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Endoplasmic reticulum (ER) stress has been linked to the pathogenesis of Parkinson's disease (PD). However, the role of microRNAs (miRNAs) in this process involved in PD remains poorly understood. Recent studies indicate that miR-384-5p plays an important role for cell survival in response to different insults, but the role of miR-384-5p in PD-associated neurotoxicity remains unknown. In this study, we investigated the role of miR-384-5p in an in vitro model of PD using dopaminergic SH-SY5Y cells treated with rotenone. We found that miR-384-5p was persistently induced by rotenone in neurons. Also, the inhibition of miR-384-5p significantly suppressed rotenone-induced neurotoxicity, while overexpression of miR-384-5p aggravated rotenone-induced neurotoxicity. Through bioinformatics and dual-luciferase reporter assay, miR-384-5p was found to directly target the 3′-untranslated region of glucose-regulated protein 78 (GRP78), the master regulator of ER stress sensors. Quantitative polymerase chain reaction and Western blotting analysis showed that miR-384-5p negatively regulated the expression of GRP78. Inhibition of miR-384-5p remarkably suppressed rotenone-evoked ER stress, which was evident by a reduction in the phosphorylation of activating transcription factor 4 (ATF4) and inositol-requiring enzyme 1 (IRE1α). The downstream target genes of ER stress including CCAAT/enhancer-binding protein-homologous protein (CHOP) and X box-binding protein-1 (XBP-1) were also decreased by the miR-384-5p inhibitor. In contrast, overexpression of miR-384-5p enhanced ER stress signaling. In addition, knockdown of GRP78 significantly abrogated the inhibitory effect of miR-384-5p inhibitors on cell apoptosis and ER stress signaling. Moreover, we observed a significant increase of miR-384-5p expression in primary neurons induced by rotenone. Taken together, our results suggest that miR-384-5p mediated ER stress by negatively regulating GRP78 and that miR-384-5p inhibition might be a novel and promising approach for the treatment of PD.
- endoplasmic reticulum stress
- Parkinson's disease
- miR-384-5p
parkinson's disease (PD) is one of the most common neurodegenerative diseases worldwide, characterized by the progressive loss of dopaminergic neurons in the substantia nigrapars compacta and a reduction of dopamine production in the striatum (6, 41, 43). The development and progress of the disease mainly depends on age, and approximately 1% of the older population (>60 yr) in industrialized countries are affected by PD (41). An increasing number of studies have suggested that numerous mechanisms, including mitochondrial defects, oxidative stress, dysimmunity, heredity, and cell apoptosis, have been implicated in the pathogenesis of PD (22, 24, 46, 48). However, the precise mechanism underlying the pathogenesis of PD remains poorly understood, hampering the development of efficient treatments for PD. The current therapeutics only temporarily relieve the symptoms, thus improving patients' quality of life to a certain degree. Recently, increasing evidence has suggested that endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of PD, which indicates a potential therapeutic option for PD treatment (50).
The hallmark of PD is the accumulation of misfolded proteins in neurons (19, 36), which could evoke cellular stress in the ER (25, 30, 53). ER stress, also termed the unfolded protein response, contributes to the protection of cells against toxic stimuli or cellular stress-induced accumulation of misfolded proteins (29, 36). However, the prolonged and excessive ER stress induces cell apoptosis (3). Glucose-regulated protein 78 (GRP78), also named binding protein (BiP), plays an important role in the initiation of ER stress. Under normal circumstances, GRP78 binds to three ER stress receptors, including inositol-requiring enzyme 1 (IRE1), activating transcription factor-6 (ATF6), and pancreatic ER kinase-like ER kinase (PERK), which become dissociated from complexes following the accumulation of misfolded proteins, resulting in the activation of IRE1-, ATF6- and PERK-mediated downstream signaling (38). The phosphorylation of PERK activates eukaryotic initiation factor 2α (eIF2α), thus inhibiting protein synthesis (15, 37). Activated eIF2α subsequently activates ATF4, which could induce cell death proapoptotic genes such as CHOP (CCAAT/enhancer-binding protein-homologous protein) (14, 51, 55). The ATF6 pathway is activated by dissociation from GRP78 followed by trafficking to the Golgi to produce cleaved ATF6, which regulates the expression of ER stress target genes such as CHOP and X box-binding protein-1 (XBP-1) (16, 54). The phosphorylation of IRE1α results in IRE1 pathway activation, which is associated with unconventional splicing of XBP-1 mRNA, thereby activating the transcription of ER stress target genes (17, 26, 54). The ER stress signaling is activated to restore the ER function and enhance the folding capacity and degradation of protein aggregates. However, if the homeostasis is not reestablished, the ER stress target genes including CHOP1, XBP-1, and caspase-12 promote cell apoptosis (47). An analysis using post mortem samples from PD patients revealed that phosphorylated PERK and eIF2α were expressed at a higher level in neuromelanin containing dopaminergic neurons in the substantia nigra, implying ER stress was activated in brain tissue (18). Furthermore, ER stress has been found to be involved in cellular models of PD (39, 44). It has been reported that the prolonged ER stress induced by toxic stimuli such as rotenone results in the apoptotic death of neurons (10). In a rotenone rat model of PD, suppression of ER stress provides neuroprotection (49). Therefore, inhibiting the prolonged ER stress-induced cell apoptosis may provide a novel insight into the treatment of PD.
MicroRNAs (miRNAs) are a group of short, noncoding RNAs that negatively regulate gene expression and thus participate in various pathological processes (2). Increasing evidence has suggested that they may be implicated in the pathogenesis of PD (7). However, their molecular mechanism is not fully understood. In recent years, miR-384-5p has been reported to play an important role for cell survival in response to different insults. Ethanol exposure causes expression changes of miR-384-5p in rat brain (20). Spinal cord injury significantly increases the expression of miR-384-5p in the serum (13). Importantly, miR-384-5p has been shown to be an indicator for trimethyltin-induced neurotoxicity (32) and is found to be differentially expressed in dopaminergic neurons following cocaine addiction (42). However, whether miR-384-5p is associated with neurotoxicity in PD remains unknown. In this study, we aimed to investigated the role and the potential underlying mechanism of miR-384-5p in an in vitro model of PD induced by rotenone. Through bioinformatics and expression analysis, we found that miR-384-5p regulated ER stress in dopaminergic SH-SY5Y cells via negatively regulating GRP78 expression, the master regulator of ER stress sensors. Overall, our study for the first time reveals a direct link between miR-384-5p and ER stress in dopaminergic SH-SY5Y cells and suggests that the miR-384-5p–GRP78 axis might serve as a potential molecular target for the prevention of dopaminergic neuron loss in PD.
Cell culture.
Human dopaminergic neuroblastoma SH-SY5Y cells were obtained from the Type Culture Collection of the Chinese Academy of Sciences (Shanghai, China) and were maintained in Dulbecco's modified Eagle's medium–Ham's Nutrient Mixture F-12 (DMEM/F12; Invitrogen, Carlsbad, CA) that was supplemented with 10% fetal calf serum (FCS) plus penicillin and streptomycin (1%). The cells were cultured in humidified atmosphere containing 5% CO2 at 37°C. Human primary neurons were isolated from the postmortem brain tissues provided by Chinese PLA General Hospital. The cells were cultured in Neuronal Medium (ScienCell Research Laboratories, Carlsbad, CA) supplemented with 1% neuronal growth supplement and 1% penicillin and streptomycin at 37°C and 5% CO2. Cells were used at passage 0. The experimental procedure was approved by the Institutional Human Experiment and Ethics Committee of Chinese PLA General Hospital and carried out in accordance with Declaration of Helsinki.
Cell treatment.
Cells were exposed to rotenone (Sigma, St. Louis, MO) at various concentrations (1, 5, 10, 20, and 50 μM) (28) for the indicated times before being harvested for analysis. For miRNA transfection, cells were transfected with miR-384-5p mimics or inhibitors using Lipofectamine 2000 (Invitrogen) at a final concentration of 50 nM for 24 h prior to rotenone (20 μM) exposure. For gene silencing, 50 nM GRP78 siRNA or control siRNA (Santa Cruz Biotechnology, Santa Cruz, CA) was transfected into SH-SY5Y cells in the presence or absence of miR-384-5p inhibitors using Lipofectamine 2000 (Invitrogen). All assays were performed in triplicate.
MTT assay.
Cell growth and viability were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Briefly, cells were seeded into 96-well plates at a density of 1 × 104 cells/well and cultured for 24 h. Then, cells were transfected with miR-384-5p mimics or inhibitors for 24 h followed by exposure to 20 μM rotenone for another 24 h. Thereafter, the old medium was replaced by fresh medium plus 20 μl of MTT solution (0.5 mg/ml) and cultured for a further 4 h. Finally, the formazan dye crystals formed in the cell culture were dissolved with 150 μl of dimethylsulfoxide per well and the optical density (OD) value at 490 nm in the solution was measured by a microplate reader (ThermoElectron, Vantaa, Finland). Results are expressed as the percentage of MTT reduction, assuming the absorbance of control cells to be 100%.
Cell apoptosis assay.
Cell apoptosis was evaluated by Annexin V/propidium iodide (PI) double staining method. Briefly, cells were harvested and digested with 2.5 g/l trypsin. After being washed with phosphate-buffered saline (PBS), cells were centrifuged, collected, and resuspended in 500 μl of PBS. Then, 5 μl of Annexin V-FITC and 5 μl of PI were added and coincubated in the dark for 15 min at room temperature. Finally, apoptotic cells were quantified by fluorescence-activated cell sorting (BD Biosciences, San Jose, CA) and then analyzed by Cell Quest software (BD Biosciences). The data are represented as cell percentage (%).
Caspase-3 activity assay.
Caspase-3 activity was measured using a commercial kit (BioVision, Milpitas, CA). Briefly, cells were lysed in ice-cold cell lysis buffer. The supernatant was collected after centrifugation (10,000 g for 1 min) and the protein concentration was measured. Then, 50 μl of cell lysis buffer containing 100 μg of protein was incubated with 5 μl of 4 mM DEVD-pNA substrate in 50 μl of reaction buffer for 2 h at 37°C. The OD value at 405 nm was determined using microplate reader.
Quantitative PCR analysis.
Total RNA was isolated using miRNeasy Mini Kit (Qiagen, Dusseldorf, Germany), which was used to synthesize cDNA using M-MLV reverse transcriptase (Clontech, Palo Alto, CA) for mRNA analysis, or using the one-step primescript miRNA cDNA synthesis kit (Takara, Dalian, China) for miRNA analysis according to the manufacturer's instructions. The PCR assay was performed using SYBR Green qPCR Master Mix (ThermoFisher, Shanghai, China). The primers used for qPCR were as follows: GRP78 forward, 5′-ggaaagaaggttacccatgc-3′ and reverse, 5′-ggaacaggtccatgttcagc-3′; miR-384-5p forward, 5′-acactccagctgggattcctagaaattg-3′ and reverse, 5′-tggtgtcgtggagtcg-3′; GAPDH forward, 5′-ggagtccactggcgtcttca-3′ and reverse, 5′-tggttcacacccatgacgaa-3′; U6 SnRNA forward, 5′-gcttcggcagcacatatactaaaat-3′, and reverse, 5′-cgcttcacgaatttgcgtgtcat-3′. Relative gene expression was calculated by comparison with the internal reference gene GAPDH or U6 SnRNA using the 2−ΔΔCt method.
Western blot analysis.
Proteins in cell samples were extracted using a protein extraction kit (Applygen Technologies, Beijing, China), and protein concentration was measured with a BCA Protein Assay Kit (Beyotime, Haimen, China) according to the manufacturers' instructions. Equivalent amounts of protein (50 μg) for each sample were run on 12.5% sodium dodecyl sulfate polyacrylamide gel electrophoresis. The proteins were then electrophoretically transferred to a PVDF membrane which was blocked by 2.5% nonfat milk for 1 h at 37°C. The membrane was blotted with anti-GRP78, anti-CHOP, anti-XBP-1, and anti-GAPDH antibodies purchased from Santa Cruz Biotechnology, and anti-ATF4, anti-phospho-ATF4, anti-IRE1α and anti-phospho-IRE1α antibodies purchased from Bioss (Beijing, China); the membrane was then incubated overnight at 4°C, followed by exposure to horseradish peroxidase-conjugated secondary antibodies (1:2,000; Bioss) for 1 h at room temperature. The immune-blot signals were developed using an enhanced chemiluminescence method.
Dual-luciferase reporter assay.
The 3′-untranslated region (UTR) of human GRP78 gene containing seed regions of miR-384-5p (300 bp) were PCR amplified from human cDNA and then cloned into pGL3 dual-luciferase miRNA target expression vector (Promega, Madison, WI). The corresponding mutant constructs were created by mutating the seed regions of the miR-384-5p binding sites by using a site-directed mutagenesis kit (Agilent Technologies, Beijing, China). SH-SY5Y cells were seeded into 24-well plates for 24 h before transfection. For reporter assays, cells were transiently cotransfected with pGL3-3′-UTR of GRP78 [wild type (WT)] or pGL3-mutant 3′-UTR of GRP78 (MT) in the presence of miR-384-5p mimics or inhibitors using Lipofectamine 2000 (Invitrogen). After incubation for 48 h, the relative luciferase activity was analyzed using dual-luciferase system (Promega).
Statistical analysis.
Data are expressed as means ± SD. Statistical analysis was performed by scientific statistic software SPSS (version 11.5; SPSS, Chicago, IL) using one-way analysis of variance followed by Bonferroni post hoc. P < 0.05 was regarded as statistically significant.
The expression of miR-384-5p is significantly induced by rotenone in SH-SY5Y cells.
To investigate whether miR-384-5p played a critical role in rotenone-induced neurotoxicity, we initially detected its expression profile in SH-SY5Y cells treated with different concentrations of rotenone (0, 1, 5, 10, 20, and 50 μM) by the qPCR method. The results showed that miR-384-5p was dose-dependently increased after rotenone treatment (Fig. 1A). Furthermore, its expression was persistently increased post-time challenge (Fig. 1B). The results indicate that miR-384-5p plays an important role in regulating rotenone-induced neurotoxicity.
Downregulation of miR-384-5p inhibits rotenone-induced neurotoxicity.
To explore the precise role of miR-384-5p in regulating rotenone-induced neurotoxicity, we detected the gain or loss of function of miR-384-5p on rotenone-induced neurotoxicity. According to the results of MTT (Fig. 2A), the viability of SH-SY5Y cells was significantly decreased by rotenone (20 μM) treatment relative to the control group. When the cells were pretreated with miR-384-5p inhibitor for 24 h, the cell viability was markedly increased compared with the rotenone-treated group (Fig. 2A). In contrast, cell viability was further decreased by treatment with miR-384-5p mimics (Fig. 2A). The results showed that downregulation of miR-384-5p exhibited a protective effect against rotenone-induced neurotoxicity. To further verify the role of miR-384-5p on rotenone-induced neurotoxicity, we detected their effect on cell apoptosis flow cytometry. The apoptotic cells were markedly increased in rotenone-treated cells compared with the control group, which could be effectively attenuated by miR-384-5p inhibitor or significantly aggravated by miR-384-5p mimics (Fig. 2, B and C). Furthermore, we detected cell apoptosis by measuring the activity of caspase-3. The results showed that rotenone treatment significantly increased the activity of caspase-3, which was decreased by miR-384-5p inhibitor or further increased by miR-384-5p mimics (Fig. 2D). Again, the data suggest that downregulation of miR-384-5p exhibited a protective effect against rotenone-induced neurotoxicity.
miR-384-5p directly targets the 3′-UTR of GRP78.
To explore the underlying mechanism of miR-384-5p, we sought to investigate its target gene. Using bioinformatics analysis, we found that GRP78 was one of the putative target genes of miR-384-5p (Fig. 3A). To confirm this relationship, we performed a dual-luciferase reporter assay. The results showed that miR-384-5p mimics significantly reduced the luciferase activity in pGL3-3′-UTR of GRP78 (WT) transfected cells, which had no effect on pGL3-mutated 3′-UTR of GRP78 (MT) transfected group (Fig. 3B). In contrast, the miR-384-5p inhibitor markedly increased luciferase activity in WT-transfected cells (Fig. 3B). Furthermore, we detected the effect of rotenone treatment on the luciferase activity of WT- or MT-transfected cells. The results showed that rotenone treatment significantly decreased the luciferase activity in WT-transfected cells, whereas it showed no obvious effect on MT-transfected cells (Fig. 3C). Taken together, these results indicate that miR-384-5p directly targets the 3′-UTR of GRP78.
miR-384-5p regulates the expression of GRP78 in SH-SY5Y cells.
Owing to the targeting relationship between miR-384-5p and the 3′-UTR of GRP78, the expression of GRP78 could be regulated by miR-384-5p. To test the hypothesis, we detected the expression of GRP78 upon treatment with miR-384-5p inhibitors or mimics. The qPCR results demonstrated that the mRNA expression level of GRP78 was obviously increased by treatment with miR-384-5p inhibitors or decreased by treatment with miR-384-5p mimics (Fig. 4A), which was consistent with the protein levels detected by Western blot analysis (Fig. 4B). These results indicate that miR-384-5p directly regulates GRP78 pathway.
Downregulation of miR-384-5p inhibits rotenone-evoked ER stress signaling.
A previous report has suggested that GRP78 is a master regulator for ER stress signaling (53). Thus, ER stress signaling could be affected by modulating miR-384-5p expression. The results showed that the expression levels of phosphorylated ATF4 (pATF4) and phosphorylated IRE1α (pIRE1α) were both significantly increased by rotenone treatment (Fig. 5, A and B), implying that rotenone treatment evoked ER stress signaling, which is consistent with the findings of Goswami et al. (10). As expected, the expression levels of pATF4 and pIRE1α were significantly decreased by miR-384-5p inhibitor treatment or further increased by treatment with miR-384-5p mimics (Fig. 4, A and B). Furthermore, the downstream target genes of ER stress signaling including CHOP and XBP-1 were also decreased by miR-384-5p inhibitor treatment or increased by treatment with miR-384-5p mimics (Fig. 5, C and D). Taken together, our data imply that miR-384-5p regulates ER stress signaling.
Silencing of GRP78 enhanced ER stress and abrogates the protective effect of miR-384-5p on rotenone-induced neurotoxicity.
To further confirm that miR-384-5p regulated ER stress via GRP78, we used a knockdown of GRP78 and detected the effect of miR-384-5p downregulation on ER stress and rotenone-induced neurotoxicity. The results exhibited that silencing of GRP78 (Fig. 6A) significantly blocked the inhibitory effect of miR-384-5p inhibitors on ER stress signaling, as indicated by the increased expression of ER stress signaling target genes including CHOP and XBP-1 (Fig. 6, B and C). Furthermore, the protective effect of miR-384-5p inhibitor on rotenone-induced neurotoxicity was also significantly attenuated by the knockdown of GRP78 (Fig. 6D). Overall, these results suggest that miR-384-5p may regulate ER stress signaling via GRP78.
Detection of miR-384-5p in human primary neurons.
To further determine the critical role of miR-384-5p involved in PD, we used human primary neurons to validate the role of miR-384-5p in regulating rotenone-induced neurotoxicity. The results showed that miR-384-5p was significantly increased in primary neurons with treatment of rotenone (Fig. 7A). Furthermore, rotenone-induced neurotoxicity was markedly reversed by miR-384-5p inhibition or further aggravated by miR-384-5p overexpression (Fig. 7B). The results indicate that miR-384-5p functions as an important regulator for neuron survival in PD.
In the present study, we have demonstrated that miR-384-5p is strongly induced in dopaminergic SH-SY5Y cells treated with rotenone. Also, the downregulation of miR-384-5p significantly attenuated rotenone-induced neurotoxicity by inhibiting ER stress. The direct link between miR-384-5p and the 3′-UTR of GRP78 was confirmed by a dual-luciferase activity and miR-384-5p negatively regulated the expression of GRP78. Thus, downregulation of miR-384-5p elevated the expression of GRP78, leading to the inhibition of rotenone-evoked ER stress. Our data are in line with the findings of Gorbatyuk et al. (9), who reported that overexpression of GRP78 relieved α-synuclein neurotoxicity in a rat model of PD by downregulating ER stress.
In this study, we used an in vitro model of PD induced by rotenone in human dopaminergic SH-SY5Y cells. Rotenone can pass through the blood-brain barrier, which induces neuronal dysfunction and neurodegeneration (31, 35). A previous study has demonstrated that rotenone induces ER stress by upregulating the phosphorylation of PERK and eIF2α and that the knockdown of eIF2α significantly blocked rotenone-induced ER stress and cytotoxicity in neuroblastoma cells (4). Wu et al. (52) reported that candesartan cilexetil inhibited rotenone-evoked ER stress by downregulating the expression of ATF4 and CHOP and protected rat dopaminergic neurons. A recent study revealed that ER stress played an important role in rotenone-induced apoptosis of mouse neuroblastoma cells (10). In line with these findings, our data also indicate that rotenone induced ER stress in human dopaminergic SH-SY5Y cells, which was evident by an increase in phosphorylation of ATF4 and IRE1α. Intriguingly, the miR-384-5p significantly inhibited the phosphorylation of ATF4 and IRE1α, leading to a reduction in ER stress signaling.
In this study, we found that the expression of miR-384-5p was significantly increased in response to rotenone treatment. Several studies have proposed that miR-384-5p serves as a potential biomarker for numerous pathological processes. It has been reported that the serum level of miR-384-5p was significantly increased in mice with acute spinal cord injury and that miR-384-5p might be used as a promising biomarker for predicting the severity of acute spinal cord injury (13). In rats treated with trimethyltin, miR-384-5p was significantly upregulated with the evolution of neural cell death that was regarded as potential indicators of neurotoxicity (32). The decreased expression of miR-384-5p is required for spine enlargement associated with long-term potentiation (12). Here, we demonstrated that miR-384-5p was upregulated in response to rotenone treatment, indicating that miR-384-5p might have the potential to be used as a biomarker for PD. Bao et al. (1) reported that miR-384-5p was an important protective factor for cardioprotection in myocardial ischemia by regulating the expression of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta. Here, we reported that GRP78 was a target gene of miR-384-5p, both of which were involved in regulating rotenone-induced neurotoxicity by affecting ER stress signaling.
To uncover the underlying mechanism of miR-384-5p in regulating ER stress, we investigated its target gene. Through bioinformatics analysis, dual-luciferase reporter assay and expression analysis, we identified that miR-384-5p directly targeted the 3′-UTR of GRP78 and negatively regulated the mRNA and protein expression of miR-384-5p. Several reports have suggested that numerous miRNAs regulate the expression of GRP78 and its downstream signaling. It was reported that increased miR-181a aggravated injury in a mouse stroke model by inhibiting GRP78 protein expression levels, whereas reduced levels of miR-181a were associated with increased GRP78 protein levels and reduced injury (33). In several cancer cell lines, GRP78 was reported to be regulated by miR-199a-5p as well as miR-30d and miR-181a and cooperatively suppressed GRP78-mediated chemoresistance (45). Similarly, Dai et al. (5) reported that miR-199a-5p was evaluated during hepatic ER stress and directly regulated the expression of GRP78 in hepatocytes. Downregulation of miR-181b produced neuroprotection against ischemic injury via upregulating GRP78 (34). Iwamune et al. (21) reported that miR-376a mediated the expression of GRP78 in rat granulosa cells (21). In the present study, we identified miR-384-5p as a novel regulator of GRP78 and provided a novel option for modulating GRP78 expression in related pathological processes.
GRP78 functions as the master regulator of ER stress, playing an important role in regulating many diseases. It was reported that silencing of GRP78 increased the expression of CHOP and induced cell apoptosis in retinal ischemia-reperfusion (27). Overexpression of GRP78 suppressed α-synuclein aggregation by alleviating ER stress (23). Consistently, Gorbatyuk et al. (9) found that overexpression of GRP78 attenuated α-synuclein neurotoxicity in a rat model of PD by inhibiting ER stress. GRP78 overexpression reduces cell apoptosis through reprograming ER stress by reducing the protein levels of cleaved pATF6 protein, phosphorylated eIF2α, and the proapoptotic protein CHOP (8). Consistent with these findings, our results demonstrated that overexpression of GRP78 by inhibiting miR-384-5p significantly suppressed neuronal apoptosis induced by rotenone, and reprogrammed ER stress signaling by inhibiting the protein levels of pATF4, pIRE1α, CHOP, and XBP-1. In addition, knockdown of GRP78 significantly abrogated the inhibitory effect of miR-384-5p inhibitor on cell apoptosis and ER stress signaling, further indicating the involvement of miR-384-5p and GRP78 in regulating ER stress.
Previous study has suggested that GRP78 functions not only as the inhibitor for ER stress signaling but also a bonafide target gene of ER stress (50). Therefore, there is a feedback loop for GRP78 in the ER stress signaling pathway. Here, we reported that rotenone treatment activated ER stress but the expression of GRP78 had no obvious change in contrast to other ER stress target genes. The rotenone-induced high expression of miR-384-5p might contribute to this discrepancies. We speculated that miR-384-5p targeted and inhibited GRP78 expression induced by rotenone treatment, thus leading to uncontrolled ER stress signaling activation. However, expression of GRP78 in response to rotenone remains to be further determined.
In this study, we have demonstrated that miR-384-5p and ER stress were persistently induced in neurons treated with rotenone. We demonstrated that miR-384-5p modulated ER stress by directly targeting and regulating GRP78. Gorbatyuk et al. (9) reported that overexpression of GRP78 diminished α-synuclein neurotoxicity in a rat model of PD by downregulating ER stress. More recently, Salganik et al. (40) found that GRP78 protein overexpression protected aging nigral dopamine neurons in the α-synuclein-induced rat model of PD. Rotenone has been reported to induce ER stress both in cell models and animal models of PD (10, 11, 49). Here, we showed that downregulating miR-384-5p increased the expression of GRP78 and reduced ER stress signaling induced by rotenone. The inhibition of miR-384-5p showed a protective effect against rotenone-evoked neurotoxicity in human SH-SY5Y cells. The expression pattern and effect of miR-384-5p on neuron survival were further validated in human primary neurons. However, certain limitations of our study should be noted. Whether miR-384-5p is dysregulated in PD patients remains unknown. In this study, we only investigated the expression and effect of miR-384-5p using an in vitro cell model of PD induced by rotenone. Whether miR-384-5p targets GRP78 to regulate ER stress and neuronal survival in an in vivo model of PD still needs to be further validated. Therefore, before concluding that miR-384-5p is an important regulator for PD, more in vivo animal and clinical detection studies are needed.
This study was supported by grants from Natural Science Foundation of Inner Mongolia Province of China (2014MS0874) and Science and Technology One Million Engineering Project of Inner Mongolia Medical University (YKD2013KJBW016).
No conflicts of interest, financial or otherwise, are declared by the author(s).
M.J. and S.Y. conception and design of research; M.J., Q.Y., and S.Y. performed experiments; M.J., Q.Y., F.S., G.N., and S.X. analyzed data; M.J., Q.Y., F.S., G.N., Y.G., and S.X. interpreted results of experiments; M.J., Q.Y., F.S., and Y.G. prepared figures; M.J. drafted manuscript; M.J. edited and revised manuscript; M.J. and S.Y. approved final version of manuscript.
- Copyright © 2016 the American Physiological Society


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Configuring Resources for the Grid . Jerry Perez Senior Administrator Texas Tech University. Outline. What is a Job Manager? Types of Job Managers PBS Pro SGE LSF Condor/Condor-DAGman Rocks + Rolls (Quick overview). What is a Job Manager?.
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Jerry Perez
Senior Administrator
Texas Tech University
A Job Management System should always be
used for a cluster:
that runs a large number of jobs.
Note: Most clusters are homogeneous with respect to hardware and software.
PBS Pro is made up of a number of components:
The complexity of cluster management (e.g., determining if all nodes have a consistent set of software) often overwhelms part-time cluster administrators, who are usually domain application scientists.
Rocks is a complete clustering solution with a goal to help deliver the computational power of clusters to a wide range of scientific users.
Thank You. environments that cross administrative boundaries.

subset: commoncrawl


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GraphicRiver Isometric City 10269448
Stock Vector \ Objects \ Buildings
Isometric \ Street \ Technology \ Skyscraper \ Residential \ VectorVector
Stock Vector - Isometric City 10269448 by alexzel @ GraphicRiver
Stock Vector \ Objects \ Buildings
Vector isometric fantasy on the theme of urban
Layered: No; Graphics Files Included: JPG Image, Vector EPS; Minimum Adobe CS Version: CS.
Industry; Set of Elements; Isometric Buildings ; Postage Stamps; Isometric Plant; Industrial District; Factory Set.
Keywords: activity, architecture, building, business, cartoon, city, computer, construction, design, development, district, domestic, estate, exterior, home, house, icon, illustration, image, isolated, isometric, plan, real, residential, scene, skyscraper, street, technology, urban, vector.
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Go Ahead Eagles vs PSV 2017 Dutch Eredivisie: Match Preview and Prediction
Fixture: Go Ahead Eagles vs PSV
Competition: Dutch Eredivisie 2016-17
Date: Saturday, 11th March, 18:45 GMT
Stadium: De Adelaarshorst.
Go Ahead Eagles vs PSV: Preview
Go Ahead Eagles vs PSV match is going to be held on 11th March at De Adelaarshorst. It's an important football clash between two Dutch football clubs where they will try to give their best efforts to win this match. Go Ahead Eagles held a 2-2 away draw against Heerenveen and PSV registered a 4-0 home win against Roda JC in their previous league matches.
At the moment, Go Ahead Eagles is performing average and they have secured 5 wins, 5 draws and 15 defeats along with 15th position in Dutch Eredivisie 2016/17 season. In other side PSV performing good with 16 wins, 7 draws and 2 defeats along with 3rd position in Dutch Eredivisie table. PSV will start the match as favorite against Go Ahead Eagles in their crucial fixture of Dutch Eredivisie at De Adelaarshorst.
Go Ahead Eagles vs PSV: Head-to-Head Stats
- Both teams have played 12 matches against each other in all the competitions. Go Ahead Eagles has registered 1 draw and 11 defeats against PSV. PSV has scored 38 goals against Go Ahead Eagles and concedes 7 goals against them.
- PSV registered a 1-0 home win against Go Ahead Eagles in their last meetings in the match of Dutch Eredivisie on 11th Dec, 2016.
Go Ahead Eagles vs PSV: Prediction
Go Ahead Eagles will try their best to secure at least a home draw from this match and PSV is ready to secure an away win from the fixture. PSV is better side to compare with Go Ahead Eagles when they will play against each other at De Adelaarshorst.
Predicted result will be an away win for PSV.
Go Ahead Eagles vs PSV: Betting Tips
Asian Handicap: PSV -1.5 at 1.775


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$35.00 - $77.00 Quick Shopby Chloe York
$36.50 - $89.50 Quick Shopby Chloe York
I am an abstract painter with a fondness for vibrant colors and oceanic forms. My work deals with issues of camouflage, defense, and the exploration of beauty and what makes something pleasing to the eye. I am especially interested in the human practice of "decorating" oneself to suit a societal standard of physical beauty.
My works are flat and dimensionless with a strong graphic quality overlaid with intense pattern work and an abundance of information to keep the viewer engaged with the surface.
I currently reside in Memphis, TN with the sculptor and monster enthusiast Eric Quick and our ferocious daughter Echo.
My goal is to visually change objects and forms deemed ugly or untouchable by society to suit its standard of what beauty is, making a statement about the manner in which we decorate ourselves, covering up what is already there. My strong use of pattern and decorating suit this idea and add visual interest to the flatness and simplicity of the pieces while maintaining a focus on aspects of strong ornamentation and the exploration of what beauty is and what makes something pleasing to the eye.
Seascapes: Recent Works by Chloe York, Playhouse On the Square, Cooper Street, Memphis, TN, United States, 2016
Deconstruct/Reconstruct, Memphis Botanic Garden, Cherry Road, Memphis, TN, United States, 2016
Party of Five, Glitch Gallery, Memphis TN, 2015
Love the Leaf, Dixon Gallery & Gardens, Park Avenue, Memphis, TN, United States, 2014
Decorators, Memphis College of Art, Poplar Avenue, Memphis, TN, United States, 2013
Overwhelming Captivations, Memphis College Of Art, Memphis, TN, United States, 2013
Exhibition Momentum: 2013, 409 S Main St, Memphis, TN, United States, 2013
Chicken Pot Painting, Marshall Arts Gallery, Marshall Avenue, Memphis, TN, United States, 2012
Haters Gonna Hate, Marshall Arts Gallery, Marshall Avenue, Memphis, TN, United States, 2012


text:
Good topic Tyno!!
I think its getting more recognized, but I still think there's lots of stigma and confusion that goes with it. I agree with Moon, too. I hope/think it doesn't become a wastepaper basket illness.
I find it interesting that some doctors... like mine.. didn't believe in it before but now suddenly do. My doctor became certified in accupunture about a year ago and his opinion about Fibro changed right about the same time. I don't know if he became more aware of it when he started training for the accupunture or if he thinks he can make more money with fibro patients and accupunture. Either way, he would LOVE it if I started getting accupunture.. but its REALLY expensive and my insurance doesn't cover it.
Take care,


text:
Capcom has launched the teaser website for its newly announced PlayStation 3 sequel Sengoku Basara 4, due out next year in Japan.
The site currently contains a teaser trailer. Watch it below.
Capcom has launched the teaser website for its newly announced PlayStation 3 sequel Sengoku Basara 4, due out next year in Japan.
The site currently contains a teaser trailer. Watch it below.
Aw man its killin me….WHO ARE THE 2 GUYS AT THE END!! TELL ME, CAPCOM! TELL ME!!!!!
The one on the left is a young Nobunaga.
Nah no way. That pic has been circulating since Basara 2., Its gotta be someone during or after Ieayasu Tokugawa
Judging by the trailer, SB4 will likely focus more on the end of the Muromachi Period, which is actually the era that served as a direct precursor to the Sengoku Jidai.
In other words, the likelihood that this game will do more to focus on Nobunaga's early lifetime and military career is actually higher now than it ever is. We might actually see that Younger Nobunaga at long last rendered in a game.
Hmm….seems a bit odd that they'd go backwards for the 4th game…I understand not much happened after Ieyasu took over but still….feels like a cop-out.
Hanzo Hattori is still missing in this series, isn't he?
He been there as a generic ninja general. The Basara series has a long running…."relationship" with Koei's Samurai Warriors. They tend to either try to 'one-up' one another or belittle or parody characters from each other.
For example, Kanetsugu Naoe in SW is a righteous warrior who fights for justice under his lord Kenshin. In Basara, hes a generic general with a big sign on his head and keeps shouting that hes invincible but can actually die with one hit.
Alot of fans have speculated that we will either not see Hanzo or Capcom might concede one day and add him coz they realise that they ran outta non-SW historical figures or something.
Ha xD
Kind of shitty to not include the most famous ninja, though.
But then thy incluse Sarutobi Sasuke, who, as far as I know, didn't even exist. ^^
Well like I said about their competition with SW, Hanzo has been in SW since the first and is played out as a cool character, so Basara made him a generic ninja :/
After SW, Basara 1 came out and Masamune was made one of the main stars with all his awesomeness. SW 2 came out with a childish brat Masamune who does things coz he wanted to :/
You can get him as an officer in Sengoku Basara Heroes or so I've heard….I havent gotten him yet
You can't. At least not playable. Hes a partner you can get but hes just a generic looking ninja with a name.
You can't. At least not playable. Hes a partner you can get but hes just a generic looking ninja with a name.
You can't. At least not playable. Hes a partner you can get but hes just a generic looking ninja with a name.
Trying to figure out whose the silhouette one on the right…It looks like they have a bow or staff on their back?
Time to put my GUNZ ON again!
Shūichi Ikeda! I bet the character he'll play will have red armor and will move 3 times faster.
cant wait for the gameplay!!!!!!
gonna be fast paced version of Dynasty Warriors :)
Oh its more than that, my friend. Much more. Although I hope they can at least increase the troop size on screen for Basara 4. I believe that is the only thing that it needs is more enemies on screen to match DW.
shanks voice xD , i will buy this game since hit in japan xD..
really hope they can include all the characters from Sengoku Basara: Utage , still contemplating on getting it.
Would be nice if they have a change spoken language and have just subs.. never really liked the English voice acting although it is 1000 times better in Sengoku Basara Heroes than Devil Kings.
Really wish I could understand Japanese ;(
Utage is well worth the money IMO. It comes with so much more characters as well as the mode where you take over Japan. Sure the downside is no story mode (or at least BARELY one) but the characters and gameplay far make up for it.
If you wanna learn more about the characters, take a look at the wikis or TV Tropes Character page for Basara.
Unfortunately I think I heard that Capcom in Japan has decided not to release any content for a US release anymore. It might not be true but I stumbled upon it while looking at Utage and possible translation to english
i love this game i hope they locaztion it
whare is oichi oda ????


text:
we stayed at the "nebelhornblick" during the beginning of october 2011. the hotel is located outside of oberstdorf in a quiet spot at the top of kornau. we had booked a studio so that we'd have a bit of space to spread out in case of inclement weather. one of the deciding factors was that the hotel offered internet access in the rooms.
service at the reception was rather good and very friendly. the same goes for the staff in the hotel restaurant, almost without exception very friendly and helpful. we had booked half-board and both breakfast (buffet style) and dinner (salad buffet plus 4 course menu) was excellent.
the room was large, but a bit on the dark side despite a couple of windows. internet didn't not work at first (it's a LAN connection and you get a fairly long LAN cable at the reception) and it took them almost 3 days to figure out that a previous guest had mucked around with the modem in our room. the beds were OK-ish, my wife's bed was good, mine a bit over too saggy. furniture in the room was a bit worn and in places threadbare — this was even more so the case for the lounge area, were most of the upholstery looked quite worn and tired. what did annoy us was the weird heating "schedule" forcing us to turn up the thermostats all the way to have a warm room to come back too (heating was only periodically turned on it seems). also annoying was the fact that it took a long time (several minutes) until hot water could be persuaded to make it up to the shower and wash basin (we resorted to turning the water on about 5min before taking a shower).
- Official Description (provided by the hotel):
- Holiday hotel in a wonderful position. Wonderfully quiet area surrounded by nature. Family-friendly, very suitable for hikers and skiers. Rest, relax, take a vacation. ... more less
- Reservation Options:
- TripAdvisor is proud to partner with Booking.com, Travelocity, HRS, Priceline, Orbitz and Cheap Tickets so you can book your Ringhotel Nebelhornblick reservations with confidence. We help millions of travelers each month to find the perfect hotel for both vacation and business trips, always with the best discounts and special offers.


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Investors put aside concerns about rising oil prices yesterday, helping the market to a late-day rally focused on generally positive economic...
NEW YORK — Investors put aside concerns about rising oil prices yesterday, helping the market to a late-day rally focused on generally positive economic news.
The Dow Jones industrial average finished up 91.48 at 10,685.89, after giving up a triple-digit advance Wednesday and closing down 21.
Microsoft, one of the 30 Dow stocks, gained 32 cents to close at $27.27 a share. Boeing, also a Dow stock, soared $1.35 to $67.31, a 52-week high.
Broader stock indicators also closed higher. The Standard & Poor's 500 index rose 8.68 to 1,237.81, and the Nasdaq composite index rose 16.74 to 2,174.55.
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The major stock indexes gained ground during the final two hours of the trading session, even after the price of oil momentarily crossed $66 a barrel. It finished at a record high close of $65.80 a barrel, up 90 cents on the New York Mercantile Exchange.
"I think in the end people want to be bullish," said Doug Sandler, chief equity strategist at Wachovia Securities in Richmond, Va. "Some of that is a trend building on a trend — the market starts to go one way and everybody seems to jump on it."
But the ups and downs in stock prices seen yesterday, following a sell-off Wednesday, reflect persistent worries by investors that, despite strong corporate earnings and upbeat economic reports, oil prices will eventually exact a toll.
The market showed yesterday it is still torn between concerns that more expensive oil will inevitably hurt consumer spending and corporate profits and evidence that the economy is coping well with higher crude.
Investors were also parsing new data from the Commerce Department showing retail sales rose 1.8 percent in July, less than analysts expected. The increase came despite weak demand at department stores. Almost all the increase derived from auto sales, which jumped 6.7 percent. Excluding autos, retail sales rose just 0.3 percent, half the gain forecast by economists.
Also yesterday, the Labor Department said the number of Americans filing claims for unemployment benefits declined last week by 6,000 — the first drop in three weeks — to 308,000.
In another Commerce Department report yesterday, inventories held by businesses on shelves and backlots were unchanged in June, marking the first time inventory levels failed to increase in nine months. That effort subtracted significantly from overall economic growth in the second quarter but set the stage for much stronger growth in coming months.


text: My buddies and I have been waiting for this for 5 years now. Last Sunday we were in Toronto to see one of the greatest Swedish metal bands ever...Darkane! They played a show at the Opera House with Strapping Young Lad and Fear Factory. It was definitely worth the wait because they put on an amazing show. The crowd went crazy for their entire set and I really think they appreciated the welcome us Torontonians gave them. Now that they've finally toured here, I think they'll definitely come back for more.


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If you are involved in, or witness an incident that causes you concern but is not an emergency, please log the incident using the online form below. Your report will be sent in a secure format to a senior staff member who will ensure that the matter is reviewed and appropriate action taken where necessary.


text:
Remember the Ulysses 31 cartoon of days gone by? Neal McCullough of Hand Drawn Creative does, creating this limited edition Ulysses 31 print as a tribute.
Month: July 2012
LIP Mach 2000 Chronograph Watch
The Mach 2000 Chronograph watch was designed for LIP in 1973 by French industrial designer Roger Tallon and is their most popular watch ever.
Retro Cycling range at The Contemporary Home
While the nation is still gripped by cycling fever, it seems a good time to feature this range of Retro Cycling range.
Adidas Samba trainers return in ecru and black colourway
A regular reissue and one fo the all-time big sellers for Adidas. But these Adidas Samba trainers in an ecru and black colourway offer something a little different.
eBay watch: The Second Real Target 25 Years Later by Sir Peter Blake limited edition silkscreen print
Not often you see a Sir Peter Blake print on eBay with both a low starting price and no reserve, but we've found one in the form of this The Second Real Target 25 Years Later limited edition silkscreen print.
John Lewis midcentury-style Thomas armchair in a dog print fabric
If you are partial to both midcentury design and dogs, this John Lewis Thomas armchair in a dog print fabric culled be just the thing for you.


text: This is an easy drive up summit that is also handicap accessible. Bring a camp chair to sit on. There is a very nice viewing platform to setup at. I had great success activating on 10 meters and some local contacts on 6 meters. 20 and 40 meters were a bit noisier I think due to the RF rich environment so I had a more difficult time picking out some of the weaker stations. It is probably the only summit I have been on where I could also listen to the local radio station blaring out music from across the parking area. There is also a geocache at this location; naturally I signed using my call sign.


text: Where has the "US leads the way" spirit of the 1960's America gone? The "we can do anything attitude" that made America the envy of the world? The smiling faces, the confident walk, the pride in one's country. An America which demanded, sought and sweated for a better life and achieved it with one income per family in record time, after the horrors and sacrifices of World War two.


text:
New Containers for Your Meals and Potlucks
Posted By: Adina Bailey, Co-Founder, TakeThemAMeal.com on Mar 24, 2017
My friends and I have been taking meals to each other for MANY years now, and honestly, I've gotten a little bored with my container options - until recently. I know that there are many functional options (like foil pans, glass jars, Gladware, etc.) and a meal from a friend tastes delicious no matter how it is transported, but sometimes it's nice to mix things up a bit.
Here are three containers that I've recently discovered and they're my current favorites:
1. Pioneer Woman Storage Containers - Aren't these beautiful? I love the patterns and you can mix an match them. Just including one of these with your meal is like including a bouquet of flowers. I'm still not a fan of putting warm food in plastic, so I stick to using these containers for fruit, dessert, and other cool sides. Best of all, they're very reasonable priced (around $4 depending on the size).
2. Reynolds Heat & Eat - I'm not certain how long these containers have been available, but I just discovered them. I like that they are recycled and the lids seal tightly. These containers are perfect for transporting meals you've made in a crockpot or on your stove top. Sadly, you cannot bake in them, but they are microwave safe with makes reheating a breeze.
3. Nora Flemming - I received this platter as a gift and I took it to my first potluck last month. I love that you can change the look of platter by changing out adorable seasonal accessories that stick right into the edge of the plate. These festive pieces make fantastic wedding gifts!
Read other recent articles by Adina Bailey:
Hello friends! As you are caring for others with meals, we hope you find our blog full of tested recipes and thoughtful ideas to encourage you along the way.
The five of us look forward to hearing from you. Please email us.
Adina, Kate, Janelle, Rachel, Maureen
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text:
It's colder than a _____.
You are welcome to finish that sentence however you'd like because you just made it through the coldest night in Atlanta in at least 18 years.
"We are facing low temperatures around sunrise between 2 and 9 in Atlanta and zero and minus 5 in the mountains," says WSB meteorologist Kirk Mellish. We broke the record low for this date of 10 set back in 1970 with an official low of 6.
But it's going to feel much worse.
The National Weather Service has issued a wind chill warning for Bartow and Cherokee Counties, plus the mountain counties until 1 p.m. Tuesday. Winds will blow between 5 and 20 mph. That will make it feel like 5 to 10 degrees below zero.
The last time a wind chill warning was issued in Georgia was back in 1993.
The rest of Atlanta is just under a wind chill advisory.
Frost bite is possible to any piece of exposed skin if you are outside too long, doctors say.
That is a major reason why pretty all every school system in metro Atlanta is closed.
But Mellish says we will slowly pull our way out of the record cold today. But we won't get above freezing until midday tomorrow.
It will be mainly sunny for your Tuesday with highs around 25. Tonight will still be very cold, but at least it's back in the teens. Mellish says lows from 12 to 17.
The ridiculous temperatures clear out of here by Wednesday as we finally get back above freezing. Look for plenty of sun with highs around 42 and lows 24-28.
Mellish says the clouds return on Thursday with highs in the low 40s and lows above freezing.
There is a 40 percent of a light shower on Friday with highs around 50. We finally get back to 60 on the weekend, but there is a 60 percent chance of rain Saturday.


text: Girls Mini Season 2017-08-30 5:30 pm - 2017-08-30 7:30 pm http://citybeach.com/programs/#mini City Beach Santa Clara City Beach, Mead Avenue, Santa Clara, CA, United States [{"latlong":["37.372332","-121.979042"],"location":"City Beach, Mead Avenue, Santa Clara, CA, United States","zoom":"9","infow":"City Beach, Mead Avenue, Santa Clara, CA, United States<\/span><\/div>\n\t\t\t <\/label>\n\t\t\t 2017-08-30 5:30 pm2017-08-30 7:30 pm <\/span>\n\t\t <\/div>","google_map_url":"https:\/\/www.google.com\/maps\/place\/City+Beach%2C+Mead+Avenue%2C+Santa+Clara%2C+CA%2C+United+States\/@37.372332,-121.979042"}] The Mini Season is a series of clinics focused on building skills in the fall with our experienced staff. All participants will be trained in individual skills (Serving, Passing, Hitting, Setting, Blocking and Defense) along with team concepts and strategy over 16 weekday sessions in September and October. When: Mondays and Wednesdays, 5:30p – 7:30p, August 30th through October 25th. PLEASE NOTE THE CHANGE IN TIME FROM PREVIOUS YEARS! (No program Labor Day Monday September 4th) Where: City Beach Santa Clara 2911 Mead Ave Santa Clara, CA 95051 Cost: $400 for the full season Our Location City Beach 2911 Mead Avenue Santa Clara, CA 95051 408-654-9330 View Map Management General Manager: Gary Mano Club Director: Dustin Moore Sports Manager: Joe Fuston Volleyball Admin: Amber Biddle Event Coordinator: Amanda Greenfield Quick LinksHome Programs Our Teams Tournaments Our Coaches Private Events Partners Calendar Contact Us Subscribe to our Newsletter


text:
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- Consolidated Balance Sheet
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Financial Data is appeared in PDF file.
In order to see PDF file, Adobe(R) Reader(R) of Adobe Systems Incorporated is necessary.


text:
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Soft PVC name badge ideal for visitors passes, drop level front pocket means that inserts are easily replaced. 60x90mm. Red.
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text:
Conditioning For Your Facial Hairs
I know what you had been thinking. Effectively, right now you see the things actually are not as easy as you believed.Even in case you've the perfectly shaped face hair, unavoidably, beards need every day care. Washing, trimming, conditioning, stroking and repeat. Just how actually are you likely to do all of this beard maintenance? The simplest way is actually to simply go on the internet and shop all the required beard kits.
It is not the sum of money which you've to spend, although it is able to be significant. Particularly, in case you are way too good with the quantity of things which you use on the beard of yours or perhaps if the brands which you select actually are expensive.
It is much more about the fact which you are the kind of beard owner which wants the very best for the beard of his. The beard of yours is actually just like the child of yours, you really want to nurture it and develop it to be strong and healthy. And also you wish to supply it the best, for the well-being of its, nutrition.
Thus, you really want to prepare for it (here's the keyword we have been looking for). You need to put together all these homemade goodies for the beard of yours, and do almost everything on your to sell.
All things considered, you do not want food that is fast for the child of yours on a every day basis, will you? But does beard growth oil work is actually among the conditioning products that actually are fantastic for just about any beard. It is perfect for all lengths and beard styles. When you begin growing a beard, beard oil is able to be much more than needed, particularly in case it is itchy as hell. When the beard of yours grows longer, beard oil is actually again important. Beard oil conditions the beard of yours and also causes it to be very easy and smooth to handle.


text:
1.1 I am Chief Executive of the New East
Manchester urban regeneration company, a not-for-profit public/private
partnership established to spearhead the regeneration of the east
Manchester area. I have occupied this position since August 2000,
having previously been Deputy Chief Executive (Regeneration) for
Manchester City Council. I have worked on the management and administration
of urban regeneration projects continuously since 1984, in London
and Oldham as well as in Manchester.
2.1 During the time I have worked in urban
regeneration there have been countless new policy initiatives
and funding programmes aimed at tackling the problems of urban
decline in our inner city areas. Whilst there have been many changes
in emphasis over this period, there have been some principles
which have remained relatively consistent:
2.1.1 The need for a comprehensive approach
which recognises the inter-relationship between economic, social
and physical or environmental issues, and which aims to tackle
these problems in an integrated manner.
2.1.2 The importance of community involvement
in, and ownership of, the changes, developments and improvements
taking place within their neighbourhoods.
2.1.3 The use of additional, time-limited
public funding of whatever kind to lever resources from other
public sources and, crucially, from the private sector to both
tackle the problems and exploit the opportunities in regeneration
2.1.4 The critical importance, in terms
of sustainable regeneration, of private sector investment. One
of the best benchmarks of success of initiatives aimed at improving
areas which have been starved of investment and development is
the extent to which they have created the conditions in which
the private sector will continue to invest, and take a return
on that investment, beyond the period of special assistance.
2.2 Manchester can claim some success in
the application of these principles. In Hulme, for example, £37.5
million of City Challenge funding levered around £70 million
from other public sources and well over £100 million of private
sector investment over the five-year period from 1992 to 1997.
Since the closure of the programme, Hulme has continued to develop
as a successful neighbourhood characterised by increasing land
and property values, and a continuing momentum for development
led by the private sector without the need for special forms of
assistance. Gap funding, no longer needed, was absolutely essential
in kick-starting this process.
2.3 In the city centre, equally, the serious
threat to the economic performance and capacity of the regional
centre in the wake of the terrorist bomb in June 1996 has not
merely been alleviated but reversed. Through the strategic use
of public funds, in which Europe played a key role, massive private
sector investment in improved commercial, retail, leisure and
residential uses has been achieved.
2.4 It is worth noting the substantial growth
in the influence of the European Union over this period. It has
become effectively one of, if not the, main source of funding
for some aspects of regeneration particularly business support,
employment and training, and EU funding is an essential component
of most major physical development projects. It is also increasingly
influential in policy terms through the Single Programme Documents
and other regulatory frameworks which govern the use of EU funds
and, in procurement terms, through OJEC requirements.
3.1 The East Manchester area is one of the
most deprived areas in the country. As a base for the traditional
manufacturing industries on which the wealth of the City was built,
the area experienced severe economic decline in the recessions
of the late 1970s/early 1980s, with a loss of business, jobs,
skills and population which has continued over the last quarter
century. The Commonwealth Gamesand specifically, the decision
to locate the major new facilities for the Games in the heart
of the areahas provided the stimulus for the physical transformation
of the area, the reconstruction of its economic base and the improvement
of social conditions for local communities. New East Manchester's
role is to develop and lead this regeneration strategy.
3.2 The scale and severity of the post-individual
dereliction and its economic and social consequences is such in
East Manchester that major transformational change is not simply
desirable but essential, to change the image and perception of
the area and to create a level of confidence in its future that
is needed to secure private sector investment. In these circumstances,
clarity as to the level and scope of pump-priming support that
can be offered is very important in developing positive and effective
working relationships with the private sector.
4.1 I would not wish to exaggerate the effect
of some two years in which it has not been possible to bring forward
gap funding schemes, in that I do not believe that we have yet
lost development partners or projects as a result of the EU's
decision. To some extent, the timing of this has been fortuitous
for East Manchester in that:
4.1.1 Certain projects in course of development
during 1999 managed to get "under the wire" before the
EU embargo on gap funding schemes took effect, and this has enabled
a degree of momentum to be maintained in the intervening period.
4.1.2 Much of 2000 was taken up by the development
of, and consultation upon, a strategic Regeneration Framework
for East Manchester which is intended to provide clear guidance
to development partners as to the nature, scale and scope of future
development. In January 2000 we were at a comparatively early
stage in the development of most of our early major initiativesnotably
our new housing programmeand we have continued to make
progress on these in the intervening period in the expectation
that some form of assistance, gap funding or otherwise, would
ultimately be available.
4.2 Nevertheless, we are now nearing a crucial
stage in the development of neighbourhood plans for four areas
in East Manchester, in conjunction with private sector partners,
where it will be necessary to be clear about the extent to which
public funding can be deployed to bridge the gap between cost
and value, and the terms under which this can be done. In these
circumstances, EU's approval of the five gap funding projects
is welcome but will only go part of the way to resolving the impasse
that has existed since December 1999. In particular:
4.2.1 Rigid differentiation between bespoke
and speculative schemes, between SMEs and larger companies as
beneficiaries of grant, and between different tiers of assisted
area are confusing, unnecessary and, in some circumstances, militate
against the achievement of regeneration objectives. The encouragement
offered to, for example, RDAs to undertake direct development
may well be beneficial in certain circumstances, and would not
be a problem in East Manchester, where the NWDA is so firmly committed
to the NEM strategy. However, it needs to be recognised that direct
development is not necessarily, in all circumstances, the most
efficient or cost-effective means of facilitating development
and RDAs will themselves need to build capacity, in resources
and skills, to take on this role.
4.2.2 The severe limitations on residential
schemesas I understand it, residential development will
only be eligible as part of mixed use schemes with a strong commercial
componentis a major problem in East Manchester, where the
failure of the housing market is one of the principal symptoms
of economic decline and where large scale intervention in the
housing market (we have a target of up to 12,000 new homes over
a 10-15 year period) is an essential component of the regeneration
strategy. We are currently working with four developers on three
initiatives, which involve the remodelling and reconstruction
of neighbourhoods with a strong residential component, and where
we anticipate the need for significant public sector incentives
to unlock private sector investment.
4.2.3 The continuing uncertainty around
gap funding is, in itself, problematic. Whilst progress on the
five schemes is most welcome, Government has signalled its intention
to continue to press for a more comprehensive framework. This
has to be right, but it needs to be recognised also that one of
the private sector's most consistent complaints is about uncertainty
and shifting goal posts. A degree of urgency therefore needs to
be attached to this framework if we are not to begin to lose potential
development partners and investment.
5.1 The Sub-Committee's interest in the
role of the EU in regeneration in the UK is welcome and timely.
It is patently absurd that European regulation aimed fundamentally
at anti-competitive practices by member states is being used in
such a way as to jeopardise even further the prospects for investment
and development in economically marginal and uncompetitive areas.
5.2 There is an urgent need to build upon
the five "temporary" schemes recently announced and
move towards a more comprehensive framework for providing essential
pump-priming incentives for the private sector. Such a framework
needs to be flexible; based on subsidiarity which recognises the
differences between areas and the primacy of local regeneration
frameworks and partnership; operated through processes which maximise
private investment; and comprehensive in nature, covering all
types of development which can be shown to contribute towards
the achievement of regeneration objectives.
5.3 A comprehensive EU regeneration framework
might also usefully consider two other important dimensions of
the EU's impact on regeneration activity in the UK, ie procurement
and policy. The first of these is least problematic. The requirement
to allow for competition across Europe for major contracts cannot
be gainsaid, although there may be scope for examining ways in
which the process of advertising through the Official Journal
could be streamlined.
5.4 In policy terms, whilst the new ware
of Objective 1 and 2 programmes have seen significant advances
in structural subsidiarityie the Commission playing a less
significant part in regional and sub-regional partnershipspolicies
governing the use of Structural Funds are still over rigid, centrally
determined and insensitive to local regeneration initiatives in
many respects. This makes it more difficult to integrate European
funds with domestic sources of funding and increases the overhead
costs to local authorities and regeneration agencies.
Tom Russell
Chief Executive
New East Manchester Urban Regeneration Company


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Delivery & Returns
Create a cleaner and organized workspace by stowing away your keyboard in this pull-out keyboard drawer. Pull the keyboard out and place it on your desk when in use and put it back in the drawer when you're finished. Or if you prefer to type at a slightly lower level, keep your keyboard permanently in that drawer and simply pull it out to type. This feature is also great for storing a laptop.
Maintain an organized office space by hiding cords away. This desk has wire management holes in the back, allowing you to connect wires directly into your wall. Wire management also helps to reduce dangerous heat build-up by increasing air circulation inside the desk doors, which means less noise from automated fans that work to keep each electronic cool.
Hide away your bulky printer with a pull-out printer drawer, allowing for a cleaner workspace. Leave the printer pushed in or easily pull it out when you need to reach back to add paper or apply settings to the printer.
Ugly, grey file cabinets are a thing of the past! This stylish piece has a ready-to-use file drawer, with a hanging file rack so you can easily organize your files.
Drawers are constructed with dovetail joinery, ensuring long-lasting strength and storage. Made up of interlocking wedge-shaped elements called pins and tails, the joint connects drawer fronts, sides, and backs, designed to withstand the daily pulling forces you apply when you open a drawer, for problem-free use. A time-tested joint that predates written history, dovetail drawers are a mark of quality furniture construction.
Transform your home office while also adding traditional style with this computer credenza. Ample storage allows you to stay organized and a spacious top makes it easy to get work done. Devoted space for files and a printer provide this piece with versatile storage. Molded features, bun feet, and antique-like hardware offer a traditional look to this computer ready credenza.
The Vintage West 4 Drawer Computer Credenza with Antique-like Bail Pulls by Hooker Furniture at Belfort Furniture in the Washington DC, Northern Virginia, Maryland and Fairfax VA area. Product availability may vary. Contact us for the most current availability on this product.
Rustic details, elegant designs, and traditional appeal from the Vintage West collection will change the way you live at home. Dark charcoal finishes along with silver accents fit easily with most decor. Striking carved features and nailhead trim adorn bedroom pieces that will draw your eye, while also offering plenty of storage space and a sophisticated place to spend your nights. Versatile dining pieces make it easy to host an incredible dinner party full of traditional ambiance. Soft curves and turned detail can be found in many pieces for intriguing and distinct looks. Make a change in one room or completely overhaul your home's style with Vintage West.
The Vintage West collection is a great option if you are looking for Traditional furniture in the Washington DC, Northern Virginia, Maryland and Fairfax VA area.
These images are representative of this group as a whole and may differ from this item.
Browse other items in the Vintage West collection from Belfort Furniture in the Washington DC, Northern Virginia, Maryland and Fairfax VA area.
This item has been tagged as: Credenzas, Storage Credenza, Desk with Storage, Low Cabinet Desk, Cabinet Desk, Computer Stations, Kneehole Desks, Kneehole Credenza, Closed Cabinets, Bookcase Desks, Home Office Furniture, Sideboard, Buffet, Office Credenza, TV Credenza, Computer Credenza, Executive Credenza, Executive Desk, Credenza with Hutch, Credenza Desk, Media Credenza, Television Credenza, Dining Room Credenza, Credenza Cabinet, Desk with Credenza, Credenza Table
Nothing on this page may be copied or reproduced without explicit permission.


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This bird was calling loudly as if trying to locate another bird (female maybe) and it's coloring was just fabulous, bright red head, golden browns to rufous against the snow covered background, just beautiful. What a great way to end a day of birding.
P.S. I was informed that not to fare from where I found the pheasant there is a private pheasant hunting business that on occasion a few luck birds escape from. It was a beautiful sight out in the natural environment......alive
story and images © 2009 Peter Manship


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Scouts Canada, the country's leading youth organization, offers challenging programs for boys, girls and youth age 5-26 in thousands of individual groups in most cities and towns across Canada.
Are you interested in working at the Haliburton Scout Reserve this coming summer? If so then please watch this page for your opportunity to fill out a secure online Application Form. Please note that applicants 18 and over will require a clean Police Record Check and Vulnerable Sector Screening.


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Celebration Cupcakes - Tempting Treats For Every Occasion
Format: Paperback Author: Tamara Jane
Free Click & Collect
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Free Delivery Available
- Free Standard over £20
- Standard delivery £2.99
- Next working day £4.99
Product Information
Imagine the surprise and delight evoked by the gift of a cupcake complete with an exquisite topping, to mark a special occasion. It is a moment to treasure. Baking cupcakes for a celebration is a pleasure in itself, starting with the anticipation involved in choosing the recipe and then selecting the most appropriate topping for the occasion.

 The range of occasions on which to savour
Stress-Free Returns
Subject to exceptions, we are happy to exchange or refund your purchase within 28 days of delivery. You can return items by post or to one of our stores.Go to full returns information
Together Rewards
5 points for every pound you spend
Rewards Points PLUS Great Prices - YES! We're proud to give even more back to you and reward all Together Rewards Card members with 5 points for every £1 spent, along with exclusive offers, bonus points promotions, member exclusive gifts and more! Interested? Order a card with your purchase and once you've registered and linked your Card, you'll receive 50 FREE points (worth 50p) and you'll receive Reward Vouchers every 3 months to spend on anything you like in-store and online! Click here to find out how to get your Together Card.


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Discussion in 'Chill Out Forum:' started by MsCliffHazel, Jul 15, 2011.
Hi guys! what do you think about my Fan Page? Thanks!:up:
I'm not a fan
Same here...
Oh but why? Can you tell me the reason?
I am open to constructive criticism
It's facebook....
You guys are awful :lol:
(in a good way)
Man talks sense.
My main problem I have with Facebook pages for designers is what is the incentive for people to 'like' your page. If it is just another place to post links to blog posts I don't see the incentive. Maybe it's just the fact that I like to keep Facebook for personal and use twitter and linked in more for business, which I think is quite common.
I've got retail clients that have great facebook pages as customers often post questions and get answers straight from the company, or other users. They offer facebook exclusive discounts, polls for new product development etc. It works because it builds a sense of community amongst the customers and gets them involved.
I don't know what the answer is for designers but I think if you are going to make a facebook page reach beyond your inners friends/ family you need to think about why someone should bother.
I know, it does happen occasionally :up:
Separate names with a comma.


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April Random Post
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Oh i love april fools day! I run in the bedroom on dh this morning slinging packin peanuts screamin avalanche lol we live in NC LOL he flipped.....then i put salt on his toothbrush and told him i was prego... i had a hysterectomy last yr so...... ive had some REALLY good laughs this morning.... not to mention i woke up my dd to go to school...haha she was funny
How about you?
Quoting anotherguatmom:
Anyone pulling any April Fool's Day jokes today?
Welcome April! April showers may bring May flowers! ;)
No, I woke my dd up and yelled "Quick get up you missed the bus, you have to hurry and get around for school." She opened her eyes said "Mom Im spring break go back to bed." I cracked up laughing and said "April Fools". She sat up looked right at me and said "Your mean.." LOL
Got to go to my hair guy last night. I love love love him! If I won a gazillion dollars I'd hire him to do my hair every day lol.
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Bø, clouds, CS 6, EV stop, fjell, fjellkjede, HDR, himmel, landscape, light, Lightroom 5, mountain range, mountains, mountaintops, natur, nature, Nix filters, Norge, Norway, photo, photography, Photomatix Pro, sky, sol, solnedgang, Southern Norway, sun, sunlight, sunset, Telemark
Here is my most recent photograph, taken yesterday at sunset from atop of Lifjell mountain range in Telemark county, Southern Norway.
It was very cold up there, the wind blows almost made the camera along with the tripod fly off of the cliff, so I had to hold on to it with both my hands while taking the pictures :).
This one is the first triple exposure image I took that evening.
Post-processing: Photomatix pro, Nix filters from within Lightroom 5.
Love this shot!
Thanks for stopping by 🙂


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The Best 2017 Events for Warehousing, Manufacturing & Safety Professionals
Advance your career and your company's profitability with these educational opportunities
It's important for professionals to retain an edge by continuing our education, exposure to new ideas, new products, and technologies. Events and Tradeshows provide great avenues to stay sharp on the latest concepts. Below is a list of upcoming events you should consider as you kick 2017 off to a productive start.
Texas Safety Council, Fort Worth TX, March 5-7
The NSC TSCE is your opportunity to meet with like-minded safety, health and environmental professionals in Texas. Educational opportunities include learning lands, technical sessions, and more. A large number of exhibitors are booked, including Cisco-Eagle. We'll be on hand with the innovative AisleCop® forklift safety system, AisleAlert warning systems, and other industrial safety innovations. Come see us!
The Operations Summit, Pittsburgh PA, March 27-27
This is a good event for logistics and order fulfillment professionals. It's described as "From warehousing and workforce management, ecommerce and contact centers, inventory and order management to payment processing; from pick, pack and ship to delivery and returns; technology, automation and systems integration, to transportation and global operations." The event features tours, educational opportunities, workshops, and an excellent roster of exhibitors.
ProMat 2017, Chicago IL, April 3-6 at McCormick Place
This is the big show for material handling, distribution, manufacturing and warehousing. There will be 850 exhibitors, scores of educational seminars, and the chance to network with peers.
What's more, by attending, you can also visit Automate 2017, co-located with ProMat. "Automate showcases the full spectrum of automation technologies and solutions. From traditional industrial applications to cutting edge new technologies, you'll find ways to automate every process in your company. It's held just once every two years, so be sure to take advantage of this opportunity to find the right solutions to meet your automation challenge."
ProFoodTech, Chicago, IL, April 4-6
This show is a critical event for food manufacturing and distribution, "where food and beverage pros gain an edge," with 150,000 feet of exhibition space with 600 exhibitors, and a variety of workshops. "This dynamic conference program is designed specifically for food and beverage professionals in operations, plant management, engineering, R&D, quality assurance, supply chain management, sales, marketing and business development."
WERC National Conference, Fort Worth, TX, April 30-May 3
According to WERC, this show features "today's fast-moving supply chain demands that you stay on top of issues that concern warehousing and logistics professionals, such a workplace safety, technology, metrics, security and productivity."
Cisco-Eagle will exhibit at this year's WERC conference. We'll be talking about ways to increase efficiency, reduce costs, enhance safety, and move ahead in any distribution or manufacturing operation. Drop by and see us!
Safety 2017, Denver CO, June 19-22, Colorado Convention Center
With its emphasis on continuing education, ASSE is a must for safety and EHS professionals. "For more than 50 years, the ASSE's Professional Development Conference has been and will continue to be the direct reflection of what is taking place in the occupational, safety and health industry." Loads of seminars, workshops, events and a large exhibition hall with thousands of new ideas are on tap for Safety 2017.
Cisco-Eagle is exhibiting our exclusive AisleCop® forklift safety system and other industrial safety technologies this year at Safety 2017 – plan to visit us!
Pack Expo & Healthcare and Packaging Expo, Las Vegas, September 25-27
"North America's largest packaging event of 2017, will bring together the solutions you need to launch a new product, solve production issues and keep your products competitive" Pack Expo delivers over 2,000 exhibitors, on-floor educational seminars, and extensive networking opportunities. Co-located with the Healthcare and Packaging Expo, this is one of the biggest events of the year.
National Safety Council Congress & Expo, Indianapolis, IN, September 23-29
Billed as "Racing to Safety", this event is one of the best safety conferences in the industry, particularly for warehousing and manufacturing professionals. Educational opportunities abound, including great keynote addresses, technical sessions, workshops, continuing education/development, and lots more. Over 1,000 exhibitors are on hand — including us.
Cisco-Eagle is exhibiting our AisleCop® forklift safety system, AisleAlert warning systems, and other industrial safety technologies at this event. Drop by and see us in action.
More to come…
We'll be updating this post with more events as the year goes on. Check back often!
Tags: conferences, ProMat, Safety & Ergonomics
Scott Stone Cisco-Eagle's Director of Marketing. He has over 25 years of experience in the industry.


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So many Americans were sweating it when they heard that no statement would be released until they found out if it was actually a hate crime. 4 thugs kidnap, torture, and humiliate a special needs boy for 24 hours, making hims say "F***k White People, F***k Donald Trump" and they didn't know it was a hate crime?
It was all caught on video…the hate crime is in the footage!
Well…at least , the wait is over.
This is what we know.
Fox News tweeted: "Breaking: 4 African-American teens who tortured & yelled ""F— white people!" at a mentally disabled man have been charged w/ a hate crime."
Breaking: 4 African-American teens who tortured & yelled ""F— white people!" at a mentally disabled man have been charged w/ a hate crime. pic.twitter.com/KQBFMItx44
— Fox News (@FoxNews) January 5, 2017
Breaking: The 4 African American attackers in that #Facebook torture video all charged with hate crimes in #Chicago.
— Matt Finn (@MattFinnFNC) January 5, 2017
he Chicago Sun Times reported:
The Cook County State's Attorney on Thursday filed hate-crime charges against the four for the beating of the 18-year-old.
They also face charges of aggravated kidnapping, hate crime, aggravated unlawful restraint and aggravated battery with a deadly weapon, according to the state's attorney's office.
As Twitchy noted: "Whether they targeted the young man for his race or his disability either way via Illinois law the crimes should be seen as 'hate crimes."
@MattFinnFNC pic.twitter.com/3uvRLvYMPB
— Eduardo Alvarez (@EdDerulo) January 5, 2017
Thank goodness they called this one right, and allowed justice to prevail. These kids will do it again…if aren't given the opportunity to pay the consequences of their actions. Now we just need to let the legal system do its thang…and hope that justice is fully served.


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2012 Toronto Breakfast - Geena Davis
Six years ago, actor Geena Davis was watching television with her two-year-old daughter and was shocked at the lack of female characters in children's programs. She was galvanized into action.
Today, the Geena Davis Institute on Gender in Media is the only research-based organization working within the media and entertainment industry regarding the portrayal of women and girls in children's entertainment.
The 2012 Toronto Annual Breakfast featured Geena Davis, Academy Award® winner and advocate for women and girls.
Funds raised will help women in Canada to move out of poverty by funding life-changing programs designed especially for them. Through these unique programs, they can learn a skilled trade, start a small business, or get work experience.
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text: It definitely does not come on right after eating. Can I ask more about the on again and off again partial obstruction? Does it go away on it's own? How is something like that treated? I haven't been examined by my current GI ever. My family Dr. orders my "yearly" colonoscopies and the GI performs the procedure and orders the Asacol for me, but I've not been "treated" for my Crohns for 17 years when I was first diagnosed. I'm a little anxious about having to take Prednisone. I absolutely do not want to unless its the only option. What sort of tests would be ordered to find something like this?


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A handful of women gathered in the living room of an old friend Thursday, clad in matching white T-shirts that read: "You can take a girl out of th' Grove … but you can't take th' Grove out of th' girl."
With smiles and chuckles, Coeta Redd, Jetta Harris, Betty Griesing, Alta Owens and Juanita Wood recalled blind dates, slumber parties and trips to the movies as they reminisced about their days at Pleasant Grove High School. The women, all members of the Class of 1948, are gearing up for their 65th high school reunion to be held June 22.
Their graduating class had about 75 students, about two-thirds of whom have died. When the reunion is held every two years, the number of occupied chairs drops, Owens said. This year they expect about 32 of their peers, not just from 1948 but from the classes of 1939-57.
"These classmates are my dearest friends," said Griesing, who stores boxes of yearbooks, photo albums and a display board of her class's 27 military veterans in her garage. She exhibits the mementos at the reunions. "They're just like brothers and sisters, and the boys, they're all the same. We love each other, we hug, we kiss. They're just part of our family, and we care what happens."
Redd recalled that a radio station once called Pleasant Grove "the garden spot of America." The once rural area on the edge of Dallas is now a densely populated urban area. "Dallas was a wonderful place to grow up," Redd said. "We didn't have shopping centers and stuff; you went downtown."
In the past 65 years, Pleasant Grove's landscape and demographics have changed and the high school, which stood near Buckner Boulevard and Lake June Road, no longer exists.
In 1954, Pleasant Grove Independent School District was annexed by Dallas Independent School District and by 1957 Samuell High School had replaced Pleasant Grove High. Over the years the area's population has transformed from predominantly white to primarily black and Hispanic.
When they went to school, the women wore poodle and ballerina skirts, canvas slip-on shoes and saddle oxfords. They weren't allowed to wear pants; entertainment was listening to the radio; and they walked and biked instead of using cars.
"We were not worried about shootings in the schools or drugs or alcohol," Griesing said. "If somebody got out of line, the principal gave him a few licks and sent him home and Dad gave him another few."
"We had the best of times, I'm convinced of that," Wood said.
As they've aged, each has fallen into a specific role within their group of friends. Griesing, who now lives in Athens, is the memorabilia keeper; Harris, of Rockwall, is the artist; Owens is the party host; the women describe Redd, of Mesquite, as their laughter; and Wood, of Dallas, makes all of the phone calls, keeping everyone close. All widowed, the close-knit group talked about how those phone conversations have evolved to focus on who is sickly and who can remember what.
"We've gone through some really tough things together," Wood said. "But the good outweighs the bad, believe me."
Among the five friends, they've raised 11 children and count 21 grandchildren and 28 great-grandchildren. After high school, two went on to open a real estate agency together and one started an auto shop with her husband. They've moved to places as distant as Florida and California, but they've all returned to Texas and still tout their Pleasant Grove roots.
"We are unique," Owens said about the members of the class of '48, who plan lunches about every two months. "And I think it's time that something good is said about Pleasant Grove, and we're a product of Pleasant Grove."


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Gear up for adventure! Last day to save 15% off any premium beanie with code: KZBEANIE15 -- Tap link in bio to shop & save! -- Kameleonz.com


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Welcome to the Alex Pettyfer Network, your best online source for young British actor Alex Pettyfer. We provide the latest information, news and photos to keep you up to date. You may know Alex from Stormbreaker, Tormented, Beastly, and Endless Love or his up and coming projects. We aim to bring you the best news, media and updates on Alex and his career.
February 13th, 2014 ● ● 0 comments
Magazines News
Hunger Magazine is getting ready to release their Mighty Blighty issue and they're releasing 20 different covers, including Alex gracing one of the covers. The other covers include: Jamie Campbell Bower, Ellie Goulding, James McAvoy, Kristin Scott Thomas, Plan B, Sam Claflin, Amber Anderson, Hayley Atwell, Nicholas Hoult, Holliday Grainger, Polly Morgan, Harvey Newton Haydon and Isaac Carew, Imogen Poots, Tinie Tempah, Damian Lewis, Jake Bugg, Rebecca Hall, Ella Eyre and Katie Eary.
Hunger issue 6, Mighty Blighty will be released on February 20th.
Photo courtesy of Alex's Instagram.
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Rooms, services Guests looking for accommodation in Manila are welcome to book 150 nicely furnished rooms at MICROTEL MANILA MALL OF ASIA Manila. To learn more about the exact range of services of MICROTEL MANILA MALL OF ASIA Manila (including services for an extra fee) and the exact equipment of the rooms, please check the information sheet below.
Payment Advance bank card payment or credit card guarantee may be required for the reservation, depending on the chosen date, room and price.
Arrival, opening hours The earliest arrival time is 14:00, the latest time to leave the rooms is 12:00. The personnel is at your service in Filipino and English languages.
MICROTEL MANILA MALL OF ASIA Manila rooms Rooms
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phone view phone(214) 365-9007 fax view fax(214) 365-9029 Address Campbell Centre Tower 1
8350 North Central Expressway, Suite 1200
Dallas, Texas 75206
United States
8350 North Central Expressway, Suite 1200
Dallas, Texas 75206
United States
|Areas of Practice
|1) Family Law, 2) Collaborative Law, 3) Tax Controversy, 4) Estate Planning and 5) Probate
|Admitted Year
|Southern Methodist University (B.A., with high hon
|Most recent firm
|Edwin W. Davis
A. Harrison Barnes is a well-known attorney throughout the United States. As a member of the Malibu community, Harrison is committed to serving the needs of Malibu residents and businesses in legal matters.
Barton W.S. Bassett is the leader of Morgan Lewis's Tax Practice. Mr. Bassett's practice focuses on international tax planning for both the outbound operations of U.S. multinationals and the inbound operations of foreign multinationals.