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Upregulated expression of brain enzymatic markers of arachidonic and docosahexaenoic acid metabolism in a rat model of the metabolic syndrome
Neurobiology of disease
In animal models, the metabolic syndrome elicits a cerebral response characterized by altered phospholipid and unesterified fatty acid concentrations and increases in pro-apoptotic inflammatory mediators that may cause synaptic loss and cognitive impairment. We hypothesized that these changes are associated with phospholipase (PLA2) enzymes that regulate arachidonic (AA, 20:4n-6) and docosahexaenoic (DHA, 22:6n-6) acid metabolism, major polyunsaturated fatty acids in brain. Male Wistar rats were fed a control or high-sucrose diet for 8 weeks. Brains were assayed for markers of AA metabolism (calcium-dependent cytosolic cPLA2 IVA and cyclooxygenases), DHA metabolism (calcium-independent iPLA2 VIA and lipoxygenases), brain-derived neurotrophic factor (BDNF), and synaptic integrity (drebrin and synaptophysin). Lipid concentrations were measured in brains subjected to high-energy microwave fixation.
The high-sucrose compared with control diet induced insulin resistance, and increased phosphorylated-cPLA2 protein, cPLA2 and iPLA2 activity and 12-lipoxygenase mRNA, but decreased BDNF mRNA and protein, and drebrin mRNA. The concentration of several n-6 fatty acids in ethanolamine glycerophospholipids and lysophosphatidylcholine was increased, as was unesterified AA concentration. Eicosanoid concentrations (prostaglandin E2, thromboxane B2 and leukotriene B4) did not change.
These findings show upregulated brain AA and DHA metabolism and reduced BDNF and drebrin, but no changes in eicosanoids, in an animal model of the metabolic syndrome. These changes might contribute to altered synaptic plasticity and cognitive impairment in rats and humans with the metabolic syndrome.
The metabolic syndrome is a clinical disorder characterized by obesity, hypertension, dyslipidemia, glucose intolerance and peripheral inflammation
The brain is highly enriched with the polyunsaturated fatty acids (PUFAs), arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3)
Brain lipid metabolism is altered in the metabolic syndrome. In a rat model of intracerebroventricular streptozotocin-induced brain insulin resistance and hypoglycemia, cerebral cortex concentrations of ethanolamine glycerophospholipid (EtnGpl) and phosphatidylserine (PtdSer) were decreased, while concentrations of unesterified palmitate, stearate and AA were increased, suggesting increased PLA2-mediated membrane degradation
Unesterified AA can be converted to pro-inflammatory and pro-apoptotic secondary mediators, such as prostaglandin E2 (PGE2), thromboxane B2 (TXB2) 82 and leukotriene B4 (LXB4),
In view of the reported changes in brain concentrations of phospholipids and PUFAs, and of neuronal loss in animal models of the metabolic syndrome
To test this hypothesis, we induced early-stage metabolic syndrome by feeding rats a high-sucrose diet for 8 weeks. In this model, feeding a high-sucrose diet induces time-dependent changes in insulin-resistance and in other markers of the metabolic syndrome after 8 weeks
Weight gain and food intake
Figure 1
(A) Body weight and (B) food intake over time in rats fed a control or high- sucrose diet
(A) Body weight and (B) food intake over time in rats fed a control or high- sucrose diet. Data are means ± SD (n = 6). Two-way repeated measures analysis of variance revealed a significant effect of time only on body weight gain and food intake.
Oral glucose tolerance test
Rats fed the high-sucrose diet showed evidence of impaired glucose metabolism, measured by an oral glucose tolerance test at 4 and 8 weeks. Two-way repeated measures analysis of variance showed a significant main effect of diet and time on whole blood glucose concentrations at 4 (Figure
Figure 2
Oral glucose tolerance test in rats fed a control or high-sucrose diet.
Oral glucose tolerance test in rats fed a control or high-sucrose diet. Blood glucose concentrations were measured by a glucometer after a 10 h fast at 0 and 15, 30, 34, 60, 90 and 120 min following gavage with 5g/kg of an oral glucose preload at (A) 4 weeks and (B) 8 weeks of treatment. Two-way repeated measures analysis of variance showed a significant main effect of diet and time on blood glucose concentrations at 4 and 8 weeks.
ß-hydroxybutyrate in whole blood
Fasting ß-hydroxybutyrate concentration in whole blood, a marker of ketosis, was measured at 4 and 8 weeks, before starting the oral glucose tolerance test (Table
Plasma insulin, glucose and triglyceride concentrations
Rats on the high-sucrose diet showed insulin resistance and hypertriglyceridemia at 8 but not 4 weeks (Table
cPLA2 mRNA and protein
mRNA and protein levels of brain cPLA2 IVA did not differ significantly between rats fed the high sucrose and the control diet for 8 weeks (Figure
Figure 3
mRNA, protein and activity of cPLA2 and phosphorylated (phospho)-cPLA2 protein in brain of rats fed the control or high-sucrose diet for 8 weeks.
mRNA, protein and activity of cPLA2and phosphorylated (phospho)-cPLA2protein in brain of rats fed the control or high-sucrose diet for 8 weeks.A) cPLA2 (IVA) mRNA, B) cPLA2 (IVA) protein, C) phospho- cPLA2 (IVA) protein and D) cPLA2 activity. Data are expressed as the relative level of the cPLA2 normalized to the endogenous control (β-globulin) using the ΔΔ
iPLA2 and sPLA2 mRNA, protein and activity
iPLA2 VIA and sPLA2 IIA mRNA and protein did not differ significantly between rats fed the high sucrose and the control diet for 8 weeks (Figure
Figure 4
Levels of A) PGE2, B) LTB4, and C) TXB2 in brain of rats fed a control or high-sucrose diet for 8 weeks
mRNA, protein and activity of brain iPLA2and sPLA2in rats fed the control or high-sucrose diet for 8 weeks. iPLA2 (VIA) A) mRNA, B) protein and C) activity; sPLA2 (IIA) E) mRNA, F) protein and G) activity. Data are expressed as the relative level of the iPLA2 and sPLA2 normalized to the endogenous control (β-globulin) using the ΔΔ
PGE2, TXB2 and LTB4 concentrations
There was no significant difference in PGE2, LTB4 or TXB2 concentration between the two groups (Figure
Figure 5
Levels of A) PGE2, B) LTB4, and C) TXB2 in brain of rats fed a control or high-sucrose diet for 8 weeks
Levels of A) PGE2, B) LTB4, and C) TXB2in brain of rats fed a control or high-sucrose diet for 8 weeks. PGE2, LTB4, and TXB2 were extracted according to the method of Radin
GFAP, TNF-α, COX and LOX mRNA
There was no significant change in GFAP or TNF-α mRNA (data not shown). mRNA levels of COX-1 and COX-2 also were not affected by the high-sucrose diet (data not shown), nor was 5- or 15-LOX mRNA changed significantly. Brain 12-LOX mRNA was increased significantly (control, 1.00 ± 0.07; high-sucrose, 1.22 ± 0.05; p < 0.05 by unpaired t-test).
mRNA and protein levels of BDNF and synaptic markers
Compared with control diet, the high-sucrose diet decreased significantly mean protein and mRNA levels of BDNF (Figure
Figure 6
Brain concentrations of unesterified AA and DHA in rats fed a control or high-sucrose diet for 8 weeks
mRNA and protein levels of BDNF and synaptic markers in brain of rats fed a control or high-sucrose diet for 8 weeks.A) BDNF mRNA, B) BDNF protein, C) synaptophysin mRNA, D) synaptophysin protein, E) drebrin mRNA and F) drebrin protein. Data are expressed as relative level of BDNF, synaptophysin and drebrin normalized to endogenous control (β-globulin) using the ΔΔ
Brain fatty acid concentrations
There were few significant differences in brain esterified fatty concentrations (data not shown): a 12-16% increase in AA (6262 ± 459 nmol/g brain wet wt, control, 7234 ± 468 nmol/g wet wt, sucrose) and adrenate (22:4n-6; 3321 ± 275 nmol/g wet wt, control, 3738 ± 158 nmol/g wet wt, sucrose) in EtnGpl, and a 29% increase in dihomo-γ-linolenic acid (20:3n-6; 7 ± 1 nmol/g wt wet, control, 9 ± 1 nmol/g wt wet, sucrose) in lysoPC in rats on the high-sucrose compared to control diet (p < 0.05). For unesterified fatty acids, one sample from the high-sucrose group was excluded from the analysis because its unesterified AA concentration was 3-fold higher than the mean, which suggests ischemia caused by incomplete microwave-fixation
Figure 7
Brain concentrations of unesterified AA and DHA in rats fed a control or high-sucrose diet for 8 weeks
Brain concentrations of unesterified AA and DHA in rats fed a control or high-sucrose diet for 8 weeks. Values are mean ± SD (n = 8 for both groups). *p < 0.05 by unpaired
Rats fed the high-sucrose diet (60% sucrose) for 8 weeks did not show obesity or increased food intake, but developed hypertriglyceridemia and insulin resistance, two components of the metabolic syndrome, as reported
The upregulation of brain cPLA2 and iPLA2 enzyme activities (Figure
The released fatty acids may be alternative energy substrates to glucose for brain metabolism, due to cerebral hypoglycemia caused by insulin-resistance. This is consistent with evidence of increased brain activity of carnitine palmitoyltransferase (which regulates fatty acid entry from the acyl-CoA pool into mitochondria for later β-oxidation) in an animal model of the metabolic syndrome
Brain cPLA2 activity and phospho-cPLA2 protein, a marker of activated cPLA2
iPLA2 is insensitive to extracellular calcium influx into the neuron
Concentrations of pro-inflammatory eicosanoids (PGE2, TXB2 and LTB4) did not differ between the groups (Figure
Whole brain BDNF mRNA and protein levels were reduced in the high-sucrose group (Figure
Contrary to reports using other models involving central insulin resistance
In summary, brain enzymatic markers of AA and DHA metabolism were increased in a rat model of early-stage metabolic syndrome, in association with reduced BDNF mRNA and protein, and drebrin mRNA. Increases in cPLA2 and iPLA2 activities support the notion of phospholipase-mediated neurodegeneration
In the future, an upregulation in brain AA and DHA metabolism associated with the metabolic syndrome might be imaged in humans with positron-emitting tomography using radiolabeled AA or DHA
The protocol was approved by the Animal Care and Use Committee of the
Brain lipids and eicosanoids (PGE2, TXB2 and LTB4) were measured in the remaining animals (n = 6 per roup) that had undergone a catheter implantation surgery followed by a 2-h infusion protocol of [D5-α-linolenic acid (17, 17, 18, 18, 18-D5) and [U-13C]-linoleic acid (Spectra Stable Isotopes, Columbia, MD, USA) to assess liver PUFA kinetics (Taha et al., unpublished). After the 2 h infusion, the rats were lightly anesthetized with sodium pentobarbital (50 mg/kg; Abbott Laboratories, Chicago, IL, USA) and subjected to head-focused microwave irradiation stop brain lipid metabolism (5.5 kW, 4.8 s; Cober Electronics, Stamford, CT, USA)
The control and high sucrose diets were obtained from Dyets Inc. (Bethlehem, PA, USA), and were based on the AIN-93G formulation
Plasma glucose, insulin, and triglyceride measurement
Blood was collected at 4 and 8 weeks from the tail vein after an overnight 10 h fast (n = 8 per group), and plasma glucose, insulin and triglyceride concentrations were determined with a glucose oxidase kit (Sigma), an Insulin ELISA kit (Alpco Diagnostics, Salem, NH, USA) and a triglyceride kit (Sigma), respectively. The insulin and glucose concentrations were used to calculate the 'homeostasis model assessment' (HOMA) index of insulin resistance, by multiplying glucose (mmol/L) and insulin (mU/L) concentrations, and dividing by 22.5
Oral glucose tolerance test and β-hydroxybutyrate measurement
An oral glucose tolerance test
Brain total fatty acid concentration
Brain total lipids were extracted by the Folch method
Preparation of cytoplasmic and membrane extracts
Cytoplasmic and membrane extracts for Western blots were prepared using a compartmental protein extraction kit according to the manufacturer's instructions (Millipore, Temecula, CA, USA). Protein concentrations of cytoplasmic and membrane extracts were determined using Bio-Rad Protein Reagent (Bio-Rad, Hercules, CA, USA).
Western Blot Analysis
Proteins from cytoplasmic (50 μg) and membrane extracts (50 μg) were separated on 4-20% SDS-polyacrylamide gels (PAGE) (Bio-Rad). Following SDS-PAGE, the proteins were electrophoretically transferred to a nitrocellulose membrane. Protein blots were incubated overnight at 4°C in Tris-buffered saline (TBS) buffer, containing 5% nonfat dried milk and 0.1% Tween-20, with specific primary antibodies (1:1000 dilution) for the group IVA cPLA2, phospho-cPLA2, group IIA secretory sPLA2, group VIA iPLA2 (Santa Cruz Biotech, Santa Cruz, CA), drebrin, synaptophysin (Cell Signaling, Beverly, MA), and β-actin (Sigma-Aldrich, St. Louis, MO). Protein blots were incubated with appropriate HRP-conjugated secondary antibodies (Cell Signaling) and visualized using a chemiluminescence reaction (Amersham, Piscataway, NJ) on X-ray film (XAR-5, Kodak, Rochester, NY). Optical densities of immunoblot bands were measured using Alpha Innotech Software (Alpha Innotech, San Leandro, CA) and were normalized to β-actin to correct for unequal loading. All experiments were carried out three times with 8 independent samples per group. Values are expressed as percent of control.
BDNF protein levels
BDNF protein levels were measured in brain cytosolic extracts using an ELISA kit. according to the manufacturer's instructions (Millipore, Temecula, CA). Values are expressed in pmol/mg protein.
Total RNA isolation and real time RT-PCR
Total RNA was prepared from brain using commercial kits (RNeasy Lipid Tissue Kit; Qiagen, Valencia, CA). cDNA was prepared from total RNA using a high-capacity cDNA Archive Kit (Applied Biosystems, Foster City, CA). mRNA levels were measured by real time quantitative RT-PCR, using the ABI PRISM 7000 sequence detection system (Applied Biosystems). For specific primers and probes for target genes, TaqManR gene expression assays, purchased from Applied Biosystems, consisted of a 20X mix of unlabeled PCR primers and Taqman minor groove binder probe (FAM dye-labeled). The fold change in gene expression was determined using the ΔΔCT method
Phospholipase A2 activities
Sample preparation
Brain tissue was homogenized with 3 vol of homogenization buffer (10 mM HEPES, pH 7.5, containing 1 mM EDTA, 0.34 μM sucrose and protease inhibitor cocktail (Roche, Indianapolis, IN)), using a glass homogenizer. The homogenized sample was centrifuged at 100,000 g for 1 h at 4°C, and the supernatant was used for all PLA2 enzyme activity analyses. Supernatants were kept at −80°C until use. The protein concentration was analyzed by the Bradford assay (Bio-Rad)
Enzyme assay with radioisotope method
The final incubation volume was 0.5 ml. To measure cPLA2 activity, the cytosolic fraction (0.3 mg protein in one assay, ~50 μl) was mixed with 100 m
Substrate preparation for radioisotope method
Substrates for the iPLA2 and cPLA2 activity analyses described above were prepared daily. Appropriate amounts of cold and radiolabeled phospholipids were added to an appropriate amount of Triton X-100, and the mixture was dried with nitrogen gas. Water was added to the residues to give a 10x lipid mixture (1 mM phospholipid, 1,000,000 dpm, and 4 mM Triton X-100), which was mixed vigorously.
Enzyme assay
The cytosolic fraction (0.3 mg in one assay) was mixed with the assay mixture (total volume of 450 μl), and 50 μl substrate mixture was added to start the enzyme reaction. The reaction mixture was incubated for 30 min at 40°C, and then 2.5 ml of Dole reagent (2-propanol, heptane: 0.5M H2SO4, 400:100:20, vol/vol/vol) was added to stop the reaction. One and a half ml of heptane and 1.5 ml H2O were added to the mixture, followed by vortexing and centrifugation at 3000 rpm for 5 minutes. The upper phase (about 2 ml) was transferred to a tube containing 200 mg of silicic acid (200–400 mesh), followed by vortexing and centrifugation. The supernatant (1.5 ml) was transferred to a scintillation vial, and scintillation cocktail was added (Ready Safe™ plus 1% glacial acetic acid). Radioactivity of the released unesterified fatty acid from the phospholipid substrate was counted on a liquid scintillation counter (2200CA, TRI-CARB®, Packard Instruments, Meriden, CT, USA). iPLA2 and cPLA2 activities were expressed as the release rate of fatty acid from phospholipids.
sPLA2 activity
sPLA2 activity was measured using an appropriate assay kit (Cayman, Ann Arbor, MI, USA), according to the manufacturer's instructions.
PGE2, TXB2, and LTB4 concentration
PGE2, TXB2, and LTB4 were extracted according to the method of Radin
Data and statistics
Data are presented as means ± SD (n = 8 for each group). A two-way repeated measured analysis of variance (ANOVA) was used to test for effects of time and treatment on body weight, food intake, and insulin, glucose, β-hydroxybutyrate and triglyceride concentrations, and the response to an oral glucose preload performed at 4 and 8 weeks. An unpaired Student's
AA: arachidonic acid; ANOVA: analysis of variance; BDNF: brain derived neurotrophic factor; cPLA2: cytosolic phospholipase A2; DHA: docosahexaenoic acid; EtnGpl: ethanolamine glycerophospholipids; HOMA: homeostasis model assessment; iPLA2: calcium-independent PLA2; i.c.v.: intracerebroventricular; LXB4: leukotriene B4; lysoPC: lysophosphatidylcholine; PAGE: polyacrylamide gels; PGE2: prostaglandin E2; PtdSer: phosphatidylserine; sPLA2: secretory PLA2; TXB2: thromboxane B2.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
AYT, FG and SIR conceived and designed the study. AYT and FG carried out the animal experiments. HWK, AYT, YC, FG and IR were involved in the analysis. AYT, HWK and SIR were involved in writing and editing the manuscript. All authors read and approved the final manuscript.
This research was supported entirely by the Intramural Research Program of the National Institute on Aging, NIH.
The metabolic syndrome–a new worldwide definition
The metabolic syndrome
Mainstreaming the metabolic syndrome: a definitive definition
Depression: an important comorbidity with metabolic syndrome in a general population
Metabolic syndrome in bipolar disorder: findings from the Bipolar Disorder Center for Pennsylvanians
Mental slowness and executive dysfunctions in patients with metabolic syndrome
The metabolic syndrome is associated with decelerated cognitive decline in the oldest old
Association of metabolic syndrome with Alzheimer disease: a population-based study
Memory impairment in obese Zucker rats: an investigation of cognitive function in an animal model of insulin resistance and obesity
Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome
Streptozotocin increases free fatty acids and decreases phospholipids in rat brain
Insulin-resistant brain state (IRBS) changes membrane composition of fatty acids in temporal and entorhinal brain cortices of rats: relevance to sporadic Alzheimer's disease?
Nutritional and functional requirements for essential fatty acids
Essential fatty acids in infant nutrition: lessons and limitations from animal studies in relation to studies on infant fatty acid requirements
Essential fatty acids in visual and brain development
Kainic acid-induced excitotoxicity in neurons and glial cells
Rat brain arachidonic acid metabolism is increased by a 6-day intracerebral ventricular infusion of bacterial lipopolysaccharide
Chronic NMDA administration increases neuroinflammatory markers in rat frontal cortex: cross-talk between excitotoxicity and neuroinflammation
Imaging brain signal transduction and metabolism via arachidonic and docosahexaenoic acid in animals and humans
Phospholipase A2 structure/function, mechanism, and signaling
A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP
Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders
The emerging role of group VI calcium-independent phospholipase A2 in releasing docosahexaenoic acid from brain phospholipids
Docosahexaenoic acid and arachidonic acid release in rat brain astrocytes is mediated by two separate isoforms of phospholipase A2 and is differently regulated by cyclic AMP and Ca2+
Group-specific assays that distinguish between the four major types of mammalian phospholipase A2
Neuroprotectin D1 (NPD1): a DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress
Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression
Arachidonic acid and the brain
Novel eicosanoid and docosanoid mediators: resolvins, docosatrienes, and neuroprotectins
Unorthodox routes to prostanoid formation: new twists in cyclooxygenase-initiated pathways
Imaging neuroinflammation in Alzheimer's disease with radiolabeled arachidonic acid and PET
Altered expression of apoptotic factors and synaptic markers in postmortem brain from bipolar disorder patients
Increased excitotoxicity and neuroinflammatory markers in postmortem frontal cortex from bipolar disorder patients
Lipid metabolism and membrane composition are altered in the brains of type II diabetic mice
Relationship between plasma and hippocampal lipid peroxidation in obese and hypertensive SHR/NDmcr-cp rats
Activation of group VI phospholipase A2 isoforms in cardiac endothelial cells
Endothelial cell prostaglandin I(2) and platelet-activating factor production are markedly attenuated in the calcium-independent phospholipase A(2)beta knockout mouse
Imaging upregulated brain arachidonic acid metabolism in HIV-1 transgenic rats
Involvement of PGE2 and PGDH but not COX-2 in thrombin-induced cortical neuron apoptosis
A BDNF autocrine loop in adult sensory neurons prevents cell death
Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats
A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning
Alzheimer-like changes in rat models of spontaneous diabetes
The effects of long-term honey, sucrose or sugar-free diets on memory and anxiety in rats
Genetic ablation of calcium-independent phospholipase A2gamma prevents obesity and insulin resistance during high fat feeding by mitochondrial uncoupling and increased adipocyte fatty acid oxidation
Lysophosphatidylcholine as an effector of fatty acid-induced insulin resistance
Dose-dependent changes in neuroinflammatory and arachidonic acid cascade markers with synaptic marker loss in rat lipopolysaccharide infusion model of neuroinflammation
Chronic NMDA administration to rats increases brain pro-apoptotic factors while decreasing anti-Apoptotic factors and causes cell death
Chronic NMDA administration to rats up-regulates frontal cortex cytosolic phospholipase A2 and its transcription factor, activator protein-2
Changes in insulin action, triglycerides, and lipid composition during sucrose feeding in rats
Quantity of sucrose alters the tissue pattern and time course of insulin resistance in young rats
Muscle lipid metabolism and insulin secretion are altered in insulin-resistant rats fed a high sucrose diet
High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour
Loss of proteins regulating synaptic plasticity in normal aging of the human brain and in Alzheimer disease
Neuroinflammation and synaptic loss
Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man
cPLA2 is phosphorylated and activated by MAP kinase
Protein kinase C-dependent activation of cytosolic phospholipase A2 and mitogen-activated protein kinase by alpha 1-adrenergic receptors in Madin-Darby canine kidney cells
Relation between free fatty acid and acyl-CoA concentrations in rat brain following decapitation
Increased brain fatty acid uptake in metabolic syndrome
Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet
Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography
Extracellular-derived calcium does not initiate in vivo neurotransmission involving docosahexaenoic acid
Central insulin resistance and synaptic dysfunction in intracerebroventricular-streptozotocin injected rodents
Metabolic syndrome as a risk factor for neurological disorders
Regulation of intracellular calcium release channel function by arachidonic acid and leukotriene B4
Integrative miRNA-mRNA Profiling of Adipose Tissue Unravels Transcriptional Circuits Induced by Sleep Fragmentation
Circuitry of mRNA regulation
Epigenetics, bioenergetics, and microRNA coordinate gene-specific reprogramming during acute systemic inflammation
Nicotine attenuates arachidonic acid-induced apoptosis of spinal cord neurons by preventing depletion of neurotrophic factors
The Metabolic Syndrome in Patients With Severe Mental Illnesses
Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production
C75 is converted to C75-CoA in the hypothalamus, where it inhibits carnitine palmitoyltransferase 1 and decreases food intake and body weight
Formation of eicosanoids, E2/D2 isoprostanes, and docosanoids following decapitation-induced ischemia, measured in high-energy-microwaved rat brain
AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet
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High multivitamin intake by Wistar rats during pregnancy results in increased food intake and components of the metabolic syndrome in male offspring
A simple method for the isolation and purification of total lipides from animal tissues
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Lincoln Action Center
City of Lincoln, Nebraska
- November 4, 2013
( 24)
The A.C.T.I.O.N. Center (Acting with Citizens To Improve Our Neighborhoods) can be used to report issues within the city limits. Issues such as graffiti, junk cars, potholes and streetlights out. Submissions are routed directly to the responsible department(s). Citizens can check the status of their submission and review the photo and location if this information has been provided.
Great app! Always nice for a simple and fast way to report issues!
Working well Thanks for the feedback!
Simple and quick way to communicate with your local government.
Doesn't Work Every time I try to take a photo, it freezes and then crashes and doesn't work anymore. It says its compatible with my phone but obviously isn't with android 2.2.
Needs a few more incident types Quite a useful app for reporting things like potholes and burned out traffic lights. They could add a few incident/problem types, including "abandoned bicycle".
It wouldnt let me see the status of my complaint, but i saw the problem being fixed less than 48 hours later, so it still worked. :-)
What's New
The latest version now includes a history of submissions made from your device. You can review a list of past submissions plus see detailed information on responses sent back from city departments. Also several bugs have been taken care of in this release.

subset: commoncrawl


text:
View full video at Cody Cummings
Well here it is, Next Door Entertainment has been doing their standard tease over this "new" Cody Cummings video. In their press package they have a graphic that says, "Guess Who's Back ?" as if the question mark gives them plausible deniability. Did you think we meant Cody was coming back? Really? You thought that? How did that question mark get in there? Whatever. Wanna know if he's back? Check out his official Cody Cummings Twitter feed @kvlar2020 where he says, "No. I'm not back." I don't care either way. I always thought Cummings was handsome, I love his big dick, and this video really showcasing the dude's low-hanging balls.


text: STILLWATER, Okla., Jan. 20, 2011 (GLOBE NEWSWIRE) -- Southwest Bancorp, Inc. (Nasdaq:OKSB) (Nasdaq:OKSBP), ("Southwest"), today reported 2010 annual net income available to common shareholders of $12.8 million compared to $8.8 million for the year ended December 31, 2009, an increase of 45%. On a per share basis, 2010 annual net income available to common shareholders was $0.71 per diluted share compared to $0.60 per diluted share for the year 2009, an increase of 18%. Per share earnings reflect additional shares issued in our $54.3 million second quarter 2010 common stock offering. Total net income for 2010 was $17.0 million compared to $13.0 million for 2009, an increase of 31%. Net income available to common shareholders for the fourth quarter 2010 was $3.3 million, or $0.17 per diluted share, compared to $2.8 million, or $0.15 per diluted share, for the third quarter of 2010 and $2.5 million, or $0.17 per diluted share, for the fourth quarter of 2009. Rick Green, Southwest Bancorp's President and Chief Executive Officer, stated, "The 2010 results put us in a position to gain momentum in 2011. Earnings for the fourth quarter were driven by stable net interest income, controlled noninterest expense, and a decrease in the required provision for loan losses. The Board of Directors and management are dedicated to the resolution of problem credits, the maintenance of capital and liquidity, stability in net interest income, and control of operating expenses. We continue to manage our loan portfolio with our ongoing, disciplined workout process focused on addressing the challenges of the commercial real estate construction and commercial mortgage sectors. Noncovered nonperforming assets at year-end were down $26.6 million, or 16%, from September 30, 2010. Our allowance for loan losses to noncovered nonperforming loans ratio was 61% at year-end 2010, compared with 53% at September 30, 2010 and 59% at year-end 2009.


text:
Midwives East Timor Australia is a non-profit organization that aims to support midwives in East Timor with education, resources and equipment so that maternal and neonatal outcomes can be improved in East Timor. Each year, we have visited East Timor since 2005, and the length of the visit has been from 1-3 months. We also partner with non-government organisations that are working with the Timorese Ministry of Health to capacity-build the Timorese Midwives and reduce both the Maternal & Neonatal Mortality rates.
1:45 Timorese Women die from pregnancy related complications – many of them preventable. (Timor-Leste Demographic and Health Survey 2009-10) This is a drop from 1:35 prior to this.
In 2010 we provided a 4WD Maternity Ambulance to Remexio in Aileu District so that pregnant and labouring women can have a trained midwife at their birth. We continue to fund the salary for the driver, fuel and maintenance for the Maternity Ambulance.
We have provided many other resources like dopplers to listen to the fetal heart; blood pressure machines; an ultrasound machine for use in pregnancy and manikins for use with teaching midwives.


text:
Flowers & Thoughts
de John Pedersen
Acerca del libro
A collection of intimate flower images along with insightful thoughts or comments.
Características y detalles
- Categoría Arte y fotografía
Apaisado estándar, 25×20 cm
30 Páginas
- Fecha de publicación nov. 13, 2013
- Idioma English
- Etiquetas flower, dahlia, tulip, nature, pretty, insightful, zen
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Acerca del creador
John Pedersen
Portland Oregon
A native Oregonian, John is located in Portland Oregon, which is centrally located to the many beautiful areas of the Pacific Northwest. The Columbia River Gorge and it's many waterfalls, the rugged Pacific Ocean coastline, the lush Willamette Valley, to the snow capped Cascade Mountains, the Pacific Northwest offers limitless photographic opportunities. John frequently travels outside the Northwest for his photography as well, covering many areas along the West Coast, the Southwest, as well as overseas locations.
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41 properties in Estepona
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Estepona overviewEstepona is a relaxing place distinct for its beaches and oceanfront, and known for its marina and spas. You'll find extensive bar and dining options. Soak up some sunshine at Estepona Beach and Rada Beach. There's plenty to explore, including local sights like Nuestra Senora de Los Remedios and El Paraíso. If you're looking for a family-friendly getaway, Estepona is for you.
Where to stay in EsteponaWhether you're planning to stay for a night or for the week, the area around Estepona has accommodations to fit every need. Search for hotels in Estepona with Hotels.com by checking our online map. Our maps display the areas and neighborhoods around all Estepona hotels so you can see how close you are from landmarks and attractions, and then refine your search within the larger area. The best Estepona hotel deals are here with our lowest price guarantee.
How to get to EsteponaFly in to Gibraltar (GIB), 21.9 mi (35.3 km) from downtown Estepona. Malaga (AGP) is the next closest major airport, 40.2 mi (64.7 km) away.
What to see around EsteponaOutdoorsy fun is on hand such as golf, strolling the marina, and sporting events, along with attractions such as:
- • El Paraíso
- • Estepona Golf
- • Finca Cortesin Golf Club
- • Casares Costa Golf
- • Dona Julia Golf Club
- • Museum of Palaeontology
- • Ralli Museum
- • Museo del Grabado
- • Grabado Espanol Museum
- • Museo del Bonsai
- • Estepona Beach
- • Rada Beach
- • Cristo Beach
- • Saladillo Beach
- • Punta de Chullera Beach
- • Nuestra Senora de Los Remedios
- • Plaza de Toros
- • Esepona Exhibition and Congress Center
- • Purobeach Marbella
- • Selwo Adventure Park
When to visit EsteponaCurious about when's the best time to visit? Here are the seasonal norms to help with your planning:
Seasonal temperature averages
- January-March: 67°F day, 52°F night
- April-June: 80°F day, 55°F night
- July-September: 83°F day, 65°F night
- October-December: 75°F day, 53°F night
- January-March: 0.24 inches
- April-June: 0.20 inches
- July-September: 0.12 inches
- October-December: 0.20 inches


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JotForm form is not showing when used with WP JotForm Feedback Button PluginAsked by Jude on March 30, 2015 at 05:41 AM
Hi i have a form on JotForm and am using the Wordpress JotForm Feedback Button plugin on Wordpress 4.1.1. I can now see the Feedback Button appear on my website but when you click on it, a blank window opens up and the JotForm form does not show itself. How do i solve this issue? Thanks.
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text: Sorting type: Most visited Most visited Alphabetical | Members of the Lawrence family. Pages in category "Lawrence" Topanga Lawrence Rhiannon Lawrence Jedidiah Lawrence Nebula Lawrence " to be added Children: Rhiannon Lawrence (daughter) and Prudence Curtis (daughter) Rosie McGee Retrieved from "http://boymeetsworld.wikia.com/wiki/Category:Lawrence?oldid=9400" Ad blocker interference detected! Wikia is a free-to-use site that makes money from advertising. We have a modified experience for viewers using ad blockers Wikia is not accessible if you've made further modifications. Remove the custom ad blocker rule(s) and the page will load as expected. Categories: Characters Add category Cancel Save


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Come Meet Some Badass Dogs At NYC Pet On Driggs !
If You're Looking To Adopt And Haven't Already, We Always Suggest Submitting An Application In Advance To Get The Process Rolling. We Do NOT Do Same-Day Applications, And Some Of These Dogs Already Have Applications In Progress. We Do, However, Work With All Approved Applicants To Find The Most Badass Match!
February 25Adoption Event at NYC Pets on Driggs- Feb 25th


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The credit card charge TAXI FARE AUCKLAND was first recorded on February 25, 2014. It has not been reported by any users.
Do you have any information regarding this credit card charge? If so, please share below! Help others avoid a potential confusion by commenting!
No users have reported this charge as suspicious.
not sure where the charge is coming from? tfl taxi fare auckland. big amount, and i did not catch a taxi on the day it charged me.


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Keep higher ed accessible and affordable for all Washington students
Six out of 10 Washington high school students currently go directly to a two- or four-year college following high school graduation.
Research tells us that without some form of postsecondary education, today's students will find it difficult to earn a living wage. By 2018, two-thirds of the jobs in Washington will require a college degree or career credential.
Yet in the last decade, the cost of going to college in Washington has sky-rocketed. The average price of tuition has gone from 5 percent to 11 percent of median family income. Increasing tuition costs require more students to take out larger student loans to cover the cost of their college degrees. This financial burden can prevent many low- and middle-income students from pursuing higher education and create more barriers to college completion. The continued increase in the number of students needing to take out student loans means that college is becoming more unaffordable for Washington families.
"If changes are not made, we face the serious risk to our economy and democracy of creating two Washingtons — not divided by the Cascades or political parties — but based on educational achievement," according to a recent report by the Washington Student Achievement Council.
The League of Education Voters is committed to keeping higher education accessible and affordable for all Washington students. During this legislative session, we are working with our partners to protect student aid and expand access to quality post-secondary learning opportunities.
Keeping college affordable can take many different forms in our state, including harnessing rising tuition and ensuring that there are supports in place to help students and families pay for school.
Washington's GET (Guaranteed Education Tuition) plan is the state's only college savings tool and one of the only state programs aimed at helping middle class families send their kids to college. It must be preserved. Mend it perhaps, but don't end it.
For low-income students, Washington's College Bound Program covers tuition and a modest book allowance for students who attend a Washington two- or four-year college. Over 88,000 Washington State students have enrolled in the College Bound Scholarship program since its inception in 2007. College Bound must be maintained. It is an important tool to closing the higher ed opportunity gap.
During this legislative session, we must do more – not less — to help our students access high-quality postsecondary opportunities so that they are prepared to meet the requirements of Washington's demanding job market.
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We were unable to get information about libraries that hold this item.
|Account books
|Named Person:
|John Andrews; Benjamin Craggin; William Dudley
|Material Type:
|Manuscript, Internet resource
|Document Type:
|Book, Archival Material, Internet Resource
|All Authors / Contributors:
|Craggin and Andrews.
|OCLC Number:
|6 v. ; folio.
This collection consists of three daybooks and three ledgers (two of which are indexed) which record the sale of general store products in Oxford, Mass., during the 1820s. The first three volumes are for the firm Craggin and Andrews and cover the period 1820 to 1824. Apparently, Dudley replaced Andrews as Craggin's partner in 1823 or 1824, as the remaining three volumes are for the firm Craggin and Dudley and cover the period 1823 to 1827.
User-contributed reviews


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NetID Claim, How do students and university affiliates claim their NetID
The following instructions will explain how new students and university affiliates can claim their NetID
In order to claim your NetID, you will need your UIN and activation code given to you by University Admissions or the Graduate College.
- Undergraduate students: After you have accepted your admission in MyIllini, you can then find your activation code in your admitted student checklist.
- Graduate students: Log in to ApplyYourself to look up your UIN and activation code.
- University Affiliates: Contact the Technology Services Help Desk to obtain information on retrieving your UIN and activation code.
- The website to claim your NetID can be found at https://netidclaim.illinois.edu
- Enter your UIN and activation token in the spaces provided and click "Log In"
- The following screen will display your NetID and begin guiding you through each step to complete the process. Click on "Continue" to proceed.
Graduate and Undergraduate Students University Affiliates
- You will now be asked to set your recovery options in the event that you forget or need to reset your password. Once you have finished entering at least one password recovery option (or have chosen to opt-out), click on "Continue".
- You will now be asked to set your password. As you type your desired password, green check marks will indicate that your password meets the security requirements.
- The next screen will take you to set your University email account. You will be returned back to this page after you have successfully completed setting up your email.
(At this point, University Affiliates will have completed the NetID Claim process and should see the confirmation page, similar to the one shown on Step 11.)
- In order to set up your University (@illinois.edu) email account, make sure any checkboxes are selected before clicking "Continue".
Undergraduate Students Graduate Students
- Undergraduate students will also need to read and accept the terms of service in the yellow box. Once you are finished, you can click on "Go to Step 2 - >"
- Undergraduate students will now be asked how you want your University emails delivered:
- The next screen will confirm your email settings. Click on "Continue with NetID Claim Process" to proceed to the final step.
Undergraduate Students Graduate Students
- The final screen will confirm that you have successfully completed the NetID claim process. You may now click on "Finish and Log Out" to exit the screen.


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Ukrainian President Viktor Yanukovych returned to work on Monday from four days of sick leave after opposition leaders appealed for Western assistance and an injured militant accused of rioting left the country for medical treatment.
The sick leave had sparked a guessing game he was taking himself out of action in preparation to step down or for a crackdown on widespread anti-government protests.
Yanukovych's sick leave was announced on Thursday, with his office saying he had an acute respiratory illness. Some opposition leaders were sceptical about it, however, and thought Yanukovych was disappearing from the limelight in preparation for imposing a state of emergency amid the deepest turmoil in Ukraine since the Orange Revolution in 2004-2005.
Yanukovych faces a crisis with no solution in sight that has dragged on for more than two months and has pitted Russia against Europe and the United States.
Opposition leaders have asked the West, which has so far pledged only verbal support for their cause, to mediate in talks with Yanukovych to prevent "misunderstandings".
They have also requested "real financial aid" after more than two months of protests that have left much of central Kiev looking like a war zone and hobbled an already frail economy.
Speaking to a protest rally of over 60,000 people on Sunday, former economy minister Arseniy Yatsenyuk said Western officials had assured him that funding was on its way. "They are ready to do it," he told the crowd.
Yanukovych's sick leave was announced the morning after the parliament voted to offer amnesty to many of those arrested during protests on the condition that demonstrators vacate some of the buildings they occupy in Kiev and government buildings elsewhere in the country.
The measure was greeted with disdain by protesters, who characterised it as the government essentially taking hostages and then using them to try to negotiate concessions. Kiev's city hall, which protesters have seized, is being used as an operations centre and dormitory key to supporting the extensive protester tent camp on the nearby Independence Square.
During Yanukovych's sick leave, a sense of stasis set in and neither side showed signs of movement. But his return to work could bring new action.
On Tuesday, parliament is expected to consider reforms to the constitution that would reduce some presidential powers and allot them to the prime minister. Yanukovych last week accepted the resignation of Prime Minister Mykola Azarov, but has not appointed a new one.
Activist allowed to leave
Meanwhile, The case of Dmytro Bulatov showed the international resonance of events in Ukraine after European Union and US officials reacted with shock to his account of being kidnapped and tortured.
Bowing to pressure, a Kiev court on Sunday allowed the 35-year-old to leave the country for treatment in Lithuania and he was quickly taken by ambulance to the airport.
The Baltic News Service reported that Bulatov arrived in Vilnius, Lithuania's capital, shortly after midnight on Sunday, and was immediately rushed to a hospital. Lithuania's Foreign Ministry did not immediately answer phone calls and e-mails.
Bulatov said he was "crucified" by his unidentified captors before being released in a forest last week and images of his bloodied face were broadcast around the world.
Ukrainian authorities have cast doubt on the veracity of his story and Foreign Minister Leonid Kozhara dismissed his injuries as "a scratch" before retracting the comment.
The case has been highlighted by the opposition as an example of what it says is a "secret repression" against protesters in which pro-government vigilantes have been employed.
On Sunday, top opposition figures spoke to the rally to urge supporters to push forward with their demands. Arseniy Yatsenyuk, one of the protest leaders, emphasised the importance of obtaining the release of all people arrested during the protests.
"We must free all," Yatsenyuk said, adding that there were 116 people being held. "Freedom to every hero."
Another protest leader, former heavyweight boxing champion Vitaly Klitschko, showed that opposition hopes for cooperation from abroad are high.
"The crisis will end at last when under the auspices of the international community we will hold new elections that will stop the regime of Yanukovych," he said.
Three-month conflict
The protests touched off in November when Yanukovych turned his back on a partnership deal with the EU under pressure from Moscow – Ukraine's former master. They have since expanded beyond Kiev into traditionally pro-opposition western Ukraine but also into central and eastern parts normally considered a heartland for Yanukovych.
Four people – two protesters and two policemen – were killed at the height of the clashes last month and more than 500 people have been injured, according to official figures.
The movement started out as a campaign for more European integration for the former Soviet republic but now reflects broader social disillusionment with Yanukovych's rule.
Yanukovych has offered the opposition concessions including the dismissal of the prime minister and the entire cabinet as well as the scrapping of draconian anti-protest laws. But protest leaders are calling for the immediate and unconditional release of activists detained during the demonstrations and for Yanukovych to announce early elections.
They also want a constitutional overhaul to take away the sweeping powers that Yanukovych has accumulated during his rule and give more weight to the government and parliament.
Yanukovych supporters, concentrated in the mainly Russian-speaking east, say the president was democratically elected in and should serve out his term until next year.
To prop up Ukraine's economy, Yanukovych also signed up for a US$15 billion bailout from Russia but that is now on hold pending a resolution of the crisis.
Russia has publicly supported Yanukovych, dismissing the protesters as far-right extremists and scathingly condemning foreign interference in Ukraine's internal affairs.
But it is not taking a more active role perhaps to avoid international complications during the Winter Olympics in Sochi where President Vladimir Putin is keen to show off Russia's new-found grandeur.


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|Message view
|« Date » · « Thread »
|« Date » · « Thread »
|Christopher Schultz <ch...@christopherschultz.net>
|Re: Tomcat access log reveals hack attempt: "HEAD /manager/html HTTP/1.0" 404
|Wed, 17 Apr 2013 17:48:33 GMT
-----BEGIN PGP SIGNED MESSAGE----- Hash: SHA256 Mark, On 4/17/13 8:49 AM, Mark H. Wood wrote: > Yes. But someone *does* own the botted computers, and their own > operations are slightly affected. I have wondered if there is > some way to make a bot so intrusive that many more owners will ask > themselves, "why is my computer so slow/weird/whatever? I'd > better get it looked at. Maybe I should install a virus scanner." People *do* do this (notice their computer sucking) but mostly (at least Americans) will just go out and buy another one, assuming that their computer just isn't fast enough to "work well" after owning it for a few years. <soapbox>It's sad that most of us have more computing resources beneath our fingertips than spacecraft do, yet we upgrade every few years because MS Office has gotten fatter. </soapbox> - -chris -----BEGIN PGP SIGNATURE----- Version: GnuPG/MacGPG2 v2.0.17 (Darwin) Comment: GPGTools - http://gpgtools.org Comment: Using GnuPG with Thunderbird - http://www.enigmail.net/ iQIcBAEBCAAGBQJRbuBwAAoJEBzwKT+lPKRY/SsQAK3l3RAxAzhW0fVBLCHlvsm3 KpV8/KztwCwJzoS6ZrsKTvMWCq8PpKsjiGFZNRTjKY60b2UAPwBEq6a5LOti1Jp+ XqTvAJGtUtNsECnO9ztxhQsXT01Ta6Jr5KcuYZTjLgBoPdkPAqKtjrdlD8qG5brz eaSJ60zz2omRJBxn6WackMvoZhp7fivrx5zvR3RfgDX5tolqChJOeiXp9zVg2d53 cUgbCIga7oSul4GmrMYwsQepPnurwQa3ZRywXmzqjQTvEc+K9ITwn0zEC5U4D4Vi CvStqUbXIJf/9q23xy33ExWOkO6eSMP3BLbtQ1IUlOnV11/o6tLrP9o1Nb9c3h1a Zpb1AGqHzY8vJaD4YSybmK8UAUQ/cSbBFsbxWFGFFp53KO7o6oV3Nmr5hxU+y5xR uetvvqs8eqyYO7ktcBui/uIunADz5eJ6eHD3JxQoFQ13lby5kOMYGWMFYdOKXjOT uMyFOGm1G/FeC6TwSSkCQiGmvGCf0k36HYFc+AaUpKcIaG52yyswlIhJnvZO069O BiagSbi04tkL+gQRfyT2x2h7ewTqcAwB1uYoG+kSBeAb5n0AJyFuVYslhnCySrQ2 zGCr/w/lWoImM6myiYtL1LwgP2zwG+Gur9RhWdoATbQgoFXncVT29u4ItUhxAar3 e91tWwraTmrjwhjOBNvo =WlUO -----END PGP SIGNATURE----- --------------------------------------------------------------------- To unsubscribe, e-mail: firstname.lastname@example.com For additional commands, e-mail: firstname.lastname@example.com
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- Healthy Eating
- About Our Products
- Recipes
- Online Ordering
- Our Mission & Values
- Blogs
- Store Departments
16 oz and 64 oz
This is where it all started. While the great folks at Sweet Leaf Tea loves all of their kids equally, we'll give their first recipe its well-deserved spotlight. Actually, this one is our favorite, so please don't tell the others.
Filtered Water, Organic Cane Sugar, Organic Black Tea and Citric Acid


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I stayed three consecutive nights here for business travel in mid-November. Overall the stay was satisfactory, but there is little to rave about this hotel. Here is a list of pros and cons I experienced:
1-The hotel serves a descent breakfast and dinner (M-TH), which is a nice benefit to save some money and time, since there really are no other restaurant options close. The breakfast was average with a couple of hot entree options, while the dinners were okay.
2-The hotel offers a shuttle that delivers you to locations within in area, including the local BART stop. This was nice and allowed me to save money by not renting a car. The shuttle runs in the morning and evening and they were relatively quick to respond when I needed a ride.
3-The view of the harbor is nice if you have a room on the waterfront side of the hotel.
4-The service of the staff was good, with little issues experienced.
5-The hotel offers complimentary internet access and a nice lobby area.
6-Rooms types vary with sizes from studio to two-bedroom to accommodate families. I also found my room to be clean in all areas (except the carpet being somewhat worn).
1-I received a smoking room, which I wasn't excited about. This may have been my error when reserving, I'm not sure. The hotel was full, so when I asked for a room change I was promptly denied. I am surprised that the hotel isn't completely smoke free. I may limit my choices in the future to smoke-free hotels.
2-The location is adequate if you have a car; however, there is nothing in the immediate area. The hotel is very close to the freeway so I imagine access is very easy, but you have to drive to get to any restaurants. I did not rent a car and was relatively pleased with the shuttle/BART system.
3-The room decor is average, with some updating done and some additional updating likely needed. The carpets could use replaced or at least cleaned.
Overall, I felt for a Hilton property this was an average stay. I would stay here again if in the area; however, I would first search for smoke-free hotels to avoid getting a smoking room. The "satellite" building must contain several smoking rooms because the entire first floor hallway smells of smoke. This was my primary complaint and the only reason I would look at other hotels first. I was relatively pleased and felt the value was good for the price. Thanks.
- Reservation Options:
- TripAdvisor is proud to partner with Booking.com, Hilton Hotels Direct, Expedia, Hotels.com, Priceline, Orbitz, Travelocity, Hotwire, HotelQuickly and getaroom.com so you can book your Homewood Suites by Hilton Oakland-Waterfront 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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Mises Wire
Redefine success with other metrics
At least, that is the hope of Sarkozy:
In the 45-minute speech, Sarkozy declared the death of the 35-hour week, suggested that large companies may have to double or triple the part of their profit they are obliged to share with employees and vowed to replace gross domestic product with a more holistic indicator of economic welfare that he has commissioned from two Nobel laureates in economics, Amarthya Sen and Joseph Stiglitz. He also said that he would put a state bank in charge of defending French industry against sovereign wealth funds and other financial predators.Oh, and he plans on taxing various technology to help fund dying business models and poorly performing firms. That will surely help spur innovation and increase productivity. See also: Happiness by Will or by Writ?


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$ 25.00
Notify me when this product is available:
Amy Brown Figurines
Type: Amy Brown
$ 3.00
Postcard by Amy Brown
Measures 4-1/2 x 6 inches.
Postcards are printed on thick card stock.
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Angel and Hummingbird Print by Amy Brown.
Measures 11 x 14 inches.
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Apprentice Fairy Print by Amy Brown.
Measures 8 x 10 inches... signed by Amy.
Out of Print... Limited Edition of 125..
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Why Breaking Down Information Silos Is a Must
In a perfect enterprise, all data and content would be entirely integrated throughout all business apps, and workflow and business process management (BPM) systems would drive most tasks. But today's organizations are only beginning to make this transition, according to a June 2016 commissioned study conducted by Forrester Consulting on behalf of Alfresco Software. The resulting paper,... Read More »
Showing Some Support for Tech Support
A clear majority of customers feel that tech support for their product purchases has improved over the last five years—and even more expect this trend to continue over the next five years, according to a recent survey from Support.com. The resulting report, titled "The Future... Read More »
The Challenges of Managing Sensitive Documents
While companies have adopted solutions and policies to more securely manage documents, many are getting compromised anyway due to poor file management practices, according to a recent survey from Accusoft. The resulting report, titled "Closing the Document Management Awareness Gap,"... Read More »
How to Ace Vendor Audits
A majority of companies have received software and hardware audit requests from vendors over the last 18 months—and many have undergone these audits several times during this time frame, according to a recent survey from BDNA. The resulting findings summary, titled the "Read More »
Delaying a Digital Transformation Is Bad Business
Very few organizations are taking advantage of digital transformation initiatives to gain business advantages over competitors, according to a recent survey from Harvard Business Review Analytic Services in association with the Genpact Research Institute. The resulting report, titled "Read More »
How CIOs Can Improve Critical QA and Testing
Organizations are facing an assortment of quality assurance and testing challenges throughout a broad range of key, business-driving assessment areas, according to a recent survey from Capgemini/Sogeti and Hewlett Packard Enterprise. The accompanying "
How Outdated Tech Wastes Billions of Dollars
Unwieldy technology in the workplace hinders productivity and results in hidden, large financial losses for U.S. businesses, according to a recent survey. Why? Technology does not fit an organization's needs, and mundane tasks that could be automated, such as password reset requests, new employee onboarding, contract review and approval, could be automated. "The findings clearly show that... Read More »
Why Dark Data Shouldn't Be Taken Lightly
For enterprises to keep up with the impending surge of data—most of which will be unstructured—they must first understand what dark data is and how it will affect their operations. Gaining that knowledge is the first step toward developing a set of data management processes that will "light up" and extract value from more data. There is a pressing need to do so. Today, 80% of all... Read More »


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The Twelve Orders were an evil group of Gundalians appearing in Bakugan: Gundalian Invaders. They were also introduced in Bakugan Dimensions. Currently all members of the Twelve Orders besides Nurzak are dead or presumed dead and one menber of the Minor Twelve Orders is dead while the rest of the Twelve Orders except for Barodius Joined Neathia.
Major Twelve OrdersEdit
- Emperor Barodius (Deceased)
- Kazarina (Deceased)
- Gill (Deceased)
- Airzel (Deceased)
- Stoica (Deceased)
- Nurzak (Sided with Neathia)
Minor Twelve OrdersEdit
- Ren Krawler (Sided with Neathia)
- Sid Arkale (Deceased)
- Lena Isis (Sided with Neathia)
- Jesse Glenn (Sided with Neathia)
- Mason Brown (Sided with Neathia)
- Zenet Surrow (Sided with Neathia)
- Barodius:
- Gill-Airzel:
- Kazarina-Stoica:


text:
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Onlap - The Awakening MP3
Artist: Onlap Check Out The Artist: https://www.facebook.com/ONLAP.Official http://www.youtube.com/user/OnlapMusik http://www.onlap-music.com/ Follow Me ...
Inner Body Awakening - Body Energy & 'Dis-ease' - Tobias Lars MP3
WEBINARS: http://www.CourseOfAwakening.com PERSONAL HEALING TOOLS: http://www.InnerBodyAwakening.com http://www.TheHeartEnergy.com ...
Taylor Davis - Awakening MP3
Taylor Davis: https://www.youtube.com/user/ViolinTay.
Solar Experience - Part 1/5 - Genesis and Awakening (mp3 demo) MP3
Listen on iTunes: http://tinyurl.com/hqxss4e Listen on Spotify: http://tinyurl.com/hqkyw9c SOLAR EXPERIENCE was released on 22 February 2016 through ...
Arkasia - The Awakening MP3
Today I bring you an epic song by Arkasia with some clever lyrics. Enjoy the day, enjoy life. Arkasia: Soundcloud: http://soundcloud.com/arkasiaconcept ...
Zymosis - Awakening MP3
Between Two Points 2012.
Awakening MP3
Provided to YouTube by TuneCore Awakening · Brian Tyler Furious 7 (Original Motion Picture Score) ℗ 2015 Back Lot Music Released on: 2015-03-31 ...
Awakening MP3
Provided to YouTube by K7 Awakening · The Souljazz Orchestra Rising Sun ℗ 2010 Strut Records Released on: 2010-02-15 Composer: Pierre Chrétien Lyricist: ...
Awakening MP3
Provided to YouTube by CDBaby Awakening · Greg Maroney The Journey ℗ 2010 Greg Maroney Released on: 2010-05-03 Auto-generated by YouTube.
Awakening MP3
Provided to YouTube by Warner Music Group Awakening · Steven Halpern Music For Healing (Sound Medicine Series) ℗ 2004 The Relaxation Company ...
Awakening MP3
Special EFX Help us caption & translate this video! http://amara.org/v/Fcl9/
Niburta - Awakening MP3
Awakening, taken from our brand new album, Scream from the East! For further information / If you'd like to purchase the album, please visit one of the sites ...
Awakening - Hillsong, Chris Tomlin (full mix) - free mp3 and loops MP3
Tutorial, charts, loops, etc: http://www.worshiptutorials.com/?p=6242.
Awakening MP3
When our heart is realized and we merge with the source of love, we arrive at the place of unconditional fulfillment. We feel whole at last. Our being is as a ...
Terranoise - Awakening MP3
subscribe, support on facebook and download on bandcamp http://www.facebook.com/terranoisemedia http://terranoise.bandcamp.com/album/awakening.
Awakening MP3
Provided to YouTube by CDBaby Awakening · Michael Mandrell and Benjy Wertheimer Anjali ℗ 2003 Benjy Wertheimer and Michael Mandrell Released on: ...
Aeoliah - Awakening MP3
Año: 1990 Álbum: Love In The Wind Autor: Aeoliah Género: New Age.
Spaze - Awakening MP3
This is a demo from my unfinished album 'The Experimental Age'. A new version will be released when the entire album is done. Download: https://Spaze.
Legend of Zelda Link's Awakening Guitar Medley MP3
MP3: http://bit.ly/1pYEfR1 WAV: http://bit.ly/1mxAT3s Not the most popular Zelda game in the series, but definitely had one of the greatest soundtracks ever.


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Extreme Ty 7: CuntorsionsFavorites [+]
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Running Time: 85 minutes
Released: 10/2008
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What to expect for Family Portrait Photography Session
Step 1. Before the shoot
You will have free phone and email consultations with me to discuss location choices, creative direction, style advice and preparation details bringing any valuable items that you wish to use during the shoot. During our pre-session discussion, we can decide together what kind of ambiance you would like us to create: classical, dynamic, playful, vintage, black and white etc.
We recommend wearing nice warm or neutral colours that coordinate. You can bring different sets of clothes for diverse family photos.
If you have any ideas and preferences for the session please let me know. However the most important thing is for you to feel comfortable and happy about the whole process.
It takes about 1-2 hours and the best Family Portrait Photography is always in places with an abundance of natural light: your home, a scenic park or other chosen location. We like to create a professional, relaxed and friendly ambiance in order to capture those precious moments that will stay forever in your family albums.
Step 2. Other Details:
Once we agree on a session date and time, a non-refundable 50% deposit is required at the time of booking in order to secure your date.
Step 3. After the shoot
Please allow up to 5 working days for editing. I will notify you via email or sms along with the password of your private online gallery for access.
Printed and additional digital products can be purchased separately through your online gallery.
Please take a look at my standard products gallery. You can also check my other products categorized according to duration of production which are the following:
14 working days for production- Glacier Acrylic, Bevelled Ice Acrylic Sandwich, Ice Acrylic, Quantum Acrylic Print, Table Top Magnetic Acrylic, Quartz Acrylic Print, Metallica Framed Prints, Single Vision, Vision Blox Acrylic
13 working days for production- Canvas Wrap Chunky
5 working days for production - Canvas Wrap Round, Canvas Wraps (2" or 3"), Multi-Aperture Framed Prints, Box Framed Prints, Coloured Edge Blocks, Square or Panoramic Format Framed Prints, Small or Large Format Framed Prints,
3 working days for production- Prints in a Luxury Slip-in Mount, Square or Panoramic Format Prints, Small or Large Format Prints, Fine Art Prints
Step 4. Special Offer:
In order to show you an appreciation for trusting me in making your family memories, I offer you special deals.
Are you a parents-to-be and know you're going to want a maternity & newborn photography session?
What about that newborn, 6 month & 1 year sessions?
How about one for you and one as a gift for your friend(s)?
Book sessions together and pay up-front to receive a discounted rate for session fees:
• Two Sessions: 15% off
• Three Sessions: 25% off
Please note that sessions must be used within one year of purchase.


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- Description
Quick Overview
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By Astd Martin
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Posted on 11/20/2016
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Great Times for a Great Cause
Supporting Big Brothers Big Sisters can be as easy as swinging a golf club, tailgating, or enjoying a gourmet meal! Check out the menu of event options that may be a fit for you or your company. Whatever you may be looking for, Big Brothers Big Sisters events are a fun way to learn about our mission, raise money for a great cause and have fun while doing it. And remember, when you give money to a Big Brothers Big Sisters event, at least $.80 of every dollar raised goes straight to the kids we serve.
Phil's BIG BBQ at the Ballpark
If you like BBQ and baseball, this event will give you your fill! Come join 2,000 guests, 1,000 Bigs, Littles, and BBBS Alumni for the largest BBQ tailgate in Southern California!
The BIG Summer Sizzle
Join Big Brothers Big Sisters for a culinary and cocktail soiree, featuring: Cooking demos Live music Prizes And more! Brought to you by: Tickets are $50 each and 100% of ticket sales benefit Big Brothers Big Sisters' Big Futures Program, a post-High School career and education readiness program.
Golfers' Jet A-Way
With private jet transportation, plush accommodations, the greatest golf courses, and terrific camaraderie, the Golfers' Jet-Away provides an exquisite charitable experience for all.
55th Annual Gourmet Dinner
The 2017 Gourmet Dinner, themed "Rockin' Role Models: Amplifying the power of one-to-one mentoring", will host San Diego's finest, starting with a lavish seafood cocktail party before entering into the ballroom for an unforgettable night and fabulous meal. Following the dinner and program, guests are invited to enjoy an after-party, complete with live music, cigars and after-dinner […]


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Ryan Baker said he enjoyed his visit to Notre Dame. "I had a lot of fun," said Baker. "I really enjoyed hanging out with the guys there."
Baker's host was defensive lineman, Dan Santucci. "He is a great guy. I hung out with most of the guys from the team. I also got to hang out with Mike Dury (Dury is a baseball player on the Notre Dame team, and a former teammate of Baker's at Bishop Chatard high school). I thought I fit in well with all of them."
What position are the Irish recruiting him for? "They told me they wanted me as a defensive end."
When does Baker plan to decide? "It's tied between Purdue and Notre Dame. Hopefully I'll decide pretty soon. Probably within the next two weeks." Will he wait until signing day? "I hope not, I hope I know before then."
Comments: We think the Irish are in good shape to land Baker. We would be surprised if he picked Purdue, but he's always been an Irish fan, and had been hoping for a chance to go to Notre Dame. We should know where he'll end up soon enough.


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Michelle Keegan's New Year holiday
Michelle Keegan likes to "go away" for New Year's Eve.
The 29-year-old actress - who married former 'The Only Way Is Essex' star Mark Wright in 2015 - has admitted "normally" the couple have jet off to Dubai to see in the New Year with one another in the sunshine.
Speaking exclusively to BANG Showbiz about her yearly trip, the brunette beauty said: "Normally we go away for New Years Eve. Well, we have been for the last few years because my friend lives in Dubai, so we normally go and see her."
However, the former 'Coronation Street' actress - who played the role of Tina McIntyre in the long running soap for four years - has yet to book the vacation, which could mean the end of the couple's festive ritual.
She added: "But, we haven't booked anything yet."
And the star has hinted she could happily spend this year at home cuddling up to her pets because she has been jetting off all over the globe for various projects she has been involved with over the past few months.
She explained: "Obviously this year I've been really busy working and I've been away from home, so even when I was filming 'Our Girl' in South Africa and then filming the rest in Manchester, then I went onto 'Bobby' and filming everything again in Manchester. So I literally haven't been home in Essex. So I feel like now, I have time now, and my dogs are there again, so I have time to take my dogs for a walk. I can have a lie-in, just do normal things that you take for granted.
"I'm enjoying being back at home at the minute, but nothing is booked [for the New Year] yet.
"I do like to be at home."