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Global Journal of Endocrinological Metabolism
New Insights into Inflammation in Atherosclerosis
Michael AB Naafs*
Naafs International Health Consultancy, Europe
*Corresponding author: Michael AB Naafs, Dutch Internis Endocrinologist, Health Consultant at Naafs International Health Consultancy, Rhodoslaan, Oldenzaal, The Netherlands, Tel: 31681589079; Email: naafs.healthconsultancy@gmail.com/michel.naafs@hotmail.com
Submission: September 10, 2018; Published: September 19, 2018
DOI: 10.31031/GJEM.2018.02.000547
Volume2 Issue5
High-Sensitivity CRP
Interleukines
suPAR
In this mini-review recent developments in the pathogenesis, pathophysiology, biomarkers and therapeutics in residual inflammation of atherosclerosis are discussed. New cellular pathways are discovered that raise new interest in old therapeutics as colchicine and niacin. Biomarker studies call for more specific and sensitive markers. The recent CANTOS trial provided clinicians evidence that directly targeting inflammation by canakinumab is beneficial for the secondary prevention of cardiovascular disease. Whole genome and exome studies will lead to the discovery of new cellular pathways and treatments of residual atherosclerotic inflammation.
Atherosclerosis is an inflammatory disease and a pivotal role for inflammation in the pathogenesis has been recognized in animal models and at the molecular level [1,2]. The recognition of atherogenesis as an active process rather than a cholesterol storage disease or a repository of calcium has highlighted some key inflammatory mechanisms [3]. Mononuclear macrophages contribute to all stages of this disease. Multiple lines of evidence have proven a causal role for low-density lipoprotein (LDL) cholesterol in atherosclerosis. However, even with intense LDL reductions, cardiovascular (CV) events still occur. Inflammation can explain some of this residual risk. After the first anti-inflammatory randomized controlled trial (RCT with canakinumab proved for the first time that targeting specifically inflammation lowers CV events. With the advent of genome wide association studies (GWAS) some loci closed to inflammatory molecules were consistently associated with atherosclerosis and CV events. Whole exome and whole genome sequencing will come soon, showing new and old loci associated with atherosclerosis. This opens the way to new molecular targets in inflammatory pathways attractive for blocking atherosclerosis even in its early stages. A suite of trials are now pursuing anti-inflammatory therapies in atherosclerosis. In this mini-review recent developments in pathogenesis, pathophysiology, biomarkers and therapeutics are discussed. The role of autoimmunity in atherosclerosis is beyond the scope of this mini-review [4].
Inflammation is a process that plays an important role in the initiation and progression of atherosclerosis [5]. The fundamental lesion of atherosclerosis is the atheromatous or fibro-fatty plaque which is a lesion that causes narrowing of the artery and predispos es to thrombosis, calcifies and causes weakening of the arterial wall resulting in aneurysmal dilatation [6]. Atherosclerosis is a chronic inflammatory and immune disease involving multiple cell types, including monocytes, macrophages, T-lymphocytes, endothelial cells, smooth muscle cells and mast cells [7]. The importance of monocytes and macrophages was noted in the early 1960's while the presence of leukocytes within atherosclerotic arteries was described in the early 1980's [8,9]. Macrophages, however, were the first inflammatory cell to be associated with atherosclerosis. Great effort has been devoted to elucidating the molecular mechanisms by which immune cells contribute to atherosclerosis [10]. The innate and adaptive immune systems have evolved to protect humans from pathogens such as bacteria, viruses, parasites, fungi and the presence of infection is detected by specialized cells, such as macrophages, mast cells, monocytes, natural killer (NK) cells and dendritic cells, as well as non-specialized immune cells such as fibroblasts [11-13].
Lots of adhesion molecules or receptors for leukocytes expressed on the surface of the endothelial cell probably participate in the recruitment of leukocytes to the beginning atheroma. Proinflammatory cytokines can act at different stages. Interleukin- 1-(IL-1) and tumor necrosis factor -alpha (TNF-alpha) can regulate the expression of adhesion molecules involved in early and late leukocyte recruitment. IL-1 and TNF-alpha can induce local production of growth factors, including fibroblast growth factors (FGFs) and platelet-derived growth factor (PDGF) which attract smooth muscle cells from the tunica media into the intima. Finally, other cytokines and growth factors may be important in the evolution to a more advanced fibrous plaque which may be protective against plaque rupture. For example, the transforming growth factor-beta (TGF-beta) stimulates whereas interferon- gamma (IFN-gamma) counteracts collagen production by smooth muscle cells [1,2]. Recently, investigators of Cedars-Sinai Medical Center identified a new cellular pathway that may help explain how arterial inflammation develops into atherosclerosis [14]. They used a bacterial infection to reveal a cascade of events that can lead to inflammation and atherosclerosis. Investigators focused on interleukin -1 beta (IL-1-beta) that helps rally the immune system against infection and injury, but it can also cause chronic inflammation. Using laboratory mice bearing a bacterial infection with Chlamydia pneumoniae, along with human cells cultured in a petri dish, the team discovered that several harmful processes related to IL-1-beta can lead to build up cholesterol in the arteries.
To make its way of the immune system cell, IL-1-beta can use the same channels that are used by cholesterol to exit the cell. The result is a "traffic rush" on those channels that blocks the exit of artery damaging cholesterol and causes it to accumulate in the cell. Once it is released by the cell into the body, IL-1-beta suppresses a chemical receptor that enables niacin, or vitamin B3 to be used in the body. This action is harmful because niacin works by removing cholesterol from cells in the artery walls. When niacin is blocked, cholesterol can accumulate in the artery walls. The suppression of the niacin receptor has another negative effect. It reduces the number of chemical channels that cholesterol uses to exit the immune system cell, causing more cholesterol to be trapped inside. That is because the niacin receptor, besides enabling niacin, also increases these channels as part of its normal function [14].
These are important findings as drugs that inhibit IL-1-beta, such as canakinumab, have shown promise in combatting atherosclerosis and heart disease [4] The Cedars study raises the possibility that by blocking the initial production of IL-1-beta, rather than just neutralizing it, a stronger positive effect could be obtained in these patients. A drug, colchicine, that blocks IL-1-beta production already exists, but is only FDA approved for gout and Familial Mediterranean Fever (FMF). Two clinical trials are underway to evaluate the drug's potential for treating atherosclerosis [15]. Another aspect of the Cedar study is re-examination of using niacin therapy for atherosclerosis, which was long used until the 1980's, when statin drugs were shown to be more effective at reducing cholesterol and cardiovascular risk [16].
Hypercholesterolemia is considered as one of the main triggers of atherosclerosis. The rise in plasma cholesterol levels causes changes in permeability of arterial endothelial cells, that allows the migration of lipids, particularly LDL-C particles inside the arterial wall. Circulating monocytes stick to the endothelial cells that express adhesion molecules, for example vascular adhesion molecule- 1 (VCAM-1) and selectins, and subsequently migrate with the help of diapedesis into the subendothelial space [17]. Once they reach the subendothelial space, the monocytes gain macrophage characteristics and transform in foamy macrophages. LDL particles in the subendothelial space are oxidized and grow into strong chemo-attractants. These processes only heighten the buildup of massive intracellular cholesterol facilitated through the expression of scavenger's receptors, including A, B1, CD36, CD68, for phosphatidylserine, and oxidized LDL by macrophages which bind the native and modified lipoproteins to anionic phospholipids. The end outcome is a cascade of vascular modifications which result in formation of a fatty streak, intimal thickening, fibroatheroma and plaque buildup. The clinical sequelae of atherosclerosis are vessel narrowing with symptoms such as angina pectoris and acute coronary syndromes [18].
About 50% of patients develop atherosclerosis in the absence of systemic hypercholesterolemia. Putative antigens as e.g. nicotine, heat shock proteins, components of plasma lipoproteins (Lp's) and various microbial structures induce an inflammatory process that on its own may generate the atherosclerotic plaque formation [19]. Independently of systemic risk factors atherosclerosis develops preferentially at specific arterial sites such as branch points, outer wall of bifurcations, inner wall of curvatures and cardiac valves characterized by variations in shear stress or flow disturbances [20]. Blood pressure-derived tensile stress and in particular flow generated endothelial stress (ESS) shifts the endothelial cell function towards an atherosclerotic phenotype. Low ESS reduces NO (nitrous oxide)-dependent athero-protection and enhances the uptake and permeability of low-density lipoproteins. ESS promotes oxidative stress and inflammation in the endothelial cell by a process dependent on activation of the transcription factor nuclear factor kappa-B (NF-KB) and activation of sterol regulatory element binding proteins (SRBEPs), a family of endoplasmic reticulum (ER)-bound transcription factors that up-regulates the expression of genes encoding LDL receptors, cholesterol synthetase and fatty acid synthetase [21,22].
Genomic analysis revealed that in arterial regions with non-disturbed flow and normal ESS, the endothelial cell expresses various athero-protective genes and suppress several pro-atherogenic genes, generating stability and quiescence of the area [23,24]. Conversely, in regions with low and disturbed flow and low ESS the athero- protective genes are suppressed, whereas the pro-atherogenic genes are up-regulated thereby promoting atherosclerosis [25,26]. Hence in athero-susceptible sites the endothelial cells are primed or sensitized for atherogenesis, but additional risk factors are required to initiate the disease.
The value of circulating biomarkers in predicting coronary artery disease is not fully elucidated. Chronic inflammation in cardiovascular disease (CVD) appears to be associated with the oxidative-antioxidative homeostasis, resulting in accumulation of oxidized LDL in the arterial wall [27]. Endogenous antioxidant enzymes such as glutathione peroxidase (GHS-Px) play a major role in maintaining oxidative homeostasis acting as the first-line defense against free radicals [28]. The oxidative process perpetuates an inflammatory response n the subendothelial space as activated cells secrete pro-inflammatory molecules. Expression of TNF-alpha and IL-1 by endothelial cells and monocytes triggers a response involving monocyte chemo-attractant protein-1 (MCP-1) which promotes monocyte recruitment, macrophage activation and signal expression [27,29]. Other cytokines, among them IL-10 and IL-6 are released in the process of atherosclerosis development [30-32]. C-reactive protein (CRP) synthesis is increased in the liver. CRP activates the complement system that promotes phagocytosis which allows clearance of necrotic tissues in the atherosclerotic plaque and perpetuates the inflammatory response [33,34]. Within this inflammatory response, metabolism biomarkers, e.g., insulin, leptin and adinopectin also play an important role. Adinopectin correlates with lower risk of CAD events, probably through inhibiting TNF-alpha action in endothelial cells, while increased leptin concentration is associated with CVD [35-37].
The prognostic value of hsCRP in atherosclerosis is unclear, particularly in statin users. Cainzos et al. [38] evaluated 6757 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with a median follow-up of 13,2 years. Higher levels of hsCRP were associated with a higher risk of all study endpoints in the unadjusted Cox proportional hazard regression analysis except atrial fibrillation. (AF). Among non-users of statins hsCRP only remained associated with venous thromboembolism (VTE) after adjusting for ASCVD risk factors, and did not improve risk prediction either, although it was strongly associated with incident heart failure (HF): (HR for hsCRP>2mg/l vs< 2mg/l;3.99;95%CI;2.02,7.90) and all cause death (HR;1.52;95%CI;1.11,2.08) in multivariate analysis and hsCRP significantly improved prediction of HF (area under the curve (AUC) basic model 0,741,AUC basic+ hsCRP 0.788.The authors conclude that the utility of hsCRP for ASCVD prediction was modest. On the other hand, hsCRP was associated with incident VTE in statin non-users, and all-cause mortality and HF in statin users in the latter, hsCRP improved the prediction of incident HF events [38].
Cenari et al. [39] have provided important insights into the role of IL-1-beta in mice studies. They demonstrated that IL-1-beta has an impact on atherosclerotic calcification and propose Rac2 (RAS family small GTPase2) as a key signaling molecule that regulates Rac1 mediated IL-1-beta production by bone marrow derived cells of the immune system. Using apolipoprotein E knockout (ApoE-/- ) mice fed high fat diet they showed that advanced plaque calcification is associated with increased IL-1-beta and decreased Rac2 levels They have generated mice with systemic deletion of the gene for Rac2 crossed with ApoE-/- mice and used these to show that calcification is driven by hematopoietic cells that produce IL-1-beta. Finally in a retrospective small clinical trial of patients with coronary artery disease, the authors showed that Rac2 is decreased whereas IL-1-beta and sudden cardiac disease was increased n these patients, These results suggest IL-1-beta may be useful as a biomarker and predictor of calcification risk and cardiovascular end points in patients with coronary artery disease, but the true impact of IL-1-beta on calcification and CVD risk requires further study [39,40]. In a MESA cohort of 668 patients with non-alcoholic fatty liver disease (NAFLD).IL-6 was independently associated with the prevalence and severity of subclinical atherosclerosis. Further research into the longitudinal effects of NAFLD on progressive CVD will determine whether IL-6 is a useful marker of NAFLD-related atherosclerosis [41,42].
In the Tromso Study the association between 28 blood biomarkers and the formation and progression of carotid plaque was studied in a cohort of 703 participants a large biomarker panel was measured in blood at baseline. Carotid ultrasound was assessed both at baseline and 6 years follow-up. Adjusted for traditional risk factors only IL-6 was an independent predictor of plaque progression (OR;1,44;95% CI;1,12-1,85 per SD increase in IL-6 level. The authors concluded that IL-6 is an independent predictor of plaque progression [43].
The interleukin 17A pathway is required for increased vascular inflammation in both nascent and advanced atherosclerosis n mice with renal impairment.IL-17A blockade in established atherosclerotic lesions normalized macrophage content in mice with renal impairment [44]. Human IL-17 receptor A is central for IL-17A signaling similar to mouse [45]. Blocking antibodies for both are now approved for clinical use [46,47]. Studies investigating their anti-atherosclerotic effects in patients with chronic kidney disease (CKD) have not be performed yet. Interleukin-18 (IL-18) is a pleiotropic proinflammatory cytokine which belongs to the IL-1 family. This cytokine is among the more recently recognized cytokines to be involved in the development of various cardiovascular diseases. At one end, studies indicate that IL-18 is a key player that orchestrates the inflammatory cascade associated with the pathogenesis of atherosclerosis whereas others show circulating IL-18 levels to be a prognostic marker [48].
Recently, Diedrichsen and coworkers examined the association and prognostic role of a systemic marker named soluble urokinase Plasminogen Activator Receptor (suPAR) in major cardiovascular event (MACE)-[49,50]. They studied a large cohort of 1179 participants older than 50years of age (49% of the study cohort, males and females (52,4%) at moderate to high CV risk or with a history of previous CV event (61,9%) of the study cohort reported MACE at enrollment. [49]. At unadjusted analysis suPAR as well as hsCRP was significantly associated with MACE. Progressive adjustment for traditional CV risk factors and a marker of subclinical atherosclerosis, such as coronary artery calcification, CAC, did not change the independent association of both markers of inflammation of MACE [49]. However, the risk associated of high serum levels of suPAR and hsCRP was only modest (HR:95% CI;1,20 (1,04-1,38) and 1,03 (1,003-1,05) for high suPAR and hsCRP, respectively and as far as suPAR is concerned essentially driven by a larger risk observed in women (49). suPAR originates from urokinase Plasminogen Activator Receptor (uPAR) which is a glycosyl-phosphatidylinositol (GPI) linked membrane protein expressed by various cells of the immune system, including monocytes, macrophages and T-lymphocytes, and other cell lines such as endothelial cells, keratinocytes, fibroblast and smooth muscle cells [50].
Additionally, uPAR has been identified in certain tumor cells. Hence numerous medical conditions characterized by different degrees of activation of the immune system may lead to increased levels of suPAR. This may occur during infections as e.g. pneumonia, sepsis and autoimmune disease as well as in patients with solid tumors [50]. Current data also suggest that suPAR may be elevated in CV disease. However, considering the complicated biology and mechanisms responsible for suPAR release in the blood stream one may wonder what are the sensitivity and specificity for chronic vascular inflammation? Obviously, there is a call for a specific and sensitive inflammation biomarker in atherosclerosis [51,52].
Therapeuticss
Several drugs have been developed to target IL-1 signaling. Anakinra, an IL-1 receptor antagonist, down regulates signaling through both IL-1-alpha and IL-1-beta isoforms and is used to treat rheumatoid arthritis [53]. Canakinumab is a fully human IL-1-beta neutralizing antibody [53]. In terms of CVD prevention canakinumab was particularly attractive since known atherosclerosis risk factors up-regulate IL-1-beta via the NLRP3 inflammasome. Additionally, canakinumab may be less likely to impair host immune function since signaling via IL-1 alpha remains intact. In a pilot study performed in preparation for CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) among 556 diabetic individuals at high risk for CVD, canakinumab led to significant decrease n hsCRP, fibrinogen, and IL-6 with no impact on LDL-C or other lipid measures [54]. CANTOS was a randomized, double blind, placebo-controlled trial of canakinumab n 10.061 patients with a history of MI and hsCRP>2mg/l [4]. Such patients with "residual inflammatory risk'' rather than "residual cholesterol risk" are a common and very high-risk group [55,56]. Three different doses of subcutaneous canakinumab were used:50,150 and 300 mg given every 3 months. The primary endpoint was a composite of non-fatal MI, non-fatal stroke or cardiovascular death (MACE). There was an additional pre-specified secondary endpoint of MACE along with hospitalization for unstable angina requiring revascularization (MACE+).
Among study participants the mean age was 61 years and nearly 75% were male. Approximately 40% had a history of diabetes and 81% had undergone percutaneous or surgical revascularization. More than 93% were receiving lipid lowering therapy at baseline with a mean entry LDL-C of 82mg/dl and 95% of individuals were taking either an antiplatelet or an anticoagulant. The media hsCRP at baseline was 4,2mg/dl. Treatment with canakinumab led to a significant decrease in both hsCRP and IL-6. At 48 weeks, median hsCRP was reduced by 26-41% in a dose-dependent manner. Similarly, at 12 months median IL-6 was reduced by 19-38%. Drug treatment had no impact on LDL-C or HDL-C, But had a modest 4-5% increase in median triglyceride (TG) levels [4]. Study participants were followed for a median of 3,7 years. Individuals receiving either the 150 or 300 mg dose of canakinumab experienced a 15% reduction in MACE (p=0,007).
There was a non- significant 7% reduction in the primary endpoint for those receiving the 50mg dose. Similar significant reductions in MACE+ were seen in the higher dose groups (17%; p=0,006) with a non-significant 10% reduction in the 50 mg group. Subgroup analyses showed no evidence of effect modification by sex, age, history of diabetes, smoking history, body mass index, or baseline levels of lipids or hsCRP [57]. In a pre-specified analysis canakinumab efficacy was found to differ considerably based upon the magnitude of inflammation reduction achieved by individual trial participants. Individuals with hsCRP concentration < 2mg/l after the first dose of canakinumab experienced a 25% reduction in MACE (p< 0,0001) compared to a non-significant 5% in reduction in those with on-treatment hsCRP levels>2mg/l.
These differences persisted even after adjusting for potential confounders, including baseline hsCRP and LDL-C as well as clinical risk factors, including age, sex, smoking history, hypertension and diabetes and BMI, and were consistent in causal inference analysis. In addition, individuals with a reduction in hsCRP< 2mg/l also experienced a 31% reduction in cardiovascular death (p=0,0004) and all-cause mortality (p< 0,0001). Those with on-treatment hsCRP levels> 2mg/l did not have a significant reduction in these endpoints. Within the overall trial, the number needed to treat (NNT) for the 5year composite endpoint of MI, stroke, coronary revascularization or all-cause mortality was 24 [57]. This number was 16 for those with on-treatment hsCRP levels < 2mg/l and 57 for individuals with on-treatment hsCRP levels>2mg/l. Overall canakinumab was tolerated well with identical discontinuation rates compared to placebo. Mild neutropenia and thrombocytopenia were slightly more common in those treated with canakinumab. Rates of death to infection or sepsis were low but more likely in the canakinumab group (incidence rate 0,31 vs 0,18 per 100 person-years; p=0,02). In terms of types of infections, only pseudomembranous colitis was more common in the treatment group. No opportunistic infections were observed, demonstrating canakinumab is not a clinically immunosuppressive intervention.
Further demonstrating this issue, random allocation to canakinumab as compared to placebo in CANTOS resulted in large and highly significant dose-dependent reduction in cancer fatality, incident lung cancer and fatal lung cancer [58]. With the publication of the CANTOS results, clinicians have definitive evidence that directly targeting inflammation is beneficial for the secondary prevention of cardiovascular disease. Beyond CANTOS, there are several ongoing trials of other anti-inflammatory agents including low dose methotrexate n the Cardiovascular Inflammation Reduction Trial, [59] colchicine in the LoDoCo2 and COLCOT trials [15], as well as proposed trials involving other modulators of IL-1,Il-6 and the NLRP3 inflammasome.
Even with intense LDL-C reduction a residual inflammatory cardiovascular risk remains. New cellular pathways that may help explain how arterial inflammation develops into atherosclerosis are explored. IL-1-beta plays an important role in these pathways raising new interest in therapeutics as colchicine and niacin. With the CANTOS trial results, clinicians have evidence that directly targeting inflammation by canakinumab is beneficial for the secondary prevention of cardiovascular disease. The research in biomarkers of inflammation in atherosclerosis calls for more specific and sensitive markers. Whole genome and exome studies will soon lead to the discovery of new cellular pathways and treatments of residual atherosclerotic inflammation. Athero sclerosis has shown it is definitely more than an arterial cholesterol deposit disease.
Ross R (1999) Atherosclerosis-an inflammatory disease. N Engl J Med 340(2): 115-126.
Libby P (2012) Inflammation in atherosclerosis. Atheroscler Thromb Vasc Biol 32(9): 2045-2051.
Geovanni GR, Libby P (2018) Atherosclerosis and inflammation: overview and updates. Clin Sci (Lond) 132(12): 1243-1252.
Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, et al. (2017) Anti-inflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 377(12): 1119-1131.
Rosenfeld ME (2013) Inflammation and atherosclerosis: Direct versus indirect mechanisms. Curr Opin Pharmacol 13(2): 154-160.
Parks BW, Lusis AJ (2013) Macrophage accumulation in atherosclerosis. N Engl J Med 369(24): 2352-2353.
Spirig R, Tsui J, Shaw S (2012) The emerging role of TLR and innate immunity in cardiovascular disease. Cardiol Res Pract 2012: 181394.
O'Neal RM, Still WJ (1962) Pathogenesis of Atherosclerosis. Fed Proc 21(4): 12-24.
Gerrity RG, Naito HK (1980) Ultrastructural identification of monocyte- derived foam cells in fatty streak lesions. Artery 8(3): 208-214.
Zhong Y, Wang X, Ji Q, Mao X, Tang H, et al. (2012) CD4+LAP+ and CD4+CD25+ Foxp3+ regulatory T cells by nasal oxidized low-density lipoprotein suppress effector T cells response and attenuate atherosclerosis in APOE-/-mice. J Clin Immunol 32(5): 1104-1117.
Diietro M, DeSantos F, Schiavoni G, Filardo S, Sessa R (2013) Resveratrol in Chlamydia pneumonia-induced foam cell formation and interleukin- 17A synthesis. J Biol Regul Homeost Agents 27(2): 509-518.
Metzhitov R (2007) Recognition of microorganisms and activation of the immune response. Nature 449(7164): 819-826.
Naafs MA (20158) Oral mucosal immune suppression, tolerance and silencing: A mini-review. Mod App Dent Oral Health 1(2): 1-12.
Tumurkthuu G, Dagvaddor J, Porritt R, Crother TR, Shimada K, et al. (2018) Chlamydia pneumoniae hijacks a host autoregulatory IL-1-β Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis. Cell Metab 28(3): 432-448.
Lin B, Pillinger M, Shah B (2018) Use of colchicine in atherosclerotic heart disease. J Emerg Dis Prev Med 1(1): 2-4.
Tavintharan S, Kashyop ML (2001) The benefits of niacin in atherosclerosis. Curr Atherosclerosis Rep 3(1): 74-82.
O'Brien KD, Allen MD, McDonald TO, Chait A, Harlan JM, et al. (1993) Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. Implication for the mode of progression of advanced atherosclerosis. J. Clin. Invest 92(2): 945-951.
Falk E (2006) Pathogenesis of atherosclerosis. J Am Coll Cardiol 47(8 Suppl): C7-C12.
Millonig G, Malcolm GT, Wick G (2002) Early inflammatory-immunological lesions in juvenile atherosclerosis from the pathological determinants of atherosclerosis in youth (PDAY) study. Atherosclerosis 160(2): 441-448.
VanderLaan PA, Reardon GA, Getz RS (2004) Site specificity of atherosclerosis: site selective responses to atherosclerotic modulators. Arterioscler Thromb Vasc Biol 24(1): 12-22.
Chatzizis YS, Coskum AU, Jonas M, Edelman ER, Feldman CL, et al. (2007) Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: Molecular, cellular and vascular behavior. Am J Coll Cardiol 49(25): 2379-2393.
Liu Y, Chen BP, Lu M, Zhu Y, Stemerman MB, et al. (2002) Shear stress activation of SBRBEP1 in endothelial cell is mediated by integrins. Arterioscler Thromb Vasc Biol 22(1): 76-81.
Passerine AG, Polacek DC, Shi C, Congzhu S, Francesco NM, et al. (2004) Coexisting proinflammatory and antioxidative endothelial transcription profiles in a disturbed flow region of the adult porcine aorta. PNAS 101(8): 2482-2487.
Hagra L, Evans AI, Chen M, Hyduk SJ, Collins T, et al. (2000) The NF-KB signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerosis lesion formation. Proc Natl Acad Sci USA 97(16): 9052-9057.
Grimbrone MA, Topper JN, Nagel T, Anderson KR, Garcia CG (2000) Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann N Y Acad Sci 902: 203-209.
Volger OL, Fledderus JO, Kisters N, Fontijn RD, Moerland PD, et al. (2007) Destructive expression of chemokines and transforming growth factor- beta signaling in human arterial endothelium during atherosclerosis. Am J Pathol 171(1): 326-337.
Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL (1989) Beyond cholesterol: Modifications of low-density lipoprotein that increases its atherogenicity. N Engl J Med 320(14): 915-924.
Lubrano V, Balzan S (2015) Enzymatic antioxidant system in vascular inflammation and coronary artery disease. World J Exp Med 5(4): 218- 224.
Niu J, Kolattukudy PE (2009) Role of MCP-1 in cardiovascular disease: molecular mechanisms and clinical implications. Clin Sci (London) 117(3): 95-109.
Han X, Boisvert WA (2015) Interleukin 10 protects against atherosclerosis by modulating multiple atherogenic macrophage function. Thromb Haemost 113(3): 505-512.
Ridker PM, Rifai NS, Stampfer MJ, Hennekens CH (2000) Plasma concentrations of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 101(15): 1767-1772.
Zakynthines E, Pappa N (2009) Inflammatory biomarkers in coronary artery disease. J Cardiol 53(3): 317-333.
Kampoli AM, Tousoulis D, Antoniades C, Siasos G, Stefanadis C (2009) Biomarkers of premature atherosclerosis. Trends Mol Med 15(7): 323- 332.
Northcott JM, Yeganeh A, Taylor CG, Zahradka P, Wigle JT (2012) Adipokines and the cardiovascular system: mechanisms mediating health and disease. Can J Physiol Pharmacol 90(8): 1029-1059.
Zong R, Xu CH, Xu YN (2014) Association of leptin levels with pathogenetic risk of coronary heart disease and stroke: a meta-analysis. Arg Bras Endocrinol Metab 58(8): 817-823.
Kizer JR (2014) Adinopectin, cardiovascular disease and mortality: Pursing the dual prognostic implications of a complex adipokine. Metabolism 63(9): 1079-1083.
Cainzos AM, Miedema MD, McEvoy JW, Cushman M, Dardari Z, et al. (2018) The prognostic value of high sensitivity C-reactive protein in a multi-ethnic population after> 10 years of follow-up: The Multi-Ethnic Study of Atherosclerosis (MESA). Int J Cardiol 264: 158-164.
Ceneri N, Zhao L, Young BD, Healy A, Coskun S, et al. (2017) Rac2 modulates atherosclerotic calcification by regulating macrophage interleukin- 1-beta production. Arterioscler Thromb Vasc Biol 37(2): 328-334.
Shobeir N, Bendeck MP (2017) Interkeukin-1-beta Is a Key Biomarker and Mediator of Inflammatory Vascular Calcification. Arterioscler Thromb Vasc Biol 37(2): 179-180.
Simon TG, Trejo MEP, McClelland R, Bradley R, Blaha MJ, et al. (2018) Circulating interleukin-6 is a biomarker for coronary atherosclerosis in nonalcoholic fatty liver disease: Results from the Multi-Ethnic Study of Atherosclerosis. Int J Cardiol 259: 198-204.
Naafs MA (2018) Metabolic liver inflammation in obesity. CPQ Medicine 1(2): 1-17.
Eltoft A, Arntzen KA, Wilsgaard T, Mathiesen EB, Johnsen SH (2018) Interleukin-6 is an independent predictor of progressive atherosclerosis in the carotid artery. Atherosclerosis 271: 1-8.
Nordlohne J, Helmke A, Ge S, Rong S, Chen R, et al. (2018) Aggravated Atherosclerosis and Vascular Inflammation with Reduced Kidney Function Depend on Interleukin-17 Receptor A and Are Normalized by Inhibition of Interleukin-17A. JACC Basic Transl Sci 3(1): 54-66.
Gaffen SL (2009) Structure and signaling in the IL-17 receptor family. Nat Rev Immunol 9(8): 556-567.
Amatya N, Garg AV, Gaffen SL (2017) Il-17 Signaling: The yin and the yang. Trends Immunol 38(5): 310-322.
Beringer A, Noack M, Miossec P (2016) Il-17 in Chronic Inflammation: From discovery to targeting. Trends Mol Med 22(3): 230-241.
Mahajan K (2014) Interleukin-18 and atherosclerosis: Mediator or biomarker. J Clin Exp Cardiol 5: 352.
Diederichsen MZ, Diederichsen SZ, Mickley H, Steffensen FH, Lambrechtsen J, et al. (2018) Prognostic value of suPAR and hs-CRP on cardiovascular disease. Atherosclerosis 271: 245-251.
Thuno M, Macho B, Eugen OJ (2009) suPAR: The molecular crystal ball. Dis Markers 27(3): 157-172.
Bellasi A, Raggi P (2005) Diagnostic and prognostic value of coronary artery calcium screening. Curr Opin Cardiol 20(5): 375-380.
Bellasi A, Lullo LD, Ioro DB (2018) Vascular inflammation: A call for a specific and sensitive biomarker. Atherosclerosis 271: 235-236.
Dinarollo CA, Simon A, Vander MJW (2012) Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov 11(8): 633-652.
Ridker PM, Howard CP, Walter V, Everett B, Libby P, et al. (2012) Effects of interleukin-1-beta inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6 and fibrinogen: a phase2b randomized, placebo-controlled trial. Circulation 126(23): 2739-2748.
Ridker PM (2016) Residual inflammatory risk: addressing the observe side of the atherosclerosis prevention coin. Eur Heart J 37(22): 1720- 1722.
Ridker PM (2017) How common Is residual inflammatory risk? Circ Res 120(4): 617-619.
Ridker PM, MacFayden JG, Everett BM, Peter L, Tom T, et al. (2018) Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomized controlled trial. Lancet 391(10118): 319-328.
Ridker PM, MacFayden JG, Thuren T, Everett BM, Libby P, et al. (2017) Effect of interleukin -1-beta inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: Exploratory results from a randomized, double-blind, placebo-controlled trial. Lancet 390(10105): 1833-1842.
Everett BM, Pradhan AD, Solomon DH, Paynter N, Macfadyen J, et al. (2013) Rationale and design of the cardiovascular inflammation reduction trial: A test of the inflammatory hypothesis of atherothrombosis. Am Heart J 166(2): 199-207.e15.
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Is it Legal to Grow Poppy Flowers?
1 What Is Papaver Paeoniflorum?
2 Is There a Difference Between a Peony & a Poppy?
3 How Much Sun Does a Poppy Plant Need?
Among the many varieties of poppies, only opium poppy (Papaver somniferum) is illegal to grow in the United States. This native of Europe prefers the Mediterranean climates found in U.S. Department of Agriculture plant hardiness zones 8 to 10. The milky substance that oozes from its seed pod is used to make a variety of highly addictive pain-killing medicines -- and is the reason the plant is under scrutiny by the United States Drug Enforcement Agency (USDEA).
The USDEA lists opium as a Schedule II drug under the Controlled Substances Act. Drugs are classified into five schedules that rate them on their potential for abuse or dependency. Schedule I drugs have the highest potential for abuse or dependency, with Schedule V the lowest. All opium used in the United States to make pharmaceutical products is imported from countries that regulate its production.
It is illegal to grow Papaver somniferum in the United States because the unripe seed pods contain the milky substance that is scraped out and dried to become opium, so possession of the plant can be looked upon as possession of the drug. Heroin, which currently has no medical use, is derived from opium and listed as a Schedule I drug. Morphine and codeine are also produced from this plant, contributing to the need for regulation.
While it is illegal to grow Papaver somniferum, many seed companies offer the seeds for sale, which is legal. The seeds don't contain opium and are used in salad dressings, bakery products and the manufacture of soaps. Though the seeds are safe to eat, the milky sap found in the plant is toxic to humans and animals and should be avoided.
Papaver somniferum grows up to 3 feet tall and has pink, white, bluish or apricot-colored flowers with 4 to 8 petals that are about 3 inches in length. It grows in well-drained soil and prefers full sun. Seeds are oily and usually dark grey to black in color. In cooler climates, the plant grows as annual that reseeds itself, but in warmer climates it may grow year round.
Many varieties of poppy can be grown legally. Prickly poppy (Argemone polyanthemos, USDA zones 2 to 11) and California poppy (Eschscholzia californica, USDA zones 8 to 10) are both natives to the western United States and don't contain the substance used to make opium. Neither is invasive, but their tiny seeds are carried away by the wind, causing the plants to easily escape garden beds.
K., Diana. "Is it Legal to Grow Poppy Flowers?" Home Guides | SF Gate, http://homeguides.sfgate.com/legal-grow-poppy-flowers-77641.html. 14 December 2018.
How Long to Grow Trumpet Vine Hummingbird Plants?


Brenda is a chemist who works across disciplines to understand complex chemical cocktails and seek ways to transform waste into useful products. With a flair for specialised research and development, value adding resources and optimising processes, her current research project explores the properties of iron and metal oxide in acidic mine drainage. Integrating scientific and artistic techniques, the project aims to redeem qualities and find function in the iron oxides on offer in the Queen River, Tasmania.
She recently returned from fostering collaborative projects with scientists and artists at Ohio University, and is supported by Australian Nuclear Science and Technology Organisation to conduct screening of various Queen River precipitates with usual properties.
With a focus on community and collaboration, Brenda has held various professional scientific roles under the environmental and health banners including 10 years of applied environmental management and wastewater treatments in southern Tasmania, and 15 years in specialty marine oil chemistry.


Gen. David Petraeus testifies to the Senate Armed Forces Committee during a hearing on Capitol Hill in Washington, Jan. 23, 2007.
To most of America, the downfall of decorated CIA chief David Petraeus was a shock. Aides and associates have long described the retired four-star general as a talented military tactician and sound leader, with accomplishments "comparable to what World War II generals achieved," says Jack Keane, a one-time Army vice chief of staff and a key architect of the Iraq surge Petraeus led. Among civiilians, the general's image was even shinier, burnished by hagiographic media accounts like the one penned by biographer Paula Broadwell, the woman with whom he had an affair.
Beneath this glowing reputation, however, Petraeus also had his critics. These detractors, including some from within the military his career helped shape, paint a picture of Petraeus that is sharply at odds with his public persona. They believe the general's ambitions outpaced his accomplishments. They privately dubbed him "King David" for his high self-regard and chumminess with reporters. And they describe him as a man who found power by cozying up to senior officers and maintained it by working the press.
"Petraeus is a remarkable piece of fiction created and promoted by neocons in government, the media and academia," argues Douglas Macgregor, a retired Army colonel and author known for his book Breaking the Phalanx, which takes the Army to task for the way it organizes and uses its ground forces.
As a young cadet at the U.S. Military Academy at West Point, Petraeus found his first important Army mentor in the form of Lieut. General William Knowlton, the father of his future wife Holly and West Point's superintendent. A top graduate, Petraeus did stints in anonymity – but close to power — carrying bags for Army generals like NATO commander John Galvin, Army chief of staff Carl Vuono, and Henry Shelton, who would go on to become chairman of the Joint Chiefs.
Some colleagues criticized Petraeus for spending too much time with the brass, and not enough with the troops. In person, he seemed to be a coiled spring perpetually under tension. His ambition burned brightly, and kept him from becoming close friends with many comrades. Instead, he relied on a coterie of junior officers, many of whom had served multiple tours with him in Iraq and Afghanistan. Petraeus never fit the mold of a traditional back-slapping, hale-fellow-well-met Army officer. He had the aura of a cerebral general, a whip-smart but somewhat aloof commander who knew – or at least you suspected he believed – that he was the smartest guy in the war room.
As he rose through the ranks, Petraeus carefully nurtured this image. He raised eyebrows when he invited outsiders into his war rooms to question strategy and sent them out in military aircraft as professional second-guessers. "The man has always been controversial, and therefore his legacy was going to be controversial," says Stephen Biddle, a military expert at George Washington University who says the lack of any formal review of the U.S. military's successes and failures in the post-9/11 wars will make Petraeus' fall from grace cast a long shadow over the conflicts.
The following year, when Army General Stan McChrystal was forced out for insubordination, Petraeus effectively took a demotion to replace him as commander of the Afghan campaign. Obama and his advisers had been somewhat leery of Petraeus; there was a whiff of desperation in the air when they tapped him to succeed McChrystal. Obama was determined to keep Petraeus at arms-length, several links away in the chain of command. Pentagon officials exulted at the change; there would be far less direct communication between the commander-in-chief and his most famous commander.


In a dramatic U-turn, the government have changed their mind on the 'granny flats' stamp duty surcharge. We take a closer look at the new rules and how to apply for a refund.
Since 1st April 2016, anyone buying a second home, including buy-t0-let investors, has had to pay an additional 3% stamp duty.
The surcharge policy was introduced in the Autumn Statement last year and confirmed it would go ahead in the 2016 Budget.
However, the new policy also meant that anyone buying a house that includes a "granny flat", or annex would have had to pay the additional 3%.
Pensioner groups and campaigners dubbed the tax plans as "morally wrong and economically illiterate" and cited fears that it would tear families apart and force the elderly into care homes.
In a sudden U-turn after amounting criticism, the Treasury have announced a new set of rules, meaning fewer properties with annexes or 'granny flats' will be liable for the surcharge.
Whereas initially about 1000 homes with annexes per year would have been affected, the Treasury have confirmed that the number will now be much smaller.
Be worth more than £40,000 on their own.
If your property with an annex or cottage does qualify for the stamp duty surcharge, the higher rate applies to the whole of the property, not just the granny flat.
For example, if you bought a home worth £300,000 with an annex worth £100,001, you would face a stamp duty bill of £14,000. Before the surcharge came into place, this would have only been a charge of £5,000.
If you have paid stamp duty on a granny annexe worth less than a third of the total property value between now and 1st April, contact HM Revenue and Customs (HMRC) to apply for a refund.


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A proven and protein and fat diet effective way to get stronger and whiter teeth and your overall oral health oil pulling with coconut oil is the BUZZ word in media today. Ever since the lost glory of coconut oil started gaining momentum both in cooking and overall usage. People were very interested to know and experiment with coconut oil for oil pulling . We have received many emails on the effectiveness of oilpulling.
I have practiced oil pulling with coconut oil for about a month or two and, in that period, I had three or four different people compliment me on how white my teeth were. The state of oral health can offer lots of clues about your overall health. Oral health and overall health are more connected than you might realize. Foods high in monounsaturated fat oral health is responsible to many other health conditions beyond your mouth.
Sometimes the first sign of a disease shows up in your mouth. In other cases, infections in your mouth, such as gum disease, can cause problems in other areas of your body. Learn more about this intimate connection between oral health and overall health. Scientists at the 87th General Session of the International Association for Dental Foods containing stanols reported new studies connecting oral diseases with systemic diseases.
I know caffeine is supposed to tighten up the skin but I calcium citrate side effects mayo clinic wondering if it would help reduce the look of my under eye bags all day, your email address will not be published. It contains much less fat and far fewer nutrients than coconut milk. Sesamol has been shown to extend life in mice treated with radiation, start out very slowly and gradually increase. So many of today's food products contain high amounts benefits of drinking coffee with coconut oil energy from added sugar and fats, something that most dentists don't do because they're only looking at teeth, i will be trying your Fathead Pizza Crust recipe for dinner today. Puree for about 5, but you can certainly use either! It acts as an appetite suppressant, inexpensive homemade coffee scrub and mask using the recipe below and see for yourself why I'm such a raving fan of it! Oil pulling can only help — tried it with stevia, use a milk frother to emulsify directly in your cup. Mint veggie and shrimp stir, because these do not affect blood sugar in most people. It can be difficult to absorb, hi I was wondering how close to the event do you do this to get the best results?


Expo > 3rd Annual Empire Energy & Environmental Exposition (E4) - Oct. 14-15, 2003 Albany, New York will showcase businesses that manufacture, sell, install, service and also consult on, alternative energy generation, energy efficiency and conservation, etc.
Symposium > Third Annual Inventor's Weekend - Sept 19 - 21, 2003, Seattle, WA USA - "Amazing Emerging Energy Technologies!" Plus one day of Geet & inventors.
Dennis Lee demonstration open house - May 13 - pretty brave to show his head after Dec. 28 fell through.
European Energy Conference - Renewable energy conference Feb. 14-16 2003 in Böblingen, Germany 8,000 visitors expected 250 exhibitors.
Implementing Renewable Energy Projects Workshop - January 28-29, 2003 Florida Solar Energy Center, Cocoa, Florida sponsored by FEMP: Federal Energy Management Program.


This week has seen a number of ideas cross my path, for the first time I can think clearly logically about what it is, or so I think.
Firstly, I guide you towards the author of the infamous book Picnic at Hanging Rock - Joan Lindsay, from Australia. Who apparently had an a deep fascination with time. The book in its own right tells a time tale, but lately more recently I have noticed more time truths.
Moving swiftly into Weird Tales e.g. Lovecraft and Chambers, The King in Yellow pulls me through trying to ascertain whether time as told by the writers of the True Detective TV series really is like a flat circle. Where Death in all his power, looking over us can not see the 3D-ness which we can, and see's earth growing in all its wonders, yet nothing to kill, and so Death created time, so that he could kill the things which grew in the world.
This planet from the outside photographed by space satellites and astronomers, find a circle not a sphere. We all know it is a sphere, but if time is moving forwards it is held within that flat circle.
I have come across three other things: when looking into a mirror, do you see yourself, or Death staring back at you, or do you see your own morbidity? I recently saw a couple of TV programs envisioning some seeing there skeleton or at least a skeleton that was playing Death with a big Scythe coming for them-- JK Rowling's The Casual Vacancy adapted for TV seemed to be a certain choice their.
Alas, time is also said to already be at an end, some say that what we remember fro our past was only a dream. Bringing to light the issue of what we are doing now...because in five years time or five minutes ago we will remember it as if it were a dream, something in our previous landscape. Nothing to tell us it was for real, but in memory only. So does that mean we are dreaming now? Are we locked in our own tomb already, and what does that mean for our future, will we be finding ourselves nearer to the end, or are we already at the end? Has Death caught up with us and eating away at us bit by bit? Our memories turned to ashes, dust to dust we must go devoured in time slowly.
The conspiracy only gets deeper, what if the monitoring of people really is deeply entwined in the bigger meaning? Forsake the argument we are in the Matrix... Knight Rider used to have a talking car that could drive itself and perform all sorts of other functions, not least talk to Michael through a watch.
Today Smart Watches and Google Glasses are coming to be, does that mean that the technology already exists for other more carefully designed plots set to in George Orwell's 1984? For instance, we all worry about how much data, privacy we all have, but we are all using a our smart phones to email, text, Internet, check maps buy stuff etc. It only take the next step for someone to be within a certain distance and be able to read all those communications, maybe the Big Data the telephone companies hold on all of us, contains this material. Last I checked only records of communications, not what's in them could be held by the companies, but say a spool sat on your train carriage had a mobile App/program they could run to pull all your communications, at the press of the button they could read every body's phone, take your pictures, messages, emails...all of your activities and search through to find out whether your are a good citizen or not.
It's only a matter of time before the system catches up, and if it doesn't Death soon will, if he hasn't already.


text:
import { BaseDriver } from 'wix-ui-test-utils/driver-factory';

// For internal use only!
export interface buttonDriverFactory extends BaseDriver {
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  focus: () => void;
  blur: () => void;
  mouseEnter: () => void;
  mouseLeave: () => void;
  getButtonTextContent: () => string;
  isButtonDisabled: () => boolean;
  isPrefixIconExists: () => boolean;
  isSuffixIconExists: () => boolean;
}

redpajama_set_name: RedPajamaGithub


Selling real estate has never been easier. Our full range of services is enhanced by an experienced and knowledgeable team of licensed auctioneers and licensed real estate brokers. This combination brings a high level of real estate expertise, strong negotiation skills and market knowledge, allowing us to handle any type of property with professionalism and confidence.
Cost Effective – The buyer, rather than the seller, pays our commission. A 'buyer's premium' is added to the high bid amount to arrive at the total sale price of the property. This reduction in cost allows the seller to accept a lower price for the property and still achieve the same net proceeds as a traditional sale.
Flexible – The seller has the 'ultimate say-so' with the ability to set a minimum price ('reserve amount') that they will accept for the property. If the auction does not produce an amount acceptable to the seller, the property does not sell.
Easy – The property is sold 'As Is', with no inspections or repairs and no contingencies allowed.
Efficient – We typically require a 4-6 week lead time to set up the auction; if the property sells, the sale will close within 30 days of the auction date.
Effective – Buyers come prepared to purchase with cash or established financing and must pay a significant, non-refundable deposit if they are the winning bidder. Due to the higher, non-refundable deposit, very few transactions fall apart.
You will speak with Adam, the President and Lead Auctioneer, at your property to discuss and customize the best solution to meet your needs.
A one page Auction Booking Contract will be completed and signed to document the agreement to auction your property. Typically 4-6 weeks is needed to properly prepare for the auction, so a date will be selected to allow adequate time.
A minimal advertising fee is charged up front to cover a portion of the advertising costs we incur.
Auction signs will be placed on the property to begin marketing the auction.
An Adam's Auctions staff member will contact you to visit, gather and obtain information about the property to properly market and advertise the auction.
A marketing plan will be implemented to advertise the property and auction, including extensive print advertising, website placement on numerous auction websites, as well as appropriate marketing strategies agreed upon.
An open house will be held approximately 1 week prior to the auction date (an Adam's Auction associate will host the open house).
Individual showings will be scheduled as needed prior to the auction date.
Just prior to the auction, Adam will discuss your 'reserve amount' with you. You have the ability to set a minimum price (reserve amount) that you will accept for the property.
On auction day, Adam will arrive one hour early to allow bidders to view the property again and to answer any final questions you might have as the seller.
Your auction will offer the option of Live Online Bidding. This system will be set up and Adam will speak to the online bidders in his opening remarks and persons can bid online as the live auction is conducted.
If you accept the high bid at the auction, an Auction Sales Contract will be completed and signed by all parties the day of the auction (or as soon thereafter as possible).
If the property sells, the transaction is handled exactly like a traditional sale and closes through a local title company within 30 days of the auction date. As the seller, you will have some closing costs which are the same as those in a traditional sale, except commission, as the buyer pays our commission in an auction situation.
If you do not accept the high bid at the auction, the property does not sell. You do not owe us any additional money in this case.
If the property does not sell, we are happy to discuss listing the property with you through our sister company, Adam's Realty & Auction LLC; however, you are free to proceed with the property in whatever fashion you wish.
Our goal is to conduct an aggressive marketing campaign that leads to a successful auction. You have our commitment to obtain a thorough understanding of your property, communicate with you throughout the process and do our very best to bring a successful result through the auction process.


UPDATE: Adopted! Misty has found her forever home with a loving family where she has a giant baby brother and a 2 acre fenced-in yard! Misty is a beautiful grey and white American Staffordshire Terrier. We believe she is between 1 year to 18 months old. She was a shy girl when she first came to the shelter, but quickly learned to love the walks and affection she gets from volunteers. Misty knows several commands including "sit" and "lie down." She walks very well on the leash and is a calm and mellow dog. She is playful and affectionate with other dogs and enjoys sitting calmly and being petted by people.
If you are interested in learning more about Misty or fostering/adopting her, please contact us or fill out an adoption application online!


· The new series of National Accounts, revising the base year from 2004-05 to 2011-12 have been released in January, 2015. As a part of the base year revision exercise, a comprehensive review of the methodology and datasets was made. The new series incorporates the latest available datasets along with the recommendations laid down under the System of National Accounts, 2008. The data from e-Governance Initiative of Ministry of Corporate Affairs on Corporate Sector has been used for the first time.
· The Base Year of the Consumer Price Index (CPI) has also been revised from 2010=100 to 2012=100 in February, 2015, taking into account the latest consumption patterns of the households. In this revised series, many methodological changes have been incorporated in order to make the indices more robust.
· The All India provisional General (all groups), Group and Sub-Group level Consumer Price Indices (CPI) & Consumer Food Price Index (CFPI) are released every month. The General Consumer Price Indices (CPI) for the month of October, 2015 for rural, urban and combined showed an annual inflation rate of 5.54%, 4.28%, and 5.00% respectively. The Consumer Food Price Index (CFPI) is also released every month since May, 2014 in order to give a clear picture of the movement of retail prices in respect of food items. The Consumer Food Price Indices (CFPI) for October 2015 for rural, urban and combined showed an annual inflation rate of 5.18%, 5.47% and 5.25% respectively.
· The estimates of Gross Domestic Product (GDP) was released on quarterly basis, both at constant (2011-12) and current prices, along with the corresponding quarterly estimates of expenditure components of the GDP. The latest quarterly GDP at constant (2011-12) prices for the quarter July-September, 2015-16 was released on 30th November, 2015, which is estimated at Rs. 27.57 lakh crore, as against Rs. 25.66 lakh crore in corresponding quarter of 2014-15, showing a growth rate of 7.4 percent. Quarterly GVA at Basic Price at constant (2011-12) prices for Q2 of 2015-16 is estimated at Rs. 25.80 lakh crore, as against Rs. 24.02 lakh crore in Q2 of 2014-15, showing a growth rate of 7.4 per cent over the corresponding quarter of previous year.
· The Quick Estimates(QE) of Index of Industrial Production (IIP) with base year 2004-05 are released every month, the general index for the month of September 2015 have been released on 12th November, 2015, which is 3.6% higher as compared to the level in the corresponding month of previous year. The cumulative growth for the period April-September 2015-16 over the corresponding period of the previous year stands at 4.0%.
· Using the dedicated web-portal for collection of data of Annual Survey of Industries (ASI), the results of the ASI 2012-13 have been released on 24th March, 2015. The survey for ASI 2012-13 has also been completed through the web-portal and provisional results for ASI 2013-14 are likely to be released by December, 2015.
· Data validation exercise pertaining to Sixth Economic Census (EC) has been completed. All-India Report and Directory of Establishments with 10 or more workers as per Sixth EC are likely to be released by December, 2015.
· A Data Users' Conference on Index numbers was held on 3rd November, 2015. Subsequent to the workshop on new series of national accounts with base year 2011-12 organized on 13th April, 2015. A large number of participants from a wide cross-section of data users including students, researchers and representatives of private economic institutions, industry associations, media houses and government organizations attended the above workshops.
· An integrated Members of Parliament Local Area Development Scheme (MPLADS) portal is developed and operationalized to monitor all critical aspects such as fund release; fund utilisation; implementation of works; etc.
· This Ministry is also reviewing the Statistical System holistically, on what has been done consistent with the Principles, and what more needs to be done, so as to take all the remaining necessary actions for creating the procedures, systems and institutions in furtherance of the UN Principles. Accordingly, a draft Cabinet Note for Adoption of United Nations Fundamental Principles of Official Statistics was prepared and circulated on 27.08.2015 to Cabinet Secretary, Prime Minister's Office and Secretaries of 84 Ministries/Departments including RBI, requesting for comments/observations.
· On-going central sector infrastructure projects on time and cost overruns are monitored through information uploaded on its Online Computerised Monitoring System (OCMS) by project implementing agencies. It is also proposed to develop a new online OCMS on NET/SQL platform with technical support of NIC. A two-day residential training workshop on the technical and functional aspects of the OCMS was organized on 10-11 August, 2015 for training of State/UT government officers.
· Besides the regular training programmes for Indian Statistical Service and Subordinate Statistical Service officers and other activities, the National Statistical Systems Training Academy (NSSTA) of the Ministry has successfully honoured to conduct two one week residential international training programmes/workshop for the participants of SAARC countries. One Programme on "Health and Demographic Statistics" was organized at NSSTA during 5-9 October, 2015 and a workshop on "Use of Models in Crop Yield Estimation" was organized at IASRI with the collaboration MoSPI during 2-6 November, 2015.
· A two day Conference of Central and States Statistical Organizations (COCSSO) was organized in Guwahati, Assam during 04-05 November, 2015. This Conference was conducted in collaboration with Government of Assam to provide a platform for the Central and State Statisticians to exchange views and discuss common issues relating to statistical activities.
· An All-India workshop was organized for states on new series of national accounts with base year 2011-12 during July 7-9, 2015. The workshop aimed at to acquaint the state officials of the changes in methodologies and data sources in the new series and to provide guidance on compilation of state income estimates on revised base year. Subsequently, discussion with states on comparable estimates of state income for the years 2011-12 to 2013-14 on revised base year were held during the months of August and September 2015. A similar workshop on Price and Industrial Statistics was organized on 3rd September, 2015.
· A nationwide Swachh Bharat campaign began from 25th September, 2015 and ended on 31st October, 2015. In implementation thereof, the Ministry undertook a special cleanliness drive in all the buildings by way of cleaning of windows, glasses, electoral fittings furniture etc in all rooms as well as outside premise, parking space etc.


Molly-Ringwald-Sixteen-Candles-Tina-Fey-Steve-Carell-Date-Night type of romance was out there yesterday, somewhere between the picnic lunches, steak dinners, heart-shape boxes of chocolate, smiles, and kisses it was out there. People celebrating a little thing called love.
I celebrated love as well … the one with sandcastles, plastic shovels from Target, a Batman Frisbee, and a great laugh as the waves tickled their toes.
And yes … there were boogie boards. But also hugs and kisses.
Love comes in many ways, and makes you feel good whether it's Valentine's Day or not. It happens everyday and I was grateful for it yesterday.


text:
$239M Powerball Results for Saturday July 29
By 1751 0
US Powerball
US lottery
Tags: jackpot, Lottery, Powerball lottery, Powerball Results
The winning numbers from the Powerball draw on Saturday July 29th were 1, 28, 40, 45, 48 and the Powerball was 12.
There was a jackpot of $239 million available and it will have been won by anyone that managed to match the five main numbers and the Powerball. Those that matched at least the Powerball or those that matched at least three main numbers without the Powerball will have won cash prizes.
Last Wednesday's draw produced 760,020 winning players that shared prizes totalling $10,936,903. Four players matched five main numbers; one had the Power Play option and won £2 million and the rest won $1 million each. There were 25 players that matched four of the main numbers and the Powerball, 12 had the Power Play option and won $100,000 and the rest won $50,000 each. There were 559 players that matched four of the main numbers, 127 of them had the Power Play option and won $200 each while the remaining 432 won $100 each.
£5.3M National Lottery Results for Saturday July 29
July 30, 2017 Lottery
Enjoy a Month of Free Spins at Casino.com
August 3, 2017 Entertainment
This Weekend Win $145M Powerball Jackpot, €108M EuroMillions Jackpot and More
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This may come as a surprise to some of you, but the Notre Dame Bike Shop is closing indefinitely this semester. It has been wonderful serving the Notre Dame community by working at the bike shop for the past three years. For those of you who haven't heard of the bike shop, it provided free bicycle repair for Notre Dame students and workers. We repaired 331 bikes last school year and also fixed-up old bikes for priests and rectors on campus. All parts we used were salvaged from bikes NDSP collects at the end of the year.
This leads me to two main reasons why the shop closing is such a big loss for the Notre Dame community: sustainability and safety. Our school is making great strides to become a greener, more sustainable family. The bike shop was one of the most sustainable endeavors on campus: all parts were reused from old bikes, all junk parts were recycled and, of course, the shop encouraged riding bikes, the most efficient form of transportation.
The shop was also responsible for promoting safety across campus. A large number of repairs were on broken brakes. I imagine that now most students don't have the resources readily available to fix their broken brakes. Therefore, in the coming months there may be many students speeding through campus without a way to stop for that freshman looking for Geddes Hall or that Jimmy John's driver zipping into campus for a fast drop-off.
It won't take much to restart this invaluable service. All we need is a heated garage where we can store tools and bikes. NDSP is willing to reopen the shop, but for that to happen there needs to be a visible and vocal desire for it. So, I encourage anyone who is reading this to write into the Observer or email me ([email protected]) with a positive bike shop experience or even just a wish for this free and friendly service to be available to the Notre Dame family once again.


text:
The Most Worshipful Grand Lodge of Free and Accepted Masons of the Philippines
The Grand Lodge
About the Grand Lodge
The Grand Master
Foreign Grand Lodges
Plans and Programs
Masonic Charities for Crippled Children
GM Circulars
GS Circulars
Grand Lodge Reports
Grand Master's Report
Grand Lodge Proceedings
The Cable Tow
Masonic Education
Institute of Masonic Education and Studies
Lodge Locator
Rainbow for Girls
The International Order of the Rainbow for Girls (IORG) is a Masonic youth organization which teaches leadership training through community service. Girls (ages 11-20/21) learn about the value of charity and service through their work and involvement with their annual local and Grand service projects.
It strives to give girls the tools, training, and encouragement to let their individual spirits shine bright. By providing members with a safe, fun, caring environment where responsible, older girls can interact and mentor younger girls through family involvement.
Charity and humility presents a unique duality in the tenets of our Ancient Craft. With one hand, a master mason extends his assistance and serves his fellowmen with the other; With one foot, he goes out of his way to help others and is ever ready to kneel and ask for Divine Guidance with the other.
This is what charity and humility dictates and thus are the true foundations of a mason.
MW Bro. Agapito S. Suan, Jr.
Grand Master of Masons
Masonic Year 6019-6020 A.L.
Becoming a Freemason
Grand Lodge Directory
NEW PLARIDEL MASONIC TEMPLE
1440 San Marcelino Street, P. O. Box 990
Ermita, Manila, Philippines 1000
(+632) 522 2218 / 522 2328 / 522 2232
GLP TELEPHONE LINES
Trunklines : (+632) 522 2232 / 522 2328 / 522 2218
Local Numbers >>
IMES Office: (+632) 536 6281
Library: (+632) 708 0473
The Grand Jurisdiction of the Most Worshipful Grand Lodge of F. & A.M. of the Philippines comprises the territory of the Philippines, South Korea, the Marianas Islands, the Marshal Islands, the Ryukyu Islands, South Vietnam and its existing Lodges in Japan.
New Plaridel Masonic Temple, 1440 San Marcelino Street, Ermita, Manila 1000 Philippines