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Sample records for accelerated atherosclerosis development

  1. Accelerated atherosclerosis in patients with chronic inflammatory rheumatologic conditions

    PubMed Central

    Hong, Jison; Maron, David J; Shirai, Tsuyoshi; Weyand, Cornelia M

    2015-01-01

    Atherosclerosis is a complex inflammatory disease involving aberrant immune and tissue healing responses, which begins with endothelial dysfunction and ends with plaque development, instability and rupture. The increased risk for coronary artery disease in patients with rheumatologic diseases highlights how aberrancy in the innate and adaptive immune system may be central to development of both disease states and that atherosclerosis may be on a spectrum of immune-mediated conditions. Recognition of the tight association between chronic inflammatory disease and complications of atherosclerosis will impact the understanding of underlying pathogenic mechanisms and change diagnostic and therapeutic approaches in patients with rheumatologic syndromes as well as patients with coronary artery disease. In this review, we provide a summary of the role of the immune system in atherosclerosis, discuss the proposed mechanisms of accelerated atherosclerosis seen in association with rheumatologic diseases, evaluate the effect of immunosuppression on atherosclerosis and provide updates on available risk assessment tools, biomarkers and imaging modalities. PMID:27042216

  2. The Effect of Mycophenolate Mofetil on Disease Development in the gld.apoE−/− Mouse Model of Accelerated Atherosclerosis and Systemic Lupus Erythematosus

    PubMed Central

    Richez, Christophe; Richards, Rocco J.; Duffau, Pierre; Weitzner, Zachary; Andry, Christopher D.; Rifkin, Ian R.; Aprahamian, Tamar

    2013-01-01

    Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is characterized by autoantibody production and inflammatory disease involving multiple organs. Premature atherosclerosis is a common complication of SLE and results in substantial morbidity and mortality from cardiovascular disease (CVD). The reasons for the premature atherosclerosis in SLE are incompletely understood, although chronic inflammation is thought to play an important role. There is currently no known preventative treatment of premature atherosclerosis in SLE. Mycophenolate mofetil (MMF) is an immunosuppressive agent that is commonly used for treatment of patients with SLE. In order to study the impact of this drug on murine lupus disease including premature atherosclerosis development, we treated gld.apoE−/− mice, a model of SLE and accelerated atherosclerosis, with MMF. We maintained seven-week old gld.apoE−/− mice on a high cholesterol Western diet with or without MMF. After 12 weeks on diet, mice receiving MMF showed decreased atherosclerotic lesion area compared to the control group. MMF treatment also improved the lupus phenotype, indicated by a significant decrease circulating autoantibody levels and ameliorating lupus nephritis associated with this model. This data suggests that the effects of MMF on the immune system may not only be beneficial for lupus, but also for inflammation driving lupus-associated atherosclerosis. PMID:23577189

  3. 56Fe accelerates development of atherosclerosis in apoE -/-mice

    NASA Astrophysics Data System (ADS)

    Kucik, Dennis; Yu, Tao; Parks, Brian; Yu, Shaohua; Srivastava, Roshni; Gupta, Kiran; Wu, Xing; Khaled, Saman; Chang, Polly; Kabarowski, Janusz

    Exposure to radiation from a variety of sources is associated with increased risk of heart disease and stroke. For example, for women with early breast cancer, the benefit of radiotherapy can be nearly offset by the increased risk of mortality from cardiovascular disease. Head and neck cancer patients who undergo radiation treatment are at significantly elevated risk of stroke, even in a relatively young patient population that would not normally be at risk for atheroscle-rosis. Similarly, atomic bomb survivors had an increased incidence of mortality from coronary artery disease and stroke. Even radiation technologists working before 1950 (when occupational exposure was higher) had increased mortality due to circulatory diseases. Although much is known about the cardiovascular consequences these exposures to X-raus and gamma radiation, the response to the type of radiation likely to be encountered in prolonged space flight has not been determined. A key component of this cosmic radiation is 56Fe, which is particularly damaging to tissues. Using collimated beams, we selectively irradiated aortic arches and carotids (only) of the well-established apoE -/-atherosclerosis mouse model to test directly whether 56Fe exposure is a cardiovascular risk factor. Mice were sacrificed at 13 weeks post-irradiation and dissected, and aortas were divided into areas that had been targeted by the ion beam and those that were not. The area that was covered by plaques was then quantified. Plaque area at 13 weeks post-irradiation was significantly greater in targeted areas of mice that had received 5 Gy of 56Fe as compared to age-and sex-matched un-irradiated controls. In the carotid arteries and aortic roots, significantly greater atherosclerosis was apparent for a 2Gy exposure as well (the lowest dose tested). This demonstrates that even a single exposure to heavy ion radiation is capable of triggering events that culminate in cardiovascular disease, even long after the exposure has

  4. [PREDICTORS OF ATHEROSCLEROSIS: NEW DEVELOPMENTS].

    PubMed

    Gozhenko, A I; Kotyuzhinskaya, S G; Kovalevskaya, L A

    2014-12-01

    The article describes known atherosclerosis predictors of endothelial origin, which are diagnostic criteria for identifying's early stages of atherosclerosis, and can prevent the development of this disease and are used to monitor the effectiveness of the therapy The authors analyzed the possibility of using heparin as an early marker of atherosclerosis, based on the fact that the inhibition of lipoprotein lipase activity due hyperheparinemia resulting from depletion of mast cells due to endothelial dysfunction, leads to the disorders of lipid transporting system in the form of the resistant hyperlipidemia with the phenomena of dyslipidemia. PMID:26638463

  5. Synergism between radiotherapy and vascular risk factors in the accelerated development of atherosclerosis: a report of three cases.

    PubMed

    Pherwani, Arun D; Reid, Julie A; Keane, Patrick F; Hannon, Raymond J; Soong, Chee Voon; Lee, Bernard

    2002-09-01

    Radiotherapy is commonly used in the management of testicular tumors. However, to date the risk of radiation-induced vascular occlusive disease in men following radiotherapy for testicular cancer has not been regarded as a major factor in their long-term care. Several animal studies have shown the importance of established vascular risk factors such as hypercholesterolemia and hypertension in the pathogenesis of radiation-induced atherosclerosis. This report presents three cases of premature chronic iliofemoral arterial disease presenting 5,13, and 16 years following exposure to therapeutic irradiation for the treatment of testicular cancer. The patients were in the age group of 40-45 years and all demonstrated associated known atherosclerotic risk factors. The patients had received radiotherapy in the dose of 3,500-4,000 rads in a standard "dog-leg" fashion to the ipsilateral aortoiliac lymphatic chain. Our results showed that young men treated with radiotherapy for testicular cancer may be targeted from the outset for atherosclerotic risk factor reduction to minimize the risk of development of late chronic occlusive arterial disease. It may be that a cohort of men so treated with historical regimes of radiotherapy and now entering middle age should be screened for arterial disease and risk factor reduction. PMID:12183769

  6. Atherosclerosis

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Atherosclerosis? Español Atherosclerosis is a disease in which plaque ... problems, including heart attack , stroke , or even death. Atherosclerosis Figure A shows a normal artery with normal ...

  7. Vascular health late after Kawasaki disease: implications for accelerated atherosclerosis.

    PubMed

    Cheung, Yiu-Fai

    2014-11-01

    Kawasaki disease (KD), an acute vasculitis that primarily affects young children, is the most common acquired paediatric cardiovascular disease in developed countries. While sequelae of arterial inflammation in the acute phase of KD are well documented, its late effects on vascular health are increasingly unveiled. Late vascular dysfunction is characterized by structural alterations and functional impairment in term of arterial stiffening and endothelial dysfunction and shown to involve both coronary and systemic arteries. Further evidence suggests that continuous low grade inflammation and ongoing active remodeling of coronary arterial lesions occur late after acute illness and may play a role in structural and functional alterations of the arteries. Potential importance of genetic modulation on vascular health late after KD is implicated by associations between mannose binding lectin and inflammatory gene polymorphisms with severity of peripheral arterial stiffening and carotid intima-media thickening. The changes in cholesterol and lipoproteins levels late after KD further appear similar to those proposed to be atherogenic. While data on adverse vascular health are less controversial in patients with persistent or regressed coronary arterial aneurysms, data appear conflicting in individuals with no coronary arterial involvements or only transient coronary ectasia. Notwithstanding, concerns have been raised with regard to predisposition of KD in childhood to accelerated atherosclerosis in adulthood. Until further evidence-based data are available, however, it remains important to assess and monitor cardiovascular risk factors and to promote cardiovascular health in children with a history of KD in the long term. PMID:25550701

  8. Increased LDL susceptibility to oxidation accelerates future carotid artery atherosclerosis

    PubMed Central

    2012-01-01

    Background We analyzed the causal relationship between LDL susceptibility to oxidation and the development of new carotid artery atherosclerosis over a period of 5 years. We previously described the determinants related to a risk of cardiovascular changes determined in a Japanese population participating in the Niigata Study, which is an ongoing epidemiological investigation of the prevention of cardiovascular diseases. Methods We selected 394 individuals (169 males and 225 females) who underwent a second carotid artery ultrasonographic examination in 2001 - 2002 for the present study. The susceptibility of LDL to oxidation was determined as the photometric absorbance and electrophoretic mobility of samples that had been collected in 1996 - 1997. The measurements were compared with ultrasonographic findings obtained in 2001 - 2002. Results The multivariate-adjusted model showed that age (odds ratio (OR), 1.034; 95% confidence interval (95%CI), 1.010 - 1.059), HbA1c (OR, 1.477; 95%CI, 0.980 - 2.225), and photometric O/N (OR, 2.012; 95%CI, 1.000 - 4.051) were significant variables that could independently predict the risk of new carotid artery atherosclerosis. Conclusion The susceptibility of LDL to oxidation was a significant parameter that could predict new carotid artery atherosclerosis over a 5-year period, and higher susceptibility was associated with a higher incidence of new carotid artery atherosclerosis. PMID:22230558

  9. Atherosclerosis

    MedlinePlus

    Atherosclerosis is a disease in which plaque builds up inside your arteries. Plaque is a sticky substance ... flow of oxygen-rich blood to your body. Atherosclerosis can lead to serious problems, including Coronary artery ...

  10. Atherosclerosis

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Atherosclerosis Updated:Jul 6,2015 View an animation of ... the arteries as you get older. How does atherosclerosis start and progress? It's a complex process. Exactly ...

  11. CD4+CXCR3+ T cells and plasmacytoid dendritic cells drive accelerated atherosclerosis associated with systemic lupus erythematosus.

    PubMed

    Clement, Marc; Charles, Nicolas; Escoubet, Brigitte; Guedj, Kevin; Chauveheid, Marie-Paule; Caligiuri, Giuseppina; Nicoletti, Antonino; Papo, Thomas; Sacre, Karim

    2015-09-01

    Cardiovascular disease due to accelerated atherosclerosis is the leading cause of death in patients with systemic lupus erythematosus (SLE). Noteworthy, accelerated atherosclerosis in SLE patients appears to be independant of classical Framingham risk factors. This suggests that aggravated atherosclerosis in SLE patients may be a result of increased inflammation and altered immune responses. However, the mechanisms that mediate the acceleration of atherosclerosis in SLE remain elusive. Based on experimental data which includes both humans (SLE patients and control subjects) and rodents (ApoE-/- mice), we herein propose a multi-step model in which the immune dysfunction associated with SLE (i.e. high level of IFN-α production by TLR 9-stimulated pDCs) is associated with, first, an increased frequency of circulating pro inflammatory CD4+CXCR3+ T cells; second, an increased production of CXCR3 ligands by endothelial cells; third, an increased recruitment of pro-inflammatory CD4+CXCR3+ T cells into the arterial wall, and fourth, the development of atherosclerosis. In showing how SLE may promote accelerated atherosclerosis, our model also points to hypotheses for potential interventions, such as pDCs-targeted therapy, that might be studied in the future. PMID:26183767

  12. Activation of the NLRP3 inflammasome in Porphyromonas gingivalis-accelerated atherosclerosis.

    PubMed

    Yamaguchi, Yohei; Kurita-Ochiai, Tomoko; Kobayashi, Ryoki; Suzuki, Toshihiko; Ando, Tomohiro

    2015-06-01

    Porphyromonas gingivalis has been shown to accelerate atherosclerotic lesion development in hyperlipidemic animals. Atherosclerosis is a disease characterized by inflammation of the arterial wall. Recent studies have suggested that the NLRP3 inflammasome plays an important role in the development of vascular inflammation and atherosclerosis. Herein, we investigated a possible association between the inflammasome in atherosclerosis and periodontal disease induced by P. gingivalis infection using apolipoprotein E-deficient, spontaneously hyperlipidemic (Apoe(shl)) mice. Oral infection with wild-type (WT) P. gingivalis significantly increased the area of aortic sinus covered with atherosclerotic plaque and alveolar bone loss, compared with KDP136 (gingipain-null mutant) or KDP150 (FimA-deficient mutant) challenge. WT challenge also increased IL-1β, IL-18 and TNF-α production in peritoneal macrophages, and gingival or aortic gene expression of Nod-like receptor family, pyrin domain containing 3 (NLRP3), pro-IL-1β, pro-IL-18 and pro-caspase-1. Porphyromonas gingivalis genomic DNA was detected more in the aorta, gingival tissue, liver and spleen of WT-challenged mice than those in KDP136- or KDP150-challenged mice. We conclude that WT P. gingivalis activates innate immune cells through the NLRP3 inflammasome compared with KDP136 or KDP150. The NLRP3 inflammasome may play a critical role in periodontal disease and atherosclerosis induced by P. gingivalis challenge through sustained inflammation. PMID:25663345

  13. Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development

    PubMed Central

    Berbée, Jimmy F. P.; Boon, Mariëtte R; Khedoe, P. Padmini S. J.; Bartelt, Alexander; Schlein, Christian; Worthmann, Anna; Kooijman, Sander; Hoeke, Geerte; Mol, Isabel M.; John, Clara; Jung, Caroline; Vazirpanah, Nadia; Brouwers, Linda P.J.; Gordts, Philip L.S.M.; Esko, Jeffrey D.; Hiemstra, Pieter S.; Havekes, Louis M.; Scheja, Ludger; Heeren, Joerg; Rensen, Patrick C.N.

    2015-01-01

    Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by β3-adrenergic receptor stimulation protects from atherosclerosis in hyperlipidemic APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism that unlike hyperlipidemic Apoe−/− and Ldlr−/− mice expresses functional apoE and LDLR. BAT activation increases energy expenditure and decreases plasma triglyceride and cholesterol levels. Mechanistically, we demonstrate that BAT activation enhances the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT, subsequently accelerating the hepatic clearance of the cholesterol-enriched remnants. These effects depend on a functional hepatic apoE-LDLR clearance pathway as BAT activation in Apoe−/− and Ldlr−/− mice does not attenuate hypercholesterolaemia and atherosclerosis. We conclude that activation of BAT is a powerful therapeutic avenue to ameliorate hyperlipidaemia and protect from atherosclerosis. PMID:25754609

  14. Mesenchymal Stem Cells Reduce Murine Atherosclerosis Development

    PubMed Central

    Frodermann, Vanessa; van Duijn, Janine; van Pel, Melissa; van Santbrink, Peter J.; Bot, Ilze; Kuiper, Johan; de Jager, Saskia C. A.

    2015-01-01

    Mesenchymal stem cells (MSCs) have regenerative properties, but recently they were also found to have immunomodulatory capacities. We therefore investigated whether MSCs could reduce atherosclerosis, which is determined by dyslipidaemia and chronic inflammation. We adoptively transferred MSCs into low-density lipoprotein-receptor knockout mice and put these on a Western-type diet to induce atherosclerosis. Initially after treatment, we found higher levels of circulating regulatory T cells. In the long-term, overall numbers of effector T cells were reduced by MSC treatment. Moreover, MSC-treated mice displayed a significant 33% reduction in circulating monocytes and a 77% reduction of serum CCL2 levels. Most strikingly, we found a previously unappreciated effect on lipid metabolism. Serum cholesterol was reduced by 33%, due to reduced very low-density lipoprotein levels, likely a result of reduced de novo hepatic lipogenesis as determined by a reduced expression of Stearoyl-CoA desaturase-1 and lipoprotein lipase. MSCs significantly affected lesion development, which was reduced by 33% in the aortic root. These lesions contained 56% less macrophages and showed a 61% reduction in T cell numbers. We show here for the first time that MSC treatment affects not only inflammatory responses but also significantly reduces dyslipidaemia in mice. This makes MSCs a potent candidate for atherosclerosis therapies. PMID:26490642

  15. Atherosclerosis

    MedlinePlus Videos and Cool Tools

    ... are smooth, allowing blood to flow unimpeded. Atherosclerosis is when harmful material collects on the wall of ... Eventually, the material builds up and a plaque is formed, narrowing the artery. When the build-up ...

  16. Age-accelerated atherosclerosis correlates with failure to upregulate antioxidant genes.

    PubMed

    Collins, Alan R; Lyon, Christopher J; Xia, Xuefeng; Liu, Joey Z; Tangirala, Rajendra K; Yin, Fen; Boyadjian, Rima; Bikineyeva, Alfiya; Praticò, Domenico; Harrison, David G; Hsueh, Willa A

    2009-03-27

    Excess food intake leads to obesity and diabetes, both of which are well-known independent risk factors for atherosclerosis, and both of which are growing epidemics in an aging population. We hypothesized that aging enhances the metabolic and vascular effects of high fat diet (HFD) and therefore examined the effect of age on atherosclerosis and insulin resistance in lipoprotein receptor knockout (LDLR(-/-)) mice. We found that 12-month-old (middle-aged) LDLR(-/-) mice developed substantially worse metabolic syndrome, diabetes, and atherosclerosis than 3-month-old (young) LDLR(-/-) mice when both were fed HFD for 3 months, despite similar elevations in total cholesterol levels. Microarray analyses were performed to analyze the mechanism responsible for the marked acceleration of atherosclerosis in middle-aged mice. Chow-fed middle-aged mice had greater aortic expression of multiple antioxidant genes than chow-fed young mice, including glutathione peroxidase-1 and -4, catalase, superoxide dismutase-2, and uncoupling protein-2. Aortic expression of these enzymes markedly increased in young mice fed HFD but decreased or only modestly increased in middle-aged mice fed HFD, despite the fact that systemic oxidative stress and vascular reactive oxygen species generation, measured by plasma F2alpha isoprostane concentration (systemic) and dihydroethidium conversion and p47phox expression (vascular), were greater in middle-aged mice fed HFD. Thus, the mechanism for the accelerated vascular injury in older LDLR(-/-) mice was likely the profound inability to mount an antioxidant response. This effect was related to a decrease in vascular expression of 2 key transcriptional pathways regulating the antioxidant response, DJ-1 and forkhead box, subgroup O family (FOXOs). Treatment of middle-aged mice fed HFD with the antioxidant apocynin attenuated atherosclerosis, whereas treatment with the insulin sensitizer rosiglitazone attenuated both metabolic syndrome and atherosclerosis

  17. Metabolomic Profiling of Arginine Metabolome Links Altered Methylation to Chronic Kidney Disease Accelerated Atherosclerosis

    PubMed Central

    Mathew, Anna V; Zeng, Lixia; Byun, Jaeman; Pennathur, Subramaniam

    2015-01-01

    Atherosclerotic cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD), but the mechanisms underlying vascular disease has not been fully understood. As the nitrogen donor in nitric oxide (NO·) synthesis, arginine and its metabolic products are integrally linked to vascular health and information. We hypothesized that derangements in this pathway could explain, in part, increased atherosclerotic risk in CKD. We developed a targeted metabolomic platform to profile quantitatively arginine metabolites in plasma by liquid chromatography tandem mass spectrometry (LC/MS). Male low-density lipoprotein receptor defcient (LDLr−/−) mice at age 6 weeks were subjected to sham or 5/6 nephrectomy surgery to induce CKD. Subsequently, the animals were maintained on high fat diet for 24 weeks. Targeted metabolomic analysis of arginine metabolites in plasma was performed by isotope dilution LC/MS including asymmetric dimethyl arginine (ADMA), symmetric dimethyl arginine (SDMA), N-mono-methylarginine (NMMA), arginine and citrulline. Although elevated plasma levels of ADMA and SDMA were found in the CKD mice, only higher ADMA level correlated with degree of atherosclerosis. No significant differences were noted in levels of NMMA between the groups. CKD mice had high levels of citrulline and arginine, but ADMA levels had no correlation with either of these metabolites. These fndings strongly implicate altered arginine methylation and accumulation of ADMA, may in part contribute to CKD accelerated atherosclerosis. It raises the possibility that interrupting pathways that generate ADMA or enhance its metabolism may have therapeutic potential in mitigating atherosclerosis. PMID:26778898

  18. RNA Interference of Myocyte Enhancer Factor 2A Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice

    PubMed Central

    Zhao, Yu-xia; Liu, Gang-qiong; Zhang, Jin-ying

    2015-01-01

    Objective Myocyte enhancer factor-2A (MEF 2A) has been shown to be involved in atherosclerotic lesion development, but its role in preexisting lesions is still unclear. In the present study we aim to assess the role of MEF 2A in the progression of pre-existing atherosclerosis. Methods Eighty apolipoprotein E-deficient mice (APOE KO) were randomly allocated to control, scramble and MEF 2A RNA interference (RNAi) groups, and constrictive collars were used to induce plaque formation. Six weeks after surgery, lentiviral shRNA construct was used to silence the expression of MEF 2A. Carotid plaques were harvested for analysis 4 weeks after viral vector transduction. Inflammatory gene expression in the plasma and carotid plaques was determined by using ELISAs and real-time RT-PCR. Results The expression level of MEF 2A was significantly reduced in plasma and plaque in the RNAi group, compared to the control and NC groups, whereas the expression level of pro-inflammatory cytokines was markedly increased. Silencing MEF 2A using lentiviral shRNA significantly reduced the plaque collagen content and fibrous cap thickness, as well as increased plaque area. However, silencing MEF 2A had no obvious effect on plaque lipid content. Conclusions Lentivirus-mediated MEF 2A shRNA accelerates inflammation and atherosclerosis in APOE KO mice, but has no effect on lipoprotein levels in plasma. PMID:25793529

  19. Thrombosis and blood cells in atherosclerosis development.

    PubMed

    Santolaya, C; Hernández, M R; Villaverde, C A

    1988-06-01

    Hemorheological changes produced in blood cells seem to be essential in atheroma plaque development and thrombotic episodes. In this study, we investigated the relationship between blood cells count, thrombogenic situations and morphological mesenteric alterations in atherosclerotic rats. Atherosclerosis was induced by an atherogenic diet made up of two phases, the first a hypervitaminic diet, and the second a hyperlipidic one. Cell counts were performed with Thoma's camera. Morphological changes were observed directly in rat mesentery. Thrombogenic situations were investigated by a mesenteric microthrombosis induction method. In atherosclerotic animals we can observe a higher mesenteric opacity, increase in blood viscosity and a thickness in vessel wall. Thrombosis time is shortened at 3 days, which indicates a thrombogenic situation although at 10 days there is a lenthening in this parameter. Blood cell counts were not modified significantly, but modifications in differential leukocyte counts were significant. We found a direct relationship between lymphocyte number and thrombosis time whereas with granulocytes this relationship was inverse: shortening in thrombosis time appearing simultaneously with an increase in cell number. PMID:3419397

  20. Imaging Macrophage Development and Fate in Atherosclerosis and Myocardial Infarction

    PubMed Central

    Swirski, Filip K.; Nahrendorf, Matthias

    2013-01-01

    Macrophages are central regulators of disease progression in both atherosclerosis and myocardial infarction. In atherosclerosis, macrophages are the dominant leukocyte population that influences lesional development. In myocardial infarction, which is caused by atherosclerosis, macrophages accumulate readily and play important roles in inflammation and healing. Molecular imaging has grown considerably as a field and can reveal biological process at the molecular, cellular, and tissue levels. Here we explore how various imaging modalities, from intravital microscopy in mice to organ-level imaging in patients, are contributing to our understanding of macrophages and their progenitors in cardiovascular disease. PMID:23207281

  1. Diabetes accelerates smooth muscle accumulation in lesions of atherosclerosis: lack of direct growth-promoting effects of high glucose levels.

    PubMed

    Suzuki, L A; Poot, M; Gerrity, R G; Bornfeldt, K E

    2001-04-01

    In combination with other factors, hyperglycemia may cause the accelerated progression of atherosclerosis in people with diabetes. Arterial smooth muscle cell (SMC) proliferation and accumulation contribute to formation of advanced atherosclerotic lesions. Therefore, we investigated the effects of hyperglycemia on SMC proliferation and accumulation in vivo and in isolated arteries and SMCs by taking advantage of a new porcine model of diabetes-accelerated atherosclerosis, in which diabetic animals are hyperglycemic without receiving exogenous insulin. We show that diabetic animals fed a cholesterol-rich diet, like humans, develop severe lesions of atherosclerosis characterized by SMC accumulation and proliferation, whereas lesions in nondiabetic animals contain fewer SMCs after 20 weeks. However, high glucose (25 mmol/l) does not directly stimulate the proliferation of SMCs in isolated arterial tissue from diabetic or nondiabetic animals, or of cultured SMCs from these animals or from humans. Furthermore, the mitogenic actions of platelet-derived growth factor, IGF-I, or serum are not enhanced by high glucose. High glucose increases SMC glucose metabolism through the citric acid cycle and the pentose phosphate pathway by 240 and 90%, respectively, but <10% of consumed glucose is metabolized through these pathways. Instead, most of the consumed glucose is converted into lactate and secreted by the SMCs. Thus, diabetes markedly accelerates SMC proliferation and accumulation in atherosclerotic lesions. The stimulatory effect of diabetes on SMCs is likely to be mediated by effects secondary to the hyperglycemic state. PMID:11289052

  2. Atherosclerosis in ancient humans, accelerated aging syndromes and normal aging: is lamin a protein a common link?

    PubMed

    Miyamoto, Michael I; Djabali, Karima; Gordon, Leslie B

    2014-06-01

    Imaging studies of ancient human mummies have demonstrated the presence of vascular calcification that is consistent with the presence of atherosclerosis. These findings have stimulated interest in the underlying biological processes that might impart to humans an inherent predisposition to the development of atherosclerosis. Clues to these processes may possibly be found in accelerated aging syndromes, such as Hutchinson-Gilford progeria syndrome (HGPS), an ultra-rare disorder characterized by premature aging phenotypes, including very aggressive forms of atherosclerosis, occurring in childhood. The genetic defect in HGPS eventuates in the production of a mutant form of the nuclear structural protein lamin A, called progerin, which is thought to interfere with normal nuclear functioning. Progerin appears to be expressed in vascular cells, resulting in vessel wall cell loss and replacement by fibrous tissue, reducing vessel compliance and promoting calcification, leading to the vascular dysfunction and atherosclerosis seen in HGPS. Interestingly, vascular progerin is detectable in lower levels, in an age-related manner, in the general population, providing the basis for further study of the potential role of abnormal forms of lamin A in the atherosclerotic process of normal aging. PMID:25667091

  3. Inhibition of Nuclear Factor of Activated T-Cells (NFAT) Suppresses Accelerated Atherosclerosis in Diabetic Mice

    PubMed Central

    Zetterqvist, Anna V.; Berglund, Lisa M.; Blanco, Fabiana; Garcia-Vaz, Eliana; Wigren, Maria; Dunér, Pontus; Andersson, Anna-Maria Dutius; To, Fong; Spegel, Peter; Nilsson, Jan; Bengtsson, Eva; Gomez, Maria F.

    2013-01-01

    Objective of the Study Diabetic patients have a much more widespread and aggressive form of atherosclerosis and therefore, higher risk for myocardial infarction, peripheral vascular disease and stroke, but the molecular mechanisms leading to accelerated damage are still unclear. Recently, we showed that hyperglycemia activates the transcription factor NFAT in the arterial wall, inducing the expression of the pro-atherosclerotic protein osteopontin. Here we investigate whether NFAT activation may be a link between diabetes and atherogenesis. Methodology and Principal Findings Streptozotocin (STZ)-induced diabetes in apolipoprotein E−/− mice resulted in 2.2 fold increased aortic atherosclerosis and enhanced pro-inflammatory burden, as evidenced by elevated blood monocytes, endothelial activation- and inflammatory markers in aorta, and pro-inflammatory cytokines in plasma. In vivo treatment with the NFAT blocker A-285222 for 4 weeks completely inhibited the diabetes-induced aggravation of atherosclerosis, having no effect in non-diabetic mice. STZ-treated mice exhibited hyperglycemia and higher plasma cholesterol and triglycerides, but these were unaffected by A-285222. NFAT-dependent transcriptional activity was examined in aorta, spleen, thymus, brain, heart, liver and kidney, but only augmented in the aorta of diabetic mice. A-285222 completely blocked this diabetes-driven NFAT activation, but had no impact on the other organs or on splenocyte proliferation or cytokine secretion, ruling out systemic immunosuppression as the mechanism behind reduced atherosclerosis. Instead, NFAT inhibition effectively reduced IL-6, osteopontin, monocyte chemotactic protein 1, intercellular adhesion molecule 1, CD68 and tissue factor expression in the arterial wall and lowered plasma IL-6 in diabetic mice. Conclusions Targeting NFAT signaling may be a novel and attractive approach for the treatment of diabetic macrovascular complications. PMID:23755169

  4. Serum Hepcidin Predicts Uremic Accelerated Atherosclerosis in Chronic Hemodialysis Patients with Diabetic Nephropathy

    PubMed Central

    Li, Han; Feng, Su-Juan; Su, Lu-Lu; Wang, Wei; Zhang, Xiao-Dong; Wang, Shi-Xiang

    2015-01-01

    Background: Hepcidin, as a regulator of body iron stores, has been recently discovered to play a critical role in the pathogenesis of anemia of chronic disease. Atherosclerotic cardiovascular disease is the most common complication and the leading cause of death in chronic hemodialysis (CHD) patients. In the current study, we aimed to explore the relationship between serum hepcidin and uremic accelerated atherosclerosis (UAAS) in CHD patients with diabetic nephropathy (CHD/DN). Methods: A total of 78 CHD/DN and 86 chronic hemodialyzed nondiabetic patients with chronic glomerulonephritis (CHD/non-DN) were recruited in this study. The level of serum hepcidin-25 was specifically measured by liquid chromatography-tandem mass spectrometry. Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. Results: High serum level of hepcidin-25 was seen in CHD patients. Serum hepcidin-25 in CHD/DN was significantly higher than that in CHD/non-DN patients. Serum hepcidin-25 was positively correlated with ferritin, high-sensitivity C-reactive protein (hs-CRP), TNF-α, and IL-6 in CHD/DN patients. CHD/DN patients exhibited higher common carotid artery intima media thickness (CCA-IMT), hs-CRP, and hepcidin-25 levels than that in CHD/non-DN patients. Moreover, in CHD/DN patients, CCA-IMT was positively correlated with serum hepcidin, hs-CRP, and low-density lipoprotein-cholesterol. On multiple regression analysis, serum hepcidin and hs-CRP level exhibited independent association with IMT in CHD/DN patients. Conclusions: These findings suggest possible linkage between iron metabolism and hepcidin modulation abnormalities that may contribute to the development of UAAS in CHD/DN patients. PMID:25963357

  5. Deletion of sirtuin 6 accelerates endothelial dysfunction and atherosclerosis in apolipoprotein E-deficient mice.

    PubMed

    Liu, Zhiping; Wang, Jiaojiao; Huang, Xiaoyang; Li, Zhuoming; Liu, Peiqing

    2016-06-01

    Sirtuin 6 (SIRT6) is a chromatin-associated deacetylase that plays a leading role in genomic stability and aging. However, the precise role of SIRT6 in atherosclerosis, an aging-associated cardiovascular disease, remains elusive. This study aims at defining the role of SIRT6 in atherosclerotic lesion development. SIRT6 messenger RNA and protein expression are markedly decreased in atherosclerotic aortas of apolipoprotein E-deficient (ApoE(-/-)) mice fed a high-cholesterol diet. SIRT6 was knocked down in ApoE(-/-) mice using small hairpin RNAs (shRNAs) lentivirus injection. SIRT6-shRNA-treated ApoE(-/-) mice showed impaired endothelium-dependent vasodilation, increased plaque size (in aortic sinus, aortic root and en face aorta), and augmented plaque vulnerability (evidenced by increased necrotic core areas and macrophage accumulation and reduced collagen content). At the cellular level, SIRT6 depletion by RNA interference in human umbilical vein endothelial cells significantly increased monocyte adhesion to endothelial cells by inducing the expression of intracellular adhesion molecule-1. Consistently, intracellular adhesion molecule-1 expression was significantly upregulated in aortic endothelium of SIRT6-shRNA-treated ApoE(-/-) mice compared with controls. In sum, the aforementioned findings suggest that SIRT6 is a primary negative regulation factor in endothelial dysfunction and atherosclerosis development. As a result, SIRT6 is a promising therapeutic target for treating atherosclerosis and its cardiovascular complications. PMID:26924042

  6. Hyperhomocysteinemia promotes inflammatory monocyte generation and accelerates atherosclerosis in transgenic cystathionine β-synthase deficient mice

    PubMed Central

    Zhang, Daqing; Jiang, Xiaohua; Fang, Pu; Yan, Yan; Song, Jian; Gupta, Sapna; Schafer, Andrew I.; Durante, William; Kruger, Warren D.; Yang, Xiaofeng; Wang, Hong

    2009-01-01

    Background Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases. Monocytes display inflammatory and resident subsets, and commit to specific functions in atherogenesis. In this study, we examined the hypothesis that HHcy modulates monocyte heterogeneity and leads to atherosclerosis. Methods and Results We established a novel atherosclerosis susceptible mouse model with both severe HHcy and hypercholesterolemia, in which the mouse cystathionine β-synthase (CBS) and apolipoprotein E (apoE) genes are deficient, and an inducible human CBS transgene is introduced to circumvent the neonatal lethality of the CBS deficiency (Tg-hCBS apoE−/− Cbs−/− mice). Severe HHcy accelerated atherosclerosis and inflammatory monocyte/macrophage accumulation in lesions and increased plasma TNFα and MCP-1 levels in Tg-hCBS apoE−/− Cbs−/− mice fed a high fat diet. Furthermore, we characterized monocyte heterogeneity in Tg-hCBS apoE−/− Cbs−/− mice and another severe HHcy mouse model (Tg-S466L Cbs−/−) with a disease relevant mutation (Tg-S466L) that lacks hyperlipidemia. HHcy increased monocyte population and selective expansion of inflammatory Ly-6Chi and Ly-6Cmid monocyte subsets in blood, spleen and bone marrow of Tg-S466L Cbs−/− and Tg-hCBS apoE−/− Cbs−/− mice. These changes were exacerbated in Tg-S466L Cbs−/− mice with aging. Addition of L-homocysteine (100–500 μM), but not L-cysteine, maintained the Ly-6Chi subset and induced the Ly-6Cmid subset in cultured mouse primary splenocytes. Homocysteine-induced differentiation of Ly-6Cmid subset was prevented by catalase plus SOD, and the NAD(P)H oxidase inhibitor, apocynin. Conclusions HHcy promotes differentiation of inflammatory monocyte subsets and their accumulation in atherosclerotic lesions via NAD(P)H oxidase-mediated oxidant stress. PMID:19858416

  7. Probucol via inhibition of NHE1 attenuates LPS-accelerated atherosclerosis and promotes plaque stability in vivo.

    PubMed

    Li, Jian-Fei; Chen, Song; Feng, Jun-Duo; Zhang, Ming-Yu; Liu, Xiao-Xia

    2014-04-01

    Activation of Na(+)/H(+) exchanger 1 (NHE1) by lipopolysaccharide (LPS) via Ca(2+)/calpain is responsible in vascular smooth muscle cell (VSMC) apoptosis and to the process of atherosclerosis. Probucol is a lipid-lowering drug which has an anti-atherosclerosis effect. The mechanism remains poorly understood. Here we hypothesized that probucol via inhibition of NHE1 in VSMCs attenuates LPS-accelerated atherosclerosis and promotes plaque stability. Our results revealed that treatment of VSMCs with LPS increased the NHE1 activity in a time-dependent manner, associated with the increased Ca(2+)i. Probucol inhibited the LPS-induced increase of NHE1 activity in a dose-dependent manner in VSMCs for 24-hour co-incubation, as well as the change of Ca(2+)i. In addition, LPS enhanced the calpain activity. Both probucol and calcium chelation of Ca(2+) abolished the LPS-induced increase of calpain activity. Treatment of VSMCs with LPS reduced the expression of Bcl-2 without altering the mRNA level. Probucol inhibited the LPS-reduced expression of Bcl-2 protein in VSMCs. Animal studies indicated administration of probucol suppressed LPS-accelerated apoptosis, atherosclerosis and plaque instability in Apoe(-/-) mice. In conclusion, probucol via inhibition of NHE1 attenuates atherosclerosis lesion growth and promotes plaque stability. PMID:24594116

  8. Advanced accelerator theory development

    SciTech Connect

    Sampayan, S.E.; Houck, T.L.; Poole, B.; Tishchenko, N.; Vitello, P.A.; Wang, I.

    1998-02-09

    A new accelerator technology, the dielectric wall accelerator (DWA), is potentially an ultra compact accelerator/pulsed power driver. This new accelerator relies on three new components: the ultra-high gradient insulator, the asymmetric Blumlein and low jitter switches. In this report, we focused our attention on the first two components of the DWA system the insulators and the asymmetric Blumlein. First, we sought to develop the necessary design tools to model and scale the behavior of the high gradient insulator. To perform this task we concentrated on modeling the discharge processes (i.e., initiation and creation of the surface discharge). In addition, because these high gradient structures exhibit favorable microwave properties in certain accelerator configurations, we performed experiments and calculations to determine the relevant electromagnetic properties. Second, we performed circuit modeling to understand energy coupling to dynamic loads by the asymmetric Blumlein. Further, we have experimentally observed a non-linear coupling effect in certain asymmetric Blumlein configurations. That is, as these structures are stacked into a complete module, the output voltage does not sum linearly and a lower than expected output voltage results. Although we solved this effect experimentally, we performed calculations to understand this effect more fully to allow better optimization of this DWA pulse-forming line system.

  9. TRAIL-deficiency accelerates vascular calcification in atherosclerosis via modulation of RANKL.

    PubMed

    Di Bartolo, Belinda A; Cartland, Siân P; Harith, Hanis H; Bobryshev, Yuri V; Schoppet, Michael; Kavurma, Mary M

    2013-01-01

    The osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) cytokine system, not only controls bone homeostasis, but has been implicated in regulating vascular calcification. TNF-related apoptosis-inducing ligand (TRAIL) is a second ligand for OPG, and although its effect in vascular calcification in vitro is controversial, its role in vivo is not yet established. This study aimed to investigate the role of TRAIL in vascular calcification in vitro using vascular smooth muscle cells (VSMCs) isolated from TRAIL(-/-) and wild-type mice, as well as in vivo, in advanced atherosclerotic lesions of TRAIL(-/-)ApoE(-/-) mice. The involvement of OPG and RANKL in this process was also examined. TRAIL dose-dependently inhibited calcium-induced calcification of human VSMCs, while TRAIL(-/-) VSMCs demonstrated accelerated calcification induced by multiple concentrations of calcium compared to wild-type cells. Consistent with this, RANKL mRNA was significantly elevated with 24 h calcium treatment, while OPG and TRAIL expression in human VSMCs was inhibited. Brachiocephalic arteries from TRAIL(-/-)ApoE(-/-) and ApoE(-/-) mice fed a high fat diet for 12 w demonstrated increased chondrocyte-like cells in atherosclerotic plaque, as well as increased aortic collagen II mRNA expression in TRAIL(-/-)ApoE(-/-) mice, with significant increases in calcification observed at 20 w. TRAIL(-/-)ApoE(-/-) aortas also had significantly elevated RANKL, BMP-2, IL-1β, and PPAR-γ expression at 12 w. Our data provides the first evidence that TRAIL deficiency results in accelerated cartilaginous metaplasia and calcification in atherosclerosis, and that TRAIL plays an important role in the regulation of RANKL and inflammatory markers mediating bone turn over in the vasculature. PMID:24040204

  10. A dual enzymatic-biosensor for simultaneous determination of glucose and cholesterol in serum and peritoneal macrophages of diabetic mice: evaluation of the diabetes-accelerated atherosclerosis risk.

    PubMed

    Huang, Qilin; An, Yarui; Tang, Linlin; Jiang, Xiaoli; Chen, Hua; Bi, Wenji; Wang, Zhongchuan; Zhang, Wen

    2011-11-30

    In this paper, a novel dual enzymatic-biosensor is described for simultaneous determination of glucose and cholesterol in serum and peritoneal macrophages (PMs) of diabetic mice to evaluate the risk of diabetes-accelerated atherosclerosis. The biosensor was constructed by a three-step method. First, a poly-thionine (PTH) film was assembled on the surface of glassy carbon electrode by cyclic voltammetric electropolymerization of thionine, which serves as an electron transfer mediator (ETM). Second, gold nanoparticles (GNPs) were covered on the surface of PTH facilitating the electron transfer between glucose oxidase (GOx), cholesterol oxidase (ChOx) and electrode. Finally, the enzymes, GOx, cholesterol esterase (ChE), and ChOx, were covalently attached to the PTH layer through a chitosan (CH) linker. The PTH coupled with GNPs provides good selectivity, high sensitivity and little crosstalk for the dual enzymatic-biosensor. The developed biosensor had good electrocatalytic activity toward the oxidations of glucose and cholesterol, exhibiting a linear range from 0.008 mM to 6.0 mM for glucose with a detection limit of 2.0 μM, and a linear range from 0.002 mM to 1.0 mM for cholesterol with a detection limit of 0.6 μM. The results of the diabetic mice demonstrated that the cholesterol level did not change obviously with the increase of glucose level in serum, while the cholesterol level was induced with the increase of the glucose level in PMs. Previous studies have shown that the large accumulation of cholesterol in macrophage could lead to macrophage foam cell formation, which is the hallmark of early atherosclerosis. This study provides useful further evidences for the development of diabetes-accelerated atherosclerosis. PMID:22027130

  11. Rosiglitazone impedes Porphyromonas gingivalis-accelerated atherosclerosis by downregulating the TLR/NF-κB signaling pathway in atherosclerotic mice.

    PubMed

    Pan, Shengbo; Lei, Lang; Chen, Shuai; Li, Houxuan; Yan, Fuhua

    2014-12-01

    Porphyromonas gingivalis,a predominant periodontal pathogen, is known to accelerate atherosclerosis in hyperlipidemic animals via aberrant inflammatory responses. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have been reported to exert anti-inflammatory effects in vitro. The purpose of the present study was to investigate the potential protective role of the PPARγ agonist rosiglitazone in pathogen accelerated atherosclerosis in an apolipoprotein E-deficient (ApoE-/-) mouse model. ApoE-/- mice were inoculated intravenously with live P. gingivalis (strain 33277) or the buffer vehicle and treated with rosiglitazone or saline over a 10-week period. Their atherosclerotic status in aortic artery was assessed through histomorphometric analysis, inflammatory agent and lipid profiles in blood was determined by ELISA, and levels of relevant cytokines and Toll-like receptors (TLRs) in aortic tissues were evaluated using immunohistochemistry and quantitative PCR. P. gingivalis inoculation was associated with increased atherosclerotic plaque formation in the aorta and higher levels of serum pro-inflammatory cytokines (tumor necrosis factor-α, monocyte chemotactic protein-1 and interleukin-1β), but the serum lipid profile was not affected by P. gingivalis infection. Levels of tumor necrosis factor-α, monocyte chemotactic protein-1 intercellular cell adhesion molecule-1 and TLRs were higher in the aortic tissues of mice exposed to P. gingivalis, and activation of nuclear factor-κB was also observed. In both P. gingivalis-treated and -untreated ApoE-/- mice, rosiglitazone treatment was associated with less atherosclerotic plaque formation; lower serum inflammatory cytokines, total cholesterol, and low density lipoprotein cholesterol; higher levels of PPARγ, lower amounts of TLR2/4 and downregulated nuclear factor-κB activity in aortic tissues. These findings suggest that rosiglitazone mitigates or prevents P. gingivalis-accelerated atherosclerosis by

  12. Oxidized high-density lipoprotein accelerates atherosclerosis progression by inducing the imbalance between treg and teff in LDLR knockout mice.

    PubMed

    Ru, Ding; Zhiqing, He; Lin, Zhu; Feng, Wu; Feng, Zhang; Jiayou, Zhang; Yusheng, Ren; Min, Fan; Chun, Liang; Zonggui, Wu

    2015-05-01

    High density lipoprotein (HDL) dysfunction has been widely reported in clinic, and oxidation of HDL (ox-HDL) was shown to be one of the most common modifications in vivo and participate in the progression of atherosclerosis. But the behind mechanisms are still elusive. In this study, we firstly analyzed and found strong relationship between serum ox-HDL levels and risk factors of coronary artery diseases in clinic, then the effects of ox-HDL in initiation and progression of atherosclerosis in LDLR knockout mice were investigated by infusion of ox-HDL dissolved in chitosan hydrogel before the formation of lesions in vivo. Several new evidence were shown: (i) the serum levels of ox-HDL peaked early before the formation of lesions in LDLR mice fed with high fat diet similar to oxidative low density lipoprotein, (ii) the formation of atherosclerotic lesions could be accelerated by infusion of ox-HDL, (iii) the pro-atherosclerotic effects of ox-HDL were accompanied by imbalanced levels of effector and regulatory T cells and relative gene expressions, which implied that imbalance of teff and treg might contribute to the pro-atherosclerosis effects of ox-HDL. PMID:25912129

  13. IL-17A is proatherogenic in high-fat diet-induced and Chlamydia pneumoniae-infection accelerated atherosclerosis in mice

    PubMed Central

    Chen, Shuang; Shimada, Kenichi; Zhang, Wenxuan; Huang, Ganghua; Crother, Timothy R.; Arditi, Moshe

    2011-01-01

    The role of IL-17 in atherogenesis remains controversial. We previously reported that the TLR/MyD88 signaling pathway plays an important role in high–fat diet, as well as Chlamydophila pneumoniae (Cpn) infection-mediated acceleration of atherosclerosis in ApoE deficient mice. Here we investigated the role of the IL-17A in high-fat diet and Cpn-induced acceleration of atherosclerosis. The aortic sinus plaque and aortic lesion size and lipid composition as well as macrophage accumulation in the lesions were significantly diminished in IL-17A−/− mice fed high-fat diet compared to wild-type C57Bl/6 control mice. As expected, Cpn infection led to a significant increase in size and lipid content of the atherosclerotic lesions in wild-type mice. However, IL-17A−/− mice developed significantly less acceleration of lesion size following Cpn infection compared to wild-type control despite similar levels of blood cholesterol levels. Furthermore, Cpn infection in wild-type but not in IL-17A−/− mice was associated with significant increases in serum concentrations of IL-12p40, CCL2, INFγ and numbers of macrophages in their plaques. Additionally, in vitro studies suggest that IL-17A activates vascular endothelial cells, which secrete cytokines that in turn enhance foam cell formation in bone marrow macrophages. Taken together, our data suggest that IL-17A is pro-atherogenic and that it plays an important role in both diet-induced atherosclerotic lesion development, and Cpn infection-mediated acceleration of atherosclerotic lesions in the presence of high fat diet. PMID:20935201

  14. Combined B, T and NK Cell Deficiency Accelerates Atherosclerosis in BALB/c Mice.

    PubMed

    Cheng, Fei; Twardowski, Laura; Reifenberg, Kurt; Winter, Kerstin; Canisius, Antje; Pross, Eva; Fan, Jianglin; Schmitt, Edgar; Shultz, Leonard D; Lackner, Karl J; Torzewski, Michael

    2016-01-01

    This study focused on the unique properties of both the Ldlr knockout defect (closely mimicking the human situation) and the BALB/c (C) inbred mouse strain (Th-2 slanted immune response). We generated two immunodeficient strains with severe combined B- and T-cell immunodeficiency with or without a complete lack of natural killer cells to revisit the role of adaptive immune responses on atherogenesis. C-Ldlr-/- Rag1-/- mice, which show severe combined B- and T-cell immunodeficiency and C-Ldlr-/- Rag1-/- Il2rg-/- mice, which combine the T- and B-cell defect with a complete lack of natural killer cells and inactivation of multiple cytokine signalling pathways were fed an atherogenic Western type diet (WTD). Both B6-Ldlr-/- and C-Ldlr-/- immunocompetent mice were used as controls. Body weights and serum cholesterol levels of both immunodeficient strains were significantly increased compared to C-Ldlr-/- controls, except for cholesterol levels of C-Ldlr-/- Rag1-/- double mutants after 12 weeks on the WTD. Quantification of the aortic sinus plaque area revealed that both strains of immunodeficient mice developed significantly more atherosclerosis compared to C-Ldlr-/- controls after 24 weeks on the WTD. Increased atherosclerotic lesion development in C-Ldlr-/- Rag1-/- Il2rg-/- triple mutants was associated with significantly increased numbers of macrophages and significantly decreased numbers of smooth muscle cells compared to both C-Ldlr-/- wild type and C-Ldlr-/- Rag1-/- double mutants pointing to a plaque destabilizing effect of NK cell loss. Collectively, the present study reveals a previously unappreciated complexity with regard to the impact of lymphocytes on lipoprotein metabolism and the role of lymphocyte subsets in plaque composition. PMID:27564380

  15. Combined B, T and NK Cell Deficiency Accelerates Atherosclerosis in BALB/c Mice

    PubMed Central

    Winter, Kerstin; Canisius, Antje; Pross, Eva; Fan, Jianglin; Schmitt, Edgar; Shultz, Leonard D.; Lackner, Karl J.; Torzewski, Michael

    2016-01-01

    This study focused on the unique properties of both the Ldlr knockout defect (closely mimicking the human situation) and the BALB/c (C) inbred mouse strain (Th-2 slanted immune response). We generated two immunodeficient strains with severe combined B- and T-cell immunodeficiency with or without a complete lack of natural killer cells to revisit the role of adaptive immune responses on atherogenesis. C-Ldlr-/- Rag1-/- mice, which show severe combined B- and T-cell immunodeficiency and C-Ldlr-/- Rag1-/- Il2rg-/- mice, which combine the T- and B-cell defect with a complete lack of natural killer cells and inactivation of multiple cytokine signalling pathways were fed an atherogenic Western type diet (WTD). Both B6-Ldlr-/- and C-Ldlr-/- immunocompetent mice were used as controls. Body weights and serum cholesterol levels of both immunodeficient strains were significantly increased compared to C-Ldlr-/- controls, except for cholesterol levels of C-Ldlr-/- Rag1-/- double mutants after 12 weeks on the WTD. Quantification of the aortic sinus plaque area revealed that both strains of immunodeficient mice developed significantly more atherosclerosis compared to C-Ldlr-/- controls after 24 weeks on the WTD. Increased atherosclerotic lesion development in C-Ldlr-/- Rag1-/- Il2rg-/- triple mutants was associated with significantly increased numbers of macrophages and significantly decreased numbers of smooth muscle cells compared to both C-Ldlr-/- wild type and C-Ldlr-/- Rag1-/- double mutants pointing to a plaque destabilizing effect of NK cell loss. Collectively, the present study reveals a previously unappreciated complexity with regard to the impact of lymphocytes on lipoprotein metabolism and the role of lymphocyte subsets in plaque composition. PMID:27564380

  16. Accelerated coronary atherosclerosis after execution of percutaneous coronary intervention in patient with HIV/HCV coinfection: case report and review of the literature.

    PubMed

    Ceccarelli, Giancarlo; d'Ettorre, Gabriella; Mancone, Massimo; Francone, Marco; Vullo, Vincenzo

    2011-01-01

    Highly active antiretroviral therapy has greatly reduced AIDS-related morbidity and mortality; however, its widespread use has been associated with a marked rise in the frequency of cardiovascular diseases in patients with HIV. Moreover, HIV infection is associated with accelerated coronary atherosclerosis and vasculopathy, although the mechanisms underlying these findings have not been determined. We describe the case of a 45-year-old woman with HIV/HCV coinfection, irritable bowel syndrome, and accelerated progression of coronary atherosclerosis after execution of percutaneous coronary intervention (PCI). In this case, the rapidity of progression of atherosclerosis seems linked principally to chronic inflammation and excess immune activation that can depend by a concourse of factors (chronic C hepatitis, irritable bowel syndrome, PCI execution) not directly associated with traditional risk factors. Caregivers following HIV-infected patients should be aware of the increased risk of accelerated atherogenesis in these subjects, principally in case of presence of causes of intense immune activation. PMID:21273145

  17. DNMT1-PPARγ pathway in macrophages regulates chronic inflammation and atherosclerosis development in mice.

    PubMed

    Yu, Jie; Qiu, Youzhu; Yang, Jie; Bian, Shizhu; Chen, Guozhu; Deng, Mengyang; Kang, Huali; Huang, Lan

    2016-01-01

    The DNA methyltransferase-mediated proinflammatory activation of macrophages is causally linked to the development of atherosclerosis (AS). However, the role of DNMT1, a DNA methylation maintenance enzyme, in macrophage polarization and AS development remains obscure. Here, we established transgenic mice with macrophage-specific overexpression of DNMT1 (Tg(DNMT1)) or PPAR-γ (Tg(PPAR-γ)) to investigate their effects on AS progression in ApoE-knockout mice fed an atherogenic diet. Primary macrophages were extracted to study the role of the DNMT1/PPAR-γ pathway in regulating inflammatory cytokine production. We demonstrated that Tg(DNMT1) significantly increased proinflammatory cytokine production in macrophages and plasma, and it accelerated the progression of AS in the atherogenic diet-treated ApoE-knockout mice. Further, we found that the DNA methylation status of the proximal PPAR-γ promoter was regulated by DNMT1 in macrophages. Notably, additional Tg(PPAR-γ) or pharmacological activation of PPAR-γ effectively prevented Tg(DNMT1)-induced proinflammatory cytokine production in macrophages and AS development in the mouse model. Finally, we demonstrated that elevated DNMT1 was correlated with decreased PPAR-γ, and increased proinflammatory cytokine production in the peripheral blood monocytes isolated from the patients with AS, compared to those of healthy donors. Our findings shed light on a novel strategy for the prevention and therapy of AS. PMID:27530451

  18. DNMT1-PPARγ pathway in macrophages regulates chronic inflammation and atherosclerosis development in mice

    PubMed Central

    Yu, Jie; Qiu, Youzhu; Yang, Jie; Bian, Shizhu; Chen, Guozhu; Deng, Mengyang; Kang, Huali; Huang, Lan

    2016-01-01

    The DNA methyltransferase-mediated proinflammatory activation of macrophages is causally linked to the development of atherosclerosis (AS). However, the role of DNMT1, a DNA methylation maintenance enzyme, in macrophage polarization and AS development remains obscure. Here, we established transgenic mice with macrophage-specific overexpression of DNMT1 (TgDNMT1) or PPAR-γ (TgPPAR-γ) to investigate their effects on AS progression in ApoE-knockout mice fed an atherogenic diet. Primary macrophages were extracted to study the role of the DNMT1/PPAR-γ pathway in regulating inflammatory cytokine production. We demonstrated that TgDNMT1 significantly increased proinflammatory cytokine production in macrophages and plasma, and it accelerated the progression of AS in the atherogenic diet-treated ApoE-knockout mice. Further, we found that the DNA methylation status of the proximal PPAR-γ promoter was regulated by DNMT1 in macrophages. Notably, additional TgPPAR-γ or pharmacological activation of PPAR-γ effectively prevented TgDNMT1-induced proinflammatory cytokine production in macrophages and AS development in the mouse model. Finally, we demonstrated that elevated DNMT1 was correlated with decreased PPAR-γ, and increased proinflammatory cytokine production in the peripheral blood monocytes isolated from the patients with AS, compared to those of healthy donors. Our findings shed light on a novel strategy for the prevention and therapy of AS. PMID:27530451

  19. A role for the apoptosis inhibitory factor AIM/Spalpha/Api6 in atherosclerosis development.

    PubMed

    Arai, Satoko; Shelton, John M; Chen, Mingyi; Bradley, Michelle N; Castrillo, Antonio; Bookout, Angie L; Mak, Puiying A; Edwards, Peter A; Mangelsdorf, David J; Tontonoz, Peter; Miyazaki, Toru

    2005-03-01

    Macrophages play a central role in the development of atherosclerosis through the accumulation of oxidized LDL (oxLDL). AIM (Spalpha/Api6) has previously been shown to promote macrophage survival; however, its function in atherogenesis is unknown. Here we identify AIM as a critical factor that protects macrophages from the apoptotic effects of oxidized lipids. AIM protein is induced in response to oxLDL loading and is highly expressed in foam cells within atherosclerotic lesions. Interestingly, both expression of AIM in lesions and its induction by oxidized lipids require the action of LXR/RXR heterodimers. AIM-/- macrophages are highly susceptible to oxLDL-induced apoptosis in vitro and undergo accelerated apoptosis in atherosclerotic lesions in vivo. Moreover, early atherosclerotic lesions in AIM-/-LDLR-/- double knockout mice are dramatically reduced when compared to AIM+/+LDLR-/- controls. We conclude that AIM production facilitates macrophage survival within atherosclerotic lesions and that loss of AIM decreases early lesion development by increasing macrophage apoptosis. PMID:16054063

  20. Atherosclerosis and Stroke

    MedlinePlus

    ... Stroke When the Beat is Off - Atrial Fibrillation Atherosclerosis and Stroke How Cardiovascular & Stroke Risks Relate Problems ... of LDL cholesterol contribute to the development of atherosclerosis as the cholesterol is deposited in artery walls, ...

  1. Development of Integrated Multimodality Intravascular Imaging System for Assessing and Characterizing Atherosclerosis

    NASA Astrophysics Data System (ADS)

    Chen, Zhongping

    Atherosclerosis is one of the major causes of morbidity and mortality in developed countries. Early detection of plaque lesions is the first and most necessary step towards preventing the lethal consequences of atherosclerosis. Currently, many biomedical imaging techniques aimed at imaging and assessing vulnerable plaques have been reported in literature. Unfortunately, atherosclerosis is often asymptomatic, as vulnerable plaques grow without causing any detrimental side effects until rupturing. Due to this complication, the information provided by a single clinical arterial imaging technique is often insufficient to diagnose vulnerable plaque formation at an early stage. Therefore, an optimal imaging modality for diagnosis and characterization of plaques should combine high spatial resolution capable of resolving fibrous cap thickness, deep imaging depth capable of assessing plaque burden and vessel remodeling, and molecular sensitivity capable of determining tissue composition and mechanical properties.

  2. Contributions of Leukocytic Angiotensin-converting Enzyme to Development of Atherosclerosis

    PubMed Central

    Chen, Xiaofeng; Lu, Hong; Zhao, Mingming; Tashiro, Katsuya; Cassis, Lisa A.; Daugherty, Alan

    2013-01-01

    Objective This study determined the role of angiotensin-converting enzyme (ACE) on the development of angiotensin I (AngI)-induced atherosclerosis and the contribution of leukocyte-specific expression of this enzyme. Approach and Results To define the contribution of ACE-dependent activity to AngII synthesis in atherosclerotic development, male LDL receptor -/- mice were fed a fat-enriched diet and infused with either AngI or AngII. The same infusion rate of these peptides had equivalent effects on atherosclerotic development. Co-infusion of an ACE inhibitor, enalapril, ablated AngI augmented atherosclerosis, but had no effect on AngII-induced lesion development. ACE protein was detected in several cell types in atherosclerotic lesions, with a predominance in macrophages. This cell type secreted AngII, which was ablated by ACE inhibition. To study whether leukocyte ACE contributed to atherosclerosis, irradiated male LDL receptor -/- mice were repopulated with bone marrow-derived cells from either ACE +/+ or -/- mice and fed the fat-enriched diet for 12 weeks. Chimeric mice with ACE deficiency in bone marrow-derived cells had modestly reduced atherosclerotic lesions in aortic arches, but had no effects in aortic roots. Conclusions ACE mediates AngI-induced atherosclerosis, and ACE expression in leukocytes modestly contributes to atherosclerotic development in hypercholesterolemic mice. PMID:23846498

  3. Intracranial atherosclerosis following radiotherapy

    SciTech Connect

    Werner, M.H.; Burger, P.C.; Heinz, E.R.; Friedman, A.H.; Halperin, E.C.; Schold, S.C. Jr.

    1988-07-01

    We describe a case of severe intracranial atherosclerosis in a young man who had received therapeutic radiation for a presumed brain neoplasm. Since there was no evidence of vascular disease outside the radiation ports, we speculate that accelerated atherosclerosis was induced by radiation and that hyperlipidemia may have predisposed him to this effect.

  4. Effects of gender and social behavior on the development of coronary artery atherosclerosis in cynomolgus macaques.

    PubMed

    Hamm, T E; Kaplan, J R; Clarkson, T B; Bullock, B C

    1983-09-01

    This experiment involved examination of the effects of gender and social status ('competitive dominance') on the coronary artery atherosclerosis of cynomolgus monkeys. Thirty-two adult Macaca fascicularis (16 males, 16 females) were fed a diet containing a moderate amount of cholesterol (0.56 mg/cal) for 16 months. The monkeys were housed in groups of 4 animals of the same sex, and all groups were stable in composition for the entire experiment. After 1 year a'competitive dominance' score was determined for each monkey, based on feeding order in 9 trials involving a preferred food as incentive. At necropsy the coronary arteries were pressure perfused; 5 sections each were then taken from the left anterior descending, left circumflex and right coronary arteries. For each animal, the mean percent lumen stenosis calculated from theses 15 sections was used as the index of extent of coronary artery atherosclerosis. Males had significantly more extensive coronary artery atherosclerosis than did females. Further, among both males and females, submissive animals (low in competitiveness) had more extensive coronary artery stenosis than did their dominant (highly competitive) counterparts. A similar pattern was observed in the thoracic and abdominal portions of the aorta with respect to competitiveness, but not gender. In the iliac artery, females had less atherosclerosis than males but there was no competitiveness effect. The gender and social status effects on atherosclerosis were each statistically independent of variability in clinical-pathological measures (serum lipid concentrations and heart weight). The results indicated that: (a) gender and psychosocial stress independently affect the development of coronary artery atherosclerosis; (b) the mechanisms mediating these effects remain unknown; and (c) the cynomolgus macaque is a good model for the study of such phenomena. PMID:6685520

  5. Prolyl hydroxylase 3 overexpression accelerates the progression of atherosclerosis in ApoE-/- mice.

    PubMed

    Liu, Hui; Xia, Yanfei; Li, Beibei; Pan, Jinyu; Lv, Mei; Wang, Xuyang; An, Fengshuang

    2016-04-22

    PHD3 belongs to the family of 2-oxoglutarate and iron-dependent dioxygenases and is a critical regulator of HIF-1α. Its expression is increased in cardiovascular diseases such as cardiomyopathy, myocardial ischemia-reperfusion injury, and congestive heart failure. However, the association between PHD3 and atherosclerosis has not been clearly elucidated. In the present study, we investigated the potential effect and mechanism of PHD3 in apolipoprotein E-deficient (ApoE-/-) mice. Murine PHD3 lentivirus and shRNA -PHD3 lentivirus were constructed and injected intravenously into ApoE-/- mice fed on a high fat diet. The aortic atherosclerotic lesion area was larger with PHD3 over-expression. With increased PHD3 levels, macrophages and smooth muscle cells were enhanced. The apoptosis of atherosclerotic plaques revealed an increase when PHD3 was elevated. Furthermore, the expression of intercellular cell adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), monocyte chemotactic protein 1 (MCP-1), interleukin-1beta (IL-1β) and tumor necrosis factor-α(TNF-α) were upregulated with PHD3 over-expression. In vitro, we explored the specific signaling pathway of PHD3 in HUVECs. PHD3 over-expression is associated with activation of ERK1/2 and JNK phosphorylation of MAPK signaling pathway. PHD3 inhibition decreased the apoptosis of HUVECs treated with ox-LDL (50 μg/ml). Our study suggests that PHD3 is not only a regulator of HIF-1α but also an active participant in atherogenesis. PMID:26995088

  6. Genetic instability and atherosclerosis: can somatic mutations account for the development of cardiovascular diseases?

    PubMed

    Andreassi, M G; Botto, N; Colombo, M G; Biagini, A; Clerico, A

    2000-01-01

    Several observations suggest that cancer and atherosclerosis may entail fundamentally common biological mechanisms. The accumulation of lipids and the proliferation of smooth muscle cells (SMCs) are the main histological features of sclerotic plaque formation. The most prominent theory concerning the pathophysiological mechanisms of atherosclerotic plaque formation is the "inflammatory response to injury" hypothesis, which states that SMC proliferation is an inflammation-fibroproliferative reaction to different insults to the artery wall. However, recent evidence suggests that alterations at the DNA level may contribute significantly to the development of the disease. In accordance with these findings, the "monoclonal" hypothesis of atherosclerosis has been suggested. This hypothesis proposes that atherosclerosis begins as a mutation or viral infection, transforming a single, isolated smooth muscle cell into the progenitor of a proliferative clone, as seen in carcinogenesis. Studies of DNA damage in atherosclerotic tissues are lacking. Biological evidence for the hypothesis that cancer and atherosclerosis may share pathological mechanisms is discussed, emphasizing the need to perform studies investigating the involvement of somatic mutations in heart diseases. PMID:10861945

  7. Compound K Attenuates the Development of Atherosclerosis in ApoE−/− Mice via LXRα Activation

    PubMed Central

    Zhou, Li; Zheng, Yu; Li, Zhuoying; Bao, Lingxia; Dou, Yin; Tang, Yuan; Zhang, Jianxiang; Zhou, Jianzhi; Liu, Ya; Jia, Yi; Li, Xiaohui

    2016-01-01

    Background: Atherosclerosis is a fundamental pathological process responded to some serious cardiovascular events. Although the cholesterol-lowering drugs are widely prescribed for atherosclerosis therapy, it is still the leading cause of death in the developed world. Here we measured the effects of compound K in atherosclerosis formation and investigated the probably mechanisms of the anti-antherosclerosis roles of compound K. Methods: We treated the atherosclerotic model animals (apoE−/− mice on western diet) with compound K and measured the size of atherosclerotic lesions, inflammatory cytokine levels and serum lipid profile. Peritoneal macrophages were collected in vitro for the foam cell and inflammasome experiments. Results: Our results show that treatment with compound K dose-dependently attenuates the formation of atherosclerotic plaques by 55% through activation of reverse cholesterol transport pathway, reduction of systemic inflammatory cytokines and inhibition of local inflammasome activity. Compound K increases the cholesterol efflux of macrophage-derived foam cells, and reduces the inflammasome activity in cholesterol crystal stimulated macrophages. The activation of LXRα may contribute to the athero-protective effects of compound K. Conclusion: These observations provide evidence for an athero-protective effect of compound K via LXRα activation, and support its further evaluation as a potential effective modulator for the prevention and treatment of atherosclerosis. PMID:27399689

  8. Novel function of histamine signaling in hyperlipidemia-induced atherosclerosis: Histamine H1 receptors protect and H2 receptors accelerate atherosclerosis.

    PubMed

    Yamada, Sohsuke; Wang, Ke-Yong; Tanimoto, Akihide; Sasaguri, Yasuyuki

    2015-02-01

    Histamine is not only essential for acute inflammatory reactions, but it also participates in a chronic inflammatory disorder. We generated apolipoprotein E (apoE) and histamine receptors (HHRs), including the major H1 and H2 receptors (HH1R, HH2R) double knockout mice (DKO) to clarify the role of HHRs in hyperlipidemia-induced atherosclerosis, in which apoE-KO and DKO mice were fed a high cholesterol diet. We found that pronounced hyperlipidemia-induced atherosclerotic progression occurred in HH1R/apoE-DKO mice, but in HH2R/apoE-DKO mice less atherosclerosis, despite pro-atherogenic serum cholesterol levels compared with apoE-KO mice. Furthermore, the increased expressions of scavenger receptors (SRs), such as SR-A, CD36 and lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), nuclear factor-kappa B (NFκB), monocyte chemoattractant protein (MCP-1), matrix metalloproteinases (MMPs) or liver X receptor (LXR)-related inflammatory signaling factors, were consistent with the pro-atherogenic phenotype of HH2R/apoE-DKO mice. We hypothesize that histamine/HH1R and HH2R signaling has conflicting innate functions, inflammatory/atherogenic and anti-inflammatory/anti-atherogenic actions, and that there are innate links between histamine signaling and hyperlipidemia-induced atherosclerosis, independently of serum cholesterol metabolism. Specific histamine signaling blockers, in particular, HH2R blockers, are a possible novel therapeutic target for hyperlipidemia-induced atherosclerosis. PMID:25581821

  9. Macrophage autophagy regulated by miR-384-5p-mediated control of Beclin-1 plays a role in the development of atherosclerosis

    PubMed Central

    Wang, Beiyun; Zhong, Yuan; Huang, Dong; Li, Jingbo

    2016-01-01

    Macrophages play an essential and complicated role in the pathogenesis of atherosclerosis. However, the regulation of macrophage autophagy as well as it role in the development of atherosclerosis is unclear. MicroRNA-384-5p (miR-384-5p) is a new miRNA that attracted attention very recently, while its effects on Beclin-1 and cell autophagy has not been reported. Here, we studied macrophage autophagy in ApoE (-/-) mice suppled with high-fat diet (HFD), a mouse model for atherosclerosis (simplified as HFD mice). We analyzed the levels of Beclin-1 and the levels of miR-384-5p in the purified F4/80+ macrophages from mouse aorta. Prediction of the binding between miR-384-5p and 3’-UTR of Beclin-1 mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. We found that HFD mice developed atherosclerosis in 12 weeks, while the control ApoE (-/-) mice that had received normal diet (simplified as NOR mice) did not. Compared to NOR mice, HFD mice had significantly lower levels of macrophage autophagy, and significantly higher levels of macrophage death, resulting from decreases in Beclin-1. The decreases in Beclin-1 in macrophages were due to HFD-induced increases in miR-384-5p, which suppressed the translation of Bectlin-1 mRNA via 3’-UTR binding. Together, our study suggests that upregulation of miR-384-5p by HFD may impair the Beclin-1-mediated protection of macrophages through autophagy to accelerate the development of atherosclerosis. PMID:27158352

  10. Accelerated leach test development program

    SciTech Connect

    Fuhrmann, M.; Pietrzak, R.F.; Heiser, J.; Franz, E.M.; Colombo, P.

    1990-11-01

    In FY 1989, a draft accelerated leach test for solidified waste was written. Combined test conditions that accelerate leaching were validated through experimental and modeling efforts. A computer program was developed that calculates test results and models leaching mechanisms. This program allows the user to determine if diffusion controls leaching and, if this is the case, to make projections of releases. Leaching mechanisms other than diffusion (diffusion plus source term partitioning and solubility limited leaching) are included in the program is indicators of other processes that may control leaching. Leach test data are presented and modeling results are discussed for laboratory scale waste forms composed of portland cement containing sodium sulfate salt, portland cement containing incinerator ash, and vinyl ester-styrene containing sodium sulfate. 16 refs., 38 figs., 5 tabs.

  11. Accelerator structure development for NLC

    SciTech Connect

    Hoag, H.A.; Deruyter, H.; Pearson, C.; Ruth, R.D.; Wang, J.W.; Schaefer, J.

    1993-04-01

    In the program of work directed towards the development of an X-Band Next Linear Collider accelerator structure, two different test accelerator sections have been completed, and a third is being fabricated. The first is a simple 30-cell constant-impedance section in which no special attention was given to surface finish, pumping, and alignment. The second is an 86-cell section in which the cells were precision diamond-turned by Texas Instruments Inc. The structure has internal water-cooling and vacuum pumping manifolds. Some design details are given for the third section, which is a 206-cell structure with cavities dimensioned to give a Gaussian distribution of dipole mode frequencies. It has conventional-machining surface finishes and external water and pumping manifolds. Component design, fabrication, and assembly brazing are described for the first two experimental sections.

  12. Changes of lysosomes in the earliest stages of the development of atherosclerosis

    PubMed Central

    Bobryshev, Yuri V; Shchelkunova, Tatyana A; Morozov, Ivan A; Rubtsov, Petr M; Sobenin, Igor A; Orekhov, Alexander N; Smirnov, Alexander N

    2013-01-01

    One of hypotheses of atherosclerosis is based on a presumption that the zones prone to the development of atherosclerosis contain lysosomes which are characterized by enzyme deficiency and thus, are unable to dispose of lipoproteins. The present study was undertaken to investigate the characteristics and changes of lysosomes in the earliest stages of the development of atherosclerosis. Electron microscopic immunocytochemistry revealed that there were certain changes in the distribution of CD68 antigen in lysosomes along the ‘normal intima-initial lesion-fatty streak’ sequence. There were no significant changes found in the key mRNAs encoding for the components of endosome/lysosome compartment in initial atherosclerotic lesions, but in fatty streaks, the contents of EEA1 and Rab5a mRNAs were found to be diminished while the contents of CD68 and p62 mRNAs were increased, compared with the intact tissue. The study reinforces a view that changes occurring in lysosomes play a role in atherogenesis from the very earlier stages of the disease. PMID:23490339

  13. Embryonic development during chronic acceleration

    NASA Technical Reports Server (NTRS)

    Smith, A. H.; Abbott, U. K.

    1982-01-01

    Experiments carried out on chicken eggs indicate that the embryo is affected during very early development, especially over the first four days, and during hatching. In the first four days, the brain develops as well as the anlage for all other organs. In addition, the heart commences to function and the extraembryonic membranes that compartmentalize the egg contents form. The latter require an appreciable extension and folding of tissue which may be disrupted by the mechanical load. Observations of embryonic abnormalities that occur during chronic acceleration suggest an inhibition of development of the axial skeleton, which is rarely seen otherwise, a general retardation of embryonic growth, and circulatory problems. The final stages of development (after 18 days) involve the uptake of fluids, the transition to aerial respiration, and the reorientation of the embryo into a normal hatching position. At 4 G mortality is very high during this period, with a majority of embryos failing to reorient into the normal hatching position.

  14. UCLA accelerator research & development. Progress report

    SciTech Connect

    1997-09-01

    This report discusses work on advanced accelerators and beam dynamics at ANL, BNL, SLAC, UCLA and Pulse Sciences Incorporated. Discussed in this report are the following concepts: Wakefield acceleration studies; plasma lens research; high gradient rf cavities and beam dynamics studies at the Brookhaven accelerator test facility; rf pulse compression development; and buncher systems for high gradient accelerator and relativistic klystron applications.

  15. UCLA accelerator research and development

    SciTech Connect

    Cline, D.B.

    1992-01-01

    This progress report covers work supported by the above DOE grant over the period November 1, 1991 to July 31, 1992. The work is a program of experimental and theoretical studies in advanced particle accelerator research and development for high energy physics applications. The program features research at particle beam facilities in the United States and includes research on novel high power sources, novel focussing systems (e.g. plasma lens), beam monitors, novel high brightness, high current gun systems, and novel flavor factories in particular the {phi} Factory.

  16. The Liver-Selective Thyromimetic T-0681 Influences Reverse Cholesterol Transport and Atherosclerosis Development in Mice

    PubMed Central

    Eller, Philipp; Duwensee, Kristina; Hoefer, Julia; Heim, Christiane; Stanzl, Ursula; Wehinger, Andreas; Auer, Kristina; Karer, Regina; Huber, Julia; Schgoer, Wilfried; Van Eck, Miranda; Vanhoutte, Jonathan; Fievet, Catherine; Stellaard, Frans; Rudling, Mats; Patsch, Josef R.; Ritsch, Andreas

    2010-01-01

    Background Liver-selective thyromimetics have been reported to efficiently reduce plasma cholesterol through the hepatic induction of both, the low-density lipoprotein receptor (LDLr) and the high-density lipoprotein (HDL) receptor; the scavenger receptor class B type I (SR-BI). Here, we investigated the effect of the thyromimetic T-0681 on reverse cholesterol transport (RCT) and atherosclerosis, and studied the underlying mechanisms using different mouse models, including mice lacking LDLr, SR-BI, and apoE, as well as CETP transgenic mice. Methodology/Principal Findings T-0681 treatment promoted bile acid production and biliary sterol secretion consistently in the majority of the studied mouse models, which was associated with a marked reduction of plasma cholesterol. Using an assay of macrophage RCT in mice, we found T-0681 to significantly increase fecal excretion of macrophage-derived neutral and acidic sterols. No positive effect on RCT was found in CETP transgenic mice, most likely due to the observed decrease in plasma CETP mass. Studies in SR-BI KO and LDLr KO mice suggested hepatic LDLr to be necessary for the action of T-0681 on lipid metabolism, as the compound did not have any influence on plasma cholesterol levels in mice lacking this receptor. Finally, prolonged treatment with T-0681 reduced the development of atherosclerosis by 60% in apoE KOs on Western type diet. In contrast, at an earlier time-point T-0681 slightly increased small fatty streak lesions, in part due to an impaired macrophage cholesterol efflux capacity, when compared to controls. Conclusions/Significance The present results show that liver-selective thyromimetics can promote RCT and that such compounds may protect from atherosclerosis partly through induction of bile acid metabolism and biliary sterol secretion. On-going clinical trials will show whether selective thyromimetics do prevent atherosclerosis also in humans. PMID:20090943

  17. New developments in atherosclerosis: clinical potential of PCSK9 inhibition

    PubMed Central

    Giunzioni, Ilaria; Tavori, Hagai

    2015-01-01

    Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a secreted 692-amino acid protein that binds surface low-density lipoprotein (LDL) receptor (LDLR) and targets it toward lysosomal degradation. As a consequence, the number of LDLRs at the cell surface is decreased, and LDL-cholesterol (LDL-C) clearance is reduced, a phenomenon that is magnified by gain-of-function mutations of PCSK9. In contrast, loss-of-function mutations of PCSK9 result in increased surface LDLR and improved LDL-C clearance. This provides the rationale for targeting PCSK9 in hypercholesterolemic subjects as a means to lower LDL-C levels. Monoclonal antibodies (mAbs) against PCSK9 that block its interaction with the LDLR have been developed in the past decade. Two companies have recently received the approval for their anti-PCSK9 mAbs by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) Regeneron/Sanofi, with alirocumab (commercial name – PRALUENT®) and, Amgen with evolocumab (commercial name – Repatha™). The introduction of anti-PCSK9 mAbs will provide an alternative therapeutic strategy to address many of the unmet needs of current lipid-lowering therapies, such as inability to achieve goal LDL-C level, or intolerance and aversion to statins. This review will focus on the kinetics of PCSK9, pharmacokinetics and pharmacodynamics of anti-PCSK9 mAbs, and recent data linking PCSK9 and anti-PCSK9 mAbs to cardiovascular events. Moreover, it will highlight the unanswered questions that still need to be addressed in order to understand the physiologic function, kinetics, and dynamics of PCSK9. PMID:26345307

  18. Paradoxical effect of a pequi oil-rich diet on the development of atherosclerosis: balance between antioxidant and hyperlipidemic properties

    PubMed Central

    Aguilar, E.C.; Jascolka, T.L.; Teixeira, L.G.; Lages, P.C.; Ribeiro, A.C.C.; Vieira, E.L.M.; Peluzio, M.C.G.; Alvarez-Leite, J.I.

    2012-01-01

    Pequi is the fruit of Caryocar brasiliense and its oil has a high concentration of monounsaturated and saturated fatty acids, which are anti- and pro-atherogenic agents, respectively, and of carotenoids, which give it antioxidant properties. Our objective was to study the effect of the intake of a cholesterol-rich diet supplemented with pequi oil, compared to the same diet containing soybean oil, on atherosclerosis development, and oxidative stress in atherosclerosis-susceptible LDL receptor-deficient mice (LDLr−/−, C57BL/6-background). Female mice were fed a cholesterol-rich diet containing 7% soybean oil (Soybean group, N = 12) or 7% pequi oil (Pequi group, N = 12) for 6 weeks. The Pequi group presented a more atherogenic lipid profile and more advanced atherosclerotic lesions in the aortic root compared to the Soybean group. However, the Pequi group presented a less advanced lesion in the aorta than the Soybean group and showed lower lipid peroxidation (Soybean group: 50.2 ± 7.1; Pequi group: 30.0 ± 4.8 µmol MDA/mg protein) and anti-oxidized LDL autoantibodies (Soybean group: 35.7 ± 9.4; Pequi group: 15.6 ± 3.7 arbitrary units). Peritoneal macrophages from the Pequi group stimulated with zymosan showed a reduction in the release of reactive oxygen species compared to the Soybean group. Our data suggest that a pequi oil-rich diet slows atherogenesis in the initial stages, possibly due to its antioxidant activity. However, the increase of serum cholesterol induces a more prominent LDL migration toward the intimae of arteries, increasing the advanced atherosclerotic plaque. In conclusion, pequi oil associated with an atherogenic diet worsens the lipid profile and accelerates the formation of advanced atherosclerotic lesions despite its antioxidant action. PMID:22570088

  19. Particle accelerator development: Selected examples

    NASA Astrophysics Data System (ADS)

    Wei, Jie

    2016-03-01

    About 30 years ago, I was among several students mentored by Professor Yang at Stony Brook to enter the field of particle accelerator physics. Since then, I have been fortunate to work on several major accelerator projects in USA and in China, guided and at times directly supported by Professor Yang. The field of accelerator physics is flourishing worldwide both providing indispensable tools for fundamental physics research and covering an increasingly wide spectrum of applications beneficial to our society.

  20. Particle Accelerator Development: Selected Examples

    NASA Astrophysics Data System (ADS)

    Wei, Jie

    About 30 years ago, I was among several students mentored by Professor Yang at Stony Brook to enter the field of particle accelerator physics. Since then, I have been fortunate to work on several major accelerator projects in USA and in China, guided and at times directly supported by Professor Yang. The field of accelerator physics is flourishing worldwide both providing indispensable tools for fundamental physics research and covering an increasingly wide spectrum of applications beneficial to our society.

  1. Atherosclerosis (image)

    MedlinePlus

    Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, ... muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

  2. Clopidogrel significantly lowers the development of atherosclerosis in ApoE-deficient mice in vivo.

    PubMed

    Heim, Christian; Gebhardt, Julia; Ramsperger-Gleixner, Martina; Jacobi, Johannes; Weyand, Michael; Ensminger, Stephan M

    2016-05-01

    The anti-platelet drug clopidogrel has been shown to modulate adhesion molecule and cytokine expression, both playing an important role in the pathogenesis of atherosclerosis. The aim of this study was to investigate the impact of clopidogrel on the development and progression of atherosclerosis. ApoE(-/-) mice fed an atherogenic diet (cholesterol: 1 %) for 6 months received a daily dose of clopidogrel (1 mg/kg) by i.p. injection. Anti-platelet treatment was started immediately in one experimental group, and in another group clopidogrel was started 2 month after beginning of the atherogenic diet. Blood was analysed at days 30, 60 and 120 to monitor the lipid profile. After 6 months the aortic arch and brachiocephalic artery were analysed by Sudan IV staining for plaque size and by morphometry for luminal occlusion. Serum levels of various adhesion molecules were investigated by ELISA and the cellular infiltrate was analysed by immunofluorescence. After daily treatment with 1 mg/kg clopidogrel mice showed a significant reduction of atherosclerotic lesions in the thoracic aorta and within cross sections of the aortic arch [plaque formation 55.2 % (clopidogrel/start) vs. 76.5 % (untreated control) n = 8, P < 0.05]. After treatment with clopidogrel P-/E-selectin levels and cytokine levels of MCP-1 and PDGFβ were significantly reduced as compared to controls. The cellular infiltrate showed significantly reduced macrophage and T-cell infiltration in clopidogrel-treated animals. These results show that clopidogrel can effectively delay the development and progression of 'de-novo' atherosclerosis. However, once atherosclerotic lesions were already present, anti-platelet treatment alone did not result in reverse remodelling of these lesions. PMID:26062773

  3. Risk factors for the development of atherosclerosis in childhood and adolescence.

    PubMed

    Santos, Maria Gisele dos; Pegoraro, Marina; Sandrini, Fabiano; Macuco, Emílio César

    2008-04-01

    Cardiovascular diseases (CVD) are a major cause of death in developed countries as well as in developing countries. In general, the clinical manifestations of CVD, such as myocardial infarction, stroke and peripheral vascular disease, are caused by an atherosclerotic process with onset as from the middle age. However, current studies indicate that the atherosclerotic process starts to develop in childhood. The pathogenesis of atherosclerosis has been studied as to its inflammatory aspect. Among the inflammatory markers, C-reactive protein (CRP) has been extensively studied in individuals with CVD, including those apparently healthy. High CRP levels have been related to risk factors for atherosclerosis: family history of coronary artery disease (CAD), dyslipidemia, hypertension, diabetes mellitus, obesity, smoking and sedentary lifestyle. A great part of these risk factors may be influenced by lifestyle modifications, such as changes in eating habits and engagement in physical activities. The effects of physical activity on CRP levels in adulthood are documented in the literature, however little is known on the influence of an active or sedentary lifestyle of children and adolescents on CRP levels. Thus, the objective of this study is to review the impact of physical activity of children and adolescents on CRP levels and the risk factors for the development of CVD. PMID:18516390

  4. BAFF Receptor mAb Treatment Ameliorates Development and Progression of Atherosclerosis in Hyperlipidemic ApoE−/− Mice

    PubMed Central

    Kyaw, Tin; Cui, Peng; Tay, Christopher; Kanellakis, Peter; Hosseini, Hamid; Liu, Edgar; Rolink, Antonius G.; Tipping, Peter

    2013-01-01

    Aims Option to attenuate atherosclerosis by depleting B2 cells is currently limited to anti-CD20 antibodies which deplete all B-cell subtypes. In the present study we evaluated the capacity of a monoclonal antibody to B cell activating factor-receptor (BAFFR) to selectively deplete atherogenic B2 cells to prevent both development and progression of atherosclerosis in the ApoE−/− mouse. Methods and Results To determine whether the BAFFR antibody prevents atherosclerosis development, we treated ApoE−/− mice with the antibody while feeding them a high fat diet (HFD) for 8 weeks. Mature CD93− CD19+ B2 cells were reduced by treatment, spleen B-cell zones disrupted and spleen CD20 mRNA expression decreased while B1a cells and non-B cells were spared. Atherosclerosis was ameliorated in the hyperlipidemic mice and CD19+ B cells, CD4+ and CD8+ T cells were reduced in atherosclerotic lesions. Expressions of proinflammatory cytokines, IL1β, TNFα, and IFNγ in the lesions were also reduced, while MCP1, MIF and VCAM-1 expressions were unaffected. Plasma immunoglobulins were reduced, but MDA-oxLDL specific antibodies were unaffected. To determine whether anti-BAFFR antibody ameliorates progression of atherosclerosis, we first fed ApoE−/− mice a HFD for 6 weeks, and then instigated anti-BAFFR antibody treatment for a further 6 week-HFD. CD93− CD19+ B2 cells were selectively decreased and atherosclerotic lesions were reduced by this treatment. Conclusion Anti-BAFFR monoclonal antibody selectively depletes mature B2 cells while sparing B1a cells, disrupts spleen B-cell zones and ameliorates atherosclerosis development and progression in hyperlipidemic ApoE−/− mice. Our findings have potential for clinical translation to manage atherosclerosis-based cardiovascular diseases. PMID:23560095

  5. Selective proteolysis of apolipoprotein B-100 by Arg-gingipain mediates atherosclerosis progression accelerated by bacterial exposure.

    PubMed

    Hashimoto, Munetaka; Kadowaki, Tomoko; Tsukuba, Takayuki; Yamamoto, Kenji

    2006-11-01

    Epidemiological studies suggest the association of periodontal infections with atherosclerosis, however, the mechanism underlying this association remains poorly understood. Porphyromonas gingivalis is the primary etiologic agent of adult periodontitis and produces a unique class of cysteine proteinases consisting of Arg-gingipain (Rgp) and Lys-gingipain (Kgp). To elucidate key mechanisms for progression of atherosclerosis by P. gingivalis infection, we tested the effects of the disruption of genes encoding Rgp and/or Kgp and inhibitors specific for the respective enzymes on atherosclerosis progression in apolipoprotein E-knockout mice. Repeated intravenous injection of wild-type P. gingivalis resulted in an increase in atherosclerotic lesions as well as an increase in the serum LDL cholesterol and a decrease of HDL cholesterol in these animals. LDL particles in P. gingivalis-injected animals were modified as a result of selective proteolysis of apoB-100 in LDL particles. This modification of LDL by P. gingivalis resulted in an increase in LDL uptake by macrophages and consequent foam cell formation in vitro. The atherosclerotic changes induced by P. gingivalis infection were attenuated by disruption of Rgp-encoding genes or by an Rgp-specific inhibitor. Our results indicate that degradation of apoB-100 by Rgp plays a crucial role in the promotion of atherosclerosis by P. gingivalis infection. PMID:17030507

  6. HIV, inflammation, and calcium in atherosclerosis.

    PubMed

    Shrestha, Sadeep; Irvin, Marguerite R; Grunfeld, Carl; Arnett, Donna K

    2014-02-01

    Atherosclerosis is consistently higher among the HIV-positive patients, with or without treatment, than among the HIV-negative population. Risk factors linked to atherosclerotic cardiovascular disease in HIV infection are both traditional and HIV specific although the underlying mechanisms are not fully delineated. Three key sequential biological processes are postulated to accelerate progression of atherosclerosis in the context of HIV: (1) inflammation, (2) transformation of monocytes to macrophages and then foam cells, and (3) apoptosis of foam cells leading to plaque development through Ca(2+)-dependent endoplasmic reticulum stress. These proatherogenic mechanisms are further affected when HIV interacts with the genes involved in various phases within this network. PMID:24265418

  7. Deletion of L-Selectin Increases Atherosclerosis Development in ApoE−/− Mice

    PubMed Central

    Rozenberg, Izabela; Sluka, Susanna H. M.; Mocharla, Pavani; Hallenberg, Anders; Rotzius, Pierre; Borén, Jan; Kränkel, Nicolle; Landmesser, Ulf; Borsig, Lubor; Lüscher, Thomas F.; Eriksson, Einar E.; Tanner, Felix C.

    2011-01-01

    Atherosclerosis is an inflammatory disease characterized by accumulation of leukocytes in the arterial intima. Members of the selectin family of adhesion molecules are important mediators of leukocyte extravasation. However, it is unclear whether L-selectin (L-sel) is involved in the pathogenesis of atherosclerosis. In the present study, mice deficient in L-selectin (L-sel−/−) animals were crossed with mice lacking Apolipoprotein E (ApoE−/−). The development of atherosclerosis was analyzed in double-knockout ApoE/L-sel (ApoE−/− L-sel−/−) mice and the corresponding ApoE−/− controls fed either a normal or a high cholesterol diet (HCD). After 6 weeks of HCD, aortic lesions were increased two-fold in ApoE−/− L-sel−/− mice as compared to ApoE−/− controls (2.46%±0.54% vs 1.28%±0.24% of total aortic area; p<0.05). Formation of atherosclerotic lesions was also enhanced in 6-month-old ApoE−/− L-sel−/− animals fed a normal diet (10.45%±2.58% vs 1.87%±0.37%; p<0.05). In contrast, after 12 weeks of HCD, there was no difference in atheroma formation between ApoE−/− L-sel−/− and ApoE−/− mice. Serum cholesterol levels remained unchanged by L-sel deletion. Atherosclerotic plaques did not exhibit any differences in cellular composition assessed by immunohistochemistry for CD68, CD3, CD4, and CD8 in ApoE−/− L-sel−/− as compared to ApoE−/− mice. Leukocyte rolling on lesions in the aorta was similar in ApoE−/− L-sel−/− and ApoE−/− animals. ApoE−/− L-sel−/− mice exhibited reduced size and cellularity of peripheral lymph nodes, increased size of spleen, and increased number of peripheral lymphocytes as compared to ApoE−/− controls. These data indicate that L-sel does not promote atherosclerotic lesion formation and suggest that it rather protects from early atherosclerosis. PMID:21760899

  8. Suppressive effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient mice.

    PubMed

    Natsume, Midori; Baba, Seigo

    2014-01-01

    Previous studies in humans have shown that the cacao polyphenols, (-)-epicatechin and its oligomers, prevent in vitro and ex vivo low-density lipoprotein oxidation mediated by free radical generators and metal ions and also reduce plasma LDL-cholesterol levels. The aim of this study was to examine the effects of cacao polyphenols on the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice. Mice aged 8 weeks (n = 90) were randomized into three groups, and fed either normal mouse chow (controls) or chow supplemented with 0.25 or 0.40 % cacao polyphenols for 16 weeks. The mean plaque area in cross-sections of the brachiocephalic trunk was measured and found to be lower in the 0.25 % cacao polyphenol group than in the control group (p < 0.05). Pathological observations showed that accumulation of cholesterol crystals in the plaque area was greater in the control group compared with the 0.40 % cacao polyphenol group (p < 0.05). Immunochemical staining in the 0.25 and 0.40 % groups showed that expression of the cell adhesion molecules (VCAM-1 and ICAM-1) and production of oxidative stress markers (4-hydroxynonenal, hexanoyl-lysine, and dityrosine) were reduced in cross-sections of the brachiocephalic trunk. These results suggest that cacao polyphenols inhibit the development of atherosclerosis in apolipoprotein E-deficient (-/-) mice by reducing oxidative stress and inflammatory responses. PMID:24374929

  9. [Carotid atherosclerosis and dementia].

    PubMed

    Harlé, Louise-Marine; Plichart, Matthieu

    2015-09-01

    Over the past decade a growing interest has been devoted to exploring the role of atherosclerosis in the development of dementia. Despite a well-known association between atherosclerosis risk factors in middle-life with later cognitive decline, the pathophysiological pathways underlying this association remain unclear. The current hypothesis is that neurodegenerative and vascular lesions coexist and have a synergistic role in the development of cognitive impairment and dementia. Carotid atherosclerosis (e.g. carotid plaques and intima-media thickness as measured by carotid ultrasonography) has been associated with cognitive decline and dementia and may help to better understand the complex interaction between the vascular and neurodegenerative processes. Furthermore, carotid atherosclerosis has been used in the recent field for dementia risk prediction. In this review, we discuss the physiopathological implications from the current available data on the relationship between carotid atherosclerosis and dementia as well as the interest of carotid biomarkers for individual dementia risk prediction. PMID:26395304

  10. Chronic intermittent hypoxia exposure-induced atherosclerosis: a brief review.

    PubMed

    Song, Dongmei; Fang, Guoqiang; Greenberg, Harly; Liu, Shu Fang

    2015-12-01

    Obstructive sleep apnea (OSA) is highly prevalent in the USA and is recognized as an independent risk factor for atherosclerotic cardiovascular disease. Identification of atherosclerosis risk factor attributable to OSA may provide opportunity to develop preventive measures for cardiovascular risk reduction. Chronic intermittent hypoxia (CIH) is a prominent feature of OSA pathophysiology and may be a major mechanism linking OSA to arteriosclerosis. Animal studies demonstrated that CIH exposure facilitated high-cholesterol diet (HCD)-induced atherosclerosis, accelerated the progression of existing atherosclerosis, and induced atherosclerotic lesions in the absence of other atherosclerosis risk factors, demonstrating that CIH is an independent causal factor of atherosclerosis. Comparative studies revealed major differences between CIH-induced and the classic HCD-induced atherosclerosis. Systemically, CIH was a much weaker inducer of atherosclerosis. CIH and HCD differentially activated inflammatory pathways. Histologically, CIH-induced atherosclerotic plaques had no clear necrotic core, contained a large number of CD31+ endothelial cells, and had mainly elastin deposition, whereas HCD-induced plaques had typical necrotic cores and fibrous caps, contained few endothelial cells, and had mainly collagen deposition. Metabolically, CIH caused mild, but HCD caused more severe dyslipidemia. Mechanistically, CIH did not, but HCD did, cause macrophage foam cell formation. NF-κB p50 gene deletion augmented CIH-induced, but not HCD-induced atherosclerosis. These differences reflect the intrinsic differences between the two types of atherosclerosis in terms of pathological nature and underlying mechanisms and support the notion that CIH-induced atherosclerosis is a new paradigm that differs from the classic HCD-induced atherosclerosis. PMID:26407987

  11. Statins attenuate the development of atherosclerosis and endothelial dysfunction induced by exposure to urban particulate matter (PM{sub 10})

    SciTech Connect

    Miyata, Ryohei; Hiraiwa, Kunihiko; Cheng, Jui Chih; Bai, Ni; Vincent, Renaud; Francis, Gordon A.; Sin, Don D.; Van Eeden, Stephan F.

    2013-10-01

    Exposure to ambient air particulate matter (particles less than 10 μm or PM{sub 10}) has been shown to be an independent risk factor for the development and progression of atherosclerosis. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have well-established anti-inflammatory properties. The aim of this study was to determine the impact of statins on the adverse functional and morphological changes in blood vessels induced by PM{sub 10}. New Zealand White rabbits fed with a high fat diet were subjected to balloon injury to their abdominal aorta followed by PM{sub 10}/saline exposure for 4 weeks ± lovastatin (5 mg/kg/day) treatment. PM{sub 10} exposure accelerated balloon catheter induced plaque formation and increased intimal macrophages and lipid accumulation while lovastatin attenuated these changes and promoted smooth muscle cell recruitment into plaques. PM{sub 10} impaired vascular acetylcholine (Ach) responses and increased vasoconstriction induced by phenylephrine as assessed by wire myograph. Supplementation of nitric oxide improved the impaired Ach responses. PM{sub 10} increased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in blood vessels and increased the plasma levels of endothelin-1 (ET-1). Incubation with specific inhibitors for iNOS, COX-2 or ET-1 in the myograph chambers significantly improved the impaired vascular function. Lovastatin decreased the expression of these mediators in atherosclerotic lesions and improved endothelial dysfunction. However, lovastatin was unable to reduce blood lipid levels to the baseline level in rabbits exposed to PM{sub 10}. Taken together, statins protect against PM{sub 10}-induced cardiovascular disease by reducing atherosclerosis and improving endothelial function via their anti-inflammatory properties. - Highlights: • Coarse particulate matter (PM{sub 10}) accelerated balloon injury-induced plaque formation. • Lovastatin decreased intimal

  12. The role and importance of gene polymorphisms in the development of atherosclerosis.

    PubMed

    Szabó, Gábor Viktor

    2013-03-01

    The development of atherosclerosis is a multifactorial process. The purpose of the study was to examine three genetic polymorphisms playing a role in the metabolic processes underlying the disease. We compared the data of 348 atherosclerotic non-diabetic patients with 260 atherosclerotic diabetic patients and 384 healthy controls. We analyzed the prevalence of myocardial infarction and stroke in three different groups of patients carrying different polymorphisms. It was proved that if the mutant TT eNOS Glu298ASP variant is present, a significantly higher number of myocardial infarctions can be observed than in patients carrying heterozygote GT or normal GG genotype. We proved that in the case of MTHFR 677CT heterozygote variants, the occurrence of myocardial infarction is significantly higher and the difference is also significant in case of the 677TT homozygote variant. It was verified that among patients with the mutant TNF-α AA genotype the occurrence of cardiovascular events was significantly higher. Screening the genetically high risk groups on the long run should be considered as an early detection opportunity that may give better chances for prevention and treatment. Understanding the inflammatory mechanisms of the atherosclerosis may give new therapeutical targets to pharmacologists. PMID:24265890

  13. Deletion of Macrophage Vitamin D Receptor Promotes Insulin Resistance and Monocyte Cholesterol Transport to Accelerate Atherosclerosis in Mice

    PubMed Central

    Oh, Jisu; Riek, Amy E.; Darwech, Isra; Funai, Katsuhiko; Shao, JianSu; Chin, Kathleen; Sierra, Oscar L.; Carmeliet, Geert; Ostlund, Richard E.; Bernal-Mizrachi, Carlos

    2015-01-01

    Summary Intense effort has been devoted to understanding predisposition to chronic systemic inflammation as this contributes to cardiometabolic disease. We demonstrate that deletion of the macrophage vitamin D receptor (VDR) in mice (KODMAC) is sufficient to induce insulin resistance by promoting M2 macrophage accumulation in the liver, as well as increase cytokine secretion and hepatic glucose production. Moreover, VDR deletion increases atherosclerosis by enabling lipid-laden M2 monocytes to adhere, migrate, and carry cholesterol into the atherosclerotic plaque, and by increasing macrophage cholesterol uptake and esterification. Increased foam cell formation results from lack of VDR-SERCA2b interaction, causing SERCA dysfunction, activation of ER stress-CaMKII-JNKp-PPARγ signaling, and induction of the scavenger receptors CD36 and SR-A1. BM transplant of VDR-expressing cells into KODMAC mice improved insulin sensitivity, suppressed atherosclerosis, and decreased foam cell formation. The immunomodulatory effects of vitamin D in macrophages are thus critical in diet-induced insulin resistance and atherosclerosis in mice. Graphical Abstract PMID:25801026

  14. Prevention and treatment of atherosclerosis with flaxseed-derived compound secoisolariciresinol diglucoside.

    PubMed

    Prasad, Kailash; Jadhav, Ashok

    2016-01-01

    Atherosclerosis is the primary cause of coronary artery disease, heart attack, strokes, and peripheral vascular disease. Alternative/complimentary medicines, although are unacceptable by medical community, may be of great help in suppression, slowing of progression and regression of atherosclerosis. Numerous natural products are in use for therapy in spite of lack of evidence. This paper discusses the basic mechanism of atherosclerosis, risk factors for atherosclerosis, and prevention, slowing of progression and regression of atherosclerosis with flaxseed-derived secoisolariciresinol diglucoside (SDG). SDG content of flaxseed varies from 6mg/g to 18 mg/g. Flaxseed is the richest source of SDG. SDG possesses antioxidant, antihypertensive, antidiabetic, hypolipidemic, anti-inflammatory and antiatherogenic activities. SDG content of some commonly used food has been described. SDG in very low dose (15 mg/ kg) suppressed the development of hypercholesterolemic atherosclerosis by 73 % and this effect was associated with reduction in serum total cholesterol, LDL-C, and oxidative stress, and an increase in the levels HDL-C. A summary of the effects of flaxseed and its components on hypercholesterolemic atherosclerosis has been provided. Reduction in hypercholesterolemic atherosclerosis by flaxseed, CDC-flaxseed, flaxseed oil, flax lignan complex and SDG are 46 %, 69 %, 0 %, 34 % and 73 % respectively in dietary cholesterol -induced rabbit model of atherosclerosis. SDG slows the progression of atherosclerosis in animal model. Long-term use of SDG regresses hypercholesterolemic atherosclerosis. It is interesting that regular diet following high cholesterol diet accelerates in this animal model of atherosclerosis. In conclusion SDG suppresses, slow the progression and regresses the atherosclerosis. It could serve as an alternative medicine for the prevention, slowing of progression and regression of atherosclerosis and hence for the treatment of coronary artery disease

  15. Animal models of atherosclerosis

    PubMed Central

    Kapourchali, Fatemeh Ramezani; Surendiran, Gangadaran; Chen, Li; Uitz, Elisabeth; Bahadori, Babak; Moghadasian, Mohammed H

    2014-01-01

    In this mini-review several commonly used animal models of atherosclerosis have been discussed. Among them, emphasis has been made on mice, rabbits, pigs and non-human primates. Although these animal models have played a significant role in our understanding of induction of atherosclerotic lesions, we still lack a reliable animal model for regression of the disease. Researchers have reported several genetically modified and transgenic animal models that replicate human atherosclerosis, however each of current animal models have some limitations. Among these animal models, the apolipoprotein (apo) E-knockout (KO) mice have been used extensively because they develop spontaneous atherosclerosis. Furthermore, atherosclerotic lesions developed in this model depending on experimental design may resemble humans’ stable and unstable atherosclerotic lesions. This mouse model of hypercholesterolemia and atherosclerosis has been also used to investigate the impact of oxidative stress and inflammation on atherogenesis. Low density lipoprotein (LDL)-r-KO mice are a model of human familial hypercholesterolemia. However, unlike apo E-KO mice, the LDL-r-KO mice do not develop spontaneous atherosclerosis. Both apo E-KO and LDL-r-KO mice have been employed to generate other relevant mouse models of cardiovascular disease through breeding strategies. In addition to mice, rabbits have been used extensively particularly to understand the mechanisms of cholesterol-induced atherosclerosis. The present review paper details the characteristics of animal models that are used in atherosclerosis research. PMID:24868511

  16. Targeted Interleukin-10 Nanotherapeutics Developed with a Microfluidic Chip Enhance Resolution of Inflammation in Advanced Atherosclerosis.

    PubMed

    Kamaly, Nazila; Fredman, Gabrielle; Fojas, Jhalique Jane R; Subramanian, Manikandan; Choi, Won Ii; Zepeda, Katherine; Vilos, Cristian; Yu, Mikyung; Gadde, Suresh; Wu, Jun; Milton, Jaclyn; Carvalho Leitao, Renata; Rosa Fernandes, Livia; Hasan, Moaraj; Gao, Huayi; Nguyen, Vance; Harris, Jordan; Tabas, Ira; Farokhzad, Omid C

    2016-05-24

    Inflammation is an essential protective biological response involving a coordinated cascade of signals between cytokines and immune signaling molecules that facilitate return to tissue homeostasis after acute injury or infection. However, inflammation is not effectively resolved in chronic inflammatory diseases such as atherosclerosis and can lead to tissue damage and exacerbation of the underlying condition. Therapeutics that dampen inflammation and enhance resolution are currently of considerable interest, in particular those that temper inflammation with minimal host collateral damage. Here we present the development and efficacy investigations of controlled-release polymeric nanoparticles incorporating the anti-inflammatory cytokine interleukin 10 (IL-10) for targeted delivery to atherosclerotic plaques. Nanoparticles were nanoengineered via self-assembly of biodegradable polyester polymers by nanoprecipitation using a rapid micromixer chip capable of producing nanoparticles with retained IL-10 bioactivity post-exposure to organic solvent. A systematic combinatorial approach was taken to screen nanoparticles, resulting in an optimal bioactive formulation from in vitro and ex vivo studies. The most potent nanoparticle termed Col-IV IL-10 NP22 significantly tempered acute inflammation in a self-limited peritonitis model and was shown to be more potent than native IL-10. Furthermore, the Col-IV IL-10 nanoparticles prevented vulnerable plaque formation by increasing fibrous cap thickness and decreasing necrotic cores in advanced lesions of high fat-fed LDLr(-/-) mice. These results demonstrate the efficacy and pro-resolving potential of this engineered nanoparticle for controlled delivery of the potent IL-10 cytokine for the treatment of atherosclerosis. PMID:27100066

  17. Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease: A Scientific Statement From the American Heart Association.

    PubMed

    Goldstein, Benjamin I; Carnethon, Mercedes R; Matthews, Karen A; McIntyre, Roger S; Miller, Gregory E; Raghuveer, Geetha; Stoney, Catherine M; Wasiak, Hank; McCrindle, Brian W

    2015-09-01

    In the 2011 "Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents," several medical conditions among youth were identified that predispose to accelerated atherosclerosis and early cardiovascular disease (CVD), and risk stratification and management strategies for youth with these conditions were elaborated. Major depressive disorder (MDD) and bipolar disorder (BD) among youth satisfy the criteria set for, and therefore merit inclusion among, Expert Panel tier II moderate-risk conditions. The combined prevalence of MDD and BD among adolescents in the United States is ≈10%, at least 10 times greater than the prevalence of the existing moderate-risk conditions combined. The high prevalence of MDD and BD underscores the importance of positioning these diseases alongside other pediatric diseases previously identified as moderate risk for CVD. The overall objective of this statement is to increase awareness and recognition of MDD and BD among youth as moderate-risk conditions for early CVD. To achieve this objective, the primary specific aims of this statement are to (1) summarize evidence that MDD and BD are tier II moderate-risk conditions associated with accelerated atherosclerosis and early CVD and (2) position MDD and BD as tier II moderate-risk conditions that require the application of risk stratification and management strategies in accordance with Expert Panel recommendations. In this scientific statement, there is an integration of the various factors that putatively underlie the association of MDD and BD with CVD, including pathophysiological mechanisms, traditional CVD risk factors, behavioral and environmental factors, and psychiatric medications. PMID:26260736

  18. Diet-induced elevation of circulating HSP70 may trigger cell adhesion and promote the development of atherosclerosis in rats.

    PubMed

    Xie, Fang; Zhan, Rui; Yan, Li-Cheng; Gong, Jing-Bo; Zhao, Yun; Ma, Jing; Qian, Ling-Jia

    2016-09-01

    Although accumulating evidence indicates that heat shock protein 70 (HSP70) could be secreted into plasma and its levels have been found to have an ambiguous association with atherosclerosis, our knowledge for the exact role of circulating HSP70 in the development of atherosclerosis is still limited. In the present study, we report an adhesion-promoting effect of exogenous HSP70 and evaluate the potential involvement of elevated circulating HSP70 in the development of atherosclerosis. Time-dependent elevation of plasma HSP70 was found in diet-induced atherosclerotic rats, whose effect was investigated through further in vitro experiments. In rat aortic endothelial cell (RAEC) cultures, exogenous HSP70 incubation neither produced cell injuries by itself nor had protective effects on cell injuries caused by Ox-LDL or homocysteine. However, exogenous HSP70 administration could lead to a higher adhesion rate between rat peripheral blood monocytes (PBMCs) and RAECs. This adhesion-promoting effect appeared only when PBMCs, rather than RAECs, were pretreated with HSP70 incubation. PBMCs in an HSP70 environment released more IL-6 to supernatant, which subsequently up-regulated the expression of ICAM-1 in RAECs. These results indicate that the diet-induced elevation of circulating HSP70 could trigger cell adhesion with the help of IL-6 as a mediator, which provides a novel possible mechanism for understanding the role of circulating HSP70 in the pathogenesis of atherosclerosis. PMID:27435079

  19. Diet and atherosclerosis.

    PubMed Central

    Kritchevsky, D.

    1976-01-01

    Because of the statistical establishment of elevated blood lipids as a risk factor in the development of atherosclerotic heart disease, most of the attempts to regulate blood lipids by diet are centered on the fat in the diet. The levels of blood lipids and the course of experimental atherosclerosis can be affected by other dietary components such as type and amount of protein, carbohydrate, and nonnutritive fiber. Interaction among the dietary components further affects serum lipids and atherosclerosis. PMID:786036

  20. [Epigenetics in atherosclerosis].

    PubMed

    Guardiola, Montse; Vallvé, Joan C; Zaina, Silvio; Ribalta, Josep

    2016-01-01

    The association studies based on candidate genes carried on for decades have helped in visualizing the influence of the genetic component in complex diseases such as atherosclerosis, also showing the interaction between different genes and environmental factors. Even with all the knowledge accumulated, there is still some way to go to decipher the individual predisposition to disease, and if we consider the great influence that environmental factors play in the development and progression of atherosclerosis, epigenetics is presented as a key element in trying to expand our knowledge on individual predisposition to atherosclerosis and cardiovascular disease. Epigenetics can be described as the discipline that studies the mechanisms of transcriptional regulation, independent of changes in the sequence of DNA, and mostly induced by environmental factors. This review aims to describe what epigenetics is and how epigenetic mechanisms are involved in atherosclerosis. PMID:26088002

  1. Paraoxonase 2 Deficiency Alters Mitochondrial Function and Exacerbates the Development of Atherosclerosis

    PubMed Central

    Devarajan, Asokan; Bourquard, Noam; Hama, Susan; Navab, Mohamad; Grijalva, Victor R.; Morvardi, Susan; Clarke, Catherine F.; Vergnes, Laurent; Reue, Karen; Teiber, John F.

    2011-01-01

    Abstract Increased production of reactive oxygen species (ROS) as a result of decreased activities of mitochondrial electron transport chain (ETC) complexes plays a role in the development of many inflammatory diseases, including atherosclerosis. Our previous studies established that paraoxonase 2 (PON2) possesses antiatherogenic properties and is associated with lower ROS levels. The aim of the present study was to determine the mechanism by which PON2 modulates ROS production. In this report, we demonstrate that PON2-def mice on the hyperlipidemic apolipoprotein E−/− background (PON2-def/apolipoprotein E−/−) develop exacerbated atherosclerotic lesions with enhanced mitochondrial oxidative stress. We show that PON2 protein is localized to the inner mitochondrial membrane, where it is found associated with respiratory complex III. Employing surface-plasmon-resonance, we demonstrate that PON2 binds with high affinity to coenzyme Q10, an important component of the ETC. Enhanced mitochondrial oxidative stress in PON2-def mice was accompanied by significantly reduced ETC complex I + III activities, oxygen consumption, and adenosine triphosphate levels in PON2-def mice. In contrast, overexpression of PON2 effectively protected mitochondria from antimycin- or oligomycin-mediated mitochondrial dysfunction. Our results illustrate that the antiatherogenic effects of PON2 are, in part, mediated by the role of PON2 in mitochondrial function. Antioxid. Redox Signal. 14, 341–351. PMID:20578959

  2. Induction accelerator development for heavy ion fusion

    SciTech Connect

    Reginato, L.L.

    1993-05-01

    For approximately a decade, the Heavy Ion Fusion Accelerator Research (HIFAR) group at LBL has been exploring the use of induction accelerators with multiple beams as the driver for inertial fusion targets. Scaled experiments have investigated the transport of space charge dominated beams (SBTE), and the current amplification and transverse emittance control in induction linacs (MBE-4) with very encouraging results. In order to study many of the beam manipulations required by a driver and to further develop economically competitive technology, a proposal has been made in partnership with LLNL to build a 10 MeV accelerator and to conduct a series of experiments collectively called the Induction Linac System Experiments (ILSE). The major components critical to the ILSE accelerator are currently under development. We have constructed a full scale induction module and we have tested a number of amorphous magnetic materials developed by Allied Signal to establish an overall optimal design. The electric and magnetic quadrupoles critical to the transport and focusing of heavy ion beams are also under development The hardware is intended to be economically competitive for a driver without sacrificing any of the physics or performance requirements. This paper will concentrate on the recent developments and tests of the major components required by the ILSE accelerator.

  3. The Knowledge Accelerating the Society Development

    NASA Astrophysics Data System (ADS)

    Šmíd, Jaroslav; Sakál, Peter

    2010-01-01

    The formation of appropriate conditions can accelerate the society development. According to the existing definitions, the society can be viewed as mankind as a whole, or a state, a region or a group of businessmen. This paper extends and supplements of the contribution [1]. It deals with the knowledge accelerating the society development using the modified formal notation of the society development according to [2]. The open innovation concept [3] presents the intentional use of external knowledge flow. This paper deals with the intentional use of knowledge in time.

  4. Autoimmune atherosclerosis in 3D: How it develops, how to diagnose and what to do.

    PubMed

    Szekanecz, Zoltán; Kerekes, György; Végh, Edit; Kardos, Zsófia; Baráth, Zsuzsa; Tamási, László; Shoenfeld, Yehuda

    2016-07-01

    Autoimmune-inflammatory rheumatic diseases, such as rheumatoid arthritis (RA) have been associated with autoimmune atherosclerosis leading to increased cardiovascular risk. Traditional risk factors, genetics, as well as the role of systemic inflammation including inflammatory cells, cytokines, chemokines, proteases, autoantibodies, adhesion receptors and others have been implicated in the development of these vascular pathologies. Cardiovascular risk may be determined by the use of currently available tools. In addition, non-invasive assessment of vascular pathophysiology by imaging, as well as laboratory biomarkers can help to refine risk assessment. With respect to prevention and therapy, traditional vasculoprotection using statins, ACE inhibitors, aspirin should be applied to patients at risk. Non-steroidal antiinflammatory drugs and corticosteroids may be pro-atherogenic, on the other hand, they may also be beneficial due to their anti-inflammatory nation. Traditional and biologic DMARDs may have significant vascular and metabolic effects. Decreasing inflammatory activity by any of these agents may lead to better CV outcome. The official EULAR recommendations on the assessment and management of cardiovascular disease in arthritides may guide the rheumatologist during the process of CV screening, prevention and treatment. PMID:26979271

  5. Inhibition of leukocyte-type 12-lipoxygenase by guava tea leaves prevents development of atherosclerosis.

    PubMed

    Takahashi, Yoshitaka; Otsuki, Akemi; Mori, Yoshiko; Kawakami, Yuki; Ito, Hideyuki

    2015-11-01

    Oxidation of low-density lipoprotein (LDL) is one of the crucial steps for atherosclerosis development, and an essential role of leukocyte-type 12-lipoxygenase expressed in macrophages in this process has been demonstrated. The biochemical mechanism of the oxidation of circulating LDL by leukocyte-type 12-lipoxygenase in macrophages has been proposed. The major ingredients in guava tea leaves which inhibited the catalytic activity of leukocyte-type 12-lipoxygenase were quercetin and ethyl gallate. Administration of extracts from guava tea leaves to apoE-deficient mice significantly attenuated atherogenic lesions in the aorta and aortic sinus. We recently showed that Qing Shan Lu Shui inhibited the catalytic activity of leukocyte-type 12-lipoxygenase. The major components inhibiting the enzyme contained in Qing Shan Lu Shui were identified to be novel monoterpene glycosides. The anti-atherogenic effect of the tea leaves might be attributed to the inhibition of leukocyte-type 12-lipoxygenase by these components. PMID:25976783

  6. Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development.

    PubMed

    Aviram, Michael; Rosenblat, Mira

    2004-11-01

    Paraoxonases PON1 and PON3, which are both associated in serum with HDL, protect the serum lipids from oxidation, probably as a result of their ability to hydrolyze specific oxidized lipids. The activity of HDL-associated PON1 seems to involve an activity (phospholipase A2-like activity, peroxidase-like activity, lactonase activity) which produces LPC. To study the possible role of PON1 in macrophage foam cell formation and atherogenesis we used macrophages from control mice, from PON1 knockout mice, and from PON1 transgenic mice. Furthermore, we analyzed PON1-treated macrophages and PON1-transfected cells to demonstrate the contribution of PON1 to the attenuation of macrophage cholesterol and oxidized lipid accumulation and foam cell formation. PON1 was shown to inhibit cholesterol influx [by reducing the formation of oxidized LDL (Ox-LDL), increasing the breakdown of specific oxidized lipids in Ox-LDL, and decreasing macrophage uptake of Ox-LDL]. PON1 also inhibits cholesterol biosynthesis and stimulates HDL-mediated cholesterol efflux from macrophages. PON2 and PON3 protect against oxidative stress, with PON2 acting mainly at the cellular level. Whereas serum PON1 and PON3 were inactivated under oxidative stress, macrophage PON2 expression and activity were increased under oxidative stress, probably as a compensatory mechanism against oxidative stress. Intervention to increase the paraoxonases (cellular and humoral) by dietary or pharmacological means can reduce macrophage foam cell formation and attenuate atherosclerosis development. PMID:15454271

  7. Nutrition and Atherosclerosis.

    PubMed

    Torres, Nimbe; Guevara-Cruz, Martha; Velázquez-Villegas, Laura A; Tovar, Armando R

    2015-07-01

    Cardiovascular disease (CVD) is a universal problem in modern society. Atherosclerosis is the leading cause of CVD resulting in high rate of mortality in the population. Nutrition science has focused on the role of essential nutrients in preventing deficiencies, at the present time, the nutritional strategies are crucial to promote health and intervene with these global noncommunicable diseases. In many cases, diet is a major driving force, which is much easier to change and follow than other factors. It is important to establish that the first strategy to treat atherosclerosis is to modify lifestyle habits, focusing on the beneficial properties of specific nutrients. In the last decades, epidemiological, clinical and experimental studies have demonstrated that diet plays a central role in the prevention of atherosclerosis. In this review we will focus on the effect of specific foods, nutrients and bioactive compounds, including epidemiological facts, potential mechanisms of action and dietary recommendations to reduce the risk of atherosclerosis. In particular, we include information about fiber, plant sterols and stanols, niacin, taurine, olive oil, omega 3 fatty acids, antioxidants, minerals, methyl nutrients and soy. In addition, we also show that dysbiosis of the intestinal microbiota associated with a consumption of certain animal food sources can generate some metabolites that are involved in the development of atherosclerosis and its consequences on CVD. According to the epidemiological, clinical and experimental studies we suggest a recommendation for some dietary foods, nutrients and bioactive compounds to support the complementary clinical management of patients with atherosclerosis. PMID:26031780

  8. Accelerated Leadership Development: Fast Tracking School Leaders

    ERIC Educational Resources Information Center

    Earley, Peter; Jones, Jeff

    2010-01-01

    "Accelerated Leadership Development" captures and communicates the lessons learned from successful fast-track leadership programmes in the private and public sector, and provides a model which schools can follow and customize as they plan their own leadership development strategies. As large numbers of headteachers and other senior staff retire,…

  9. Advanced Microgravity Acceleration Measurement Systems Being Developed

    NASA Technical Reports Server (NTRS)

    Sicker, Ronald J.; Kacpura, Thomas J.

    2002-01-01

    The Advanced Microgravity Acceleration Measurement Systems (AMAMS) project at the NASA Glenn Research Center is part of the Instrument Technology Development program to develop advanced sensor systems. The primary focus of the AMAMS project is to develop microelectromechanical (MEMS) acceleration sensor systems to replace existing electromechanical-sensor-based systems presently used to assess relative gravity levels aboard spacecraft. These systems are used in characterizing both vehicle and payload responses to low-gravity vibroacoustic environments. The collection of microgravity acceleration data has cross-disciplinary utility to the microgravity life and physical sciences and the structural dynamics communities. The inherent advantages of semiconductor-based systems are reduced size, mass, and power consumption, while providing enhanced stability.

  10. Acceleration in dental development: fact or fiction.

    PubMed

    Holtgrave, E A; Kretschmer, R; Müller, R

    1997-12-01

    The aim of this investigation was to determine whether an actual acceleration in dental development has taken place over the last 30 years in a European population group, as is so readily observable in relation to body height. In this study, radiographs of 1038 healthy European children, 516 boys and 522 girls, were evaluated. The methodology and norms given by Nolla (1960) for both sexes were used and compared with the tooth developmental stages in our subjects. In girls, no difference to Nolla's norms could be detected. However, in boys, dental development has accelerated. This difference was most apparent in the 3- to 9-year-old age group and was statistically significant. Thus, over the last 30 years, a small acceleration in dental development has taken place in very young males. PMID:9458603

  11. Antihypercholesterolemic and antioxidant efficacies of zerumbone on the formation, development, and establishment of atherosclerosis in cholesterol-fed rabbits

    PubMed Central

    Hemn, Hassan Othman; Noordin, Muhammad Mustapha; Rahman, Heshu Sulaiman; Hazilawati, Hamza; Zuki, Abubakr; Chartrand, Max Stanley

    2015-01-01

    Owing to the high incidence of cholesterol-induced cardiovascular disease, particularly atherosclerosis, the current study was designed to investigate the preventive and therapeutic efficacies of dietary zerumbone (ZER) supplementation on the formation and development of atherosclerosis in rabbits fed with a high cholesterol diet. A total of 72 New Zealand white rabbits were divided randomly on two experimental studies carried out 8 weeks apart. The first experiment was designed to investigate the prophylactic efficacy of ZER in preventing early developed atheromatous lesion. The second experimental trial was aimed at investigating the therapeutic effect of ZER in reducing the atherosclerotic lesion progression and establishment. Sudanophilia, histopathological, and ultrastructural changes showed pronounced reduction in the plaque size in ZER-medicated aortas. On the other hand, dietary supplementation of ZER for almost 10 weeks as a prophylactic measure indicated substantially decreasing lipid profile values, and similarly, plaque size in comparison with high-cholesterol non-supplemented rabbits. Furthermore, the results of oxidative stress and antioxidant biomarker evaluation indicated that ZER is a potent antioxidant in suppressing the generation of free radicals in terms of atherosclerosis prevention and treatment. ZER significantly reduced the value of malondialdehyde and augmented the value of superoxide dismutase. In conclusion, our data indicated that dietary supplementation of ZER at doses of 8, 16, and 20 mg/kg alone as a prophylactic measure, and as a supplementary treatment with simvastatin, significantly reduced early plague formation, development, and establishment via significant reduction in serum lipid profile, together with suppression of oxidative damage, and therefore alleviated atherosclerosis lesions. PMID:26347047

  12. Vehicle Systems Integration Laboratory Accelerates Powertrain Development

    SciTech Connect

    2014-04-15

    ORNL's Vehicle Systems Integration (VSI) Laboratory accelerates the pace of powertrain development by performing prototype research and characterization of advanced systems and hardware components. The VSI Lab is capable of accommodating a range of platforms from advanced light-duty vehicles to hybridized Class 8 powertrains with the goals of improving overall system efficiency and reducing emissions.

  13. Vehicle Systems Integration Laboratory Accelerates Powertrain Development

    ScienceCinema

    None

    2014-06-25

    ORNL's Vehicle Systems Integration (VSI) Laboratory accelerates the pace of powertrain development by performing prototype research and characterization of advanced systems and hardware components. The VSI Lab is capable of accommodating a range of platforms from advanced light-duty vehicles to hybridized Class 8 powertrains with the goals of improving overall system efficiency and reducing emissions.

  14. The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes.

    PubMed

    Marfella, Raffaele; D' Amico, Michele; Di Filippo, Clara; Siniscalchi, Mario; Sasso, Ferdinando Carlo; Ferraraccio, Franca; Rossi, Francesco; Paolisso, Giuseppe

    2007-01-01

    We have reviewed the impact of the ubiquitin proteasome system (UPS) on atherosclerosis progression of diabetic patients. A puzzle of many pieces of evidence suggests that UPS, in addition to its role in the removal of damaged proteins, is involved in a number of biological processes including inflammation, proliferation and apoptosis, all of which constitute important characteristics of atherosclerosis. From what can be gathered from the very few studies on the UPS in diabetic cardiovascular diseases published so far, the system seems to be functionally active to a different extent in the initiation, progression, and complication stage of atherosclerosis in the diabetic people. Further evidence for this theory, however, has to be given, for instance by specifically targeted antagonism of the UPS. Nonetheless, this hypothesis may help us understand why diverse therapeutic interventions, which have in common the ability to reduce ubiquitin-proteasome activity, can impede or delay the onset of diabetes and cardiovascular diseases (CVD). People with type 2 diabetes are disproportionately affected by CVD, compared with those without diabetes 1. The prevalence, incidence, and mortality from all forms of CVD (myocardial infarction, cerebro-vascular disease and congestive heart failure) are strikingly increased in persons with diabetes compared with those withoutdiabetes 2. Furthermore, diabetic patients have not benefited by the advances in the management of obesity, dyslipidemia, and hypertension that have resulted in a decrease in mortality for coronary heart disease (CHD) patients without diabetes 3. Nevertheless, these risk factors do not fully explain the excess risk for CHD associated with diabetes 45. Thus, the determinants of progression of atherosclerosis in persons with diabetes must be elucidated. Beyond the major risk factors, several studies have demonstrated that such factors, strictly related to diabetes, as insulin-resistance, post-prandial hyperglycemia

  15. FcgammaRIIB inhibits the development of atherosclerosis in low-density lipoprotein receptor-deficient mice.

    PubMed

    Zhao, Ming; Wigren, Maria; Dunér, Pontus; Kolbus, Daniel; Olofsson, Katarina E; Björkbacka, Harry; Nilsson, Jan; Fredrikson, Gunilla Nordin

    2010-03-01

    The immune processes associated with atherogenesis have received considerable attention during recent years. IgG FcRs (FcgammaR) are involved in activating the immune system and in maintaining peripheral tolerance. However, the role of the inhibitory IgG receptor FcgammaRIIB in atherosclerosis has not been defined. Bone marrow cells from FcgammaRIIB-deficient mice and C57BL/6 control mice were transplanted to low-density lipoprotein receptor-deficient mice. Atherosclerosis was induced by feeding the recipient mice a high-fat diet for 8 wk and evaluated using Oil Red O staining of the descending aorta at sacrifice. The molecular mechanisms triggering atherosclerosis was studied by examining splenic B and T cells, as well as Th1 and Th2 immune responses using flow cytometry and ELISA. The atherosclerotic lesion area in the descending aorta was ~5-fold larger in mice lacking FcgammaRIIB than in control mice (2.75 +/- 2.57 versus 0.44 +/- 0.42%; p < 0.01). Moreover, the FcgammaRIIB deficiency resulted in an amplified splenocyte proliferative response to Con A stimulation (proliferation index 30.26 +/- 8.81 versus 2.96 +/- 0.81%, p < 0.0001) and an enhanced expression of MHC class II on the B cells (6.65 +/- 0.64 versus 2.33 +/- 0.25%; p < 0.001). In accordance, an enlarged amount of CD25-positive CD4 T cells was found in the spleen (42.74 +/- 4.05 versus 2.45 +/- 0.31%; p < 0.0001). The plasma Ab and cytokine pattern suggested increased Th1 and Th2 immune responses, respectively. These results show that FcgammaRIIB inhibits the development of atherosclerosis in mice. In addition, they indicate that absence of the inhibiting IgG receptor cause disease, depending on an imbalance of activating and inhibiting immune cells. PMID:20097865

  16. Sulforaphane attenuates the development of atherosclerosis and improves endothelial dysfunction in hypercholesterolemic rabbits.

    PubMed

    Shehatou, George S G; Suddek, Ghada M

    2016-02-01

    The aim of the present work was to explore possible protective effects of sulforaphane (SFN) against atherosclerosis development and endothelial dysfunction in hypercholesterolemic rabbits. Rabbits were assigned to three groups of five: group I fed normal chow diet for four weeks, group II fed 1% high cholesterol diet (HCD) and group III fed HCD + SFN (0.25 mg/kg/day). Blood samples were collected for measurement of serum triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), lactate dehydrogenase (LDH) and C-reactive protein (CRP). Aortic malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and total nitrite/nitrate (NOx) were measured. Vascular reactivity and intima/media (I/M) ratio were analyzed. Nuclear factor-kappa B (NF-κB) activation in aortic endothelial cells was identified immunohistochemically. HCD induced significant increases in serum TGs, TC, LDL-C, LDH, and CRP, and aortic MDA and SOD. Moreover, HCD caused significant reductions in serum HDL-C, aortic GSH and NOx. SFN administration significantly decreased HCD-induced elevations in serum TC, LDL-C, CRP, and LDH. while significantly increased HDL-C and GSH levels and normalized aortic SOD and NOx. Additionally, SFN significantly improved rabbit aortic endothelium-dependent relaxation to acetylcholine. Moreover, SFN significantly reduced the elevation in I/M ratio. This effect was confirmed by aortic histopathologic examination. The expression of NF-κB in aortic tissue showed a marked reduction upon treatment with SFN. In conclusion, this study reveals that SFN has the ability to ameliorate HCD-induced atherosclerotic lesions progression and vascular dysfunction, possibly via its lipid-lowering and antioxidant effects and suppression of NF-κB-mediated inflammation. PMID:26490346

  17. Role of Nucleotide-binding and Oligomerization Domain 2 Protein (NOD2) in the Development of Atherosclerosis

    PubMed Central

    2015-01-01

    NOD2 (nucleotide-binding and oligomerization domain 2) was initially reported as a susceptibility gene for Crohn's disease, with several studies focused on elucidating its molecular mechanism in the progression of Crohn's disease. We now know that NOD2 is an intracellular bacterial sensing receptor, and that MDP-mediated NOD2 activation drives inflammatory signaling. Various mutations in NOD2 have been reported, with NOD2 loss of function being associated with the development of Crohn's disease and other autoimmune diseases. These results suggest that NOD2 not only has an immune stimulatory function, but also an immune regulatory function. Atherosclerosis is a chronic inflammatory disease of the arterial wall; its pathologic progression is highly dependent on the immune balance. This immune balance is regulated by infiltrating monocytes and macrophages, both of which express NOD2. These findings indicate a potential role of NOD2 in atherosclerosis. The purpose of this review is to outline the known roles of NOD2 signaling in the pathogenesis of atherosclerosis. PMID:26557013

  18. Hydrogen Sulfide Inhibits the Development of Atherosclerosis with Suppressing CX3CR1 and CX3CL1 Expression

    PubMed Central

    Wu, Duojiao; Zhang, Alian; Gu, Ting; Wang, Liansheng; Wang, Changqian

    2012-01-01

    Hydrogen sulfide, as a novel gaseous mediator, has been suggested to play a key role in atherogenesis. However, the precise mechanisms by which H2S affects atherosclerosis remain unclear. Therefore, the present study aimed to investigate the potential role of H2S in atherosclerosis and the underlying mechanism with respect to chemokines (CCL2, CCL5 and CX3CL1) and chemokine receptors (CCR2, CCR5, and CX3CR1) in macrophages. Mouse macrophage cell line RAW 264.7 or mouse peritoneal macrophages were pre-incubated with saline or NaHS (50 µM, 100 µM, 200 µM), an H2S donor, and then stimulated with interferon-γ (IFN-γ) or lipopolysaccharide (LPS). It was found that NaHS dose-dependently inhibited IFN-γ or LPS-induced CX3CR1 and CX3CL1 expression, as well as CX3CR1-mediated chemotaxis in macrophages. Overexpression of cystathionine γ-lyase (CSE), an enzyme that catalyzes H2S biosynthesis resulted in a significant reduction in CX3CR1 and CX3CL1 expression as well as CX3CR1-mediated chemotaxis in stimulated macrophages. The inhibitory effect of H2S on CX3CR1 and CX3CL1 expression was mediated by modulation of proliferators-activated receptor-γ (PPAR-γ) and NF-κB pathway. Furthermore, male apoE−/− mice were fed a high-fat diet and then randomly given NaHS (1 mg/kg, i.p., daily) or DL-propargylglycine (PAG, 10 mg/kg, i.p., daily). NaHS significantly inhibited aortic CX3CR1 and CX3CL1 expression and impeded aortic plaque development. NaHS had a better anti-atherogenic benefit when it was applied at the early stage of atherosclerosis. However, inhibition of H2S formation by PAG increased aortic CX3CR1 and CX3CL1 expression and exacerbated the extent of atherosclerosis. In addition, H2S had minimal effect on the expression of CCL2, CCL5, CCR2 and CCR5 in vitro and in vivo. In conclusion, these data indicate that H2S hampers the progression of atherosclerosis in fat-fed apoE−/− mice and downregulates CX3CR1 and CX3CL1 expression on macrophages and in lesion

  19. The effects of endothelial lipase gene (LIPG) variants on inflammation marker levels and atherosclerosis development.

    PubMed

    Dalan, Altay Burak; Toptaş, Bahar; Buğra, Zehra; Polat, Nihat; Yılmaz-Aydoğan, Hülya; Çimen, Arif; Isbir, Turgay

    2013-08-01

    Atherosclerosis is a major pathological process related with several important adverse vascular events including coronary artery disease, stroke, and peripheral arterial disease. Endothelial lipase is an enzyme the activity of which affects all of lipoproteins, whereas HDL is the main substrate. The purpose of our study was to investigate the effects of endothelial lipase gene polymorphism and inflammation markers (CRP, IL-1β, IL-6, IL-8 and TNF-α) in the atherosclerosis. 104 patients with atherosclerosis and 76 healthy individuals were included in the study. LIPG -584C/T polymorphism gene polymorphisms were assessed with PCR-RFLP method. The serum CRP levels were measured by turbidimetric method using a biochemistry autoanalyzer, whereas serum IL-1β, IL-6, IL-8, TNF-α levels were determined by enzyme-linked immunosorbent assay. In this study, we found that the frequencies of TC genotype are more prevalent in patients than controls. We found a statistically significant difference of IL-6 levels between patient and control group. Our findings suggest that T allele might play a potential role in the susceptibility to atherogenesis in the Turkish population. PMID:23673478

  20. Spontaneous Atherosclerosis in Pigeons

    PubMed Central

    Santerre, Robert F.; Wight, Thomas N.; Smith, Samuel C.; Brannigan, David

    1972-01-01

    The interpretation of metabolic studies related to early changes in spontaneous atherosclerosis has been hampered by the focal nature of the disease and by the lack of a well-defined model system of the disease process. Gross, histologic and ultrastructural observations of lesion development at the celiac bifurcation of the aorta in atherosclerosis-susceptible White Carneau and atherosclerosis-resistant Show Racer pigeons are compared and discussed in terms of hemodynamics, muscular aggregation and altered metabolism of smooth muscle cells. Detailed knowledge of the morphologic sequence of events in lesion localization makes the celiac bifurcation in White Carneau and Show Racer pigeons a useful model for genetic comparisons of arterial wall metabolism and for investigating metabolic alterations occurring with atherogenesis. ImagesFig 9Fig 10Fig 1Fig 2Fig 10Fig 11Fig 3Fig 4Fig 12Fig 5Fig 6Fig 7Fig 8 PMID:4261591

  1. Molecular imaging in atherosclerosis

    PubMed Central

    Glaudemans, Andor W. J. M.; Slart, Riemer H. J. A.; Bozzao, Alessandro; Bonanno, Elena; Arca, Marcello; Dierckx, Rudi A. J. O.

    2010-01-01

    Atherosclerosis is the major cause of cardiovascular disease, which still has the leading position in morbidity and mortality in the Western world. Many risk factors and pathobiological processes are acting together in the development of atherosclerosis. This leads to different remodelling stages (positive and negative) which are both associated with plaque physiology and clinical presentation. The different remodelling stages of atherosclerosis are explained with their clinical relevance. Recent advances in basic science have established that atherosclerosis is not only a lipid storage disease, but that also inflammation has a fundamental role in all stages of the disease. The molecular events leading to atherosclerosis will be extensively reviewed and described. Further on in this review different modalities and their role in the different stages of atherosclerosis will be discussed. Non-nuclear invasive imaging techniques (intravascular ultrasound, intravascular MRI, intracoronary angioscopy and intravascular optical coherence tomography) and non-nuclear non-invasive imaging techniques (ultrasound with Doppler flow, electron-bean computed tomography, coronary computed tomography angiography, MRI and coronary artery MR angiography) will be reviewed. After that we focus on nuclear imaging techniques for detecting atherosclerotic plaques, divided into three groups: atherosclerotic lesion components, inflammation and thrombosis. This emerging area of nuclear imaging techniques can provide measures of biological activity of atherosclerotic plaques, thereby improving the prediction of clinical events. As we will see in the future perspectives, at present, there is no special tracer that can be called the diagnostic tool to diagnose prospective stroke or infarction in patients. Nevertheless, we expect such a tracer to be developed in the next few years and maybe, theoretically, it could even be used for targeted therapy (in the form of a beta-emitter) to combat

  2. Imaging Atherosclerosis.

    PubMed

    Tarkin, Jason M; Dweck, Marc R; Evans, Nicholas R; Takx, Richard A P; Brown, Adam J; Tawakol, Ahmed; Fayad, Zahi A; Rudd, James H F

    2016-02-19

    Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic. PMID:26892971

  3. Imaging Atherosclerosis

    PubMed Central

    Tarkin, Jason M.; Dweck, Marc R.; Evans, Nicholas R.; Takx, Richard A.P.; Brown, Adam J.; Tawakol, Ahmed; Fayad, Zahi A.

    2016-01-01

    Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic. PMID:26892971

  4. Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice.

    PubMed

    Dorighello, Gabriel G; Rovani, Juliana C; Luhman, Christopher J F; Paim, Bruno A; Raposo, Helena F; Vercesi, Anibal E; Oliveira, Helena C F

    2014-03-28

    Different regimens of food restriction have been associated with protection against obesity, diabetes and CVD. In the present study, we hypothesised that food restriction would bring benefits to atherosclerosis- and diabetes-prone hypercholesterolaemic LDL-receptor knockout mice. For this purpose, 2-month-old mice were submitted to an intermittent fasting (IF) regimen (fasting every other day) over a 3-month period, which resulted in an overall 20 % reduction in food intake. Contrary to our expectation, epididymal and carcass fat depots and adipocyte size were significantly enlarged by 15, 72 and 68 %, respectively, in the IF mice compared with the ad libitum-fed mice. Accordingly, plasma levels of leptin were 50 % higher in the IF mice than in the ad libitum-fed mice. In addition, the IF mice showed increased plasma levels of total cholesterol (37 %), VLDL-cholesterol (195 %) and LDL-cholesterol (50 %). As expected, in wild-type mice, the IF regimen decreased plasma cholesterol levels and epididymal fat mass. Glucose homeostasis was also disturbed by the IF regimen in LDL-receptor knockout mice. Elevated levels of glycaemia (40 %), insulinaemia (50 %), glucose intolerance and insulin resistance were observed in the IF mice. Systemic inflammatory markers, TNF-α and C-reactive protein, were significantly increased and spontaneous atherosclerosis development were markedly increased (3-fold) in the IF mice. In conclusion, the IF regimen induced obesity and diabetes and worsened the development of spontaneous atherosclerosis in LDL-receptor knockout mice. Although being efficient in a wild-type background, this type of food restriction is not beneficial in the context of genetic hypercholesterolaemia. PMID:24176004

  5. Guidelines for Developing an Academic Acceleration Policy

    ERIC Educational Resources Information Center

    Colangelo, Nicholas; Assouline, Susan G.; Marron, Maureen A.; Castellano, Jaime A.; Clinkenbeard, Pamela R.; Rogers, Karen; Calvert, Eric; Malek, Rosanne; Smith, Donnajo

    2010-01-01

    As an educational intervention, acceleration is decidedly effective for high-ability students. The research support for acceleration that has accumulated over many decades is robust and consistent and allows us to confidently state that carefully planned acceleration decisions are successful. Both grade-based and content-based acceleration are…

  6. Decreased Bone Mineral Density Is an Independent Predictor for the Development of Atherosclerosis: A Systematic Review and Meta-Analysis

    PubMed Central

    Ye, Chenyi; Xu, Mingyuan; Wang, Shengdong; Jiang, Shuai; Chen, Xi; Zhou, Xiaoyu; He, Rongxin

    2016-01-01

    Background There is conflicting evidence regarding the association between decreased bone mineral density (BMD) and atherosclerosis. To this end, we performed a systematic review and meta-analysis to clarify the association. Methods To identify relevant studies, PubMed, Embase, and the Cochrane Library were systematically searched up to November 2015. All observational and comparative studies directly investigating the relationship between decreased BMD and clinical consequences of atherosclerotic vascular abnormalities, including carotid artery calcification (CAC), cardiovascular disease (CAD), and coronary artery disease (CAD) were obtained, without limitation of language or publication year. Results A total of 25 studies involving 10,299 patients were included. The incidence of atherosclerotic vascular abnormalities was significantly increased in low BMD patients, compared to patients with normal BMD (OR, 1.81, 95% CI [1.01, 2.19], p<0.00001)). Similar results were also observed for postmenopausal women (OR, 2.23, 95% CI [1.72, 2.89], p<0.00001). Subgroup analyses of osteopenia, osteoporosis, and normal BMD also revealed that the combined ORs for the incidence of atherosclerotic vascular abnormalities increased as BMD decreased. Of note, after adjusting for age, sex, body mass index (BMI) and other vascular risk factors, decreased BMD remained significantly associated with the incidence of atherosclerotic vascular abnormalities (OR, 2.96, 95% CI [2.25, 3.88], p < 0.00001). Conclusions Based on the results of this study, decreased BMD is an independent predictor for the development of atherosclerosis in elderly individuals. Moreover, the risk of atherosclerotic vascular abnormalities increased as BMD decreased. Future studies focusing on individuals with different severities of atherosclerosis and comorbidities are of interest. PMID:27149062

  7. Immune mechanisms in atherosclerosis, especially in diabetes type 2.

    PubMed

    Frostegård, Johan

    2013-01-01

    Atherosclerosis and ensuing cardiovascular disease (CVD) are major complications of diabetes type 2. Atherosclerosis is a chronic inflammatory condition involving immunocompetent cells of different types present in the lesions. Even though inflammation and immune activation may be more pronounced in atherosclerosis in diabetes type 2, there does not appear to be any major differences between diabetics and non-diabetics. Similar factors are thus implicated in atherosclerosis-associated immune activation in both groups. The cause of immune activation is not known and different mutually non-exclusive possibilities exist. Oxidized and/or enzymatically modified forms of low-density lipoprotein (OxLDL) and dead cells are present in atherosclerotic plaques. OxLDL could play a role, being pro-inflammatory and immunostimulatory as it activates T-cells and is cytotoxic at higher concentrations. Inflammatory phospholipids in OxLDL are implicated, with phosphorylcholine (PC) as one of the exposed antigens. Antibodies against PC (anti-PC) are anti-atherogenic in mouse studies, and anti-PC is negatively associated with development of atherosclerosis and CVD in humans. Bacteria and virus have been discussed as potential causes of immune activation, but it has been difficult to find direct evidence supporting this hypothesis, and antibiotic trials in humans have been negative or inconclusive. Heat shock proteins (HSP) could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include cytokines such as interleukin 1β (IL-1β), tumor necrosis factor (TNF), and also lipid mediators as leukotrienes. In addition, in diabetes, hyperglycemia and oxidative stress appear to accelerate the development of atherosclerosis, one mechanism could be via promotion of immune reactions. To prove that immune reactions are causative of atherosclerosis and CVD, further studies with immune-modulatory treatments are needed. PMID:24194733

  8. Gradient Echo MRI Characterization of Development of Atherosclerosis in the Abdominal Aorta in Watanabe Heritable Hyperlipidemic Rabbits

    SciTech Connect

    Wang, Yi-Xiang J. Kuribayashi, Hideto; Wagberg, Maria; Holmes, Andrew P.; Tessier, Jean J.; Waterton, John C.

    2006-08-15

    Purpose. The Watanabe Heritable Hyperlipidemic (WHHL) rabbit provides an important model of spontaneous atherosclerosis. With a strain of WHHL rabbits which do not develop abdominal aorta lumen stenosis even with advanced atherosclerosis, we studied the MRI-histology correlation, and the natural progression of atherosclerosis in the abdominal aorta. In addition, intra-reader segmentation repeatability and scan-rescan reproducibility were assessed. Methods. Two batches of female WHHL rabbits were used. The first batch of 6 rabbits was scanned at 20 weeks old. A second batch of 17 rabbits was scanned at 50 weeks old and then randomly divided into two subgroups: 8 were killed for histologic investigation; 9 were kept alive for follow-up, with repeat scanning a week later to assess scan-rescan reproducibility, and again at 73 weeks old to assess disease progression. MR images were acquired at 4.7 T using a chemical shift selective fat suppression gradient echo with a saturation band suppressing blood signal within the aortic lumen. Five slices per animal were acquired, centered around the renal artery region of the abdominal aorta, with in-plane resolution of 0.195 mm and slice thickness of 3 mm. Results. The coefficient of variation for intra-reader reproducibility for aortic wall thickness measurements was 2.5% for repeat segmentations of the same scans on the same day, but segmentations of these same scans made 8 months later showed a systematic change, suggesting that intra-reader bias as well as increased variability could compromise assessments made over time. Comparative analyses were therefore performed in one postprocessing session. The coefficient of variation for scan-rescan reproducibility for aortic wall thickness was 5.5% for nine pairs of scans acquired a week apart and segmented on the same day. Good MRI-histology correlation was obtained. The MRI-measured mean aortic wall thickness of animals at 20 weeks of age was 76% that of animals at 50 weeks of

  9. What Causes Atherosclerosis?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Causes Atherosclerosis? The exact cause of atherosclerosis isn't known. ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  10. How Is Atherosclerosis Treated?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Is Atherosclerosis Treated? Treatments for atherosclerosis may include heart-healthy ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  11. Ozone oxidative preconditioning prevents atherosclerosis development in New Zealand White rabbits.

    PubMed

    Delgado-Roche, Livan; Martínez-Sánchez, Gregorio; Re, Lamberto

    2013-02-01

    Atherosclerosis is a major cause of death in the Western World. It is known that Lipofundin 20% induces atherosclerotic lesions, whereas ozone at low doses has been satisfactorily used in the prevention of oxidative stress-associated pathologies, such as coronary artery diseases. The aim of the present work was to evaluate the effects of ozone therapy on Lipofundin-induced atherosclerotic lesions in New Zealand White rabbits. Ozone (1 mg), mixed with oxygen as passive carrier, was administered by rectal insufflation during 15 sessions in 5 weeks. Then, the animals were intravenously treated with 2 mL/kg of Lipofundin, daily during 8 days. Animals were euthanized and eosin and hematoxylin staining was used for aortic histopathological analysis. The biomarkers of oxidative stress and lipid profile in serum were determined by spectrophotometric techniques. The results demonstrated that ozone induced inhibitory effects on aortic lesions formation. On the other hand, a reduction of biomolecular damage and an increase of antioxidant systems were observed at the end of the experiment. The serum lipids profiles were not modified after only 1 cycle of ozone treatment. Our results reinforced the hypotheses that antioxidant effects induced by ozone in the context of atherosclerosis demonstrate the antiatherogenic properties of the gas in the experimental conditions of this study. PMID:23222311

  12. Endothelial Expression of Scavenger Receptor Class B, Type I Protects against Development of Atherosclerosis in Mice

    PubMed Central

    Vaisman, Boris L.; Vishnyakova, Tatyana G.; Freeman, Lita A.; Amar, Marcelo J.; Demosky, Stephen J.; Liu, Chengyu; Stonik, John A.; Sampson, Maureen L.; Pryor, Milton; Bocharov, Alexander V.; Eggerman, Thomas L.; Patterson, Amy P.; Remaley, Alan T.

    2015-01-01

    The role of scavenger receptor class B, type I (SR-BI) in endothelial cells (EC) was examined in several novel transgenic mouse models expressing SR-BI in endothelium of mice with normal C57Bl6/N, apoE-KO, or Scarb1-KO backgrounds. Mice were also created expressing SR-BI exclusively in endothelium and liver. Endothelial expression of the Tie2-Scarb1 transgene had no significant effect on plasma lipoprotein levels in mice on a normal chow diet but on an atherogenic diet, significantly decreased plasma cholesterol levels, increased plasma HDL cholesterol (HDL-C) levels, and protected mice against atherosclerosis. In 8-month-old apoE-KO mice fed a normal chow diet, the Tie2-Scarb1 transgene decreased aortic lesions by 24%. Mice expressing SR-BI only in EC and liver had a 1.5 ± 0.1-fold increase in plasma cholesterol compared to mice synthesizing SR-BI only in liver. This elevation was due mostly to increased HDL-C. In EC culture studies, SR-BI was found to be present in both basolateral and apical membranes but greater cellular uptake of cholesterol from HDL was found in the basolateral compartment. In summary, enhanced expression of SR-BI in EC resulted in a less atherogenic lipoprotein profile and decreased atherosclerosis, suggesting a possible role for endothelial SR-BI in the flux of cholesterol across EC. PMID:26504816

  13. Accelerated Vascular Disease in Systemic Lupus Erythematosus: Role of Macrophage

    PubMed Central

    Al Gadban, Mohammed M.; Alwan, Mohamed M.; Smith, Kent J.; Hammad, Samar M.

    2015-01-01

    Atherosclerosis is a chronic inflammatory condition that is considered a major cause of death worldwide. Striking phenomena of atherosclerosis associated with systemic lupus erythematosus (SLE) is its high incidence in young patients. Macrophages are heterogeneous cells that differentiate from hematopoietic progenitors and reside in different tissues to preserve tissue integrity. Macrophages scavenge modified lipids and play a major role in the development of atherosclerosis. When activated, macrophages secret inflammatory cytokines. This activation triggers apoptosis of cells in the vicinity of macrophages. As such, macrophages play a significant role in tissue remodeling including atherosclerotic plaque formation and rupture. In spite of studies carried on identifying the role of macrophages in atherosclerosis, this role has not been studied thoroughly in SLE-associated atherosclerosis. In this review, we address factors released by macrophages as well as extrinsic factors that may control macrophage behavior and their effect on accelerated development of atherosclerosis in SLE. PMID:25638414

  14. Computational modelling of atherosclerosis.

    PubMed

    Parton, Andrew; McGilligan, Victoria; O'Kane, Maurice; Baldrick, Francina R; Watterson, Steven

    2016-07-01

    Atherosclerosis is one of the principle pathologies of cardiovascular disease with blood cholesterol a significant risk factor. The World Health Organization estimates that approximately 2.5 million deaths occur annually because of the risk from elevated cholesterol, with 39% of adults worldwide at future risk. Atherosclerosis emerges from the combination of many dynamical factors, including haemodynamics, endothelial damage, innate immunity and sterol biochemistry. Despite its significance to public health, the dynamics that drive atherosclerosis remain poorly understood. As a disease that depends on multiple factors operating on different length scales, the natural framework to apply to atherosclerosis is mathematical and computational modelling. A computational model provides an integrated description of the disease and serves as an in silico experimental system from which we can learn about the disease and develop therapeutic hypotheses. Although the work completed in this area to date has been limited, there are clear signs that interest is growing and that a nascent field is establishing itself. This article discusses the current state of modelling in this area, bringing together many recent results for the first time. We review the work that has been done, discuss its scope and highlight the gaps in our understanding that could yield future opportunities. PMID:26438419

  15. Recent Highlights of ATVB Atherosclerosis

    PubMed Central

    Lu, Hong; Daugherty, Alan

    2015-01-01

    Summary Mechanistic studies over the past decades using in vitro systems, animal models, and human tissues have highlighted the complexity of pathophysiological processes of atherosclerosis. Hypercholesterolemia, as one of the major risk factors for the development and progression of atherosclerosis, is still the focus of many mechanistic studies and the major therapeutic target of atherosclerosis. Although there is a dire need to validate many experimental findings in humans, there is a large number of approaches that have been showing promise for contributing to future therapeutic strategies. PMID:25717174

  16. Rapid Progression of Coronary Atherosclerosis: A Review

    PubMed Central

    Shah, Priyank; Bajaj, Sharad; Virk, Hartaj; Bikkina, Mahesh; Shamoon, Fayez

    2015-01-01

    Atherosclerosis is chronic disease, the prevalence of which has increased steadily as the population ages. Vascular injury is believed to be critical initiating event in pathogenesis of spontaneous atherosclerosis. Syndrome of accelerated atherosclerosis has been classically described in patients undergoing heart transplantation, coronary artery bypass graft, and percutaneous transluminal coronary angioplasty. In contrast to spontaneous atherosclerosis, denuding endothelial injury followed by thrombus formation and initial predominant smooth muscle cell proliferation is believed to be playing a significant role in accelerated atherosclerosis. There is no universal definition of rapid progression of atherosclerosis. However most studies describing the phenomenon have used the following definition: (i) > or = 10% diameter reduction of at least one preexisting stenosis > or = 50%, (ii) > or = 30% diameter reduction of a preexisting stenosis <50%, and (iii) progression of a lesion to total occlusion within few months. Recent studies have described the role of coronary vasospasm, human immunodeficiency virus, various inflammatory markers, and some genetic mutations as predictors of rapid progression of atherosclerosis. As research in the field of vascular biology continues, more factors are likely to be implicated in the pathogenesis of rapid progression of atherosclerosis. PMID:26823982

  17. Cytochrome P450 1B1 Contributes to the Development of Atherosclerosis and Hypertension in Apolipoprotein E-Deficient Mice.

    PubMed

    Song, Chi Young; Ghafoor, Khuzema; Ghafoor, Hafiz U; Khan, Nayaab S; Thirunavukkarasu, Shyamala; Jennings, Brett L; Estes, Anne M; Zaidi, Sahar; Bridges, Dave; Tso, Patrick; Gonzalez, Frank J; Malik, Kafait U

    2016-01-01

    Cytochrome P450 (CYP) 1B1 contributes to vascular smooth muscle cell growth and hypertension in male mice. This study was conducted to determine the contribution of CYP1B1 to the development of atherosclerosis and hypertension and associated pathogenesis in 8-week-old male apolipoprotein E-deficient (ApoE(-/-)/Cyp1b1(+/+)), and ApoE- and CYP1B1-deficient (ApoE(-/-)/Cyp1b1(-/-)) mice fed a normal or atherogenic diet for 12 weeks. A separate group of ApoE(-/-)/Cyp1b1(+/+) mice on an atherogenic diet was injected every third day with the CYP1B1 inhibitor, 2,3',4,5'-tetramethoxystilbene (300 μg/kg), or its vehicle, dimethyl sulfoxide (30 μL, IP); systolic blood pressure was measured by the tail cuff method. After 12 weeks, mice were euthanized, blood collected for lipid analysis, and aortas harvested for measuring lesions and remodeling, and for infiltration of inflammatory cells by histological and immunohistochemical analysis, respectively, and for reactive oxygen species production. Blood pressure, areas of lipids and collagen deposition, elastin breaks, infiltration of macrophages and T lymphocytes, reactive oxygen species generation in the aorta, and plasma lipid levels were increased in ApoE(-/-)/Cyp1b1(+/+) mice on an atherogenic diet; these changes were minimized in mice given 2,3',4,5'-tetramethoxystilbene, and in ApoE(-/-)/Cyp1b1(-/-) mice on an atherogenic diet; absorption/production of lipids remained unaltered in these mice. These data suggest that aortic lesions, hypertension, and associated pathogenesis in ApoE(-/-)/Cyp1b1(+/+) mice on an atherogenic diet are most likely dependent on CYP1B1-generated oxidative stress and increased plasma lipid levels independent of blood pressure and absorption of lipids. CYP1B1 could serve as a novel target for developing drugs to treat atherosclerosis and hypertension caused by hypercholesterolemia. PMID:26573711

  18. MicroRNAs and atherosclerosis

    PubMed Central

    Madrigal-Matute, Julio; Rotllan, Noemi; Aranda, Juan F.; Fernández-Hernando, Carlos

    2014-01-01

    MicroRNAs (miRNAs) are small (~22nucleotide) sequences of RNA that regulate gene expression at posttranscriptional level. MiRNA/mRNA base pairing complementarity provokes mRNA decay and consequent gene silencing. These endogenous gene expression inhibitors were primarily described in cancer but recent exciting findings have also demonstrated a key role in cardiovascular diseases (CVDs) including atherosclerosis. MiRNAs controls endothelial cell (EC), vascular smooth muscle cell (VSMC) and macrophage functions, and thereby regulate the progression of atherosclerosis. MiRNAs expression is modulated by different stimuli involved in every stage of atherosclerosis and conversely miRNAs modulates several pathways implicated in plaque development such as cholesterol metabolism. In the present review, we focus on the importance of miRNAs in atherosclerosis and we further discuss their potential use as biomarkers and therapeutic targets in CVDs. PMID:23512606

  19. Targeting hydrogen sulfide as a promising therapeutic strategy for atherosclerosis.

    PubMed

    Xu, Suowen; Liu, Zhiping; Liu, Peiqing

    2014-03-15

    Physiological concentrations of nitric oxide (NO) and carbon monoxide (CO) have multiple protective effects in the cardiovascular system. Recent studies have implicated hydrogen sulfide (H2S) as a new member of vasculoprotective gasotransmitter family, behaving similarly to NO and CO. H2S has been demonstrated to inhibit multiple key aspects of atherosclerosis, including atherogenic modification of LDL, monocytes adhesion to the endothelial cells, macrophage-derived foam cell formation and inflammation, smooth muscle cell proliferation, neointimal hyperplasia, vascular calcification, and thrombogenesis. H2S also decreases plasma homocysteine levels in experimental animal models. In the human body, H2S production is predominantly catalyzed by cystathionine-β-synthase (CBS) and cystathionine γ-lyase (CSE). CSE is the primary H2S-producing enzyme in the vasculature. Growing evidence suggests that atherosclerosis is associated with vascular CSE/H2S deficiency and that H2S supplementation by exogenous H2S donors (such as NaHS and GYY4137) attenuates, and H2S synthesis suppression by inhibitors (such as D, L-propargylglycine) aggravates the development of atherosclerotic plaques. However, it remains elusive whether CSE deficiency plays a causative role in atherosclerosis. A recent study (Circulation. 2013; 127: 2523-2534) demonstrates that decreased endogenous H2S production by CSE genetic deletion accelerates atherosclerosis in athero-prone ApoE-/- mice, pinpointing that endogenously produced H2S by CSE activation may be of benefit in the prevention and treatment of atherosclerosis. This study will facilitate the development of H2S-based pharmaceuticals with therapeutic applications in atherosclerosis-related cardiovascular diseases. PMID:24491853

  20. Accelerator System Development at High Voltage Engineering

    SciTech Connect

    Klein, M. G.; Gottdang, A.; Haitsma, R. G.; Mous, D. J. W.

    2009-03-10

    Throughout the years, HVE has continuously extended the capabilities of its accelerator systems to meet the rising demands from a diverse field of applications, among which are deep level ion implantation, micro-machining, neutron production for biomedical research, isotope production or accelerator mass spectrometry. Characteristic for HVE accelerators is the coaxial construction of the all solid state power supply around the acceleration tubes. With the use of solid state technology, the accelerators feature high stability and very low ripple. Terminal voltages range from 1 to 6 MV for HVE Singletrons and Tandetrons. The high-current versions of these accelerators can provide ion beams with powers of several kW. In the last years, several systems have been built with terminal voltages of 1.25 MV, 2 MV and 5 MV. Recently, the first system based on a 6 MV Tandetron has passed the factory tests. In this paper we describe the characteristics of the HVE accelerator systems and present as example recent systems.

  1. Technologies using accelerator-driven targets under development at BNL

    SciTech Connect

    Van Tuyle, G.J.

    1994-08-01

    Recent development work conducted at Brookhaven National Laboratory on technologies which use particle accelerator-driven targets is summarized. These efforts include development of the Spallation-Induced Lithium Conversion (SILC) Target for the Accelerator Production of Tritium (APT), the Accelerator-Driven Assembly for Plutonium Transformation (ADAPT) Target for the Accelerator-Based Conversion (ABC) of excess weapons plutonium. The PHOENIX Concept for the accelerator-driven transmutation of minor actinides and fission products from the waste stream of commercial nuclear power plants, and other potential applications.

  2. Kif14 overexpression accelerates murine retinoblastoma development.

    PubMed

    O'Hare, Michael; Shadmand, Mehdi; Sulaiman, Rania S; Sishtla, Kamakshi; Sakisaka, Toshiaki; Corson, Timothy W

    2016-10-15

    The mitotic kinesin KIF14 has an essential role in the recruitment of proteins required for the final stages of cytokinesis. Genomic gain and/or overexpression of KIF14 has been documented in retinoblastoma and a number of other cancers, such as breast, lung and ovarian carcinomas, strongly suggesting its role as an oncogene. Despite evidence of oncogenic properties in vitro and in xenografts, Kif14's role in tumor progression has not previously been studied in a transgenic cancer model. Using a novel Kif14 overexpressing, simian virus 40 large T-antigen retinoblastoma (TAg-RB) double transgenic mouse model, we aimed to determine Kif14's role in promoting retinal tumor formation. Tumor initiation and development in double transgenics and control TAg-RB littermates were documented in vivo over a time course by optical coherence tomography, with subsequent ex vivo quantification of tumor burden. Kif14 overexpression led to an accelerated initiation of tumor formation in the TAg-RB model and a significantly decreased tumor doubling time (1.8 vs. 2.9 weeks). Moreover, overall percentage tumor burden was also increased by Kif14 overexpression. These data provide the first evidence that Kif14 can promote tumor formation in susceptible cells in vivo. PMID:27270502

  3. Macrophage phenotypes in atherosclerosis.

    PubMed

    Colin, Sophie; Chinetti-Gbaguidi, Giulia; Staels, Bart

    2014-11-01

    Initiation and progression of atherosclerosis depend on local inflammation and accumulation of lipids in the vascular wall. Although many cells are involved in the development and progression of atherosclerosis, macrophages are fundamental contributors. For nearly a decade, the phenotypic heterogeneity and plasticity of macrophages has been studied. In atherosclerotic lesions, macrophages are submitted to a large variety of micro-environmental signals, such as oxidized lipids and cytokines, which influence the phenotypic polarization and activation of macrophages resulting in a dynamic plasticity. The macrophage phenotype spectrum is characterized, at the extremes, by the classical M1 macrophages induced by T-helper 1 (Th-1) cytokines and by the alternative M2 macrophages induced by Th-2 cytokines. M2 macrophages can be further classified into M2a, M2b, M2c, and M2d subtypes. More recently, additional plaque-specific macrophage phenotypes have been identified, termed as Mox, Mhem, and M4. Understanding the mechanisms and functional consequences of the phenotypic heterogeneity of macrophages will contribute to determine their potential role in lesion development and plaque stability. Furthermore, research on macrophage plasticity could lead to novel therapeutic approaches to counteract cardiovascular diseases such as atherosclerosis. The present review summarizes our current knowledge on macrophage subsets in atherosclerotic plaques and mechanism behind the modulation of the macrophage phenotype. PMID:25319333

  4. Accelerated Application Development: The ORNL Titan Experience

    SciTech Connect

    Joubert, Wayne; Archibald, Richard K.; Berrill, Mark A.; Brown, W. Michael; Eisenbach, Markus; Grout, Ray; Larkin, Jeff; Levesque, John; Messer, Bronson; Norman, Matthew R.; Philip, Bobby; Sankaran, Ramanan; Tharrington, Arnold N.; Turner, John A.

    2015-05-09

    The use of computational accelerators such as NVIDIA GPUs and Intel Xeon Phi processors is now widespread in the high performance computing community, with many applications delivering impressive performance gains. However, programming these systems for high performance, performance portability and software maintainability has been a challenge. In this paper we discuss experiences porting applications to the Titan system. Titan, which began planning in 2009 and was deployed for general use in 2013, was the first multi-petaflop system based on accelerator hardware. To ready applications for accelerated computing, a preparedness effort was undertaken prior to delivery of Titan. In this paper we report experiences and lessons learned from this process and describe how users are currently making use of computational accelerators on Titan.

  5. Accelerated Application Development: The ORNL Titan Experience

    DOE PAGESBeta

    Joubert, Wayne; Archibald, Richard K.; Berrill, Mark A.; Brown, W. Michael; Eisenbach, Markus; Grout, Ray; Larkin, Jeff; Levesque, John; Messer, Bronson; Norman, Matthew R.; et al

    2015-05-09

    The use of computational accelerators such as NVIDIA GPUs and Intel Xeon Phi processors is now widespread in the high performance computing community, with many applications delivering impressive performance gains. However, programming these systems for high performance, performance portability and software maintainability has been a challenge. In this paper we discuss experiences porting applications to the Titan system. Titan, which began planning in 2009 and was deployed for general use in 2013, was the first multi-petaflop system based on accelerator hardware. To ready applications for accelerated computing, a preparedness effort was undertaken prior to delivery of Titan. In this papermore » we report experiences and lessons learned from this process and describe how users are currently making use of computational accelerators on Titan.« less

  6. SIRT1 improves VSMC functions in atherosclerosis.

    PubMed

    Zhang, Ming-Jie; Zhou, Yi; Chen, Lei; Wang, Xu; Long, Chun-Yan; Pi, Yan; Gao, Chang-Yue; Li, Jing-Cheng; Zhang, Li-Li

    2016-05-01

    Despite advancements in diagnosis and treatment of cardiovascular diseases (CVDs), the morbidity and mortality of CVDs are still rising. Atherosclerosis is a chronic inflammatory disease contributing to multiple CVDs. Considering the complexity and severity of atherosclerosis, it is apparent that exploring the mechanisms of atherosclerotic formation and seeking new therapies for patients with atherosclerosis are required to overcome the heavy burden of CVDs on the quality and length of life of the global population. Vascular smooth muscle cells (VSMCs) play a dominant role in functional and structural changes of the arterial walls in response to atherogenic factors. Therefore, improvement of VSMC functions will slow down the development of atherosclerosis to a large extent. Given its protective performances on regulation of cholesterol metabolism and inflammatory responses, SIRT1 has long been known as an anti-atherosclerosis factor. In this review, we focus on the effects of SIRT1 on VSMC functions and thereby the development of atherosclerosis. PMID:27080738

  7. Tolerization against atherosclerosis using heat shock protein 60.

    PubMed

    Wick, Cecilia

    2016-03-01

    Atherosclerosis is a chronic inflammatory disease of the artery wall, and both innate and adaptive immunity play important roles in the pathogenesis of this disease. In several experimental and human experiments of early atherosclerotic lesions, it has been shown that the first pathogenic event in atherogenesis is intimal infiltration of T cells at predilection sites. These T cells react to heat shock protein 60 (HSP60), which is a ubiquitous self-antigen expressed on the surface of endothelial cells (ECs) together with adhesion molecules in response to classical risk factors for atherosclerosis. When HSP60 is expressed on the EC surface, it can act as a "danger-signal" for both cellular and humoral immune reactions. Acquired by infection or vaccination, beneficial protective immunity to microbial HSP60 and bona fide autoimmunity to biochemically altered autologous HSP60 is present in all humans. Thus, the development of atherosclerosis during aging is paid by the price for lifelong protective preexisting anti-HSP60 immunity by harmful (auto)immune cross-reactive attack on arterial ECs maltreated by atherosclerosis risk factors. This is supported by experiments, which shows that bacterial HSP60 immunization can lead and accelerate experimental atherosclerosis. This review article presents accumulating proof that supports the idea that tolerization with antigenic HSP60 protein or its peptides may arrest or even prevent atherosclerosis by increased production of regulatory T cells and/or anti-inflammatory cytokines. Recent data indicates that HSP60, or more likely some of its derivative peptides, has immunoregulatory functions. Therefore, these peptides may have important potential for being used as diagnostic agents or therapeutic targets. PMID:26577462

  8. High charge short electron bunches for wakefield accelerator structures development.

    SciTech Connect

    Conde, M. E.

    1998-09-25

    The Argonne Wakefield Accelerator group develops accelerating structures based on dielectric loaded waveguides. We use high charge short electron bunches to excite wakefields in dielectric loaded structures, and a second (low charge) beam to probe the wakefields left behind by the drive beam. We report measurements of beam parameters and also initial results of the dielectric loaded accelerating structures. We have studied acceleration of the probe beam in these structures and we have also made measurements on the RF pulses that are generated by the drive beam. Single drive bunches, as well as multiple bunches separated by an integer number of RF periods have been used to generate the accelerating wakefields.

  9. Accelerator development for a radioactive beam facility based on ATLAS.

    SciTech Connect

    Shepard, K. W.

    1998-01-08

    The existing superconducting linac ATLAS is in many respects an ideal secondary beam accelerator for an ISOL (Isotope separator on-line) type radioactive beam facility. Such a facility would require the addition of two major accelerator elements: a low charge state injector for the existing heavy ion linac, and a primary beam accelerator providing 220 MV of acceleration for protons and light ions. Development work for both of these elements, including the option of superconducting cavities for the primary beam accelerator is discussed.

  10. Sex Differences in Inflammation During Atherosclerosis

    PubMed Central

    Fairweather, DeLisa

    2014-01-01

    Atherosclerosis is the leading cause of death in the United States and worldwide, yet more men die from atherosclerosis than women, and at a younger age. Women, on the other hand, mainly develop atherosclerosis following menopause, and particularly if they have one or more autoimmune diseases, suggesting that the immune mechanisms that increase disease in men are different from those in women. The key processes in the pathogenesis of atherosclerosis are vascular inflammation, lipid accumulation, intimal thickening and fibrosis, remodeling, and plaque rupture or erosion leading to myocardial infarction and ischemia. Evidence indicates that sex hormones alter the immune response during atherosclerosis, resulting in different disease phenotypes according to sex. Women, for example, respond to infection and damage with increased antibody and autoantibody responses, while men have elevated innate immune activation. This review describes current knowledge regarding sex differences in the inflammatory immune response during atherosclerosis. Understanding sex differences is critical for improving individualized medicine. PMID:25983559

  11. Enteric lactoferrin attenuates the development of high-fat and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis in Microminipigs.

    PubMed

    Morishita, Satoru; Kawaguchi, Hiroaki; Ono, Tomoji; Miura, Naoki; Murakoshi, Michiaki; Sugiyama, Keikichi; Kato, Hisanori; Tanimoto, Akihide; Nishino, Hoyoku

    2016-01-01

    Previously, we found that enteric lactoferrin (eLF) could reduce the visceral fat accumulation known to associate strongly with metabolic syndrome symptoms and consequently with an increased risk of atherosclerosis. In this study, the atherosclerosis-preventive potential of LF was assessed in a high-fat and high-cholesterol diet (HFCD)-induced hypercholesterolemia and atherosclerosis model using Microminipig™. Eight-week orally administered eLF remarkably reduced the HFCD-induced serum total and low-density lipoprotein cholesterol levels but not high-density lipoprotein cholesterol levels. A histological analysis of 15 arteries revealed that eLF systemically inhibited the development of atherosclerotic lesions. Pathway analysis using identified genes that characterized eLF administration in liver revealed significant changes in the steroid biosynthesis pathway (ssc00100) and all affected genes in this pathway were upregulated, suggesting that cholesterol synthesis inhibited by HFCD was recovered by eLF. In summary, eLF could potentially prevent the hypercholesterolemia and atherosclerosis through protecting homeostasis from HFCD-induced dysfunction of cholesterol metabolism. PMID:26549014

  12. Role of long non-coding RNA-RNCR3 in atherosclerosis-related vascular dysfunction.

    PubMed

    Shan, K; Jiang, Q; Wang, X-Q; Wang, Y-N-Z; Yang, H; Yao, M-D; Liu, C; Li, X-M; Yao, J; Liu, B; Zhang, Y-Y; J, Yong; Yan, B

    2016-01-01

    Atherosclerosis is one of the most common vascular disorders. Endothelial cell (EC) dysfunction and vascular smooth muscle cell (VSMC) proliferation contributes to the development of atherosclerosis. Long non-coding RNAs (lncRNAs) have been implicated in several biological processes and human diseases. Here we show that lncRNA-RNCR3 is expressed in ECs and VSMCs. RNCR3 expression is significantly upregulated in mouse and human aortic atherosclerotic lesions, and cultured ECs and VSMCs upon ox-LDL treatment in vitro. RNCR3 knockdown accelerates the development of atherosclerosis, aggravates hypercholesterolemia and inflammatory factor releases, and decreases EC and VSMC proliferation in vivo. RNCR3 knockdown also reduces the proliferation and migration, and accelerates apoptosis development of EC and VSMC in vitro. RNCR3 acts as a ceRNA, and forms a feedback loop with Kruppel-like factor 2 and miR-185-5p to regulate cell function. This study reveals that RNCR3 has an atheroprotective role in atherosclerosis, and its intervention is a promising strategy for treating atherosclerosis-related vascular dysfunction. PMID:27253412

  13. Technology development for high power induction accelerators

    SciTech Connect

    Birx, D.L.; Reginato, L.L.

    1985-06-11

    The marriage of Induction Linac technology with Nonlinear Magnetic Modulators has produced some unique capabilities. It appears possible to produce electron beams with average currents measured in amperes, at gradients exceeding 1 MeV/meter, and with power efficiencies approaching 50%. A 2 MeV, 5 kA electron accelerator has been constructed at the Lawrence Livermore National Laboratory (LLNL) to demonstrate these concepts and to provide a test facility for high brightness sources. The pulse drive for the accelerator is based on state-of-the-art magnetic pulse compressors with very high peak power capability, repetition rates exceeding a kilohertz and excellent reliability.

  14. Cytochrome P450 1B1 Contributes to the Development of Atherosclerosis and Hypertension in Apolipoprotein E–Deficient Mice

    PubMed Central

    Song, Chi Young; Ghafoor, Khuzema; Ghafoor, Hafiz U.; Khan, Nayaab S.; Thirunavukkarasu, Shyamala; Jennings, Brett L.; Estes, Anne M.; Zaidi, Sahar; Bridges, Dave; Tso, Patrick; Gonzalez, Frank J.

    2016-01-01

    Cytochrome P450 (CYP) 1B1 contributes to vascular smooth muscle cell growth and hypertension in male mice. This study was conducted to determine the contribution of CYP1B1 to the development of atherosclerosis and hypertension and associated pathogenesis in 8-week-old male apolipoprotein E–deficient (ApoE−/−/Cyp1b1+/+), and ApoE- and CYP1B1-deficient (ApoE−/−/Cyp1b1−/−) mice fed a normal or atherogenic diet for 12 weeks. A separate group of ApoE−/−/Cyp1b1+/+ mice on an atherogenic diet was injected every third day with the CYP1B1 inhibitor, 2,3′,4,5′-tetramethoxystilbene (300 μg/kg), or its vehicle, dimethyl sulfoxide (30 μL, IP); systolic blood pressure was measured by the tail cuff method. After 12 weeks, mice were euthanized, blood collected for lipid analysis, and aortas harvested for measuring lesions and remodeling, and for infiltration of inflammatory cells by histological and immunohistochemical analysis, respectively, and for reactive oxygen species production. Blood pressure, areas of lipids and collagen deposition, elastin breaks, infiltration of macrophages and T lymphocytes, reactive oxygen species generation in the aorta, and plasma lipid levels were increased in ApoE−/−/Cyp1b1+/+ mice on an atherogenic diet; these changes were minimized in mice given 2,3′,4,5′-tetramethoxystilbene, and in ApoE−/−/Cyp1b1−/− mice on an atherogenic diet; absorption/production of lipids remained unaltered in these mice. These data suggest that aortic lesions, hypertension, and associated pathogenesis in ApoE−/−/Cyp1b1+/+ mice on an atherogenic diet are most likely dependent on CYP1B1-generated oxidative stress and increased plasma lipid levels independent of blood pressure and absorption of lipids. CYP1B1 could serve as a novel target for developing drugs to treat atherosclerosis and hypertension caused by hypercholesterolemia. PMID:26573711

  15. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

    SciTech Connect

    Lin, Yan-Jie; Juan, Chi-Chang; Kwok, Ching-Fai; Hsu, Yung-Pei; Shih, Kuang-Chung; Chen, Chin-Chang; Ho, Low-Tone

    2015-05-08

    Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET{sub A}R during insulin resistance, ET{sub A}R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET{sub A}R expression, but not ET{sub B}R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET{sub A}R pathway

  16. Grape powder polyphenols attenuate atherosclerosis development in apolipoprotein E deficient (E0) mice and reduce macrophage atherogenicity.

    PubMed

    Fuhrman, Bianca; Volkova, Nina; Coleman, Raymond; Aviram, Michael

    2005-04-01

    The beneficial health effects of red wine have been attributed to the antioxidant activity of its polyphenols. The present study investigated the effects of a standardized freeze-dried powder made from fresh grapes, rich in grape-specific polyphenols and free of alcohol, on oxidative stress, atherogenicity of macrophages, and the development of atherosclerotic lesions in apolipoprotein E deficient (E(0)) mice. Thirty E(0) mice were assigned to 3 groups. Mice consumed water alone (control), 150 mug total polyphenols/d in the form of grape powder (grape powder), or the equivalent amount of glucose and fructose (placebo) in drinking water for 10 wk. Consumption of grape powder reduced the atherosclerotic lesion area by 41% (P < 0.0002) compared to the control or placebo mice. The antiatherosclerotic effect was at least partly due to a significant 8% reduction in serum oxidative stress, an up to 22% increase in serum antioxidant capacity, a significant 33% reduction in macrophage uptake of oxidized LDL, and a 25% decrease in macrophage-mediated oxidation of LDL relative to controls. Grape powder directly protected both plasma LDL and macrophages from oxidative stress in vitro. We conclude that polyphenols from fresh grape powder directly affect macrophage atherogenicity by reducing macrophage-mediated oxidation of LDL and cellular uptake of oxidized LDL. Both of these processes can eventually reduce macrophage cholesterol accumulation and foam cell formation and hence attenuate atherosclerosis development. PMID:15795424

  17. The role of bifurcation angles on collective smooth muscle cell biomechanics and the implication in atherosclerosis development.

    PubMed

    Zhang, Ying; Menon, Nishanth V; Li, Chuan; Chan, Vincent; Kang, Yuejun

    2016-03-01

    Vascular smooth muscle cells (SMCs) are located in the middle of the tunica media and regulate the vasodilation and vasoconstriction of the blood vessels. SMCs also play a critical role during the development of atherosclerotic lesions, which are mainly found at sites of disturbed blood flow such as arterial branch points and bifurcations. Although the migratory and proliferative activities of SMCs and their phenotypic switch have been widely studied, the mechanotransduction of the SMC layer underlying atherosclerotic plaques remains unclear. In this study, bifurcate micropatterns with different angles were fabricated with polydimethylsiloxane and polyacrylamide gel for SMC culture and characterization of cell traction force. The cellular morphology, density and orientation-specific adaptation during branched cell layer formation on this platform were monitored until they became confluence. The results indicated that the characteristic cell traction forces and the von Mises stresses were dependent on bifurcation angles, which might provide important geometrical cues associated with the development of atherosclerosis. Immunofluorescence staining and gene analysis further revealed the proliferative and migratory states of SMCs in response to different bifurcation angles, which might elucidate the localization and progression of atherosclerotic lesions. PMID:26648015

  18. Epigenetic regulation of NKG2D ligands is involved in exacerbated atherosclerosis development in Sirt6 heterozygous mice.

    PubMed

    Zhang, Zhu-Qin; Ren, Si-Chong; Tan, Ying; Li, Zuo-Zhi; Tang, Xiaoqiang; Wang, Ting-Ting; Hao, De-Long; Zhao, Xiang; Chen, Hou-Zao; Liu, De-Pei

    2016-01-01

    Sirt6 is a member of the class III histone deacetylase family which is associated with aging and longevity. Sirt6 deficient mice show an aging-like phenotype, while male transgenic mice of Sirt6 show increased longevity. Sirt6 acts as a tumor suppressor and deficiency of Sirt6 leads to cardiac hypertrophy and heart failure. Whether Sirt6 is involved in atherosclerosis development, the major cause of cardiovascular diseases, is unknown. We found that the expression of Sirt6 is lower in human atherosclerotic plaques than that in controls. When Sirt6(+/-)ApoE(-/-) and ApoE(-/-) mice are fed with high fat diet for 16 weeks, Sirt6(+/-)ApoE(-/-) mice show increased plaque fromation and exhibit feature of plaque instability. Furthermore, Sirt6 downregulation increases expression of NKG2D ligands, which leads to increased cytokine expression. Blocking NKG2D ligand almost completely blocks this effect. Mechanistically, Sirt6 binds to promoters of NKG2D ligand genes and regulates the H3K9 and H3K56 acetylation levels. PMID:27045575

  19. Heart type fatty acid binding protein response and subsequent development of atherosclerosis in insulin resistant polycystic ovary syndrome patients

    PubMed Central

    2012-01-01

    Background Women with polycystic ovary syndrome (PCOS) have higher risk for cardiovascular disease (CVD). Heart type fatty acid binding protein (HFABP) has been found to be predictive for myocardial ischemia.Wet ested whether HFABP is the predictor for CVD in PCOS patients, who have an increased risk of cardiovascular disease. Methods This was a prospective, cross sectional controlled study conducted in a training and research hospital.The study population consisted of 46 reproductive-age PCOS women and 28 control subjects. We evaluated anthropometric and metabolic parameters, carotid intima media thickness and HFABP levels in both PCOS patients and control group. Results Mean fasting insulin, homeostasis model assessment insulin resistance index (HOMA-IR), triglyceride, total cholesterol, low density lipoprotein cholesterol, free testosterone, total testosterone, carotid intima media thickness (CIMT) levels were significantly higher in PCOS patients. Although HFABP levels were higher in PCOS patients, the difference did not reach statistically significant in early age groups. After adjustment for age and body mass index, HFABP level was positive correlated with hsCRP, free testosterone levels, CIMT and HOMA-IR. Conclusions Heart type free fatty acid binding protein appeared to have an important role in metabolic response and subsequent development of atherosclerosis in insulin resistant, hyperandrogenemic PCOS patients. PMID:23249450

  20. Epigenetic regulation of NKG2D ligands is involved in exacerbated atherosclerosis development in Sirt6 heterozygous mice

    PubMed Central

    Zhang, Zhu-Qin; Ren, Si-Chong; Tan, Ying; Li, Zuo-Zhi; Tang, Xiaoqiang; Wang, Ting-Ting; Hao, De-Long; Zhao, Xiang; Chen, Hou-Zao; Liu, De-Pei

    2016-01-01

    Sirt6 is a member of the class III histone deacetylase family which is associated with aging and longevity. Sirt6 deficient mice show an aging-like phenotype, while male transgenic mice of Sirt6 show increased longevity. Sirt6 acts as a tumor suppressor and deficiency of Sirt6 leads to cardiac hypertrophy and heart failure. Whether Sirt6 is involved in atherosclerosis development, the major cause of cardiovascular diseases, is unknown. We found that the expression of Sirt6 is lower in human atherosclerotic plaques than that in controls. When Sirt6+/−ApoE−/− and ApoE−/− mice are fed with high fat diet for 16 weeks, Sirt6+/−ApoE−/− mice show increased plaque fromation and exhibit feature of plaque instability. Furthermore, Sirt6 downregulation increases expression of NKG2D ligands, which leads to increased cytokine expression. Blocking NKG2D ligand almost completely blocks this effect. Mechanistically, Sirt6 binds to promoters of NKG2D ligand genes and regulates the H3K9 and H3K56 acetylation levels. PMID:27045575

  1. Vacuum Insulator Development for the Dielectric Wall Accelerator

    SciTech Connect

    Harris, J R; Blackfield, D; Caporaso, G J; Chen, Y; Hawkins, S; Kendig, M; Poole, B; Sanders, D M; Krogh, M; Managan, J E

    2008-03-17

    At Lawrence Livermore National Laboratory, we are developing a new type of accelerator, known as a Dielectric Wall Accelerator, in which compact pulse forming lines directly apply an accelerating field to the beam through an insulating vacuum boundary. The electrical strength of this insulator may define the maximum gradient achievable in these machines. To increase the system gradient, we are using 'High Gradient Insulators' composed of alternating layers of dielectric and metal for the vacuum insulator. In this paper, we present our recent results from experiment and simulation, including the first test of a High Gradient Insulator in a functioning Dielectric Wall Accelerator cell.

  2. Arrayed Diagnostic Development on the HyperV Plasma Accelerators

    NASA Astrophysics Data System (ADS)

    Brockington, Samuel; Case, Andrew; Messer, Sarah; Bomgardner, Richard; Witherspoon, F. D.

    2008-11-01

    The sparkgap injected plasma accelerator is one of several coaxial railguns constructed at HyperV to accelerate dense plasmas to high velocities. A circumferential array of 112 high voltage tungsten electrodes ablates polyethylene to form and inject a toroidally shaped plasma into the annular breech at the rear of the accelerator. A pulse forming network then applies several hundred kiloamps to the coaxial electrodes to accelerate the plasma. A 4-chord laser deflectometer and a 32-sensor fast photodiode array are being developed to help resolve the structure, density, and velocity of the accelerated plasma jet for different accelerator parameters. We present details of the diagnostic designs and initial data. Work supported by the U.S. DOE Office of Fusion Energy Sciences.

  3. Development of a dedicated superconducting accelerator for positron production

    NASA Astrophysics Data System (ADS)

    O'Rourke, B. E.; Oshima, N.; Kuroda, R.; Suzuki, R.; Ohdaira, T.; Kinomura, A.; Hayashizaki, N.; Minehara, E.; Yamauchi, H.; Fukamizu, Y.; Shikibu, M.; Kawamoto, T.; Minehara, Y.

    2011-01-01

    We report on the current status of a project to develop a dedicated superconducting accelerator for slow positron production at AIST. Two 500 MHz, 5 cell cavities will form the basis of the new accelerator. Initial set-up and preliminary design activities are reported.

  4. Advanced Microgravity Acceleration Measurement Systems (AMAMS) Being Developed

    NASA Technical Reports Server (NTRS)

    Sicker, Ronald J.; Kacpura, Thomas J.

    2003-01-01

    The Advanced Microgravity Acceleration Measurement Systems (AMAMS) project is part of NASA s Instrument Technology Development program to develop advanced sensor systems. The primary focus of the AMAMS project is to develop microelectromechanical systems (MEMS) for acceleration sensor systems to replace existing electromechanical sensor systems presently used to assess relative gravity levels aboard spacecraft. These systems are used to characterize both vehicle and payload responses to low-gravity vibroacoustic environments. The collection of microgravity acceleration data is useful to the microgravity life sciences, microgravity physical sciences, and structural dynamics communities. The inherent advantages of semiconductor-based systems are reduced size, mass, and power consumption, with enhanced long-term calibration stability.

  5. Development of compact linear accelerator in KBSI

    SciTech Connect

    Yoon, Jang-Hee; Lee, Byoung-Seob; Choi, Seyong; Park, Jin Yong; Ok, Jung-Woo; Won, Mi-Sook

    2012-02-15

    The compact linear accelerator using a 28 GHz ECRIS is under construction in KBSI, South Korea. The main capability of this facility is the production of fast neurons for the neutron radiography. The designing of a superconducting magnet, microwave transmission system, beam extraction, and plasma chamber of ECRIS were finished. The nominal axial design fields of the magnets are 3.6 T at injection and 2.2 T at extraction; the nominal radial design field strength at the plasma chamber wall is 2.1 T. We already installed 10 kW, 28 GHz gyrotron, and tested a microwave power from gyrotron using a dummy load. The current status will be discussed in this paper.

  6. Development of compact linear accelerator in KBSI.

    PubMed

    Yoon, Jang-Hee; Lee, Byoung-Seob; Choi, Seyong; Park, Jin Yong; Ok, Jung-Woo; Won, Mi-Sook

    2012-02-01

    The compact linear accelerator using a 28 GHz ECRIS is under construction in KBSI, South Korea. The main capability of this facility is the production of fast neurons for the neutron radiography. The designing of a superconducting magnet, microwave transmission system, beam extraction, and plasma chamber of ECRIS were finished. The nominal axial design fields of the magnets are 3.6 T at injection and 2.2 T at extraction; the nominal radial design field strength at the plasma chamber wall is 2.1 T. We already installed 10 kW, 28 GHz gyrotron, and tested a microwave power from gyrotron using a dummy load. The current status will be discussed in this paper. PMID:22380162

  7. Liposomal prednisolone promotes macrophage lipotoxicity in experimental atherosclerosis.

    PubMed

    van der Valk, Fleur M; Schulte, Dominik M; Meiler, Svenja; Tang, Jun; Zheng, Kang He; Van den Bossche, Jan; Seijkens, Tom; Laudes, Matthias; de Winther, Menno; Lutgens, Esther; Alaarg, Amr; Metselaar, Josbert M; Dallinga-Thie, Geesje M; Mulder, Willem J M; Stroes, Erik S G; Hamers, Anouk A J

    2016-08-01

    Atherosclerosis is a lipid-driven inflammatory disease, for which nanomedicinal interventions are under evaluation. Previously, we showed that liposomal nanoparticles loaded with prednisolone (LN-PLP) accumulated in plaque macrophages, however, induced proatherogenic effects in patients. Here, we confirmed in low-density lipoprotein receptor knockout (LDLr(-/-)) mice that LN-PLP accumulates in plaque macrophages. Next, we found that LN-PLP infusions at 10mg/kg for 2weeks enhanced monocyte recruitment to plaques. In follow up, after 6weeks of LN-PLP exposure we observed (i) increased macrophage content, (ii) more advanced plaque stages, and (iii) larger necrotic core sizes. Finally, in vitro studies showed that macrophages become lipotoxic after LN-PLP exposure, exemplified by enhanced lipid loading, ER stress and apoptosis. These findings indicate that liposomal prednisolone may paradoxically accelerate atherosclerosis by promoting macrophage lipotoxicity. Hence, future (nanomedicinal) drug development studies are challenged by the multifactorial nature of atherosclerotic inflammation. PMID:27015770

  8. Therapeutic approaches to drug targets in atherosclerosis.

    PubMed

    Jamkhande, Prasad G; Chandak, Prakash G; Dhawale, Shashikant C; Barde, Sonal R; Tidke, Priti S; Sakhare, Ram S

    2014-07-01

    Non-communicable diseases such as cancer, atherosclerosis and diabetes are responsible for major social and health burden as millions of people are dying every year. Out of which, atherosclerosis is the leading cause of deaths worldwide. The lipid abnormality is one of the major modifiable risk factors for atherosclerosis. Both genetic and environmental components are associated with the development of atherosclerotic plaques. Immune and inflammatory mediators have a complex role in the initiation and progression of atherosclerosis. Understanding of all these processes will help to invent a range of new biomarkers and novel treatment modalities targeting various cellular events in acute and chronic inflammation that are accountable for atherosclerosis. Several biochemical pathways, receptors and enzymes are involved in the development of atherosclerosis that would be possible targets for improving strategies for disease diagnosis and management. Earlier anti-inflammatory or lipid-lowering treatments could be useful for alleviating morbidity and mortality of atherosclerotic cardiovascular diseases. However, novel drug targets like endoglin receptor, PPARα, squalene synthase, thyroid hormone analogues, scavenger receptor and thyroid hormone analogues are more powerful to control the process of atherosclerosis. Therefore, the review briefly focuses on different novel targets that act at the starting stage of the plaque form to the thrombus formation in the atherosclerosis. PMID:25061401

  9. [Atherosclerosis in childhood: the role of obesity].

    PubMed

    Sarni, P; Vinci, A; Fierro, S; Del Buono, S

    1997-01-01

    A variety of studies indicates that the process of atherosclerosis begins in childhood and progresses during adulthood. Chronic obesity, inadequate caloric intake, and hypertension and smoke, are associated with an increased cardiovascular disease. The aim of this study is to investigate if the presence of some risk factors during adolescence may involve in accelerated atherosclerosis disease. 50 subjects, median age 11 +/- 0.6 SD (27 females, and 23 males) are admitted to the study. After overnight fasting we have investigated: lipoproteina A (nephelometric test), glycemia and insulin baseline and after load 120', tryglycerides, cholesterolo, apolipoproteina A, B, plasma concentrations. In addition to general medical evaluation, anthropometric measurements of weight, height, blood pressure, BMI, overnight ratio were calculated according to Tanner's charts. The means anthropometric and metabolic values in different groups were compared. One group affected with abdominal obesity state (waist-hips ratio > 0.9), the second with mid obesity condition (waist-hip ratio < 0.9). Tryglycerides, cholesterolo, insulin plasma concentrations in both groups were considered similar. However in the first group higher levels of apolipoproteina A (means 102 + 10.2 SD) and lipoproteina A were demonstrated (P = 0.03 in males, P = 0.01 Statview for Mann Whitney test). Childhood is an important period for the development of the atherosclerosis such as the presence of obesity during this time has a very high likelihood of persisting into adulthood. The severity of obesity in adults is greater in those who were obese as adolescents. In accord with other authors we have not observed abnormal tryglicerides and cholesterolo plasma concentrations, which probably are found in adulthood obesity. We believe indeed the risk factors are different in obesity of childhood, atherosclerosis may be induced by high endogenous insulin secretion and abnormal uptake of lipoprotein. However the potential

  10. Neutrophil's weapons in atherosclerosis.

    PubMed

    Chistiakov, Dimitry A; Bobryshev, Yuri V; Orekhov, Alexander N

    2015-12-01

    Neutrophils are important components of immunity associated with inflammatory responses against a broad spectrum of pathogens. These cells could be rapidly activated by proinflammatory stimuli and migrate to the inflamed and infected sites where they release a variety of cytotoxic molecules with antimicrobial activity. Neutrophil antibacterial factors include extracellular proteases, redox enzymes, antimicrobial peptides, and small bioactive molecules. In resting neutrophils, these factors are stored in granules and released upon activation during degranulation. These factors could be also secreted in a neutrophil-derived microparticle-dependent fashion. Neutrophils exhibit a unique property to produce neutrophil extracellular traps (NETs) composed of decondensed chromatin and granular proteins to catch and kill bacteria. Neutrophil-released factors are efficient in inactivation and elimination of pathogens through oxidation-dependent or independent damage of bacterial cells, inactivation and neutralization of virulence factors and other mechanisms. However, in chronic atherosclerosis-associated inflammation, protective function of neutrophils could be impaired and misdirected against own cells. This could lead to deleterious effects and progressive vascular injury. In atherogenesis, a pathogenic role of neutrophils could be especially seen in early stages associated with endothelial dysfunction and induction of vascular inflammation and in late atherosclerosis associated with plaque rupture and atherothrombosis. Assuming a prominent impact of neutrophils in cardiovascular pathology, developing therapeutic strategies targeting neutrophil-specific antigens could have a promising clinical potential. PMID:26551083

  11. Endothelial caveolin-1 plays a major role in the development of atherosclerosis

    PubMed Central

    Pavlides, Stephanos; Gutierrez-Pajares, Jorge L.; Iturrieta, Jeannette; Lisanti, Michael P.

    2015-01-01

    Clinical studies have established the important impact of atherosclerotic disease in Western societies. This disease is characterized by the accumulation of lipids and the migration of various cell types in the sub-endothelial space of blood vessels. As demonstrated by many studies, endothelial cells play an essential role in the development of this disease. The endothelium acts as a gatekeeper of blood vessel integrity and cardiovascular health status. For instance, the transfer of lipids via the transport of lipoproteins in the arterial intima is believed to be mediated by endothelial cells through a process termed transcytosis. In addition, lipoproteins that accumulate in the sub-endothelial space may also be modified, in a process that can direct the activation of endothelial cells. These steps are essential for the initiation of an atherosclerotic plaque and may be mediated, at least in part, by caveolae and their associated protein caveolin-1. In the present study, we evaluate the role of caveolin-1/caveolae in the regulation of these two steps in endothelial cells. Our data clearly demonstrate that caveolin-1 is involved in the regulation of lipoprotein transcytosis across endothelial cells and in the regulation of vascular inflammation. PMID:24390341

  12. Atherosclerosis Prevention in Youth

    PubMed Central

    2012-01-01

    Atherosclerosis-associated circulatory disturbance is one of the most important global issues. In patients with atherosclerosis, eccentric intimal thickening and lipid deposition progress over a long period (at least 20 to 30 years). On the other hand, in patients with atherosclerosis-associated circulatory disturbance represented by myocardial infarction, the direct cause of death is thrombus formation rather than marked stenosis; wall destruction may lead to a fatal outcome. In the future, atherosclerosis susceptibility, that is, intrinsic genes, should be investigated. PMID:23641261

  13. Transcriptional Profiling Uncovers a Network of Cholesterol-Responsive Atherosclerosis Target Genes

    PubMed Central

    Nilsson, Roland; Noori, Peri; Maleki, Shohreh; Köhler, Marina; Hamsten, Anders; Tegnér, Jesper; Björkegren, Johan

    2008-01-01

    Despite the well-documented effects of plasma lipid lowering regimes halting atherosclerosis lesion development and reducing morbidity and mortality of coronary artery disease and stroke, the transcriptional response in the atherosclerotic lesion mediating these beneficial effects has not yet been carefully investigated. We performed transcriptional profiling at 10-week intervals in atherosclerosis-prone mice with human-like hypercholesterolemia and a genetic switch to lower plasma lipoproteins (Ldlr−/−Apo100/100 Mttpflox/flox Mx1-Cre). Atherosclerotic lesions progressed slowly at first, then expanded rapidly, and plateaued after advanced lesions formed. Analysis of lesion expression profiles indicated that accumulation of lipid-poor macrophages reached a point that led to the rapid expansion phase with accelerated foam-cell formation and inflammation, an interpretation supported by lesion histology. Genetic lowering of plasma cholesterol (e.g., lipoproteins) at this point all together prevented the formation of advanced plaques and parallel transcriptional profiling of the atherosclerotic arterial wall identified 37 cholesterol-responsive genes mediating this effect. Validation by siRNA-inhibition in macrophages incubated with acetylated-LDL revealed a network of eight cholesterol-responsive atherosclerosis genes regulating cholesterol-ester accumulation. Taken together, we have identified a network of atherosclerosis genes that in response to plasma cholesterol-lowering prevents the formation of advanced plaques. This network should be of interest for the development of novel atherosclerosis therapies. PMID:18369455

  14. Computational Tools for Accelerating Carbon Capture Process Development

    SciTech Connect

    Miller, David; Sahinidis, N V; Cozad, A; Lee, A; Kim, H; Morinelly, J; Eslick, J; Yuan, Z

    2013-06-04

    This presentation reports development of advanced computational tools to accelerate next generation technology development. These tools are to develop an optimized process using rigorous models. They include: Process Models; Simulation-Based Optimization; Optimized Process; Uncertainty Quantification; Algebraic Surrogate Models; and Superstructure Optimization (Determine Configuration).

  15. MafB deficiency accelerates the development of obesity in mice.

    PubMed

    Tran, Mai Thi Nhu; Hamada, Michito; Nakamura, Megumi; Jeon, Hyojung; Kamei, Risa; Tsunakawa, Yuki; Kulathunga, Kaushalya; Lin, Yuan-Yu; Fujisawa, Kumiko; Kudo, Takashi; Takahashi, Satoru

    2016-06-01

    MafB, a transcription factor expressed selectively in macrophages, has important roles in some macrophage-related diseases, especially in atherosclerosis. In this study, we investigated the mechanism by which hematopoietic-specific MafB deficiency induces the development of obesity. Wild-type and hematopoietic cell-specific Mafb-deficient mice were fed a high-fat diet for 10 weeks. The Mafb-deficient mice exhibited higher body weights and faster rates of body weight increase than control mice. The Mafb-deficient mice also had a higher percentage of body fat than the wild-type mice, due to increased adipocyte size and serum cholesterol levels. Reverse transcription-PCR analysis showed a reduction in apoptosis inhibitor of macrophage (AIM) in Mafb-deficient adipose tissue. AIM is known as an inhibitor of lipogenesis in adipocytes and is expressed in adipose tissue macrophages. Collectively, our data suggest that Mafb deficiency in hematopoietic cells accelerates the development of obesity. PMID:27419056

  16. Research and development of capacitive transducer with linear acceleration

    NASA Astrophysics Data System (ADS)

    Korobova, Natalia; Kochurina, Elena; Timoshenkov, Sergey; Chaplygin, Yuriy; Anchutin, Stepan; Kosolapov, Andrey

    2015-05-01

    Paper presents the study results and modeling of functional characteristics of the linear acceleration transducers, enabling sensors creation with the specified parameters. Sensing element made for linear acceleration transducer with torsion cruciform section has been proposed on the based design and technological principles. It allows minimizing the impact of cross-acceleration and gives the maximum of center mass displacement for high sensors sensitivity in the given dimensions. The range of measured acceleration from ± 0.2g to ± 50g was provided by changing the torsion bar thickness n = 34 ÷ 56 microns. The transducers frequency range of linear acceleration 100-150 Hz depends on the gas pressure P = 700-800Pa in which the sensor element was located. Methods converting displacement of sensing element in the sensor output have been provided. On their basis the linear acceleration transducers with analog output signal having a predetermined frequency range and high linearity of the transformation (nonlinearity 0.2-1.5%) was developed. Also the linear acceleration transducers with digital signal consuming little (no more than 850 μA), low noisy (standard deviation to 0.1mg/rt-Hz) and high sensitivity (up to 0.1mg) to the accelerations was made. Errors in manufacturing process of sensitive elements and operating environment temperature affect the changes in the characteristics of the linear acceleration transducers. It has been established that different plate thickness up to 3.6% leads to the scale factor error to 4.7%. Irreproducibility of depth anisotropic etching of silicon up to 6.6% introduces an error in the output signal of 2.9 ... 13.8mg.

  17. Computational Tools to Accelerate Commercial Development

    SciTech Connect

    Miller, David C

    2013-01-01

    The goals of the work reported are: to develop new computational tools and models to enable industry to more rapidly develop and deploy new advanced energy technologies; to demonstrate the capabilities of the CCSI Toolset on non-proprietary case studies; and to deploy the CCSI Toolset to industry. Challenges of simulating carbon capture (and other) processes include: dealing with multiple scales (particle, device, and whole process scales); integration across scales; verification, validation, and uncertainty; and decision support. The tools cover: risk analysis and decision making; validated, high-fidelity CFD; high-resolution filtered sub-models; process design and optimization tools; advanced process control and dynamics; process models; basic data sub-models; and cross-cutting integration tools.

  18. Status of high temperature superconductor development for accelerator magnets

    NASA Technical Reports Server (NTRS)

    Hirabayashi, H.

    1995-01-01

    High temperature superconductors are still under development for various applications. As far as conductors for magnets are concerned, the development has just been started. Small coils wound by silver sheathed Bi-2212 and Bi-2223 oxide conductors have been reported by a few authors. Essential properties of high T(sub c) superconductors like pinning force, coherent length, intergrain coupling, weak link, thermal property, AC loss and mechanical strength are still not sufficiently understandable. In this talk, a review is given with comparison between the present achievement and the final requirement for high T(sub c) superconductors, which could be particularly used in accelerator magnets. Discussions on how to develop high T(sub c) superconductors for accelerator magnets are included with key parameters of essential properties. A proposal of how to make a prototype accelerator magnet with high T(sub c) superconductors with prospect for future development is also given.

  19. Nb3Sn accelerator magnet development around the world

    SciTech Connect

    Michael J. Lamm

    2003-06-23

    During the past 30 years superconducting magnet systems have enabled accelerators to achieve energies and luminosities that would have been impractical if not impossible with resistive magnets. By far, NbTi has been the preferred conductor for this application because of its ductility and insensitivity of Jc to mechanical strain. This is despite the fact that Nb{sub 3}Sn has a more favorable Jc vs. B dependence and can operate at much higher temperatures. Unfortunately, NbTi conductor is reaching the limit of it usefulness for high field applications. Despite incremental increases in Jc and operation at superfluid temperatures, magnets are limited to approximately a 10 T field. Improvements in conductor performance combined with future requirements for accelerator magnets to have bore fields greater than 10 T or operate in areas of large beam-induced heat loads now make Nb{sub 3}Sn look attractive. Thus, laboratories in several countries are actively engaged in programs to develop Nb{sub 3}Sn accelerator magnets for future accelerator applications. A summary of this important research activity is presented along with a brief history of Nb{sub 3}Sn accelerator magnet development and a discussion of requirements for future accelerator magnets.

  20. Accelerated larvae development of Ascaris lumbricoides eggs with ultraviolet radiation

    NASA Astrophysics Data System (ADS)

    Aladawi, M. A.; Albarodi, H.; Hammoudeh, A.; Shamma, M.; Sharabi, N.

    2006-01-01

    In order to investigate the effect of UV radiation on the development of Ascaris lumbricoides larvae, eggs were exposed to increasing UV doses. Filtered wastewater from the secondary effluent taken from the Damascus wastewater treatment plant (DWTP) was used as irradiation and incubation medium. The progressive and accelerated embryonation stages were microscopically observed and the percentages of completely developed larvae were determined weekly. Results indicated that the UV radiation accelerated the development of larvae with increasing UV dose. Preliminary information about the relationship between the UV radiation dose and rate of embryonation is also presented.

  1. Space Launch System Accelerated Booster Development Cycle

    NASA Technical Reports Server (NTRS)

    Arockiam, Nicole; Whittecar, William; Edwards, Stephen

    2012-01-01

    With the retirement of the Space Shuttle, NASA is seeking to reinvigorate the national space program and recapture the public s interest in human space exploration by developing missions to the Moon, near-earth asteroids, Lagrange points, Mars, and beyond. The would-be successor to the Space Shuttle, NASA s Constellation Program, planned to take humans back to the Moon by 2020, but due to budgetary constraints was cancelled in 2010 in search of a more "affordable, sustainable, and realistic" concept2. Following a number of studies, the much anticipated Space Launch System (SLS) was unveiled in September of 2011. The SLS core architecture consists of a cryogenic first stage with five Space Shuttle Main Engines (SSMEs), and a cryogenic second stage using a new J-2X engine3. The baseline configuration employs two 5-segment solid rocket boosters to achieve a 70 metric ton payload capability, but a new, more capable booster system will be required to attain the goal of 130 metric tons to orbit. To this end, NASA s Marshall Space Flight Center recently released a NASA Research Announcement (NRA) entitled "Space Launch System (SLS) Advanced Booster Engineering Demonstration and/or Risk Reduction." The increased emphasis on affordability is evident in the language used in the NRA, which is focused on risk reduction "leading to an affordable Advanced Booster that meets the evolved capabilities of SLS" and "enabling competition" to "enhance SLS affordability. The purpose of the work presented in this paper is to perform an independent assessment of the elements that make up an affordable and realistic path forward for the SLS booster system, utilizing advanced design methods and technology evaluation techniques. The goal is to identify elements that will enable a more sustainable development program by exploring the trade space of heavy lift booster systems and focusing on affordability, operability, and reliability at the system and subsystem levels5. For this study

  2. Can hydromorphic conditions accelerate soil development?

    NASA Astrophysics Data System (ADS)

    Ringer, Marianna; Kiss, Klaudia; Horváth-Szabó, Kata; Réka Balázs, Brigitta; Németh, Tibor; Sipos, Péter; Szabó, Máté; Jakab, Gergely; Madarász, Balázs; Szalai, Zoltán

    2016-04-01

    The formation and development of waterlogged (hydromorphic) soils are primarily determined by long-term water saturation. The presence of water in the profile can result increasing speed of soil forming processes including the accumulation of organic matter or other components and mineralogical transformations. Original papers refer more than hundreds of years for this kinds of mineral transformations. We suppose that this process could be more rapid. This study focuses on the mineralogical investigation of a sandy meadow soil (calcic, gleyic Phaeozem ferric, arenic) located in a swampy area in Central Hungary. The starting time of the soil formation is a well documented fact: the parent material deposited during an extremely heavy flood event in the 1960s. Therefore, the studied soil profile is the result of the last half century. Our aim was to explore the degree of mineral phase alteration via soil formation during a half-century under hydromorphic conditions. Routine laboratory measurements (selective dissolution methods for the determination of amorphous and crystalline Fe, and Mn content, X-ray fluorescence spectroscopy measurements for elemental composition determination, X-ray powder diffraction for mineralogical composition, and particle sizing by laser diffraction) were implemented. Morphological and chemical study of carbonate and iron nodules was carried out by electron microprobe. Simple chemical tests (eg. Fe2+ indication by dipiridil test) and morphological observations were performed on the field. Redox potential (Eh) and pH were measured in 20 cm and 40 cm depths by field monitoring station during the vegetation period. Results show that well developed horizons have emerged during fifty years in the studied soil profile. The most intense mineralogical transformations developed in the zone of the heaviest redox oscillation. Soil formation under hydromorphic conditions proceeds at higher speeds contrariwise to the century time scale reported in

  3. Bone marrow NR4A expression is not a dominant factor in the development of atherosclerosis or macrophage polarization in mice.

    PubMed

    Chao, Lily C; Soto, Erin; Hong, Cynthia; Ito, Ayaka; Pei, Liming; Chawla, Ajay; Conneely, Orla M; Tangirala, Rajendra K; Evans, Ronald M; Tontonoz, Peter

    2013-03-01

    The formation of the atherosclerotic lesion is a complex process influenced by an array of inflammatory and lipid metabolism pathways. We previously demonstrated that NR4A nuclear receptors are highly induced in macrophages in response to inflammatory stimuli and modulate the expression of genes linked to inflammation in vitro. Here we used mouse genetic models to assess the impact of NR4A expression on atherosclerosis development and macrophage polarization. Transplantation of wild-type, Nur77⁻/⁻, or Nor1⁻/⁻ null hematopoetic precursors into LDL receptor (LDLR)⁻/⁻ recipient mice led to comparable development of atherosclerotic lesions after high-cholesterol diet. We also observed comparable induction of genes linked to M1 and M2 responses in wild-type and Nur77-null macrophages in response to lipopolysaccharides and interleukin (IL)-4, respectively. In contrast, activation of the nuclear receptor liver X receptor (LXR) strongly suppressed M1 responses, and ablation of signal transductor and activator of transcription 6 (STAT6) strongly suppressed M2 responses. Recent studies have suggested that alterations in levels of Ly6C(lo) monocytes may be a contributor to inflammation and atherosclerosis. In our study, loss of Nur77, but not Nor1, was associated with decreased abundance of Ly6C(lo) monocytes, but this change was not correlated with atherosclerotic lesion development. Collectively, our results suggest that alterations in the Ly6C(lo) monocyte population and bone marrow NR4A expression do not play dominant roles in macrophage polarization or the development of atherosclerosis in mice. PMID:23288947

  4. Pathway analysis of coronary atherosclerosis.

    PubMed

    King, Jennifer Y; Ferrara, Rossella; Tabibiazar, Raymond; Spin, Joshua M; Chen, Mary M; Kuchinsky, Allan; Vailaya, Aditya; Kincaid, Robert; Tsalenko, Anya; Deng, David Xing-Fei; Connolly, Andrew; Zhang, Peng; Yang, Eugene; Watt, Clifton; Yakhini, Zohar; Ben-Dor, Amir; Adler, Annette; Bruhn, Laurakay; Tsao, Philip; Quertermous, Thomas; Ashley, Euan A

    2005-09-21

    Large-scale gene expression studies provide significant insight into genes differentially regulated in disease processes such as cancer. However, these investigations offer limited understanding of multisystem, multicellular diseases such as atherosclerosis. A systems biology approach that accounts for gene interactions, incorporates nontranscriptionally regulated genes, and integrates prior knowledge offers many advantages. We performed a comprehensive gene level assessment of coronary atherosclerosis using 51 coronary artery segments isolated from the explanted hearts of 22 cardiac transplant patients. After histological grading of vascular segments according to American Heart Association guidelines, isolated RNA was hybridized onto a customized 22-K oligonucleotide microarray, and significance analysis of microarrays and gene ontology analyses were performed to identify significant gene expression profiles. Our studies revealed that loss of differentiated smooth muscle cell gene expression is the primary expression signature of disease progression in atherosclerosis. Furthermore, we provide insight into the severe form of coronary artery disease associated with diabetes, reporting an overabundance of immune and inflammatory signals in diabetics. We present a novel approach to pathway development based on connectivity, determined by language parsing of the published literature, and ranking, determined by the significance of differentially regulated genes in the network. In doing this, we identify highly connected "nexus" genes that are attractive candidates for therapeutic targeting and followup studies. Our use of pathway techniques to study atherosclerosis as an integrated network of gene interactions expands on traditional microarray analysis methods and emphasizes the significant advantages of a systems-based approach to analyzing complex disease. PMID:15942018

  5. An accelerated fusion power development plan

    NASA Astrophysics Data System (ADS)

    Dean, Stephen O.; Baker, Charles C.; Cohn, Daniel R.; Kinkead, Susan D.

    1991-06-01

    Energy for electricity and transportation is a national issue with worldwide environmental and political implications. The world must have energy options for the next century that are not vulnerable to possible disruption for technical, environmental, public confidence, or other reasons. Growing concerns about the greenhouse effect and the safety of transporting oil may lead to reduced burning of coal and other fossil fuels, and the incidents at Three Mile Island and Chernobyl, as well as nuclear waste storage problems, have eroded public acceptance of nuclear fission. Meeting future world energy needs will require improvements in energy efficiency and conservation. However, the world will soon need new central station power plants and increasing amounts of fuel for the transportation sector. The use of fossil fuels, and possibly even fission power, will very likely be restricted because of environmental, safety, and, eventually, supply considerations. Time is running out for policymakers. New energy technologies cannot be brought to the marketplace overnight. Decades are required to bring a new energy production technology from conception to full market penetration. With the added urgency to mitigate deleterious environmental effects of energy use, policymakers must act decisively now to establish and support vigorous energy technology development programs. The U.S. has invested 8 billion over the past 40 years in fusion research and development. If the U.S. fusion program proceeds according to its present strategy, an additional 40 years, and more money, will be expended before fusion will provide commercial electricity. Such an extended schedule is neither cost-effective nor technically necessary. It is time to launch a national venture to construct and operate a fusion power pilot plant. Such a plant could be operational within 15 years of a national commitment to proceed.

  6. Dendritic cells: an important link between antiphospholipid antibodies, endothelial dysfunction, and atherosclerosis in autoimmune and non-autoimmune diseases.

    PubMed

    Broder, Anna; Chan, Jimmy J; Putterman, Chaim

    2013-03-01

    The presence of dendritic cells, antigen-presenting cells that link innate and adaptive immunity, is necessary to generate and maintain the production of antiphospholipid antibodies in response to exposed intracellular phospholipids on the outer surface of apoptotic cells. In turn, antiphospholipid antibodies enhance dendritic cell-induced inflammatory and proatherogenic responses in a number of conditions that are associated with accelerated atherosclerosis, including diabetes, chronic kidney disease, periodontal infections, and aging. While altering dendritic cells by modifying the ubiquitin-proteasome system enhances antiphospholipid antibody production and leads to development of accelerated atherosclerosis and autoimmune features, inducing tolerance by dendritic cell manipulation leads to decreased atherosclerosis and thrombosis. Therefore, further translational studies are needed to understand the interplay between dendritic cells and antiphospholipid antibodies, and to develop potential new therapies for antiphospholipid syndrome and atherosclerosis. Here we review current experimental and translational studies that have examined the role of dendritic cells in antiphospholipid antibody formation and in antiphospholipid-associated atherosclerosis and thrombosis. PMID:23376063

  7. Accelerating Leadership Development via Immersive Learning and Cognitive Apprenticeship

    ERIC Educational Resources Information Center

    Backus, Clark; Keegan, Kevin; Gluck, Charles; Gulick, Lisa M. V.

    2010-01-01

    The authors put forward an approach to leadership development that builds on the principle of accelerated learning. They argue that leadership development, particularly in a period of recession or slow economic growth, needs to deliver results more quickly and with fewer resources. Indeed, they raise the question of whether or not this is what is…

  8. No Time To Kill: Entrainment and Accelerating Courseware Development.

    ERIC Educational Resources Information Center

    Millington, Paula Crnkovich

    This paper examines the concept of time in multimedia, World Wide Web-based courseware development. The biological concept of entrainment (the alignment of rhythms within and between systems) to accelerate courseware development is explored. The discussion begins with the foundational concepts of entrainment from biological systems and social…

  9. Human-like atherosclerosis in minipigs: a new model for detection and treatment of vulnerable plaques.

    PubMed

    Thim, Troels

    2010-07-01

    Advanced atherosclerosis, through thrombosis, leads to ischemic heart disease and ischemic stroke, the leading causes of death and disability worldwide. Advanced atherosclerosis and imaging of atherosclerosis are the focus of this dissertation with particular emphasis on the vulnerable plaque and vulnerable plaque detection. Aspects of advanced atherosclerosis and the vulnerable plaque in humans are described along with the basis for the selected minipig models and methods for atherosclerosis acceleration used. The overall aims of the studies were to develop an animal model of advanced atherosclerosis with human like vulnerable plaque morphology and use this animal model to test an imaging modality aimed at vulnerable plaque detection. The first aim is addressed in 3 papers, where accelerated plaque development in the coronary and carotid arteries is investigated in down sized Rapacz pigs. Down-sized Rapacz pigs are minipigs with familial hypercholesterolemia caused by a mutation in the low density lipoprotein receptor. Paper 1 describes the lipid profile in the down-sized Rapacz on chow and atherogenic diets and spontaneously developed and balloon accelerated coronary plaque with a morphology that resembles the morphology of human vulnerable plaque. Paper 2 describes vein graft disease in internal jugular vein grafts inserted into the common carotid artery. Plaques with necrotic cores were found in oversized vein grafts only indicating an effect of flow and shear stress on plaque development. Paper 3 describes the effects of wall shear stress on local plaque development in surgically stenosed common carotid arteries in the down-sized Rapacz pigs. This study indicated that the combination of low and oscillatory wall shear stress was needed for development of advanced plaque. In paper 4, we interrogated coronary lesions in the down-sized Rapacz with a commercially available diagnostic tool VH IVUS. It is claimed that VH IVUS can characterize the tissue components

  10. Separations technology development to support accelerator-driven transmutation concepts

    SciTech Connect

    Venneri, F.; Arthur, E.; Bowman, C.

    1996-10-01

    This is the final report of a one-year Laboratory-Directed Research and Development (LDRD) Project at the Los Alamos National Laboratory (LANL). This project investigated separations technology development needed for accelerator-driven transmutation technology (ADTT) concepts, particularly those associated with plutonium disposition (accelerator-based conversion, ABC) and high-level radioactive waste transmutation (accelerator transmutation of waste, ATW). Specific focus areas included separations needed for preparation of feeds to ABC and ATW systems, for example from spent reactor fuel sources, those required within an ABC/ATW system for material recycle and recovery of key long-lived radionuclides for further transmutation, and those required for reuse and cleanup of molten fluoride salts. The project also featured beginning experimental development in areas associated with a small molten-salt test loop and exploratory centrifugal separations systems.

  11. Aorta Atherosclerosis Lesion Analysis in Hyperlipidemic Mice

    PubMed Central

    Mohanta, Sarajo; Yin, Changjun; Weber, Christian; Hu, Desheng; Habenicht, Andreas JR

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries. Apolipoprotein E-deficient (ApoE-/-) mice are used as experimental models to study human atherosclerosis. ApoE-/- mice are constitutively hyperlipidemic and develop intima plaques that resemble human plaques. Various issues including experimental design for lesion analysis, dietary conditions, isolation of the aorta, staining methods, morphometry, group size, age, the location within the arterial tree, and statistical analyses are important parameters that need to be addressed to obtain robust data. Here, we provide detailed methods to quantify aorta atherosclerosis. PMID:27366759

  12. Methylarginines in Mice with Experimental Atherosclerosis.

    PubMed

    Gilinsky, M A; Sukhovershin, R A; Cherkanova, M S

    2015-11-01

    We studied the dynamics of indexes for the system of endogenous regulation of NO bioavailability. The content of NO synthase inhibitors (monomethylarginine and asymmetric dimethylarginine) in the blood of mice was measured after intraperitoneal injections of a nonionic surfactant poloxamer 407 for 2 and 14 weeks. The concentrations of both methylarginines in animals with atherosclerosis due to 14-week administration of poloxamer were much higher than in control specimens. The amount of arginine and symmetric dimethylarginine practically did not differ from the control. Poloxamer-induced model of atherosclerosis is characterized by increased content of NO synthase inhibitors. These changes contribute to the development of endothelial dysfunction and atherosclerosis. PMID:26601840

  13. Development of wide area environment accelerator operation and diagnostics method

    NASA Astrophysics Data System (ADS)

    Uchiyama, Akito; Furukawa, Kazuro

    2015-08-01

    Remote operation and diagnostic systems for particle accelerators have been developed for beam operation and maintenance in various situations. Even though fully remote experiments are not necessary, the remote diagnosis and maintenance of the accelerator is required. Considering remote-operation operator interfaces (OPIs), the use of standard protocols such as the hypertext transfer protocol (HTTP) is advantageous, because system-dependent protocols are unnecessary between the remote client and the on-site server. Here, we have developed a client system based on WebSocket, which is a new protocol provided by the Internet Engineering Task Force for Web-based systems, as a next-generation Web-based OPI using the Experimental Physics and Industrial Control System Channel Access protocol. As a result of this implementation, WebSocket-based client systems have become available for remote operation. Also, as regards practical application, the remote operation of an accelerator via a wide area network (WAN) faces a number of challenges, e.g., the accelerator has both experimental device and radiation generator characteristics. Any error in remote control system operation could result in an immediate breakdown. Therefore, we propose the implementation of an operator intervention system for remote accelerator diagnostics and support that can obviate any differences between the local control room and remote locations. Here, remote-operation Web-based OPIs, which resolve security issues, are developed.

  14. Mid-infrared Laser System Development for Dielectric Laser Accelerators

    NASA Astrophysics Data System (ADS)

    Jovanovic, Igor; Xu, Guibao; Wandel, Scott

    Laser-driven particle accelerators based on dielectric laser acceleration are under development and exhibit unique and challenging pump requirements. Operation in the mid-infrared (5 μm) range with short pulses (<1 ps FWHM), high pulse energy (>500 μJ) and good beam quality is required. We present our progress on the design and development of a novel two- stage source of mid-infrared pulses for this application, which is based on optical parametric amplification. Beta barium borate and zinc germanium phosphide crystals are used, and are pumped by a Ti:sapphire ultrashort laser and seeded by self-phase modulation and parametric generation-based sources.

  15. Platelets and the complement cascade in atherosclerosis

    PubMed Central

    Patzelt, Johannes; Verschoor, Admar; Langer, Harald F.

    2015-01-01

    Atherosclerosis and its late sequels are still the number one cause of death in western societies. Platelets are a driving force not only during the genesis of atherosclerosis, but especially in its late stages, as evidenced by complications such as arterial thrombosis, myocardial infarction, and ischemic stroke. Atherosclerosis is increasingly recognized as an inflammatory disease, influenced by various immune mechanisms. The complement system is part of our innate immune system, and its diverse roles in atherosclerosis have become evident over the past years. In this review we identify points of intersection between platelets and the complement system and discuss their relevance for atherosclerosis. Specifically, we will focus on roles for platelets in the onset as well as progression of the disease, a possible dual role for complement in the genesis and development of atherosclerosis, and review emerging literature revealing previously unrecognized cross-talk between platelets and the complement system and discuss its possible impact for atherosclerosis. Finally, we identify limitations of current research approaches and discuss perspectives of complement modulation in the control of the disease. PMID:25784879

  16. Atherosclerosis in chronic kidney disease: the role of macrophages

    PubMed Central

    Kon, Valentina; Linton, MacRae F.; Fazio, Sergio

    2013-01-01

    Patients with chronic kidney disease (CKD) are at increased risk of atherosclerotic cardiovascular disease and loss of renal parenchyma accelerates atherosclerosis in animal models. Macrophages are central to atherogenesis because they regulate cholesterol traffic and inflammation in the arterial wall. CKD influences macrophage behavior at multiple levels, rendering them proatherogenic. Even at normal creatinine levels, macrophages from uninephrectomized Apoe−/− mice are enriched in cholesterol owing to downregulation of cholesterol transporter ATP-binding cassette subfamily A member 1 levels and activation of nuclear factor κB, which leads to impaired cholesterol efflux. Interestingly, treatment with an angiotensin-II-receptor blocker (ARB) improves these effects. Moreover, atherosclerotic aortas from Apoe−/− mice transplanted into renal-ablated normocholesterolemic recipients show plaque progression and increased macrophage content instead of the substantial regression seen in recipient mice with intact kidneys. ARBs reduce atherosclerosis development in mice with partial renal ablation. These results, combined with the clinical benefits of angiotensin-converting-enzyme (ACE) inhibitors and ARBs in patients with CKD, suggest an important role for the angiotensin system in the enhanced susceptibility to atherosclerosis seen across the spectrum of CKD. The role of macrophages could explain why these therapies may be effective in end-stage renal disease, one of the few conditions in which statins show no clinical benefit. PMID:21102540

  17. Hyperhomocysteinemia and atherosclerosis.

    PubMed

    Yang, Fan; Tan, Hong-Mei; Wang, Hong

    2005-04-25

    Arteriosclerosis and its complications, such as heart attack and stroke, are the major causes of death in developed countries. It was believed that age, hyperlipidemia, hypertension, diabetes and smoking are common risk factors for cardiovascular disease. In addition, overwhelming clinical and epidemiological studies have identified homocysteine (Hcy) as a significant and independent risk factor for cardiovascular disease. In healthy individuals, plasma Hcy is between 5 and 10 micromol/L. One cause of severe hypehomocys- teinemia (HHcy) is the deficiency of cystathionine beta-synthase (CBS), which converts Hcy to cystathionine. CBS homozygous deficiency results in severe HHcy with Hcy levels up to 100 to 500 micromol/L. Patients with severe HHcy usually present with neurological abnormalities, premature arteriosclerosis. It has been reported that lowering plasma Hcy improved endothelial dysfunction and reduced incidence of major adverse events after percutaneous coronary intervention. The mechanisms by which Hcy induces atherosclerosis are largely unknown. Several biological mechanisms have been proposed to explain cardiovascular pathological changes associated with HHcy. These include: (1) endothelial cell damage and impaired endothelial function; (2) dysregulation of cholesterol and triglyceride biosynthesis; (3) stimulation of vascular smooth muscle cell proliferation; (4) thrombosis activation and (5) activation of monocytes. Four major biochemical mechanisms have been proposed to explain the vascular pathology of Hcy. These include: (1) autooxidation through the production of reactive oxygen species; (2) hypomethylation by forming SAH, a potent inhibitor of biological transmethylations; (3) nitrosylation by binding to nitric oxide or (4) protein homocysteinylation by incorporating into protein. In summary, our studies, as well as data from other laboratories support the concept that Hcy is causally linked to atherosclerosis, and is not merely associated with

  18. DEVELOPMENT OF A COMPACT RADIOGRAPHY ACCELERATOR USING DIELECTRIC WALL ACCELERATOR TECHNOLOGY

    SciTech Connect

    Sampayan, S; Caporaso, G; Chen, Y; Hawkins, S; Holmes, C; Krogh, M; McCarrick, J; Nelson, S; Nunnally, W; Poole, B; Rhodes, M; Sanders, D; Selenes, K; Sullivan, J; Wang, L; Watson, J

    2005-06-02

    We are developing an inexpensive compact accelerator system primarily intended for pulsed radiography. Design characteristics are an 8 MeV endpoint energy, 2 kA beam current, a cell gradient of approximately 3 MV/m (for an overall accelerator length is 2-3 m), and <$1/Volt capital costs. Such designs have been made possible with the development of high specific energy dielectrics (>10J/cm{sup 3}), specialized transmission line designs and multi-gap laser triggered low jitter (<1 ns) gas switches. In this geometry, the pulse forming lines, switches, and insulator/beam pipe are fully integrated within each cell to form a compact, stand-alone, stackable unit. We detail our research and modeling to date, recent high voltage test results, and the integration concept of the cells into a radiographic system.

  19. A study on regression of hypercholesterolemic atherosclerosis in rabbits by flax lignan complex.

    PubMed

    Prasad, Kailash

    2007-12-01

    Flax lignan complex (FLC) isolated from flaxseed suppresses the development of hypercholesterolemic atherosclerosis. The objectives of this study were to investigate if FLC produces regression of atherosclerosis and if regression is associated with reductions in serum lipids and oxidative stress. The studies were conducted in 4 groups of rabbits: group I, control diet (2 months); group II, 0.25% cholesterol diet (2 months); group III, 0.25% cholesterol diet (2 months) followed by regular diet (4 months); and group IV, 0.25% cholesterol diet (2 months) followed by regular diet and FLC (4 months). Serum lipids and oxidative stress parameters were measured before and at various intervals thereafter on their respective diets. The aortas were removed at the end of the protocol for assessment of atherosclerotic plaques and oxidative parameters. Atherosclerosis in group II was associated with hyperlipidemia and increased oxidative stress. Atherosclerotic changes were accelerated in group III, and this was associated with reductions in serum lipids and oxidative stress. Atherosclerotic lesions in group IV were similar to group II, but significantly smaller than those in group III, and were associated with reductions in serum lipids and oxidative stress similar to that in group III. These results indicate that FLC does not produce regression but prevents the acceleration of atherosclerosis due to the removal of cholesterol in the diet. These effects of FLC are not associated with reductions in serum lipids and oxidative stress. PMID:18172225

  20. Roles of antibody against oxygenized low density lipoprotein in atherosclerosis: recent advances

    PubMed Central

    Zhang, Jing; Wang, Daxin; He, Shenghu

    2015-01-01

    Atherosclerosis is a chronic immune inflammatory disease. Atherosclerosis and relevant disease are threatening human life and health. Oxygenized low density lipoprotein (oxLDL) is a molecular basis in the pathogenesis of atherosclerosis and able to induce inflammation, stimulate immune system and interfere with lipid metabolism in the occurrence and development of atherosclerosis. Antibody against oxLDL has been an important molecule in the immune related pathogenesis of atherosclerosis. In available studies on atherosclerosis, antibody against oxLDL has been a focus, but how oxLDL acts to affect the atherosclerosis and relevant diseases, whether oxLDL is protective or detrimental, and whether oxLDL acts in different ways at different stages of atherosclerosis are still unclear. This paper focuses on the role of antibody against oxLDL in the atherosclerosis and relevant diseases, and summarizes the advances in this field, aiming to provide new clue and new methods for the therapy of atherosclerosis. PMID:26550105

  1. Accelerating Child Survival and Development in Dark Times.

    ERIC Educational Resources Information Center

    Grant, James P.

    Measures were proposed that would enable UNICEF, in association with others and despite prevailing difficult economic circumstances, to more effectively bring well-being and hope to hundreds of millions of children. Specific proposals were designed to help most countries accelerate child survival and development. Most particularly, it was…

  2. Accelerating Early Language Development with Multi-Sensory Training

    ERIC Educational Resources Information Center

    Bjorn, Piia M.; Kakkuri, Irma; Karvonen, Pirkko; Leppanen, Paavo H. T.

    2012-01-01

    This paper reports the outcome of a multi-sensory intervention on infant language skills. A programme titled "Rhyming Game and Exercise Club", which included kinaesthetic-tactile mother-child rhyming games performed in natural joint attention situations, was intended to accelerate Finnish six- to eight-month-old infants' language development. The…

  3. Development of a wireless displacement measurement system using acceleration responses.

    PubMed

    Park, Jong-Woong; Sim, Sung-Han; Jung, Hyung-Jo; Spencer, Billie F

    2013-01-01

    Displacement measurements are useful information for various engineering applications such as structural health monitoring (SHM), earthquake engineering and system identification. Most existing displacement measurement methods are costly, labor-intensive, and have difficulties particularly when applying to full-scale civil structures because the methods require stationary reference points. Indirect estimation methods converting acceleration to displacement can be a good alternative as acceleration transducers are generally cost-effective, easy to install, and have low noise. However, the application of acceleration-based methods to full-scale civil structures such as long span bridges is challenging due to the need to install cables to connect the sensors to a base station. This article proposes a low-cost wireless displacement measurement system using acceleration. Developed with smart sensors that are low-cost, wireless, and capable of on-board computation, the wireless displacement measurement system has significant potential to impact many applications that need displacement information at multiple locations of a structure. The system implements an FIR-filter type displacement estimation algorithm that can remove low frequency drifts typically caused by numerical integration of discrete acceleration signals. To verify the accuracy and feasibility of the proposed system, laboratory tests are carried out using a shaking table and on a three storey shear building model, experimentally confirming the effectiveness of the proposed system. PMID:23881123

  4. Histone deacetylases and atherosclerosis.

    PubMed

    Zheng, Xia-xia; Zhou, Tian; Wang, Xin-An; Tong, Xiao-hong; Ding, Jia-wang

    2015-06-01

    Atherosclerosis is the most common pathological process that leads to cardiovascular diseases, a disease of large- and medium-sized arteries that is characterized by a formation of atherosclerotic plaques consisting of necrotic cores, calcified regions, accumulated modified lipids, smooth muscle cells (SMCs), endothelial cells, leukocytes, and foam cells. Recently, the question about how to suppress the occurrence of atherosclerosis and alleviate the progress of cardiovascular disease becomes the hot topic. Accumulating evidence suggests that histone deacetylases(HDACs) play crucial roles in arteriosclerosis. This review summarizes the effect of HDACs and HDAC inhibitors(HDACi) on the progress of atherosclerosis. PMID:25875381

  5. Innate and Adaptive Immunity in Atherosclerosis

    PubMed Central

    Packard, René R. S.; Lichtman, Andrew H.; Libby, Peter

    2010-01-01

    Atherosclerosis, a chronic inflammatory disorder, involves both the innate and adaptive arms of the immune response that mediate the initiation, progression, and ultimate thrombotic complications of atherosclerosis. Most fatal thromboses, which may manifest as acute myocardial infarction or ischemic stroke, result from frank rupture or superficial erosion of the fibrous cap overlying the atheroma, processes that occur in inflammatorily active, rupture-prone plaques. Appreciation of the inflammatory character of atherosclerosis has led to the application of C-reactive protein as a biomarker of cardiovascular risk, and the characterization of the anti-inflammatory and immunomodulatory actions of the statin class of drugs. An improved understanding of the pathobiology of atherosclerosis and further studies of its immune mechanisms provide avenues for the development of future strategies directed toward better risk stratification of patients as well as the identification of novel anti-inflammatory therapies. This review retraces leukocyte subsets involved in innate and adaptive immunity and their contributions to atherogenesis. PMID:19449008

  6. How Is Atherosclerosis Diagnosed?

    MedlinePlus

    ... sign that you're at risk for atherosclerosis. EKG (Electrocardiogram) An EKG is a simple, painless test that detects and ... beating and its rhythm (steady or irregular). An EKG also records the strength and timing of electrical ...

  7. Plasmacytoid Dendritic Cells in Atherosclerosis

    PubMed Central

    Döring, Yvonne; Zernecke, Alma

    2012-01-01

    Atherosclerosis, a chronic inflammatory disease of the vessel wall and the underlying cause of cardiovascular disease, is initiated and maintained by innate and adaptive immunity. Accumulating evidence suggests an important contribution of autoimmune responses to this disease. Plasmacytoid dendritic cells (pDCs), a specialized cell type known to produce large amounts of type I interferons (IFNs) in response to bacterial and viral infections, have recently been revealed to play important roles in atherosclerosis. For example, the development of autoimmune complexes consisting of self-DNA and antimicrobial peptides, which trigger chronic type I IFN production by pDCs, promote early atherosclerotic lesion formation. pDCs and pDC-derived type I IFNs can also induce the maturation of conventional DCs and macrophages, and the development of autoreactive B cells and antibody production. These mechanisms, known to play a role in the pathogenesis of other autoimmune diseases such as systemic lupus erythematosus and psoriasis, may also affect the development and progression of atherosclerotic lesion formation. This review discusses emerging evidence showing a contribution of pDCs in the onset and progression of atherosclerosis. PMID:22754539

  8. Association of blood pressure variability with induction of atherosclerosis in cholesterol-fed rats.

    PubMed

    Sasaki, S; Yoneda, Y; Fujita, H; Uchida, A; Takenaka, K; Takesako, T; Itoh, H; Nakata, T; Takeda, K; Nakagawa, M

    1994-05-01

    The influence of increased lability of blood pressure on the development of aortic atherosclerosis was examined. Because sinoaortic denervation (SAD) produced increased lability of blood pressure without blood pressure elevation, the development of atheromatous plaque was examined in SAD rats. These rats were fed a high-cholesterol diet and were denuded of endothelium so that development of atherosclerosis was accelerated. Five groups of male Wistar rats were used: A) controls, B) high-cholesterol diet (HC), C) HC+denudation (DN), D) HC+DN+renal artery clipping (2K1C), and E) HC+DN+sinoaortic denervation (SAD). Denudation was accomplished by scraping the aortic lumen with a balloon catheter, and hypertension was induced by clipping the left renal artery. After recording blood pressure and heart rate for 6 weeks, the rats were killed, blood samples were collected, and thoracic aortas were removed for pathologic examination. All the groups of rats fed a high-cholesterol diet developed marked hypercholesterolemia and hypotriglyceridemia. High-cholesterol diet alone could not induce aortic atherosclerosis, whereas aorta of HC+DN rats showed slight intimal thickening with smooth muscle cell proliferation. On the other hand, aorta of HC+DN + 2K1C rats showed marked atheromatous plaque with prominent cellular proliferation, and aorta of SAD rats also showed mild to moderate atheromatous plaque. Accordingly, we concluded that increased variability in circadian blood pressure per se, as well as hypertension, could induce aortic atherosclerosis in the hypercholesterolemic and endothelium-denuded rats. PMID:8060580

  9. Development of an artificial climatic complex accelerated corrosion tester and investigation of complex accelerated corrosion test methods

    SciTech Connect

    Li, J.; Li, M.; Sun, Z. )

    1999-05-01

    During recent decades, accelerated corrosion test equipment and methods simulating atmospheric corrosion have been developed to incorporate the many factors involved in complex accelerated corrosion. A new accelerated corrosion tester was developed to simulate various kinds of atmospheric corrosion environments. The equipment can be used to simulate various types of atmospheric corrosion environments with up to eight factors and can be used to carry out 18 kinds of standard corrosion and environmental tasks.

  10. Protective Role of the Interleukin 33 rs3939286 Gene Polymorphism in the Development of Subclinical Atherosclerosis in Rheumatoid Arthritis Patients

    PubMed Central

    Robustillo-Villarino, Montserrat; García-Bermúdez, Mercedes; Llorca, Javier; Corrales, Alfonso; González-Juanatey, Carlos; Ubilla, Begoña; Miranda-Filloy, José A.; Mijares, Verónica; Pina, Trinitario; Blanco, Ricardo; Alegre-Sancho, Juan J.; Ramírez Huaranga, Marco A.; Mínguez Sánchez, María D.; Tejera Segura, Beatriz; Ferraz-Amaro, Iván; Vicente, Esther; Carmona, F. David; Castañeda, Santos; Martín, Javier; González-Gay, Miguel A.

    2015-01-01

    Objectives To determine whether the interleukin-33 (IL-33)-interleukin-1 receptor like 1 (IL-1RL1) signaling pathway is implicated in the risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA). Methods A total of 576 Spanish RA patients from Northern Spain were genotyped for 6 well-known IL33-IL1RL1 polymorphisms (IL33 rs3939286, IL33 rs7025417, IL33 rs7044343, IL1RL1 rs2058660, IL1RL1 rs2310173 and IL1RL1 rs13015714) by TaqMan genotyping assay. The presence of subclinical atherosclerosis was determined by the assessment of carotid intima-media thickness (cIMT) by carotid ultrasound (US). Results RA patients carrying the TT genotype of the IL33 rs3939286 polymorphism had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.71 ± 0.14 mm versus 0.76 ± 0.16 mm, respectively) while patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). Moreover, RA patients carrying the mutant allele T of the IL33 rs3939286 polymorphism exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm respectively; p = 0.04). The association of both genotype and allele frequencies of IL33 rs3939286 and cIMT levels remained statistically significant after adjustment for sex, age at the time of US study, follow-up and center (p = 0.006 and p = 0.0023, respectively), evidencing that the potential effect conferred by IL33 rs3939286 may be independent of confounder factors. No association with other IL33-IL1RL1 genetic variants was observed. Conclusions In conclusion, our results may suggest a potential protective effect of the IL33 rs3939286 allele T in the risk of subclinical atherosclerosis in patients with RA. PMID:26571131

  11. Application of accelerators for the research and development of scintillators.

    PubMed

    Shibuya, Kengo; Koshimizu, Masanori; Asai, Keisuke; Muroya, Yusa; Katsumura, Yosuke; Inadama, Naoko; Yoshida, Eiji; Nishikido, Fumihiko; Yamaya, Taiga; Murayama, Hideo

    2007-08-01

    We introduce experimental systems which use accelerators to evaluate scintillation properties such as scintillation intensity, wavelength, and lifetime. A single crystal of good optical quality is often unavailable during early stages in the research and development (R&D) of new scintillator materials. Because of their beams' high excitation power and/or low penetration depth, accelerators facilitate estimation of the properties of early samples which may only be available as powders, thin films, and very small crystals. We constructed a scintillation spectrum measurement system that uses a Van de Graaff accelerator and an optical multichannel analyzer to estimate the relative scintillation intensity. In addition, we constructed a scintillation time profile measurement system that uses an electron linear accelerator and a femtosecond streak camera or a microchannel plate photomultiplier tube followed by a digital oscilloscope to determine the scintillation lifetimes. The time resolution is approximately 10 ps. The scintillation spectra or time profiles can be obtained in a significantly shorter acquisition time in comparison with that required by conventional measuring systems. The advantages of the systems described in this study can significantly promote the R&D of novel scintillator materials. PMID:17764319

  12. Environmental carcinogens and mutational pathways in atherosclerosis.

    PubMed

    Pulliero, A; Godschalk, R; Andreassi, M G; Curfs, D; Van Schooten, F J; Izzotti, A

    2015-05-01

    Atherosclerosis is associated with DNA damage in both circulating and vessel-wall cells and DNA adducts derived from exposure to environmental mutagens are abundant in atherosclerotic vessels. Environmental chemical carcinogens identified as risk factor for atherosclerosis include polycyclic aromatic hydrocarbons (benzo(a)pyrene, dimethylbenz(a)anthracene, beta-naphthoflavone, pyrene, 3-methylcolanthrene), arsenic, cadmium, 1,3-butadiene, cigarette smoke. Accordingly, polymorphisms of genes encoding for phase I/II metabolic reaction and DNA repair are risk factor for cardiovascular diseases, although their role is negligible as compared to other risk factors. The pathogenic relevance of mutation-related molecular damage in atherosclerosis has been demonstrated in experimental animal models involving the exposure to chemical mutagens. The relevance of mutation-related events in worsening atherosclerosis prognosis has been demonstrated in human clinical studies mainly as referred to mitochondrial DNA damage. Atherosclerosis is characterized by the occurrence of high level of oxidative damage in blood vessel resulting from both endogenous and exogenous sources. Mitochondrial damage is a main endogenous source of oxidative stress whose accumulation causes activation of intrinsic apoptosis through BIRC2 inhibition and cell loss contributing to plaque development and instability. Environmental physical mutagens, including ionizing radiation, are a risk factor for atherosclerosis even at the low exposure dose occurring in case of occupational exposure or the high exposure doses occurring during radiotherapy. Conversely, the role of exciting UV radiation in atherosclerosis is still uncertain. This review summarizes the experimental and clinical evidence supporting the pathogenic role of mutation-related pathway in atherosclerosis examining the underlying molecular mechanisms. PMID:25704189

  13. Advances in Parallel Electromagnetic Codes for Accelerator Science and Development

    SciTech Connect

    Ko, Kwok; Candel, Arno; Ge, Lixin; Kabel, Andreas; Lee, Rich; Li, Zenghai; Ng, Cho; Rawat, Vineet; Schussman, Greg; Xiao, Liling; /SLAC

    2011-02-07

    Over a decade of concerted effort in code development for accelerator applications has resulted in a new set of electromagnetic codes which are based on higher-order finite elements for superior geometry fidelity and better solution accuracy. SLAC's ACE3P code suite is designed to harness the power of massively parallel computers to tackle large complex problems with the increased memory and solve them at greater speed. The US DOE supports the computational science R&D under the SciDAC project to improve the scalability of ACE3P, and provides the high performance computing resources needed for the applications. This paper summarizes the advances in the ACE3P set of codes, explains the capabilities of the modules, and presents results from selected applications covering a range of problems in accelerator science and development important to the Office of Science.

  14. Positron Emission Tomography Imaging of Atherosclerosis

    PubMed Central

    Orbay, Hakan; Hong, Hao; Zhang, Yin; Cai, Weibo

    2013-01-01

    Atherosclerosis-related cardiovascular events are the leading causes of death in the industrialized world. Atherosclerosis develops insidiously and the initial manifestation is usually sudden cardiac death, stroke, or myocardial infarction. Molecular imaging is a valuable tool to identify the disease at an early stage before fatal manifestations occur. Among the various molecular imaging techniques, this review mainly focuses on positron emission tomography (PET) imaging of atherosclerosis. The targets and pathways that have been investigated to date for PET imaging of atherosclerosis include: glycolysis, cell membrane metabolism (phosphatidylcholine synthesis), integrin αvβ3, low density lipoprotein (LDL) receptors (LDLr), natriuretic peptide clearance receptors (NPCRs), fatty acid synthesis, vascular cell adhesion molecule-1 (VCAM-1), macrophages, platelets, etc. Many PET tracers have been investigated clinically for imaging of atherosclerosis. Early diagnosis of atherosclerotic lesions by PET imaging can help to prevent the premature death caused by atherosclerosis, and smooth translation of promising PET tracers into the clinic is critical to the benefit of patients. PMID:24312158

  15. Development of X-Band Dielectric-Loaded Accelerating Structures

    SciTech Connect

    Gold, S. H.; Jing, C.; Kanareykin, A.; Gai, W.; Konecny, R.; Power, J. G.; Kinkead, A. K.

    2010-11-04

    This paper presents a progress report on the development and testing of X-band dielectric-loaded accelerating structures. Recent tests on several quartz DLA structures with different inner diameters are reported. Designs for gap-free DLA structures are presented. Also, planned new experiments are discussed, including higher gradient traveling-wave and standing-wave structures and special grooved structures for multipactor suppression.

  16. Systemic lupus erythematosus and atherosclerosis: Review of the literature.

    PubMed

    Frieri, Marianne; Stampfl, Heather

    2016-01-01

    The purpose of this manuscript is to extensively review the literature related to systemic lupus erythematosus and atherosclerosis. The conclusion of this review has covered accelerated atherosclerosis in systemic lupus erythematosus, the role of complement, interferon in premature atherosclerosis, inflammatory mediators such as cytokines, leukocytes, innate and adaptive immunity, hydrolytic enzymes, reactive oxygen species, vascular endothelial growth factor, toll receptors in lupus nephritis, several specific anti-inflammatory pharmacological therapies, and potential prevention strategies for atherothrombotic events, interferons and the inflammasome. It is important for allergist-immunologists, rheumatologists both in academic institutions and in practice to understand this important disorder. PMID:26299985

  17. Developments in Laser and Plasma-Based Accelerators

    NASA Astrophysics Data System (ADS)

    Downer, Michael

    2001-04-01

    The explosive growth of multiterawatt laser technology combined with the increasing size and cost of conventional RF particle accelerators has driven intense research into more compact laser-driven and/or plasma based acceleration concepts. Although schemes for direct laser acceleration without plasmas or, conversely, plasma acceleration without lasers have been studied, the greatest recent progress has been made with concepts that combine lasers and plasmas [1]. Tajima and Dawson [2] proposed in 1979 that a sufficiently intense single laser pulse of duration t ω_p-1, or a pair of laser pulses with Δω ω_p, could be efficiently drive a longitudinal electron plasma wave with phase velocity approaching c via the ponderomotive force. Charged particles that "surf" such waves experience accelerating gradients (E 10^9 V/cm) as much as a thousand times greater than conventional RF accelerators. Numerous experiments have now demonstrated acceleration of up to 10^9 electrons per laser pulse to energies exceeding 100 MeV, with wide energy spread, but competitive beam emittance. Such sources have proven useful for nuclear activation analysis in their current form. However for such accelerators to be useful to a wider community, including high energy physics, key challenges must be addressed. These include: 1) Guiding terawatt laser pulses. Achieving useful laser intensities requires focusing, thus limiting interaction length to < 1 mm, whereas interaction lengths of several cm are needed to use laser energy efficiently and reach GeV acceleration in a single stage. Several groups are now developing high-throughput plasma "fibers" that have supported peak powers near a terawatt over > 1 cm without distortion [3]. 2) Phased injection. Since plasma waves with useful gradients have wavelengths of micron dimensions, charged particles must be injected with unprecedented spatial and temporal precision to achieve a monochromatic output beam. Several groups are developing new laser

  18. Local factors modify the dose dependence of 56Fe-induced atherosclerosis.

    NASA Astrophysics Data System (ADS)

    Kucik, Dennis; Gupta, Kiran; Wu, Xing; Yu, Tao; Chang, Polly; Kabarowski, Janusz; Yu, Shaohua

    2012-07-01

    Radiation exposure from a number of terrestrial sources is associated with an increased risk of cardiovascular disease, but evidence establishing whether high-LET radiation has similar effects has been lacking. We recently demonstrated that 600 MeV/n 56Fe induces atherosclerosis as well. Ten-week old male apolipoprotein-E deficient mice, a well-characterized atherosclerosis animal model, were exposed to 0 (control) 2, or 5Gy 56Fe targeted to the chest and neck. In these mice, 56Fe-induced atherosclerosis was similar in character to that induced by X-rays in the same mouse model and to that resulting from therapeutic radiation in cancer patients. Atherosclerosis was exacerbated by 56Fe only in targeted areas, however, suggesting a direct effect of the radiation on the arteries themselves. This is in contrast to some other risk factors, such as high cholesterol or tobacco use, which have systemic effects. The radiation dose required to accelerate development of atherosclerotic plaques, however, differed depending on the vessel that was irradiated and even the location within the vessel. For example, atherosclerosis in the aortic arch was accelerated only by the highest dose (5 Gy), while the carotid arteries and the aortic root showed effects at 2 Gy (a dose four- to eight-fold lower than the dose of X-rays that produces similar effects in this model). Since shear stress is disrupted in the area of the aortic root, it is likely that at least part of the site-specificity is due to additive or synergistic effects of radiation and local hydrodynamics. Other factors, such as local oxidative stress or gene expression may also have been involved. Since the pro-atherogenic effects of 56Fe depend on additional local factors, this suggests that radiation exposure, when unavoidable, might be mitigated by modification of factors unrelated to the radiation itself.

  19. Insulin decreases atherosclerosis by inducing endothelin receptor B expression

    PubMed Central

    Park, Kyoungmin; Mima, Akira; Li, Qian; Rask-Madsen, Christian; He, Pingnian; Mizutani, Koji; Katagiri, Sayaka; Maeda, Yasutaka; Wu, I-Hsien; Khamaisi, Mogher; Preil, Simone Rordam; Maddaloni, Ernesto; Sørensen, Ditte; Rasmussen, Lars Melholt; Huang, Paul L.; King, George L.

    2016-01-01

    Endothelial cell (EC) insulin resistance and dysfunction, caused by diabetes, accelerates atherosclerosis. It is unknown whether specifically enhancing EC-targeted insulin action can decrease atherosclerosis in diabetes. Accordingly, overexpressing insulin receptor substrate-1 (IRS1) in the endothelia of Apoe−/− mice (Irs1/Apoe−/−) increased insulin signaling and function in the aorta. Atherosclerosis was significantly reduced in Irs1/ApoE−/− mice on diet-induced hyperinsulinemia and hyperglycemia. The mechanism of insulin’s enhanced antiatherogenic actions in EC was related to remarkable induction of NO action, which increases endothelin receptor B (EDNRB) expression and intracellular [Ca2+]. Using the mice with knockin mutation of eNOS, which had Ser1176 mutated to alanine (AKI), deleting the only known mechanism for insulin to activate eNOS/NO pathway, we observed that IRS1 overexpression in the endothelia of Aki/ApoE−/− mice significantly decreased atherosclerosis. Interestingly, endothelial EDNRB expression was selectively reduced in intima of arteries from diabetic patients and rodents. However, endothelial EDNRB expression was upregulated by insulin via P13K/Akt pathway. Finally EDNRB deletion in EC of Ldlr−/− and Irs1/Ldlr−/− mice decreased NO production and accelerated atherosclerosis, compared with Ldlr−/− mice. Accelerated atherosclerosis in diabetes may be reduced by improving insulin signaling selectively via IRS1/Akt in the EC by inducing EDNRB expression and NO production. PMID:27200419

  20. New Developments in the Simulation of Advanced Accelerator Concepts

    SciTech Connect

    Bruhwiler, David L.; Cary, John R.; Cowan, Benjamin M.; Paul, Kevin; Mullowney, Paul J.; Messmer, Peter; Geddes, Cameron G. R.; Esarey, Eric; Cormier-Michel, Estelle; Leemans, Wim; Vay, Jean-Luc

    2009-01-22

    Improved computational methods are essential to the diverse and rapidly developing field of advanced accelerator concepts. We present an overview of some computational algorithms for laser-plasma concepts and high-brightness photocathode electron sources. In particular, we discuss algorithms for reduced laser-plasma models that can be orders of magnitude faster than their higher-fidelity counterparts, as well as important on-going efforts to include relevant additional physics that has been previously neglected. As an example of the former, we present 2D laser wakefield accelerator simulations in an optimal Lorentz frame, demonstrating >10 GeV energy gain of externally injected electrons over a 2 m interaction length, showing good agreement with predictions from scaled simulations and theory, with a speedup factor of {approx}2,000 as compared to standard particle-in-cell.

  1. New Developments in the Simulation of Advanced Accelerator Concepts

    SciTech Connect

    Paul, K.; Cary, J.R.; Cowan, B.; Bruhwiler, D.L.; Geddes, C.G.R.; Mullowney, P.J.; Messmer, P.; Esarey, E.; Cormier-Michel, E.; Leemans, W.P.; Vay, J.-L.

    2008-09-10

    Improved computational methods are essential to the diverse and rapidly developing field of advanced accelerator concepts. We present an overview of some computational algorithms for laser-plasma concepts and high-brightness photocathode electron sources. In particular, we discuss algorithms for reduced laser-plasma models that can be orders of magnitude faster than their higher-fidelity counterparts, as well as important on-going efforts to include relevant additional physics that has been previously neglected. As an example of the former, we present 2D laser wakefield accelerator simulations in an optimal Lorentz frame, demonstrating>10 GeV energy gain of externally injected electrons over a 2 m interaction length, showing good agreement with predictions from scaled simulations and theory, with a speedup factor of ~;;2,000 as compared to standard particle-in-cell.

  2. Research and Development for Ultra-High Gradient Accelerator Structures

    NASA Astrophysics Data System (ADS)

    Tantawi, Sami G.; Dolgashev, Valery; Higashi, Yasuo; Spataro, Bruno

    2010-11-01

    Research on the basic physics of high-gradient, high frequency accelerator structures and the associated RF/microwave technology are essential for the future of discovery science, medicine and biology, energy and environment, and national security. We will review the state-of-the-art for the development of high gradient linear accelerators. We will present the research activities aimed at exploring the basic physics phenomenon of RF breakdown. We present the experimental results of a true systematic study in which the surface processing, geometry, and materials of the structures have been varied, one parameter at a time. The breakdown rate or alternatively, the probability of breakdown/pulse/meter has been recorded for different operating parameters. These statistical data reveal a strong dependence of breakdown probability on surface magnetic field, or alternatively on surface pulsed heating. This is in contrast to the classical view of electric field dependence.

  3. Development of the brine shrimp Artemia is accelerated during spaceflight

    NASA Technical Reports Server (NTRS)

    Spooner, B. S.; Metcalf, J.; DeBell, L.; Paulsen, A.; Noren, W.; Guikema, J. A.

    1994-01-01

    Developmentally arrested brine shrimp cysts have been reactivated during orbital spaceflight on two different Space Shuttle missions (STS-50 and STS-54), and their subsequent development has been compared with that of simultaneously reactivated ground controls. Flight and control brine shrimp do not significantly differ with respect to hatching rates or larval morphology at the scanning and transmission EM levels. A small percentage of the flight larvae had defective nauplier eye development, but the observation was not statistically significant. However, in three different experiments on two different flights, involving a total of 232 larvae that developed in space, a highly significant difference in degree of flight to control development was found. By as early as 2.25 days after reactivation of development, spaceflight brine shrimp were accelerated, by a full instar, over ground control brine shrimp. Although developing more rapidly, flight shrimp grew as long as control shrimp at each developmental instar or stage.

  4. Who Is at Risk for Atherosclerosis?

    MedlinePlus

    ... NHLBI on Twitter. Who Is at Risk for Atherosclerosis? The exact cause of atherosclerosis isn't known. ... role in atherosclerosis risk. Other Factors That Affect Atherosclerosis Other factors also may raise your risk for ...

  5. The paradoxical role of IL-17 in atherosclerosis.

    PubMed

    Gong, Fangchen; Liu, Zhengxia; Liu, Jingning; Zhou, Ping; Liu, Ying; Lu, Xiang

    2015-09-01

    Atherosclerosis is a chronic inflammatory disease mediated by innate and adaptive immune responses. In recent years, CD4(+) T cells (Th1, Th2, Treg, and Th17) have been increasingly studied for their role in atherosclerosis pathophysiology, atheroma stability, plaque rupture, and life-threatening acute coronary syndrome. IL-17, a marker cytokine of Th17 cells, has been reported to be involved in the pathogenesis of rheumatoid arthritis, inflammatory bowel disease, and asthma. However, its role in atherosclerosis has been poorly characterized. This article provides a comprehensive overview of the role of IL-17 in the development of atherosclerosis and human coronary artery diseases. PMID:26077826

  6. Regression of hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed.

    PubMed

    Prasad, Kailash

    2008-03-01

    Secoisolariciresinol diglucoside (SDG) isolated from flaxseed is a lipid-lowering and antioxidant agent. It suppresses the development of hypercholesterolemic atherosclerosis in rabbits. It is however not known if SDG would produce regression of atherosclerosis. The objectives of this study were to determine (i) if SDG produces regression of atherosclerosis; (ii) if regression is associated with reduction in serum lipids, oxidative stress or both; and (iii) if the duration of treatment has an effect on regression. Rabbits were assigned to five groups: Group I, regular diet (control); Group II, 0.5% cholesterol diet for 2 months (mo); Group III, same as Group II but followed by regular diet for 2 mo; Group IV, same as Group II and followed by regular diet with SDG (20mg x kg body wt(-1) x day(-1) PO) for 2 mo; and Group V, same as Group IV but SDG treatment for an additional 2 mo. Blood samples were collected from rabbits before and at monthly intervals thereafter on their respective diet regimen for measurement of triglycerides (TG), total cholesterol (TC), LDL-C, HDL-C and malondialdehyde (MDA), a lipid peroxidation product. At the end of the protocol, the aorta was removed for assessment of atherosclerotic lesions, aortic MDA and aortic chemiluminescence (Aortic-CL), a measure of antioxidant reserve. MDA and Aortic-CL provide an index of oxidative stress. Increases in serum TG, TC, LDL-C, HDL-C and the risk ratio TC/HDL-C in Group II were associated with an increase in oxidative stress and development of atherosclerosis (57% of aortic intimal surface covered with lesions). Serum lipids decreased to a similar extent in Groups III-V, however atherosclerotic lesions were 84%, 63% and 44%, respectively in Groups III-V. There were more atherosclerotic lesions in Group III (+48.9%) as compared to Group II. The atherosclerotic lesions decreased by 24% and 45%, respectively in Groups IV and V compared to Group III. The reduction in atherosclerotic lesions was associated

  7. Clinical significance of high-density lipoproteins and the development of atherosclerosis: focus on the role of the adenosine triphosphate-binding cassette protein A1 transporter.

    PubMed

    Brewer, H Bryan; Santamarina-Fojo, Silvia

    2003-08-21

    , reduced LDL, increased HDL-mediated cholesterol flux to the liver, and reduced atherosclerosis. Ongoing investigation of mechanisms by which HDL acts to reduce the risk of atherosclerosis will provide several new targets for the development of drugs to decrease the risk of atherosclerosis. PMID:12948871

  8. Mitochondrial genome sequencing in atherosclerosis: what's next?

    PubMed

    Sazonova, Margarita A; Shkurat, Tatiana P; Demakova, Natalya A; Zhelankin, Andrey V; Barinova, Valeria A; Sobenin, Igor A; Orekhov, Alexander N

    2016-01-01

    Cardiovascular diseases are currently a basic cause of mortality in highly developed countries. The major reason for genesis and development of cardiovascular diseases is atherosclerosis. At the present time high technology methods of molecular genetic diagnostics can significantly simplify early presymptomatic recognition of patients with atherosclerosis, to detect risk groups and to perform a family analysis of this pathology. A Next-Generation Sequencing (NGS) technology can be characterized by high productivity and cheapness of full genome analysis of each DNA sample. We suppose that in the nearest future NGS methods will be widely used for scientific and diagnostic purposes, including personalized medicine. In the present review article literature data on using NGS technology were described in studying mitochondrial genome mutations associated with atherosclerosis and its risk factors, such as mitochondrial diabetes, mitochondrial cardiomyopathy, diabetic nephropathy and left ventricular hypertrophy. With the use of the NGS technology it proved to be possible to detect a range of homoplasmic and heteroplasmic mutations and mitochondrial genome haplogroups which are associated with these pathologies. Meanwhile some mutations and haplogroups were detected both in atherosclerosis and in its risk factors. It conveys the suggestion that there are common pathogenetic mechanisms causing these pathologies. What comes next? New paradigm of crosstalk between non-pharmaceutical (including molecular genetic) and true pharmaceutical approaches may be developed to fill the niche of effective and pathogenically targeted pretreatment and treatment of preclinical and subclinical atherosclerosis to avoid the development of chronic life-threatening disease. PMID:26561059

  9. Macrophage Autophagy in Atherosclerosis

    PubMed Central

    Maiuri, Maria Chiara; Grassia, Gianluca; Platt, Andrew M.; Carnuccio, Rosa; Ialenti, Armando; Maffia, Pasquale

    2013-01-01

    Macrophages play crucial roles in atherosclerotic immune responses. Recent investigation into macrophage autophagy (AP) in atherosclerosis has demonstrated a novel pathway through which these cells contribute to vascular inflammation. AP is a cellular catabolic process involving the delivery of cytoplasmic contents to the lysosomal machinery for ultimate degradation and recycling. Basal levels of macrophage AP play an essential role in atheroprotection during early atherosclerosis. However, AP becomes dysfunctional in the more advanced stages of the pathology and its deficiency promotes vascular inflammation, oxidative stress, and plaque necrosis. In this paper, we will discuss the role of macrophages and AP in atherosclerosis and the emerging evidence demonstrating the contribution of macrophage AP to vascular pathology. Finally, we will discuss how AP could be targeted for therapeutic utility. PMID:23401644

  10. Development of an accelerating-piston implosion-driven launcher

    NASA Astrophysics Data System (ADS)

    Huneault, Justin; Loiseau, Jason; Higgins, Andrew

    2013-06-01

    The ability to soft-launch projectiles at velocities exceeding 10 km/s is of interest to several scientific fields, including orbital debris impact testing and equation of state research. Current soft-launch technologies have reached a performance plateau below this operating range. The energy and power density of high explosives provides a possible avenue to reach this velocity if used to dynamically compress a light driver gas to significantly higher pressures and temperatures compared to light-gas guns. In the implosion-driven launcher (IDL), linear implosion of a pressurized tube drives a strong shock into the gas ahead of the tube pinch, thereby forming an increasingly long column of compressed gas which can be used to propel a projectile. The McGill IDL has demonstrated the ability to launch a 0.1-g projectile to 9.1 km/s. This study focuses on the implementation of a novel launch cycle wherein the explosively driven pinch is accelerated down the length of the tube in order to maintain a relatively constant projectile base pressure early in the launch cycle. The experimental development of an accelerating driver which utilizes an explosive lens to phase the detonation wave is presented. The design and experimental performance of an accelerating-piston IDL is also discussed.

  11. Development of a sealed-accelerator-tube neutron generator

    PubMed

    Verbeke; Leung; Vujic

    2000-10-01

    Sealed-accelerator-tube neutron generators are being developed in Lawrence Berkeley National Laboratory (LBNL) for applications ranging from neutron radiography to boron neutron capture therapy and neutron activation analysis. The new generation of high-output neutron generators is based on the D-T fusion reaction, producing 14.1-MeV neutrons. The main components of the neutron tube--the ion source, the accelerator and the target--are all housed in a sealed metal container without external pumping. Thick-target neutron yield computations are performed in this paper to estimate the neutron yield of titanium and scandium targets. With an average deuteron beam current of 1 A and an energy of 120 keV, a time-averaged neutron production of approximately 10(14) n/s can be estimated for a tritiated target, for both pulsed and cw operations. In mixed deuteron/triton beam operation, a beam current of 2 A at 150 keV is required for the same neutron output. Recent experimental results on ion sources and accelerator columns are presented and discussed. PMID:11003523

  12. The UPR in atherosclerosis.

    PubMed

    Zhou, Alex X; Tabas, Ira

    2013-05-01

    Multiple systemic factors and local stressors in the arterial wall can disturb the functions of endoplasmic reticulum (ER), causing ER stress in endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages during the initiation and progression of atherosclerosis. As a protective response to restore ER homeostasis, the unfolded protein response (UPR) is initiated by three major ER sensors: protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α), and activating transcription factor 6 (ATF6). The activation of the various UPR signaling pathways displays a temporal pattern of activation at different stages of the disease. The ATF6 and IRE1α pathways that promote the expression of protein chaperones in ER are activated in ECs in athero-susceptible regions of pre-lesional arteries and before the appearance of foam cells. The PERK pathway that reduces ER protein client load by blocking protein translation is activated in SMCs and macrophages in early lesions. The activation of these UPR signaling pathways aims to cope with the ER stress and plays a pro-survival role in the early stage of atherosclerosis. However, with the progression of atherosclerosis, the extended duration and increased intensity of ER stress in lesions lead to prolonged and enhanced UPR signaling. Under this circumstance, the PERK pathway induces expression of death effectors, and possibly IRE1α activates apoptosis signaling pathways, leading to apoptosis of macrophages and SMCs in advanced lesions. Importantly, UPR-mediated cell death is associated with plaque instability and the clinical progression of atherosclerosis. Moreover, UPR signaling is linked to inflammation and possibly to macrophage differentiation in lesions. Therapeutic approaches targeting the UPR may have promise in the prevention and/or regression of atherosclerosis. However, more progress is needed to fully understand all of the roles of the UPR in atherosclerosis and to harness this information

  13. SUSCEPTIBILITY TO ATHEROSCLEROSIS IN AORTAS AND CORONARY ARTERIES OF SWINE WITH VON WILLEBRAND'S DISEASE

    EPA Science Inventory

    The development of coronary and aortic atherosclerosis was determined after balloon catheter injury of coronary arteries and administration of an atherogenic diet in normal pigs and pigs that were homozygous and heterozygous for von Willebrand's disease. Coronary atherosclerosis ...

  14. Chemokines and their receptors in Atherosclerosis.

    PubMed

    van der Vorst, Emiel P C; Döring, Yvonne; Weber, Christian

    2015-09-01

    Atherosclerosis, a chronic inflammatory disease of the medium- and large-sized arteries, is the main underlying cause of cardiovascular diseases (CVDs) most often leading to a myocardial infarction or stroke. However, atherosclerosis can also develop without this clinical manifestation. The pathophysiology of atherosclerosis is very complex and consists of many cells and molecules interacting with each other. Over the last years, chemokines (small 8-12 kDa cytokines with chemotactic properties) have been identified as key players in atherogenesis. However, this remains a very active and dynamic field of research. Here, we will give an overview of the current knowledge about the involvement of chemokines in all phases of atherosclerotic lesion development. Furthermore, we will focus on two chemokines that recently have been associated with atherogenesis, CXCL12, and macrophage migration inhibitory factor (MIF). Both chemokines play a crucial role in leukocyte recruitment and arrest, a critical step in atherosclerosis development. MIF has shown to be a more pro-inflammatory and thus pro-atherogenic chemokine, instead CXCL12 seems to have a more protective function. However, results about this protective role are still quite debatable. Future research will further elucidate the precise role of these chemokines in atherosclerosis and determine the potential of chemokine-based therapies. PMID:26175090

  15. Latest Diagnostic Electronics Development for the PROSCAN Proton Accelerator

    SciTech Connect

    Duperrex, P.A.; Frei, U.; Gamma, G.; Mueller, U.; Rezzonico, L.

    2004-11-10

    New VME-based diagnostic electronics are being developed for PROSCAN, a proton accelerator for medical application presently under construction at PSI. One new development is a VME-based multi-channel logarithmic amplifier for converting current to voltage (LogIV). The LogIV boards are used for measuring current from the multiple wire (harp) profile monitors. The LogIV calibration method, current dependant bandwidth and temperature stability are presented. Another development is a BPM front end, based on the newest digital receiver techniques. Features of this new system are the remote control of the preamplifier stage and the continuous monitoring of each individual signal overall gain. Characteristics of the developed prototype are given.

  16. Activation of protein kinase C and disruption of endothelial monolayer integrity by sodium arsenite-Potential mechanism in the development of atherosclerosis

    SciTech Connect

    Pereira, Flavia E. . E-mail: flavia.pereira@umontana.edu; Coffin, J. Douglas . E-mail: douglas.coffin@umontana.edu; Beall, Howard D. . E-mail: howard.beall@umontana.edu

    2007-04-15

    Arsenic exposure has been shown to exacerbate atherosclerosis, beginning with activation of the endothelium that lines the vessel wall. Endothelial barrier integrity is maintained by proteins of the adherens junction (AJ) such as vascular endothelial cadherin (VE-cadherin) and {beta}-catenin and their association with the actin cytoskeleton. In the present study, human aortic endothelial cells (HAECs) were exposed to 1, 5 and 10 {mu}M sodium arsenite [As(III)] for 1, 6, 12 and 24 h, and the effects on endothelial barrier integrity were determined. Immunofluorescence studies revealed formation of actin stress fibers and non-uniform VE-cadherin and {beta}-catenin staining at cell-cell junctions that were concentration- and time-dependent. Intercellular gaps were observed with a measured increase in endothelial permeability. In addition, concentration-dependent increases in tyrosine phosphorylation (PY) of {beta}-catenin and activation of protein kinase C{alpha} (PKC{alpha}) were observed. Inhibition of PKC{alpha} restored VE-cadherin and {beta}-catenin staining at cell-cell junctions and abolished the As(III)-induced formation of actin stress fibers and intercellular gaps. Endothelial permeability and PY of {beta}-catenin were also reduced to basal levels. These results demonstrate that As(III) induces activation of PKC{alpha}, which leads to increased PY of {beta}-catenin downstream of PKC{alpha} activation. Phosphorylation of {beta}-catenin plausibly severs the association of VE-cadherin and {beta}-catenin, which along with formation of actin stress fibers, results in intercellular gap formation and increased endothelial permeability. To the best of our knowledge, this is the first report demonstrating that As(III) causes a loss of endothelial monolayer integrity, which potentially could contribute to the development of atherosclerosis.

  17. [Lipoproteins, free radicals and atherosclerosis].

    PubMed

    Manso, C

    1990-10-01

    The Author reviews vascular, lipidic and oxidative factors in the genesis of atherosclerosis. He admits the possibility that an alteration in the arterial wall, an increase in circulating lipids or an oxidative stress may influence the precocity of atherosclerosis. The transport of lipoperoxides or of oxidized cholesterol by lipoproteins renders them toxic and susceptible to aggravate atherosclerosis. PMID:2291852

  18. The thyromimetic T-0681 protects from atherosclerosis

    PubMed Central

    Tancevski, Ivan; Wehinger, Andreas; Demetz, Egon; Hoefer, Julia; Eller, Philipp; Huber, Eva; Stanzl, Ursula; Duwensee, Kristina; Auer, Kristina; Schgoer, Wilfried; Kuhn, Volker; Fievet, Catherine; Stellaard, Frans; Rudling, Mats; Foeger, Bernhard; Patsch, Josef R.; Ritsch, Andreas

    2009-01-01

    This report describes studies in hyperlipidemic New Zealand White (NZW) rabbits investigating the impact of the liver-selective thyromimetic T-0681 on lipoprotein metabolism and the development of atherosclerosis. Prolonged treatment with T-0681 increased the hepatic expression of both LDL receptor and scavenger receptor class B, type I without affecting cholesteryl ester transfer protein activity. Upregulation of hepatic lipoprotein receptors was accompanied by a marked decrease of apolipoprotein B-containing lipoproteins, reflected by a 60% reduction of plasma cholesterol and a >70% reduction of plasma triglyceride levels. Most importantly, T-0681 reduced the development of atherosclerosis by 80% in NZW rabbits on high-cholesterol chow. Our data suggest that liver-selective thyromimetics, such as T-0681, may prove to be useful therapeutic agents against the development of atherosclerosis in humans. PMID:19106072

  19. Development of the accelerator-driven energy production concept

    SciTech Connect

    Venneri, F.; Beard, C.; Bowman, C.

    1996-10-01

    This is the final report of a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). Accelerator Driven Transmutation Technology (ADTT) offers a means of generating nuclear energy in a clean, safe way that can be attractive to the general public. However, there are issues associated with the energy story (both at the system level and technical detail) that have to be seriously addressed before the scientific community, the public, and potential industrial sponsors can be compellingly convinced of its cost/benefit.

  20. Short-term administration of basic fibroblast growth factor enhances coronary collateral development without exacerbating atherosclerosis and balloon injury-induced vasoproliferation in atherosclerotic rabbits with acute myocardial infarction.

    PubMed

    Zhang, Chunxiang; Yang, Jian; Feng, Jianzhang; Jennings, Lisa K

    2002-08-01

    We evaluated the effect of basic fibroblast growth factor (bFGF) on the extent of atherosclerosis and balloon injury-induced vasoproliferation in atherosclerotic animals with acute myocardial infarction (AMI). Fifty-six rabbits were fed a 1% cholesterol diet. Balloon injury of iliac arteries and experimental acute myocardial infarction were induced in the same animals. Rabbits were then randomized to a bFGF group (20 pg/day, intravenously) or a control group (intravenous saline solution). The beneficial effects of bFGF on cardiac function, infarct size, and collateral vessel development, and the possible effect on vasoproliferation of balloon-injured vessels, were measured after 1 and 2 weeks. The extent of atherosclerosis was measured after 1, 2, and 4 weeks. Our results showed that bFGF significantly reduced infarct size and increased collateral-vessel density (P <.01) in infarct areas. Cardiac function was better in the bFGF group than in corresponding controls (P <.05). Similar beneficial effects of bFGF were noted in animals after 1- and 2-week treatments. However, the extent of atherosclerosis and the vasoproliferation in chronic atherosclerotic vessels induced by balloon injury and cholesterol diet were not significantly different between the two groups. Our results suggest that short-term treatment with bFGF enhances collateral development and produces maximum therapeutic benefits without exacerbating atherosclerosis and cell proliferation in stenotic vessels after AMI in atherosclerotic rabbits. PMID:12228768

  1. Subclinical Atherosclerosis in Rheumatoid Arthritis and Systemic Lupus Erythematosus

    PubMed Central

    Salmon, Jane E.; Roman, Mary J.

    2008-01-01

    Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are associated with increased mortality, largely as a consequence of cardiovascular disease. Increased cardiovascular morbidity and mortality in patients with RA and SLE cannot be entirely explained by traditional risk factors, suggesting that the systemic inflammation that characterizes these diseases may accelerate atherosclerosis. We used carotid ultrasonography to investigate the prevalence and correlates to preclinical atherosclerosis in patients with RA and SLE. Because atherosclerosis is a systemic disease, assessment of carotid plaque by ultrasonography provides a robust, direct measure of systemic atherosclerosis. We observed a substantially increased prevalence of carotid plaque in RA and SLE patients compared with age- and sex-matched controls, which remained after adjustment for traditional risk factors. The presence of carotid atherosclerosis was associated with disease duration in both RA and SLE and damage in SLE. These data support the hypothesis that inflammation associated with RA and SLE contributes to accelerated atherosclerosis and argue that RA and SLE disease activity should be more aggressively managed. PMID:18926167

  2. Specific autoantigens in experimental autoimmunity-associated atherosclerosis.

    PubMed

    Merched, Aksam J; Daret, Danièle; Li, Lan; Franzl, Nathalie; Sauvage-Merched, Maria

    2016-06-01

    Higher cardiovascular morbidity in patients with a wide range of autoimmune diseases highlights the importance of autoimmunity in promoting atherosclerosis. Our purpose was to investigate the mechanisms of accelerated atherosclerosis and identified vascular autoantigens targeted by autoimmunity. We created a mouse model of autoimmunity-associated atherosclerosis by transplanting bone marrow from FcγRIIB knockout (FcRIIB(-/-)) mice into LDL receptor knockout mice. We characterized the cellular and molecular mechanisms of atherogenesis and identified specific aortic autoantigens using serologic proteomic studies. En face lesion area analysis showed more aggressive atherosclerosis in autoimmune mice compared with control mice (0.64 ± 0.12 vs 0.32 ± 0.05 mm(2); P < 0.05, respectively). At the cellular level, FcRIIB(-/-) macrophages showed significant reduction (46-72%) in phagocytic capabilities. Proteomic analysis revealed circulating autoantibodies in autoimmune mice that targeted 25 atherosclerotic lesion proteins, including essential components of adhesion complex, cytoskeleton, and extracellular matrix, and proteins involved in critical functions and pathways. Microscopic examination of atherosclerotic plaques revealed essential colocalization of autoantibodies with endothelial cells, their adherence to basement membranes, the internal elastica lamina, and necrotic cores. The new vascular autoimmunosome may be a useful target for diagnostic and immunotherapeutic interventions in autoimmunity-associated diseases that have accelerated atherosclerosis.-Merched, A. J., Daret, D., Li, L., Franzl, N., Sauvage-Merched, M. Specific autoantigens in experimental autoimmunity-associated atherosclerosis. PMID:26891734

  3. Design and development of pulsed electron beam accelerator 'AMBICA - 600'

    NASA Astrophysics Data System (ADS)

    Verma, Rishi; Deb, Pankaj; Shukla, Rohit; Sharma, Surender; Shyam, Anurag

    2012-11-01

    Short duration, high power pulses with fast rise time and good flat-top are essentially required for driving pulsed electron beam diodes. To attain this objective, a dual resonant Tesla transformer based pulsed power accelerator 'AMBICA-600' has been developed. In this newly developed system, a coaxial water line is charged through single turn Tesla transformer that operates in the dual resonant mode. For making the accelerator compact, in the high power pulse forming line, water has been used as dielectric medium because of its high dielectric constant, high dielectric strength and high energy density. The coaxial waterline can be pulsed charged up to 600kV, has impedance of ~5Ω and generates pulse width of ~60ns. The integrated system is capable of producing intense electron beam of 300keV, 60kA when connected to impedance matched vacuum diode. In this paper, system hardware details and experimental results of gigawatt electron beam generation have been presented.

  4. Microdomains, Inflammation, and Atherosclerosis.

    PubMed

    Sorci-Thomas, Mary G; Thomas, Michael J

    2016-02-19

    Elevated levels of cholesteryl ester (CE)-enriched apoB containing plasma lipoproteins lead to increased foam cell formation, the first step in the development of atherosclerosis. Unregulated uptake of low-density lipoprotein cholesterol by circulating monocytes and other peripheral blood cells takes place through scavenger receptors and over time causes disruption in cellular cholesterol homeostasis. As lipoproteins are taken up, their CE core is hydrolyzed by liposomal lipases to generate free cholesterol (FC). FC can be either re-esterified and stored as CE droplets or shuttled to the plasma membrane for ATP-binding cassette transporter A1-mediated efflux. Because cholesterol is an essential component of all cellular membranes, some FC may be incorporated into microdomains or lipid rafts. These platforms are essential for receptor signaling and transduction, requiring rapid assembly and disassembly. ATP-binding cassette transporter A1 plays a major role in regulating microdomain cholesterol and is most efficient when lipid-poor apolipoprotein AI (apoAI) packages raft cholesterol into soluble particles that are eventually catabolized by the liver. If FC is not effluxed from the cell, it becomes esterified, CE droplets accumulate and microdomain cholesterol content becomes poorly regulated. This dysregulation leads to prolonged activation of immune cell signaling pathways, resulting in receptor oversensitization. The availability of apoAI or other amphipathic α-helix-rich apoproteins relieves the burden of excess microdomain cholesterol in immune cells allowing a reduction in immune cell proliferation and infiltration, thereby stimulating regression of foam cells in the artery. Therefore, cellular balance between FC and CE is essential for proper immune cell function and prevents chronic immune cell overstimulation and proliferation. PMID:26892966

  5. Improving and Accelerating Drug Development for Nervous System Disorders

    PubMed Central

    Pankevich, Diana E.; Altevogt, Bruce M.; Dunlop, John; Gage, Fred H.; Hyman, Steve E.

    2014-01-01

    Advances in the neurosciences have placed the field in the position where it is poised to significantly reduce the burden of nervous system disorders. However, drug discovery, development and translation for nervous system disorders still pose many unique challenges. The key scientific challenges can be summarized as follows: mechanisms of disease, target identification and validation, predictive models, biomarkers for patient stratification and as endpoints for clinical trials, clear regulatory pathways, reliability and reproducibility of published data, and data sharing and collaboration. To accelerate nervous system drug development the Institute of Medicine’s Forum on Neuroscience and Nervous System Disorders has hosted a series of public workshops that brought together representatives of industry, government (including both research funding and regulatory agencies), academia, and patient groups to discuss these challenges and offer potential strategies to improve the translational neuroscience. PMID:25442933

  6. Development of high purity niobium used in SRF accelerating cavity

    NASA Astrophysics Data System (ADS)

    Chen, Lin; Xie, Wei-Ping; Li, Ming-Yang; He, Ji-Lin; Fan, Hui-Ru; Zhang, Bao-Cheng; He, Fei-Si; Zhao, Kui; Chen, Jia-Er; Liu, Ke-Xin

    2008-12-01

    Niobium is widely used in SRF (Superconducting Radio Frequency) cavities due to its excellent superconductivity and workability. With the continuous development of technology, higher demands of material are raised. One of the key issues is that RRR (Residual Resistance Ratio) of the Nb material should be more than 300, which requires that the Nb ingot have even higher RRR. This article introduces the development and the experimental results of high purity niobium in OTIC in Ningxia (Ningxia Orient Tantalum Industry Co. Ltd.), and the test results of the single cell TESLA (Tera Electron volt energy Superconducting Linear Accelerator) shaped cavity manufactured by Peking University using Nb material from OTIC. Supported by National Basic Research Program of China (2002CB713600)

  7. Highly Productive Application Development with ViennaCL for Accelerators

    NASA Astrophysics Data System (ADS)

    Rupp, K.; Weinbub, J.; Rudolf, F.

    2012-12-01

    The use of graphics processing units (GPUs) for the acceleration of general purpose computations has become very attractive over the last years, and accelerators based on many integrated CPU cores are about to hit the market. However, there are discussions about the benefit of GPU computing when comparing the reduction of execution times with the increased development effort [1]. To counter these concerns, our open-source linear algebra library ViennaCL [2,3] uses modern programming techniques such as generic programming in order to provide a convenient access layer for accelerator and GPU computing. Other GPU-accelerated libraries are primarily tuned for performance, but less tailored to productivity and portability: MAGMA [4] provides dense linear algebra operations via a LAPACK-comparable interface, but no dedicated matrix and vector types. Cusp [5] is closest in functionality to ViennaCL for sparse matrices, but is based on CUDA and thus restricted to devices from NVIDIA. However, no convenience layer for dense linear algebra is provided with Cusp. ViennaCL is written in C++ and uses OpenCL to access the resources of accelerators, GPUs and multi-core CPUs in a unified way. On the one hand, the library provides iterative solvers from the family of Krylov methods, including various preconditioners, for the solution of linear systems typically obtained from the discretization of partial differential equations. On the other hand, dense linear algebra operations are supported, including algorithms such as QR factorization and singular value decomposition. The user application interface of ViennaCL is compatible to uBLAS [6], which is part of the peer-reviewed Boost C++ libraries [7]. This allows to port existing applications based on uBLAS with a minimum of effort to ViennaCL. Conversely, the interface compatibility allows to use the iterative solvers from ViennaCL with uBLAS types directly, thus enabling code reuse beyond CPU-GPU boundaries. Out-of-the-box support

  8. Development of an annular arc accelerator shock tube driver

    NASA Technical Reports Server (NTRS)

    Leibowitz, L. P.

    1973-01-01

    An annular arc accelerator (ANAA) shock tube driver has been developed that deposits the energy of an arc discharge into a flowing gas, which then expands and cools without any delay for the opening of a diaphragm. A simplified one-dimensional flow analysis of the ANAA shock tube has been performed, which indicates that shock velocities greater than 40 km/sec may be obtained using a 300-kJ capacitor bank. The ANAA driver consists of a high-pressure driver, an expansion section, and an electrode section. In operation, the cold gas driver is pressurized until the diaphragm bursts, sending a pressure front down the expansion tube to the arc section. When the accelerated flow arrives at the electrode section, a 100-capacitor, 300-kJ capacitor bank is discharged either by breaking an insulating diaphragm between the electrodes or by the triggering of a series of external switches. Shock velocities of 28 km/sec have been obtained, and modifications are described that are expected to improve performance.

  9. Development of Dielectric-Based High Gradient Accelerating Structures

    SciTech Connect

    Jing, C.; Gai, W.; Konecny, R.; Power, J.; Liu, W.; Gold, S. H.; Kinkead, A. K.; Kanareykin, A.; Kazakov, S.

    2006-11-27

    High gradient accelerating structures using dielectric-lined circular waveguides have been developed for a number of years at Argonne National Laboratory. In this article, we first report the experimental results of high power rf testing on the quartz based Dielectric-Loaded Accelerating (DLA) structure carried out on Feb. 2006 at the Naval Research Laboratory. The motivation for this experiment is to test the multipactor effect on different materials under high power and high vacuum condition. Up to 12 MW pulsed rf went through the tube without breakdown. Multipactor appeared during the experiment but with different features compared to other materials like alumina. Photomultiplier Tube (PMT) measurements were introduced into the experiment for the first time to observe the light emission time and intensity. In the second part of this paper, ways to achieve higher gradient for DLA structures are proposed: 1) smaller ID and longitudinal gap free DLA structures to reduce multipactor and obtain higher gradient; 2) new coaxial type coupler to avoid dielectric gap and improve impedance matching; 3) double layered DLA structure to reduce rf loss and enhance shunt impedance as well.

  10. Atherosclerosis: a chronic inflammatory disease mediated by mast cells.

    PubMed

    Conti, Pio; Shaik-Dasthagirisaeb, Yazdami

    2015-01-01

    Inflammation is a process that plays an important role in the initiation and progression of atherosclerosis and immune disease, involving multiple cell types, including macrophages, T-lymphocytes, endothelial cells, smooth muscle cells and mast cells. The fundamental damage of atherosclerosis is the atheromatous or fibro-fatty plaque which is a lesion that causes several diseases. In atherosclerosis the innate immune response, which involves macrophages, is initiated by the arterial endothelial cells which respond to modified lipoproteins and lead to Th1 cell subset activation and generation of inflammatory cytokines and chemoattractant chemokines. Other immune cells, such as CD4+ T inflammatory cells, which play a critical role in the development and progression of atherosclerosis, and regulatory T cells [Treg], which have a protective effect on the development of atherosclerosis are involved. Considerable evidence indicates that mast cells and their products play a key role in inflammation and atherosclerosis. Activated mast cells can have detrimental effects, provoking matrix degradation, apoptosis, and enhancement as well as recruitment of inflammatory cells, which actively contributes to atherosclerosis and plaque formation. Here we discuss the relationship between atherosclerosis, inflammation and mast cells. PMID:26648785

  11. Atherosclerosis: a chronic inflammatory disease mediated by mast cells

    PubMed Central

    Shaik-Dasthagirisaeb, Yazdami

    2015-01-01

    Inflammation is a process that plays an important role in the initiation and progression of atherosclerosis and immune disease, involving multiple cell types, including macrophages, T-lymphocytes, endothelial cells, smooth muscle cells and mast cells. The fundamental damage of atherosclerosis is the atheromatous or fibro-fatty plaque which is a lesion that causes several diseases. In atherosclerosis the innate immune response, which involves macrophages, is initiated by the arterial endothelial cells which respond to modified lipoproteins and lead to Th1 cell subset activation and generation of inflammatory cytokines and chemoattractant chemokines. Other immune cells, such as CD4+ T inflammatory cells, which play a critical role in the development and progression of atherosclerosis, and regulatory T cells [Treg], which have a protective effect on the development of atherosclerosis are involved. Considerable evidence indicates that mast cells and their products play a key role in inflammation and atherosclerosis. Activated mast cells can have detrimental effects, provoking matrix degradation, apoptosis, and enhancement as well as recruitment of inflammatory cells, which actively contributes to atherosclerosis and plaque formation. Here we discuss the relationship between atherosclerosis, inflammation and mast cells. PMID:26648785

  12. Adipokines, diabetes and atherosclerosis: an inflammatory association

    PubMed Central

    Freitas Lima, Leandro C.; Braga, Valdir de Andrade; do Socorro de França Silva, Maria; Cruz, Josiane de Campos; Sousa Santos, Sérgio H.; de Oliveira Monteiro, Matheus M.; Balarini, Camille de Moura

    2015-01-01

    Cardiovascular diseases can be considered the most important cause of death in diabetic population and diabetes can in turn increase the risk of cardiovascular events. Inflammation process is currently recognized as responsible for the development and maintenance of diverse chronic diseases, including diabetes and atherosclerosis. Considering that adipose tissue is an important source of adipokines, which may present anti and proinflammatory effects, the aim of this review is to explore the role of the main adipokines in the pathophysiology of diabetes and atherosclerosis, highlighting the therapeutic options that could arise from the manipulation of these signaling pathways both in humans and in translational models. PMID:26578976

  13. Long Noncoding RNA: Recent Updates in Atherosclerosis

    PubMed Central

    Li, Hao; Zhu, Hongming; Ge, Junbo

    2016-01-01

    Long noncoding RNAs belong to a class of noncoding RNAs longer than 200 nucleotides with the epigenetic regulation potential. As a novel molecular regulator, lncRNAs are often dysregulated in various pathological conditions and display multiple functions in a wide range of biological processes. Given that recent studies have indicated that lncRNAs are involved in atherosclerosis-related smooth muscle cell, endothelial cell, macrophage and lipid metabolism regulation, it is pertinent to understand the potential function of lncRNAs in atherosclerosis development. This review will highlight the recent updates of lncRNAs in atherogenesis and also discuss their potential roles as novel therapeutic targets. PMID:27314829

  14. Positron emission tomography imaging of coronary atherosclerosis.

    PubMed

    Moss, Alastair J; Adamson, Philip D; Newby, David E; Dweck, Marc R

    2016-07-01

    Inflammation has a central role in the progression of coronary atherosclerosis. Recent developments in cardiovascular imaging with the advent of hybrid positron emission tomography have provided a window into the molecular pathophysiology underlying coronary plaque inflammation. Using novel radiotracers targeted at specific cellular pathways, the potential exists to observe inflammation, apoptosis, cellular hypoxia, microcalcification and angiogenesis in vivo. Several clinical studies are now underway assessing the ability of this hybrid imaging modality to inform about atherosclerotic disease activity and the prediction of future cardiovascular risk. A better understanding of the molecular mechanisms governing coronary atherosclerosis may be the first step toward offering patients a more stratified, personalized approach to treatment. PMID:27322032

  15. Developing an Accelerator Driven System (ADS) based on electron accelerators and heavy water

    NASA Astrophysics Data System (ADS)

    Feizi, H.; Ranjbar, A. H.

    2016-02-01

    An ADS based on electron accelerators has been developed specifically for energy generation and medical applications. Monte Carlo simulations have been performed using FLUKA code to design a hybrid electron target and the core components. The composition, geometry of conversion targets and the coolant system have been optimized for electron beam energies of 20 to 100 MeV . Furthermore, the photon and photoneutron energy spectra, distribution and energy deposition for various incoming electron beam powers have been studied. Light-heavy water of various mixtures have been used as heat removal for the targets, as γ-n converters and as neutron moderators. We have shown that an electron LINAC, as a neutron production driver for ADSs, is capable of producing a neutron output of > 3.5 × 1014 (n/s/mA). Accordingly, the feasibility of an electron-based ADS employing the designed features is promising for energy generation and high intense neutron production which have various applications such as medical therapies.

  16. Development of an Accelerator Mass Spectrometer based on a Cyclotron

    SciTech Connect

    Kim, Dogyun; Bhang, Hyeongchan; Kim, Jongwon

    2011-12-13

    An accelerator mass spectrometer based on a cyclotron has been developed, and a prototype of the injection beam line has been constructed. Mass resolution of the cyclotron is designed to be over 4000. A sawtooth RF buncher in the beam line and a flat-topping RF system for the cyclotron were utilized to enhance beam transmission efficiency, which is a primary factor for improvement compared to previous cyclotron mass spectrometers. The injection beam line comprises an ion source, Einzel lens, RF buncher, 90 deg. dipole magnet and a slit box containing beam diagnostic devices. A carbon beam was measured at the location of the slit box, and beam phase spaces will be measured. The design of a cyclotron magnet was done, and orbit tracking was carried out using cyclotron optics codes. A scheme of radial injection was chosen to place a beam on the equilibrium orbit of the cyclotron. The injection scheme will be optimized after the beam measurements are completed.

  17. Status and Future Developments in Large Accelerator Control Systems

    SciTech Connect

    Karen S. White

    2006-10-31

    Over the years, accelerator control systems have evolved from small hardwired systems to complex computer controlled systems with many types of graphical user interfaces and electronic data processing. Today's control systems often include multiple software layers, hundreds of distributed processors, and hundreds of thousands of lines of code. While it is clear that the next generation of accelerators will require much bigger control systems, they will also need better systems. Advances in technology will be needed to ensure the network bandwidth and CPU power can provide reasonable update rates and support the requisite timing systems. Beyond the scaling problem, next generation systems face additional challenges due to growing cyber security threats and the likelihood that some degree of remote development and operation will be required. With a large number of components, the need for high reliability increases and commercial solutions can play a key role towards this goal. Future control systems will operate more complex machines and need to present a well integrated, interoperable set of tools with a high degree of automation. Consistency of data presentation and exception handling will contribute to efficient operations. From the development perspective, engineers will need to provide integrated data management in the beginning of the project and build adaptive software components around a central data repository. This will make the system maintainable and ensure consistency throughout the inevitable changes during the machine lifetime. Additionally, such a large project will require professional project management and disciplined use of well-defined engineering processes. Distributed project teams will make the use of standards, formal requirements and design and configuration control vital. Success in building the control system of the future may hinge on how well we integrate commercial components and learn from best practices used in other industries.

  18. Quantification of carotid vessel atherosclerosis

    NASA Astrophysics Data System (ADS)

    Chiu, Bernard; Egger, Micaela; Spence, J. D.; Parraga, Grace; Fenster, Aaron

    2006-03-01

    Atherosclerosis is characterized by the development of plaques in the arterial wall, which ultimately leads to heart attacks and stroke. 3D ultrasound (US) has been used to screen patients' carotid arteries. Plaque measurements obtained from these images may aid in the management and monitoring of patients, and in evaluating the effect of new treatment options. Different types of measures for ultrasound phenotypes of atherosclerosis have been proposed. Here, we report on the development and application of a method used to analyze changes in carotid plaque morphology from 3D US images obtained at two different time points. We evaluated our technique using manual segmentations of the wall and lumen of the carotid artery from images acquired in two US scanning sessions. To incorporate the effect of intraobserver variability in our evaluation, manual segmentation was performed five times each for the arterial wall and lumen. From this set of five segmentations, the mean wall and lumen surfaces were reconstructed, with the standard deviation at each point mapped onto the surfaces. A correspondence map between the mean wall and lumen surfaces was then established, and the thickness of the atherosclerotic plaque at each point in the vessel was estimated to be the distance between each correspondence pairs. The two-sample Student's t-test was used to judge whether the difference between the thickness values at each pair corresponding points of the arteries in the two 3D US images was statistically significant.

  19. Photoacoustic tomography: applications for atherosclerosis imaging

    NASA Astrophysics Data System (ADS)

    Sangha, Gurneet S.; Goergen, Craig J.

    2016-08-01

    Atherosclerosis is a debilitating condition that increases a patient’s risk for intermittent claudication, limb amputation, myocardial infarction, and stroke, thereby causing approximately 50% of deaths in the western world. Current diagnostic imaging techniques, such as ultrasound, digital subtraction angiography, computed tomography angiography, magnetic resonance angiography, and optical imaging remain suboptimal for detecting development of early stage plaques. This is largely due to the lack of compositional information, penetration depth, and/or clinical efficiency of these traditional imaging techniques. Photoacoustic imaging has emerged as a promising modality that could address some of these limitations to improve the diagnosis and characterization of atherosclerosis-related diseases. Photoacoustic imaging uses near-infrared light to induce acoustic waves, which can be used to recreate compositional images of tissue. Recent developments in photoacoustic techniques show its potential in noninvasively characterizing atherosclerotic plaques deeper than traditional optical imaging approaches. In this review, we discuss the significance and development of atherosclerosis, current and novel clinical diagnostic methods, and recent works that highlight the potential of photoacoustic imaging for both experimental and clinical studies of atherosclerosis.

  20. Impact of age and sex on the development of atherosclerosis and expression of the related genes in apoE deficient mice.

    PubMed

    Liu, Mengyang; Zhang, Wenwen; Li, Xiaoju; Han, Jihong; Chen, Yuanli; Duan, Yajun

    2016-01-15

    Development of atherosclerosis is a chronic pathological process. ApoE deficient (apoE(-/-)) mice spontaneously develop atherosclerotic lesions. However, the impact of age and sex on lesions and expression of the related genes have not been fully elucidated. In this study, we collected blood and tissue samples from normal chow fed male and female apoE(-/-) mice at different ages, and determined serum lipids, PCSK9 levels, en face aortic lesions and expression of some pro- or anti-atherogenic genes. We determined that lesion development was clearly associated with age, and more lesions in males than females (12.6 ± 1.7% vs. 8.9 ± 1.1% at 8 months old, P < 0.05). Associated with age, serum total, LDL- and HDL-cholesterol and PCSK9 levels increased with more PCSK9 in females than males (313 ± 31 ng/mL vs. 239 ± 28 ng/mL at 8 months old, P < 0.05); expression of liver LDLR and ABCA1 decreased while of SR-BI increased; expression of macrophage ABCA1 and SR-BI decreased but of CD36 increased. Estrogen and tamoxifen induced ABCA1 and SR-BI expression, respectively, in macrophages isolated from female mice at the different age. Taken together, our study suggests that aging facilitates lesion development in apoE(-/-) mice with greater effect on male mice. The lesion development is also related to expression of pro- or anti-atherogenic genes in tissues, particularly in macrophages. PMID:26592663

  1. Accelerating technology development through integrated computation and experimentation

    SciTech Connect

    Shekhawat, Dushyant; Srivastava, Rameshwar

    2013-01-01

    This special section of Energy & Fuels comprises a selection of papers presented at the topical conference “Accelerating Technology Development through Integrated Computation and Experimentation”, sponsored and organized by the United States Department of Energy’s National Energy Technology Laboratory (NETL) as part of the 2012 American Institute of Chemical Engineers (AIChE) Annual Meeting held in Pittsburgh, PA, Oct 28−Nov 2, 2012. That topical conference focused on the latest research and development efforts in five main areas related to fossil energy, with each area focusing on the utilization of both experimental and computational approaches: (1) gas separations (membranes, sorbents, and solvents for CO{sub 2}, H{sub 2}, and O{sub 2} production), (2) CO{sub 2} utilization (enhanced oil recovery, chemical production, mineralization, etc.), (3) carbon sequestration (flow in natural systems), (4) advanced power cycles (oxy-combustion, chemical looping, gasification, etc.), and (5) fuel processing (H{sub 2} production for fuel cells).

  2. Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources.

    PubMed

    Oki, Noffisat O; Nelms, Mark D; Bell, Shannon M; Mortensen, Holly M; Edwards, Stephen W

    2016-03-01

    The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity (HTT) testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledge base; however, this process is currently labor-intensive and time-consuming. Publicly available data sources provide a wealth of information that could be used to define computationally predicted AOPs (cpAOPs), which could serve as a basis for creating expert-derived AOPs in a much more efficient way. Computational tools for mining large datasets provide the means for extracting and organizing the information captured in these public data sources. Using cpAOPs as a starting point for expert-derived AOPs should accelerate AOP development. Coupling this with tools to coordinate and facilitate the expert development efforts will increase the number and quality of AOPs produced, which should play a key role in advancing the adoption of HTT testing, thereby reducing the use of animals in toxicity testing and greatly increasing the number of chemicals that can be tested. PMID:26809562

  3. Strong correlation between early stage atherosclerosis and electromechanical coupling of aorta.

    PubMed

    Liu, X Y; Yan, F; Niu, L L; Chen, Q N; Zheng, H R; Li, J Y

    2016-03-24

    Atherosclerosis is the underlying cause of cardiovascular diseases that are responsible for many deaths in the world, and the early diagnosis of atherosclerosis is highly desirable. The existing imaging methods, however, are not capable of detecting the early stage of atherosclerosis development due to their limited spatial resolution. Using piezoresponse force microscopy (PFM), we show that the piezoelectric response of an aortic wall increases as atherosclerosis advances, while the stiffness of the aorta shows a less evident correlation with atherosclerosis. Furthermore, we show that there is strong correlation between the coercive electric field necessary to switch the polarity of the artery and the development of atherosclerosis. Thus by measuring the electromechanical coupling of the aortic wall, it is possible to probe atherosclerosis at the early stage of its development, not only improving the spatial resolution by orders of magnitude, but also providing comprehensive quantitative information on the biomechanical properties of the artery. PMID:26972797

  4. Strong correlation between early stage atherosclerosis and electromechanical coupling of aorta

    NASA Astrophysics Data System (ADS)

    Liu, X. Y.; Yan, F.; Niu, L. L.; Chen, Q. N.; Zheng, H. R.; Li, J. Y.

    2016-03-01

    Atherosclerosis is the underlying cause of cardiovascular diseases that are responsible for many deaths in the world, and the early diagnosis of atherosclerosis is highly desirable. The existing imaging methods, however, are not capable of detecting the early stage of atherosclerosis development due to their limited spatial resolution. Using piezoresponse force microscopy (PFM), we show that the piezoelectric response of an aortic wall increases as atherosclerosis advances, while the stiffness of the aorta shows a less evident correlation with atherosclerosis. Furthermore, we show that there is strong correlation between the coercive electric field necessary to switch the polarity of the artery and the development of atherosclerosis. Thus by measuring the electromechanical coupling of the aortic wall, it is possible to probe atherosclerosis at the early stage of its development, not only improving the spatial resolution by orders of magnitude, but also providing comprehensive quantitative information on the biomechanical properties of the artery.

  5. Insulin resistance, metabolic stress, and atherosclerosis

    PubMed Central

    Pansuria, Meghana; Xi, Hang; Li, Le; Yang, Xiao-Feng; Wang, Hong

    2012-01-01

    Atherosclerosis, a pathological process that underlies the development of cardiovascular disease, is the primary cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). T2DM is characterized by hyperglycemia and insulin resistance (IR), in which target tissues fail to respond to insulin. Systemic IR is associated with impaired insulin signaling in the metabolic tissues and vasculature. Insulin receptor is highly expressed in the liver, muscle, pancreas, and adipose tissue. It is also expressed in vascular cells. It has been suggested that insulin signaling in vascular cells regulates cell proliferation and vascular function. In this review, we discuss the association between IR, metabolic stress, and atherosclerosis with focus on 1) tissue and cell distribution of insulin receptor and its differential signaling transduction and 2) potential mechanism of insulin signaling impairment and its role in the development of atherosclerosis and vascular function in metabolic disorders including hyperglycemia, hypertension, dyslipidemia, and hyperhomocysteinemia. We propose that insulin signaling impairment is the foremost biochemical mechanism underlying increased cardiovascular morbidity and mortality in atherosclerosis, T2DM, and metabolic syndrome. PMID:22202099

  6. Accelerated Nuclear Energy Materials Development with Multiple Ion Beams

    SciTech Connect

    Fluss, M J; Bench, G

    2009-08-19

    A fundamental issue in nuclear energy is the changes in material properties as a consequence of time, temperature, and neutron fluence. Usually, candidate materials for nuclear energy applications are tested in nuclear reactors to understand and model the changes that arise from a combination of atomic displacements, helium and hydrogen production, and other nuclear transmutations (e.g. fission and the production of fission products). Experiments may be carried out under neutron irradiation conditions in existing nuclear materials test reactors (at rates of 10 to 20 displacements per atom (DPA) per year or burn-up rates of a few percent per year for fertile fuels), but such an approach takes much too long for many high neutron fluence scenarios (300 DPA for example) expected in reactors of the next generation. Indeed it is reasonable to say that there are no neutron sources available today to accomplish sufficiently rapid accelerated aging let alone also provide the temperature and spectral characteristics of future fast spectrum nuclear energy systems (fusion and fission both). Consequently, materials research and development progress continues to be severely limited by this bottleneck.

  7. Ectasia and Severe Atherosclerosis

    PubMed Central

    Adiloglu, Ali K.; Can, Rabia; Nazli, Cem; Ocal, Ahmet; Ergene, Oktay; Tinaz, Gulgun; Kisioglu, Nesimi

    2005-01-01

    To date, there has been no convincing evidence for an association between Chlamydia pneumoniae or Helicobacter pylori and ectasia. In this case-control study, we have investigated the association of H. pylori and C. pneumoniae seropositivity with ectasia, severe coronary atherosclerosis, and normal vessels, which were so classified by coronary angiography. We have also evaluated the influence of these infections on inflammatory markers such as high-sensitive C-reactive protein (hsCRP) and interleukin 6 (IL-6). Of the 796 patients undergoing coronary angiography for suspected ischemic heart disease, 244 patients were recruited. Of these, 91 had normal vessels, 88 had 3 or more obstructed vessels, and 65 had ectatic vessels without atherosclerosis. Eighty-seven atherosclerotic patients (98.9%) were positive for C. pneumoniae IgG, as were 64 ectatic patients (98.5%) and 76 controls (83.5%) (P < 0.001). Forty-two atherosclerotic patients (47.7%) were positive for C. pneumoniae IgM, as were 43 ectatic patients (66.2%) and 43 controls (47.3%) (P = 0.036). Seventy-two atherosclerotic patients (81.8%) were positive for H. pylori IgA, as were 26 ectatic patients (40.0%) and 44 controls (48.4%) (P < 0.001). High-sensitive CRP levels were significantly higher in ectatic patients (5.639 mg/L) than in controls (4.390 mg/L) (P = 0.032), and IL-6 levels were significantly higher in atherosclerotic patients (33.92 U/L) than in controls (14.01 U/L) (P < 0.001). Interleukin-6 levels were higher in H. pylori seropositive patients, and hsCRP levels were higher in C. pneumoniae seropositive patients, when compared with seronegatives. We suggest that, as in atherosclerosis, C. pneumoniae infection is related to ectasia, with raised CRP levels. PMID:15902817

  8. Development of Bipolar Pulse Accelerator for Pulsed Ion Beam Implantation to Semiconductor

    NASA Astrophysics Data System (ADS)

    Masugata, Katsumi; Kawahara, Yoshihiro; Mitsui, Chihiro; Kitamura, Iwao; Takahashi, Takakazu; Tanaka, Yasunori; Tanoue, Hisao; Arai, Kazuo

    2002-12-01

    To improve the purity of the ion beams new type of pulsed power ion accelerator named "bipolar pulse accelerator" was proposed. The accelerator consists of two acceleration gaps (an ion source gap and a post acceleration gap) and a drift tube, and a bipolar pulse is applied to the drift tube to accelerate the beam. In the accelerator intended ions are selectively accelerated and the purity of the ion beam is enhanced. As the first step of the development of the accelerator, a Br-type magnetically insulated acceleration gap is developed. The gap has an ion source of coaxial gas puff plasma gun on the grounded anode and a negative pulse is applied to the cathode to accelerate the ion beam. By using the plasma gun, ion source plasma (nitrogen) of current density around 100 A/cm2 is obtained. In the paper, the experimental results of the evaluation of the ion beam and the characteristics of the gap are shown with the principle and the design concept of the proposed accelerator.

  9. Accelerated molecular dynamics methods: introduction and recent developments

    SciTech Connect

    Uberuaga, Blas Pedro; Voter, Arthur F; Perez, Danny; Shim, Y; Amar, J G

    2009-01-01

    reaction pathways may be important, we return instead to a molecular dynamics treatment, in which the trajectory itself finds an appropriate way to escape from each state of the system. Since a direct integration of the trajectory would be limited to nanoseconds, while we are seeking to follow the system for much longer times, we modify the dynamics in some way to cause the first escape to happen much more quickly, thereby accelerating the dynamics. The key is to design the modified dynamics in a way that does as little damage as possible to the probability for escaping along a given pathway - i.e., we try to preserve the relative rate constants for the different possible escape paths out of the state. We can then use this modified dynamics to follow the system from state to state, reaching much longer times than we could reach with direct MD. The dynamics within any one state may no longer be meaningful, but the state-to-state dynamics, in the best case, as we discuss in the paper, can be exact. We have developed three methods in this accelerated molecular dynamics (AMD) class, in each case appealing to TST, either implicitly or explicitly, to design the modified dynamics. Each of these methods has its own advantages, and we and others have applied these methods to a wide range of problems. The purpose of this article is to give the reader a brief introduction to how these methods work, and discuss some of the recent developments that have been made to improve their power and applicability. Note that this brief review does not claim to be exhaustive: various other methods aiming at similar goals have been proposed in the literature. For the sake of brevity, our focus will exclusively be on the methods developed by the group.

  10. Infectious burden and atherosclerosis: A clinical issue

    PubMed Central

    Sessa, Rosa; Pietro, Marisa Di; Filardo, Simone; Turriziani, Ombretta

    2014-01-01

    Atherosclerotic cardiovascular diseases, chronic inflammatory diseases of multifactorial etiology, are the leading cause of death worldwide. In the last decade, more infectious agents, labeled as “infectious burden”, rather than any single pathogen, have been showed to contribute to the development of atherosclerosis through different mechanisms. Some microorganisms, such as Chlamydia pneumoniae (C. pneumoniae), human cytomegalovirus, etc. may act directly on the arterial wall contributing to endothelial dysfunction, foam cell formation, smooth muscle cell proliferation, platelet aggregation as well as cytokine, reactive oxygen specie, growth factor, and cellular adhesion molecule production. Others, such as Helicobacter pylori (H. pylori), influenza virus, etc. may induce a systemic inflammation which in turn may damage the vascular wall (e.g., by cytokines and proteases). Moreover, another indirect mechanism by which some infectious agents (such as H. pylori, C. pneumoniae, periodontal pathogens, etc.) may play a role in the pathogenesis of atherosclerosis is molecular mimicry. Given the complexity of the mechanisms by which each microorganism may contribute to atherosclerosis, defining the interplay of more infectious agents is far more difficult because the pro-atherogenic effect of each pathogen might be amplified. Clearly, continued research and a greater awareness will be helpful to improve our knowledge on the complex interaction between the infectious burden and atherosclerosis. PMID:25032197

  11. Inflammation, Atherosclerosis, and Coronary Artery Disease: PET/CT for the Evaluation of Atherosclerosis and Inflammation.

    PubMed

    Alie, Nadia; Eldib, Mootaz; Fayad, Zahi A; Mani, Venkatesh

    2014-01-01

    Atherosclerosis is a prevalent cardiovascular disease marked by inflammation and the formation of plaque within arterial walls. As the disease progresses, there is an increased risk of major cardiovascular events. Owing to the nature of atherosclerosis, it is imperative to develop methods to further understand the physiological implications and progression of the disease. The combination of positron emission tomography (PET)/computed tomography (CT) has proven to be promising for the evaluation of atherosclerotic plaques and inflammation within the vessel walls. The utilization of the radiopharmaceutical tracer, 18F-fluorodeoxyglucose ((18)F-FDG), with PET/CT is invaluable in understanding the pathophysiological state involved in atherosclerosis. In this review, we will discuss the use of (18)F-FDG-PET/CT imaging for the evaluation of atherosclerosis and inflammation both in preclinical and clinical studies. The potential of more specific novel tracers will be discussed. Finally, we will touch on the potential benefits of using the newly introduced combined PET/magnetic resonance imaging (MRI) for non-invasive imaging of atherosclerosis. PMID:25674025

  12. Inflammation, Atherosclerosis, and Coronary Artery Disease: PET/CT for the Evaluation of Atherosclerosis and Inflammation

    PubMed Central

    Alie, Nadia; Eldib, Mootaz; Fayad, Zahi A; Mani, Venkatesh

    2014-01-01

    Atherosclerosis is a prevalent cardiovascular disease marked by inflammation and the formation of plaque within arterial walls. As the disease progresses, there is an increased risk of major cardiovascular events. Owing to the nature of atherosclerosis, it is imperative to develop methods to further understand the physiological implications and progression of the disease. The combination of positron emission tomography (PET)/computed tomography (CT) has proven to be promising for the evaluation of atherosclerotic plaques and inflammation within the vessel walls. The utilization of the radiopharmaceutical tracer, 18F-fluorodeoxyglucose (18F-FDG), with PET/CT is invaluable in understanding the pathophysiological state involved in atherosclerosis. In this review, we will discuss the use of 18F-FDG-PET/CT imaging for the evaluation of atherosclerosis and inflammation both in preclinical and clinical studies. The potential of more specific novel tracers will be discussed. Finally, we will touch on the potential benefits of using the newly introduced combined PET/magnetic resonance imaging (MRI) for non-invasive imaging of atherosclerosis. PMID:25674025

  13. Molecular imaging in atherosclerosis, thrombosis and vascular inflammation

    PubMed Central

    Choudhury, Robin P.; Fisher, Edward A.

    2009-01-01

    Appreciation of the molecular and cellular processes of atherosclerosis, thrombosis and vascular inflammation has identified new targets for imaging. The common goals of molecular imaging approaches are to accelerate and refine diagnosis, provide insights that reveal disease diversity, guide specific therapies and monitor the effects of those therapies. Here we undertake a comparative analysis of imaging modalities that have been used in this disease area. We consider the elements of contrast agents, emphasizing how an understanding of the biology of atherosclerosis and its complications can inform optimal design. We address the potential and limitations of current contrast approaches in respect of translation to clinically usable agents and speculate on future applications. PMID:19213945

  14. Atherosclerosis and atheroma plaque rupture: normal anatomy of vasa vasorum and their role associated with atherosclerosis.

    PubMed

    Sun, Zhonghua

    2014-01-01

    Atherosclerosis is primarily a degenerative disorder related to aging with a chronic inflammatory component. There are differences in expression among different vascular beds, inflicting a range of vascular diseases. The majority of studies focus on the inner and medial vascular layers, which are affected at the development of atherosclerosis. Recent evidence shows that the outer layer of blood vessels, composed of the adventitial layer and the vasa vasorum, not only plays a significant role in maintaining vessel integrity, but also reacts to atheroma. What is not clear is the extent of contribution of the outer layer to the process of atherosclerosis. Is it involved in the initiation, progression, and clinical expression of atheroma? Is the inflammation associated with atheroma limited to being merely reactive or is there a proactive element? This paper provides an overview of the normal anatomy of vasa vasorum and potential mechanism of plaque formation due to vascular injury (vasa vasorum) and microhemorrhage. PMID:24790560

  15. Atherosclerosis and Atheroma Plaque Rupture: Normal Anatomy of Vasa Vasorum and Their Role Associated with Atherosclerosis

    PubMed Central

    2014-01-01

    Atherosclerosis is primarily a degenerative disorder related to aging with a chronic inflammatory component. There are differences in expression among different vascular beds, inflicting a range of vascular diseases. The majority of studies focus on the inner and medial vascular layers, which are affected at the development of atherosclerosis. Recent evidence shows that the outer layer of blood vessels, composed of the adventitial layer and the vasa vasorum, not only plays a significant role in maintaining vessel integrity, but also reacts to atheroma. What is not clear is the extent of contribution of the outer layer to the process of atherosclerosis. Is it involved in the initiation, progression, and clinical expression of atheroma? Is the inflammation associated with atheroma limited to being merely reactive or is there a proactive element? This paper provides an overview of the normal anatomy of vasa vasorum and potential mechanism of plaque formation due to vascular injury (vasa vasorum) and microhemorrhage. PMID:24790560

  16. Accelerator developments since the ZGS by ZGS people

    SciTech Connect

    Cho, Y.

    1994-12-31

    The ZGS was a facility, as well as an organization, where people got together to pursue a common goal of doing exciting science of the day. In this note, the authors describe notable events related to accelerators and accelerator people since the closing of the ZGS program some 15 years ago. Many of the same ZGS people have been carrying out the state-of-the art accelerator work around the Laboratory with the same dedication that characterized their work in the earlier days. First the authors describe how the activities were re-organized after the closing of the ZGS, the migration of people, and the organizational evolution since that time. Doing this shows the similarity between the birth of the ZGS and the birth of the Advanced Photon Source (APS). Then, some of the accelerator work by the former ZGS people are described. These include: (1) Intense Pulsed Neutron Source (IPNS), (2) GeV Electron Microtron (GEM), (3) Wake Field Accelerator Test Facility, (4) Advanced Photon Source, and (5) IPNS Upgrade.

  17. Residual acceleration data on IML-1: Development of a data reduction and dissemination plan

    NASA Technical Reports Server (NTRS)

    Rogers, Melissa J. B.; Alexander, J. Iwan D.; Wolf, Randy

    1991-01-01

    A residual acceleration data analysis plan is developed that will allow principal investigators of low-gravity experiments to efficiently process their experimental results in conjunction with accelerometer data. The basic approach consisted of the following program of research: (1) identification of sensitive experiments and sensitivity ranges by order of magnitude estimates, numerical modelling, and investigator input; (2) research and development towards reduction, supplementation, and dissemination of residual acceleration data; and (3) implementation of the plan on existing acceleration data bases.

  18. Interleukin-13 protects from atherosclerosis and modulates plaque composition by skewing the macrophage phenotype

    PubMed Central

    Cardilo-Reis, Larissa; Gruber, Sabrina; Schreier, Sabine M; Drechsler, Maik; Papac-Milicevic, Nikolina; Weber, Christian; Wagner, Oswald; Stangl, Herbert; Soehnlein, Oliver; Binder, Christoph J

    2012-01-01

    Atherosclerotic lesions are characterized by the accumulation of oxidized LDL (OxLDL) and the infiltration of macrophages and T cells. Cytokine expression in the microenvironment of evolving lesions can profoundly contribute to plaque development. While the pro-atherogenic effect of T helper (Th) 1 cytokines, such as IFN-γ, is well established, the role of Th2 cytokines is less clear. Therefore, we characterized the role of the Th2 cytokine interleukin (IL)-13 in murine atherosclerosis. Here, we report that IL-13 administration favourably modulated the morphology of already established atherosclerotic lesions by increasing lesional collagen content and reducing vascular cell adhesion molecule-1 (VCAM-1)-dependent monocyte recruitment, resulting in decreased plaque macrophage content. This was accompanied by the induction of alternatively activated (M2) macrophages, which exhibited increased clearance of OxLDL compared to IFN-γ-activated (M1) macrophages in vitro. Importantly, deficiency of IL-13 results in accelerated atherosclerosis in LDLR−/− mice without affecting plasma cholesterol levels. Thus, IL-13 protects from atherosclerosis and promotes a favourable plaque morphology, in part through the induction of alternatively activated macrophages. PMID:23027612

  19. Niobium resonator development for high-brightness ion beam acceleration

    SciTech Connect

    Delayen, J.R.; Bohn, C.L.; Roche, C.T.

    1990-01-01

    Two niobium resonant cavities for high-brightness ion beam acceleration have been constructed and tested. The first was based on a coaxial quarter-wave geometry and was optimized for phase velocity {beta}{sub o} = 0.15. This cavity, which resonates at 400 MHz in the fundamental mode, operated at an average (wall-to-wall) accelerating gradient of 12.9 MV/m under continuous-wave (cw) fields. At this gradient, a cavity Q of 1.4 {times} 10{sup 8} was measured. The second was based on a coaxial half-wave geometry and was optimized for {beta}{sub o} = 0.12. This cavity, which resonates at 355 MHz in the fundamental mode, operated at an average accelerating gradient of 18.0 MV/m under cw fields. This is the highest average accelerating gradient achieved to date in low-velocity structures designed for cw operation. At this gradient, a cavity Q of 1.2 {times} 10{sup 8} was measured.

  20. Developing and Maintaining Accelerated Degree Programs within Traditional Institutions.

    ERIC Educational Resources Information Center

    Husson, William J.; Kennedy, Tom

    2003-01-01

    Successful accelerated degree programs should be learner focused, market sensitive, accessible, and high quality. They should offer a variety of options and excellent customer service. Key elements include institutional purpose, decision-making process, curricular design, adjunct faculty, marketing, and promotional materials. (SK)

  1. Atherosclerosis and aortic aneurysm - is inflammation a common denominator?

    PubMed

    Peshkova, Iuliia O; Schaefer, Giulia; Koltsova, Ekaterina K

    2016-05-01

    Cardiovascular diseases (CVD) are the major cause of death in developed countries. Various risk factors including host genetics and, more importantly, environmental factors such as lifestyle, diet and smoking influence CVD progression. Two common forms of CVD are atherosclerosis and abdominal aortic aneurysm (AAA). Emerging evidence suggests that inflammation plays a pivotal role in CVD. However, it remains unclear whether the same inflammatory pathways prove essential for atherosclerosis and AAA because, in some cases, the same mechanisms uniformly promote both diseases, while in others they function in opposite ways. Cytokines, key mediators of inflammation, play an important role in the development of atherosclerosis but have only been scarcely studied in AAA. In this review, we discuss the importance of immune-mediated mechanisms and cytokines in the pathogenesis of atherosclerosis and AAA. PMID:26700480

  2. E-beam accelerator cavity development for the ground-based free electron laser

    NASA Astrophysics Data System (ADS)

    Bultman, N. K.; Spalek, G.

    Los Alamos National Laboratory is designing and developing four prototype accelerator cavities for high power testing on the Modular Component Technology Development (MCTD) test stand at Boeing. These cavities provide the basis for the e-beam accelerator hardware that will be used in the Ground Based Free Electron Laser (GBFEL) to be sited at the White Sands Missile Range (WSMR) in New Mexico.

  3. On the Boundaries of the Acceleration of the Development of Intelligence.

    ERIC Educational Resources Information Center

    Kingma, Johannes; Tomic, Welko

    This paper examines the possibility of accelerating the development of intelligence when applying stringent Piagetian standards to evaluate the effects of short- and long-term intervention or instruction programs. The paper reviews previous Genevan and American research that shows that development can be accelerated by means of only a few…

  4. [Major pathogenic links of atherosclerosis].

    PubMed

    Antelava, N A; Pachkoriia, K Z; Kezeli, T D; Nikuradze, N S; Shamkulashvili, G G

    2005-11-01

    The experimental and clinical data concerning pathogenesis of the atherosclerosis are summarized and analyzed in this article. Major concepts that explain initiation and progressive growth of atherosclerosis such as lipid infiltrations, response to disturbing factors, "response on the keeping of particles" and inflammatory processes are discussed. These concepts are considered as base for integral theory of atherosclerosis according which the inflammatory process in atherosclerosis are the result of the universal response reaction of endothelium to the various disturbing risk factors. Chronic inflammation leads to complex cellular and molecular interactions among cells derived from the endothelium, smooth muscle and several blood cell components and causes oxidative stress, proliferation of smooth muscle cells, oxidative modification of LDL, uptake and macrophage foam cell formation, endothelium dysfunction. Major pathogenic links of atherosclerosis, such as inflammation, oxidative stress, oxidative modification of LDL, lipid infiltration, endothelial dysfunction closely interact, forming close vicious circles which leads to metabolic and morphological disturbances, re-modulation of blood vessels, cardiovascular diseases and such complication as cardiac infarction and stroke. Pathogenic peculiarities of atherosclerosis are the theoretic base to the elaboration of therapeutic strategy. Endothelium may be discussed as a new therapeutic target in atherosclerosis. So far as the leukotrienes play an important role in inflammatory processes, it is suggested that the leukotrienes may be as a potential therapeutic target in cardiovascular diseases. PMID:16369071

  5. Defining the Relationship Between Biomarkers of Oxidation and Inflammatory Stress and the Risk for Atherosclerosis in Astronauts During and After Long-Duration Spaceflight

    NASA Technical Reports Server (NTRS)

    Lee, Stuart M. C.; Stenger, Michael B.; Smith, Scott M.; Zwart, Sara R.

    2016-01-01

    Future human space travel will consist primarily of long-duration missions onboard the International Space Station (ISS) or exploration-class missions to Mars, its moons, or nearby asteroids. These missions will expose astronauts to increased risk of oxidative and inflammatory damage from a variety of sources, including radiation, psychological stress, reduced physical activity, diminished nutritional status, and hyperoxic exposure during extravehicular activity. Evidence exists that increased oxidative damage and inflammation can accelerate the development of atherosclerosis.

  6. Analytical validation of accelerator mass spectrometry for pharmaceutical development

    PubMed Central

    Keck, Bradly D; Ognibene, Ted; Vogel, John S

    2011-01-01

    The validation parameters for pharmaceutical analyses were examined for the accelerator mass spectrometry measurement of 14C/C ratio, independent of chemical separation procedures. The isotope ratio measurement was specific (owing to the 14C label), stable across samples storage conditions for at least 1 year, linear over four orders of magnitude with an analytical range from 0.1 Modern to at least 2000 Modern (instrument specific). Furthermore, accuracy was excellent (between 1 and 3%), while precision expressed as coefficient of variation was between 1 and 6% determined primarily by radiocarbon content and the time spent analyzing a sample. Sensitivity, expressed as LOD and LLOQ was 1 and 10 attomoles of 14C, respectively (which can be expressed as compound equivalents) and for a typical small molecule labeled at 10% incorporated with 14C corresponds to 30 fg equivalents. Accelerator mass spectrometry provides a sensitive, accurate and precise method of measuring drug compounds in biological matrices. PMID:21083256

  7. High Temperature μSR Experiments for Accelerator Developments

    NASA Astrophysics Data System (ADS)

    Ohmori, Chihiro; Koda, Akihiro; Miyake, Yasuhiro; Nishiyama, Kusuo; Shimomura, Koichiro; Schnase, Alexander; Ezura, Eiji; Hara, Keigo; Hasegawa, Katsushi; Nomura, Masahiro; Shimada, Taihei; Takata, Koji; Tamura, Fumihiko; Toda, Makoto; Yamamoto, Masanobu; Yoshii, Masahito

    High temperature μSR is a powerful technique to study magnetic materials. In J-PARC accelerator synchrotrons, the Rapid Cycling Synchrotron (RCS) and Main Ring (MR), a unique magnetic alloy-loaded cavity is used for the beam acceleration and much higher field gradient has been achieved. Such high field gradient cavities made a compact RCS possible by reducing the length for beam acceleration. Now, further upgrades of the J-PARC, RF cavities with higher RF voltage and less power loss in the magnetic core are needed for the MR. For the improvements of the magnetic property of magnetic alloy core, the high temperature μSR (muon Spin Rotation/Relaxation) was used to investigate the crystallization process of the material. Based on the measurement results, the test production of the large ring cores of a magnetic alloy, FT3L, was tried. The FT3L is the magnetic alloy which has two times better performance than the present one, FT3M. For the FT3L production, the magnetic annealing is needed to control the easy-magnetized axis of the crystalline. After the success of the test production, a mass production was started in the industry to replace all existing cavities in the MR. The first 5-cell FT3L cavity is assembled for the bench test before the installation in the accelerator tunnel. By the new cavities, the total RF voltage of J-PARC MR will be doubled to increase the beam power for neutrino experiment. In future, the cavities will be also used for the RCS to increase the beam power beyond 1 MW.

  8. Computer assessment of atherosclerosis from angiographic images

    NASA Technical Reports Server (NTRS)

    Selzer, R. H.; Blankenhorn, D. H.; Brooks, S. H.; Crawford, D. W.; Cashin, W. L.

    1982-01-01

    A computer method for detection and quantification of atherosclerosis from angiograms has been developed and used to measure lesion change in human clinical trials. The technique involves tracking the vessel edges and measuring individual lesions as well as the overall irregularity of the arterial image. Application of the technique to conventional arterial-injection femoral and coronary angiograms is outlined and an experimental study to extend the technique to analysis of intravenous angiograms of the carotid and cornary arteries is described.

  9. TRI-SERVICE SITE CHARACTERIZATION AND ANALYSIS PENETROMETER SYSTEM (SCAPS) ACCELERATED SENSOR DEVELOPMENT PROJECT

    EPA Science Inventory

    In 1994, the Strategic Environmental Research and Development Program (SERDP) funded a Tri-Service effort to accelerate the development and fielding of environmental sensing technologies to extend the capabilities of the Site Characterization and Analysis Penetrometer System (SCA...

  10. [Pathogenesis of atherosclerosis: an update on the three main theories].

    PubMed

    Capron, L

    1989-12-30

    The causes and mechanisms of atherosclerosis remain incompletely understood. Almost all the present investigations are still connected with one of the main three historical theories of atherosclerosis: 1) the incrustation theory, as developed by von Rokitansky, has now led to the many studies on the roles of thrombosis and platelets; 2) the irritation theory, as opposed to the preceding one by Virchow and his school, is reviving through the rediscovery that leukocytes are present in the plaques, and that atherosclerosis (Virchow's endarteritis chronica deformans sive nodosa) has the features of a chronic inflammatory reaction; 3) the lipid infiltration theory, as initiated by the experiments of Anitschkov and Chalatov in rabbits fed a cholesterol enriched diet, motivates the huge mass of studies devoted to plasma lipids and their cellular metabolism. This article provides a brief update on each of these three complementary approaches of atherosclerosis. PMID:2698116

  11. Coronary Atherosclerosis: Pathophysiologic Basis for Diagnosis and Management.

    PubMed

    Boudoulas, Konstantinos Dean; Triposciadis, Filippos; Geleris, Paraschos; Boudoulas, Harisios

    2016-01-01

    Coronary atherosclerosis is a long lasting and continuously evolving disease with multiple clinical manifestations ranging from asymptomatic to stable angina, acute coronary syndrome (ACS), heart failure (HF) and sudden cardiac death (SCD). Genetic and environmental factors contribute to the development and progression of coronary atherosclerosis. In this review, current knowledge related to the diagnosis and management of coronary atherosclerosis based on pathophysiologic mechanisms will be discussed. In addition to providing state-of-the-art concepts related to coronary atherosclerosis, special consideration will be given on how to apply data from epidemiologic studies and randomized clinical trials to the individual patient. The greatest challenge for the clinician in the twenty-first century is not in absorbing the fast accumulating new knowledge, but rather in applying this knowledge to the individual patient. PMID:27091673

  12. Development of a 20-MeV Dielectric-Loaded Accelerator Test Facility

    SciTech Connect

    Gold, S.H.; Kinkead, A.K.; Gai, W.; Power, J.G.; Konecny, R.; Jing, C.G.; Tantawi, S.G.; Nantista, C.D.; Hu, Y.; Chen, H.; Tang, C.; Lin, Y.; Bruce, R.W.; Bruce, R.L.; Fliflet, A.W.; Lewis, D.; /Naval Research Lab, Wash., D.C. /LET Corp., Washington /Argonne /SLAC /Tsinghua U., Beijing

    2005-06-22

    This paper describes a joint project by the Naval Research Laboratory (NRL) and Argonne National Laboratory (ANL), in collaboration with the Stanford Linear Accelerator Center (SLAC), to develop a dielectric-loaded accelerator (DLA) test facility powered by a high-power 11.424-GHz magnicon amplifier. The magnicon can presently produce 25 MW of output power in a 250-ns pulse at 10 Hz, and efforts are in progress to increase this to 50 MW. The facility will include a 5 MeV electron inector being developed by the Accelerator Laboratory of Tsinghua University in Beijing, China. The DLA test structures are being developed by ANL, and some have undergone testing at NRL at gradients up to {approx} 8 MV/m. SLAC is developing a means to combine the two magnicon output arms, and to drive an injector and accelerator with separate control of the power ratio and relative phase. RWBruce Associates, Inc., working with NRl, is developing a means to join short ceramic sections into a continuous accelerator tube by ceramic brazing using an intense millimeter-wave beam. The installation and testing of the first dielectric-loaded test accelerator, including injector, DLA structure, and spectrometer, should take place within the next year. The facility will be used for testing DLA structures using a variety of materials and configurations, and also for testing other X-band accelerator concepts. The initial goal is to produce a compact 20 MeV dielectric-loaded test accelerator.

  13. Development of the Accelerator Mass Spectrometry technology at the Comenius University in Bratislava

    NASA Astrophysics Data System (ADS)

    Povinec, Pavel P.; Masarik, Jozef; Ješkovský, Miroslav; Kaizer, Jakub; Šivo, Alexander; Breier, Robert; Pánik, Ján; Staníček, Jaroslav; Richtáriková, Marta; Zahoran, Miroslav; Zeman, Jakub

    2015-10-01

    An Accelerator Mass Spectrometry (AMS) laboratory has been established at the Centre for Nuclear and Accelerator Technologies (CENTA) at the Comenius University in Bratislava comprising of a MC-SNICS ion source, 3 MV Pelletron tandem accelerator, and an analyzer of accelerated ions. The preparation of targets for 14C and 129I AMS measurements is described in detail. The development of AMS techniques for potassium, uranium and thorium analysis in radiopure materials required for ultra-low background underground experiments is briefly mentioned.

  14. Development of a New Diabetes Risk Prediction Tool for Incident Coronary Heart Disease Events: The Multi-Ethnic Study of Atherosclerosis and the Heinz Nixdorf Recall Study

    PubMed Central

    Yeboah, Joseph; Erbel, Raimund; Delaney, Joseph Chris; Nance, Robin; Guo, Mengye; Bertoni, Alain G.; Budoff, Matthew; Moebus, Susanne; Jöckel, Karl-Heinz; Burke, Gregory L; Wong, Nathan D; Lehmann, Nils; Herrington, David M; Möhlenkamp, Stefan; Greenland, Philip

    2014-01-01

    Objective We develop a new diabetes CHD risk estimator using traditional risk factors plus coronary artery calcium (CAC), ankle-brachial index (ABI), high sensitivity C-reactive protein, family history of CHD, and carotid intima-media thickness and compared it with United Kingdom Prospective Diabetes study (UKPDS), Framingham risk and the NCEP/ATP III risk scores in type 2 diabetes mellitus (T2DM). Methods and Results We combined data from T2DM without clinical CVD in the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (N=1343). After a mean follow-up of 8.5 years, 85(6.3%) participants had incident CHD. Among the novel risk markers, CAC best predicted CHD independent of the FRS [hazard ratio: HR (95% CI): log (CAC +25):1.69(1.45 – 1.97), p<0.0001; CAC categories: CAC ≤ 25 as reference, >25 and ≤ 125:2.29(0.87 – 5.95), >125 and ≤ 400: 3.87(1.57– 9.57), >400: 5.97(2.57– 13.84), respectively). The MESA-HNR diabetes CHD risk score has better accuracy for the main outcome versus the FRS or UKPDS [area under curve (AUC) of 0.76 vs. 0.70 and 0.69, respectively; all p<0.05]. The MESA-HNR risk score improved risk classification versus the FRS (net reclassification improvement (NRI) = 0.19 and integrated discrimination improvement (IDI) =0.046, p<0.05) and UKPDS (NRI=0.215 and IDI = 0.046, p<0.05). Compared with the ATP III guidelines, the MESA-HNR score has an NRI of 0.74 for the main outcome. Conclusions This new CHD risk estimator has better discriminative ability for incident CHD than the FRS, UKPDS, and the ATP III/NCEP recommendations in a multi-ethnic cohort with T2DM. PMID:25150939

  15. Current status of carotid ultrasound in atherosclerosis

    PubMed Central

    2016-01-01

    Cardiovascular disease (CVD) primarily caused by atherosclerosis is a major cause of death and disability in developed countries. Sonographic carotid intima-media thickness (CIMT) is widely studied as a surrogate marker for detecting subclinical atherosclerosis for risk prediction and disease progress to guide medical intervention. However, there is no standardized CIMT measurement methodology in clinical studies resulting in inconsistent findings, thereby undermining the clinical value of CIMT. Increasing evidences show that CIMT alone has weak predictive value for CVD while CIMT including plaque presence consistently improves the predictive power. Quantification of plaque burden further enhances the predictive power beyond plaque presence. Sonographic carotid plaque characteristics have been found to be predictive of cerebral ischaemic events. With advances in ultrasound technology, enhanced assessment of carotid plaques is feasible to detect high-risk/vulnerable plaques, and provide risk assessment for ischemic stroke beyond measurement of luminal stenosis. PMID:27429912

  16. Residual acceleration data on IML-1: Development of a data reduction and dissemination plan

    NASA Technical Reports Server (NTRS)

    Rogers, Melissa J. B.; Alexander, J. Iwan D.

    1993-01-01

    The research performed consisted of three stages: (1) identification of sensitive IML-1 experiments and sensitivity ranges by order of magnitude estimates, numerical modeling, and investigator input; (2) research and development towards reduction, supplementation, and dissemination of residual acceleration data; and (3) implementation of the plan on existing acceleration databases.

  17. Jefferson Lab Accelerator Operations Training and Development Program

    SciTech Connect

    Michael A. Epps

    2008-01-23

    The mission of the Jefferson Lab Operations Group is to provide safe and efficient delivery of high quality electron beam for Jefferson Laboratory's nuclear and accelerator physics programs. The Operations staff must be able to setup, transport, maintain, and troubleshoot beam to all three experimental halls in a safe, efficient, and expeditious manner. Due to the nature of shift work, high employee turnover is always as issue. This creates a unique situation where highly trained staff members must quickly be produced and maintained in order to meet the needs of the Laboratory. Some methods used to address this problem will be presented here.

  18. Development of a low-energy beam transport system at KBSI heavy-ion accelerator

    NASA Astrophysics Data System (ADS)

    Bahng, Jungbae; Lee, Byoung-Seob; Sato, Yoichi; Ok, Jung-Woo; Park, Jin Yong; Yoon, Jang-Hee; Choi, Seyong; Won, Mi-Sook; Kim, Eun-San

    2015-01-01

    The Korea Basic Science Institute has developed a heavy ion accelerator for fast neutron radiography [1]. To meet the requirements for fast neutron generation, we have developed an accelerator system that consists of an electron cyclotron resonance ion source (ECR-IS), low-energy beam transport (LEBT) system, radio-frequency quadrupole (RFQ), medium-energy beam transport system, and drift tube linac. In this paper, we present the development of the LEBT system as a part of the heavy ion accelerator system, which operates from the ECR-IS to the RFQ entrance.

  19. Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with (18)F positron emission tomography.

    PubMed

    Scherer, Daniel J; Psaltis, Peter J

    2016-08-01

    Atherosclerosis is characterized by the formation of complex atheroma lesions (plaques) in arteries that pose risk by their flow-limiting nature and propensity for rupture and thrombotic occlusion. It develops in the context of disturbances to lipid metabolism and immune response, with inflammation underpinning all stages of plaque formation, progression and rupture. As the primary disease process responsible for myocardial infarction, stroke and peripheral vascular disease, atherosclerosis is a leading cause of morbidity and mortality on a global scale. A precise understanding of its pathogenic mechanisms is therefore critically important. Integral to this is the role of vascular wall imaging. Over recent years, the rapidly evolving field of molecular imaging has begun to revolutionize our ability to image beyond just the anatomical substrate of vascular disease, and more dynamically assess its pathobiology. Nuclear imaging by positron emission tomography (PET) can target specific molecular and biological pathways involved in atherosclerosis, with the application of (18)Fluoride PET imaging being widely studied for its potential to identify plaques that are vulnerable or high risk. In this review, we discuss the emergence of (18)Fluoride PET as a promising modality for the assessment of coronary atherosclerosis, focusing on the strengths and limitations of the two main radionuclide tracers that have been investigated to date: 2-deoxy-2-((18)F)fluoro-D-glucose ((18)F-FDG) and sodium (18)F-fluoride ((18)F-NaF). PMID:27500093

  20. Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis with 18F positron emission tomography

    PubMed Central

    Psaltis, Peter J.

    2016-01-01

    Atherosclerosis is characterized by the formation of complex atheroma lesions (plaques) in arteries that pose risk by their flow-limiting nature and propensity for rupture and thrombotic occlusion. It develops in the context of disturbances to lipid metabolism and immune response, with inflammation underpinning all stages of plaque formation, progression and rupture. As the primary disease process responsible for myocardial infarction, stroke and peripheral vascular disease, atherosclerosis is a leading cause of morbidity and mortality on a global scale. A precise understanding of its pathogenic mechanisms is therefore critically important. Integral to this is the role of vascular wall imaging. Over recent years, the rapidly evolving field of molecular imaging has begun to revolutionize our ability to image beyond just the anatomical substrate of vascular disease, and more dynamically assess its pathobiology. Nuclear imaging by positron emission tomography (PET) can target specific molecular and biological pathways involved in atherosclerosis, with the application of 18Fluoride PET imaging being widely studied for its potential to identify plaques that are vulnerable or high risk. In this review, we discuss the emergence of 18Fluoride PET as a promising modality for the assessment of coronary atherosclerosis, focusing on the strengths and limitations of the two main radionuclide tracers that have been investigated to date: 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) and sodium 18F-fluoride (18F-NaF). PMID:27500093

  1. Human oral, gut, and plaque microbiota in patients with atherosclerosis

    PubMed Central

    Koren, Omry; Spor, Aymé; Felin, Jenny; Fåk, Frida; Stombaugh, Jesse; Tremaroli, Valentina; Behre, Carl Johan; Knight, Rob; Fagerberg, Björn; Ley, Ruth E.; Bäckhed, Fredrik

    2011-01-01

    Periodontal disease has been associated with atherosclerosis, suggesting that bacteria from the oral cavity may contribute to the development of atherosclerosis and cardiovascular disease. Furthermore, the gut microbiota may affect obesity, which is associated with atherosclerosis. Using qPCR, we show that bacterial DNA was present in the atherosclerotic plaque and that the amount of DNA correlated with the amount of leukocytes in the atherosclerotic plaque. To investigate the microbial composition of atherosclerotic plaques and test the hypothesis that the oral or gut microbiota may contribute to atherosclerosis in humans, we used 454 pyrosequencing of 16S rRNA genes to survey the bacterial diversity of atherosclerotic plaque, oral, and gut samples of 15 patients with atherosclerosis, and oral and gut samples of healthy controls. We identified Chryseomonas in all atherosclerotic plaque samples, and Veillonella and Streptococcus in the majority. Interestingly, the combined abundances of Veillonella and Streptococcus in atherosclerotic plaques correlated with their abundance in the oral cavity. Moreover, several additional bacterial phylotypes were common to the atherosclerotic plaque and oral or gut samples within the same individual. Interestingly, several bacterial taxa in the oral cavity and the gut correlated with plasma cholesterol levels. Taken together, our findings suggest that bacteria from the oral cavity, and perhaps even the gut, may correlate with disease markers of atherosclerosis. PMID:20937873

  2. Development of accelerator mass spectrometer based on a compact cyclotron

    NASA Astrophysics Data System (ADS)

    Kim, J.-W.; Kim, D.-G.

    2011-07-01

    A small cyclotron has been designed for accelerator mass spectrometry, and the injection beam line is constructed as part of prototyping. Mass resolution of the cyclotron is estimated to be around 4000. The design of the cyclotron was performed with orbit-tracking computations using 3D magnetic and electric fields, and beam optics of the injection line was calculated using the codes such as IGUN and TRANSPORT. The radial injection scheme is chosen to place a beam on equilibrium orbit of the cyclotron. The injection line includes an ion source, Einzel lens, rf buncher, 90° dipole magnet, and quadrupole triplet magnet. A carbon beam was extracted from the front part of the injection line. An rf cavity system for the cyclotron was built and tested. A multi channel plates (MCP) detector to measure low-current ion beams was also tested. Design considerations are given to analyzing a few different radioisotopes in form of positive ions as well as negative ions.

  3. Development of a dual layered dielectric-loaded accelerating structure.

    SciTech Connect

    Gai, W.; Liu, W.; Jing, C.; Kanareykin, A.; Antipov, S.; Nenasheva, E.; Schoessow, P.; High Energy Physics; Euclid Techlabs, LLC; Illinois Inst. of Tech.; KEK

    2008-09-01

    Due to the high magnetic field-induced surface currents on its conducting sleeve, a conventional single layer Dielectric-Loaded Accelerating (DLA) structure exhibits a relatively high RF loss. One possible way to solve this problem is to use multilayered DLA structures. In these devices, the RF power attenuation is reduced by making use of the Bragg Fiber concept: the EM fields are well confined by multiple reflections from multiple dielectric layers. This paper presents the design of an X-band dual layer DLA structure as well as the results of bench tests of the device. We will also present results on the design, numerical modeling, and fabrication of structures for coupling RF into multilayer DLAs such as a novel TM{sub 03} mode launcher and a TM{sub 01}-TM{sub 03} mode converter using dielectric-loaded corrugated waveguide.

  4. Coronary atherosclerosis -- a postmortem histopathological study.

    PubMed

    Kumar, S; Kumar, Verma A; Kumar, N; Baranwal, R K; Kumar, Verma R; Singh, M

    2012-01-01

    Cardiovascular disease in general and coronary heart disease in particular remains the leading cause of morbidity and mortality in developed countries. The aim of this study was to look at the prevalence of coronary atherosclerosis, its severity and site of involvement in postmortem hearts. The hearts of 30-60 yrs old, fifty dead victims were considered who died from various natural and unnatural deaths. After autopsy, coronary arteries were inspected grossly and microscopically. Out of all these cases, 10 cases (20 %) showed no pathological lesions. Total distribution of lesions in the coronaries are as follows; 34 (68 %) atheromatous lesions in Left Anterior Descending Artery, 25 (50 %) lesions in the Right Coronary Artery, 18 (36 %) lesions in Left Circumflex. Proximal involvement was more common except in the right coronary artery, which was involved distally. The overall prevalence of coronary atherosclerosis in the present study was comparable with that noted by other investigators in autopsy studied. There is a higher prevalence of atherosclerosis in Indians, which may be due to changes in life-styles and other risks factors (Tab. 1, Ref. 14). Full Text in PDF www.elis.sk. PMID:22502752

  5. Development of a 20 MeV Dielectric-Loaded Test Accelerator

    SciTech Connect

    Gold, S.H.; Kinkead, A.K.; Gai, W.; Power, J.G.; Konecny, R.; Jing, C.; Long, J.; Tantawi, S.G.; Nantista, C.D.; Fliflet, A.W.; Lombardi, M.; Lewis, D.; Bruce, R.W.; /Unlisted

    2007-04-13

    This paper presents a progress report on a joint project by the Naval Research Laboratory (NRL) and Argonne National Laboratory (ANL), in collaboration with the Stanford Linear Accelerator Center (SLAC), to develop a dielectric-loaded test accelerator in the magnicon facility at NRL. The accelerator will be powered by an experimental 11.424-GHz magnicon amplifier that presently produces 25 MW of output power in a {approx}250-ns pulse at up to 10 Hz. The accelerator will include a 5-MeV electron injector originally developed at the Tsinghua University in Beijing, China, and can incorporate DLA structures up to 0.5 m in length. The DLA structures are being developed by ANL, and shorter test structures fabricated from a variety of dielectric materials have undergone testing at NRL at gradients up to {approx}8 MV/m. SLAC has developed components to distribute the power from the two magnicon output arms to the injector and to the DLA accelerating structure with separate control of the power ratio and relative phase. RWBruce Associates, Inc., working with NRL, has investigated means to join short ceramic sections into a continuous accelerator tube by a brazing process using an intense 83-GHz beam. The installation and testing of the first dielectric-loaded test accelerator, including injector, DLA test structure, and spectrometer, should take place within the next year.

  6. Development of a 20 MeV Dielectric-Loaded Test Accelerator

    SciTech Connect

    Gold, Steven H.; Fliflet, Arne W.; Lombardi, Marcie; Kinkead, Allen K.; Gai, Wei; Power, John G.; Konecny, Richard; Long, Jidong; Jing, Chunguang; Tantawi, Sami G.; Nantista, Christopher D.; Bruce, Ralph W.; Lewis, David III

    2006-11-27

    This paper presents a progress report on a joint project by the Naval Research Laboratory (NRL) and Argonne National Laboratory (ANL), in collaboration with the Stanford Linear Accelerator Center (SLAC), to develop a dielectric-loaded test accelerator in the magnicon facility at NRL. The accelerator will be powered by an experimental 11.424-GHz magnicon amplifier that presently produces 25 MW of output power in a {approx}250-ns pulse at up to 10 Hz. The accelerator will include a 5-MeV electron injector originally developed at the Tsinghua University in Beijing, China, and can incorporate DLA structures up to 0.5 m in length. The DLA structures are being developed by ANL, and shorter test structures fabricated from a variety of dielectric materials have undergone testing at NRL at gradients up to {approx}8 MV/m. SLAC has developed components to distribute the power from the two magnicon output arms to the injector and to the DLA accelerating structure with separate control of the power ratio and relative phase. RWBruce Associates, Inc., working with NRL, has investigated means to join short ceramic sections into a continuous accelerator tube by a brazing process using an intense 83-GHz beam. The installation and testing of the first dielectric-loaded test accelerator, including injector, DLA test structure, and spectrometer, should take place within the next year.

  7. Fe-Radiation-Induced Alterations in Circulating Leukocyte Populations in the ApoE Mouse Atherosclerosis Model are Temporary

    NASA Astrophysics Data System (ADS)

    Yu, Tao; Yu, Shaohua; Parks, Brian W.; Gupta, Kiran; Wu, Xing; Khaled, Saman; Chang, Polly Y.; Srivastava, Roshni; Kabarowski, Janusz H. S.; Kucik, Dennis F.

    2008-06-01

    Radiation is associated with an increased risk of heart disease and stroke, likely due in part to vascular inflammation. One model used to understand this is the apoE mouse, where gamma irradiation accelerates development of atherosclerosis. Less is known, though, about the effects of high linear energy transfer (LET) radiation, such as 56Fe, likely to be encountered by astronauts in deep space. Radiation, however, also affects leukocyte numbers. For example, whole-body 56Fe irradiation has been shown to decrease circulating B-cells and T-cells, but whether this was due to radiation of the thymus, of the bone marrow, or both was not determined. We irradiated ApoE mice with 56Fe focused to the aorta and carotids to determine how irradiation of the thymus with 56Fe affects circulating lymphocyte number, and ultimately to determine the effect of iron ion irradiation on development of atherosclerosis. We found that only T-cells were affected at 13 weeks post-irradiation, but even these recovered at 40 weeks, suggesting that effects on the immune system are limited and temporary. Analysis of atherosclerosis development is pending sacrifice and histological analysis of irradiated mice.

  8. FETAL DEXAMETHASONE EXPOSURE ACCELERATES DEVELOPMENT OF RENAL FUNCTION: RELATIONSHIP TO DOSE, CELL DIFFERENTIATION AND GROWTH INHIBITION

    EPA Science Inventory

    Fetal exposure to high doses of glucocorticoids slows cellular development and impairs organ performance, in association with growth retardation. evertheless, low doses of glucocorticoids may enhance cell differentiation and accelerate specific functions. he current study examine...

  9. NASA - 77M prototype hall thruster built under the High Voltage Hall accelerator development project

    NASA Technical Reports Server (NTRS)

    2005-01-01

    NASA - 77M prototype hall thruster built under the High Voltage Hall accelerator development project funded by the Science Mission Directorate ; potential use is propulsion for deep space science missions

  10. Development of High Power Vacuum Tubes for Accelerators and Plasma Heating

    NASA Astrophysics Data System (ADS)

    Srivastava, Vishnu

    2012-11-01

    High pulsed power magnetrons and klystrons for medical and industrial accelerators, and high CW power klystrons and gyrotrons for plasma heating in tokamak, are being developed at CEERI. S-band 2.0MW pulsed tunable magnetrons of centre frequency 2856MHz and 2998 MHz were developed, and S-band 2.6MW pulsed tunable magnetron is being developed for medical LINAC, and 3MW pulsed tunable magnetron is being developed for industrial accelerator. S-band (2856MHz), 5MW pulsed klystron was developed for particle accelerator, and S-band 6MW pulsed klystron is under development for 10MeV industrial accelerator. 350MHz, 100kW (CW) klystron is being developed for proton accelerator, and C-band 250kW (CW) klystron is being developed for plasma heating. 42GHz, 200kW (CW/Long pulse) gyrotron is under development for plasma heating. Plasma filled tubes are also being developed for switching. 25kV/1kA and 40kV/3kA thyratrons were developed for high voltage high current switching in pulse modulators for magnetrons and klystrons. 25kV/3kA Pseudospark switch of current rise time of 1kA/|a-sec and pulse repetition rate of 500Hz is being developed. Plasma assisted high power microwave device is also being investigated.

  11. EuCARD2: enhanced accelerator research and development in Europe

    NASA Astrophysics Data System (ADS)

    Romaniuk, Ryszard S.

    2013-10-01

    Accelerator science and technology is one of a key enablers of the developments in the particle physic, photon physics and also applications in medicine and industry. EuCARD2 is an European research project which will be realized during 2013-2017 inside the EC FP7 framework. The project concerns the development and coordination of European Accelerator Research and Development. The project is particularly important, to a number of domestic laboratories, due to some plans to build large accelerator infrastructure in Poland. Large accelerator infrastructure of fundamental and applied research character stimulates around it the development and industrial applications as well as biomedical of advanced accelerators, material research and engineering, cryo-technology, mechatronics, robotics, and in particular electronics - like networked measurement and control systems, sensors, computer systems, automation and control systems. The paper presents a digest of the European project EuCARD2 which is Enhanced European Coordination for Accelerator Research and Development. The paper presents a digest of the research results and assumptions in the domain of accelerator science and technology in Europe, shown during the final fourth annual meeting of the EuCARD - European Coordination of Accelerator R&D, and the kick-off meeting of the EuCARD2. There are debated a few basic groups of accelerator systems components like: measurement - control networks of large geometrical extent, multichannel systems for large amounts of metrological data acquisition, precision photonic networks of reference time, frequency and phase distribution, high field magnets, superconducting cavities, novel beam collimators, etc. The paper bases on the following materials: Internet and Intranet documents combined with EuCARD2, Description of Work FP7 EuCARD-2 DoW-312453, 2013-02-13, and discussions and preparatory materials worked on by Eucard-2 initiators.

  12. Nitric oxide function in atherosclerosis

    PubMed Central

    Matthys, K. E.

    1997-01-01

    Atherosclerosis is a chronic inflammatory process in the intima of conduit arteries, which disturbs the endothelium-dependent regulation of the vascular tone by the labile liposoluble radical nitric oxide (NO) formed by the constitutive endothelial nitric oxide synthase (eNOS). This defect predisposes to coronary vasospasm and cardiac ischaemia, with anginal pain as the typical clinical manifestation. It is now appreciated that endothelial dysfunction is an early event in atherogenesis and that it may also involve the microcirculation, in which atherosclerotic lesions do not develop. On the other hand, the inflammatory environment in atherosclerotic plaques may result in the expression of the inducible NO synthase (iNOS) isozyme. Whether the dysfunction in endothelial NO production is causal to, or the result of, atherosclerotic lesion formation is still highly debated. Most evidence supports the hypothesis that constitutive endothelial NO release protects against atherogenesis e.g. by preventing smooth muscle cell proliferation and leukocyte adhesion. Nitric oxide generated by the inducible isozyme may be beneficial by replacing the failing endothelial production but excessive release may damage the vascular wall cells, especially in combination with reactive oxygen intermediates. PMID:18472828

  13. [Is atherosclerosis an autoimmunological process?].

    PubMed

    Partyka, Ł; Hartwich, J; Kieć-Wilk, B; Polus, A; Wybrańska, I; Dembińska-Kieć, A

    2001-01-01

    The theories formulated to explain atherogenesis evolved from simple vessel wall lipid accumulation assumption to endothelial dysfunction with adverse vascular wall remodelling hypothesis. The theory that has been accepted lately integrates the former hypotheses and allows for introducing the local immunological activation concept. This immunological activation is initiated by negatively charged and oxidatively modified lipids (e.g. oxPAPC) and their complexes with proteins (like beta 2-GP I). Antibodies and cellular response against chaperonins: HSP 60 and their analogues from bacterial pathogens such as HSP 65, GroEi etc.) as well as release of cytokines, adhesion molecules and inflammatory mediators (CD 40/CD 40-L, IL 15, IFN gamma, IL 1 beta, TNF alpha) also take part in the process. Another important element of atherogenesis is the pathological angiogenic response within the plaque connected with the expression of angiogenic growth factors (such as VEGF, bFGF and PDGF), metallo-proteinases and local hemostasis regulators. This complex activation of local inflammatory and immunological process initiates such phenomena as development of unstable plaque, vascular remodelling, vessel lumen constriction and ischemic, thromboembolic complications of atherosclerosis. PMID:12041024

  14. Role of infections in atherosclerosis.

    PubMed

    Valtonen, V V

    1999-11-01

    A growing amount of epidemiologic, experimental, and clinical evidence has linked infection as a risk factor to variousatherosclerotic diseases including acute myocardial infarction and cerebral infarction. Bacteremic infections with and without endocarditis carry a high risk for both stroke and acute myocardial infarction. During the last decade, chronic bacterial infections such as Chlamydia pneumoniae and dental infections have been associated as risk factors for various atherosclerotic diseases. These chronic bacterial infections are risk factors for acute cardiovascular events, but they may also have some role in the etiopathogenesis of atherosclerotic process itself. There are many known mechanisms that might explain the observed association of infection and atherosclerotic diseases, but it is probable that these mechanisms are complex and multifactorial and probably differ from infection to infection and from patient to patient. Infection theory is by no means against classic risk factor theory in the etiopathogenesis of atherosclerosis. Infection may also act as a synergistic risk factor together with classic risk factors in the development of various atherosclerotic diseases. PMID:10539842

  15. Superoxide and peroxynitrite in atherosclerosis.

    PubMed Central

    White, C R; Brock, T A; Chang, L Y; Crapo, J; Briscoe, P; Ku, D; Bradley, W A; Gianturco, S H; Gore, J; Freeman, B A

    1994-01-01

    The role of reactive oxygen species in the vascular pathology associated with atherosclerosis was examined by testing the hypothesis that impaired vascular reactivity results from the reaction of nitric oxide (.NO) with superoxide (O2-), yielding the oxidant peroxynitrite (ONOO-). Contractility studies were performed on femoral arteries from rabbits fed a cholesterol-supplemented diet. Cholesterol feeding shifted the EC50 for acetylcholine (ACh)-induced relaxation and impaired the maximal response to ACh. We used pH-sensitive liposomes to deliver CuZn superoxide dismutase (SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) to critical sites of .NO reaction with O2-. Intravenously injected liposomes (3000 units of SOD per ml) augmented ACh-induced relaxation in the cholesterol-fed group to a greater extent than in controls. Quantitative immunocytochemistry demonstrated enhanced distribution of SOD in both endothelial and vascular smooth muscle cells as well as in the extracellular matrix. SOD activity in vessel homogenates of liposome-treated rabbits was also increased. Incubation of beta very low density lipoprotein with ONOO- resulted in the rapid formation of conjugated dienes and thiobarbituric acid-reactive substances. Our results suggest that the reaction of O2- with .NO is involved in the development of atherosclerotic disease by yielding a potent mediator of lipoprotein oxidation, as well as by limiting .NO stimulation of vascular smooth muscle guanylate cyclase activity. Images PMID:8302829

  16. The chylomicron: relationship to atherosclerosis.

    PubMed

    Tomkin, Gerald H; Owens, Daphne

    2012-01-01

    The B-containing lipoproteins are the transporters of cholesterol, and the evidence suggests that the apo B48-containing postprandial chylomicron particles and the triglyceride-rich very low density lipoprotein (VLDL) particles play an important part in the development of the plaque both directly and indirectly by their impact on LDL composition. The ratio of dietary to synthesised cholesterol is variable but tightly regulated: hence intervention with diet at best reduces serum cholesterol by <20% andusually <10%. Statins are the mainstay of cholesterol reduction therapy, but they increase cholesterol absorption, an example of the relationship between synthesis and absorption. Inhibition of cholesterol absorption with Ezetimibe, an inhibitor of Niemann Pick C1-like 1 (NPC1-L1), the major regulator of cholesterol absorption, increases cholesterol synthesis and hence the value of adding an inhibitor of cholesterol absorption to an inhibitor of cholesterol synthesis. Apo B48, the structural protein of the chylomicron particle, is synthesised in abundance so that the release of these particles is dependent on the amount of cholesterol and triglyceride available in the intestine. This paper will discuss cholesterol absorption and synthesis, chylomicron formation, and the effect of postprandial lipoproteins on factors involved in atherosclerosis. PMID:22007304

  17. Development of a Compact Dielectric-Loaded Test Accelerator at 11.4 GHz

    SciTech Connect

    Gold, S. H.; Fliflet, A. W.; Kinkead, A. K.; Gai, W.; Power, J. G.; Konecny, R.; Jing, C.

    2009-01-22

    This paper presents a progress report on the development of a dielectric-loaded test accelerator in the Magnicon Facility at the Naval Research Laboratory (NRL). The accelerator will be powered by an 11.4-GHz magnicon amplifier that provides up to 25 MW of output power in a {approx}250-ns pulse at up to 10 Hz. The accelerator includes a 5-MeV electron injector originally developed at the Tsinghua University in Beijing, China, and can incorporate dielectric-loaded accelerating (DLA) structures of up to 0.5 m in length. The DLA structures are being developed by Argonne National Laboratory and Euclid Techlabs, and shorter test structures fabricated from a variety of dielectric materials have undergone rf testing at NRL at accelerating gradients up to 15 MV/m. The first stage of the accelerator, including the 5-MeV injector, has recently begun operation, and initial operation of the complete dielectric-loaded test accelerator, including injector, DLA test structure, and spectrometer, should take place within the next year.

  18. Atherosclerosis in parrots. A review.

    PubMed

    Bavelaar, F J; Beynen, A C

    2004-06-01

    Atherosclerosis is a common disease in parrots. The disease is found in all common parrot species, but especially in African Grey parrots and Amazons. It is a disease of older birds that is seen in both males and females. The most common sign is sudden death, but clinical symptoms that can be found include dyspnea, lethargy and nervous signs, such as paresis and collapses. Because the clinical signs are seldomly seen, it is difficult to diagnose atherosclerosis and therefore it is mostly an unexpected finding at necropsy. Age and species are determinants of atherosclerosis in parrots. Suggested risk factors include an elevated plasma cholesterol level, diet composition, social stress and inactivity, but research is needed to confirm this. PMID:15230050

  19. Rate of Atherosclerosis Progression in ApoE−/− Mice Long After Discontinuation of Cola Beverage Drinking

    PubMed Central

    Otero-Losada, Matilde; Cao, Gabriel; Mc Loughlin, Santiago; Rodríguez-Granillo, Gastón; Ottaviano, Graciela; Milei, José

    2014-01-01

    This study was conducted in order to evaluate the effect of cola beverages drinking on atherosclerosisand test the hypothesis whether cola beverages consumption at early life stages might affect the development and progression of atherosclerosis later in life. ApoE−/− C57BL/6J mice (8 week-old) were randomized in 3 groups (n = 20 each) according to free accessto water (W), sucrose sweetened carbonated cola drink(C) or aspartame-acesulfame K sweetened carbonated ‘light’ cola drink (L)for the next 8 weeks. Drinking treatment was ended by switching C and L groups to drinking water. Four mice per group and time were sequentially euthanized: before treatment (8weeks-old), at the end of treatment (16 weeks-old) and after treatment discontinuation (20 weeks-old, 24 weeks-old, 30 week-old mice). Aortic roots and livers were harvested, processed for histology and serial cross-sections were stained. Aortic plaque area was analyzed and plaque/media-ratio was calculated. Early consumption of cola drinks accelerated atherosclerotic plaque progression favoring the interaction between macrophages and myofibroblasts, without the participation of either T lymphocytes or proliferative activity. Plaque/media-ratio varied according to drink treatment (F2,54 = 3.433, p<0.04) and mice age (F4,54 = 5.009, p<0.03) and was higher in C and L groups compared with age-matched W group (p<0.05 at 16 weeks and 20 weeks, p<0.01 at 24 weeks and 30 weeks). Natural evolution of atherosclerosis in ApoE−/− mice (W group) evidenced atherosclerosis acceleration in parallel with a rapid increase in liver inflammation around the 20 weeks of age. Cola drinking within the 8–16 weeks of age accelerated atherosclerosis progression in ApoE−/− mice favoring aortic plaque enlargement (inward remodeling) over media thinning all over the study time. Data suggest that cola drinking at early life stages may predispose to atherosclerosis progression later in life in ApoE−/− mice

  20. Group living accelerates bed bug (Hemiptera: Cimicidae) development.

    PubMed

    Saenz, Virna L; Santangelo, Richard G; Vargo, Edward L; Schal, Coby

    2014-01-01

    For many insect species, group living provides physiological and behavioral benefits, including faster development. Bed bugs (Cimex lectularius L.) live in aggregations composed of eggs, nymphs, and adults of various ages. Our aim was to determine whether bed bug nymphs reared in groups develop faster than solitary nymphs. We reared first instars either in isolation or in groups from hatching to adult emergence and recorded their development time. In addition, we investigated the effects of group housing on same-age nymphs versus nymphs reared with adults. Nymphal development was 2.2 d faster in grouped nymphs than in solitary-housed nymphs, representing 7.3% faster overall development. However, this grouping effect did not appear to be influenced by group composition. Thus, similar to other gregarious insect species, nymph development in bed bugs is faster in aggregations than in isolation. PMID:24605482

  1. How Can Atherosclerosis Be Prevented or Delayed?

    MedlinePlus

    ... page from the NHLBI on Twitter. How Can Atherosclerosis Be Prevented or Delayed? Taking action to control ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  2. Developments in laser wakefield accelerators: From single-stage to two-stage

    NASA Astrophysics Data System (ADS)

    Li, Wen-Tao; Wang, Wen-Tao; Liu, Jian-Sheng; Wang, Cheng; Zhang, Zhi-Jun; Qi, Rong; Yu, Chang-Hai; Li, Ru-Xin; Xu, Zhi-Zhan

    2015-01-01

    Laser wakefield accelerators (LWFAs) are compact accelerators which can produce femtosecond high-energy electron beams on a much smaller scale than the conventional radiofrequency accelerators. It is attributed to their high acceleration gradient which is about 3 orders of magnitude larger than the traditional ones. The past decade has witnessed the major breakthroughs and progress in developing the laser wakfield accelerators. To achieve the LWFAs suitable for applications, more and more attention has been paid to optimize the LWFAs for high-quality electron beams. A single-staged LWFA does not favor generating controllable electron beams beyond 1 GeV since electron injection and acceleration are coupled and cannot be independently controlled. Staged LWFAs provide a promising route to overcome this disadvantage by decoupling injection from acceleration and thus the electron-beam quality as well as the stability can be greatly improved. This paper provides an overview of the physical conceptions of the LWFA, as well as the major breakthroughs and progress in developing LWFAs from single-stage to two-stage LWFAs. Project supported by the National Natural Science Foundation of China (Grant Nos. 11127901, 11425418, and 61221064), the National Basic Research Program of China (Grant No. 2011CB808100), and the Science and Technology Talent Project of Shanghai City, China (Grant Nos. 12XD1405200 and 12ZR1451700).

  3. Accelerating NASA GN&C Flight Software Development

    NASA Technical Reports Server (NTRS)

    Tamblyn, Scott; Henry, Joel; Rapp, John

    2010-01-01

    When the guidance, navigation, and control (GN&C) system for the Orion crew vehicle undergoes Critical Design Review (CDR), more than 90% of the flight software will already be developed - a first for NASA on a project of this scope and complexity. This achievement is due in large part to a new development approach using Model-Based Design.

  4. Imaging and Nanomedicine in Inflammatory Atherosclerosis

    PubMed Central

    Mulder, Willem J. M.; Jaffer, Farouc A.; Fayad, Zahi A.; Nahrendorf, Matthias

    2014-01-01

    Bioengineering provides unique opportunities to better understand and manage atherosclerotic disease. The field is entering a new era that merges the latest biological insights into inflammatory disease processes with targeted imaging and nanomedicine. Preclinical cardiovascular molecular imaging allows the in vivo study of targeted nanotherapeutics specifically directed toward immune system components that drive atherosclerotic plaque development and complication. The first multicenter trials highlight the potential contribution of multimodality imaging to more efficient drug development. This review describes how the integration of engineering, nanotechnology, and cardiovascular immunology may yield precision diagnostics and efficient therapeutics for atherosclerosis and its ischemic complications. PMID:24898749

  5. Endoplasmic reticulum stress and atherosclerosis

    PubMed Central

    Hotamisligil, Gökhan S

    2010-01-01

    Atherosclerosis and related cardiovascular diseases represent one of the greatest threats to human health worldwide. Despite important progress in prevention and treatment, these conditions still account for one third of all deaths annually. Often presented together with obesity, insulin resistance and type 2 diabetes, these chronic diseases are strongly influenced by pathways that lie at the interface of chronic inflammation and nutrient metabolism. Here I discuss recent advances in the study of endoplasmic reticulum stress as one mechanism that links immune response with nutrient sensing in the pathogenesis of atherosclerosis and its complications. PMID:20376052

  6. Latest Development in Superconducting RF Structures for beta=1 Particle Acceleration

    SciTech Connect

    Peter Kneisel

    2006-06-26

    Superconducting RF technology is since nearly a decade routinely applied to different kinds of accelerating devices: linear accelerators, storage rings, synchrotron light sources and FEL's. With the technology recommendation for the International Linear Collider (ILC) a year ago, new emphasis has been placed on improving the performance of accelerating cavities both in Q-value and in accelerating gradients with the goal to achieve performance levels close to the fundamental limits given by the material parameters of the choice material, niobium. This paper will summarize the challenges to SRF technology and will review the latest developments in superconducting structure design. Additionally, it will give an overview of the newest results and will report on the developments in alternative materials and technologies.

  7. Periodontal Disease-Induced Atherosclerosis and Oxidative Stress

    PubMed Central

    Kurita-Ochiai, Tomoko; Jia, Ru; Cai, Yu; Yamaguchi, Yohei; Yamamoto, Masafumi

    2015-01-01

    Periodontal disease is a highly prevalent disorder affecting up to 80% of the global population. Recent epidemiological studies have shown an association between periodontal disease and cardiovascular disease, as oxidative stress plays an important role in chronic inflammatory diseases such as periodontal disease and cardiovascular disease. In this review, we focus on the mechanisms by which periodontopathic bacteria cause chronic inflammation through the enhancement of oxidative stress and accelerate cardiovascular disease. Furthermore, we comment on the antioxidative activity of catechin in atherosclerosis accelerated by periodontitis. PMID:26783845

  8. Why did ancient people have atherosclerosis?: from autopsies to computed tomography to potential causes.

    PubMed

    Thomas, Gregory S; Wann, L Samuel; Allam, Adel H; Thompson, Randall C; Michalik, David E; Sutherland, M Linda; Sutherland, James D; Lombardi, Guido P; Watson, Lucia; Cox, Samantha L; Valladolid, Clide M; Abd El-Maksoud, Gomaa; Al-Tohamy Soliman, Muhammad; Badr, Ibrahem; el-Halim Nur el-Din, Abd; Clarke, Emily M; Thomas, Ian G; Miyamoto, Michael I; Kaplan, Hillard S; Frohlich, Bruno; Narula, Jagat; Stewart, Alexandre F R; Zink, Albert; Finch, Caleb E

    2014-06-01

    Computed tomographic findings of atherosclerosis in the ancient cultures of Egypt, Peru, the American Southwest and the Aleutian Islands challenge our understanding of the fundamental causes of atherosclerosis. Could these findings be true? Is so, what traditional risk factors might be present in these cultures that could explain this apparent paradox? The recent computed tomographic findings are consistent with multiple autopsy studies dating as far back as 1852 that demonstrate calcific atherosclerosis in ancient Egyptians and Peruvians. A nontraditional cause of atherosclerosis that could explain this burden of atherosclerosis is the microbial and parasitic inflammatory burden likely to be present in ancient cultures inherently lacking modern hygiene and antimicrobials. Patients with chronic systemic inflammatory diseases of today, including systemic lupus erythematosus, rheumatoid arthritis, and human immunodeficiency virus infection, experience premature atherosclerosis and coronary events. Might the chronic inflammatory load of ancient times secondary to infection have resulted in atherosclerosis? Smoke inhalation from the use of open fires for daily cooking and illumination represents another potential cause. Undiscovered risk factors could also have been present, potential causes that technologically cannot currently be measured in our serum or other tissue. A synthesis of these findings suggests that a gene-environmental interplay is causal for atherosclerosis. That is, humans have an inherent genetic susceptibility to atherosclerosis, whereas the speed and severity of its development are secondary to known and potentially unknown environmental factors. PMID:25667093

  9. Sustainable Energy in Remote Indonesian Grids. Accelerating Project Development

    SciTech Connect

    Hirsch, Brian; Burman, Kari; Davidson, Carolyn; Elchinger, Michael; Hardison, R.; Karsiwulan, D.; Castermans, B.

    2015-06-30

    Sustainable Energy for Remote Indonesian Grids (SERIG) is a U.S. Department of Energy (DOE) funded initiative to support Indonesia’s efforts to develop clean energy and increase access to electricity in remote locations throughout the country. With DOE support, the SERIG implementation team consists of the National Renewable Energy Laboratory (NREL) and Winrock International’s Jakarta, Indonesia office. Through technical assistance that includes techno-economic feasibility evaluation for selected projects, government-to-government coordination, infrastructure assessment, stakeholder outreach, and policy analysis, SERIG seeks to provide opportunities for individual project development and a collective framework for national replication office.

  10. Effects of ezetimibe on atherosclerosis in preclinical models.

    PubMed

    Davis, Harry R; Lowe, Robert S; Neff, David R

    2011-04-01

    Ezetimibe (Zetia(®), Ezetrol(®), Merck, Whitehouse Station, NJ) is a potent inhibitor of sterol absorption, which selectively blocks the uptake of biliary and dietary cholesterol in the small intestine. Clinical trials have demonstrated the beneficial effects of ezetimibe on the reduction of atherogenic lipoproteins and the attainment of guideline-recommended lipid levels. Direct evidence that these improvements translate to a reduction in atherosclerosis or cardiovascular events is limited, although reductions in major atherosclerotic events that are consistent with the LDL-C lowering achieved have recently been presented for patients with chronic kidney disease treated with ezetimibe/simvastatin 10/20mg in the SHARP trial. Animal models of atherosclerosis have played a central role in defining the mechanisms involved in initiation and development of disease and have been used in drug development to evaluate potential therapeutic efficacy. The effect of ezetimibe on atherosclerosis has been examined in several of these animal model systems. ApoE knockout mice develop severe hypercholesterolemia and premature atherosclerosis with features similar to that seen in humans and techniques ranging from gross visualization of plaque to high-resolution MRI have demonstrated the consistent ability of ezetimibe to significantly inhibit atherosclerosis. sr-b1(-/-)/apoE(-/-) double knockout mice exhibit additional characteristics common to human coronary heart disease (CHD), and the one study of ezetimibe in sr-b1(-/-)/apoE(-/-) mice showed a significant reduction in aortic sinus plaque (57%), coronary arterial occlusion (68%), myocardial fibrosis (57%), and cardiomegaly (12%) compared with untreated controls. The effects of ezetimibe have also been evaluated in ldlr(-/-)/apoE(-/-) double knockout mice, demonstrating that functional LDL receptors were not required for ezetimibe-mediated reduction of plasma cholesterol or atherosclerosis. For the few studies that have been

  11. Serine protease inhibitor A3 in atherosclerosis and aneurysm disease.

    PubMed

    Wågsäter, Dick; Johansson, Daniel; Fontaine, Vincent; Vorkapic, Emina; Bäcklund, Alexandra; Razuvaev, Anton; Mäyränpää, Mikko I; Hjerpe, Charlotta; Caidahl, Kenneth; Hamsten, Anders; Franco-Cereceda, Anders; Wilbertz, Johannes; Swedenborg, Jesper; Zhou, Xinghua; Eriksson, Per

    2012-08-01

    Remodeling of extracellular matrix (ECM) plays an important role in both atherosclerosis and aneurysm disease. Serine protease inhibitor A3 (serpinA3) is an inhibitor of several proteases such as elastase, cathepsin G and chymase derived from mast cells and neutrophils. In this study, we investigated the putative role of serpinA3 in atherosclerosis and aneurysm formation. SerpinA3 was expressed in endothelial cells and medial smooth muscle cells in human atherosclerotic lesions and a 14-fold increased expression of serpinA3n mRNA was found in lesions from Apoe-/- mice compared to lesion-free vessels. In contrast, decreased mRNA expression (-80%) of serpinA3 was found in biopsies of human abdominal aortic aneurysm (AAA) compared to non-dilated aortas. Overexpression of serpinA3n in transgenic mice did not influence the development of atherosclerosis or CaCl2-induced aneurysm formation. In situ zymography analysis showed that the transgenic mice had lower cathepsin G and elastase activity, and more elastin in the aortas compared to wild-type mice, which could indicate a more stable aortic phenotype. Differential vascular expression of serpinA3 is clearly associated with human atherosclerosis and AAA but serpinA3 had no major effect on experimentally induced atherosclerosis or AAA development in mouse. However, serpinA3 may be involved in a phenotypic stabilization of the aorta. PMID:22580763

  12. Fast Track Teaching: Beginning the Experiment in Accelerated Leadership Development

    ERIC Educational Resources Information Center

    Churches, Richard; Hutchinson, Geraldine; Jones, Jeff

    2009-01-01

    This article provides an overview of the development of the Fast Track teaching programme and personalised nature of the training and support that has been delivered. Fast Track teacher promotion rates are compared to national statistics demonstrating significant progression for certain groups, particularly women. (Contains 3 tables and 3 figures.)

  13. [The infection theory in atherosclerosis].

    PubMed

    Capron, L; Wyplosz, B

    1998-10-01

    Atherosclerosis displays all the features of a chronic inflammatory process. Aggressions that ignite and fuel atherosclerotic inflammation warrant keen attention. Infection is a potential clue, implying microbes with certain discrete characteristics: a wide epidemiologic distribution, a tropism for the arterial wall, and an aptitude for persistence, latency and recurrence. The infectious theory has built up from the pioneering observations of Fabricant et al. (1978) on the arterial lesions provoked by Marek's disease herpesvirus in chicken. So far one virus (cytomegalovirus) and two bacteria (Chlamydia pneumoniae and Helicobacter pylori) have been implicated in human atherosclerosis, based upon experimental, sero-epidemiologic, or pathologic evidence. None of these potential contributions has yet been established beyond reasonable doubt. However, grounded on the suspicion about C. pneumoniae, provocative therapeutic evidence has added recently: according to two pilot studies, treatment with macrolide antibiotics appear to improve the prognosis of coronary artery disease in both its chronic and acute forms. If ongoing larger-scale studies confirm these preliminary results, a novel era will open in our capacity for explaining, treating and preventing atherosclerosis. An infectious aetiology of atherosclerosis is now to be considered earnestly, and is already being submitted to more intensive clinical and experimental investigation. PMID:9833076

  14. Vitamin K Intake and Atherosclerosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been hypothesized that insufficient intake of vitamin K may increase soft tissue calcification due to impaired gamma-carboxylation of the vitamin K-dependent protein, matrix gamma-carboxyglutamic acid (MGP). The evidence to support this putative role of vitamin K intake in atherosclerosis is ...

  15. Development of polarized ion source for the JINR accelerator complex

    NASA Astrophysics Data System (ADS)

    Fimushkin, V. V.; Kovalenko, A. D.; Kutuzova, L. V.; Prokofichev, Yu V.; Shutov, B.; Belov, A. S.; Zubets, V. N.; Turbabin, A. V.

    2016-02-01

    Status of the JINR polarized ion source development is described. The source is under tests at the test-bench of LHEP, JINR. A charge-exchange plasma ionizer has been tested initially without a storage cell in the ionization region. An unpolarized deuterium ion beam with peak current of 160 mA, 23 keV energy, pulse duration of 100 μs and repetition rate of 1 Hz has been extracted from the ionizer. With a free polarized atomic hydrogen beam injected into the ionizer a polarized proton beam with peak current of 1.4 mA has been obtained. The nearest plans for the source development include tests of the ionizer with the storage cell and tuning of the high frequency transition units installed in their operating position with a Breit-Rabi polarimeter.

  16. Computational Tools for Accelerating Carbon Capture Process Development

    SciTech Connect

    Miller, David

    2013-01-01

    The goals of the work reported are: to develop new computational tools and models to enable industry to more rapidly develop and deploy new advanced energy technologies; to demonstrate the capabilities of the CCSI Toolset on non-proprietary case studies; and to deploy the CCSI Toolset to industry. Challenges of simulating carbon capture (and other) processes include: dealing with multiple scales (particle, device, and whole process scales); integration across scales; verification, validation, and uncertainty; and decision support. The tools cover: risk analysis and decision making; validated, high-fidelity CFD; high-resolution filtered sub-models; process design and optimization tools; advanced process control and dynamics; process models; basic data sub-models; and cross-cutting integration tools.

  17. Project development teams: a novel mechanism for accelerating translational research.

    PubMed

    Sajdyk, Tammy J; Sors, Thomas G; Hunt, Joe D; Murray, Mary E; Deford, Melanie E; Shekhar, Anantha; Denne, Scott C

    2015-01-01

    The trend in conducting successful biomedical research is shifting from individual academic labs to coordinated collaborative research teams. Teams of experienced investigators with a wide variety of expertise are now critical for developing and maintaining a successful, productive research program. However, assembling a team whose members have the right expertise requires a great deal of time and many resources. To assist investigators seeking such resources, the Indiana Clinical and Translational Sciences Institute (Indiana CTSI) created the Project Development Teams (PDTs) program to support translational research on and across the Indiana University-Purdue University Indianapolis, Indiana University, Purdue University, and University of Notre Dame campuses. PDTs are multidisciplinary committees of seasoned researchers who assist investigators, at any stage of research, in transforming ideas/hypotheses into well-designed translational research projects. The teams help investigators capitalize on Indiana CTSI resources by providing investigators with, as needed, mentoring and career development; protocol development; pilot funding; institutional review board, regulatory, and/or nursing support; intellectual property support; access to institutional technology; and assistance with biostatistics, bioethics, recruiting participants, data mining, engaging community health, and collaborating with other investigators.Indiana CTSI leaders have analyzed metrics, collected since the inception of the PDT program in 2008 from both investigators and team members, and found evidence strongly suggesting that the highly responsive teams have become an important one-stop venue for facilitating productive interactions between basic and clinical scientists across four campuses, have aided in advancing the careers of junior faculty, and have helped investigators successfully obtain external funds. PMID:25319172

  18. Photoneutron target development for the RPI linear accelerator

    NASA Astrophysics Data System (ADS)

    Overberg, M. E.; Moretti, B. E.; Slovacek, R. E.; Block, R. C.

    1999-12-01

    Two new photoneutron targets have been developed for neutron time-of-flight experiments, the axial water-moderated target (AWMT) and the bare bounce target (BBT). These targets operate without any lead shielding nearby and both have superior neutron resolution compared to the older bounce target. The BBT has been selected over the AWMT for general time-of-flight measurements because it exhibited lower neutron background in the keV energy region.

  19. Accelerated field facility development for hot sour gas

    SciTech Connect

    Kuntz, L.K.

    1983-10-01

    This paper presents the chronological plan by which a grass roots sweetening facility was constructed in a minimum amount of time. The facility design was based on production with 9% carbon dioxide and 40 ppm hydrogen sulfide. Flowing wellhead temperatures were predicted to be approximately 300/sup 0/F with flowing wellhead pressures to 11,500 psi. The production facility, with a current total nominal capacity of 100 MMcf/D, was installed as five separate parallel sweetening units. The units were put on-stream in phases in order to maintain a sweetening capacity schedule compatible with wells being put on production. The first units were available for service in three months. All five units were complete in nine months, and a permanent facility installation was commissioned three months later. The process design, equipment procurement, and installation phases of the project were pursued concurrently. Three different sweetening systems were operated during the facility development. A conventional DEA (diethanolamine) system was used because of its simple operation. Conversions were made to a proprietary MDEA (methyldiethanolamine) system in order to increase capacity. A proprietary activated MDEA was tested and operated in order to determine sweetening system selection for future facility capacity and for other applications. Included is a discussion of the project development procedure and key considerations that led to minimal development time. General comparisons are made concerning the performance of several sweetening systems.

  20. Using pattern enumeration to accelerate process development and ramp yield

    NASA Astrophysics Data System (ADS)

    Zhuang, Linda; Pang, Jenny; Xu, Jessy; Tsai, Mengfeng; Wang, Amy; Zhang, Yifan; Sweis, Jason; Lai, Ya-Chieh; Ding, Hua

    2016-03-01

    During a new technology node process setup phase, foundries do not initially have enough product chip designs to conduct exhaustive process development. Different operational teams use manually designed simple test keys to set up their process flows and recipes. When the very first version of the design rule manual (DRM) is ready, foundries enter the process development phase where new experiment design data is manually created based on these design rules. However, these IP/test keys contain very uniform or simple design structures. This kind of design normally does not contain critical design structures or process unfriendly design patterns that pass design rule checks but are found to be less manufacturable. It is desired to have a method to generate exhaustive test patterns allowed by design rules at development stage to verify the gap of design rule and process. This paper presents a novel method of how to generate test key patterns which contain known problematic patterns as well as any constructs which designers could possibly draw based on current design rules. The enumerated test key patterns will contain the most critical design structures which are allowed by any particular design rule. A layout profiling method is used to do design chip analysis in order to find potential weak points on new incoming products so fab can take preemptive action to avoid yield loss. It can be achieved by comparing different products and leveraging the knowledge learned from previous manufactured chips to find possible yield detractors.

  1. Advanced low-beta cavity development for proton and ion accelerators

    NASA Astrophysics Data System (ADS)

    Conway, Z. A.; Kelly, M. P.; Ostroumov, P. N.

    2015-05-01

    Recent developments in designing and processing low-beta superconducting cavities at Argonne National Laboratory are very encouraging for future applications requiring compact proton and ion accelerators. One of the major benefits of these accelerating structures is achieving real-estate accelerating gradients greater than 3 MV/m very efficiently either continuously or for long-duty cycle operation (>1%). The technology has been implemented in low-beta accelerator cryomodules for the Argonne ATLAS heavy-ion linac where the cryomodules are required to have real-estate gradients of more than 3 MV/m. In offline testing low-beta cavities with even higher gradients have already been achieved. This paper will review this work where we have achieved surface fields greater than 166 mT magnetic and 117 MV/m electric in a 72 MHz quarter-wave resonator optimized for β = 0.077 ions.

  2. Development of a 10 MW, 91 GHz gyroklystron for accelerator applications

    NASA Astrophysics Data System (ADS)

    Ives, R. Lawrence; Lawson, Wes; Neilson, Jeff M.; Read, Michael

    2001-05-01

    A 10 MW, 91 GHz gyroklystron is under development for W-Band accelerator applications. The device will generate 1.5 microsecond pulses at 120 Hz and will be provided to Stanford Linear Accelerator Center for testing of W-Band accelerator components and subsystems. A magnetron injection gun operating at 500 kV will provide a 55 amp beam for interaction in a 5 cavity circuit. The output will be in a hybrid TE01/TE02 mode that can be converted to a more suitable mode at the accelerator. The device is expected to operate with efficiency close to 40% with a gain of 55 dB. A depressed collector will be implemented to allow improvement in the total efficiency to more than 50%.

  3. Development of repetitive railgun pellet accelerator and steady-state pellet supply system

    SciTech Connect

    Oda, Y.; Onozuka, M.; Azuma, K.; Kasai, S.; Hasegawa, K.

    1995-12-31

    A railgun system for repetitive high-speed pellet acceleration and steady-state pellet supply system has been developed and investigated. Using a 2m-long railgun system, the hydrogen pellet was accelerated to 2.6km/sec by the supplied energy of 1.7kJ. It is expected that the hydrogen pellet can be accelerated to 3km/sec using the present pneumatic pellet accelerator and a 2m-long augment railgun. Screw-driven hydrogen-isotope filament extruding system has been fabricated and will be tested to examine its applicability to the steady-state extrusion of the solid hydrogen-isotope filament.

  4. Caveolae and Caveolin-1 Integrate Reverse Cholesterol Transport and Inflammation in Atherosclerosis

    PubMed Central

    Qin, Li; Zhu, Neng; Ao, Bao-Xue; Liu, Chan; Shi, Ya-Ning; Du, Ke; Chen, Jian-Xiong; Zheng, Xi-Long; Liao, Duan-Fang

    2016-01-01

    Lipid disorder and inflammation play critical roles in the development of atherosclerosis. Reverse cholesterol transport is a key event in lipid metabolism. Caveolae and caveolin-1 are in the center stage of cholesterol transportation and inflammation in macrophages. Here, we propose that reverse cholesterol transport and inflammation in atherosclerosis can be integrated by caveolae and caveolin-1. PMID:27011179

  5. Compact Dielectric Wall Accelerator Development For Intensity Modulated Proton Therapy And Homeland Security Applications

    SciTech Connect

    Chen, Y -; Caporaso, G J; Guethlein, G; Sampayan, S; Akana, G; Anaya, R; Blackfield, D; Cook, E; Falabella, S; Gower, E; Harris, J; Hawkins, S; Hickman, B; Holmes, C; Horner, A; Nelson, S; Paul, A; Pearson, D; Poole, B; Richardson, R; Sanders, D; Stanley, J; Sullivan, J; Wang, L; Watson, J; Weir, J

    2009-06-17

    Compact dielectric wall (DWA) accelerator technology is being developed at the Lawrence Livermore National Laboratory. The DWA accelerator uses fast switched high voltage transmission lines to generate pulsed electric fields on the inside of a high gradient insulating (HGI) acceleration tube. Its high electric field gradients are achieved by the use of alternating insulators and conductors and short pulse times. The DWA concept can be applied to accelerate charge particle beams with any charge to mass ratio and energy. Based on the DWA system, a novel compact proton therapy accelerator is being developed. This proton therapy system will produce individual pulses that can be varied in intensity, energy and spot width. The system will be capable of being sited in a conventional linac vault and provide intensity modulated rotational therapy. The status of the developmental new technologies that make the compact system possible will be reviewed. These include, high gradient vacuum insulators, solid dielectric materials, SiC photoconductive switches and compact proton sources. Applications of the DWA accelerator to problems in homeland security will also be discussed.

  6. Pre-Implementation and Performance Plan for the Latino Development and Technology Accelerator Center

    SciTech Connect

    Quiroga, Marcelo

    2007-03-30

    This report discusses the Latino Development and Technology Accelerator Center (Center) and its innovative economic development program. The chapters describe the organization and the operations of a two-pillar model for training and business acceleration and how the program focuses on the economic development of a disadvantaged Chicago, Illinois, Hispanic community located in Humboldt Park. The Humboldt Park community is located 3 miles west of Chicago's affluent downtown. Humboldt Park residents have income levels below the poverty line and unemployment rates twice the national average.

  7. Accelerating materials discovery through the development of polymer databases

    NASA Astrophysics Data System (ADS)

    Audus, Debra

    In our line of business we create chemical solutions for a wide range of applications, such as home and personal care, printing and packaging, automotive and structural coatings, and structural plastics and foams applications. In this environment, stable and highly automated workflows suitable to handle complex systems are a must. By satisfying these prerequisites, efficiency for the development of new materials can be significantly improved by combining modeling and experimental approaches. This is in fact in line with recent Materials Genome Initiative efforts sponsored by the US administration. From our experience, we know, that valuable contributions to product development are possible today by combining existing modeling techniques in an intelligent fashion, provided modeling and experiment work closely together. In my presentation I intend to review approaches to build and parameterize soft matter systems. As an example of our standard workflow, I will show a few applications, which include the design of a stabilizer molecule for dispersing polymer particles and the simulation of polystyrene dispersions.

  8. Replacement of Dietary Saturated Fat by PUFA-Rich Pumpkin Seed Oil Attenuates Non-Alcoholic Fatty Liver Disease and Atherosclerosis Development, with Additional Health Effects of Virgin over Refined Oil

    PubMed Central

    Morrison, Martine C.; Mulder, Petra; Stavro, P. Mark; Suárez, Manuel; Arola-Arnal, Anna; van Duyvenvoorde, Wim; Kooistra, Teake; Wielinga, Peter Y.; Kleemann, Robert

    2015-01-01

    Background and Aims As dietary saturated fatty acids are associated with metabolic and cardiovascular disease, a potentially interesting strategy to reduce disease risk is modification of the quality of fat consumed. Vegetable oils represent an attractive target for intervention, as they largely determine the intake of dietary fats. Furthermore, besides potential health effects conferred by the type of fatty acids in a vegetable oil, other minor components (e.g. phytochemicals) may also have health benefits. Here, we investigated the potential long-term health effects of isocaloric substitution of dietary fat (i.e. partial replacement of saturated by unsaturated fats), as well as putative additional effects of phytochemicals present in unrefined (virgin) oil on development of non-alcoholic fatty liver disease (NAFLD) and associated atherosclerosis. For this, we used pumpkin seed oil, because it is high in unsaturated fatty acids and a rich source of phytochemicals. Methods ApoE*3Leiden mice were fed a Western-type diet (CON) containing cocoa butter (15% w/w) and cholesterol (1% w/w) for 20 weeks to induce risk factors and disease endpoints. In separate groups, cocoa butter was replaced by refined (REF) or virgin (VIR) pumpkin seed oil (comparable in fatty acid composition, but different in phytochemical content). Results Both oils improved dyslipidaemia, with decreased (V)LDL-cholesterol and triglyceride levels in comparison with CON, and additional cholesterol-lowering effects of VIR over REF. While REF did not affect plasma inflammatory markers, VIR reduced circulating serum amyloid A and soluble vascular adhesion molecule-1. NAFLD and atherosclerosis development was modestly reduced in REF, and VIR strongly decreased liver steatosis and inflammation as well as atherosclerotic lesion area and severity. Conclusions Overall, we show that an isocaloric switch from a diet rich in saturated fat to a diet rich in unsaturated fat can attenuate NAFLD and atherosclerosis

  9. Suppression of atherosclerosis by synthetic REV-ERB agonist

    SciTech Connect

    Sitaula, Sadichha; Billon, Cyrielle; Kamenecka, Theodore M.; Solt, Laura A.; Burris, Thomas P.

    2015-05-08

    The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.

  10. Biomarkers of Subclinical Atherosclerosis in Patients with Autoimmune Disorders

    PubMed Central

    Profumo, Elisabetta; Di Franco, Manuela; Buttari, Brigitta; Masella, Roberta; Filesi, Carmelina; Tosti, Maria Elena; Scrivo, Rossana; Scarno, Antongiulio; Spadaro, Antonio; Saso, Luciano; Riganò, Rachele

    2012-01-01

    Atherosclerosis is accelerated in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We investigated a possible association of oxidized low-density lipoproteins (ox-LDLs), nitric oxide (NO), 3-nitrotyrosine, vitamin A, vitamin E, and β-carotene serum levels with subclinical atherosclerosis in RA and PsA. By the use of ELISA, we observed higher ox-LDL levels in patients with intima-media thickness (IMT) > 1 than in patients with IMT ≤ 1 and a negative correlation between NO levels and IMT values. By the use of high-performance liquid chromatography, we determined higher levels of vitamin A in patients with PsA and IMT ≤ 1 than in controls and lower levels of β-carotene in patients with RA and PsA than in controls. β-carotene concentrations were negatively correlated to the duration of disease in RA. Our study confirms that ox-LDLs and NO may be markers of accelerated atherosclerosis in RA and PsA whereas vitamins seem to be associated only to the presence of the autoimmune disorders. PMID:22529523

  11. Biomarkers of subclinical atherosclerosis in patients with autoimmune disorders.

    PubMed

    Profumo, Elisabetta; Di Franco, Manuela; Buttari, Brigitta; Masella, Roberta; Filesi, Carmelina; Tosti, Maria Elena; Scrivo, Rossana; Scarno, Antongiulio; Spadaro, Antonio; Saso, Luciano; Riganò, Rachele

    2012-01-01

    Atherosclerosis is accelerated in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). We investigated a possible association of oxidized low-density lipoproteins (ox-LDLs), nitric oxide (NO), 3-nitrotyrosine, vitamin A, vitamin E, and β-carotene serum levels with subclinical atherosclerosis in RA and PsA. By the use of ELISA, we observed higher ox-LDL levels in patients with intima-media thickness (IMT) > 1 than in patients with IMT ≤ 1 and a negative correlation between NO levels and IMT values. By the use of high-performance liquid chromatography, we determined higher levels of vitamin A in patients with PsA and IMT ≤ 1 than in controls and lower levels of β-carotene in patients with RA and PsA than in controls. β-carotene concentrations were negatively correlated to the duration of disease in RA. Our study confirms that ox-LDLs and NO may be markers of accelerated atherosclerosis in RA and PsA whereas vitamins seem to be associated only to the presence of the autoimmune disorders. PMID:22529523

  12. Development of accelerator radiation protection at the SSC

    SciTech Connect

    Toohig, T.

    1993-11-01

    The design of the Superconducting Super Collider evolved over a series of studies from 1984 to 1989. Considerations of concentration of radiation sources and provisions for operational control and monitoring of radiation were determining elements in the design concepts for the facility. The development of the designs involved an extension of the range of applicability of energy deposition and radiation shielding codes beyond the 3 TeV level of the proposed UNK collider to 20 TeV for single beam effects and to 40 TeV in the collision regions. This extrapolation was complicated by the newly discovered, very energetic muons from short-lived states associated with heavy quark states. The design guideline for radiation protection was specified to be 10 mRem/yr, 10% of the Federal limit. In order to limit the amount of land required for the facility, which would extend over some 250 mi. sq., the configuration of the land to be acquired was tailored to the requirements for radiation containment below the levels of the guideline.

  13. Accelerating development of a predictive science of climate.

    SciTech Connect

    Drake, John B; Jones, Phil

    2007-01-01

    Climate change and studies of its implications are front page news. Could the heat waves of July 2006 in Europe and the US be caused by global warming? Are increased incidences of strong tropical storms and hurricanes like Katrina to be expected? Will coastal cities be flooded due to sea level rise? The National Climatic Data Center (NCDC) which archives all weather data for the nation reports that global surface temperatures have increased at a rate near 0.6 C over the last century but that the trend is three times larger since 1976 [Easterling, 2006]. Will this rate continue or will climate change be even more abrupt? Stepping back from the flurry of questions, scientists must take a systematic approach and develop a predictive framework. With responsibility for advising on energy and technology strategies, the Department of Energy Office of Biological and Environmental Research has chosen to bolster the science of climate in order to get the story straight on the factors that cause climate change and the role of carbon loading from fossil fuel use.

  14. Synapsin IIa accelerates functional development of neuromuscular synapses.

    PubMed Central

    Schaeffer, E; Alder, J; Greengard, P; Poo, M M

    1994-01-01

    We have investigated the possible involvement of the synaptic vesicle protein synapsin IIa in synapse development. Synapsin IIa was introduced into Xenopus embryonic spinal neurons by early blastomere injection, and nerve-muscle cultures were prepared. Synaptic currents were measured by comparing synapses in which the presynaptic neuron either contained [syn IIa (+)] or lacked (control) exogenous synapsin IIa. Syn IIa (+) synapses had a 3.6-fold increase in the frequency and a 2.1-fold increase in the amplitude of spontaneous synaptic currents, compared to controls, after 2 days in culture. Synapsin IIa also increased the amplitude of evoked synaptic currents by 2.3-fold in 2-day cultures. The evoked synaptic current amplitudes of syn IIa (+) synapses had a lower coefficient of variation indicating a more stable evoked response. These enhanced synaptic activities were independent of the presence or absence of the protein in the postsynaptic muscle cell. The findings indicate a role for synapsin IIa in synapse maturation. Images PMID:8171006

  15. Noninvasive Laser Probing of Ultrashort Single Electron Bunches for Accelerator And Light Source Development

    SciTech Connect

    Bolton, P.R.; /SLAC

    2007-06-11

    Companion development of ultrafast electron beam diagnostics capable of noninvasively resolving single bunch detail is essential for the development of high energy, high brightness accelerator facilities and associated beam-based light source applications. Existing conventional accelerators can exhibit timing-jitter down to the 100 femtosecond level which exceeds their single bunch duration capability. At the other extreme, in relatively jitterless environments, laser-plasma wakefield accelerators (LWFA) can generate single electron bunches of duration estimated to be of order 10 femtoseconds making this setting a valuable testbed for development of broadband electron bunch diagnostics. Characteristics of electro-optic schemes and laser-induced reflectance are discussed with emphasis on temporal resolution.

  16. Collaborative workbench for cyberinfrastructure to accelerate science algorithm development

    NASA Astrophysics Data System (ADS)

    Ramachandran, R.; Maskey, M.; Kuo, K.; Lynnes, C.

    2013-12-01

    There are significant untapped resources for information and knowledge creation within the Earth Science community in the form of data, algorithms, services, analysis workflows or scripts, and the related knowledge about these resources. Despite the huge growth in social networking and collaboration platforms, these resources often reside on an investigator's workstation or laboratory and are rarely shared. A major reason for this is that there are very few scientific collaboration platforms, and those that exist typically require the use of a new set of analysis tools and paradigms to leverage the shared infrastructure. As a result, adoption of these collaborative platforms for science research is inhibited by the high cost to an individual scientist of switching from his or her own familiar environment and set of tools to a new environment and tool set. This presentation will describe an ongoing project developing an Earth Science Collaborative Workbench (CWB). The CWB approach will eliminate this barrier by augmenting a scientist's current research environment and tool set to allow him or her to easily share diverse data and algorithms. The CWB will leverage evolving technologies such as commodity computing and social networking to design an architecture for scalable collaboration that will support the emerging vision of an Earth Science Collaboratory. The CWB is being implemented on the robust and open source Eclipse framework and will be compatible with widely used scientific analysis tools such as IDL. The myScience Catalog built into CWB will capture and track metadata and provenance about data and algorithms for the researchers in a non-intrusive manner with minimal overhead. Seamless interfaces to multiple Cloud services will support sharing algorithms, data, and analysis results, as well as access to storage and computer resources. A Community Catalog will track the use of shared science artifacts and manage collaborations among researchers.

  17. Residual acceleration data on IML-1: Development of a data reduction and dissemination plan

    NASA Technical Reports Server (NTRS)

    Rogers, Melissa J. B.; Alexander, J. Iwan D.; Wolf, Randy

    1992-01-01

    The main thrust of our work in the third year of contract NAG8-759 was the development and analysis of various data processing techniques that may be applicable to residual acceleration data. Our goal is the development of a data processing guide that low gravity principal investigators can use to assess their need for accelerometer data and then formulate an acceleration data analysis strategy. The work focused on the flight of the first International Microgravity Laboratory (IML-1) mission. We are also developing a data base management system to handle large quantities of residual acceleration data. This type of system should be an integral tool in the detailed analysis of accelerometer data. The system will manage a large graphics data base in the support of supervised and unsupervised pattern recognition. The goal of the pattern recognition phase is to identify specific classes of accelerations so that these classes can be easily recognized in any data base. The data base management system is being tested on the Spacelab 3 (SL3) residual acceleration data.

  18. IRF5 deficiency ameliorates lupus but promotes atherosclerosis and metabolic dysfunction in a mouse model of lupus-associated atherosclerosis

    PubMed Central

    Watkins, Amanda A.; Yasuda, Kei; Wilson, Gabriella E.; Aprahamian, Tamar; Xie, Yao; Maganto-Garcia, Elena; Shukla, Prachi; Oberlander, Lillian; Laskow, Bari; Menn-Josephy, Hanni; Wu, Yuanyuan; Duffau, Pierre; Fried, Susan K.; Lichtman, Andrew H.; Bonegio, Ramon G.; Rifkin, Ian R.

    2015-01-01

    Premature atherosclerosis is a severe complication of lupus and other systemic autoimmune disorders. Gain-of-function polymorphisms in interferon regulatory factor 5 (IRF5) are associated with an increased risk of developing lupus and IRF5 deficiency in lupus mouse models ameliorates disease. However, whether IRF5 deficiency also protects against atherosclerosis development in lupus is not known. Here we addressed this question using the gld.apoE−/− mouse model. IRF5 deficiency markedly reduced lupus disease severity. Unexpectedly, despite the reduction in systemic immune activation, IRF5-deficient mice developed increased atherosclerosis and also exhibited metabolic dysregulation characterized by hyperlipidemia, increased adiposity and insulin resistance. Levels of the atheroprotective cytokine IL-10 were reduced in aortae of IRF5-deficient mice and in vitro studies demonstrated that IRF5 is required for IL-10 production downstream of TLR7 and TLR9 signaling in multiple immune cell types. Chimera studies showed that IRF5 deficiency in bone marrow-derived cells prevents lupus development and contributes in part to the increased atherosclerosis. Notably, IRF5 deficiency in non-bone marrow-derived cells also contributes to the increased atherosclerosis through the generation of hyperlipidemia and increased adiposity. Together, our results reveal a protective role for IRF5 in lupus-associated atherosclerosis that is mediated through the effects of IRF5 in both immune and non-immune cells. These findings have implications for the proposed targeting of IRF5 in the treatment of autoimmune disease as global IRF5 inhibition may exacerbate cardiovascular disease in these patients. PMID:25595782

  19. Polymicrobial Infection with Major Periodontal Pathogens Induced Periodontal Disease and Aortic Atherosclerosis in Hyperlipidemic ApoEnull Mice

    PubMed Central

    Rivera, Mercedes F.; Lee, Ju-Youn; Aneja, Monika; Goswami, Vishalkant; Liu, Liying; Velsko, Irina M.; Chukkapalli, Sasanka S.; Bhattacharyya, Indraneel; Chen, Hao; Lucas, Alexandra R.; Kesavalu, Lakshmyya N.

    2013-01-01

    Periodontal disease (PD) and atherosclerosis are both polymicrobial and multifactorial and although observational studies supported the association, the causative relationship between these two diseases is not yet established. Polymicrobial infection-induced periodontal disease is postulated to accelerate atherosclerotic plaque growth by enhancing atherosclerotic risk factors of orally infected Apolipoprotein E deficient (ApoEnull) mice. At 16 weeks of infection, samples of blood, mandible, maxilla, aorta, heart, spleen, and liver were collected, analyzed for bacterial genomic DNA, immune response, inflammation, alveolar bone loss, serum inflammatory marker, atherosclerosis risk factors, and aortic atherosclerosis. PCR analysis of polymicrobial-infected (Porphyromonas gingivalis [P. gingivalis], Treponema denticola [T. denticola], and Tannerella forsythia [T. forsythia]) mice resulted in detection of bacterial genomic DNA in oral plaque samples indicating colonization of the oral cavity by all three species. Fluorescent in situ hybridization detected P. gingivalis and T. denticola within gingival tissues of infected mice and morphometric analysis showed an increase in palatal alveolar bone loss (p<0.0001) and intrabony defects suggesting development of periodontal disease in this model. Polymicrobial-infected mice also showed an increase in aortic plaque area (p<0.05) with macrophage accumulation, enhanced serum amyloid A, and increased serum cholesterol and triglycerides. A systemic infection was indicated by the detection of bacterial genomic DNA in the aorta and liver of infected mice and elevated levels of bacterial specific IgG antibodies (p<0.0001). This study was a unique effort to understand the effects of a polymicrobial infection with P. gingivalis, T. denticola and T. forsythia on periodontal disease and associated atherosclerosis in ApoEnull mice. PMID:23451182

  20. [Some historical considerations on the inflammatory theory of atherosclerosis].

    PubMed

    Marson, P; Zanchin, G; Stefanutti, C

    2004-01-01

    In the past 20 years several clinical and experimental observations have led to the hypothesis that an inflammatory response can trigger some key processes during the development of atherosclerosis. Here we briefly review, from the historical viewpoint, the inflammatory theory of atherosclerosis, as proposed by the Berliner pathologist Rudolf Virchow in the XIX century. Contrary to this hypothesis, in the same period the Viennese Karl von Rokitansky recognized blood dyscrasia (particularly fibrin-induced alterations) as the promoting factor in the process of atherogenesis. Moreover, we outline the relationship between atherosclerosis and arthritis, by reporting some passages from two scientific works published in the late XIX century, the former by the Italian Achille De Giovanni ("Sull'arterite. Sue forme cliniche e sua patogenesi", 1882) and the latter by the French Theophile Guyot ("L'arthritis. Maladie Constitutionnelle", 1890). PMID:15470528

  1. Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis

    PubMed Central

    Chistiakov, Dimitry A.; Nikiforov, Nikita G.

    2016-01-01

    Atherosclerosis can be regarded as a chronic inflammatory state, in which macrophages play different and important roles. Phagocytic proinflammatory cells populate growing atherosclerotic lesions, where they actively participate in cholesterol accumulation. Moreover, macrophages promote formation of complicated and unstable plaques by maintaining proinflammatory microenvironment. At the same time, anti-inflammatory macrophages contribute to tissue repair and remodelling and plaque stabilization. Macrophages therefore represent attractive targets for development of antiatherosclerotic therapy, which can aim to reduce monocyte recruitment to the lesion site, inhibit proinflammatory macrophages, or stimulate anti-inflammatory responses and cholesterol efflux. More studies are needed, however, to create a comprehensive classification of different macrophage phenotypes and to define their roles in the pathogenesis of atherosclerosis. In this review, we provide an overview of the current knowledge on macrophage diversity, activation, and plasticity in atherosclerosis and describe macrophage-based cellular tests for evaluation of potential antiatherosclerotic substances. PMID:27493969

  2. The MIT Accelerator Laboratory for Diagnostic Development for OMEGA, Z and the NIF

    NASA Astrophysics Data System (ADS)

    Petrasso, R.; Gatu Johnson, M.; Armstrong, E.; Orozco, D.; Rinderknecht, H. G.; Rojas Herrera, J.; Rosenberg, M.; Sio, H.; Zylstra, A.; Frenje, J.; Li, C. K.; Seguin, F. H.; Hahn, K.; Jones, B.; Ruiz, C. L.; Sangster, T. C.

    2014-10-01

    The MIT Linear Electrostatic Ion Accelerator generates D-D and D-3He fusion products, which are used for development of nuclear diagnostics for OMEGA, Z, and the NIF. Fusion reaction rates around 106 s-1 are routinely achieved with this accelerator, and fluence and energy of the fusion products are accurately characterized. Diagnostics developed and calibrated at this facility include CR-39 based charged-particle spectrometers, neutron detectors, and the particle Time-Of-Flight (pTOF) CVD-diamond-based bang time detector. The accelerator is also a vital tool in the education of graduate and undergraduate students at MIT. This work was supported in part by SNL, DOE, LLE and LLNL.

  3. Development of and flight results from the Space Acceleration Measurement System (SAMS)

    NASA Technical Reports Server (NTRS)

    Delombard, Richard; Finley, Brian D.; Baugher, Charles R.

    1992-01-01

    Described here is the development of and the flight results from the Space Acceleration Measurement System (SAMS) flight units used in the Orbiter middeck, Spacelab module, and the Orbitercargo bay. The SAMS units are general purpose microgravity accelerometers designed to support a variety of science experiments with microgravity acceleration measurements. A total of six flight units have been fabricated; four for use in the Orbiter middeck and Spacelab module, and two for use in the Orbiter cargo bay. The design of the units is briefly described. The initial two flights of SAMS units on STS-40 (June 1991) and STS-43 (August 1991) resulted in 371 megabytes and 2.6 gigabytes of data respectively. Analytical techniques developed to examine this quantity of acceleration data are described and sample plots of analyzed data are illustrated. Future missions for the SAMS units are listed.

  4. Development of a Patient-Specific Multi-Scale Model to Understand Atherosclerosis and Calcification Locations: Comparison with In vivo Data in an Aortic Dissection

    PubMed Central

    Alimohammadi, Mona; Pichardo-Almarza, Cesar; Agu, Obiekezie; Díaz-Zuccarini, Vanessa

    2016-01-01

    Vascular calcification results in stiffening of the aorta and is associated with hypertension and atherosclerosis. Atherogenesis is a complex, multifactorial, and systemic process; the result of a number of factors, each operating simultaneously at several spatial and temporal scales. The ability to predict sites of atherogenesis would be of great use to clinicians in order to improve diagnostic and treatment planning. In this paper, we present a mathematical model as a tool to understand why atherosclerotic plaque and calcifications occur in specific locations. This model is then used to analyze vascular calcification and atherosclerotic areas in an aortic dissection patient using a mechanistic, multi-scale modeling approach, coupling patient-specific, fluid-structure interaction simulations with a model of endothelial mechanotransduction. A number of hemodynamic factors based on state-of-the-art literature are used as inputs to the endothelial permeability model, in order to investigate plaque and calcification distributions, which are compared with clinical imaging data. A significantly improved correlation between elevated hydraulic conductivity or volume flux and the presence of calcification and plaques was achieved by using a shear index comprising both mean and oscillatory shear components (HOLMES) and a non-Newtonian viscosity model as inputs, as compared to widely used hemodynamic indicators. The proposed approach shows promise as a predictive tool. The improvements obtained using the combined biomechanical/biochemical modeling approach highlight the benefits of mechanistic modeling as a powerful tool to understand complex phenomena and provides insight into the relative importance of key hemodynamic parameters. PMID:27445834

  5. Development of a Patient-Specific Multi-Scale Model to Understand Atherosclerosis and Calcification Locations: Comparison with In vivo Data in an Aortic Dissection.

    PubMed

    Alimohammadi, Mona; Pichardo-Almarza, Cesar; Agu, Obiekezie; Díaz-Zuccarini, Vanessa

    2016-01-01

    Vascular calcification results in stiffening of the aorta and is associated with hypertension and atherosclerosis. Atherogenesis is a complex, multifactorial, and systemic process; the result of a number of factors, each operating simultaneously at several spatial and temporal scales. The ability to predict sites of atherogenesis would be of great use to clinicians in order to improve diagnostic and treatment planning. In this paper, we present a mathematical model as a tool to understand why atherosclerotic plaque and calcifications occur in specific locations. This model is then used to analyze vascular calcification and atherosclerotic areas in an aortic dissection patient using a mechanistic, multi-scale modeling approach, coupling patient-specific, fluid-structure interaction simulations with a model of endothelial mechanotransduction. A number of hemodynamic factors based on state-of-the-art literature are used as inputs to the endothelial permeability model, in order to investigate plaque and calcification distributions, which are compared with clinical imaging data. A significantly improved correlation between elevated hydraulic conductivity or volume flux and the presence of calcification and plaques was achieved by using a shear index comprising both mean and oscillatory shear components (HOLMES) and a non-Newtonian viscosity model as inputs, as compared to widely used hemodynamic indicators. The proposed approach shows promise as a predictive tool. The improvements obtained using the combined biomechanical/biochemical modeling approach highlight the benefits of mechanistic modeling as a powerful tool to understand complex phenomena and provides insight into the relative importance of key hemodynamic parameters. PMID:27445834

  6. Fetal programming of atherosclerosis: possible role of the mitochondria.

    PubMed

    Leduc, Line; Levy, Emile; Bouity-Voubou, Maurice; Delvin, Edgard

    2010-04-01

    Growing evidence indicates that being small size at birth from malnutrition is associated with an increased risk of developing type 2 diabetes (T2D), metabolic syndrome and cardiovascular disease in adulthood. Atherosclerosis is common to these aforementioned disorders, and oxidative stress and chronic inflammation are now considered as initiating events in its development, with endothelial cell dysfunction being an early, fundamental step. According to the fetal programming hypothesis, growth-restricted neonates exposed to placental insufficiency exhibit endothelial cell dysfunction very early in life that later on predisposes them to atherosclerosis. Although many investigations have reported early alterations in vascular function in children and adolescents with low birth weight, the mechanisms of such fetal programming of atherosclerosis remain largely unknown. Experimental studies have demonstrated that low birth weight infants are prenatally subjected to conditions of oxidative stress and inflammation that might be involved in the later occurrence of atherosclerosis. Arterial endothelial dysfunction has been encountered in term infants, children and young adults with low birth weight. The loss of appropriate endothelium function with decreased nitric oxide production or activity, manifested as impaired vasodilatation, is considered a basic step in atherosclerosis development and progression. Several lines of evidence indicate that mitochondrial damage is central to this process and that reactive oxygen species (ROS) may act as a double-edged sword. On the one hand, it is well-accepted that the mitochondria are a major source of chronic ROS production under physiological conditions. On the other hand, it is known that ROS generation damages lipids, proteins and mitochondrial DNA, leading to dysregulated mitochondrial function. Elevated mitochondrial ROS production is associated with endothelial cell dysfunction as well as vascular smooth muscle cell

  7. Tissue Factor Pathway Inhibitor-2 Gene Polymorphisms Associate With Coronary Atherosclerosis in Chinese Population

    PubMed Central

    Yu, Jia; Liu, Rong-Le; Luo, Xin-Ping; Shi, Hai-ming; Ma, Duan; Pan, Jun-Jie; Ni, Huan-Chun

    2015-01-01

    Abstract Tissue factor pathway inhibitor-2 (TFPI-2) may play critical roles in the pathogenesis of atherosclerosis. In this study, we aimed to investigate the association between TFPI-2 gene polymorphisms and coronary atherosclerosis. Four hundred and seven patients with coronary atherosclerosis and 306 individuals with normal coronary artery were enrolled in the present study. Nine single-nucleotide polymorphisms (SNPs) (rs3763473, rs59805398, rs60215632, rs59999573, rs59740167, rs34489123, rs4517, rs4264, and rs4271) were detected with polymerase chain reaction-direct sequencing method. Severity of coronary atherosclerosis was assessed by Gensini score. After the baseline investigation, patients with coronary atherosclerosis were followed up for incidence of cardiovascular events (CVEs). Eight SNPs were in accordance with the Hardy–Weinberg equilibrium, and 8 haplotypes were constructed based on rs59999573, rs59740167, and rs34489123 after linkage disequilibrium and haplotype analysis. Two SNPs (rs59805398 and rs34489123) and 5 haplotypes correlated with coronary atherosclerosis even after adjustment by Gensini score. At follow-up (median 53 months, range 1–60 months), 85 patients experienced CVE. However, there was no strong association between the gene polymorphisms and the occurrence of CVE. Tissue factor pathway inhibitor-2 gene polymorphisms were associated with coronary atherosclerosis in the Chinese population, suggesting that the information about TFPI-2 gene polymorphisms was useful for assessing the risk of developing coronary atherosclerosis, but there was not enough evidence showing it could predict occurrence of CVE. PMID:26496276

  8. Immunity, atherosclerosis and cardiovascular disease

    PubMed Central

    2013-01-01

    Atherosclerosis, the major cause of cardiovascular disease (CVD), is a chronic inflammatory condition with immune competent cells in lesions producing mainly pro-inflammatory cytokines. Dead cells and oxidized forms of low density lipoproteins (oxLDL) are abundant. The major direct cause of CVD appears to be rupture of atherosclerotic plaques. oxLDL has proinflammatory and immune-stimulatory properties, causes cell death at higher concentrations and contains inflammatory phospholipids with phosphorylcholine (PC) as an interesting epitope. Antibodies against PC (anti-PC) may be atheroprotective, one mechanism being anti-inflammatory. Bacteria and virus have been discussed, but it has been difficult to find direct evidence, and antibiotic trials have not been successful. Heat shock proteins could be one major target for atherogenic immune reactions. More direct causes of plaque rupture include pro-inflammatory cytokines, chemokines, and lipid mediators. To prove that inflammation is a cause of atherosclerosis and CVD, clinical studies with anti-inflammatory and/or immune-modulatory treatment are needed. The potential causes of immune reactions and inflammation in atherosclerosis and how inflammation can be targeted therapeutically to provide novel treatments for CVD are reviewed. PMID:23635324

  9. Intestinal Microbiota Metabolism and Atherosclerosis

    PubMed Central

    Liu, Tian-Xing; Niu, Hai-Tao; Zhang, Shu-Yang

    2015-01-01

    Objective: This review aimed to summarize the relationship between intestinal microbiota metabolism and cardiovascular disease (CVD) and to propose a novel CVD therapeutic target. Data Sources: This study was based on data obtained from PubMed and EMBASE up to June 30, 2015. Articles were selected using the following search terms: “Intestinal microbiota”, “trimethylamine N-oxide (TMAO)”, “trimethylamine (TMA)”, “cardiovascular”, and “atherosclerosis”. Study Selection: Studies were eligible if they present information on intestinal microbiota metabolism and atherosclerosis. Studies on TMA-containing nutrients were also included. Results: A new CVD risk factor, TMAO, was recently identified. It has been observed that several TMA-containing compounds may be catabolized by specific intestinal microbiota, resulting in TMA release. TMA is subsequently converted to TMAO in the liver. Several preliminary studies have linked TMAO to CVD, particularly atherosclerosis; however, the details of this relationship remain unclear. Conclusions: Intestinal microbiota metabolism is associated with atherosclerosis and may represent a promising therapeutic target with respect to CVD management. PMID:26481750

  10. Temporal Development of Auroral Acceleration Potentials: High-Altitude Evolutionary Sequences, Drivers and Consequences

    NASA Astrophysics Data System (ADS)

    Hull, A. J.; Wilber, M.; Chaston, C.; Bonnell, J.; Mozer, F.; McFadden, J.; Goldstein, M.; Fillingim, M.

    2007-12-01

    The region above the auroral acceleration region is an integral part of the auroral zone electrodynamic system. At these altitudes (≥ 3 Re) we find the source plasma and fields that determine acceleration processes occurring at lower altitudes, which play a key role in the transport of mass and energy into the ionosphere. Dynamic changes in these high-altitude regions can affect and/or control lower-altitude acceleration processes according to how field-aligned currents and specific plasma sources form and decay and how they are spatially distributed, and through magnetic configuration changes deeper in the magnetotail. Though much progress has been made, the time development and consequential effects of the high-altitude plasma and fields are still not fully understood. We present Cluster multi-point observations at key instances within and above the acceleration region (> 3 RE) of evolving auroral arc current systems. Results are presented from events occurring under different conditions, such as magnetospheric activity, associations with density depletions or gradients, and Alfvenic turbulence. A preliminary survey, primarily at or near the plasma sheet boundary, indicates quasi- static up-down current pair systems are at times associated with density depletions and other instances occur in association with density gradients. The data suggest that such quasi-static current systems may be evolving from structured Alfvenic current systems. We will discuss the temporal development of auroral acceleration potentials, plasma and currents, including quasi-static system formation from turbulent systems of structured Alfvenic field-aligned currents, density depletion and constituent reorganization of the source and ionospheric plasma that transpire in such systems. Of particular emphasis is how temporal changes in magnetospheric source plasma and fields affect the development of auroral acceleration potentials at lower altitudes.

  11. Targeting macrophage necroptosis for therapeutic and diagnostic interventions in atherosclerosis

    PubMed Central

    Karunakaran, Denuja; Geoffrion, Michele; Wei, Lihui; Gan, Wei; Richards, Laura; Shangari, Prakriti; DeKemp, Ella M.; Beanlands, Rachelle A.; Perisic, Ljubica; Maegdefessel, Lars; Hedin, Ulf; Sad, Subash; Guo, Liang; Kolodgie, Frank D.; Virmani, Renu; Ruddy, Terrence; Rayner, Katey J.

    2016-01-01

    Atherosclerosis results from maladaptive inflammation driven primarily by macrophages, whose recruitment and proliferation drive plaque progression. In advanced plaques, macrophage death contributes centrally to the formation of plaque necrosis, which underlies the instability that promotes plaque rupture and myocardial infarction. Hence, targeting macrophage cell death pathways may offer promise for the stabilization of vulnerable plaques. Necroptosis is a recently discovered pathway of programmed cell necrosis regulated by RIP3 and MLKL kinases that, in contrast to apoptosis, induces a proinflammatory state. We show herein that necroptotic cell death is activated in human advanced atherosclerotic plaques and can be targeted in experimental atherosclerosis for both therapeutic and diagnostic interventions. In humans with unstable carotid atherosclerosis, expression of RIP3 and MLKL is increased, and MLKL phosphorylation, a key step in the commitment to necroptosis, is detected in advanced atheromas. Investigation of the molecular mechanisms underlying necroptosis showed that atherogenic forms of low-density lipoprotein increase RIP3 and MLKL transcription and phosphorylation—two critical steps in the execution of necroptosis. Using a radiotracer developed with the necroptosis inhibitor necrostatin-1 (Nec-1), we show that 123I-Nec-1 localizes specifically to atherosclerotic plaques in Apoe−/− mice, and its uptake is tightly correlated to lesion areas by ex vivo nuclear imaging. Furthermore, treatment of Apoe−/− mice with established atherosclerosis with Nec-1 reduced lesion size and markers of plaque instability, including necrotic core formation. Collectively, our findings offer molecular insight into the mechanisms of macrophage cell death that drive necrotic core formation in atherosclerosis and suggest that this pathway can be used as both a diagnostic and therapeutic tool for the treatment of unstable atherosclerosis. PMID:27532042

  12. Hematopoietic Akt2 deficiency attenuates the progression of atherosclerosis

    PubMed Central

    Rotllan, Noemi; Chamorro-Jorganes, Aránzazu; Araldi, Elisa; Wanschel, Amarylis C.; Aryal, Binod; Aranda, Juan F.; Goedeke, Leigh; Salerno, Alessandro G.; Ramírez, Cristina M.; Sessa, William C.; Suárez, Yajaira; Fernández-Hernando, Carlos

    2015-01-01

    Atherosclerosis is the major cause of death and disability in diabetic and obese subjects with insulin resistance. Akt2, a phosphoinositide-dependent serine-threonine protein kinase, is highly express in insulin-responsive tissues; however, its role during the progression of atherosclerosis remains unknown. Thus, we aimed to investigate the contribution of Akt2 during the progression of atherosclerosis. We found that germ-line Akt2-deficient mice develop similar atherosclerotic plaques as wild-type mice despite higher plasma lipids and glucose levels. It is noteworthy that transplantation of bone marrow cells isolated from Akt2−/− mice to Ldlr−/− mice results in marked reduction of the progression of atherosclerosis compared with Ldlr−/− mice transplanted with wild-type bone marrow cells. In vitro studies indicate that Akt2 is required for macrophage migration in response to proatherogenic cytokines (monocyte chemotactic protein-1 and macrophage colony-stimulating factor). Moreover, Akt2−/− macrophages accumulate less cholesterol and have an alternative activated or M2-type phenotype when stimulated with proinflammatory cytokines. Together, these results provide evidence that macrophage Akt2 regulates migration, the inflammatory response and cholesterol metabolism and suggest that targeting Akt2 in macrophages might be beneficial for treating atherosclerosis.—Rotllan, N., Chamorro-Jorganes, A., Araldi, E., Wanschel, A. C., Aryal, B., Aranda, J. F., Goedeke, L., Salerno, A. G., Ramírez, C. M., Sessa,W. C., Suárez, Y., Fernández-Hernando, C. Hematopoietic Akt2 deficiency attenuates the progression of atherosclerosis. PMID:25392271

  13. Basic Mechanisms in Atherosclerosis: The Role of Calcium.

    PubMed

    Kalampogias, Aimilios; Siasos, Gerasimos; Oikonomou, Evangelos; Tsalamandris, Sotirios; Mourouzis, Konstantinos; Tsigkou, Vasiliki; Vavuranakis, Manolis; Zografos, Thodoris; Deftereos, Spyridon; Stefanadis, Christodoulos; Tousoulis, Dimitris

    2016-01-01

    In the beginning, atherosclerosis was considered to be the result of passive lipid accumulation in the vascular walls. After tremendous technological advancements in research, we are now able to almost admire the complexity of the atherosclerotic process. Atherosclerosis is a chronicinflammatory condition that begins with the formation of calcified plaque, influenced by a number of different factors inside the vascular wall in large and mid-sized arteries. Calcium mineralization of the lumen in the atherosclerotic artery promotes and solidifies plaque formation causing narrowing of the vessel. Soft tissue calcification associated with tissue denegation or necrosis is a passive precipitation event. The process of atherogenesis is mainly driven by CD4+ T cells, CD40L, macrophages, foam cells with elevated transcription of many matrix metalloproteinases, osteoblasts, cytokines, selectins, myeloperoxidases, vascular adhesion molecules (VCAM), and smooth muscle cells. Our knowledge in the genesis of atherosclerosis has changed dramatically in the last few years. New imaging techniques such as intravascular ultrasound or IVUS have made possible to investigate atherosclerosis in early stages. Arterial calcification emerges from two different types, the medial-elastin dependent and the intimal, both of which are directly related to atherosclerosis due to osteoblast differentiation of vascular smooth muscle cells. The deposition of minerals in the form of calcium (Ca(2+)) initially emerges from the inorganing mineral octacalcium phosphate [Ca8H2(PO4)6.5H2O] to the form of Hydroxylapatite [Ca10(PO4)6(OH)2]. This review is devoted to broaden the understanding regarding atherosclerosis and the central role of calcium in the development of the condition. PMID:26411606

  14. Methoprene and protein supplements accelerate reproductive development and improve mating success of male tephritid flies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have been studying the physiological mechanisms responsible for coordination of reproductive maturity and sex pheromone communication in males of tephritid flies in order to develop methods for acceleration of reproductive maturity among sterilized males. Our studies revealed that the juvenile ho...

  15. Future Development Of The Flerov Laboratory Accelerator Complex (Project DRIBs-III)

    NASA Astrophysics Data System (ADS)

    Gulbekian, G. G.; Dmitriev, S. N.; Itkis, M. G.; Oganessian, Yu. Ts.; Popeko, A. G.

    2010-04-01

    Future development of the FLNR accelerator complex (project DRIBs-III) includes modernization of existing cyclotrons, construction of a new experimental hall, creation of a new high current cyclotron and of next generation experimental set-ups. Realization of the project is planned for 2010-2016.

  16. Accelerating the Early Numeracy Development of Kindergartners with Limited Working Memory Skills through Remedial Education

    ERIC Educational Resources Information Center

    Toll, Sylke W. M.; Van Luit, Johannes E. H.

    2013-01-01

    Background: Young children with limited working memory skills are a special interest group among all children that score below average on early numeracy tests. This study examines the effect of accelerating the early numeracy development of these children through remedial education, by comparing them with children with typically working memory…

  17. Accelerated Professional Development and Peer Consultation: Two Strategies for Continuing Professional Education for Nurses.

    ERIC Educational Resources Information Center

    Hart, Gail; Clinton, Michael; Edwards, Helen; Evans, Katie; Lunney, Paul; Posner, Natasha; Tooth, Barbara; Weir, Derek; Ryan, Yoni

    2000-01-01

    A comparison was made of accelerated professional development (APD) for nurses (n=64), involving peer consultation and reflective practice, and peer consultation alone (n=30). Although APD participants had a higher completion rate, improvements in caregiver behaviors and work environment were not significantly different. (SK)

  18. Accelerating the Development of Expertise: A Step-Change in Social Science Research Capacity Building

    ERIC Educational Resources Information Center

    Wray, Alison; Wallace, Mike

    2011-01-01

    It is argued that future research capacity building for the social sciences needs to incorporate methods to accelerate the acquisition by researchers of holistic expertise relevant to their roles as researchers and as developers of others. An agenda is presented, based on a model of learning that highlights missing elements of current provision,…

  19. AIBP: A Novel Molecule at the Interface of Cholesterol Transport, Angiogenesis, and Atherosclerosis

    PubMed Central

    Zhu, Laurence; Fang, Longhou

    2015-01-01

    Cardiovascular disease, which is often driven by hypercholesterolemia and subsequent coronary atherosclerosis, is the number-one cause of morbidity and mortality in the United States. Based on long-term epidemiological studies, high-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with risk for coronary artery disease (CAD). HDL-mediated reverse cholesterol transport (RCT) is responsible for cholesterol removal from the peripheral tissues and return to the liver for final elimination.1 In atherosclerosis, intraplaque angiogenesis promotes plaque growth and increases plaque vulnerability. Conceivably, the acceleration of RCT and disruption of intraplaque angiogenesis would inhibit atherosclerosis and reduce CAD. We have identified a protein called apoA-I binding protein (AIBP) that augments HDL functionality by accelerating cholesterol efflux. Furthermore, AIBP inhibits vascular endothelial growth factor receptor 2 activation in endothelial cells and limits angiogenesis.2 The following discusses the prospect of using AIBP as a novel therapeutic approach for the treatment of CAD. PMID:26634023

  20. Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis

    PubMed Central

    Ng, Chun-Yi; Jaarin, Kamsiah

    2015-01-01

    Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Compared to human models, an animal model is easily manageable, as compounding effects of dietary and environmental factors can be controlled. Blood vessels and cardiac tissue samples can be taken for detailed experimental and biomolecular examination. Choice of animal model is often determined by the research aim, as well as financial and technical factors. A thorough understanding of the animal models used and complete analysis must be validated so that the data can be extrapolated to humans. In conclusion, animal models for hypertension and atherosclerosis are invaluable in improving our understanding of cardiovascular disease and developing new pharmacological therapies. PMID:26064920

  1. Interferon-γ: Promising therapeutic target in atherosclerosis

    PubMed Central

    Moss, Joe WE; Ramji, Dipak P

    2015-01-01

    Atherosclerosis is a chronic inflammatory disorder of the vasculature and is the primary cause of cardiovascular disease (CVD). CVD is currently the world’s leading cause of death and the numbers are predicted to rise further because of a global increase in risk factors such as diabetes and obesity. Current therapies such as statins have had a major impact in reducing mortality from CVD. However, there is a marked residual CVD risk in patients on statin therapy. It is therefore important to understand the molecular basis of this disease in detail and to develop alternative novel therapeutics. Interferon-γ (IFN-γ) is a pro-inflammatory cytokine that is often regarded as a master regulator of atherosclerosis development. IFN-γ is able to influence several key steps during atherosclerosis development, including pro-inflammatory gene expression, the recruitment of monocytes from the blood to the activated arterial endothelium and plaque stability. This central role of IFN-γ makes it a promising therapeutic target. The purpose of this editorial is to describe the key role IFN-γ plays during atherosclerosis development, as well as discuss potential strategies to target it therapeutically. PMID:26309816

  2. Helicon Plasma Injector and Ion Cyclotron Acceleration Development in the VASIMR Experiment

    NASA Technical Reports Server (NTRS)

    Squire, Jared P.; Chang, Franklin R.; Jacobson, Verlin T.; McCaskill, Greg E.; Bengtson, Roger D.; Goulding, Richard H.

    2000-01-01

    In the Variable Specific Impulse Magnetoplasma Rocket (VASIMR) radio frequency (rf) waves both produce the plasma and then accelerate the ions. The plasma production is done by action of helicon waves. These waves are circular polarized waves in the direction of the electron gyromotion. The ion acceleration is performed by ion cyclotron resonant frequency (ICRF) acceleration. The Advanced Space Propulsion Laboratory (ASPL) is actively developing efficient helicon plasma production and ICRF acceleration. The VASIMR experimental device at the ASPL is called VX-10. It is configured to demonstrate the plasma production and acceleration at the 10kW level to support a space flight demonstration design. The VX-10 consists of three electromagnets integrated into a vacuum chamber that produce magnetic fields up to 0.5 Tesla. Magnetic field shaping is achieved by independent magnet current control and placement of the magnets. We have generated both helium and hydrogen high density (>10(exp 18) cu m) discharges with the helicon source. ICRF experiments are underway. This paper describes the VX-10 device, presents recent results and discusses future plans.

  3. Quantum dot mediated imaging of atherosclerosis

    NASA Astrophysics Data System (ADS)

    Jayagopal, Ashwath; Su, Yan Ru; Blakemore, John L.; Linton, MacRae F.; Fazio, Sergio; Haselton, Frederick R.

    2009-04-01

    The progression of atherosclerosis is associated with leukocyte infiltration within lesions. We describe a technique for the ex vivo imaging of cellular recruitment in atherogenesis which utilizes quantum dots (QD) to color-code different cell types within lesion areas. Spectrally distinct QD were coated with the cell-penetrating peptide maurocalcine to fluorescently-label immunomagnetically isolated monocyte/macrophages and T lymphocytes. QD-maurocalcine bioconjugates labeled both cell types with a high efficiency, preserved cell viability, and did not perturb native leukocyte function in cytokine release and endothelial adhesion assays. QD-labeled monocyte/macrophages and T lymphocytes were reinfused in an ApoE-/- mouse model of atherosclerosis and age-matched controls and tracked for up to four weeks to investigate the incorporation of cells within aortic lesion areas, as determined by oil red O (ORO) and immunofluorescence ex vivo staining. QD-labeled cells were visible in atherosclerotic plaques within two days of injection, and the two cell types colocalized within areas of subsequent ORO staining. Our method for tracking leukocytes in lesions enables high signal-to-noise ratio imaging of multiple cell types and biomarkers simultaneously within the same specimen. It also has great utility in studies aimed at investigating the role of distinct circulating leukocyte subsets in plaque development and progression.

  4. DEVELOPING THE PHYSICS DESIGN FOR NDCX-II, A UNIQUE PULSE-COMPRESSING ION ACCELERATOR

    SciTech Connect

    Friedman, A.; Barnard, J. J.; Cohen, R. H.; Grote, D. P.; Lund, S. M.; Sharp, W. M.; Faltens, A.; Henestroza, E.; Jung, J-Y.; Kwan, J. W.; Lee, E. P.; Leitner, M. A.; Logan, B. G.; Vay, J.-L.; Waldron, W. L.; Davidson, R.C.; Dorf, M.; Gilson, E.P.; Kaganovich, I.

    2009-07-20

    The Heavy Ion Fusion Science Virtual National Laboratory(a collaboration of LBNL, LLNL, and PPPL) is using intense ion beams to heat thin foils to the"warm dense matter" regime at<~;; 1 eV, and is developing capabilities for studying target physics relevant to ion-driven inertial fusion energy. The need for rapid target heating led to the development of plasma-neutralized pulse compression, with current amplification factors exceeding 50 now routine on the Neutralized Drift Compression Experiment (NDCX). Construction of an improved platform, NDCX-II, has begun at LBNL with planned completion in 2012. Using refurbished induction cells from the Advanced Test Accelerator at LLNL, NDCX-II will compress a ~;;500 ns pulse of Li+ ions to ~;;1 ns while accelerating it to 3-4 MeV over ~;;15 m. Strong space charge forces are incorporated into the machine design at a fundamental level. We are using analysis, an interactive 1D PIC code (ASP) with optimizing capabilities and centroid tracking, and multi-dimensional Warpcode PIC simulations, to develop the NDCX-II accelerator. This paper describes the computational models employed, and the resulting physics design for the accelerator.

  5. Accelerated stress testing of thin film solar cells: Development of test methods and preliminary results

    NASA Technical Reports Server (NTRS)

    Lathrop, J. W.

    1985-01-01

    If thin film cells are to be considered a viable option for terrestrial power generation their reliability attributes will need to be explored and confidence in their stability obtained through accelerated testing. Development of a thin film accelerated test program will be more difficult than was the case for crystalline cells because of the monolithic construction nature of the cells. Specially constructed test samples will need to be fabricated, requiring committment to the concept of accelerated testing by the manufacturers. A new test schedule appropriate to thin film cells will need to be developed which will be different from that used in connection with crystalline cells. Preliminary work has been started to seek thin film schedule variations to two of the simplest tests: unbiased temperature and unbiased temperature humidity. Still to be examined are tests which involve the passage of current during temperature and/or humidity stress, either by biasing in the forward (or reverse) directions or by the application of light during stress. Investigation of these current (voltage) accelerated tests will involve development of methods of reliably contacting the thin conductive films during stress.

  6. Developing The Physics Desing for NDCS-II, A Unique Pulse-Compressing Ion Accelerator

    SciTech Connect

    Friedman, A; Barnard, J J; Cohen, R H; Grote, D P; Lund, S M; Sharp, W M; Faltens, A; Henestroza, E; Jung, J; Kwan, J W; Lee, E P; Leitner, M A; Logan, B G; Vay, J -; Waldron, W L; Davidson, R C; Dorf, M; Gilson, E P; Kaganovich, I

    2009-09-24

    The Heavy Ion Fusion Science Virtual National Laboratory (a collaboration of LBNL, LLNL, and PPPL) is using intense ion beams to heat thin foils to the 'warm dense matter' regime at {approx}< 1 eV, and is developing capabilities for studying target physics relevant to ion-driven inertial fusion energy. The need for rapid target heating led to the development of plasma-neutralized pulse compression, with current amplification factors exceeding 50 now routine on the Neutralized Drift Compression Experiment (NDCX). Construction of an improved platform, NDCX-II, has begun at LBNL with planned completion in 2012. Using refurbished induction cells from the Advanced Test Accelerator at LLNL, NDCX-II will compress a {approx}500 ns pulse of Li{sup +} ions to {approx} 1 ns while accelerating it to 3-4 MeV over {approx} 15 m. Strong space charge forces are incorporated into the machine design at a fundamental level. We are using analysis, an interactive 1D PIC code (ASP) with optimizing capabilities and centroid tracking, and multi-dimensional Warpcode PIC simulations, to develop the NDCX-II accelerator. This paper describes the computational models employed, and the resulting physics design for the accelerator.

  7. Endothelial dysfunction and progressive coronary atherosclerosis: sequential invasive studies in a patient with multiple cardiac risk factors.

    PubMed

    Chander, R; Kuhner, P A; Laws Houghton, J

    2001-08-01

    This manuscript describes sequential angiographic, endothelial and vasoreactivity characteristics of the coronary arterial circulation in a middle-aged patient with multiple cardiac risk factors who developed hemodynamically significant coronary atherosclerosis over a 6-year period. A 56-year-old woman demonstrated marked angiographic progression of coronary atherosclerosis over time beginning with minor luminal irregularities in the setting of severe endothelial dysfunction. The association of endothelial dysfunction, ineffective cardiac risk factor management and progressive atherosclerosis is discussed. PMID:11481511

  8. Analysis of requirements for accelerating the development of geothermal energy resources in California

    NASA Technical Reports Server (NTRS)

    Fredrickson, C. D.

    1978-01-01

    Various resource data are presented showing that geothermal energy has the potential of satisfying a singificant part of California's increasing energy needs. General factors slowing the development of geothermal energy in California are discussed and required actions to accelerate its progress are presented. Finally, scenarios for developing the most promising prospects in the state directed at timely on-line power are given. Specific actions required to realize each of these individual scenarios are identified.

  9. Multi-Ethnic Study of Atherosclerosis (MESA)

    ClinicalTrials.gov

    2016-07-28

    Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Coronary Artery Disease; Coronary Disease; Stroke; Myocardial Infarction; Heart Failure; Diabetes Mellitus, Type 2; Hypertension; Diabetes Mellitus

  10. Cholesterol-Lowering Atherosclerosis Study (CLAS)

    ClinicalTrials.gov

    2013-12-12

    Arterial Occlusive Diseases; Cardiovascular Diseases; Carotid Artery Diseases; Cerebral Arteriosclerosis; Cerebrovascular Disorders; Coronary Arteriosclerosis; Coronary Disease; Heart Diseases; Myocardial Ischemia; Atherosclerosis

  11. Recent developments in the application of electron accelerators for polymer processing

    NASA Astrophysics Data System (ADS)

    Chmielewski, A. G.; Al-Sheikhly, M.; Berejka, A. J.; Cleland, M. R.; Antoniak, M.

    2014-01-01

    There are now over 1700 high current, electron beam (EB) accelerators being used world-wide in industrial applications, most of which involve polymer processing. In contrast to the use of heat, which transfers only about 5-10% of input energy into energy useful for materials modification, radiation processing is very energy efficient, with 60% or more of the input energy to an accelerator being available for affecting materials. Historic markets, such as the crosslinking of wire and cable jacketing, of heat shrinkable tubings and films, of partial crosslinking of tire components and of low-energy EB to cure or dry inks and coatings remain strong. Accelerator manufacturers have made equipment more affordable by down-sizing units while maintaining high beam currents. Very powerful accelerators with 700 kW output have made X-ray conversion a practical alternative to the historic use of radioisotopes, mainly cobalt-60, for applications as medical device sterilization. New EB end-uses are emerging, such as the development of nano-composites and nano-gels and the use of EB processing to facilitate biofuel production. These present opportunities for future research and development.

  12. What Are the Signs and Symptoms of Atherosclerosis?

    MedlinePlus

    ... Twitter. What Are the Signs and Symptoms of Atherosclerosis? Atherosclerosis usually doesn't cause signs and symptoms ... Rate This Content: NEXT >> Featured Video What is atherosclerosis? 05/22/2014 Describes how the build-up ...

  13. Progress In Plasma Accelerator Development for Dynamic Formation of Plasma Liners

    NASA Technical Reports Server (NTRS)

    Thio, Y. C. Francis; Eskridge, Richard; Martin, Adam; Smith, James; Lee, Michael; Cassibry, Jason T.; Griffin, Steven; Rodgers, Stephen L. (Technical Monitor)

    2002-01-01

    An experimental plasma accelerator for magnetic target fusion (MTF) applications under development at the NASA Marshall Space Flight Center is described. The accelerator is a coaxial pulsed plasma thruster (Figure 1). It has been tested experimentally and plasma jet velocities of approx.50 km/sec have been obtained. The plasma jet has been photographed with 10-ns exposure times to reveal a stable and repeatable plasma structure (Figure 2). Data for velocity profile information has been obtained using light pipes and magnetic probes embedded in the gun walls to record the plasma and current transit respectively at various barrel locations. Preliminary spatially resolved spectral data and magnetic field probe data are also presented. A high speed triggering system has been developed and tested as a means of reducing the gun "jitter". This jitter is being characterized and future work for second generation "ultra-low jitter" gun development is being identified.

  14. A Wind-Tunnel Investigation of the Development of Lift on Wings in Accelerated Longitudinal Motion

    NASA Technical Reports Server (NTRS)

    Turner, Thomas R.

    1960-01-01

    An investigation was made in the Langley 300 MPH 7- by 10-foot tunnel to determine the development of lift on a wing during a simulated constant-acceleration catapult take-off. The investigation included models of a two-dimensional wing, an unswept wing having an aspect ratio of 6, a 35 deg. swept wing having an aspect ratio of 3.05, and a 60 deg. delta wing having an aspect ratio of 2.31. All the wings investigated developed at least 90 percent of their steady-state lift in the first 7 chord lengths of travel. The development of lift was essentially independent of the acceleration when based on chord lengths traveled, and was in qualitative agreement with theory.

  15. Reduction of mouse atherosclerosis by urokinase inhibition or with a limited-spectrum matrix metalloproteinase inhibitor

    PubMed Central

    Hu, Jie Hong; Touch, Phanith; Zhang, Jingwan; Wei, Hao; Liu, Shihui; Lund, Ida K.; Høyer-Hansen, Gunilla; Dichek, David A.

    2015-01-01

    Aims Elevated activity of urokinase plasminogen activator (uPA) and MMPs in human arteries is associated with accelerated atherosclerosis, aneurysms, and plaque rupture. We used Apoe-null mice with macrophage-specific uPA overexpression (SR-uPA mice; a well-characterized model of protease-accelerated atherosclerosis) to investigate whether systemic inhibition of proteolytic activity of uPA or a subset of MMPs can reduce protease-induced atherosclerosis and aortic dilation. Methods and results SR-uPA mice were fed a high-fat diet for 10 weeks and treated either with an antibody inhibiting mouse uPA (mU1) or a control antibody. mU1-treated mice were also compared with PBS-treated non-uPA-overexpressing Apoe-null mice. Other SR-uPA mice were treated with one of three doses of a limited-spectrum synthetic MMP inhibitor (XL784) or vehicle. mU1 reduced aortic root intimal lesion area (20%; P = 0.05) and aortic root circumference (12%; P = 0.01). All XL784 doses reduced aortic root intimal lesion area (22–29%) and oil-red-O-positive lesion area (36–42%; P < 0.05 for all doses and both end points), with trends towards reduced aortic root circumference (6–10%). Neither mU1 nor XL784 significantly altered percent aortic surface lesion coverage. Several lines of evidence identified MMP-13 as a mediator of uPA-induced aortic MMP activity. Conclusions Pharmacological inhibition of either uPA or selected MMPs decreased atherosclerosis in SR-uPA mice. uPA inhibition decreased aortic dilation. Differential effects of both agents on aortic root vs. distal aortic atherosclerosis suggest prevention of atherosclerosis progression vs. initiation. Systemic inhibition of uPA or a subset of MMPs shows promise for treating atherosclerosis. PMID:25616415

  16. Oxyradical Stress, Endocannabinoids, and Atherosclerosis

    PubMed Central

    Matthews, Anberitha T.; Ross, Matthew K.

    2015-01-01

    Atherosclerosis is responsible for most cardiovascular disease (CVD) and is caused by several factors including hypertension, hypercholesterolemia, and chronic inflammation. Oxidants and electrophiles have roles in the pathophysiology of atherosclerosis and the concentrations of these reactive molecules are an important factor in disease initiation and progression. Overactive NADPH oxidase (Nox) produces excess superoxide resulting in oxidized macromolecules, which is an important factor in atherogenesis. Although superoxide and reactive oxygen species (ROS) have obvious toxic properties, they also have fundamental roles in signaling pathways that enable cells to adapt to stress. In addition to inflammation and ROS, the endocannabinoid system (eCB) is also important in atherogenesis. Linkages have been postulated between the eCB system, Nox, oxidative stress, and atherosclerosis. For instance, CB2 receptor-evoked signaling has been shown to upregulate anti-inflammatory and anti-oxidative pathways, whereas CB1 signaling appears to induce opposite effects. The second messenger lipid molecule diacylglycerol is implicated in the regulation of Nox activity and diacylglycerol lipase β (DAGLβ) is a key biosynthetic enzyme in the biosynthesis eCB ligand 2-arachidonylglycerol (2-AG). Furthermore, Nrf2 is a vital transcription factor that protects against the cytotoxic effects of both oxidant and electrophile stress. This review will highlight the role of reactive oxygen species (ROS) in intracellular signaling and the impact of deregulated ROS-mediated signaling in atherogenesis. In addition, there is also emerging knowledge that the eCB system has an important role in atherogenesis. We will attempt to integrate oxidative stress and the eCB system into a conceptual framework that provides insights into this pathology. PMID:26702404

  17. Twin-Screw Extruder and Pellet Accelerator Integration Developments for ITER

    SciTech Connect

    Meitner, Steven J; Baylor, Larry R; Combs, Stephen Kirk; Fehling, Dan T; Foust, Charles R; McGill, James M; Rasmussen, David A; Maruyama, So

    2011-01-01

    The ITER pellet injection system consisting of a twinscrew frozen hydrogen isotope extruder, coupled to a combination solenoid actuated pellet cutter and pneumatic pellet accelerator, is under development at the Oak Ridge National Laboratory. A prototype extruder has been built to produce a continuous solid deuterium extrusion and will be integrated with a secondary section, where pellets are cut, chambered, and launched with a single-stage pneumatic accelerator into the plasma through a guide tube. This integrated pellet injection system is designed to provide 5 mm fueling pellets, injected at a rate up to 10 Hz, or 3 mm edge localized mode (ELM) triggering pellets, injected at higher rates up to 20 Hz. The pellet cutter, chamber mechanism, and the solenoid operated pneumatic valve for the accelerator are optimized to provide pellet velocities between 200-300 m/s to ensure high pellet survivability while traversing the inner wall fueling guide tubes, and outer wall ELMpacing guide tubes. This paper outlines the current twin-screwextruder design, pellet accelerator design, and the integrationrequired for both fueling and ELM pacing pellets.

  18. The role of oxidative stress and autophagy in atherosclerosis.

    PubMed

    Perrotta, Ida; Aquila, Saveria

    2015-01-01

    Atherosclerosis is a multifactorial, multistep disorder of large- and medium-sized arteries involving, in addition to age, gender and menopausal status, a complex interplay between lifestyle and genetic risk factors. Atherosclerosis usually begins with the diffusion and retention of atherogenic lipoproteins into the subendothelial space of the artery wall where they become oxidized by local enzymes and accumulate, leading to the formation of a cushion called atheroma or atheromatous or fibrofatty plaque, composed of a mixture of macrophages, lymphocytes, smooth muscle cells (SMCs), cholesterol cleft, necrotic debris, and lipid-laden foam cells. The pathogenesis of atherosclerosis still remains incompletely understood but emerging evidence suggests that it may involve multiple cellular events, including endothelial cell (EC) dysfunction, inflammation, proliferation of vascular SMCs, matrix (ECM) alteration, and neovascularization. Actually, a growing body of evidence indicates that autophagy along with the chronic and acute overproduction of reactive oxygen species (ROS) is integral to the development and progression of the disease and may represent fruitful avenues for biological investigation and for the identification of new therapeutic targets. In this review, we give an overview of ROS and autophagy in atherosclerosis as background to understand their potential role in this vascular disease. PMID:25866599

  19. Suppression of atherosclerosis by synthetic REV-ERB agonist.

    PubMed

    Sitaula, Sadichha; Billon, Cyrielle; Kamenecka, Theodore M; Solt, Laura A; Burris, Thomas P

    2015-05-01

    The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. PMID:25800870

  20. Priority research areas to accelerate the development of practical ultraconductive copper conductors

    SciTech Connect

    Lee, Dominic F.; Burwell, Malcolm; Stillman, H.

    2015-09-01

    This report documents the findings at an Ultraconductive Copper Strategy Meeting held on March 11, 2015 in Washington DC. The aim of this meeting was to bring together researchers of ultraconductive copper in the U.S. to identify and prioritize critical non-proprietary research activities that will enhance the understanding in the material and accelerate its development into practical conductors. Every effort has been made to ensure that the discussion and findings are accurately reported in this document.

  1. Development of an accelerated reliability test schedule for terrestrial solar cells

    NASA Technical Reports Server (NTRS)

    Lathrop, J. W.; Prince, J. L.

    1981-01-01

    An accelerated test schedule using a minimum amount of tests and a minimum number of cells has been developed on the basis of stress test results obtained from more than 1500 cells of seven different cell types. The proposed tests, which include bias-temperature, bias-temperature-humidity, power cycle, thermal cycle, and thermal shock tests, use as little as 10 and up to 25 cells, depending on the test type.

  2. Development of a photovoltaic module qualification test based on combined-environment accelerated stress data

    NASA Astrophysics Data System (ADS)

    Trenchard, S. E.; Royal, E.; Anderson, R. T.

    The U.S. Coast Guard has developed a qualification test to screen photovoltaic modules for utilization on marine aids to navigation. The test is based on a combined-environment of hot and cold saltwater immersion and air pressurization. The test has demonstrated a very high acceleration factor and excellent correlation of electrical failures with modules in a concurrent real-time marine exposure.

  3. Development of a photovoltaic module qualification test based on combined-environment accelerated stress data

    NASA Technical Reports Server (NTRS)

    Trenchard, S. E.; Royal, E.; Anderson, R. T.

    1982-01-01

    The U.S. Coast Guard has developed a qualification test to screen photovoltaic modules for utilization on marine aids to navigation. The test is based on a combined-environment of hot and cold saltwater immersion and air pressurization. The test has demonstrated a very high acceleration factor and excellent correlation of electrical failures with modules in a concurrent real-time marine exposure.

  4. Endothelium Preserving Microwave Treatment for Atherosclerosis

    NASA Technical Reports Server (NTRS)

    Fink, Patrick; Arndt, G. D.; Ngo, Phong

    2003-01-01

    This slide presentation reviews the use of microwave technology for treating Atherosclerosis while preserving the endothelium. The system uses catheter antennas as part of the system that is intended to treat atherosclerosis. The concept is to use a microwave catheter for heating the atherosclerotic lesions, and reduce constriction in the artery.

  5. Subclinical Atherosclerosis and Obesity Phenotypes Among Mexican Americans

    PubMed Central

    Laing, Susan T.; Smulevitz, Beverly; Vatcheva, Kristina P.; Rahbar, Mohammad H.; Reininger, Belinda; McPherson, David D.; McCormick, Joseph B.; Fisher‐Hoch, Susan P.

    2015-01-01

    Background Data on the influence of obesity on atherosclerosis in Hispanics are inconsistent, possibly related to varying cardiometabolic risk among obese individuals. We aimed to determine the association of obesity and cardiometabolic risk with subclinical atherosclerosis in Mexican‐Americans. Methods and Results Participants (n=503) were drawn from the Cameron County Hispanic Cohort. Metabolic health was defined as <2 of the following: blood pressure ≥130/85; triglyceride ≥150 mg/dL; high‐density lipoprotein cholesterol <40 mg/dL (men) or <50 mg/dL (women); fasting glucose ≥100 mg/dL; homeostasis model assessment of insulin resistance value >5.13; or high‐sensitivity C‐reactive protein >3 mg/L. Carotid intima media thickness (cIMT) was measured. A high proportion of participants (77.8%) were metabolically unhealthy; they were more likely to be male, older, with fewer years of education, and less likely to meet daily recommendations regarding fruit and vegetable servings. One‐third (31.8%) had abnormal carotid ultrasound findings. After adjusting for covariates, mean cIMT varied across the obesity phenotypes (P=0.0001); there was no difference among the metabolically unhealthy regardless of whether they were obese or not. In multivariable analysis, after adjusting for covariates, cardiometabolic risk (P=0.0159), but not obesity (P=0.1446), was significantly associated with subclinical atherosclerosis. Conclusions In Mexican‐Americans, cardiometabolic risk has a greater effect on early atherosclerosis development than body mass index. Non‐obese but metabolically unhealthy participants had similar development of subclinical atherosclerosis as their obese counterparts. Interventions to maintain metabolic health among obese and non‐obese patients may be a more important goal than weight loss alone. PMID:25787312

  6. Beyond vascular inflammation--recent advances in understanding atherosclerosis.

    PubMed

    Wolf, Dennis; Zirlik, Andreas; Ley, Klaus

    2015-10-01

    Atherosclerosis is the most life-threatening pathology worldwide. Its major clinical complications, stroke, myocardial infarction, and heart failure, are on the rise in many regions of the world--despite considerable progress in understanding cause, progression, and consequences of atherosclerosis. Originally perceived as a lipid-storage disease of the arterial wall (Die cellularpathologie in ihrer begründung auf physiologische und pathologische gewebelehre. August Hirschwald Verlag Berlin, [1871]), atherosclerosis was recognized as a chronic inflammatory disease in 1986 (New Engl J Med 314:488-500, 1986). The presence of lymphocytes in atherosclerotic lesions suggested autoimmune processes in the vessel wall (Clin Exp Immunol 64:261-268, 1986). Since the advent of suitable mouse models of atherosclerosis (Science 258:468-471, 1992; Cell 71:343-353, 1992; J Clin Invest 92:883-893, 1993) and the development of flow cytometry to define the cellular infiltrate in atherosclerotic lesions (J Exp Med 203:1273-1282, 2006), the origin, lineage, phenotype, and function of distinct inflammatory cells that trigger or inhibit the inflammatory response in the atherosclerotic plaque have been studied. Multiphoton microscopy recently enabled direct visualization of antigen-specific interactions between T cells and antigen-presenting cells in the vessel wall (J Clin Invest 122:3114-3126, 2012). Vascular immunology is now emerging as a new field, providing evidence for protective as well as damaging autoimmune responses (Int Immunol 25:615-622, 2013). Manipulating inflammation and autoimmunity both hold promise for new therapeutic strategies in cardiovascular disease. Ongoing work (J Clin Invest 123:27-36, 2013; Front Immunol 2013; Semin Immunol 31:95-101, 2009) suggests that it may be possible to develop antigen-specific immunomodulatory prevention and therapy-a vaccine against atherosclerosis. PMID:26100516

  7. Requirements and Development of an Acceleration Measurement System for International Space Station Microgravity Science Payloads

    NASA Technical Reports Server (NTRS)

    Sutliff, Thomas J.

    1997-01-01

    The International Space Station is being developed by NASA and international partners as a versatile user platform to allow long term on-orbit investigations of a variety of scientific and technology arenas. In particular, scientific studies are planned within a research class known as microgravity science in areas such as biotechnology, combustion, fluid physics, and materials sciences. An acceleration measurement system is in development to aid such research conducted in the on-orbit conditions of apparent weightlessness. This system provides a general purpose acceleration measurement capability in support of these payloads and investigators. Such capability allows for systematic study of scientific phenomena by obtaining information regarding the local accelerations present during experiment operations. Preparations for implementing this flight measurement system involves two distinct stages: requirements development prior to initiating the design activity, and the design activity itself. This paper defines the requirements definition approach taken, provides an overview of the results of the requirements phase, and outlines the initial design considerations being addressed for this measurement system. Some preliminary engineering approaches are also described.

  8. Role of LCAT in Atherosclerosis.

    PubMed

    Ossoli, Alice; Simonelli, Sara; Vitali, Cecilia; Franceschini, Guido; Calabresi, Laura

    2016-01-01

    Lecithin:cholesterol acyltransferase (LCAT) is the only enzyme capable of esterifying cholesterol in plasma, thus determining the maturation of high-density lipoproteins. Because it maintains an unesterified cholesterol gradient between peripheral cells and extracellular acceptors, for a long time, LCAT has been considered as a key enzyme in reverse cholesterol transport. However, despite the fact that it has been more than 50 years since the identification of LCAT, the role of this enzyme in the pathogenesis of atherosclerosis is still debated. A number of studies have been conducted in different animal models, with contradictory results. Studies in humans, in particular in the general population, in subjects at high cardiovascular risk, and in carriers of genetic LCAT deficiency in an excellent model to evaluate the correlation between the reduction of LCAT activity and atherosclerosis also gave conflicting results. This review provides a comprehensive overview of the controversial findings obtained in animals and humans, strengthening the necessity of further investigation to establish how LCAT could be regulated in a promising therapeutic strategy to reduce cardiovascular risk. PMID:26607351

  9. The roles of macrophage autophagy in atherosclerosis

    PubMed Central

    Shao, Bo-zong; Han, Bin-ze; Zeng, Yan-xia; Su, Ding-feng; Liu, Chong

    2016-01-01

    Although various types of drugs and therapies are available to treat atherosclerosis, it remains a major cause of mortality throughout the world. Macrophages are the major source of foam cells, which are hallmarks of atherosclerotic lesions. Consequently, the roles of macrophages in the pathophysiology of atherosclerosis are increasingly investigated. Autophagy is a self-protecting cellular catabolic pathway. Since its discovery, autophagy has been found to be associated with a variety of diseases, including cardiovascular diseases, malignant tumors, neurodegenerative diseases, and immune system disorders. Accumulating evidence demonstrates that autophagy plays an important role in inhibiting inflammation and apoptosis, and in promoting efferocytosis and cholesterol efflux. These facts suggest the induction of autophagy may be exploited as a potential strategy for the treatment of atherosclerosis. In this review we mainly discuss the relationship between macrophage autophagy and atherosclerosis and the molecular mechanisms, as well as the recent advances in targeting the process of autophagy to treat atherosclerosis. PMID:26750103

  10. Vasa Vasorum in Atherosclerosis and Clinical Significance

    PubMed Central

    Xu, Junyan; Lu, Xiaotong; Shi, Guo-Ping

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease that leads to several acute cardiovascular complications with poor prognosis. For decades, the role of the adventitial vasa vasorum (VV) in the initiation and progression of atherosclerosis has received broad attention. The presence of VV neovascularization precedes the apparent symptoms of clinical atherosclerosis. VV also mediates inflammatory cell infiltration, intimal thickening, intraplaque hemorrhage, and subsequent atherothrombosis that results in stroke or myocardial infarction. Intraplaque neovessels originating from VV can be immature and hence susceptible to leakage, and are thus regarded as the leading cause of intraplaque hemorrhage. Evidence supports VV as a new surrogate target of atherosclerosis evaluation and treatment. This review provides an overview into the relationship between VV and atherosclerosis, including the anatomy and function of VV, the stimuli of VV neovascularization, and the available underlying mechanisms that lead to poor prognosis. We also summarize translational researches on VV imaging modalities and potential therapies that target VV neovascularization or its stimuli. PMID:26006236

  11. The trade-off between maturation and growth during accelerated development in frogs.

    PubMed

    Mueller, Casey A; Augustine, Starrlight; Kooijman, Sebastiaan A L M; Kearney, Michael R; Seymour, Roger S

    2012-09-01

    Developmental energetics are crucial to a species' life history and ecology but are poorly understood from a mechanistic perspective. Traditional energy and mass budgeting does not distinguish between costs of growth and maturation, making it difficult to account for accelerated development. We apply a metabolic theory that uniquely considers maturation costs (Dynamic Energy Budget theory, DEB) to interpret empirical data on the energetics of accelerated development in amphibians. We measured energy use until metamorphosis in two related frogs, Crinia georgiana and Pseudophryne bibronii. Mass and energy content of fresh ova were comparable between the species. However, development to metamorphosis was 1.7 times faster in C. georgiana while P. bibronii produced nine times the dry biomass at metamorphosis and had lower mass-specific oxygen requirements. DEB theory explained these patterns through differences in ontogenetic energy allocation to maturation. P. bibronii partitioned energy in the same (constant) way throughout development whereas C. georgiana increased the fraction of energy allocated to maturation over growth between hatching and the onset of feeding. DEB parameter estimation for additional, direct-developing taxa suggests that a change in energy allocation during development may result from a selective pressure to increase development rate, and not as a result of development mode. PMID:22613786

  12. Development of a Dielectric-Loaded Accelerator Test Facility Based on an X-Band Magnicon Amplifier

    SciTech Connect

    Gold, S. H.; Fliflet, A. W.; Kinkead, A. K.; Gai, W.; Power, J. G.; Konecny, R.; Jing, C.; Tantawi, S. G.; Nantista, C. D.; Hu, Y.; Du, X.; Tang, C.; Lin, Y.; Bruce, R. W.; Bruce, R. L.; Lewis, D. III

    2006-01-03

    The Naval Research Laboratory (NRL) and Argonne National Laboratory (ANL), in collaboration with the Stanford Linear Accelerator Center (SLAC), are developing a dielectric-loaded accelerator (DLA) test facility powered by the 11.424-GHz magnicon amplifier that was developed jointly by NRL and Omega-P, Inc. Thus far, DLA structures developed by ANL have been tested at the NRL Magnicon Facility without injected electrons, including tests of alumina and magnesium calcium titanate structures at gradients up to {approx}8 MV/m. The next step is to inject electrons in order to build a compact DLA test accelerator. The Accelerator Laboratory of Tsinghua University in Beijing, China has developed a 5-MeV electron injector for the accelerator, and SLAC is developing a means to combine the two magnicon output arms, and to drive the injector and an accelerator section with separate control of the power ratio and relative phase. Also, RWBruce Associates, working with NRL, is developing a means to join ceramic tubes to produce long accelerating sections using a microwave brazing process. The installation and commissioning of the first dielectric-loaded test accelerator, including injector, DLA structure, and spectrometer, should take place within the next year.

  13. Can Accelerators Accelerate Learning?

    NASA Astrophysics Data System (ADS)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  14. [Fibrinogen--acute phase protein as a marker of immunological process as atherosclerosis].

    PubMed

    Rajtari, Renata; Kloch, Małgorzata; Kiec-Wilk, Beata; Kolasińska-Kloch, Władysława

    2005-01-01

    The most important CAD risk factors are: smoking, high level of LDL-cholesterol and low level of HDL-cholesterol, hypertriglyceridemia, diabetes, obesity, hypertension, men sex, age over 45 in men and over 55 in women. Carl von Rokitański was the first who suggested the role of thrombosis and fibrynolisis in the development of atherosclerosis and was the author of thrombolic theory. The recently studies show that atherosclerosis is an immuno-inflamatory process. Fibrinogen as an acute phase protein is a new marker of ischemic heart disease and its role in atherosclerosis needs further investigations. PMID:17037285

  15. Atherosclerosis

    MedlinePlus

    ... disease in which plaque builds up inside your arteries. Plaque is a sticky substance made up of ... blood. Over time, plaque hardens and narrows your arteries. That limits the flow of oxygen-rich blood ...

  16. Atherosclerosis

    MedlinePlus

    ... heart health as EPA and DHA. Red yeast rice. A common seasoning in Asian countries, red yeast rice may help reduce the amount of cholesterol your ... Talk to your doctor before taking red yeast rice, especially if you take another cholesterol-lowering medicine ...

  17. Adaptive (T and B cells) immunity and control by dendritic cells in atherosclerosis.

    PubMed

    Ait-Oufella, Hafid; Sage, Andrew P; Mallat, Ziad; Tedgui, Alain

    2014-05-01

    Chronic inflammation in response to lipoprotein accumulation in the arterial wall is central in the development of atherosclerosis. Both innate and adaptive immunity are involved in this process. Adaptive immune responses develop against an array of potential antigens presented to effector T lymphocytes by antigen-presenting cells, especially dendritic cells. Functional analysis of the role of different T-cell subsets identified the Th1 responses as proatherogenic, whereas regulatory T-cell responses exert antiatherogenic activities. The effect of Th2 and Th17 responses is still debated. Atherosclerosis is also associated with B-cell activation. Recent evidence established that conventional B-2 cells promote atherosclerosis. In contrast, innate B-1 B cells offer protection through secretion of natural IgM antibodies. This review discusses the recent development in our understanding of the role of T- and B-cell subsets in atherosclerosis and addresses the role of dendritic cell subpopulations in the control of adaptive immunity. PMID:24812352

  18. Development of an ion beam analyzing system for the KBSI heavy-ion accelerator.

    PubMed

    Bahng, Jungbae; Hong, Jonggi; Park, Jin Yong; Kim, Seong Jun; Ok, Jung-Woo; Choi, Seyong; Shin, Chang Seouk; Yoon, Jang-Hee; Won, Mi-Sook; Lee, Byoung-Seob; Kim, Eun-San

    2016-02-01

    The Korea Basic Science Institute (KBSI) has been developing a heavy ion accelerator system to accelerate high current, multi-charge state ions produced by a 28 GHz superconducting electron cyclotron ion source. A beam analyzing system as a part of the low energy beam transport apparatus was developed to select charged particles with desirable charge states from the ion beams. The desired species of ion, which is generated and extracted from the ECR ion source including various ion particles, can be selected by 90° dipole electromagnet. Due to the non-symmetrical structure in the coil as well as the non-linear permeability of the yoke material coil, a three dimensional analysis was carried out to confirm the design parameters. In this paper, we present the experimental results obtained as result of an analysis of KBSI accelerator. The effectiveness of beam selection was confirmed during the test of the analyzing system by injecting an ion beam from an ECR ion source. PMID:26932105

  19. Development of an ion beam analyzing system for the KBSI heavy-ion accelerator

    NASA Astrophysics Data System (ADS)

    Bahng, Jungbae; Hong, Jonggi; Park, Jin Yong; Kim, Seong Jun; Ok, Jung-Woo; Choi, Seyong; Shin, Chang Seouk; Yoon, Jang-Hee; Won, Mi-Sook; Lee, Byoung-Seob; Kim, Eun-San

    2016-02-01

    The Korea Basic Science Institute (KBSI) has been developing a heavy ion accelerator system to accelerate high current, multi-charge state ions produced by a 28 GHz superconducting electron cyclotron ion source. A beam analyzing system as a part of the low energy beam transport apparatus was developed to select charged particles with desirable charge states from the ion beams. The desired species of ion, which is generated and extracted from the ECR ion source including various ion particles, can be selected by 90° dipole electromagnet. Due to the non-symmetrical structure in the coil as well as the non-linear permeability of the yoke material coil, a three dimensional analysis was carried out to confirm the design parameters. In this paper, we present the experimental results obtained as result of an analysis of KBSI accelerator. The effectiveness of beam selection was confirmed during the test of the analyzing system by injecting an ion beam from an ECR ion source.

  20. Update on the development of externally powered dielectric-loaded accelerating structures.

    SciTech Connect

    Jing, C.; Gai, W.; Konecny, R.; Power, J. G.; Liu, W.; Kanareykin, A.; Gold, S.; Kinkead, A. K.; High Energy Physics; EuclidTechlabs,; Naval Research Lab.; Icarus Research

    2009-01-01

    We report on recent progress in a program to develop an RF-driven Dielectric-Loaded Accelerating (DLA) structure, capable of supporting high gradient acceleration. Previous high power tests revealed that the earlier DLA structures suffered from multipactor and arcing at the dielectric joint. A few new DLA structures have been designed to alleviate this limitation including the coaxial coupler based DLA structure and the clamped DLA structure. These structures were recently fabricated and high power tested at the NRL X-band Magnicon facility. Results show the multipactor can be reduced by the TiN coating on the dielectric surface. Gradient of 15 MV/m has also been tested without dielectric breakdown in the test of the clamped DLA structure. Detailed results are reported, and future plans discussed.

  1. Testing Done for Lorentz Force Accelerators and Electrodeless Propulsion Technology Development

    NASA Technical Reports Server (NTRS)

    Pencil, Eric J.; Gilland, James H.; Arrington, Lynn A.; Kamhawi, Hani

    2004-01-01

    The NASA Glenn Research Center is developing Lorentz force accelerators and electrodeless plasma propulsion for a wide variety of space applications. These applications range from precision control of formation-flying spacecraft to primary propulsion for very high power interplanetary spacecraft. The specific thruster technologies being addressed are pulsed plasma thrusters, magnetoplasmadynamic thrusters, and helicon-electron cyclotron resonance acceleration thrusters. The pulsed plasma thruster mounted on the Earth Observing-1 spacecraft was operated successfully in orbit in 2002. The two-axis thruster system is fully incorporated in the attitude determination and control system and is being used to automatically counteract disturbances in the pitch axis of the spacecraft. Recent on-orbit operations have focused on extended operations to add flight operation time to the total accumulated thruster life. The results of the experiments pave the way for electric propulsion applications on future Earth-imaging satellites.

  2. Update on the Development of Externally Powered Dielectric-Loaded Accelerating Structures

    SciTech Connect

    Jing, C.; Kanareykin, A.; Gai, W.; Konecny, R.; Power, J. G.; Liu, W.; Gold, S. H.; Kinkead, A. K.

    2009-01-22

    We report on recent progress in a program to develop an RF-driven Dielectric-Loaded Accelerating (DLA) structure, capable of supporting high gradient acceleration. Previous high power tests revealed that the earlier DLA structures suffered from multipactor and arcing at the dielectric joint. A few new DLA structures have been designed to alleviate this limitation including the coaxial coupler based DLA structure and the clamped DLA structure. These structures were recently fabricated and high power tested at the NRL X-band Magnicon facility. Results show the multipactor can be reduced by the TiN coating on the dielectric surface. Gradient of 15 MV/m has also been tested without dielectric breakdown in the test of the clamped DLA structure. Detailed results are reported, and future plans discussed.

  3. Development of Wind-and-React Bi-2212 Accelerator Magnet Technology

    SciTech Connect

    Godeke, A.; Cheng, D.; Dietderich, D. R.; English, C. D.; Felice, H.; Hannaford, C. R.; Prestemon, S. O.; Sabbi, G.; Scanlan, R. M.; Hikichi, Y.; Nishioka, J.; Hasegawa, T.

    2007-08-28

    We report on the progress in our R&D program, targeted to develop the technology for the application of Bi2Sr2CaCu2Ox (Bi-2212) in accelerator magnets. The program uses subscale coils, wound from insulated cables, to study suitable materials, heat treatment homogeneity, stability, and effects of magnetic field and thermal and electro-magnetic loads. We have addressed material and reaction related issues and report on the fabrication, heat treatment, and analysis of subscale Bi-2212 coils. Such coils can carry a current on the order of 5000 A and generate, in various support structures, magnetic fields from 2.6 to 9.9 T. Successful coils are therefore targeted towards a hybrid Nb3Sn-HTS magnet which will demonstrate the feasibility of Bi-2212 for accelerator magnets, and open a new magnetic field realm, beyond what is achievable with Nb3Sn.

  4. Recent Progress in the Development of a Circular Ion Induction Accelerator for Space Charge Dominated Beams

    NASA Astrophysics Data System (ADS)

    Ahle, L.; Sangster, T. C.; Autrey, D.; Barnard, J.; Craig, G.; Friedman, A.; Grote, D. P.; Halaxa, E.; Hanks, R. L.; Hernandez, M.; Kirbie, H. C.; Logan, B. G.; Lund, S. M.; Mant, G.; Molvik, A.; Sharp, W.; Berners, D.; Eylon, S.; Judd, D. L.; Reginato, L.; Debeling, A.; Fritz, W.

    1998-11-01

    The Heavy Ion Fusion Group at Lawrence Livermore National Laboratory has been developing the world's first ion induction accelerator. This machine has recently been extended to 90 degress, or 10 half-lattice periods(HLP) with full beam transport. As part of this extension, two new diagnostic systems have been fully enabled, the Capacitive Beam Probes(C-probes) and the Gated Beam Imager(GBI). The C-probes measure the charge centroid of the beam in each HLP and the GBI measures emittance in both transverse planes. Output from both diagnostics will be presented. In addition, induction cores have been installed on five of the HLP's, in anticipation of the first attempts at acceleration. The status of these attempts will also be discussed.

  5. Development of an S-band accelerating structure with quasi-symmetric single-feed racetrack couplers

    NASA Astrophysics Data System (ADS)

    Heo, Hoon; Joo, Young-Do; Park, Yong-Jung; Kang, Heung-Sik; Lee, Heung-Soo; Oh, Kyoung-Min; Seo, Hyung-Seok; Noh, Sung-Ju

    2015-03-01

    We developed an S-band traveling-wave accelerating structure for the Pohang Accelerator Laboratory's X-ray free-electron laser (PAL-XFEL), and we fabricated and tested a full-scale prototype. In order to reduce the field asymmetry inside the coupler cavity, we used the SUPERFISH code and the CST MWS electromagnetic field solvers to design the constant-gradient traveling-wave accelerator to use quasi-symmetric single-feed racetrack couplers. The RF measurement results indicate that the accelerating gradient of the prototype structure is as high as 27 MV/m for an input RF power of 65 MW.

  6. Increasing Spontaneous Retinal Activity before Eye Opening Accelerates the Development of Geniculate Receptive Fields

    PubMed Central

    Davis, Zachary W.; Chapman, Barbara

    2015-01-01

    Visually evoked activity is necessary for the normal development of the visual system. However, little is known about the capacity for patterned spontaneous activity to drive the maturation of receptive fields before visual experience. Retinal waves provide instructive retinotopic information for the anatomical organization of the visual thalamus. To determine whether retinal waves also drive the maturation of functional responses, we increased the frequency of retinal waves pharmacologically in the ferret (Mustela putorius furo) during a period of retinogeniculate development before eye opening. The development of geniculate receptive fields after receiving these increased neural activities was measured using single-unit electrophysiology. We found that increased retinal waves accelerate the developmental reduction of geniculate receptive field sizes. This reduction is due to a decrease in receptive field center size rather than an increase in inhibitory surround strength. This work reveals an instructive role for patterned spontaneous activity in guiding the functional development of neural circuits. SIGNIFICANCE STATEMENT Patterned spontaneous neural activity that occurs during development is known to be necessary for the proper formation of neural circuits. However, it is unknown whether the spontaneous activity alone is sufficient to drive the maturation of the functional properties of neurons. Our work demonstrates for the first time an acceleration in the maturation of neural function as a consequence of driving patterned spontaneous activity during development. This work has implications for our understanding of how neural circuits can be modified actively to improve function prematurely or to recover from injury with guided interventions of patterned neural activity. PMID:26511250

  7. Recent developments in rf superconductivity for high-brightness and high-gradient ion beam accelerators

    SciTech Connect

    Delayen, J.R.; Bohn, C.L.; Kennedy, W.L.; Nichols, G.L.; Roche, C.T.; Sagalovsky, L.

    1992-01-01

    Recent progress in on-going development program leading to the design of superconducting continuous-wave (cw) linear accelerators for high-brightness ion beams is reviewed. A new spoke-resonator geometry incorporating a half-wavelength resonant line was fabricated and tested. This geometry serves as the basis for the constituent cavities of a superconducting section being designed for high-current testing with a deuterium beam. Considerable progress has been made in the design of this section. A multi-phased program leading to the development of a superconducting radio-frequency quadrupole (SCRFQ) has been initiated. Design considerations and test results from the various activities are presented.

  8. Recent developments in rf superconductivity for high-brightness and high-gradient ion beam accelerators

    SciTech Connect

    Delayen, J.R.; Bohn, C.L.; Kennedy, W.L.; Nichols, G.L.; Roche, C.T.; Sagalovsky, L.

    1992-02-01

    Recent progress in on-going development program leading to the design of superconducting continuous-wave (cw) linear accelerators for high-brightness ion beams is reviewed. A new spoke-resonator geometry incorporating a half-wavelength resonant line was fabricated and tested. This geometry serves as the basis for the constituent cavities of a superconducting section being designed for high-current testing with a deuterium beam. Considerable progress has been made in the design of this section. A multi-phased program leading to the development of a superconducting radio-frequency quadrupole (SCRFQ) has been initiated. Design considerations and test results from the various activities are presented.

  9. Education and Skills for Development in South Africa: Reflections on the Accelerated and Shared Growth Initiative for South Africa

    ERIC Educational Resources Information Center

    McGrath, S.; Akoojee, Salim

    2007-01-01

    In July 2005, President Mbeki announced the launch of the Accelerated and Shared Growth Initiative for South Africa (AsgiSA), a new development strategy designed to help the South African state meet the ANC's 2004 election pledges, namely: (1) halve unemployment; (2) halve poverty; (3) accelerate employment equity; and (4) improve broad-based…

  10. Calcified coronary artery plaque measurement with cardiac CT in population-based studies: standardized protocol of Multi-Ethnic Study of Atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) study.

    PubMed

    Carr, J Jeffrey; Nelson, Jennifer Clark; Wong, Nathan D; McNitt-Gray, Michael; Arad, Yadon; Jacobs, David R; Sidney, Stephan; Bild, Diane E; Williams, O Dale; Detrano, Robert C

    2005-01-01

    Calcified coronary artery plaque, measured at cardiac computed tomography (CT), is a predictor of cardiovascular disease and may play an increasing role in cardiovascular disease risk assessment. The Multi-Ethnic Study of Atherosclerosis (MESA) and the Coronary Artery Risk Development in Young Adults (CARDIA) study of the National Heart, Lung, and Blood Institute are population-based studies in which calcified coronary artery plaque was measured with electron-beam and multi-detector row CT and a standardized protocol in 6814 (MESA) and 3044 (CARDIA study) participants. The studies were approved by the appropriate institutional review board from the study site or agency, and written informed consent was obtained from each participant. Participation in the CT examination was high, image quality was good, and agreement for the presence of calcified plaque was high (kappa = 0.92, MESA; kappa = 0.77, CARDIA study). Extremely high agreement was observed between and within CT image analysts for the presence (kappa > 0.90, all) and amount (intraclass correlation coefficients, >0.99) of calcified plaque. Measurement of calcified coronary artery plaque with cardiac CT is well accepted by participants and can be implemented with consistently high-quality results with a standardized protocol and trained personnel. If predictive value of calcified coronary artery plaque for cardiovascular events proves sufficient to justify screening a segment of the population, then a standardized cardiac CT protocol is feasible and will provide reproducible results for health care providers and the public. PMID:15618373

  11. α-Defensins Induce a Post-translational Modification of Low Density Lipoprotein (LDL) That Promotes Atherosclerosis at Normal Levels of Plasma Cholesterol.

    PubMed

    Abu-Fanne, Rami; Maraga, Emad; Abd-Elrahman, Ihab; Hankin, Aviel; Blum, Galia; Abdeen, Suhair; Hijazi, Nuha; Cines, Douglas B; Higazi, Abd Al-Roof

    2016-02-01

    Approximately one-half of the patients who develop clinical atherosclerosis have normal or only modest elevations in plasma lipids, indicating that additional mechanisms contribute to pathogenesis. In view of increasing evidence that inflammation contributes to atherogenesis, we studied the effect of human neutrophil α-defensins on low density lipoprotein (LDL) trafficking, metabolism, vascular deposition, and atherogenesis using transgenic mice expressing human α-defensins in their polymorphonuclear leukocytes (Def(+/+)). Accelerated Def(+/+) mice developed α-defensin·LDL complexes that accelerate the clearance of LDL from the circulation accompanied by enhanced vascular deposition and retention of LDL, induction of endothelial cathepsins, increased endothelial permeability to LDL, and the development of lipid streaks in the aortic roots when fed a regular diet and at normal plasma levels of LDL. Transplantation of bone marrow from Def(+/+) to WT mice increased LDL clearance, increased vascular permeability, and increased vascular deposition of LDL, whereas transplantation of WT bone marrow to Def(+/+) mice prevented these outcomes. The same outcome was obtained by treating Def(+/+) mice with colchicine to inhibit the release of α-defensins. These studies identify a potential new link between inflammation and the development of atherosclerosis. PMID:26518877

  12. Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis

    PubMed Central

    Baumgartl, Julia; Baudler, Stephanie; Scherner, Maximilian; Babaev, Vladimir; Makowski, Liza; Suttles, Jill; McDuffie, Marcia; Fazio, Sergio; Kahn, C. Ronald; Hotamisligil, Gökhan S.; Krone, Wilhelm; Linton, MacRae; Brüning, Jens C.

    2014-01-01

    Summary Inflammatory processes play an important role in the pathogenesis of vascular diseases, and insulin-resistant diabetes mellitus type 2 represents an important risk factor for the development of atherosclerosis. To directly address the role of insulin resistance in myeloid lineage cells in the development of atherosclerosis, we have created mice with myeloid lineagespecific inactivation of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice developed smaller atherosclerotic lesions. There was a dramatic decrease in LPS-stimulated IL-6 and IL-1β expression in the presence of macrophage autonomous insulin resistance. Consistently, while insulin-resistant IRS-2-deficient mice on an ApoE-deficient background display aggravated atherosclerosis, fetal liver cell transplantation of IRS-2–/–ApoE–/– cells ameliorated atherosclerosis in Apo-E-deficient mice. Thus, systemic versus myeloid cell-restricted insulin resistance has opposing effects on the development of atherosclerosis, providing direct evidence that myeloid lineage autonomous insulin signaling provides proinflammatory signals predisposing to the development of atherosclerosis. PMID:16581002

  13. Accelerating vaccine development and deployment: report of a Royal Society satellite meeting

    PubMed Central

    Bregu, Migena; Draper, Simon J.; Hill, Adrian V. S.; Greenwood, Brian M.

    2011-01-01

    The Royal Society convened a meeting on the 17th and 18th November 2010 to review the current ways in which vaccines are developed and deployed, and to make recommendations as to how each of these processes might be accelerated. The meeting brought together academics, industry representatives, research sponsors, regulators, government advisors and representatives of international public health agencies from a broad geographical background. Discussions were held under Chatham House rules. High-throughput screening of new vaccine antigens and candidates was seen as a driving force for vaccine discovery. Multi-stakeholder, small-scale manufacturing facilities capable of rapid production of clinical grade vaccines are currently too few and need to be expanded. In both the human and veterinary areas, there is a need for tiered regulatory standards, differentially tailored for experimental and commercial vaccines, to allow accelerated vaccine efficacy testing. Improved cross-fertilization of knowledge between industry and academia, and between human and veterinary vaccine developers, could lead to more rapid application of promising approaches and technologies to new product development. Identification of best-practices and development of checklists for product development plans and implementation programmes were seen as low-cost opportunities to shorten the timeline for vaccine progression from the laboratory bench to the people who need it. PMID:21893549

  14. Accelerating vaccine development and deployment: report of a Royal Society satellite meeting.

    PubMed

    Bregu, Migena; Draper, Simon J; Hill, Adrian V S; Greenwood, Brian M

    2011-10-12

    The Royal Society convened a meeting on the 17th and 18th November 2010 to review the current ways in which vaccines are developed and deployed, and to make recommendations as to how each of these processes might be accelerated. The meeting brought together academics, industry representatives, research sponsors, regulators, government advisors and representatives of international public health agencies from a broad geographical background. Discussions were held under Chatham House rules. High-throughput screening of new vaccine antigens and candidates was seen as a driving force for vaccine discovery. Multi-stakeholder, small-scale manufacturing facilities capable of rapid production of clinical grade vaccines are currently too few and need to be expanded. In both the human and veterinary areas, there is a need for tiered regulatory standards, differentially tailored for experimental and commercial vaccines, to allow accelerated vaccine efficacy testing. Improved cross-fertilization of knowledge between industry and academia, and between human and veterinary vaccine developers, could lead to more rapid application of promising approaches and technologies to new product development. Identification of best-practices and development of checklists for product development plans and implementation programmes were seen as low-cost opportunities to shorten the timeline for vaccine progression from the laboratory bench to the people who need it. PMID:21893549

  15. Performance and Environmental Test Results of the High Voltage Hall Accelerator Engineering Development Unit

    NASA Technical Reports Server (NTRS)

    Kamhawi, Hani; Haag, Thomas; Huang, Wensheng; Shastry, Rohit; Pinero, Luis; Peterson, Todd; Mathers, Alex

    2012-01-01

    NASA Science Mission Directorate's In-Space Propulsion Technology Program is sponsoring the development of a 3.5 kW-class engineering development unit Hall thruster for implementation in NASA science and exploration missions. NASA Glenn and Aerojet are developing a high fidelity high voltage Hall accelerator that can achieve specific impulse magnitudes greater than 2,700 seconds and xenon throughput capability in excess of 300 kilograms. Performance, plume mappings, thermal characterization, and vibration tests of the high voltage Hall accelerator engineering development unit have been performed. Performance test results indicated that at 3.9 kW the thruster achieved a total thrust efficiency and specific impulse of 58%, and 2,700 sec, respectively. Thermal characterization tests indicated that the thruster component temperatures were within the prescribed material maximum operating temperature limits during full power thruster operation. Finally, thruster vibration tests indicated that the thruster survived the 3-axes qualification full-level random vibration test series. Pre and post-vibration test performance mappings indicated almost identical thruster performance. Finally, an update on the development progress of a power processing unit and a xenon feed system is provided.

  16. Naringenin and atherosclerosis: a review of literature.

    PubMed

    Orhan, Ilkay E; Nabavi, Seyed F; Daglia, Maria; Tenore, Gian C; Mansouri, Kowsar; Nabavi, Seyed M

    2015-01-01

    Atherosclerosis is a multifactorial disease mainly caused by deposition of low-density lipoprotein (LD) cholesterol in macrophages of arterial walls. Atherosclerosis leads to heart attacks as well as stroke. Epidemiological studies showed that there is an inverse correlation between fruit and vegetable consumption and the risk of atherosclerosis. The promising effect of high vegetable and fruit containing diet on atherosclerosis is approved by several experimental studies on isolated phytochemicals such as flavonoids. Flavonoids are known to up-regulate endogenous antioxidant system, suppress oxidative and nitrosative stress, decrease macrophage oxidative stress through cellular oxygenase inhibition as well as interaction with several signal transduction pathways and from these ways, have therapeutic effects against atherosclerosis. Naringenin is a well known flavonoid belonging to the chemical class of flavanones. It is especially abundant in citrus fruits, especially grapefruits. A plethora of evidences ascribes to naringenin antiatherosclerotic effects. Naringenin abilities to decrease LDL and triglycerides as well as inhibit glucose uptake; increase high-density lipoprotein (HDL); co-oxidation of NADH; suppress protein oxidation; protect against intercellular adhesion molecule-1(ICAM-1); suppress macrophage inflammation; inhibit leukotriene B4, monocyte adhesion and foam cell formation; induce of HO-1 and G 0/G 1 cell cycle arrest in vascular smooth muscle cells (VSMC) and down regulate atherosclerosis related genes are believed to have crucial role in the promising role against atherosclerosis. In the present review, we have summarized the available literature data on the anti-atherosclerotic effects of naringenin and its possible mechanisms of action. PMID:25483717

  17. Hypercholesterolemia links hematopoiesis with atherosclerosis.

    PubMed

    Soehnlein, Oliver; Swirski, Filip K

    2013-03-01

    Atherosclerosis is characterized by the progressive accumulation of lipids and leukocytes in the arterial wall. Leukocytes such as macrophages accumulate oxidized lipoproteins in the growing atheromata and give rise to foam cells, which can then contribute to the necrotic core of lesions. Lipids and leukocytes also interact in other important ways. In experimental models, systemic hypercholesterolemia is associated with severe neutrophilia and monocytosis. Recent evidence indicates that cholesterol-sensing pathways control the proliferation of hematopoietic stem-cell progenitors. Here we review some of the studies that are forging this particular link between metabolism and inflammation, and propose several strategies that could target this axis for the treatment of cardiovascular disease. PMID:23228326

  18. WInd-and-react Bi-2212 coil development for accelerator magnets

    SciTech Connect

    Godeke, A.; Acosta, P.; Cheng, D.; Dietderich, D. R.; Mentink, M. G. T.; Prestemon, S. O.; Meinesz, M.; Hong, S.; Huang, Y.; Miao, H.; Parrell, J.; Sabbi, G.L.

    2009-10-13

    Sub-scale coils are being manufactured and tested at Lawrence Berkeley National Laboratory in order to develop wind-and-react Bi{sub 2}Sr{sub 2}CaCu{sub 2}O{sub x} (Bi-2212) magnet technology for future graded accelerator magnet use. Previous Bi-2212 coils showed significant leakage of the conductors core constituents to the environment, which can occur during the partial melt reaction around 890 C in pure oxygen. The main origin of the observed leakage is intrinsic leakage of the wires, and the issue is therefore being addressed at the wire manufacturing level. We report on further compatibility studies, and the performance of new sub-scale coils that were manufactured using improved conductors. These coils exhibit significantly reduced leakage, and carry currents that are about 70% of the witness wire critical current (I{sub c}). The coils demonstrate, for the first time, the feasibility of round wire Bi-2212 conductors for accelerator magnet technology use. Successful high temperature superconductor coil technology will enable the manufacture of graded accelerator magnets that can surpass the, already closely approached, intrinsic magnetic field limitations of Nb-based superconducting magnets.

  19. Accelerator production of tritium plant design and supporting engineering development and demonstration work

    SciTech Connect

    Lisowski, P.W.

    1997-11-01

    Tritium is an isotope of hydrogen with a half life of 12.3 years. Because it is essential for US thermonuclear weapons to function, tritium must be periodically replenished. Since K reactor at Savannah River Site stopped operating in 1988, tritium has been recycled from dismantled nuclear weapons. This process is possible only as long as many weapons are being retired. Maintaining the stockpile at the level called for in the present Strategic Arms Reduction Treaty (START-I) will require the Department of Energy to have an operational tritium production capability in the 2005--2007 time frame. To make the required amount of tritium using an accelerator based system (APT), neutrons will be produced through high energy proton reactions with tungsten and lead. Those neutrons will be moderated and captured in {sup 3}He to make tritium. The APT plant design will use a 1,700 MeV linear accelerator operated at 100 mA. In preparation for engineering design, starting in October 1997 and subsequent construction, a program of engineering development and demonstration is underway. That work includes assembly and testing of the first 20 MeV of the low energy plant linac at 100 mA, high-energy linac accelerating structure prototyping, radiofrequency power system improvements, neutronic efficiency measurements, and materials qualifications.

  20. Vibration-Based Method Developed to Detect Cracks in Rotors During Acceleration Through Resonance

    NASA Technical Reports Server (NTRS)

    Sawicki, Jerzy T.; Baaklini, George Y.; Gyekenyesi, Andrew L.

    2004-01-01

    In recent years, there has been an increasing interest in developing rotating machinery shaft crack-detection methodologies and online techniques. Shaft crack problems present a significant safety and loss hazard in nearly every application of modern turbomachinery. In many cases, the rotors of modern machines are rapidly accelerated from rest to operating speed, to reduce the excessive vibrations at the critical speeds. The vibration monitoring during startup or shutdown has been receiving growing attention (ref. 1), especially for machines such as aircraft engines, which are subjected to frequent starts and stops, as well as high speeds and acceleration rates. It has been recognized that the presence of angular acceleration strongly affects the rotor's maximum response to unbalance and the speed at which it occurs. Unfortunately, conventional nondestructive evaluation (NDE) methods have unacceptable limits in terms of their application for online crack detection. Some of these techniques are time consuming and inconvenient for turbomachinery service testing. Almost all of these techniques require that the vicinity of the damage be known in advance, and they can provide only local information, with no indication of the structural strength at a component or system level. In addition, the effectiveness of these experimental techniques is affected by the high measurement noise levels existing in complex turbomachine structures. Therefore, the use of vibration monitoring along with vibration analysis has been receiving increasing attention.

  1. Advanced laser particle accelerator development at LANL: from fast ignition to radiation oncology

    SciTech Connect

    Flippo, Kirk A; Gaillard, Sandrine A; Offermann, D T; Cobble, J A; Schmitt, M J; Gautier, D C; Kwan, T J T; Montgomery, D S; Kluge, Thomas; Bussmann, Micheal; Bartal, T; Beg, F N; Gall, B; Geissel, M; Korgan, G; Kovaleski, S; Lockard, T; Malekos, S; Schollmeier, M; Sentoku, Y; Cowan, T E

    2010-01-01

    Laser-plasma accelerated ion and electron beam sources are an emerging field with vast prospects, and promise many superior applications in a variety of fields such as hadron cancer therapy, compact radioisotope generation, table-top nuclear physics, laboratory astrophysics, nuclear forensics, waste transmutation, SN M detection, and inertial fusion energy. LANL is engaged in several projects seeking to develop compact high current and high energy ion and electron sources. We are especially interested in two specific applications: ion fast ignition/capsule perturbation and radiation oncology in conjunction with our partners at the ForschungsZentrum Dresden-Rossendorf (FZD). Laser-to-beam conversion efficiencies of over 10% are needed for practical applications, and we have already shown inherent etliciencies of >5% from flat foils, on Trident using only a 5th of the intensity and energy of the Nova Petawatt. With clever target designs, like structured curved cone targets, we have also been able to achieve major ion energy gains, leading to the highest energy laser-accelerated proton beams in the world. These new target designs promise to help usher in the next generation of particle sources realizing the potential of laser-accelerated beams.

  2. Development of High Gradient Laser Wakefield Accelerators Towards Nuclear Detection Applications at LBNL

    SciTech Connect

    Geddes, Cameron G. R.; Gonsalves, Anthony J.; Lin Chen; Cormier-Michel, Estelle; Matlis, Nicholas H.; Panasenko, Dmitriy; Plateau, Guillaume R.; Schroeder, Carl B.; Toth, Csaba; Bruhwiler, David L.; Cary, John R.; Esarey, Eric H.; Nakamura, Kei; Bakeman, Mike; Leemans, Wim P.

    2009-03-10

    Compact high-energy linacs are important to applications including monochromatic gamma sources for nuclear material security applications. Recent laser wakefield accelerator experiments at LBNL demonstrated narrow energy spread beams, now with energies of up to 1 GeV in 3 cm using a plasma channel at low density. This demonstrates the production of GeV beams from devices much smaller than conventional linacs, and confirms the anticipated scaling of laser driven accelerators to GeV energies. Stable performance at 0.5 GeV was demonstrated. Experiments and simulations are in progress to control injection of particles into the wake and hence to improve beam quality and stability. Using plasma density gradients to control injection, stable beams at 1 MeV over days of operation, and with an order of magnitude lower absolute momentum spread than previously observed, have been demonstrated. New experiments are post-accelerating the beams from controlled injection experiments to increase beam quality and stability. Thomson scattering from such beams is being developed to provide collimated multi-MeV monoenergetic gamma sources for security applications from compact devices. Such sources can reduce dose to target and increase accuracy for applications including photofission and nuclear resonance fluorescence.

  3. Development of high gradient laser wakefield accelerators towards nuclear detection applications at LBNL

    SciTech Connect

    Geddes, Cameron GR; Bruhwiler, David L.; Cary, John R.; Esarey, Eric H.; Gonsalves, Anthony J.; Lin, Chen; Cormier-Michel, Estelle; Matlis, Nicholas H.; Nakamura, Kei; Bakeman, Mike; Panasenko, Dmitriy; Plateau, Guillaume R.; Schroeder, Carl B.; Toth, Csaba; Leemans, Wim P.

    2008-09-08

    Compact high-energy linacs are important to applications including monochromatic gamma sources for nuclear material security applications. Recent laser wakefield accelerator experiments at LBNL demonstrated narrow energy spread beams, now with energies of up to 1 GeV in 3 cm using a plasma channel at low density. This demonstrates the production of GeV beams from devices much smaller than conventional linacs, and confirms the anticipated scaling of laser driven accelerators to GeV energies. Stable performance at 0.5 GeV was demonstrated. Experiments and simulations are in progress to control injection of particles into the wake and hence to improve beam quality and stability. Using plasma density gradients to control injection, stable beams at 1 MeV over days of operation, and with an order of magnitude lower absolute momentum spread than previously observed, have been demonstrated. New experiments are post-accelerating the beams from controlled injection experiments to increase beam quality and stability. Thomson scattering from such beams is being developed to provide collimated multi-MeV monoenergetic gamma sources for security applications from compact devices. Such sources can reduce dose to target and increase accuracy for applications including photofission and nuclear resonance fluorescence.

  4. Development of backsheet tests and measurements to improve correlation of accelerated exposures to fielded modules

    NASA Astrophysics Data System (ADS)

    Felder, Thomas C.; Gambogi, William J.; Kopchick, James G.; Amspacher, Lucas; Peacock, R. Scott; Foltz, Benjamin; Stika, Katherine M.; Bradley, Alexander Z.; Hamzavy, Babak; Yu, Bao-Ling; Garreau-iles, Lucie; Fu, Oakland; Hu, Hongjie; Trout, T. John

    2015-09-01

    Matching accelerated test results to field observations is an important objective in the photovoltaic industry. We continue to develop test methods to strengthen correlations. We have previously reported good correlation of FTIR spectra between accelerated tests and field measurements. The availability of portable FTIR spectrometers has made measurement in the field convenient and reliable. Recently, nano-indentation has shown promise to correlate changes in backsheet mechanical properties. A precisely shaped stylus is pressed into a sample, load vs displacement recorded and mechanical properties of interest calculated in a nondestructive test. This test can be done on full size modules, allowing area variations in mechanical properties to be recorded. Finally, we will discuss optical profilometry. In this technique a white light interferogram of a surface is Fourier transformed to produce a three-dimensional image. Height differences from 1 nm to 5 mm can be detected over an area of a few cm. This technique can be used on minimodules, and is useful to determine crack and defect dimensions. Results will be presented correlating accelerated tests with fielded modules covering spectroscopic, mechanical, and morphological changes.

  5. Development of a multiplexed electrospray micro-thruster with post-acceleration and beam containment

    NASA Astrophysics Data System (ADS)

    Lenguito, G.; Gomez, A.

    2013-10-01

    We report the development of a compact thruster based on Multiplexed ElectroSprays (MES). It relied on a microfabricated Si array of emitters coupled with an extractor electrode and an accelerator electrode. The accelerator stage was introduced for two purposes: containing beam opening and avoiding electrode erosion due to droplet impingement, as well as boosting specific impulse and thrust. Multiplexing is generally necessary as a thrust multiplier to reach eventually the level required (O(102) μN) by small satellites. To facilitate system optimization and debugging, we focused on a 7-nozzle MES device and compared its performance to that of a single emitter. To ensure uniformity of operation of all nozzles their hydraulic impedance was augmented by packing them with micrometer-size beads. Two propellants were tested: a solution of 21.5% methyl ammonium formate in formamide and the better performing pure ionic liquid ethyl ammonium nitrate (EAN). The 7-MES device spraying EAN at ΔV = 5.93 kV covered a specific impulse range from 620 s to 1900 s and a thrust range from 0.6 μN to 5.4 μN, at 62% efficiency. Remarkably, less than 1% of the beam was demonstrated to impact on the accelerator electrode, which bodes well for long-term applications in space.

  6. Using Uncertainty Analysis to Guide the Development of Accelerated Stress Tests (Presentation)

    SciTech Connect

    Kempe, M.

    2014-03-01

    Extrapolation of accelerated testing to the long-term results expected in the field has uncertainty associated with the acceleration factors and the range of possible stresses in the field. When multiple stresses (such as temperature and humidity) can be used to increase the acceleration, the uncertainty may be reduced according to which stress factors are used to accelerate the degradation.

  7. Teacher Attitudes toward Subject-Specific Acceleration: Instrument Development and Validation

    ERIC Educational Resources Information Center

    Rambo, Karen E.; McCoach, D. Betsy

    2012-01-01

    Despite the research supporting acceleration, some teachers are still hesitant to recommend acceleration for advanced students. The Teacher Attitudes Toward Subject-Specific Acceleration (TATSSA) instrument was designed to uncover the factors that influence teacher decisions to recommend students for subject-specific acceleration. First, we…

  8. TWIST1 Integrates Endothelial Responses to Flow in Vascular Dysfunction and Atherosclerosis

    PubMed Central

    Mahmoud, Marwa M.; Kim, Hyejeong Rosemary; Xing, Rouyu; Hsiao, Sarah; Mammoto, Akiko; Chen, Jing; Serbanovic-Canic, Jovana; Feng, Shuang; Bowden, Neil P.; Maguire, Richard; Ariaans, Markus; Francis, Sheila E.; Weinberg, Peter D.; van der Heiden, Kim; Jones, Elizabeth A.; Chico, Timothy J.A.; Ridger, Victoria

    2016-01-01

    Rationale: Blood flow–induced shear stress controls endothelial cell (EC) physiology during atherosclerosis via transcriptional mechanisms that are incompletely understood. The mechanosensitive transcription factor TWIST is expressed during embryogenesis, but its role in EC responses to shear stress and focal atherosclerosis is unknown. Objective: To investigate whether TWIST regulates endothelial responses to shear stress during vascular dysfunction and atherosclerosis and compare TWIST function in vascular development and disease. Methods and Results: The expression and function of TWIST1 was studied in EC in both developing vasculature and during the initiation of atherosclerosis. In zebrafish, twist was expressed in early embryonic vasculature where it promoted angiogenesis by inducing EC proliferation and migration. In adult porcine and murine arteries, TWIST1 was expressed preferentially at low shear stress regions as evidenced by quantitative polymerase chain reaction and en face staining. Moreover, studies of experimental murine carotid arteries and cultured EC revealed that TWIST1 was induced by low shear stress via a GATA4-dependent transcriptional mechanism. Gene silencing in cultured EC and EC-specific genetic deletion in mice demonstrated that TWIST1 promoted atherosclerosis by inducing inflammation and enhancing EC proliferation associated with vascular leakiness. Conclusions: TWIST expression promotes developmental angiogenesis by inducing EC proliferation and migration. In addition to its role in development, TWIST is expressed preferentially at low shear stress regions of adult arteries where it promotes atherosclerosis by inducing EC proliferation and inflammation. Thus, pleiotropic functions of TWIST control vascular disease and development. PMID:27245171

  9. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    SciTech Connect

    Hsieh, Yi-Chen; Lien, Li-Ming; Chung, Wen-Ting; Hsieh, Fang-I; Hsieh, Pei-Fan; Wu, Meei-Maan; Tseng, Hung-Pin; Chiou, Hung-Yi; Chen, Chien-Jen

    2011-08-15

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

  10. History of Discovery: Inflammation in Atherosclerosis

    PubMed Central

    Libby, Peter

    2012-01-01

    Experimental work has elucidated molecular and cellular pathways of inflammation that promote atherosclerosis. Unraveling the roles of cytokines as inflammatory messengers provided a mechanism whereby risk factors for atherosclerosis can alter arterial biology, and produce a systemic milieu that favors atherothrombotic events. The discovery of the immune basis of allograft arteriosclerosis demonstrated that inflammation per se can drive arterial hyperplasia, even in the absence of traditional risk factors. Inflammation regulates aspects of plaque biology that trigger the thrombotic complications of atherosclerosis. Translation of these discoveries to humans has enabled both novel mechanistic insights and practical clinical advances. PMID:22895665

  11. The Impact of Organokines on Insulin Resistance, Inflammation, and Atherosclerosis.

    PubMed

    Choi, Kyung Mook

    2016-03-01

    Immoderate energy intake, a sedentary lifestyle, and aging have contributed to the increased prevalence of obesity, sarcopenia, metabolic syndrome, type 2 diabetes, and cardiovascular disease. There is an urgent need for the development of novel pharmacological interventions that can target excessive fat accumulation and decreased muscle mass and/or strength. Adipokines, bioactive molecules derived from adipose tissue, are involved in the regulation of appetite and satiety, inflammation, energy expenditure, insulin resistance and secretion, glucose and lipid metabolism, and atherosclerosis. Recently, there is emerging evidence that skeletal muscle and the liver also function as endocrine organs that secrete myokines and hepatokines, respectively. Novel discoveries and research into these organokines (adipokines, myokines, and hepatokines) may lead to the development of promising biomarkers and therapeutics for cardiometabolic disease. In this review, I summarize recent data on these organokines and focus on the role of adipokines, myokines, and hepatokines in the regulation of insulin resistance, inflammation, and atherosclerosis. PMID:26996418

  12. Defects in Regulation of Local Immune Responses Resulting in Atherosclerosis

    PubMed Central

    Ferenčík, Miroslav; Štvrtinová, Viera; Hulín, Ivan

    2005-01-01

    Atherosclerosis is nowadays generally accepted as an inflammatory disease but the mechanism of its origin and development have not yet been fully clarified. The present review focuses on the role of the local immune system as one of the key players in the pathogenesis of the complex process. Its part represented by vascular-associated lymphoid tissue (VALT) within the arterial wall participates directly in the vascular wall's homeostatis. Its inordinate activation during ontogenic development of an individual, this formerly defensive and physiologic mechanism transform into a pathological process resulting in an impairing inflammation. Hsp60, CRP and oxidized or otherwise modified LDL are serious candidates for triggering these pathological changes. The principal role is played by anti-Hsp60 antibodies and by shear stress originating on the surface of endothelium due to blood flow. The experimental and clinical data supporting this immunological hypothesis of atherosclerosis are discussed. PMID:16295529

  13. The Impact of Organokines on Insulin Resistance, Inflammation, and Atherosclerosis

    PubMed Central

    2016-01-01

    Immoderate energy intake, a sedentary lifestyle, and aging have contributed to the increased prevalence of obesity, sarcopenia, metabolic syndrome, type 2 diabetes, and cardiovascular disease. There is an urgent need for the development of novel pharmacological interventions that can target excessive fat accumulation and decreased muscle mass and/or strength. Adipokines, bioactive molecules derived from adipose tissue, are involved in the regulation of appetite and satiety, inflammation, energy expenditure, insulin resistance and secretion, glucose and lipid metabolism, and atherosclerosis. Recently, there is emerging evidence that skeletal muscle and the liver also function as endocrine organs that secrete myokines and hepatokines, respectively. Novel discoveries and research into these organokines (adipokines, myokines, and hepatokines) may lead to the development of promising biomarkers and therapeutics for cardiometabolic disease. In this review, I summarize recent data on these organokines and focus on the role of adipokines, myokines, and hepatokines in the regulation of insulin resistance, inflammation, and atherosclerosis. PMID:26996418

  14. Angiotensin-(1-7): new perspectives in atherosclerosis treatment

    PubMed Central

    Zhang, Feng; Liu, Jun; Li, Su-Fang; Song, Jun-Xian; Ren, Jing-Yi; Chen, Hong

    2015-01-01

    Angiotensin (Ang)-(1-7) is recognized as a new bioactive peptide in renin-angiotensin system (RAS). Ang-(1-7) is a counter-regulatory mediator of Ang-II which appears to be protective against cardiovascular disease. Recent studies have found that Ang-(1-7) played an important role in reducing smooth muscle cell proliferation and migration, improving endothelial function and regulating lipid metabolism, leading to inhibition of atherosclerotic lesions and increase of plaque stability. Although clinical application of Ang-(1-7) is restricted due to its pharmacokinetic properties, identification of stabilized compounds, including more stable analogues and specific delivery compounds, has enabled clinical application of Ang-(1-7). In this review, we discussed recent findings concerning the biological role of Ang-(1-7) and related mechanism during atherosclerosis development. In addition, we highlighted the perspective to develop therapeutic strategies using Ang-(1-7) to treat atherosclerosis. PMID:26788046

  15. Increasing Spontaneous Retinal Activity before Eye Opening Accelerates the Development of Geniculate Receptive Fields.

    PubMed

    Davis, Zachary W; Chapman, Barbara; Cheng, Hwai-Jong

    2015-10-28

    Visually evoked activity is necessary for the normal development of the visual system. However, little is known about the capacity for patterned spontaneous activity to drive the maturation of receptive fields before visual experience. Retinal waves provide instructive retinotopic information for the anatomical organization of the visual thalamus. To determine whether retinal waves also drive the maturation of functional responses, we increased the frequency of retinal waves pharmacologically in the ferret (Mustela putorius furo) during a period of retinogeniculate development before eye opening. The development of geniculate receptive fields after receiving these increased neural activities was measured using single-unit electrophysiology. We found that increased retinal waves accelerate the developmental reduction of geniculate receptive field sizes. This reduction is due to a decrease in receptive field center size rather than an increase in inhibitory surround strength. This work reveals an instructive role for patterned spontaneous activity in guiding the functional development of neural circuits. PMID:26511250

  16. UCLA accelerator research and development. Progress report, [November 1, 1991--July 31, 1992

    SciTech Connect

    Cline, D.B.

    1992-09-01

    This progress report covers work supported by the above DOE grant over the period November 1, 1991 to July 31, 1992. The work is a program of experimental and theoretical studies in advanced particle accelerator research and development for high energy physics applications. The program features research at particle beam facilities in the United States and includes research on novel high power sources, novel focussing systems (e.g. plasma lens), beam monitors, novel high brightness, high current gun systems, and novel flavor factories in particular the {phi} Factory.

  17. Statins Promote the Regression of Atherosclerosis via Activation of the CCR7-Dependent Emigration Pathway in Macrophages

    PubMed Central

    Feig, Jonathan E.; Shang, Yueting; Rotllan, Noemi; Vengrenyuk, Yuliya; Wu, Chaowei; Shamir, Raanan; Torra, Ines Pineda; Fernandez-Hernando, Carlos; Fisher, Edward A.; Garabedian, Michael J.

    2011-01-01

    HMG-CoA reductase inhibitors (statins) decrease atherosclerosis by lowering low-density-lipoprotein cholesterol. Statins are also thought to have additional anti-atherogenic properties, yet defining these non-conventional modes of statin action remains incomplete. We have previously developed a novel mouse transplant model of atherosclerosis regression in which aortic segments from diseased donors are placed into normolipidemic recipients. With this model, we demonstrated the rapid loss of CD68+ cells (mainly macrophages) in plaques through the induction of a chemokine receptor CCR7-dependent emigration process. Because the human and mouse CCR7 promoter contain Sterol Response Elements (SREs), we hypothesized that Sterol Regulatory Element Binding Proteins (SREBPs) are involved in increasing CCR7 expression and through this mechanism, statins would promote CD68+ cell emigration from plaques. We examined whether statin activation of the SREBP pathway in vivo would induce CCR7 expression and promote macrophage emigration from plaques. We found that western diet-fed apoE-/- mice treated with either atorvastatin or rosuvastatin led to a substantial reduction in the CD68+ cell content in the plaques despite continued hyperlipidemia. We also observed a significant increase in CCR7 mRNA in CD68+ cells from both the atorvastatin and rosuvastatin treated mice associated with emigration of CD68+ cells from plaques. Importantly, CCR7-/-/apoE-/- double knockout mice failed to display a reduction in CD68+ cell content upon statin treatment. Statins also affected the recruitment of transcriptional regulatory proteins and the organization of the chromatin at the CCR7 promoter to increase the transcriptional activity. Statins promote the beneficial remodeling of plaques in diseased mouse arteries through the stimulation of the CCR7 emigration pathway in macrophages. Therefore, statins may exhibit some of their clinical benefits by not only retarding the progression of

  18. Pdcd4 deficiency enhances macrophage lipoautophagy and attenuates foam cell formation and atherosclerosis in mice

    PubMed Central

    Wang, L; Jiang, Y; Song, X; Guo, C; Zhu, F; Wang, X; Wang, Q; Shi, Y; Wang, J; Gao, F; Zhao, W; Chen, Y H; Zhang, L

    2016-01-01

    Macrophage foam cells, a major component of the atherosclerotic lesion, have vital roles in the development of atherosclerosis. Lipoautophagy, a type of autophagy characterized by selective delivery of lipid droplet for lysosomal degradation, may impact atherosclerosis by regulating macrophage foam cell formation. Previously, we reported that programmed cell death 4 (PDCD4), a tumor suppressor, negatively regulated autophagy in tumor cells. However, its roles in macrophage lipoautophagy, foam cell formation and atherosclerosis remain to be established. Here we found that Pdcd4 deficiency clearly improved oxidized low-density lipoproteins-impaired autophagy efflux, promoted autophagy-mediated lipid breakdown in murine macrophages and thus prevented macrophage conversion into foam cells. Importantly, Pdcd4 deficiency in mice significantly upregulated macrophage autophagy in local plaques along with attenuated lipid accumulation and atherosclerotic lesions in high-fat-fed Apolipoprotein E knockout mice. Bone marrow transplantation experiment demonstrated that PDCD4-mediated autophagy in hematopoietic cells contributed to the development of atherosclerosis. These results indicate that endogenous PDCD4 promotes for macrophage foam cell formation and atherosclerosis development via inhibiting autophagy and provides new insights into atherogenesis, suggesting that promoting macrophage autophagy through downregulating PDCD4 expression may be beneficial for treating atherosclerosis. PMID:26775706

  19. Pdcd4 deficiency enhances macrophage lipoautophagy and attenuates foam cell formation and atherosclerosis in mice.

    PubMed

    Wang, L; Jiang, Y; Song, X; Guo, C; Zhu, F; Wang, X; Wang, Q; Shi, Y; Wang, J; Gao, F; Zhao, W; Chen, Y H; Zhang, L

    2016-01-01

    Macrophage foam cells, a major component of the atherosclerotic lesion, have vital roles in the development of atherosclerosis. Lipoautophagy, a type of autophagy characterized by selective delivery of lipid droplet for lysosomal degradation, may impact atherosclerosis by regulating macrophage foam cell formation. Previously, we reported that programmed cell death 4 (PDCD4), a tumor suppressor, negatively regulated autophagy in tumor cells. However, its roles in macrophage lipoautophagy, foam cell formation and atherosclerosis remain to be established. Here we found that Pdcd4 deficiency clearly improved oxidized low-density lipoproteins-impaired autophagy efflux, promoted autophagy-mediated lipid breakdown in murine macrophages and thus prevented macrophage conversion into foam cells. Importantly, Pdcd4 deficiency in mice significantly upregulated macrophage autophagy in local plaques along with attenuated lipid accumulation and atherosclerotic lesions in high-fat-fed Apolipoprotein E knockout mice. Bone marrow transplantation experiment demonstrated that PDCD4-mediated autophagy in hematopoietic cells contributed to the development of atherosclerosis. These results indicate that endogenous PDCD4 promotes for macrophage foam cell formation and atherosclerosis development via inhibiting autophagy and provides new insights into atherogenesis, suggesting that promoting macrophage autophagy through downregulating PDCD4 expression may be beneficial for treating atherosclerosis. PMID:26775706

  20. New therapy via targeting androgen receptor in monocytes/macrophages to battle atherosclerosis.

    PubMed

    Huang, Chiung-Kuei; Pang, Haiyan; Wang, Lin; Niu, Yuanjie; Luo, Jie; Chang, Eugene; Sparks, Janet D; Lee, Soo Ok; Chang, Chawnshang

    2014-06-01

    The male sex has a higher risk to develop coronary artery diseases, including atherosclerosis. The androgen receptor (AR) is expressed in several atherosclerosis-associated cell types, including monocytes/macrophages, endothelial cells (ECs), and smooth muscle cells (SMCs), but its pathophysiological role in each cell type during the development of atherosclerotic lesions remains unclear. Using the Cre-loxP system, we selectively knocked out AR in these 3 cell types and the resultant AR knockout (ARKO) mice, monocyte/macrophage ARKO, EC-ARKO, and SMC-ARKO, were then crossed with the low-density lipoprotein receptor (LDLR) deficient (LDLR(-/-)) mice to develop monocyte/macrophage ARKO-LDLR(-/-), EC-ARKO-LDLR(-/-), and SMC-ARKO-LDLR(-/-) mice for the study of atherosclerosis. The results showed that the monocyte/macrophage ARKO-LDLR(-/-) mice had reduced atherosclerosis compared with the wild-type-LDLR(-/-) control mice. However, no significant difference was detected in EC-ARKO-LDLR(-/-) and SMC-ARKO-LDLR(-/-) mice compared with wild-type-LDLR(-/-) mice, suggesting that the AR in monocytes/macrophages, and not in ECs and SMCs, plays a major role to promote atherosclerosis. Molecular mechanism dissection suggested that AR in monocytes/macrophages upregulated the tumor necrosis factor-α, integrin β2, and lectin-type oxidized LDL receptor 1 molecules that are involved in 3 major inflammation-related processes in atherosclerosis, including monocytes/macrophages migration and adhesion to human umbilical vein ECs, and subsequent foam cell formation. Targeting AR via the AR degradation enhancer, ASC-J9, in wild-type-LDLR(-/-) mice showed similar effects as seen in monocyte/macrophage ARKO-LDLR(-/-) mice with little influence on lipid profile. In conclusion, the AR in monocytes/macrophages plays key roles in atherosclerosis and targeting AR with ASC-J9 may represent a new potential therapeutic approach to battle atherosclerosis. PMID:24688120

  1. Niobium cavity development for the high-energy linac of the rare isotope accelerator

    SciTech Connect

    D. Barni; C. Pagani; P. Pierini; C. Compton; T. Grimm; W. Hartung; H. Podlech; R. York; G. Ciovati; P. Kneisel

    2001-08-01

    The Rare Isotope Accelerator (RIA) is being designed to supply an intense beam of exotic isotopes for nuclear physics research [1]. Superconducting cavities are to be used to accelerate the CW beam of heavy ions to 400 MeV per nucleon, with a beam power of up to 400 kW. Because of the varying velocity of the ion beam along the linac, a number of different types of superconducting structures are needed. The RIA linac will accelerate heavy ions over the same velocity range as the proton linac for the Spallation Neutron Source (SNS). It was decided to use the 6-cell axisymmetric 805 MHz cavities and cryostats of SNS for the downstream portion of the RIA linac, thereby saving the non-recurring development and engineering costs. For additional cost saving, it was decided to extend the SNS multi-cell axisymmetric cavity design to lower velocity, {beta} = v/c = 0.4, using the same cryostats and RF systems. Axisymmetric cavities will thus constitute about three-quarters of RIA's total accelerating voltage, and most of that voltage will be provided by cavities already developed for SNS. The axisymmetric cavities will accelerate the RIA beam from {beta} = 0.4 to {beta} = 0.72. This velocity range can be efficiently covered with two different types of 6-cell cavities, one with a geometric {beta}, {beta}{sub g}, of 0.47, and the other with a {beta}{sub g} of 0.61. The {beta}{sub g} = 0.61 cavity will be of the existing SNS design; some {beta}{sub g} = 0.81 SNS cavities may also be desired at the end of the RIA linac for acceleration of light ions above 400 MeV per nucleon. Prototypes for both {beta}{sub g} = 0.61 and {beta}{sub g} = 0.81 have been fabricated and tested [2]. The {beta}{sub g} = 0.47 cavity is the focus of the present work. The reduction in {beta}{sub g} to 0.47 results in less favourable electromagnetic and mechanical properties, and opens up the possibility of multipacting, but several groups have already designed and prototyped cavities in this range. These

  2. Soil Potassium Deficiency Reduces Cotton Fiber Strength by Accelerating and Shortening Fiber Development

    PubMed Central

    Yang, Jia-Shuo; Hu, Wei; Zhao, Wenqing; Meng, Yali; Chen, Binglin; Wang, Youhua; Zhou, Zhiguo

    2016-01-01

    Low potassium (K)-induced premature senescence in cotton has been observed worldwide, but how it affects cotton fiber properties remain unclear. We hypothesized that K deficiency affects cotton fiber properties by causing disordered fiber development, which may in turn be caused by the induction of a carbohydrate acquisition difficulty. To investigate this issue, we employed a low-K-sensitive cotton cultivar Siza 3 and a low-K-tolerant cultivar Simian 3 and planted them in three regions of different K supply. Data concerning lint yield, Pn and main fiber properties were collected from three years of testing. Soil K deficiency significantly accelerated fiber cellulose accumulation and dehydration processes, which, together with previous findings, suggests that the low-K induced carbohydrate acquisition difficulty could cause disordered fiber development by stimulating the expression of functional proteins such as CDKA (cyclin-dependent kinase). As a result, fiber strength and lint weight were reduced by up to 7.8% and 2.1%, respectively. Additional quantitative analysis revealed that the degree of accelerated fiber development negatively correlated with fiber strength. According to the results of this study, it is feasible to address the effects of soil K deficiency on fiber properties using existing cultivation strategies to prevent premature senescence of cotton plants. PMID:27350236

  3. Atherosclerosis in Sjögren's syndrome: evidence, possible mechanisms and knowledge gaps.

    PubMed

    Valim, Valéria; Gerdts, Eva; Jonsson, Roland; Ferreira, Gilda Aparecida; Brokstad, Karl Albert; Brun, Johan G; Midtbø, Helga; Mydel, Piotr Mateusz

    2016-01-01

    Inflammation has been associated with higher cardiovascular risk in rheumatic autoimmune diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus. More recently, primary Sjögren's syndrome (pSS) was also demonstrated as an independent risk factor for cardiovascular disease, emerging as a new interesting model to study atherosclerosis in autoimmune diseases. Patients with pSS have a higher prevalence of developing traditional cardiovascular risk factors like hypertension and dyslipidaemia predisposing for endothelial dysfunction and premature atherosclerosis. However, the disease-specific mechanisms for premature atherosclerosis in pSS are not fully understood. The aim of this review was to critically analyse the current literature on cardiovascular risks in pSS and to discuss the traditional and disease-associated risk factors. We also suggest possible new mechanisms that should be explored in future research to close the current knowledge gaps on the association of pSS, premature atherosclerosis, and clinical cardiovascular disease. PMID:26812164

  4. 2015 Russell Ross Memorial Lecture in Vascular Biology: Protective Autoimmunity in Atherosclerosis.

    PubMed

    Ley, Klaus

    2016-03-01

    Atherosclerosis is an inflammatory disease of the arterial wall. It is accompanied by an autoimmune response against apolipoprotein B-100, the core protein of low-density lipoprotein, which manifests as CD4 T cell and antibody responses. To assess the role of the autoimmune response in atherosclerosis, the nature of the CD4 T cell response against apolipoprotein B-100 was studied with and without vaccination with major histocompatibility complex-II-restricted apolipoprotein B-100 peptides. The immunologic basis of autoimmunity in atherosclerosis is discussed in the framework of theories of adaptive immunity. Older vaccination approaches are also discussed. Vaccinating Apoe(-/-) mice with major histocompatibility complex-II-restricted apolipoprotein B-100 peptides reduces atheroma burden in the aorta by ≈40%. The protective mechanism likely includes secretion of interleukin-10. Protective autoimmunity limits atherosclerosis in mice and suggests potential for developing preventative and therapeutic vaccines for humans. PMID:26821946

  5. Atherosclerosis and the internal mammary arteries

    SciTech Connect

    Singh, R.N.

    1983-06-01

    One hundred and fifty patients with coronary artery disease (CAD), 14 (9.3%) of whom had coexisting peripheral vascular disease, underwent bilateral internal mammary arteriography to study the incidence and extent of atherosclerosis in these vessels. Significant atherosclerosis of the internal mammary arteries (IMAs) was present in three patients (2%), of whom one had coexisting peripheral vascular disease. Lesions in the IMAs were found either proximally, close to the origin or distally, around the terminal bifurcation. Six of the 14 patients with peripheral vascular disease (4% of total subjects) had significant atherosclerosis of the brachiocephalic arteries. Atherosclerotic involvement of the IMA is very unusual and rarely interferes with the use of these vessels for coronary bypass. More common, however, is atherosclerosis of the subclavian arteries, a contraindication for IMA grafting if the lesion is proximal to the IMA origin.

  6. Atherosclerosis is an inflammatory disorder after all.

    PubMed

    Meng, Charles Q

    2006-01-01

    Inflammation has been increasingly recognized as an important player in the pathophysiology of numerous human disorders. Accumulating evidence has led to the conclusion that atherosclerosis is an inflammatory disease, although it was believed to be a disorder of high cholesterol levels in the bloodstream for over a century. Cholesterol does contribute to the pathogenesis of atherosclerosis, but through inflammatory mechanisms. Statins lower cholesterol levels and hence reduce inflammation in the vasculature and prevent heart disease. Statins may also exert anti-inflammatory effects through mechanisms independent of cholesterol lowering. Adhesion molecules, cytokines, oxidative stress, etc. appear to contribute to the inflammatory state of atherosclerosis and therapeutic approaches directed toward these markers or targets have the potential to be effective in reducing inflammation and treating atherosclerosis. PMID:16454761

  7. A nuclear microscopy study of trace elements Ca, Fe, Zn and Cu in atherosclerosis

    NASA Astrophysics Data System (ADS)

    Watt, F.; Rajendran, R.; Ren, M. Q.; Tan, B. K. H.; Halliwell, B.

    2006-08-01

    Quantitative mapping of trace elements Ca, Fe, Zn and Cu can be achieved in biological tissue using a nuclear microprobe. Presented here is a brief review of the work we have carried out in the last decade using the nuclear microscope to try and elucidate the role of trace elements Fe, Zn, Cu and Ca in induced atherosclerosis in New Zealand White rabbits fed on a 1% cholesterol diet. The lesions were studied using nuclear microscopy, incorporating a combination of ion beam techniques: particle induced X-ray emission (PIXE), Rutherford backscattering spectrometry (RBS) and scanning transmission ion microscopy (STIM). Iron is present in early lesions at concentrations around seven times higher than the artery wall. Measurements of localized lesion iron concentrations were observed to be highly correlated with the depth of the lesion in the artery wall for each individual animal, implying that local elevated concentrations may provide an accelerated process of atherosclerosis in specific regions of the artery. When the rabbits were kept mildly anaemic, thereby reducing iron levels in the lesion, the progression of the disease was significantly slowed. Iron chelation using desferal showed that early treatment (three weeks into the high fat diet) for relatively long periods (nine weeks) significantly retarded the progression of the disease. Zinc is depleted in the lesion and is also observed to be anti-correlated with local lesion development and feeding the rabbits on a high fat diet with zinc supplements inhibited lesion development, although since no significant increase in lesion zinc levels was measured, this anti-atherosclerotic effect may be indirect. Copper, measured at low levels (∼3 ppm) in the early lesion, is also depleted compared to the artery wall, suggesting that it is not a major factor in atherogenesis. Calcium is also depleted in early lesions, although at a later stage mineral deposition (hydroxyapatite) is observed to take place in the lesion

  8. WIPO Re:Search: Accelerating anthelmintic development through cross-sector partnerships

    PubMed Central

    Ramamoorthi, Roopa; Graef, Katy M.; Dent, Jennifer

    2014-01-01

    Neglected tropical diseases (NTDs), malaria, and tuberculosis have a devastating effect on an estimated 1.6 billion people worldwide. The World Intellectual Property Organization (WIPO) Re:Search consortium accelerates the development of new drugs, vaccines, and diagnostics for these diseases by connecting the assets and resources of pharmaceutical companies, such as compound libraries and expertise, to academic or nonprofit researchers with novel product discovery or development ideas. As the WIPO Re:Search Partnership Hub Administrator, BIO Ventures for Global Health (BVGH) fields requests from researchers, identifies Member organizations able to fulfill these requests, and helps forge mutually beneficial collaborations. Since its inception in October 2011, WIPO Re:Search membership has expanded to more than 90 institutions, including leading pharmaceutical companies, universities, nonprofit research institutions, and product development partnerships from around the world. To date, WIPO Re:Search has facilitated over 70 research agreements between Consortium Members, including 11 collaborations focused on anthelmintic drug discovery. PMID:25516832

  9. Surface water geochemical and isotopic variations in an area of accelerating Marcellus Shale gas development.

    PubMed

    Pelak, Adam J; Sharma, Shikha

    2014-12-01

    Water samples were collected from 50 streams in an area of accelerating shale gas development in the eastern U.S.A. The geochemical/isotopic characteristics show no correlation with the five categories of Marcellus Shale production. The sub-watersheds with the greatest density of Marcellus Shale development have also undergone extensive coal mining. Hence, geochemical/isotopic compositions were used to understand sources of salinity and effects of coal mining and shale gas development in the area. The data indicates that while some streams appear to be impacted by mine drainage; none appear to have received sustained contribution from deep brines or produced waters associated with shale gas production. However, it is important to note that our interpretations are based on one time synoptic base flow sampling of a few sampling stations and hence do account potential intermittent changes in chemistry that may result from major/minor spills or specific mine discharges on the surface water chemistry. PMID:25201226

  10. Development of an accelerated leach test(s) for low-level waste forms

    SciTech Connect

    Dougherty, D.R.; Fuhrmann, M.; Colombo, P.

    1985-01-01

    An accelerated leach test(s) is being developed to predict long-term leaching behavior of low-level radioactive waste (LLW) forms in their disposal environments. As necessary background, a literature survey of reported leaching mechanisms, available mathematical models and factors that affect leaching of LLW forms has been compiled. Mechanisms which have been identified include diffusion, dissolution, ion exchange, corrosion and surface effects. A computerized data base of LLW leaching data and mathematical models is being developed. The data is being used for model evaluation by curve fitting and statistical analysis according to standard procedures of statistical quality control. Long-term leach tests on portland cement, bitumen and vinyl ester-styrene (VES) polymer waste forms are underway which are designed to identify and evaluate factors that accelerate leaching without changing the mechanisms. Initial results on the effect of temperature on leachability indicate that the leach rates of cement and VES waste forms increase with increasing temperature, whereas, the leach rate of bitumen is little affected. 10 refs., 5 figs.

  11. OpenMP-accelerated SWAT simulation using Intel C and FORTRAN compilers: Development and benchmark

    NASA Astrophysics Data System (ADS)

    Ki, Seo Jin; Sugimura, Tak; Kim, Albert S.

    2015-02-01

    We developed a practical method to accelerate execution of Soil and Water Assessment Tool (SWAT) using open (free) computational resources. The SWAT source code (rev 622) was recompiled using a non-commercial Intel FORTRAN compiler in Ubuntu 12.04 LTS Linux platform, and newly named iOMP-SWAT in this study. GNU utilities of make, gprof, and diff were used to develop the iOMP-SWAT package, profile memory usage, and check identicalness of parallel and serial simulations. Among 302 SWAT subroutines, the slowest routines were identified using GNU gprof, and later modified using Open Multiple Processing (OpenMP) library in an 8-core shared memory system. In addition, a C wrapping function was used to rapidly set large arrays to zero by cross compiling with the original SWAT FORTRAN package. A universal speedup ratio of 2.3 was achieved using input data sets of a large number of hydrological response units. As we specifically focus on acceleration of a single SWAT run, the use of iOMP-SWAT for parameter calibrations will significantly improve the performance of SWAT optimization.

  12. Vascular Smooth Muscle Cells in Atherosclerosis.

    PubMed

    Bennett, Martin R; Sinha, Sanjay; Owens, Gary K

    2016-02-19

    The historical view of vascular smooth muscle cells (VSMCs) in atherosclerosis is that aberrant proliferation of VSMCs promotes plaque formation, but that VSMCs in advanced plaques are entirely beneficial, for example preventing rupture of the fibrous cap. However, this view has been based on ideas that there is a homogenous population of VSMCs within the plaque, that can be identified separate from other plaque cells (particularly macrophages) using standard VSMC and macrophage immunohistochemical markers. More recent genetic lineage tracing studies have shown that VSMC phenotypic switching results in less-differentiated forms that lack VSMC markers including macrophage-like cells, and this switching directly promotes atherosclerosis. In addition, VSMC proliferation may be beneficial throughout atherogenesis, and not just in advanced lesions, whereas VSMC apoptosis, cell senescence, and VSMC-derived macrophage-like cells may promote inflammation. We review the effect of embryological origin on VSMC behavior in atherosclerosis, the role, regulation and consequences of phenotypic switching, the evidence for different origins of VSMCs, and the role of individual processes that VSMCs undergo in atherosclerosis in regard to plaque formation and the structure of advanced lesions. We think there is now compelling evidence that a full understanding of VSMC behavior in atherosclerosis is critical to identify therapeutic targets to both prevent and treat atherosclerosis. PMID:26892967

  13. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

    SciTech Connect

    Cai, Yujun; Li, Jian-Dong; Yan, Chen

    2013-05-10

    Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

  14. Lysophospholipids and their G protein-coupled receptors in atherosclerosis.

    PubMed

    Li, Ya-Feng; Li, Rong-Shan; Samuel, Sonia B; Cueto, Ramon; Li, Xin-Yuan; Wang, Hong; Yang, Xiao-Feng

    2016-01-01

    Lysophospholipids (LPLs) are bioactive lipid-derived signaling molecules generated by the enzymatic and chemical processes of regiospecific phospholipases on substrates such as membrane phospholipids (PLs) and sphingolipids (SLs). They play a major role as extracellular mediators by activating G-protein coupled receptors (GPCRs) and stimulating diverse cellular responses from their signaling pathways. LPLs are involved in various pathologies of the vasculature system including coronary heart disease and hypertension. Many studies suggest the importance of LPLs in their association with the development of atherosclerosis, a chronic and severe vascular disease. This paper focuses on the pathophysiological effects of different lysophospholipids on atherosclerosis, which may promote the pathogenesis of myocardial infarction and strokes. Their atherogenic biological activities take place in vascular endothelial cells, vascular smooth muscle cells, fibroblasts, monocytes and macrophages, dendritic cells, T-lymphocytes, platelets, etc. PMID:26709762

  15. Extracellular vesicles as new pharmacological targets to treat atherosclerosis.

    PubMed

    Yin, Min; Loyer, Xavier; Boulanger, Chantal M

    2015-09-15

    Extracellular vesicles released by most cell types, include apoptotic bodies (ABs), microvesicles (MVs) and exosomes. They play a crucial role in physiology and pathology, contributing to "cell-to-cell" communication by modifying the phenotype and the function of target cells. Thus, extracellular vesicles participate in the key processes of atherosclerosis from endothelial dysfunction, vascular wall inflammation to vascular remodeling. The purpose of this review is to summarize recent findings on extracellular vesicle formation, structure, release and clearance. We focus on the deleterious and beneficial effects of extracellular vesicles in the development of atherosclerosis. The potential role of extracellular vesicles as biomarkers and pharmacological targets, their innate therapeutic capacity, or their use for novel drug delivery devices in atherosclerotic cardiovascular diseases will also be discussed. PMID:26142082

  16. Development of a quantitative accelerated sulphate attack test for mine backfill

    NASA Astrophysics Data System (ADS)

    Shnorhokian, Shahe

    Mining operations produce large amounts of tailings that are either disposed of in surface impoundments or used in the production of backfill to be placed underground. Their mineralogy is determined by the local geology, and it is not uncommon to come across tailings with a relatively high sulphide mineral content, including pyrite and pyrrhotite. Sulphides oxidize in the presence of oxygen and water to produce sulphate and acidity. In the concrete industry, sulphate is known to produce detrimental effects by reacting with the cement paste to produce the minerals ettringite and gypsum. Because mine backfill uses tailings and binders---including cement---it is therefore prone to sulphate attack where the required conditions are met. Currently, laboratory tests on mine backfill mostly measure mechanical properties such as strength parameters, and the study of the chemical aspects is restricted to the impact of tailings on the environment. The potential of sulphate attack in mine backfill has not been studied at length, and no tests are conducted on binders used in backfill for their resistance to attack. Current ASTM guidelines for sulphate attack tests have been deemed inadequate by several authors due to their measurement of only expansion as an indicator of attack. Furthermore, the tests take too long to perform or are restricted to cement mortars only, and not to mixed binders that include pozzolans. Based on these, an accelerated test for sulphate attack was developed in this work through modifying and compiling procedures that had been suggested by different authors. Small cubes of two different binders were fully immersed in daily-monitored sodium sulphate and sulphuric acid solutions for a total of 28 days, after 7 days of accelerated curing at 50°C. In addition, four binders were partially immersed in the same solutions for 8 days for an accelerated attack process. The two procedures were conducted in tandem with leach tests using a mixed solution of

  17. High Voltage Hall Accelerator Propulsion System Development for NASA Science Missions

    NASA Technical Reports Server (NTRS)

    Kamhawi, Hani; Haag, Thomas; Huang, Wensheng; Shastry, Rohit; Pinero, Luis; Peterson, Todd; Dankanich, John; Mathers, Alex

    2013-01-01

    NASA Science Mission Directorates In-Space Propulsion Technology Program is sponsoring the development of a 3.8 kW-class engineering development unit Hall thruster for implementation in NASA science and exploration missions. NASA Glenn Research Center and Aerojet are developing a high fidelity high voltage Hall accelerator (HiVHAc) thruster that can achieve specific impulse magnitudes greater than 2,700 seconds and xenon throughput capability in excess of 300 kilograms. Performance, plume mappings, thermal characterization, and vibration tests of the HiVHAc engineering development unit thruster have been performed. In addition, the HiVHAc project is also pursuing the development of a power processing unit (PPU) and xenon feed system (XFS) for integration with the HiVHAc engineering development unit thruster. Colorado Power Electronics and NASA Glenn Research Center have tested a brassboard PPU for more than 1,500 hours in a vacuum environment, and a new brassboard and engineering model PPU units are under development. VACCO Industries developed a xenon flow control module which has undergone qualification testing and will be integrated with the HiVHAc thruster extended duration tests. Finally, recent mission studies have shown that the HiVHAc propulsion system has sufficient performance for four Discovery- and two New Frontiers-class NASA design reference missions.

  18. Development and use of molecular markers to accelerate peanut cultivar development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Close cooperation between conventional plant breeders and molecular geneticists will be needed to efficiently and effectively utilize modern genetic tools in the development of peanut cultivars. We have used this approach at Tifton to develop molecular markers for resistance to the peanut root-knot...

  19. IKKβ links vascular inflammation to obesity and atherosclerosis

    PubMed Central

    Sui, Yipeng; Park, Se-Hyung; Xu, Jinxian; Monette, Sébastien; Helsley, Robert N.; Han, Seong-Su

    2014-01-01

    IκB kinase β (IKKβ), a central coordinator of inflammatory responses through activation of NF-κB, has been implicated in vascular pathologies, but its role in atherogenesis remains elusive. Here, we demonstrate that IKKβ functions in smooth muscle cells (SMCs) to regulate vascular inflammatory responses and atherosclerosis development. IKKβ deficiency in SMCs driven by a SM22Cre-IKKβ-flox system rendered low density lipoprotein receptor-null mice resistant to vascular inflammation and atherosclerosis induced by high-fat feeding. Unexpectedly, IKKβ-deficient mice were also resistant to diet-induced obesity and metabolic disorders. Cell lineage analysis revealed that SM22Cre is active in primary adipose stromal vascular cells and deficiency of IKKβ diminished the ability of these cells to differentiate, leading to accumulation of adipocyte precursor cells in adipose tissue. Mechanistically, reduction of IKKβ expression or pharmacological inhibition of IKKβ inhibited proteasome-mediated β-catenin ubiquitination and degradation in murine preadipocytes, resulting in elevated β-catenin levels and impaired adipocyte differentiation. Further, chronic treatment of mice with a potent IKKβ inhibitor decreased adipogenesis and ameliorated diet-induced obesity. Our findings demonstrate a pivotal role of IKKβ in linking vascular inflammation to atherosclerosis and adipose tissue development, and provide evidence for using appropriate IKKβ inhibitors in the treatment of obesity and metabolic disorders. PMID:24799533

  20. Adaptive Response of T and B Cells in Atherosclerosis.

    PubMed

    Ketelhuth, Daniel F J; Hansson, Göran K

    2016-02-19

    Atherosclerosis is a chronic inflammatory disease that is initiated by the retention and accumulation of cholesterol-containing lipoproteins, particularly low-density lipoprotein, in the artery wall. In the arterial intima, lipoprotein components that are generated through oxidative, lipolytic, and proteolytic activities lead to the formation of several danger-associated molecular patterns, which can activate innate immune cells as well as vascular cells. Moreover, self- and non-self-antigens, such as apolipoprotein B-100 and heat shock proteins, can contribute to vascular inflammation by triggering the response of T and B cells locally. This process can influence the initiation, progression, and stability of plaques. Substantial clinical and experimental data support that the modulation of adaptive immune system may be used for treating and preventing atherosclerosis. This may lead to the development of more selective and less harmful interventions, while keeping host defense mechanisms against infections and tumors intact. Approaches such as vaccination might become a realistic option for cardiovascular disease, especially if they can elicit regulatory T and B cells and the secretion of atheroprotective antibodies. Nevertheless, difficulties in translating certain experimental data into new clinical therapies remain a challenge. In this review, we discuss important studies on the function of T- and B-cell immunity in atherosclerosis and their manipulation to develop novel therapeutic strategies against cardiovascular disease. PMID:26892965

  1. Effects of Prenatal Irradiation with an Accelerated Heavy-Ion Beam on Postnatal Development in Rats

    NASA Astrophysics Data System (ADS)

    Wang, B.; Murakami, M.; Eguchi-Kasai, K.; Nojima, K.; Shang, Y.; Tanaka, K.; Fujita, K.; Coffigny, H.; Hayata, I.

    Effects on postnatal neurophysiological development in offspring were studied following exposure of pregnant Wistar rats to accelerated neon-ion beams with a LET value of about 30 keV mu m at a dose range from 0 1 Gy to 2 0Gy on the 15th day of gestation The age at which four physiologic markers appeared and five reflexes were acquired was examined prior to weaning Gain in body weight was monitored until the offspring were 3 months old Male offspring were evaluated as young adults using two behavioral tests The effects of X-rays at 200 kVp measured for the same biological end points were studied for comparison Our previous study on carbon-ion beams with a LET value of about 13 keV mu m was also cited to elucidate a possible LET-related effect For most of the endpoints at early age significant alteration was even observed in offspring prenatally received 0 1 Gy of accelerated neon ions while neither X rays nor carbon-ions under the same dose resulted in such a significant alteration compared to that from the sham-irradiated dams All offspring whose mothers received 2 0 Gy died prior to weaning Offspring from dams irradiated with accelerated neon ions generally showed higher incidences of prenatal death and preweaning mortality markedly delayed accomplishment in their physiological markers and reflexes and gain in body weight compared to those exposed to X-rays or carbon ions at doses of 0 1 to 1 5 Gy Significantly reduced ratios of main organ weight to body weight at postnatal ages of 30 60 and 90 days were also observed

  2. Elevated Sodium and Dehydration Stimulate Inflammatory Signaling in Endothelial Cells and Promote Atherosclerosis

    PubMed Central

    Dmitrieva, Natalia I.; Burg, Maurice B.

    2015-01-01

    Cardiovascular diseases (CVDs) are a leading health problem worldwide. Epidemiologic studies link high salt intake and conditions predisposing to dehydration such as low water intake, diabetes and old age to increased risk of CVD. Previously, we demonstrated that elevation of extracellular sodium, which is a common consequence of these conditions, stimulates production by endothelial cells of clotting initiator, von Willebrand Factor, increases its level in blood and promotes thrombogenesis. In present study, by PCR array, using human umbilical vein endothelial cells (HUVECs), we analyzed the effect of high NaCl on 84 genes related to endothelial cell biology. The analysis showed that the affected genes regulate many aspects of endothelial cell biology including cell adhesion, proliferation, leukocyte and lymphocyte activation, coagulation, angiogenesis and inflammatory response. The genes whose expression increased the most were adhesion molecules VCAM1 and E-selectin and the chemoattractant MCP-1. These are key participants in the leukocyte adhesion and transmigration that play a major role in the inflammation and pathophysiology of CVD, including atherosclerosis. Indeed, high NaCl increased adhesion of mononuclear cells and their transmigration through HUVECs monolayers. In mice, mild water restriction that elevates serum sodium by 5 mmol/l, increased VCAM1, E-selectin and MCP-1 expression in mouse tissues, accelerated atherosclerotic plaque formation in aortic root and caused thickening or walls of coronary arteries. Multivariable linear regression analysis of clinical data from the Atherosclerosis Risk in Communities Study (n=12779) demonstrated that serum sodium is a significant predictor of 10 Years Risk of coronary heart disease. These findings indicate that elevation of extracellular sodium within the physiological range is accompanied by vascular changes that facilitate development of CVD. The findings bring attention to serum sodium as a risk factor for

  3. Curcumin retunes cholesterol transport homeostasis and inflammation response in M1 macrophage to prevent atherosclerosis.

    PubMed

    Chen, Fang-Yuan; Zhou, Juan; Guo, Ning; Ma, Wang-Ge; Huang, Xin; Wang, Huan; Yuan, Zu-Yi

    2015-11-27

    Lipoprotein cholesterol metabolism dysfunction in the arterial wall is a major contributor to atherosclerosis, and excessive lipid intake and failed cholesterol homeostasis may accelerate the atherogenic process. Curcumin exerts multiple effects by alleviating inflammation, hyperlipidemia, and atherosclerosis; however, its role in cholesterol transport homeostasis and its underlying impact on inflammatory M1 macrophages are poorly understood. This work aimed to investigate the effect of curcumin on cholesterol transport, the inflammatory response and cell apoptosis in M1 macrophages. RAW264.7 macrophages (M0) were induced with LPS plus IFN-γ for 12 h to develop a M1 subtype and were then incubated with curcumin at different concentrations (6.25 and 12.5 μmol/L) in the presence or absence of oxLDL. Then, cholesterol influx/efflux and foam cell formation as well as inflammation and apoptosis were evaluated. It was found that curcumin increased cholesterol uptake measured by the Dil-oxLDL binding assay, and simultaneously increased cholesterol efflux carried out by Apo-A1 and HDL in M1 cells. Curcumin further reinforced ox-LDL-induced cholesterol esterification and foam cell formation as determined by Oil Red O and BODIPY staining. Moreover, curcumin dramatically reduced ox-LDL-induced cytokine production such as IL-1β, IL-6 as well as TNF-α and M1 cell apoptosis. We also found that curcumin upregulated CD36 and ABCA1 in M1 macrophages. Curcumin increased PPARγ expression, which in turn promoted CD36 and ABCA1 expression. In conclusion, curcumin may increase the ability of M1 macrophages to handle harmful lipids, thus promoting lipid processing, disposal and removal, which may support cholesterol homeostasis and exert an anti-atherosclerotic effect. PMID:26471308

  4. MALVAC 2012 scientific forum: accelerating development of second-generation malaria vaccines

    PubMed Central

    2012-01-01

    The World Health Organization (WHO) convened a malaria vaccines committee (MALVAC) scientific forum from 20 to 21 February 2012 in Geneva, Switzerland, to review the global malaria vaccine portfolio, to gain consensus on approaches to accelerate second-generation malaria vaccine development, and to discuss the need to update the vision and strategic goal of the Malaria Vaccine Technology Roadmap. This article summarizes the forum, which included reviews of leading Plasmodium falciparum vaccine candidates for pre-erythrocytic vaccines, blood-stage vaccines, and transmission-blocking vaccines. Other major topics included vaccine candidates against Plasmodium vivax, clinical trial site capacity development in Africa, trial design considerations for a second-generation malaria vaccine, adjuvant selection, and regulatory oversight functions including vaccine licensure. PMID:23140365

  5. Accelerating Development of EV Batteries Through Computer-Aided Engineering (Presentation)

    SciTech Connect

    Pesaran, A.; Kim, G. H.; Smith, K.; Santhanagopalan, S.

    2012-12-01

    The Department of Energy's Vehicle Technology Program has launched the Computer-Aided Engineering for Automotive Batteries (CAEBAT) project to work with national labs, industry and software venders to develop sophisticated software. As coordinator, NREL has teamed with a number of companies to help improve and accelerate battery design and production. This presentation provides an overview of CAEBAT, including its predictive computer simulation of Li-ion batteries known as the Multi-Scale Multi-Dimensional (MSMD) model framework. MSMD's modular, flexible architecture connects the physics of battery charge/discharge processes, thermal control, safety and reliability in a computationally efficient manner. This allows independent development of submodels at the cell and pack levels.

  6. Omics-based approaches to understand mechanosensitive endothelial biology and atherosclerosis.

    PubMed

    Simmons, Rachel D; Kumar, Sandeep; Thabet, Salim Raid; Sur, Sanjoli; Jo, Hanjoong

    2016-09-01

    Atherosclerosis is a multifactorial disease that preferentially occurs in arterial regions exposed to d-flow can be used to indicate disturbed flow or disturbed blood flow. The mechanisms by which d-flow induces atherosclerosis involve changes in the transcriptome, methylome, proteome, and metabolome of multiple vascular cells, especially endothelial cells. Initially, we begin with the pathogenesis of atherosclerosis and the changes that occur at multiple levels owing to d-flow, especially in the endothelium. Also, there are a variety of strategies used for the global profiling of the genome, transcriptome, miRNA-ome, DNA methylome, and metabolome that are important to define the biological and pathophysiological mechanisms of endothelial dysfunction and atherosclerosis. Finally, systems biology can be used to integrate these 'omics' datasets, especially those that derive data based on a single animal model, in order to better understand the pathophysiology of atherosclerosis development in a holistic manner and how this integrative approach could be used to identify novel molecular diagnostics and therapeutic targets to prevent or treat atherosclerosis. WIREs Syst Biol Med 2016, 8:378-401. doi: 10.1002/wsbm.1344 For further resources related to this article, please visit the WIREs website. PMID:27341633

  7. Decreased bone mineral density is associated with coronary atherosclerosis in healthy postmenopausal women

    PubMed Central

    Seo, Seok Kyo; Yun, Bo Hyon; Noe, Eun Bee; Suh, Jong Wook; Choi, Young Sik

    2015-01-01

    Objective This study aimed to assess the association between bone mineral density (BMD) and coronary atherosclerosis in healthy postmenopausal women. Methods We performed a retrospective review of 252 postmenopausal women who had visited a health promotion center for a routine checkup. BMD of the lumbar spine (L1-L4) and femoral neck was evaluated using dual-energy X-ray absorptiometry, and coronary atherosclerosis was assessed using 64-row multidetector computed tomography. Participants were divided into normal BMD and osteopenia-osteoporosis groups, according to the T-scores of their lumbar spine or femoral neck. Results Participants with osteopenia-osteoporosis had a significantly higher proportion of coronary atherosclerosis than did those with normal BMD at the lumbar spine (P=0.003) and femoral neck (P=0.004). Osteopenia-osteoporosis at the lumbar spine (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.12 to 7.27) or femoral neck (OR, 3.35; 95% CI, 1.07 to 10.57) was associated with coronary atherosclerosis, after controlling for age and cardiovascular risk factors. Conclusion Decreased BMD is associated with coronary atherosclerosis in healthy postmenopausal women, independent of age and cardiovascular risk factors. Postmenopausal women with decreased BMD may have a higher risk of developing coronary atherosclerosis. PMID:25798428

  8. Nonlinear development of strong current-driven instabilities and selective acceleration of ^3He ions

    NASA Astrophysics Data System (ADS)

    Toida, Mieko; Okumura, Hayato

    2003-10-01

    In some solar flares, the abundance of high-energy ^3He ions is extremely increased. As a mechanism for these ^3He rich events, current-driven instabilities are believed to be important. Nonlinear development of the strong current-driven instabilities and associated energy transfer to ^3He ions are studied theoretically and numerically [1]. First, by means of a two-dimensional, electrostatic, particle simulation code, it is demonstrated that ^3He ions are selectively accelerated by fundamental H cyclotron waves with frequencies ω ≃ 2Ω_3He (Ω_3He is the cyclotron frequency of ^3He). Then, from the analysis of the dispersion relation of these waves, it is found that the ω ≃ 2 Ω_ 3He waves have the greatest growth rate, if Te > 10 T_H. Energies of the ^3He ions are also discussed. Theoretical expression for the maximum ^3He energy is presented, which is in good agreement with the simulation results. Based on this theory, it is shown that when the initial electron drift energy is of the order of 10 keV, many ^3He ions can be accelerated to energies of the order of MeV/n. [1] M. Toida and H. Okumura, J. Phys. Soc. Jpn. 72,1098 (2003)

  9. Development of a remote control console for the HHIRF 25-MV tandem accelerator

    SciTech Connect

    Hasanul Basher, A.M.

    1991-09-01

    The CAMAC-based control system for the 25-MV Tandem Accelerator at HHIRF uses two Perkin-Elmer, 32-bit minicomputers: a message-switching computer and a supervisory computer. Two operator consoles are located on one of the six serial highways. Operator control is provided by means of a console CRT, trackball, assignable shaft encoders and meters. The message-switching computer transmits and receives control information on the serial highways. At present, the CRT pages with updated parameters can be displayed and parameters can be controlled only from the two existing consoles, one in the Tandem control room and the other in the ORIC control room. It has become necessary to expand the control capability to several other locations in the building. With the expansion of control and monitoring capability of accelerator parameters to other locations, the operators will be able to control and observe the result of the control action at the same time. Since the new control console will be PC-based, the existing page format will be changed. The PC will be communicating with the Perkin-Elmer through RS-232 and a communication software package. Hardware configuration has been established, a communication software program that reads the pages from the shared memory has been developed. In this paper, we present the implementation strategy, works completed, existing and new page format, future action plans, explanation of pages and use of related global variables, a sample session, and flowcharts.

  10. Development of Wind-and-React Bi-2212 Accelerator Magnet Technology

    SciTech Connect

    Cheng, Daniel; Dietderich, Daniel R.; English, C.D.; Felice, Helene; Hannaford, Charles R.; Prestemon, Soren O.; Sabbi, GianLuca; Scanlan, Ron M.; Hikichi, Y.; Nishioka, J.; Hasegawa, T.; Godeke, A.

    2007-06-01

    We report on the progress in our R&D program, targeted to develop the technology for the application of Bi{sub 2}Sr{sub 2}CaCu{sub 2}O{sub x} (Bi-2212) in accelerator magnets. The program uses subscale coils, wound from insulated cables, to study suitable materials, heat treatment homogeneity, stability, and effects of magnetic field and thermal and electro-magnetic loads. We have addressed material and reaction related issues and report on the fabrication, heat treatment, and analysis of subscale Bi-2212 coils. Such coils can carry a current on the order of 5000 A and generate, in various support structures, magnetic fields from 2.6 to 9.9 T. Successful coils are therefore targeted towards a hybrid Nb{sub 3}Sn-HTS magnet which will demonstrate the feasibility of Bi-2212 for accelerator magnets, and open a new magnetic field realm, beyond what is achievable with Nb{sub 3}Sn.

  11. Recent advances in the development of high average power induction accelerators for industrial and environmental applications

    SciTech Connect

    Neau, E.L.

    1994-09-01

    Short-pulse accelerator technology developed during the early 1960`s through the late 1980`s is being extended to high average power systems capable of use in industrial and environmental applications. Processes requiring high dose levels and/or high volume throughput will require systems with beam power levels from several hundreds of kilowatts to megawatts. Beam accelerating potentials can range from less than 1 MeV to as much as 10 MeV depending on the type of beam, depth of penetration required, and the density of the product being treated. This paper addresses the present status of a family of high average power systems, with output beam power levels up to 200 kW, now in operation that use saturable core switches to achieve output pulse widths of 50 to 80 nanoseconds. Inductive adders and field emission cathodes are used to generate beams of electrons or x-rays at up to 2.5 MeV over areas of 1000 cm{sup 2}. Similar high average power technology is being used at {le} 1 MeV to drive repetitive ion beam sources for treatment of material surfaces over 100`s of cm{sup 2}.

  12. Development of an H- ion source for Japan Proton Accelerator Research Complex upgradea)

    NASA Astrophysics Data System (ADS)

    Ohkoshi, K.; Namekawa, Y.; Ueno, A.; Oguri, H.; Ikegami, K.

    2010-02-01

    A cesium (Cs) free H- ion source driven with a lanthanum hexaboride (LaB6) filament was adopted as an ion source for the first stage of the Japan Proton Accelerator Research Complex (J-PARC). At present, the maximum H- ion current produced by the ion source is 38 mA, using which J-PARC can produce a proton beam power of 0.6 MW by accelerating it with the 181 MeV linac and the 3 GeV rapid cycling synchrotron. In order to satisfy the beam power of 1 MW required for the second stage of the J-PARC in the near future, we have to increase the ion current to more than 60 mA. Therefore, we have started to develop a Cs-seeded ion source by adding an external Cs-seeding system to a J-PARC test ion source that has a structure similar to that of the J-PARC ion source except for the fact that the plasma chamber is slightly larger. As a result, a H- ion current of more than 70 mA was obtained from the ion source using a tungsten filament instead of a LaB6 filament with a low arc discharge power of 15 kW (100 V, 150 A).

  13. The development of seismic guidelines for the Stanford Linear Accelerator Center

    SciTech Connect

    Huggins, R.

    1996-08-01

    This paper describes the development of Seismic Guidelines for the Stanford Linear Accelerator Center (SLAC). Although structures have always been built conservatively, SLAC management decided to review and update their seismic guidelines. SLAC is about mid-way between the epicenters of the 8.3 Richter magnitude 1906 San Francisco and the 7.2 Loma Prieta Earthquakes. The west end of the two mile long electron/positron particle accelerator lies a half mile from the large San Andreas Fault. Suggestions for seismic planning processes were solicited from local computer manufacturing firms, universities, and federal laboratories. A Committee of the various stakeholders in SLAC`s seismic planning retained an internationally known Seismic Planning Consultant and reviewed relevant standards and drafted Guidelines. A panel of seismic experts was convened to help define the hazard, site response spectra, probabilistic analysis of shaking, and near field effects. The Facility`s structures were assigned to seismic classes of importance, and an initial assessment of a sample of a dozen buildings conducted. This assessment resulted in emergency repairs to one structure, and provided a {open_quotes}reality basis{close_quotes} for establishing the final Guidelines and Administrative Procedures, and a program to evaluate remaining buildings, shielding walls, tunnels, and other special structures.

  14. New options for developing of nuclear energy using an accelerator-driven reactor

    SciTech Connect

    Takahashi, Hiroshi

    1997-09-01

    Fissile fuel can be produced at a high rate using an accelerator-driven Pu-fueled subcritical fast reactor. Thus, the necessity of early introduction of the fast reactor can be moderated. High reliability of the proton accelerator, which is essential to implementing an accelerator-driven reactor in the nuclear energy field can be achieved by a slight extension of the accelerator`s length, with only a small economical penalty. Subcritical operation provides flexible nuclear energy options including high neutron economy producing the fuel, transmuting high-level wastes, such as minor actinides, and of converting efficiently the excess Pu and military Pu into proliferation-resistant fuel.

  15. Molecular Imaging of Inflammation in Atherosclerosis

    PubMed Central

    Wildgruber, Moritz; Swirski, Filip K.; Zernecke, Alma

    2013-01-01

    Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic. PMID:24312156

  16. Bisphenol A Exposure Enhances Atherosclerosis in WHHL Rabbits

    PubMed Central

    Fang, Chao; Ning, Bo; Waqar, Ahmed Bilal; Niimi, Manabu; Li, Shen; Satoh, Kaneo; Shiomi, Masashi; Ye, Ting; Dong, Sijun; Fan, Jianglin

    2014-01-01

    Bisphenol A (BPA) is an environmental endocrine disrupter. Excess exposure to BPA may increase susceptibility to many metabolic disorders, but it is unclear whether BPA exposure has any adverse effects on the development of atherosclerosis. To determine whether there are such effects, we investigated the response of Watanabe heritable hyperlipidemic (WHHL) rabbits to 400-µg/kg BPA per day, administered orally by gavage, over the course of 12 weeks and compared aortic and coronary atherosclerosis in these rabbits to the vehicle group using histological and morphometric methods. In addition, serum BPA, cytokines levels and plasma lipids as well as pathologic changes in liver, adipose and heart were analyzed. Moreover, we treated human umbilical cord vein endothelial cells (HUVECs) and rabbit aortic smooth muscle cells (SMCs) with different doses of BPA to investigate the underlying molecular mechanisms involved in BPA action(s). BPA treatment did not change the plasma lipids and body weights of the WHHL rabbits; however, the gross atherosclerotic lesion area in the aortic arch was increased by 57% compared to the vehicle group. Histological and immunohistochemical analyses revealed marked increases in advanced lesions (37%) accompanied by smooth muscle cells (60%) but no significant changes in the numbers of macrophages. With regard to coronary atherosclerosis, incidents of coronary stenosis increased by 11% and smooth muscle cells increased by 73% compared to the vehicle group. Furthermore, BPA-treated WHHL rabbits showed increased adipose accumulation and hepatic and myocardial injuries accompanied by up-regulation of endoplasmic reticulum (ER) stress and inflammatory and lipid metabolism markers in livers. Treatment with BPA also induced the expression of ER stress and inflammation related genes in cultured HUVECs. These results demonstrate for the first time that BPA exposure may increase susceptibility to atherosclerosis in WHHL rabbits. PMID:25333893

  17. Bisphenol A exposure enhances atherosclerosis in WHHL rabbits.

    PubMed

    Fang, Chao; Ning, Bo; Waqar, Ahmed Bilal; Niimi, Manabu; Li, Shen; Satoh, Kaneo; Shiomi, Masashi; Ye, Ting; Dong, Sijun; Fan, Jianglin

    2014-01-01

    Bisphenol A (BPA) is an environmental endocrine disrupter. Excess exposure to BPA may increase susceptibility to many metabolic disorders, but it is unclear whether BPA exposure has any adverse effects on the development of atherosclerosis. To determine whether there are such effects, we investigated the response of Watanabe heritable hyperlipidemic (WHHL) rabbits to 400-µg/kg BPA per day, administered orally by gavage, over the course of 12 weeks and compared aortic and coronary atherosclerosis in these rabbits to the vehicle group using histological and morphometric methods. In addition, serum BPA, cytokines levels and plasma lipids as well as pathologic changes in liver, adipose and heart were analyzed. Moreover, we treated human umbilical cord vein endothelial cells (HUVECs) and rabbit aortic smooth muscle cells (SMCs) with different doses of BPA to investigate the underlying molecular mechanisms involved in BPA action(s). BPA treatment did not change the plasma lipids and body weights of the WHHL rabbits; however, the gross atherosclerotic lesion area in the aortic arch was increased by 57% compared to the vehicle group. Histological and immunohistochemical analyses revealed marked increases in advanced lesions (37%) accompanied by smooth muscle cells (60%) but no significant changes in the numbers of macrophages. With regard to coronary atherosclerosis, incidents of coronary stenosis increased by 11% and smooth muscle cells increased by 73% compared to the vehicle group. Furthermore, BPA-treated WHHL rabbits showed increased adipose accumulation and hepatic and myocardial injuries accompanied by up-regulation of endoplasmic reticulum (ER) stress and inflammatory and lipid metabolism markers in livers. Treatment with BPA also induced the expression of ER stress and inflammation related genes in cultured HUVECs. These results demonstrate for the first time that BPA exposure may increase susceptibility to atherosclerosis in WHHL rabbits. PMID:25333893

  18. Analytical Validation of Accelerator Mass Spectrometry for Pharmaceutical Development: the Measurement of Carbon-14 Isotope Ratio.

    SciTech Connect

    Keck, B D; Ognibene, T; Vogel, J S

    2010-02-05

    Accelerator mass spectrometry (AMS) is an isotope based measurement technology that utilizes carbon-14 labeled compounds in the pharmaceutical development process to measure compounds at very low concentrations, empowers microdosing as an investigational tool, and extends the utility of {sup 14}C labeled compounds to dramatically lower levels. It is a form of isotope ratio mass spectrometry that can provide either measurements of total compound equivalents or, when coupled to separation technology such as chromatography, quantitation of specific compounds. The properties of AMS as a measurement technique are investigated here, and the parameters of method validation are shown. AMS, independent of any separation technique to which it may be coupled, is shown to be accurate, linear, precise, and robust. As the sensitivity and universality of AMS is constantly being explored and expanded, this work underpins many areas of pharmaceutical development including drug metabolism as well as absorption, distribution and excretion of pharmaceutical compounds as a fundamental step in drug development. The validation parameters for pharmaceutical analyses were examined for the accelerator mass spectrometry measurement of {sup 14}C/C ratio, independent of chemical separation procedures. The isotope ratio measurement was specific (owing to the {sup 14}C label), stable across samples storage conditions for at least one year, linear over 4 orders of magnitude with an analytical range from one tenth Modern to at least 2000 Modern (instrument specific). Further, accuracy was excellent between 1 and 3 percent while precision expressed as coefficient of variation is between 1 and 6% determined primarily by radiocarbon content and the time spent analyzing a sample. Sensitivity, expressed as LOD and LLOQ was 1 and 10 attomoles of carbon-14 (which can be expressed as compound equivalents) and for a typical small molecule labeled at 10% incorporated with {sup 14}C corresponds to 30 fg

  19. Residual acceleration data on IML-1: Development of a data reduction and dissemination plan

    NASA Technical Reports Server (NTRS)

    Rogers, Melissa J. B.; Alexander, J. Iwan D.; Wolf, Randy

    1992-01-01

    The need to record some measure of the low-gravity environment of an orbiting space vehicle was recognized at an early stage of the U.S. Space Program. Such information was considered important for both the assessment of an astronaut's physical condition during and after space missions and the analysis of the fluid physics, materials processing, and biological sciences experiments run in space. Various measurement systems were developed and flown on space platforms beginning in the early 1970's. Similar in concept to land based seismometers that measure vibrations caused by earthquakes and explosions, accelerometers mounted on orbiting space vehicles measure vibrations in and of the vehicle due to internal and external sources, as well as vibrations in a sensor's relative acceleration with respect to the vehicle to which it is attached. The data collected over the years have helped to alter the perception of gravity on-board a space vehicle from the public's early concept of zero-gravity to the science community's evolution of thought from microgravity to milligravity to g-jitter or vibrational environment. Since the advent of the Shuttle Orbiter Program, especially since the start of Spacelab flights dedicated to scientific investigations, the interest in measuring the low-gravity environment in which experiments are run has increased. This interest led to the development and flight of numerous accelerometer systems dedicated to specific experiments. It also prompted the development of the NASA MSAD-sponsored Space Acceleration Measurement System (SAMS). The first SAMS units flew in the Spacelab on STS-40 in June 1991 in support of the first Spacelab Life Sciences mission (SLS-1). SAMS is currently manifested to fly on all future Spacelab missions.

  20. Role of Brown Fat in Lipoprotein Metabolism and Atherosclerosis.

    PubMed

    Hoeke, Geerte; Kooijman, Sander; Boon, Mariëtte R; Rensen, Patrick C N; Berbée, Jimmy F P

    2016-01-01

    Atherosclerosis, for which hyperlipidemia is a major risk factor, is the leading cause of morbidity and mortality in Western society, and new therapeutic strategies are highly warranted. Brown adipose tissue (BAT) is metabolically active in human adults. Although positron emission tomography-computed tomography using a glucose tracer is the golden standard to visualize and quantify the volume and activity of BAT, it has become clear that activated BAT combusts fatty acids rather than glucose. Here, we review the role of brown and beige adipocytes in lipoprotein metabolism and atherosclerosis, with evidence derived from both animal and human studies. On the basis of mainly data from animal models, we propose a model in which activated brown adipocytes use their intracellular triglyceride stores to generate fatty acids for combustion. BAT rapidly replenishes these stores by internalizing primarily lipoprotein triglyceride-derived fatty acids, generated by lipoprotein lipase-mediated hydrolysis of triglycerides, rather than by holoparticle uptake. As a consequence, BAT activation leads to the generation of lipoprotein remnants that are subsequently cleared via the liver provided that an intact apoE-low-density lipoprotein receptor pathway is present. Through these mechanisms, BAT activation reduces plasma triglyceride and cholesterol levels and attenuates diet-induced atherosclerosis development. Initial studies suggest that BAT activation in humans may also reduce triglyceride and cholesterol levels, but potential antiatherogenic effects should be assessed in future studies. PMID:26837747

  1. Iron overload diminishes atherosclerosis in apoE-deficient mice

    PubMed Central

    Kirk, Elizabeth A.; Heinecke, Jay W.; LeBoeuf, Renée C.

    2001-01-01

    It has been proposed that elevated levels of tissue iron increase the risk for atherosclerosis, perhaps by favoring the formation of pro-atherogenic oxidized LDL. Working with apoE-deficient (apoE–/–) mice, which do not require a high-fat diet to develop atherosclerosis, we compared the effects of standard diet (0.02% iron) or a 2% carbonyl iron diet. After 24 weeks, mice fed the 2% carbonyl iron diet had twice as much iron in their plasma, a ninefold increase in bleomycin-detectable free iron in their plasma, and ten times as much iron in their livers as control mice. Dietary iron overload caused a modest (30%) rise in plasma triglyceride and cholesterol. Nevertheless, this regimen did not exacerbate, but rather reduced the severity of atherosclerosis by 50%, and it failed to elevate hepatic levels of heme oxygenase mRNA, which is induced by many different oxidative insults in vitro. Moreover, hepatic levels of protein-bound dityrosine and ortho-tyrosine, two markers of metal-catalyzed oxidative damage in vitro, failed to rise in iron-overloaded animals. Our observations suggest that elevated serum and tissue levels of iron are not atherogenic in apoE–/– mice. Moreover, they call into question the hypothesis that elevated levels of tissue iron promote LDL oxidation and oxidative stress in vivo. PMID:11413162

  2. SIRT6 protects against endothelial dysfunction and atherosclerosis in mice

    PubMed Central

    Xu, Suowen; Yin, Meimei; Koroleva, Marina; Mastrangelo, Michael A.; Zhang, Wenbo; Bai, Peter; Little, Peter J.; Jin, Zheng Gen

    2016-01-01

    SIRT6 is an important member of sirtuin family that represses inflammation, aging and DNA damage, three of which are causing factors for endothelial dysfunction. SIRT6 expression is decreased in atherosclerotic lesions from ApoE−/− mice and human patients. However, the role of SIRT6 in regulating vascular endothelial function and atherosclerosis is not well understood. Here we show that SIRT6 protects against endothelial dysfunction and atherosclerosis. Global and endothelium-specific SIRT6 knockout mice exhibited impaired endothelium-dependent vasorelaxation. Moreover, SIRT6+/− haploinsufficient mice fed a high-fat diet (HFD) also displayed impaired endothelium-dependent vasorelaxation. Importantly, SIRT6+/−;ApoE−/− mice after HFD feeding exhibited exacerbated atherosclerotic lesion development, concurrent with increased expression of the proinflammatory cytokine VCAM-1. Loss- and gain-of-SIRT6 function studies in cultured human endothelial cells (ECs) showed that SIRT6 attenuated monocyte adhesion to ECs. RNA-sequencing profiling revealed that SIRT6 overexpression decreased the expression of multiple atherosclerosis-related genes, including proatherogenic gene TNFSF4 (tumor necrosis factor superfamily member 4). Chromatin immunoprecipitation assays showed that SIRT6 decreased TNFSF4 gene expression by binding to and deacetylating H3K9 at TNFSF4 gene promoter. Collectively, these findings demonstrate that SIRT6 play a pivotal role in maintaining endothelial function and increased SIRT6 activity could be a new therapeutic strategy to combat atherosclerotic disease. PMID:27249230

  3. Curcumin analog L3 alleviates diabetic atherosclerosis by multiple effects.

    PubMed

    Zheng, Bin; Yang, Liu; Wen, Caixia; Huang, Xiuwang; Xu, Chenxia; Lee, Kuan-Han; Xu, Jianhua

    2016-03-15

    L3, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aims to explore the efficacy of L3 on diabetic atherosclerosis and the related mechanism. The effect of L3 was studied on glucose and lipid metabolism, antioxidant status, atherosclerosis-related indexes and pathological changes of main organs in the mice model of diabetes induced by streptozotocin and high-fat diet. The results showed that L3 treatment could meliorate dyslipidemia and hyperglycemia, reduce oxidative stress, enhance the activity of antioxidases, increase the nitric oxide level in plasma and aortic arch, decrease the production of reactive oxygen species in pancreas and lectin-like oxidized low-density lipoprotein receptor-1 expression in aortic arch, and meliorate the fatty and atherosclerotic degeneration in aortic arch, thereby preventing the development of diabetes and its complications. These results suggested that L3 can alleviate the diabetic atherosclerosis by multiple effects. This study provided scientific basis for the further research and clinical application of L3. PMID:26852952

  4. SIRT6 protects against endothelial dysfunction and atherosclerosis in mice.

    PubMed

    Xu, Suowen; Yin, Meimei; Koroleva, Marina; Mastrangelo, Michael A; Zhang, Wenbo; Bai, Peter; Little, Peter J; Jin, Zheng Gen

    2016-05-01

    SIRT6 is an important member of sirtuin family that represses inflammation, aging and DNA damage, three of which are causing factors for endothelial dysfunction. SIRT6 expression is decreased in atherosclerotic lesions from ApoE(-/-) mice and human patients. However, the role of SIRT6 in regulating vascular endothelial function and atherosclerosis is not well understood. Here we show that SIRT6 protects against endothelial dysfunction and atherosclerosis. Global and endothelium-specific SIRT6 knockout mice exhibited impaired endothelium-dependent vasorelaxation. Moreover, SIRT6(+/-) haploinsufficient mice fed a high-fat diet (HFD) also displayed impaired endothelium-dependent vasorelaxation. Importantly, SIRT6(+/-); ApoE(-/-) mice after HFD feeding exhibited exacerbated atherosclerotic lesion development, concurrent with increased expression of the proinflammatory cytokine VCAM-1. Loss- and gain-of-SIRT6 function studies in cultured human endothelial cells (ECs) showed that SIRT6 attenuated monocyte adhesion to ECs. RNA-sequencing profiling revealed that SIRT6 overexpression decreased the expression of multiple atherosclerosis-related genes, including proatherogenic gene TNFSF4 (tumor necrosis factor superfamily member 4). Chromatin immunoprecipitation assays showed that SIRT6 decreased TNFSF4 gene expression by binding to and deacetylating H3K9 at TNFSF4 gene promoter. Collectively, these findings demonstrate that SIRT6 play a pivotal role in maintaining endothelial function and increased SIRT6 activity could be a new therapeutic strategy to combat atherosclerotic disease. PMID:27249230

  5. Nitric oxide in atherosclerosis: vascular protector or villain?

    PubMed

    Dusting, G J; Fennessy, P; Yin, Z L; Gurevich, V

    1998-11-01

    1. Nitric oxide (NO) has important roles in physiological vasodilatation, cytotoxicity and vascular disease. Nitric oxide and prostacyclin (PGI2), both released from the endothelium, act synergistically to inhibit platelet aggregation and adhesion. These autacoids also inhibit the adhesion and migration of leucocytes and, in some arteries, they synergize in terms of vasodilation. 2. The development of atherosclerosis and hyperlipaemia per se is accompanied by impairment of endothelium-dependent vasodilation. 3. Atherosclerosis is associated with marked changes in the activity of isoforms of NO synthase (NOS) in the artery wall, including increased expression of the NOS2 (inducible) isoform in complex human lesions as well as in the neointima of experimental animal models. 4. Failure of NO release from the endothelium with normal physiological stimuli, which has been attributed to a defect in the operation of the endothelial NOS (NOS3), provides conditions propitious for leucocyte adhesion, vasospasm, thrombosis and, in addition, may promote increased proliferation of intimal cells. 5. Nitric oxide and superoxide anions generated by inflammatory cells in atherosclerosis react to form cytodestructive peroxynitrite radicals, potentially causing injury to the endothelium and myocytes, and this may be a factor in apoptosis of cells leading to plaque rupture. 6. We have been able to reverse these NO defects with therapeutic agents, including angiotensin-converting enzyme inhibitors, antagonists of platelet-activating factor and NO donor compounds, all offering promise in protecting against some manifestations of vascular disease. PMID:9809190

  6. Lasting monitoring of immune state in patients with coronary atherosclerosis

    NASA Astrophysics Data System (ADS)

    Malinova, Lidia I.; Denisova, Tatyana P.; Tuchin, Valery V.

    2007-02-01

    Immune state monitoring is an expensive, invasive and sometimes difficult necessity in patients with different disorders. Immune reaction dynamics study in patients with coronary atherosclerosis provides one of the leading components to complication development, clinical course prognosis and treatment and rehabilitation tactics. We've chosen intravenous glucose injection as metabolic irritant in the following four groups of patients: men with proved coronary atherosclerosis (CA), non insulin dependent diabetes mellitus (NIDDM), men hereditary burden by CA and NIDDM and practically healthy persons with longlivers in generation. Immune state parameters such as quantity of leukocytes and lymphocytes, circulating immune complexes levels, serum immunoglobulin levels, HLA antigen markers were studied at 0, 30 and 60 minutes during glucose loading. To obtain continues time function of studied parameters received data were approximated by polynomials of high degree with after going first derivatives. Time functions analyze elucidate principally different dynamics studied parameters in all chosen groups of patients, which couldn't be obtained from discontinuous data compare. Leukocyte and lymphocyte levels dynamics correlated HLA antigen markers in all studied groups. Analytical estimation of immune state in patients with coronary atherosclerosis shows the functional "margin of safety" of immune system state under glucose disturbance. Proposed method of analytical estimation also can be used in immune system monitoring in other groups of patients.

  7. Accelerated development of Zr-containing new generation ferritic steels for advanced nuclear reactors

    SciTech Connect

    Tan, Lizhen; Yang, Ying; Sridharan, K.

    2015-12-01

    The mission of the Nuclear Energy Enabling Technologies (NEET) program is to develop crosscutting technologies for nuclear energy applications. Advanced structural materials with superior performance at elevated temperatures are always desired for nuclear reactors, which can improve reactor economics, safety margins, and design flexibility. They benefit not only new reactors, including advanced light water reactors (LWRs) and fast reactors such as the sodium-cooled fast reactor (SFR) that is primarily designed for management of high-level wastes, but also life extension of the existing fleet when component exchange is needed. Developing and utilizing the modern materials science tools (experimental, theoretical, and computational tools) is an important path to more efficient alloy development and process optimization. The ultimate goal of this project is, with the aid of computational modeling tools, to accelerate the development of Zr-bearing ferritic alloys that can be fabricated using conventional steelmaking methods. The new alloys are expected to have superior high-temperature creep performance and excellent radiation resistance as compared to Grade 91. The designed alloys were fabricated using arc-melting and drop-casting, followed by hot rolling and conventional heat treatments. Comprehensive experimental studies have been conducted on the developed alloys to evaluate their hardness, tensile properties, creep resistance, Charpy impact toughness, and aging resistance, as well as resistance to proton and heavy ion (Fe2+) irradiation.

  8. PPM focused X-band klystron development at the Stanford Linear Accelerator Center

    SciTech Connect

    Sprehn, D.; Caryotakis, G.; Eppley, K.; Phillips, R.M.

    1996-07-01

    X-band klystrons capable of 50 MW and utilizing Periodic Permanent Magnet (PPM) focusing are undergoing design and fabrication at the Stanford Linear Accelerator Center (SLAC). The klystron development is part of an effort to realize components necessary for the construction of the Next Linear Collider (NLC). The first klystron to be tested this year has a 0.6 microK beam at 465 kV, a 5 cells traveling wave output structure and a predicted efficiency of 63%. A 465 kV, 190 A beam stick with 12 periods of PPM focusing has recently operated to verify the gun optics and transmission of the beam in the absence of rf bunching. Beam transmission greater than 99.8% has been measured. Design and simulation of the beam stick and klystron are discussed, along with performance of the beam stick under confined flow and shielded conditions.

  9. Development of a 15 T $Nb_3Sn$ Accelerator Dipole Demonstrator at Fermilab

    SciTech Connect

    Novitski, I.; Andreev, N.; Barzi, E.; Carmichael, J.; Kashikhin, V. V.; Turrion, D.; Yu, M.; Zlobin, A. V.

    2015-01-01

    100 TeV scale Hadron Collider (HC) with a nominal operation field of at least 15 T is being considered for the post-LHC era, which requires using the $Nb_3Sn$ technology. Practical demonstration of this field level in an accelerator-quality magnet and substantial reduction of the magnet costs are the key conditions for realization of such a machine. FNAL has started the development of a 15 T Nb3Sn dipole demonstrator for a 100 TeV scale HC. The magnet design is based on 4-layer shell type coils, graded between the inner and outer layers to maximize the performance and reduce the cost. The experience gained during the Nb3Sn magnet R&D is applied to different aspects of the magnet design. This paper describes the magnetic and structural designs and parameters of the 15 T Nb3Sn dipole and the steps towards the demonstration model fabrication.

  10. Development of a Lorentz Force Accelerator Injector for the VASIMR Engine

    NASA Astrophysics Data System (ADS)

    Glover, T. W.; Chan, A. A.; Díaz, F. R. Chang; Squire, J.

    1998-11-01

    We report on the effort to develop a Lorentz Force Accelerator for use as a plasma injector for the VASIMR(Variable Specific Impulse Magnetoplasma Rocket) engine. Advantages of the LFA, also known as a magnetoplasmadynamic thruster, include simplicity of construction, the ability to use a wide variety of propellant gases without modification, and minimal power processing requirements. As a plasma source for the VASIMR engine, its feature of ejecting plasma in a tightly collimated jet allows it to inject plasma through the loss cone of the VASIMR magnetic field into the engine's central cell. This passage from weak to strong magnetic field regions may result in a desirable increase in plasma density in the central cell. Work to date has focused on achieving reliable start-up and steady-state operation.

  11. Development of a Nb 3Sn multifilamentary wire for accelerator magnet applications

    NASA Astrophysics Data System (ADS)

    Durante, M.; Bredy, P.; Devred, A.; Otmani, R.; Reytier, M.; Schild, T.; Trillaud, F.

    2001-05-01

    CEA/Saclay and Alstom/MSA have carried out a program to develop a Nb 3Sn multifilamentary wire for accelerator magnet applications relying on the internal-tin process. The main wire specifications are: an overall diameter of 0.825 mm, a critical current larger than 405 A at 4.2 K and 7 T, hysteresis losses lower than 450 mJ/cm 3 for a±3 T trapezoidal cycle, and a copper-to-non-copper ratio greater than 1. The last phase of the optimization program was based on four different strands and we present here the results of the characterization tests, including residual resistivity ratio, critical current and AC loss measurements.

  12. Development of Wind-and-React Bi-2212 Accelerator MagnetTechnology

    SciTech Connect

    Godeke, A.; Cheng, D.; Dietderich, D.R.; English, C.D.; Felice,H.; Hannaford, C.R.; Prestemon, S.O.; Sabbi, G.; Scanlan, R.M.; Hikichi,Y.; Nishioka, J.; Hasegawa, T.

    2007-08-28

    We report on the progress in our R&D program, targetedto develop the technology for the application of Bi2Sr2CaCu2Ox (Bi-2212)in accelerator magnets. The program uses subscale coils, wound frominsulated cables, to study suitable materials, heat treatmenthomogeneity, stability, and effects ofmagnetic field and thermal andelectro-magnetic loads. We have addressed material and reaction relatedissues and report onthe fabrication, heat treatment, and analysis ofsubscale Bi-2212 coils. Such coils can carry a current on the order of5000 A and generate, in various support structures, magnetic fields from2.6 to 9.9 T. Successful coils are therefore targeted towards a hybridNb3Sn-HTS magnet which will demonstrate the feasibility of Bi-2212 foraccelerator magnets, and open a new magnetic field realm, beyond what isachievable with Nb3Sn.

  13. Self-accelerated development of salt karst during flash floods along the Dead Sea Coast, Israel

    NASA Astrophysics Data System (ADS)

    Avni, Yoav; Lensky, Nadav; Dente, Elad; Shviro, Maayan; Arav, Reuma; Gavrieli, Ittai; Yechieli, Yoseph; Abelson, Meir; Lutzky, Hallel; Filin, Sagi; Haviv, Itai; Baer, Gidon

    2016-01-01

    We document and analyze the rapid development of a real-time karst system within the subsurface salt layers of the Ze'elim Fan, Dead Sea, Israel by a multidisciplinary study that combines interferometric synthetic aperture radar and light detection and ranging measurements, sinkhole mapping, time-lapse camera monitoring, groundwater level measurements and chemical and isotopic analyses of surface runoff and groundwater. The >1 m/yr drop of Dead Sea water level and the subsequent change in the adjacent groundwater system since the 1960s resulted in flushing of the coastal aquifer by fresh groundwater, subsurface salt dissolution, gradual land subsidence and formation of sinkholes. Since 2010 this process accelerated dramatically as flash floods at the Ze'elim Fan were drained by newly formed sinkholes. During and immediately after these flood events the dissolution rates of the subsurface salt layer increased dramatically, the overlying ground surface subsided, a large number of sinkholes developed over short time periods (hours to days), and salt-saturated water resurged downstream. Groundwater flow velocities increased by more than 2 orders of magnitudes compared to previously measured velocities along the Dead Sea. The process is self-accelerating as salt dissolution enhances subsidence and sinkhole formation, which in turn increase the ponding areas of flood water and generate additional draining conduits to the subsurface. The rapid terrain response is predominantly due to the highly soluble salt. It is enhanced by the shallow depth of the salt layer, the low competence of the newly exposed unconsolidated overburden and the moderate topographic gradients of the Ze'elim Fan.

  14. Accelerated renal disease is associated with the development of metabolic syndrome in a glucolipotoxic mouse model

    PubMed Central

    Martínez-García, Cristina; Izquierdo, Adriana; Velagapudi, Vidya; Vivas, Yurena; Velasco, Ismael; Campbell, Mark; Burling, Keith; Cava, Fernando; Ros, Manuel; Orešič, Matej; Vidal-Puig, Antonio; Medina-Gomez, Gema

    2012-01-01

    SUMMARY Individuals with metabolic syndrome are at high risk of developing chronic kidney disease (CKD) through unclear pathogenic mechanisms. Obesity and diabetes are known to induce glucolipotoxic effects in metabolically relevant organs. However, the pathogenic role of glucolipotoxicity in the aetiology of diabetic nephropathy is debated. We generated a murine model, the POKO mouse, obtained by crossing the peroxisome proliferator-activated receptor gamma 2 (PPARγ2) knockout (KO) mouse into a genetically obese ob/ob background. We have previously shown that the POKO mice showed: hyperphagia, insulin resistance, hyperglycaemia and dyslipidaemia as early as 4 weeks of age, and developed a complete loss of normal β-cell function by 16 weeks of age. Metabolic phenotyping of the POKO model has led to investigation of the structural and functional changes in the kidney and changes in blood pressure in these mice. Here we demonstrate that the POKO mouse is a model of renal disease that is accelerated by high levels of glucose and lipid accumulation. Similar to ob/ob mice, at 4 weeks of age these animals exhibited an increased urinary albumin:creatinine ratio and significantly increased blood pressure, but in contrast showed a significant increase in the renal hypertrophy index and an associated increase in p27Kip1 expression compared with their obese littermates. Moreover, at 4 weeks of age POKO mice showed insulin resistance, an alteration of lipid metabolism and glomeruli damage associated with increased transforming growth factor beta (TGFβ) and parathyroid hormone-related protein (PTHrP) expression. At this age, levels of proinflammatory molecules, such as monocyte chemoattractant protein-1 (MCP-1), and fibrotic factors were also increased at the glomerular level compared with levels in ob/ob mice. At 12 weeks of age, renal damage was fully established. These data suggest an accelerated lesion through glucolipotoxic effects in the renal pathogenesis in POKO mice

  15. Development of a four cavity second-harmonic gyroklystron as driver for a linear accelerator

    NASA Astrophysics Data System (ADS)

    Gouveia, Emmanuel Steve

    Gyroklystrons are microwave amplifiers that combine the multi-cavity configuration of a klystron with the energy extraction mechanism of the cyclotron maser instability. These devices have been studied at the University of Maryland for several years. This work is focused on the development of a 17.14 GHz four-cavity frequency-doubling gyroklystron circuit. This device was designed specifically to drive a high gradient linear accelerator recently developed by the Haimson Corporation. The gyroklystron was designed using the code MAGYKL, yielding a predicted output power of 87 MW for an input drive power of 250 W, with a velocity pitch ratio (alpha) of 1.4. The tube was later fabricated, and underwent a series of experimental tests to evaluate its performance. The highest peak power observed was 18.5 +/- 1.7 MW, corresponding to an efficiency of 7.0% and a gain of 24.0 dB. This result fell short of the theoretical design, yet it was consistent with the low value of the velocity pitch ratio (alpha = 0.85) realized in the experiments. This limitation on alpha was linked to the onset of instabilities in the input cavity. The ultimate cause of these instabilities was the thermal non-uniformity in the emitter of our electron gun, which led to a significant variation (approximately 50%) of the current density across the beam. In order to remedy this problem, we have radically redesigned the input cavity, changing both its geometry and Q factor. These measures should dramatically reduce the probability of instabilities, thus allowing us to remove the experimental limitations imposed on alpha. This new design is presented here. We also describe advanced designs of an output cavity with radial power extraction, and a compact circular to rectangular mode converter. A detailed description of the present experimental setup is given, along with an overview of the power transport system necessary to feed the accelerator with output power from the gyroklystron.

  16. "State-of-Art" paper of the Italian Working Group on Atherosclerosis: Preclinical assessment of early coronary atherosclerosis.

    PubMed

    Madonna, Rosalinda; Selvaggio, Stefano; Selvaggio, Giancarlo; Coronelli, Maurizio; Cocco, Nino

    2016-07-01

    Although the early diagnosis and treatment for acute myocardial infarction have improved over the past decades, the morbidity and mortality from coronary artery disease (CAD) remain significant in Europe and worldwide. It is estimated that the majority of people in the developed countries who die suddenly from CAD, have no prior manifestation of disease, and the majority of these individuals are not considered to be at high risk. Accurate identification of individuals at risk of such events before the clinical manifestations is therefore required. This "State-of-Art" paper of the Italian Working Group on Atherosclerosis aims to i. provide an overview of both the traditional and emerging non-invasive imaging techniques used to detect early atherosclerosis in the general population with moderate cardiovascular risk; ii. identify the rationale for screening asymptomatic patients with preclinical atherosclerotic lesions and the optimal algorithm that should be used to detect them; iii. discuss the future directions of atherosclerosis research, with special focus on nanotechnology, aimed at early identification and treatment of low- and intermediate-risk patients. PMID:27093681

  17. B Cells and Humoral Immunity in Atherosclerosis

    PubMed Central

    Tsiantoulas, Dimitrios; Diehl, Cody J.; Witztum, Joseph L.; Binder, Christoph J.

    2014-01-01

    Insights into the important contribution of inflammation and immune functions in the development and progression of atherosclerosis have greatly improved our understanding of this disease. Although the role of T cells has been extensively studied for decades, only recently has the role of B cells gained more attention. Recent studies have identified differential effects of different B-cell subsets and helped to clarify the still poorly understood mechanisms by which these act. B1 cells have been shown to prevent lesion formation, whereas B2 cells have been suggested to promote it. Natural IgM antibodies, mainly derived from B1 cells, have been shown to mediate atheroprotective effects, but the functional role of other immunoglobulin classes, particularly IgG, still remains elusive. In this review, we will focus on recent insights on the role of B cells and various immunoglobulin classes and how these may mediate their effects in atherosclerotic lesion formation. Moreover, we will highlight potential therapeutic approaches focusing on B-cell depletion that could be used to translate experimental evidence to human disease. PMID:24855199

  18. Genomic correlates of atherosclerosis in ancient humans.

    PubMed

    Zink, Albert; Wann, L Samuel; Thompson, Randall C; Keller, Andreas; Maixner, Frank; Allam, Adel H; Finch, Caleb E; Frohlich, Bruno; Kaplan, Hillard; Lombardi, Guido P; Sutherland, M Linda; Sutherland, James D; Watson, Lucia; Cox, Samantha L; Miyamoto, Michael I; Narula, Jagat; Stewart, Alexandre F R; Thomas, Gregory S; Krause, Johannes

    2014-06-01

    Paleogenetics offers a unique opportunity to study human evolution, population dynamics, and disease evolution in situ. Although histologic and computed x-ray tomographic investigations of ancient mummies have clearly shown that atherosclerosis has been present in humans for more than 5,000 years, limited data are available on the presence of genetic predisposition for cardiovascular disease in ancient human populations. In a previous whole-genome study of the Tyrolean Iceman, a 5,300-year-old glacier mummy from the Alps, an increased risk for coronary heart disease was detected. The Iceman's genome revealed several single nucleotide polymorphisms that are linked with cardiovascular disease in genome-wide association studies. Future genetic studies of ancient humans from various geographic origins and time periods have the potential to provide more insights into the presence and possible changes of genetic risk factors in our ancestors. The study of ancient humans and a better understanding of the interaction between environmental and genetic influences on the development of heart diseases may lead to a more effective prevention and treatment of the most common cause of death in the modern world. PMID:25667090

  19. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming.

    PubMed

    Zimmer, Sebastian; Grebe, Alena; Bakke, Siril S; Bode, Niklas; Halvorsen, Bente; Ulas, Thomas; Skjelland, Mona; De Nardo, Dominic; Labzin, Larisa I; Kerksiek, Anja; Hempel, Chris; Heneka, Michael T; Hawxhurst, Victoria; Fitzgerald, Michael L; Trebicka, Jonel; Björkhem, Ingemar; Gustafsson, Jan-Åke; Westerterp, Marit; Tall, Alan R; Wright, Samuel D; Espevik, Terje; Schultze, Joachim L; Nickenig, Georg; Lütjohann, Dieter; Latz, Eicke

    2016-04-01

    Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol concentrations. Despite ongoing advances in the prevention and treatment of atherosclerosis, cardiovascular disease remains the leading cause of death worldwide. Continuous retention of apolipoprotein B-containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Because cholesterol accumulation and deposition of cholesterol crystals (CCs) trigger a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that increases cholesterol solubility in preventing and reversing atherosclerosis. We showed that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production in both macrophages and human atherosclerotic plaques and promoted liver X receptor (LXR)-mediated transcriptional reprogramming to improve cholesterol efflux and exert anti-inflammatory effects. In vivo, this CD-mediated LXR agonism was required for the antiatherosclerotic and anti-inflammatory effects of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis. PMID:27053774

  20. Vinpocetine attenuates lipid accumulation and atherosclerosis formation.

    PubMed

    Cai, Yujun; Li, Jian-Dong; Yan, Chen

    2013-05-10

    Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis. PMID:23583194