crystal Tokyo fics.
Disclaimer: The characters of Sailor Moon belong to Toei, Bandai and Naoko Takeuchi. I make no profit from this fan-based venture.
She only looked once, once when it was too hard to resist. When her people would clamouring for more than she could offer, when she saw her lost, lonely little girl wandering around the palace; when that terrible day drew closer and closer.
It was so easy, to hold the crystal to her and wish for the visions. It was the only way she had ever asked the crystal for anything, wishing for something.
It had been like the crystal had been waiting for her, seeing her faltering, her weakness and offering her something in return.
And in the end, it was nice. It was nothing amazingly special nor difficult. At thirteen, she found a plump black cat being tormented on the street, and took her home, even named her Luna. She grew up with Umino and Naru, laughing and smiling throughout it all – the less-than-stellar academic record, the hours devoted to shopping, the arcade and swooning over boys.
And all her friends passed her by – Mamoru mocked her test result once, and she never saw him again. Ami, Rei, Makoto and Minako never gave her a second glance.
Then there were the little things – a tiny death notice in the newspaper for one Hotaru Tomoe. Haruka and Michiru staring out of separate photographs in the paper. No sign of Setsuna Meioh at all.
She watched herself grow up, and go to art school, fall in love and walk away heart-broken.
Meeting the man she would marry.
Moving out of her childhood home, into a tiny apartment.
Being a bridesmaid at Naru and Umino's wedding.
Having her children, all golden haired cherubs.
Chastising her daughters.
Scolding her son.
A chain of happy days and sad days, birthdays, funerals, graduations, laughter, tears – where she was never anything special, just a normal girl, a normal mother and wife.
It would be so easy, she knew, to hold the crystal tight and replace her worries, her sadness, with easy happiness. Replace one sad-eyed girl with three smiling blonde children. Replace desperate citizens and paperwork with days of playing with her babies and baking misshapen cookies. Simple joys, instead of the grief and frustration of having everybody waiting for her, begging for her...
It would be so very easy.


text:
- Please select a date to see the proper prices!
Description of the Accommodation
Rooms, services Travelling to Ames and looking for accommodation? Take a look at what Holiday Inn Express & Suites AMES Ames has to offer! 75 comfortably furnished rooms are offered by the hotel to guests looking for accommodation in Ames. In case you ever feel like eating in, you may taste delicious local dishes in the restaurant of the hotel. Relaxing wellness services will be available to you at the hotel, an indoor pool will also be waiting for you. You can also bring your laptop for the holiday, for there is wireless Internet connection (WiFi) available at the hotel. An exact and detailed list of equipment in the rooms and of the services provided by Holiday Inn Express & Suites AMES Ames you will find on the information sheet below, including any applicable additional fees.
Payment Depending on the selected date, room and price, you may need to provide credit card guarantee or advance bank card payment to finalize your reservation.
Arrival, opening hours The earliest time for arrival and check-in is 15:00, the latest time for departure and check-out is 11:00. The personnel can communicate with you in English.
Holiday Inn Express & Suites AMES Ames rooms Rooms
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Accommodation services
Free WiFi in shared places
- Indoor pool
Own restaurant
Hairdryer, Fridge, Desk in the room, Microwave oven, Tea/coffee-maker


text:
Pushed to boiling point
As Masterchef: The Professionals begins its fourth series, two of the judges tell why trained cooks can't always cut it under the glare of the TV cameras
Together, Michelin-starred Michel Roux Jr and his cooking protegee Monica Galetti seem to embody the precision and perfectionism required to make it as a top chef.
Steely-eyed yet charming, all those years of enduring eye-wateringly anti-social working hours and the rigours of kitchen life have left them with an uncannily ability to appear calm at all times while spotting every mistake.
These are handy qualities indeed for judging Masterchef: The Professionals, a competition that puts 40 trained chefs through their paces before a winner is crowned.
Last year the title went to Claire Lara and the talented chef has now opened her first restaurant, La Mouette, in the Wirral.
With the fourth series about to start, Galetti is quite clear what she's looking for. "At the start of this particular series, I picked two chefs that I thought would make it all the way through," she says, adding: "And they did."
She explains: "They were both quite young and, under the pressure, still delivered and outshone the others.
"The big difference between the amateurs and the professionals is often something won't work out on the day, but they can go back to their skills and know how to rescue [the dish]."
Fans of the show have come to expect frank talk from Galetti, who began working with Michel Roux Jr more than 10 years ago, and is now senior sous chef at his two Michelin-starred restaurant Le Gavroche in London.
"Maybe I come across harsh," she says of her withering put-downs. "But when they mess up, they shouldn't. I don't think you should put yourself up for this programme and then mess up, at something you should never mess up... like plucking a bird.
"For me, these are supposed to be professional chefs, so they represent us to the general public."
Ever the supportive boss, Roux adds: "Once Monica's in her chef's whites she is a true professional and doesn't want to let anyone through who would cast her in a bad light."
Both Galetti and Roux, the son of Michelin-starred Albert Roux and now a familiar face on foodie television, understand the pressures of competitive cooking and the exacting tasks the contestants have to undertake.
"A lot of the mistakes come from nerves. They might have been calm when they arrived, but it's a good couple of hours before they get to come and see me. They're sitting there with no idea what to expect," says Galetti.
Such anticipation can lead to shaking hands and nervous breakdowns, as chefs struggle to perform highly-skilled tasks, such as dessert decoration, against the clock.
"They psyche themselves up, thinking about what the task might be," says Samoan-born, New Zealand-raised Galetti. "Then they walk in and see the task and their minds go blank, because it's not what they were imagining they were going to get."
In order to give the chefs a fair chance to prove themselves before they face these 'skills tests', this year the first challenge will be an invention test in which contestants are given six ingredients and 50 minutes to makes a show-stopping dish of their choice.
Galetti says it gives her an opportunity to assess their abilities before the knockout round in which they have just 10 minutes to impress her plus Masterchef regular Gregg Wallace.
But despite the show's efforts to encourage creativity, nerves will still get in the way, say Galetti and Roux.
"It's gut-wrenching when you see a professional not manage to do the job he loves," says Roux. "Some do break down in tears, and you really feel for them."
Galetti adds: "It's horrible. You want them to do well, because you can see so many of them can do it.
"They're shaking and you're thinking, 'C'mon, hold it together, you can do this'. And you cannot help them."
Having worked together for years, Galetti knows just how good the chefs will need to be to impress Roux, who judges the final winner. That's why she's so hard on them.
"Many years ago, [Roux] got me to break down in tears. But I probably deserved it... it's the heat of the moment," she says. "It happens to everyone. And you get angry, but you hold it in."
After the first four weeks of knockouts, the remaining chefs will go on to face the brutality of the restaurant critics, cook a busy lunch at a Michelin-starred restaurant and be expected to prepare a three-course menu for 30 of the world's leading Michelin chefs with 40 stars between them, before the final cook-off at the Masterchef kitchen for Roux Jr and Wallace.
"I reckon I can spot a talented chef very quickly - within a day's working with them," says Roux. "And I definitely saw that in Monica.
"It's all the cliches: drive, passion and commitment. When you see that, coupled with great cooking skills and knowledge, then you know they're going to be a success."
Ironically, when the chefs are given free rein to show what they can do, the results can often be uniform.
Roux explains: "Without giving too much away, later in the series we asked for a classic dish and got five Sole Veroniques, a true classic of the Seventies, which when it's cooked well is absolutely beautiful.
"Funnily enough, Gregg had never come across it. He was like, 'Oh my God, sole with grape'. But after a bite he was sold."
Three generations of the Roux family are cooking up a storm in British kitchens...
:: Michel Roux Jr's daughter Emily is soon to graduate from a hotel and catering school in Lyon run by acclaimed chef Paul Bocuse, and her father admits he'd like to work with her in future, although she can be "a bit bossy".
:: Alain Roux (Roux Jr's cousin) is head chef at the Waterside Inn in Bray, Berkshire, which remains the only UK restaurant to retain three Michelin stars for more than 25 years.
:: Michel Roux Sr and Albert Roux (fathers of Alain and Michel Roux Jr), who opened the acclaimed Le Gavroche together in 1967, will appear in a new series called The Roux Legacy in January 2012, along with their sons.
:: Masterchef: The Professionals starts on BBC Two on Monday, November 7
Press Association


text:
From au revoir to arrivederci.
Italy joined France on the sidelines of the World Cup, the first time both previous finalists have been eliminated in the opening round when they qualified for the succeeding tournament.
The four-time champion Italians lost to Slovakia 3-2 at Ellis Park, allowing the Slovaks to advance to the round of 16 from Group F along with Paraguay, which drew 0-0 with New Zealand and won the group.
"I take full responsibility," Italy coach Marcello Lippi said. "If the squad went out with fear in their legs and hearts it means the coach didn't prepare the match well tactically or psychologically."
Italy came into the World Cup with most of the same players who won the title four years ago in Germany under Lippi. But this year, defender Fabio Cannavaro was far from his best and the attack failed to produce goals until the team was facing elimination.
Too late.
"Tonight," midfielder Gennaro Gattuso said, "we touched rock bottom."
That's a place the French reached earlier this week. Like Italy, they finished last in their group and went home in disarray.
Meanwhile, the celebrations for the Slovakian nation had just begun.
"We've shown that we're not here for a holiday," Slovakia forward Erik Jendrisek said.
Robert Vittek scored goals in the 25th and 73rd minutes. The second goal seemed to finally wake Italy's struggling front line and Antonio Di Natale pulled one back for the Italians in the 81st.
Substitute Kamil Kopunek restored the two-goal lead for Slovakia with a smart lob in the 89th, and Fabio Quagliarella added the final goal for Italy in injury time.
"That's my message to all fans at home: enjoy football," said coach Vladimir Weiss: "Let's celebrate ... a present to all our fans at home."
Paraguay won Group F despite a 0-0 draw with New Zealand at Polokwane, which went home with three ties. In its only other World Cup, in 1982, New Zealand lost all three matches.
In Group E, Japan advanced to the next round along with the Netherlands. The Japanese beat Denmark 3-1 in Rustenburg, while the Dutch defeated Cameroon 2-1 in Cape Town as Arjen Robben made his World Cup debut at this year's tournament.
The Netherlands will next face Slovakia on Monday in Durban, while Paraguay takes on Japan on Tuesday in Pretoria.
Paraguay moved into the round of 16 for the fourth time in its history. The Paraguayans also reached the second round at the World Cup in 1986, 1998 and 2002.
"Obviously, the first goal was to advance," Paraguay striker Roque Santa Cruz said. "We had some good moments in the first three games and obviously there are some things that we need to improve."
Paraguay emphasized the strength of South American teams so far. They have won 10 times, drawn three and not lost a game.
For the Kiwis, the departure was much sweeter than for Italy or France.
"We are proud and disappointed at the same time now," New Zealand coach Ricki Herbert said. "We remained unbeaten but are still eliminated. I am proud, and no one takes away from me what we have done here."
Keisuke Honda and Yusuhito Endo scored from free kicks in the first half, and Shinji Okazaki added a late goal for Japan, which advanced to the round of 16 for the second time in history.
Jon Dahl Tomasson scored the lone goal for Denmark, tapping in a rebound after Eiji Kawashima saved his penalty kick.
"I'm glad we won but I am not satisfied," Honda said. "The next game is more important. I want to show the Japanese that nothing is impossible."
The Netherlands finally produced some flair at the tournament in South Africa, and Robben was one of the main contributors after coming on as a 73rd-minute substitute.
After misplaying a long pass, Robben took control of the ball and sent a bending shot off the post. Klaas Jan Huntelaar was there to tap it in and give the Dutch a 2-1 lead in the 83rd.
"Our play was good," Netherlands winger Robin van Persie said. "We can be really pleased with this."
Van Persie scored the first goal in the 36th, while Samuel Eto'o briefly equalized in the 65th by scoring from the penalty spot.


text:
We've just announced the forthcoming deprecation of a number of our Cards formats: the Photo, Gallery and Product cards will cease to display and will be replaced with other Card types from July 3, 2015.
See the announcement post for full details of the plans, and feel free to ask questions here in the Cards category. We're here to help!
July 6, 2015 Still no change about Cards formats...Do you have news about that ?
If we're switching out Twitter product card markup, could we instead use summary card with large image, or can it only be summary card?
summry_large_image was specified, but not the image is displayed in a large size . appearance of summry card . Why not?
You can choose whichever one is most appropriate for your use case.
I'm trying to use a summry_large_image card, on the validation page it looks great, but when I tweet it, it crops the image.Are there any known issues with using it?
There's a related thread here - currently the validator doesn't show an exact preview, and the cards formats are being tweaked - I'm going to close out this announcement thread, please open new ones for new issues.


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Contact Us
The Out-of-Sync Child Has Fun
Carol Stock Kranowitz Books
This book, additionally titled "Activities for Kids with Sensory Integration Dysfunction," begins with a chapter describing Sensory Integration Dysfunction and follows up with chapters on activities for the specific sensory systems (it addresses touch, balance and movement, body position, seeing, hearing and smell) and activities for sensory-related skills (oral-motor skills, motor planning, fine motor skills, and bilateral coordination and crossing the midline).
The Out-Of-Sync Child, The: Recognizing and Coping with Sensory Integration Dysfunction
Carol Kranowitz Books
If your child is difficult, picky, oversensitive, clumsy, unpredictable, inattentive or a combination of these, he or she may have Sensory Integration Disorder, a frequently misdiagnosed condition that can lead to abnormal activity levels, problems with motor coordination, or inappropriate sensitivity to sensation and movement. "The Out-of-Sync Child" explains how to recognize and treat children with this common disorder.
Raising A Sensory Smart Child: The Definitive Handbook for Helping Your Child with Sensory Integration Issues
Lindsey and Nancy Biel and Peske Books
This handbook has chapters on finding and working with occupational therapists; practical solutions for daily problems; a wide range of developmental issues; advocating for your child at school; special challenges for teenagers; empowering your child in the world; and much more.
Raising Resilient Rascals 2008: Disk 1 (DVD)
This disk includes the following presentations from the 2008 conference: "The Nature and Nurture of the Brain" with Julian Davies; "The Dichotomy of Foster Care Adoption" with Paulette Caswell; and "Raising Resilient Rascals in a Raging Rambunctious World" – on sensory processing – with Stephen T. Glass.
Seeing Clearly: A Synergistic Blend of Behavioral Optometry and Occupational Therapy Focused on Enhancing Visual Perception
Lois Hickman Books
This booklet provides an overview of the development of vision, with a checklist of warning signs of vision problems – based on the studies of behavioral optometry; a discussion of the importance of integrating all the senses equally in the development of optimal visual skills – rooted in the field of occupational therapy; and practical, playful activities designed to improve visual skills in both adults and children.
Answers to Questions Teachers Ask About Sensory Integration
Carol Stock, Stacey Kranowitz, Szklut Books
This handbook/guidebook, from the author of The Out-of-Sync Child, is full of forms, checklists, usable descriptions and definitions, monitoring charts, diagnostic devices, to-do lists, and other practical tools to help parents and teachers monitor and understand their children's functioning.
Brain Gym: Simple Activities for Whole Brain Learning
Paul E.and Gail E Dennison Books
This book, in first-person story format, includes the 26 Brain Gym movements and simple instructions for how to perform them correctly. Included are specific routines of movement for specific skills such as reading comprehension and hand-eye coordination. If you know that you or your child has the ability or the information but can't seem to call upon it at will, you might benefit from having a copy of Brain Gym.
Fragile X Syndrome: Medical and Educational Approaches Toward Intervention (Audiotape)
Belle Curve Records Audiotapes
This 90-minute audio cassette contains a discussion of medical and educational approaches toward the treatment of individuals with Fragile X Syndrome. This discussion includes a framework for understanding sensory integration theory as it applies to the child's functional roles as family member, student and member of the community.
How Does Your Engine Run?: A Leader's Guide to The Alert Program for Self-Regulationr:
Mary Sue Williams Books
This "Leader's Guide" is intended for professionals who use sensory integration techniques. Those who are unfamiliar with this theory can implement the program with consultation from an occupational therapist or other professional trained in sensory integration. All will find the introductory booklet (See next entry.) useful, whether or not they are familiar with sensory integration theory.
Little Heroes Sensory Integration and Behavior Problems in the Young Child
Cheryl, Linda, Lindsay, Alissa Pratt, Schwartz, Smith Children's Books
This booklet is designed to help parents explain sensory integration and behavioral problems to their children. It is about a boy named Jeff who experiences many different sensory and behavior problems during preschool. It can also be used to help siblings in the family understand their own feeling about a new child in the home. The accompanying Parents' Guide provides a much fuller explanation of sensory integration and behavioral problems.
Love is a Start
Donna Shilts Books
Telling of her own courageous experience with two adoptive sons, Shilts demonstrates the incredible progress that is possible for children with neurological impairments.
Making Sense of Sensory Integration (Audiotape)
This tape and accompanying 37 page booklet with reproducible checklists and resource material tell parents and caregivers what SI is, how problems with SI affect children, how a diagnosis is made and what the appropriate treatment might be, and how SI difficulties might affect the child and family in their daily lives – at home, at school, and in the community.
Misunderstood Child, The: Understanding Sensory Integration (Audiotape)
Lynnette Burke Audiotapes
This tape of an ORPARC sponsored training at PSU explores the role Sensory Integration (defined as the ability to organize and process sensory input and to use that information to respond to the demands of our daily lives) plays in the lives of some children neurologically affected by pre-natal exposure to drugs or alcohol, or early exposure to violence, terror, or severe neglect. In other words, many of the children the state places into foster and adoptive homes! This video highlights the power of understanding Sensory Integration and its relationship to children's behavior.
Sensabilities: Understanding Sensory Integration
Maryann Colby Trott Non-Return Items
This booklet, written in easy-to-understand language for parents of children who have problems integrating sensory input, opens the door to understanding and treating the disorder. It introduces some of the difficulties the child may encounter, examines specific types of problems related to the disorder, and offers ways to help remediate those problems. Suggested techniques are straightforward and nurturing, respecting the child's dignity. They are easy to implement and fun too.
Sensory Integration and the Child
A. Jean Ayres Books
The chapters in this book are divided into three sections, "Sensory Integration and the Brain," which explains how systems normally function; "Sensory Integrative Dysfunction," which describes dysfunctional systems; and "What Can Be Done About the Problem."
Sensory Processing for Parents: From Roots to Wings (DVD)
This DVD presents information about sensory processing disorders, addressing difficulties in motor coordination/planning, selfregulation and sensory defensiveness. Children are seen doing the kinds of sensory activities that help them to be successful in daily life and to feel good about themselves. Parents explain the impact these difficulties have had on the lives of their children. A major focus of this video is on strategies for addressing these sensory concerns.
Sensory Integration Sensory Processing for Parents: From Roots to Wings (VHS)
This video presents information about sensory processing disorders, addressing difficulties in motor coordination/planning, self-regulation and sensory defensiveness. Children are seen doing the kinds of sensory activities that help them to be successful in daily life and to feel good about themselves. Parents explain the impact these difficulties have had on the lives of their children. A major focus of this video is on strategies for addressing these sensory concerns.
Songames For Sensory Integration (Audiotape)
Belle Curve Records Audiotapes
This tape and accompanying 37 page booklet offers 25 therapist-created "Songames" to enhance oral motor skills, and expressive language play, while decreasing tactile, auditory, visual and sensory defensiveness in kids from age 3 to 8.
Teachers Ask About Sensory Integration (Audiotape)
Belle Curve Records Audiotapes
This tape and accompanying 42-page booklet with reproducible checklists is for you to share with any teacher willing to make an attempt to understand why problems in sensory integration affect learning, to learn useful strategies for helping these kids engage and focus, and to improve the educational and social performance of kids with SI challenges.
Too Loud, Too Bright, Too Fast, Too Tight: What to Do If You Are Sensory Defensive in an Overstimulating World
Sharon Heller Books
The author of this book about treating people who have sensory integration difficulties is herself sensory defensive. She shows how the condition, if untreated, can cause secondary effects, and she offers practical treatments based on a recognition that this is a neurological, not a psychological condition.
Family Education


text:
Service Oriented Architecture and Virtualization have emerged as the front running approaches to extending and managing complex, IT infrastructures. Now, convergence between SOA, Grids and Virtualization is a reality. For the first time Management and Technology experts are talking the same language: the language of "Services". Services, that originate from business yet extend to technology. Services, that can be created by aggregating existing resources. It is the services that can be managed seamlessly, the services that enable managers to see ROI on the fly. The list goes on.
SOA is a paradigm shift and JeanMartin is one of the earliest adopters of SOA and Web Services. We help you manage your Service Portfolios using our top-tier Governance Methodology and our vendor neutrality assurance.
Steady Progress, Complete Solutions
Start small, build incrementally, break down silos and manage the Portfolio. Our unique offerings range from a single Service Lifecycle Solution to helping you establish a complete SOA Roadmap.
- Development and Testing web services
- Benchmarking for services against WS standards
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- Assistance in establishing SOA Architecture Blueprint
- Extensions of SOA Architecture to our Utility Network
- Assistance in establishing SOA Governance Models
- Guidance on SOA Tools and Technologies
- Guidance on SOA Strategy and SOA-enabled Organization
- Leadership in conducting SOA Feasibility Studies
- Design and Implementation of Service Networks


text:
If you're now buying a manufactured home financing loan, there are a couple things which you must consider to make sure that you get a loan which suits your needs. You do not need a mortgage that feels like monetary anchor because this Won't allow you to enjoy your new house. This might be due to the fact that home buying can be a stressful endeavour and a lot of people give in their perceived need to be in possession of a house without totally looking at all their choices.
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The very first thing a manufactured home financing lender will need to know just how much equity you are bringing to the table. Equity could be seen in two ways; how much value to you have built up in your current home and just how much washable assets, or cash do you've got available for a down payment. The more equity you've got, the better the conditions of your loan since you can place a bigger down payment on your new home and reduce the sum needed on loan by that amount. This makes for a better interest rate and payments that do not break the bank every month. There's a great number of lenders out there, therefore it's in your best interest to take good advantage of multiple price quotes and duration's. You have many choices when it comes to lenders including national and local banks, mortgage brokers,
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224 San Rafael Circle, Placentia CA, 92870 (Residential)
Sold Price:
3 beds , 2 Full/1 Three-Qtr baths
3,000 sqft
Status: Sold
Last Updated: 11/20/2017 1:19 AM
Description for 224 San Rafael Circle Placentia, CA 92870
Beautiful and spacious Placentia home. Features include over sized rooms throughout. 3 bedrooms and 3 bathrooms. In close proximity to Alta Vista Country Club.
Sold Price:
Sold Date:09/09/2015
2 Full/1 Three-Qtr
3,000 (approx)
Beautiful and spacious Placentia home. Features include over sized rooms throughout. 3 bedrooms and 3 bathrooms. In close proximity to Alta Vista Country Club.
Listing Information
Public Water Service
Sewer at Street
Room Information
Family Room
Interior Features
Central Air
Family Room, Gas Burning
Exterior / Lot Features
3 Garage Spaces, 3 Parking Spaces
No Pool
Gutters, Sidewalks
Driving Directions
Chapman Ave. to Central. Go South to San Juan, Turn Right Go to San Rafael and Turn Left. The house is on the right
Financial Considerations
Listing Price History
Placentia Real Estate
Placentia is located in California. Placentia, California 92870 has a population of 52,495.
The median household income in Placentia, California 92870 is $79,275. The median household income for the surrounding county is $75,998 compared to the national median of $53,482. The median age of people living in Placentia 92870 is 36.8 years.
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text: On Thu, 18 Oct 2001, Michael Ashton wrote: > Hi Tomas, > > On Wed, Oct 17, 2001 at 09:02:19PM +0200, Tomas Pospisek wrote: > > I'm trying to compile stuff from kde-cvs. Since libqt3-dev wants to > > remove libqt-dev I have copied everything out from the deb manually (I > > I can reccommend using the Qt tarball. [...] > This is another reason I like the tarball approach: it keeps the > "alternate" Qt system, in its entirety, under a single directory. [...] > Ivan has so far refused to make Qt3-dev packages that can be > installed in parallel with the Qt2 ones, and while I wish such existed, > I think I understand his reasons for not doing so. [...] I'm doing the thing now in a chrooted environment. That way I can keep up with Ivan - maybe report eventual problems and maybe spare some time on my own when he gets to fix things. I'm compiling now and things look good :-) Thanks !! *t ---------------------------------------------------------------------------- Tomas Pospisek SourcePole - Linux & Open Source Solutions http://sourcepole.ch Elestastrasse 18, 7310 Bad Ragaz, Switzerland Tel: +41 (81) 330 77 11 ----------------------------------------------------------------------------


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The Reckoning Trailer (2015)
"Two worlds, one choice" 11 October 2015 Romance, TV Movie
Katie Mayfield is now the mistress of Mayfield Manor. In her new world she finds herself torn between two worlds and grieves for her plain Amish life. Does Katie choose her new life or the simple heritage she left behind?
Watch the official The Reckoning 2015 trailer in HD below or find more The Reckoning videos on Vidimovie.